(A), 1998 Antimicrobial ae Ther, apy ] n 1997 and 1998 4 NoftHAmerican 7 ( erinayt Exotics *aaAntimicrobial -eeasas Therapy in Exotics Ss Asada) Made possible by an educational grant from Bayer Corporation, as part of its ongoing commitment to help educate practicing veterinarians worldwide by sponsoring and underwriting the publication of independent scientific forums presented at major international veterinary meetings.‘Antimicrobial therapy in exotic animals is a challenge for the practicing veterinarian. To facilitate practitioners/surgeons in this endeavor, Bayer is proud to provide selected Papers on antimicrobial therapy in exotics from two symposia at the 1997 and 1998, North American Veterinary Conference. Bayer has an ongoing commitment to the veterinary profession, exemplified not only by its sponsorship of educational programs with up-to-date information on major topics of relevance but also by its continued commitment to research and development in the field of animal health. Bayer Corporation Agriculture Division Animal Health Shawnee Mission, Kansas 66201 ISSN 0193-1903 Copyright © 1998, Bayer Corporation and Bayer AG Leverkusen Al rights reserved. Front cover photography: Iguana 1995 Douglas R. Mader; koi~courtesy of Scott Purdin; ferret—courtesy of Karen Rosenthal; scarlet macaw—courtesy of Keven Flammer No part ofthis publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any electronic or mechanical means, by photocopying or recording, or otherwise without the prior permission of the copyright owner, ‘The views expressed in this publication represent those of the authors and do not necessarily reflect those of Bayer or Bayer subsidiaries. This manual is primarily intended as an overview of a scientific topic, as dosages are cited for several pharmacologic agents that may not be the same as those stated on their data sheets in a given country. {in addition, dosages are included for pharmacologic products that may not be licensed for veterinary use in a given country, Veterinary practtioners/surgeons should consult their local data sheet or equivalent for licensing/prescribing conditions in their particular country. Queries relating to the enclosed information should be addressed to the Bayer Animal Health Business Group in each individual county. Printed in USA, Designed and Published by Veterinary Learning Systems, a division of MediMediaCONTENTS ie and Management. Gregory A. Lewbart, MS,VMD TABLE 1—Important Questions for the Koi Client. TABLE 2—Manufacturers of Water Quality Test Kit5 nemo a Z Ty TABLE 3-Medical Conditions of Koi and Treatments. TABLE 4—Gelatinized Food Recipe Bacterial Infections and Antibiotic Therapy in Small Mammals... Karen L. Rosenthal, MS, DVM TABLE 1—Questions to Consider Before Beginning Empiric Antibiotic Treatment in Small Mammals....19 ‘TABLE 2—Antibiotic Use in Rabbits and Rodents in Relation to the Gastrointestinal Tract. TABLE 3—Commonly Used Antibiotics in Small Mammals. Common Bacterial Disease and Antibiotic Therapy in Reptiles. Douglas R. Mader, MS, DVM TABLE 1—Common Bacterial Isolates, Pathogenicity, and Recommended Antibiotics in Reptiles ....28 TABLE 2—Ten Steps for Rational An a tcbona S jicrobial Use. en ‘TABLE 3~Common Antimicrobials Used in Reptilian Practice... 7 ae 29 Common Bacterial Infections and Antibiotic Use in Companion Birds. Keven Flammer, DVM TABLE 1—Commonly Reported Bacterial Diseases in Companion Birds. TABLE 2—Uncommonly Reported Bacterial Diseases in Companion BitdS venue TABLE 3—Common Culture Sites and Normal Flora in Companion Birds. TABLE 4—Treatment Guidelines for Avian Microbial Disease with Unknown Susceptibilit TABLE 5—Potential Toxic Side Effects of Antibiotics Used in Companion Birds... TABLE 6—Commonly Used Antibiotics in Companion Birds.. a2AUTHORS Keven Flammer, DVM Diplomate ABVP (Avian Practice) Dr. Flammer received his DVM from the University of California-Davis in 1980 and later worked as a staff veterinarian for Avicuture Institute, a facility that housed a large collection of exotic birds for breeding and research. He joined the faculty at North Carolina State University College of Veterinary Medicine in 1984 and is currently Associate Professor of ‘Companion and Wild Avian Medicine in the Department of Companion Animal and Special ‘Species Medicine. Dr. Flammer's research interests include treatment and control of microbial diseases in companion birds, pharmacokinetics of antimicrobial drugs, and conservation and breeding of endangered species. Gregory A. Lewbart, MS, VMD Dr. Lewbart is currently Assistant Professor of Aquatic Medicine in the Department of Companion Animal and Special Species Medicine at North Carolina State University College of Veterinary Medicine. He received his MS from Northeastern University in 1985 and VMD from the University of Pennsylvania School of Veterinary Medicine in 1988. Prior to joining the faculty at the North Carolina State University College of Veterinary Medicine, Dr. Lewbart worked for a large importer and wholesaler of tropical fish for more than 4 years, He is the author of numerous popular and scientific articles on marine invertebrates, fish, amphibians, and reptiles and is a frequent lecturer, both nationally and internationally, on these subjects. Douglas R. Mader, MS, DVM. Diplomate ABVP (Companion Animal) Dr. Mader received his DVM from the University of California-Davis in 1986. After completing his residency, he owned the Long Beach Animal Hospital in Long Beach, California for 9 years. Dr. Mader currently owns Pet Health Services, an exotic animal medicine and surgery con- sulting business located in Big Pine Key, Florida. Some of his clients include the Marathon Sea Turtle Hospital and the Key West Aquarium. He is also a consultant for Antech Diagnostics. Dt. ‘Mader is an internationally acclaimed speaker and is on the review boards of several scien- tific journals. He has published numerous articles in peer-reviewed journals and is the author and editor of Reptile Medicine and Surgery. Karen L. Rosenthal, MS, DVM Diplomate ABVP (Avian Practice) Dr, Rosenthal is currently National Director of Avian and Exotic Animal Services and National Director of Consultation Services for Antech Diagnostics in Farmingdale, New York. She is aso staff veterinarian for the Long Island Reptile Museum. Prior to these positions, she served as staff veterinarian at The Avian and Exotic Pet Service of The Animal Medical Center in New York. Dr. Rosenthal received her MS from Duke University in 1982 and DVM from North Carolina State University in 1988. She has a broad range of interests and is a frequent lectur- er on topics concerning small mammals, birds, and reptiles. Her current research interest is in endocrine diseases of ferrets.‘Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998 Koi Medicine and Management Gregory A. Lewbart, MS, VMD Department of Companion Animal and Special Species Medicine Collegeof Veterinary Medicine North Carolina State Univesity leigh, North Corcina ach year veterinarians see an increasing number E: ‘ormamental fish patients, and knowledge of how to manage them is advancing dramatically with every passing month. A large percentage of these patients are nishikigoi (Cyprinus carpio), which taxo- nomically are ornamental carp. n the United States and other parts of the world, nishikigoi are simply referred to as koi. These fish have been selectively bred in Asia for hundreds of years for color, pattern, and size—quali- ties that are of utmost importance in terms of desirabil- ity and value. In Japan, koi are symbols of masculinity and longevity. In the United States, koi owners often invest between $1,000 and $25,000 in fish, excluding the value of the pond and filtration equipment. The following article reviews the basic principles in koi medicine and management. Included are discussions Cn the history, water quality, biopsy and necropsy procedures, and treatment of, common pathogens. History ‘An accurate and concise history is essential when performing a workup of a koi or koi pond case. Table 1 lists per- tinent questions that can be posed to ‘koi owners when acquiring a koi clinical history. Obtaining an accurate history should precede any time-consuming water quality testing or biopsy diagnos- tic procedures, as the common prob- J operate Bieri ctee ie} root lay meee ag SUCH MyestetKaa commonly lead to irceaiteerteanite bacterial, fungal, Purearie tit iene lem of pond predation must be ruled out. This leading. ‘cause of acute mortality and morbidity among koi can be identified by close monitoring of the pond for preda- tory birds, reptiles, and mammals. Injuries sustained as ‘a result of contact with a predator commonly lead to life-threatening bacterial, fungel, and parasitic disease (Figures 1 and 2). Water Quality Because this article focuses on koi medicine and management, this section emphasizes field tests that can yield immediate results. Several companies manu- facture test kits that accurately and inexpensively test the appropriate water quality parameters. These com- panies can be found in Table 2. ‘The basic koi diagnostic laboratory must be equipped to test for temperature, pH, dissolved oxygen, and total alkalinity (buffering capacity of the water), as ‘well as for ammonia, nitrite, and nitrate levels. Kits that also measure copper and chlorine levels are desirable. Poor water quality is a leading killer of koi. Good, lean water is the first step in keeping koi healthy. Adequate water temperature is critical to fish health and is an easy parameter to control. Koi thrive at tem- peratures around 20°C (68°F) but can be kept between 5°C and 30°C (41°F and 86°F), depending on the geo- graphic location and time of year. Onygen Oxygen is the most important element dissolved in water. Koi generally require between 5 and 10 parts per million (ppm) dissolved oxygen to sur- vive. Hypoxia is more commonly a problem in outdoor ponds during the warm summer months. During the day- light hours, plants and algae in the pond undergo photosynthesis and pro- vide oxygen for the pond. Most plants utilize oxygen at night, making it unavailable to the fish. A pond that is heavily planted, shallow, and warm can become hypoxic, and the fish will be negatively affected. If the clinician sus- pects an oxygen problem, the water should be tested at dawn when dis- solved oxygen levels are at their lowest. pH Levels ‘The actual pH value is not as impor- tant as its relationship to other water [o' iS S 2 = 2 = E x a =& Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A) 1998 TABLE 1 IMPORTANT QUESTIONS FOR THE KOI CLIENT How long have you been keeping koi? ‘What are the problems with the fish today? When did you first notice these problems? How long have you owned the sick koi and where were they obtained/purchaced? Are there other fish in the same tank or pond with the sick fish, and if so, how ate they? ML Whats the size (volume) of the pond and how is it heated, fitered, and aerated? Do you have a water test kt, and if so, how often do you test the water? What are your most current What and how often do you feed your fi Have the fish already been treated? i so, by ‘medications? Is there a pot atthe fish were exposed to some type of toxin? chemistry parameters. Ammonia is much less toxic to fish when the pH is more acidic. The ideal pH level of a pond ranges between 6.5 and 75. Koi can tolerate a wide range of pH values as long as the changes are gradual. Abrupt changes must be avoided. Established ponds (ie, those that do not undergo water changes) may become acidic, due to a build-up of organic acids. Nitrfying bacteria in a biological filter usually do not break down ammonia efficiently at pH levels below 5.0. Routine water changes of 10% every 10 to 14 days usu- ally prevent this problem. Very soft water with a low total alkalinity (buffering capacity) has difficulty main- taining a stable pH. Dolomite or crushed coral may be ‘added to the filter to solve this problem. Other pH-reg- Ulating compounds are readily available at most pet stores and garden centers that specialize in ornamental ponds. Ammonia In water, ammonia occurs in the toxic un-ionized form and the relatively nontoxic ionized form. The total ammonia concentration is a measurement of both types of ammonia, As the pH increases, ammonia becomes more unionized and hence more toxic. An ‘ammonia reading of 1.0 ppm at a pH of 8.5 is much more serious than the same amount of ammonia in water with a pH of 6.5. In cases of high ammonia (over 1.0 ppm), a 30% to 50% water change with dechlori- nated water should be performed as soon as possible. ANTIMICROBIAL THERAPY IN EXOTICS Figure 1—This took kot was likely in pair ofthe wound shown LAs rupted pattern with 4-0 absorbable suture was use. This emergency procedure should be repeated every 12 to 24 hours and will “buy some time” while the cause of the problem is determined. Pond overpopulating (with fish), overfeeding, and inadequate filtration are the most common causes of elevated pond ammonia levels. Nitrite Nitrite isan intermediate compound in the nitrogen cycle and is converted to nitrate by a healthy biological filter. Nitrite levels above 0.5 ppm should be considered serious. AS in terrestrial animals, nitrite causes the for- mation of methemoglobin in the blood and results in respiratory compromise. High nitrite levels in the pond can be treated effectively with 1.0 parts per thousand (pt) of sodium chloride, since nitrite ions must com- pete with chloride ions for uptake by the gill epithelium, Daily 30% to 50% water changes should help the fish Until the primary cause can be determined, An alterna- tive isto simply move the fish to a clean system.KOI MEDICINE AND MANAGEMENT TABLE 2 MANUFACTURERS OF WATER QUALITY TEST KITS Chestertown, MD 21260 301-778-3100 1 Orion Research, inc. {840 Memorial Drive Cambridge, MA 02139 617-264-5400 Chlorine and Chloramine Chlorine and/or chloramine are added to most municipal drinking water supplies as a means of sterik ization. Chlorine is deadly to pet fish because it causes acute necrosis of gill epithelial tissue. The amount of chlorine in tap water is usually between 0.5 and 2.0 ppm. Most pet stores stock commercially prepared compounds that neutralize chlorine. Chloramine is simply chlorine combined with ammonia. Chlorine neutralizers remove the chlorine but not the ammonia. A properly functioning biological or chemical fiter will remove the ammonia, which usually measures between 0.5 and 1.0 ppm. Biopsy and Necropsy Procedures ‘Once the history has been taken and the water test- ed, biopsy and/or necropsy procedures may be neces- sary. As a rule, koi are strong, fractious animals that usually require sedation before attempting biopsy pro- cedures. One of the most widely used anesthetic agents is tricaine methanesulfonate or MS-222 (Finquel*, Argent). Concentrations of 150 to 200 mg/L usually anesthetize a koi in 3 to 5 minutes, Preparing an MS- 222 stock solution of 10 g/L is recommended for accu- rate dilutions.’ A practical altemative to MS-222 is clove oil, which is available as an over-the-counter prepara- tion at most pharmacies. Clove oil, also known as eugenol, is distilled from the clove tree (Eugenia aro- matica). Eugenol is not completely soluble in water and should be diluted with ethanol at a clove oil:ethanol ratio of 1:10 to yield a working stock solution of 100 Figure 3—An anesthetized sanke koi boing moved on a moist sur= sical towel Figure 4—A large syringe filled with 200 mg/L of MS~222 is ‘used to maintain anesthesia while treating this ko mg/ml, since each milliliter of clove oil contains approx- imately 1g of drug. Concentrations between 40 and 120. mg/L are effective in freshwater and marine species, and results are comparable to MS-222, except that recovery may be prolonged.” The anesthetized koi should be placed on a soft, moist substrate such as a wet towel or foam pad (Figure 3). The fish can be maintained in this manner for 10 or 15 minutes by using a large syringe filled with anesthetic to irrigate the gills (Figure 4). Antemortem biopsy samples can be obtained with a sterile scalpel blade, scissors, and forceps (Figure 5). Suspect areas of ‘skin and fins can be scraped or removed and placed on 2 glass slide containing 2 drop of water. Once a cover- slip has been applied, the sample can be examined Under the microscope for the presence of pathogens. A small gil biopsy usually can be safely taken by remov- ing a few millimeters of gill lamellae from a single gill arch (Figure 6). Other diagnostic procedures include radiography* (Figure 7), ultrasonography, and blood collection (Figure 8); fine-needle aspiration can be per- formed while the fish is sedated. Abdominal surgery8 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998 ANTIMICROBIAL THERAPY IN EXOTICS Figure 7—A portable r Figure 6—A gill biopsy from an ai culun deflected with forceps, several ie biopsied directly on a scopic evaluat n be placed (Figure 9) and other protonged procedures may require the use of a recirculating anesthesia machine, which can be readily constructed using a submersible pump, plastic tubing, and glass or plastic reservoirs:+® ‘Treatment of Common Pathogens Bacterial Disease Most bacterial pathogens of koi are gram-negative rods and include such genera as Aeromonas and Pseudomonas. Flexibacter columnaris has also been identified as a lethal pathogen in koi ponds. Bacterial infections can be severe, and lethal bacteremias and septicemias are not uncommon. Antemortem blood cultures can be diagnostic, and if a necropsy is per- formed, renal tissue should be sampled for culture and sensitviys” Once a diagnosis of bacterial disease has been made or is at least suspected, a treatment plan should be for- mulated. Larger koi may be injected intraperitoneally or ure 8—Blood col d kok. The caudal blood sample from a ko intramuscularly with antibiotics that are effective against gram-negative pathogens (Table 3). Once cul- ture and sensitivity results have been obtained, the antibiotic regimen may be altered. ‘An altemative to injectable antibiotic therapy is uti- liging the oral route. Antibiotics may be mixed into a gelatinized food (Table 4) or given as a bolus via a gas- tic tube if the fish is refusing food. Koi are easy to force- feed since there is no risk of aspiration. A flexible, blunt tube such as a ted rubber catheter can be used to administer a faitly viscous gruel. Commercial flake or pelleted food can be mixed with small amounts of water to formulate the gruel, Because koi do not have a true stomach, special care should be taken when passing the gastric tube to avoid perforation of the gas- trointestinal lining. The clinician will benefit by be familiar with the general internal anatomy of the koi patient A third and less desirable approach to chemothera- py is to administer the treatment as a bath. Antibiotics and other compounds can be added directly to theKOI MEDICINE AND MANAGEMENT AL Figure 9A Figure 9—(A) A show k of an abdominal mas. Note the cear plastic separate the pel exposure, (C) This large undifferentiated sarcoma was suc ove, and the patient recovered. Total ime of anesthesa was te. water. This type of treatment is more appropriate for ectoparasite infections. Fish treated in this manner should be removed from the pond and placed in a hos- pital tank or pool (Figure 10). The treatment tank should be well aerated, and any carbon filtration should be discontinued. Table 3 contains doses and duration of treatment for a number of compounds. Fungal and Protozoa! Diseases Fungal diseases are usually external and are most always secondary to a break in the integrity of the epi- dermis and associated mucus coating, The most com- mon fungal pathogen is the water mold Saprolegnia. Fungal hyphae and spores can be ‘observed in a skin or fin biopsy sample under the microscope. If the infection is rot severe, many fish heal with sup- portive care. The fungal colony can be gently removed with a cotton swab, and the underlying wound may be treated topically with a disinfectant or antibiotic cream, ‘An overwhelming protozoal disease can constitute an emergency situation for a koi pond. Some protozoans such as Ichthyophthirius ("ch") have an encysted stage that is resistant to chemotherapeutic treatment (Figure 11). When faced with a protozoal out- break, the clinician must look for a source. Most commonly this source is the addition of an unquarantined ani- aterm cert ietes usually external Putra tig EMR ose tray ORM mait integrity of the igure 9C mal to the pond or the presence of a stressor, such as ‘overcrowding or poor water quality. Several antiproto- zoal compounds appear in Table 3. ‘Adding salt to the water in the proper quantities kill some protozoans and can help reduce stress on koi by decreasing the osmotic gradient. Since freshwater fish are hyperosmotic to their environment, water tends to "leak" into them. The kidneys and gills remove this excess water, but debilitat- ed fish have a problem if their normal water-removing mechanisms are work- ing poorly. Koi can tolerate between 0.1% and 0.5% salt in their water, which is about 1 to 5 g of salt per liter of water. (Artificial sea salt is best, although water softener salt is ade- quate.) An adequate salt level for the koi patient is approximately 1 pound of salt per 100 gallons of water, which equals 1.2 ppt or 0.12%. This amount can be doubled to 2 pounds of salt per 100 gallons of pond water to treat cer- tain ectoparasitic diseases.10 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3(A}, 1998 ANTIMICROBIAL THERAPY IN EXOTICS TABLE 3 MEDICAL CONDITIONS OF KOI AND TREATMENTS Condition Treatment ‘Hypoxia : ‘Common when fish have been inappropriately transported to clinic. Place affected fish in plastic bag containing « volume of water and fill rest of bag with 100% oxygen from anes- ‘thesia machine, Close beg tightly with rubber band or surgical tape, Keep fish in bag until ithas resumed normal swimming and respiratory behavior, t jamental' Fish) Elevated ammonia, nitite, Water changes. Examine filtration, biological load, and feeding practices. Measure pH to or nitrate help determine the tosicty ofthe total ammonia in the aquarium or pond. Og ‘Abnormal pH Gradual water changes to bring pH back into normal range. Measure total alkalinity (butfering capacity). IF ow (below S0 ppm), add crushed coral or dolomite to the system to increase buffering capacity. CChlorine/Chloramine toxicity Water should be immediately tated with a dechlorinating agent, or the fish should be emoved to a pool, bucket, or cooler containing clean, dechlorinated water Chlorine caus: es gill necrosis, resulting in decreased respiratory surface area. Use ice packs in water to lower temperature, which will increase amount of dissolved onygen in the water. The ‘water temperature for koi and goldfish may be loweted to 60'F. In addition, an oxygen bottle may be used to bubble 1003 oxygen into the water to help increase dissolved oxy gen levels Artificial sea salt (1 to 2 g/t of water) should algo be added to treatment tank. Dexamethasone at a dose of 2 mg/kg q24h IP o IV for 3 days may also increase chance ‘of survival. This treatment regimen may be necessary for more than 3 days, depending on the severity ofthe toxic, Topical bacterial disease Apply Panolog* Cream Veterinary (Solvay) or Silvadene® Cream 19% (Hoechst Marion Roussel) directly to wound qi2h. Allow affected area to remain out of water for 30 to 60. seconds while medication is absorbed. ills should remain submerged. Parenteral antibi- ‘tic therapy may be warranted (see below), Systemic bacterial disease _Enrofloxacin at a dose of 5 mg/kg IM or IP q48h for 15 days, 5 mg/kg PO for 10 to 14 days, oF 0.195 in food and fed to fish for 10 to 14 days; 2.5 mg/L as a5 hour bath, repeat. ed q2ah for 5 to 7 days, and a 50% to 75% water change between treatments ‘Timethoprim-sulfamethoxazole at 2 dose of 30 mg/kg IM or IP q24h for 7 to 10 days, 30 mg/kg PO q24h for 10 to 14 days, ot 0.294 in food and fed to fish for 10 to 14 days Culture and sensitivity tesuts may indicate a more appropriate antibiotic R | Protozoa disease Fish with ectoparasic protozoans must be treated witha dip or bath. Most koi and gold a) fish will tolerate a 4 to 5 minute dip in full strength (30 to 35 g of salt/L) seawater. Aerate . well and monitor very closely ‘ ‘ . Formaldehyde at 2 dose of 20 to 25 mg/L for 12 to 24 hours, followed by a 50% water : change, Encysted parasites like “Ich” will require several treatments. Always change water between treatments, Metronidazole as a bath treatment kills some external flagellates. Use a dose of 400 mg/L q24h for 3 consecutive days, and change water between treatments, For internal fa sgellates use in food at 0.2% (200 mg/100 g of food) and feed for 10 days. Tiematode disease Ectoparasitic monogenean: n be serious. Found on skin and gills Praziquantel at a dose of 5 to 10 mg/L as a 3 to 6 hour bath, Repeat in 7 days. Remove fish to treatment tank if possible and aerate water well. May not kil all species of mono. geneans. This treatment wil kill most internal cestodes, Seawater dips may be effective against some parasites. See protozoal protocol above. ‘Acetic acid at a dose of 2 mi of glacial acetic acid/L of Sate for goldfish and koi, but test one fish fist (biotest 30 to od dip.KOI MEDICINE AND MANAGEMENT u TABLE 3 (continued) nbendazole combined Vito 2 days ‘Levamisole at a dose of 20 mg/l. as a bath for 12 to 24 hours, Prariquantel bath treatment (see trematode protocol above) oF at a dose of 5 mg/ke/ish PO in food and repeat in 14 to 21 days; 5 mg/kg IP and repeat in 14 to 21 days. Injectable treatment may also work for intemal digenean trematodes. Crustacean disease ‘Common ectoparasites of goldfish and koi (fish louse, anchor worm). More common in a ‘ponds than in aquarium. Dimethyl phosphonate at 0.5 mg/l, three treatments 10 days apart, and 20% to 30% water change 24 to 48 hours following treatment. Use extreme caution when handling these organophosphate compounds. The liquid form commonly used to kill cattle grubs is easy to handle, measure, and dispense. ‘Acetic acid dip procedure described above for tematodes is effective in treating new arrivals to a pond for crustacean parasites. Always test with one fish first, if possible. Diflubenzuron (chitin synthesis inhibitor) can be used at a concentration of 0.1. mg/L. ‘his is an environmental toxin in that it will kil native arthropods. Use may be resticted. Consult EPA guidelines TABLE 4 GELATINIZED FOOD RECIPE* 1M Weigh 125 g of fake or pelleted fish food and place into a blender. Add 250 ml of clean water and mix well Add one can of sardines (with of to this slurry and haifa jar of baby food or some fresh spinach. Blend well ‘Add any medications at this time. Ina separate pan, heat 250 ml of dean water to near boiling. Add three packets (7 g each) of gelatin and stir well. low the gelatin ‘minture to cool for about 10 minutes and then add the food/medication mixture. ia firmer food is desired, more gelatin can be added. Wm Stirthe mixture wel and pour into ie cube trays or small bags to make feeding easier. Place in refrigerator. 1m The food should be allowed to set for several hours and can be fed at that time. ‘Atleast one commer feed company (Mazur) has 3 Figure 1—Mierscopc view of fin tissue from a koi infested with powdered geltinited aquatic cit lehthyophehirius muleifilis (ch). Note the characteristic ces cent-shaped nucleus of the mature trophoms. Numerous inmature Iie sages are aso vide. Figure 10—A fine-mesbed koi “sock” net is used to safely rans 4Jet-« patient from a large pond t0 an isolation treament poo!i lamental' Fish i in Educ Pract Vet Vol. 20, No. 3(A), 1998 Figure 12—Microscopic view of a single primary gill lamella with ‘numerous monogenean parasites of the genus Dactylogyrus. Helminths The helminths are 2 broad group of parasites that includes the skin and gill flukes (monogeneans), ces- todes, nematodes, trematodes, and crustacean para~ sites. Koi are most commonly affected by monogenean trematodes and crustacean ectoparasites (Figure 12). Gross observation for the presence of fish lice (Argulus sp.) or anchor worms (Laernea sp.) along with skin and gill biopsies, can aid in the diagnosis of ectopara- sitic problems. Antemortem fecal examination or a thor- ough necropsy is used to diagnose an internal helminth problem. Acknowledgments This work was pattially supported by the Department of Companion Animal and Special Species Medicine at the North Carolina State University College ‘of Veterinary Medicine. The author would like to thank the North Carolina State University College of Veterinary Medicine Biomedical Communications Department for Photographic assistance and Debbie Whitt-Smith, Jori Miller, Betty Akiba, and Drs. Robert Bakal and Gary Spodnick for their contributions. Additional thanks goes to Scott Purdin of Purdin Koi Farm, Glynn, Louisiana, for providing the cover photograph. ANTIMICROBIAL THERAPY IN EXOTIC References 1. Stoskopf MK; Anesthesia of pet fishes, in Bonagura 0 (ed) Kik’s Current Veterinary Therapy XI. Philadelphia, WS Saunders, 1995, pp 1365-1369. 2. Anderson WG, McKinley RS, Colavecchia Mi The use of clove oil as an anesthetic for rainbow trout and its effects ‘on swimming performance. North Am J Fish Manage 17 301-307, 1997 3. Love NE, Lewbart GA: Pet fish radiography: Technique and case history reports. Vet Radiol Ultrasound 38(1):24-2, 1997 4. Lewbart GA, Stone EA, Love NE: Pneumocystectomy in a Midas cichlid. JAVA 207(3):319-321, 1995, 5. Harms CA, Bakal RS, Khoo LH, et al: Microsurgical excision ‘of an abdominal mass in a gourami JAVMA 207(9): 1215-1217, 1995. 6. deGuzman E, Shotts EB: Bacterial culture and evaluation of diseases of ish, Vet Clin North Am Small Anim Pract 18(2):565-374, 1988, 7 Shotts £8, Bullock Gi: Rapid diagnostic approach in the identification of gram negative bacterial diseases of fish. Fish Pathe 102:187-190, 1976. Suggested Readings Blasiola GCI: Koi: A Complete Owners Manual. Hauppauge, NY, Barrons, 1995 Gratzek 1B: Aquariology: The Science of Fish Health ‘Management. Mortis Plains, NL, Tetra Press, 1992. Johnson EJ: Koi Health and Disease. Marietta, GA, Johnson Veterinary Senices, 1997 Lewbart GA: Emergency pet fish medicine, in Bonagura JD (ed): Kirk's Current Veterinary Therapy i, Philadelphia, WB Saunders, 1995, pp 1369-1374, Noga : Fish Disease: Diagnosis and Treatment. St Louis, Mosby, 1996. Stoskopf NK: Fish Medicine. Philadelphia, WB Saunders, 1993. Periodicals ‘Freshwater and Marine Aquarium, P.O. Box 47, Sierra Macre, A 91025, 610-355-6415, Koi Corp Megazine, Freestyle Publications Ltd, Alexander House, Ling Road, Tower Park, Poole, Dorset, BHI2 4NZ, England oi Health Quarterly, Futura Printing Limited, The Koi Health Group, 3 Sunnydale Avenue, Brighton, East Sussex, BNI NR, England. Koi USA, Associated Koi Clibs of America, Midway City, CA 92655. Tropical Fish Hobbyist Magarine, TH. Pu ‘NJ, 908-985-8400, tions, Neptune,‘Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3), 1998 Bacterial Infections and Antibiotic Therapy in Small Mammals Karen L. Rosenthal, MS, DVM Diplomate ABVP (Avian Practice) Antech Diagnostics Farmingdale, NY acterial infections in small mammals are best Ben by grouping animals into (1) ferets and (2) rabbits and rodents, Ferrets react to bacterial infections as do dogs and cats. Rabbits and rodents are ‘more likely to form walled-off abscesses filled with caseat- ed, purulent material. Both gram-positive and gram-nega~ tive bacteria cause infection in small mammals. Most infections are due to aerobic bacteria, but anaerobes can also cause disease. Rather than describing each species of bacteria that commonly infect small mammals, its more illustrative to examine small mammals and their organ systems and how each system is affected by and reacts to bacterial infection. Bacterial Infections Ferrets Primary bacterial infections in pet ferrets are not common. If present, ‘these infections are secondary events to a more severe primary disease, usu- ally viral, sometimes trauma. Still, it is imperative to consider bacterial infec- tions in a differential list of ferret dis- eases, as untreated disease can cause morbidity and mortality. oem sta Retacoaclatnccas(iny are expected to have distinct hematology profile. Ferrets with bacteria infections are expected to have distinct alterations in their hematology profile. A rise in the white blood cell count above 8000, with neu- trophils as the predominant cells, is noted in bacterial infections. In acute, severe infections, band cells are expected. As the bacterial disease becomes chronic, an increase in monocytes is seen. Changes in the bio- chemistry profile depend on the degree of inflamma- tion and the organs affected. Bacterial infections in ferrets should be diagnosed primarily by history, clinical signs, cultures, and response to treatment. Since bacterial infections in fer- rets are usually a rare occurrence, this should be lower on a list of differential diagnoses. Treatment of bacteri- al infections in ferrets depends on the system involved and the severity of disease. Urinary Tract ‘The ferret urinary tract is an uncommon area for bac- terial infection, Bacterial nephritis is rarely seen. Bacte- Fial cystitis, although uncommon, is usually noted in n with urolithiasis. An infrequent complication of adrenal gland disease in male ferrets is bacterial prostatitis. Signs of prostatic disease include dysuria, ‘mucoid urine, and hematuria. Not all prostatic disease is complicated with a bacterial infection. Bacterial pros- tatitis is diagnosed by exploratory laparotomy and is characterized by multiple cystic areas of the prostate filed with purulent material. The cystic areas of the prostate should be cultured during exploratory laparot- ‘omy. Frequently, the bacteria found in the prostate have resistant patterns to antibiotics. Pseudomonas is com- monly isolated. The cystic nature of this disease and the resistant bacteria make treatment difficult. Cystic bacte- rial prostatitis should be treated by removing the affect- ed adrenal glands, draining the cysts during surgery, and administering appropriate antibiotics. it is not uncom- mon to “marsupialize" the prostate to the body wall because the prostatic cysts persist after surgery. Bacterial pro- statitis can remain even when there is ro longer adrenal gland androgen influ- cence over the prostate. Ferrets with pro- longed bacterial prostatitis are hyper- thermic, lethargic, and can become septic. asso alterations in their Respiratory Tract The ferret respiratory tract is an uncommon area for bacterial infection: 14 Supp! Compend Cor SAI, 1998 Figure |—Feree with bacterial respiratory infection (igure 1). Both canine distemper virus (CDV) and influenza virus can be complicated by secondary bacterial respiratory disease. Canine distemper virus infection can lead to bacterial pneumonia, Realistically, bacterial peu- monia secondary to CDV infection is rarely treated, as CDV itself is fatal in ferrets. Bacterial respiratory disease secondary to influenza virus infection is rare in immune- competent ferrets. Upper respiratory tract bacterial infec- tion is very uncommon; however if present, signs include sneezing and nasal discharge. Ferrets are usually lethar- gic and have a decreased appetite. Diagnosis of bacterial Upper respiratory disease is based on response to treat- ‘ment. Culture of the nasal discharge is difficult to inter- pret because itis dificult to determine normal bacterial inhabitants versus disease-causing bacteria. Lower respiratory tract bacterial infections are almost always secondary to vial disease. Bacterial pneumonia «an also occur secondary to aspiration from megaesoph- ‘agus. Ferrets with bacterial pneumonia cough and are lethargic and hyperthermic. With advanced bacterial pneumonia, ferrets are dyspneic with cyanotic mucous membranes. Diagnosis of bacterial pneumonia is based con dinical signs and thoracic radiographs (Figure 2). Cultures obtained from a lung wash are feasible but rarely done in ferrets. Ferrets with bacterial pneumonia general- ly require hospitalization. Antibiotics should be given and supportive care provided to ferrets with pneumonia. Primary causes of bacterial pneumonia might indude Puncture wounds and inhalation of plant material Skin Primary bacterial dermatitis is rare in ferrets. Causes of breakage of the skin integrity that allow bacterial der- mmatitis to occur include scratching and bite wounds, It is important to realize that skin tumors are common in. ferrets. A skin tumor, especially a mast cell tumor, ANTIMICROBIAL THERAPY IN EXOTICS Aig ire 2—Thoracic radiograph of a ferret with bacterial paeumenia should not be mistaken for bacterial dermatitis. Unlike skin tumors, bacterial dermatitis is usually intensely pru- fitic with @ purulent character. Bacterial dermatitis is diagnosed by cytology or biopsy and culture of the affected area. Treatment depends on the depth of infec- tion. Superficial infections should be treated with topi- cal antibiotics. Deep infections require debridement and systemic antibiotics and flushes. Primary problems should always be ruled out if the condition is not caused by trauma Gastrointestinal Tract Ferrets commonly have gastrointestinal disease; bac- terial infections likely account for some of these prob- lems. The incidence of bacterial gastroenteritis is unknown. Possibly, the most common infection is caused by Helicobacter mustelea. Helicobacter is likely Present in all ferrets. It causes ulceration of the gas trointestinal mucosa and is most commonly associated with gastric ulcers. An active Helicobacter infection is characterized by lethargy, vomiting, anorexia, melena, and weight loss. Definitive diagnosis of Helicobacter disease is best made based on clinical signs coupled with gastric biopsy and response to treatment.BACTERIAL INFECTIONS AND ANTIBIOTIC THERAPY IN SMALL MAMMALS Treatment includes amoxicillin, metronidazole, and Pepto-Bismol” (Procter & Gamble). Other gastrointesti- nal bacterial infections appear to be uncommon in fer- rets. Diarrhea, lethargy, and hyperthermia are signs of a primary bacterial gastroenteritis. A fecal culture can be difficult to interpret as to disease-causing organism(s) versus incidentals. Response to antibiotic treatment and supportive care may assist in the diagnosis of gastroen- teritis. In practical terms, noninfectious etiologies are more likely a cause of diarthea in ferrets and include foreign bodies, trichobezoars, and neoplasia. Rarely does a foreign body puncture the gastrointestinal tract and lead to bacterial peritonitis This is a severe disease that should be treated aggressively. Oral Cavity Although pet ferrets commonly have dental tartar, rarely is bacterial periodontitis associated with this problem. However, dental tartar can lead to periodontal disease accompanied by bacterial infection of the oral mucosa. Swollen, reddened, and bleeding oral mucosa are signs of bacterial infection. Treatment includes a dentistry examination, antibiotics, and improvement of dental hygiene. Ear Canal Ferrets commonly have ceruminous discharge in their ears. Rarely does this progress to bacterial otitis, Occasionally, an ear mite infestation is present but rarely leads to a bacterial otitis. Subsequently there is ttle need to use antibacterial otic preparations in ferrets. Typically removing the discharge with a swab is all that is required. Rabbits Unlike in ferrets, bacterial infections are common in rabbits and incite an inflammatory reaction characterized by caseated pus and walled-off abscesses. These two attributes of rabbit bacterial infections make antibiotic treatment ‘alone usually unsuccessful. This, cou- pled with the lack of safe antibiotics in rabbits, only makes treatment of bacte- rial infections in this species much more difficult Clinical pathology changes in rabbits due to bacterial infections are not similar to those found in other mammals. Unlike in ferrets, Tevocoar let are common in rabbits and incite Pr ert etc a reaction characterized by PeeCee tee titte walled-off Plena Figure 3—Robbit with severe respiratory infection (‘snes’). Rabbits with bacterial infections may not show an increase in total white blood cell count. Instead, the rela- tive heterophil count may increase and account for more than 90% of the total white blood cell count. Nucleated red blood cells may also be seen in rabbits with acute bacterial infections. Blood chemistry changes may reflect affected organs. Signs of bacterial disease also reflect the body system affected. More general signs of disease include hyperthermia, lethargy, and anorexia. Possibly incorrectly, much bacterial disease in rabbits is attributed to Pasteurella multocida. Tests other than cultures are used to assess Pasteurella infection in rabbits. Titers of antibodies to Pasteurella must be interpreted as such. ‘They are only a measurement of exposure, not infection, ‘which may make them less useful than a culture. Respiratory Tract Possibly the most common area for bacterial infections in rabbits is the re- spiratory tract. Both the lower and upper respiratory tract frequently devel- op infections. Upper respiratory tract infection is possibly the most common reason rabbits are presented to the vet- erinarian. Signs of upper respiratory dis- cease include nasal discharge, sneezing, and difficulty in breathing. The lay term for upper respiratory disease in rabbits is “snutfles” (Figure 3). Bacterial pneumonia, both clinical and subclinical, is common in pet rab- bits. Bacterial pneumonia is character- ized by dyspnea, tachypnea, and hyper- thermia. Rabbits do not appear to cough with this disease. Diagnosis of respiratory bacterial disease in rabbits is rater) CEUTA 1)16 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3(A), 1998 Figure 4—Radiograph of a rabbit with bacterial resiraory dis= ease, Note the consolidated lang mas. not difficult. It is based on signs, history, and radio- sraphs (Figure 4). Ideally, diagnosis is further based on culture and sensitivity results. However, most respirato- 'y bacterial infections in rabbits are in anatomic places inaccessible to culture techniques. A rabbit with bacte- fial pneumonia is a poor candidate to undergo the stress of a tracheal wash. Pasteurella multocida is com- monly implicated as the cause of respiratory disease in rabbits, but many species of bacteria are likely the ‘cause of this problem. Treatment of respiratory disease is not always successful, Rabbits with upper respiratory infections are more likely to respond to antibiotic treat- ‘ment than those with lower respiratory tract infections, and recurrence is common after a period of time. This is due to the abscessed nature of bac- terial infections in rabbits and the lack of penetration of the diseased area. Ear Canal Bacterial infections of the respiratory tract likely act as the nidus for which bacteria spread to other areas of the body, either through septicemia or local invasion. Bacterial respiratory infection leading to local invasion of the ear canal may be the cause of otitis. Common areas of spreading include the inner and middle ear. Bacterial oti tis is common in rabbits. Aural dis- charge and inflammation along with hhead tit are the most common signs of bacterial otitis. It is possible that aural bacterial infections may seed from the ‘ear and follow the cranial nerves into the central nervous system. Peetu art crusty Oat becyutc\ad [ictal coher tage) the nidus for Dose Gaconud tg areas of the body, either through septicemia or local pine oie ANTIMICROBIAL THERAPY IN EXOTICS are also common in rab- bits (Figure 5). In pet rabbits, common areas of infec- tion include the conjunctiva, cornea, nasolacrimal duct, ‘and retrobulbar abscess, Presentations of ocular bacte- ‘ial infection include blepharospasm, excessive tearing, discharge, reddening, and swelling of the ocular tissues. Intraocular infections are also common and are charac- terized by hypopyon and even abscesses that can be attached to intraocular tissue. Diagnosis is based on physical examination, corneal staining, and flushing of the nasolacrimal duct. Retrobulbar abscess diagnosis is more complicated and may require the use of radio: sraphs, ultrasound, and computed tomography. Finally, diagnosis is made by biopsy and removal of the abscess. Urinary Tract The rabbit urinary tract is another fre- quent site of bacterial infections, probably an occasional cause of renal disease in rabbits. Bacterial cystitis is Beaters?) common and is believed to be one of the predisposing causes for urolithia in rabbits. Signs of bacterial cystitis include stranguria, dysutia, hematuria, anorexia, and lethargy. Diagnosis of bacterial infections of the urinary tract in rabbits should be based on urinaly- sis, urine culture or culture of the blad- der wall, and response to treatment. When urolithiasis is present, some believe it is best to assume that an Underlying bacterial infection is alsoBACTERIAL INFECTIONS AND ANTIBIOTIC THERAPY IN SMALL MAMMALS Figure 6—Rabbic with abdominal urine scald and resulting der nats. present, and part of ur treatment should include culture for bacterial antibiotics. Skin Bacterial dermatitis in rabbits, characterized by sub- cutaneous abscess formation, is common. Skin abscesses are typically encapsulated. It is common for these abscess to spontaneously erupt. Likely, the bacte- tial etiology of these spontaneous abscesses is a bacte- rial nidus of infection located elsewhere in the body. Superficial bacterial dermatitis is usually secondary to other conditions, such as perineal ulceration due to urine scald (Figure 6). Diagnosis of bacterial dermatitis is based on cytology, biopsy, and culture. Although it may seem unnecessary to biopsy these lesions, skin abscesses are not always just bacterial infections. Cancer can appear as skin abscesses. Skin abscesses should be treated with an antibiotic and the abscess removed. Reproductive Tract Bacterial infection of the reproductive tract in rabbits is uncommon, In males, bacterial infection of the scro tal area and surrounding tissue as a consequence of Figure 7—Radiograph of a jaw abscess in a rabbit. improper surgical technique occurs more commonly in rabbits than in other species. Infection of the female reproductive tract is uncommon. Infection of the ovatio- hysterectomy surgical site occurs more commonly in rabbits than in other species. Gastrointestinal Tract The incidence of bacterial enteritis is unknown in rabbits. Diarrhea is common in rabbits, but bacteria as 2 primary cause is unlikely in most instances. Diet and inappropriate use of antibiotics are likely causes. Oral Cavity Bacterial osteomyelitis is most commonly observed in the mandible of the rabbit and is usually caused by dissemination of bacteria from other areas of the body. This infection appears as a firm swelling on the jaw of a rabbit, with or without superficial ulceration. Radio- graphs should be used to determine the extent of the lesion (Figure 7). Most mandibular abscesses are non- resectable and therefore carry a poor prognosis. Rodents Bacterial infections in particular species of pet rodents are not uncommon. A distinction is made between pet rodents and laboratory animals. Pet rodents are usually kept as a solitary pet or in a small group. As a result, they are less susceptible to bacterial infections that may spread easily from animal to animal ‘as opposed to rodents kept in large groups. Therefore, when developing a differential diagnosis for a rodent bacterial infection, signalment is an important factor. Respiratory Tract Bacterial infections in guinea pigs, rats, and mice are commonly found in the respiratory tract (Figute 8)3 oc 3 3 is = Sinai 18 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1996 Figure 8—Thoracic radiograph of a guinea pig with pneumonia, However, itis likely that most bacterial respiratory dis- ease in rodents is secondary to primary viral infection Treatment of the bacterial infection is usually less than rewarding because elimination of the viral infection is ‘not possible. Treatment also includes improving poor husbandry conditions. Mycoplasma respiratory disease also occurs Skin Bacterial dermatitis, secondary to other coni can occur. Ectoparasites are the most common primary condition causing bacterial dermatitis. Treatment of bacterial dermatitis includes eliminating the ectoparasites, cleaning the environment, and use of antibiotics. ns, Gastrointestinal Tract Rodent bacterial enteritis occurs most commonly in hamsters. Most enteritis is characterized by diarrhea. In yung hamsters, this condition is called “wet tal" and the most common bacte- tial etiology is Lowsonia intracellular. Older hamsters with diarthea of bacte- tial origin may have Clostridium spp. as the etiology. Treatment of hamsters with bacterial enteritis includes husbandry improvements and supportive care. Antibiotic Therapy in Small Mammals Thousands of doses of antil are dispensed each year to treat small mammals because of owner pressure. Little do owners realize that small mam- ntibiotic therapy Pewee tented Rev Geert) Os Put myceretrve rtd need to have othe knowledge of the LC yam adits Petacortarv etic pharmacology of tm the antibiotic they are using. ANTIMICROBIAL THERAPY IN EXOTICS mal veterinarians are faced with a dilemma: the abuse of antibiotics benign in their actions in dogs and cats can make small mammals severely ill. Giving in to the demands of clients and dispensing antibiotics can lead to the death of a small mammal patient because often it is unnecessary treatment. Not one single dose of any antibiotic is approved for use in the small mammal receiving the medication. At present, no antibiotics are approved by the Food and Drug Administration (FDA) for small mammal pets classified as minor species. Most likely, owners of these animals do not realize that ‘the antibiotics are not approved for use in their pets Although this does not change the fact that antibiotics are important medications for small mammals, itis best that owners be informed of this information. ‘An important consequence of the lack of studies to ‘gain FDA approval is that there are few pharmacokinet- ic investigations of antibiotics in small mammals. Veterinarians do not have studies of antibiotics in small mammals that provide direction to either dose, length of treatment, of frequency of administration. There are no drug company brochures guiding veterinarians to the indications of certain antibiotic use in small mam- mals. Veterinarians who treat small mammals must rely largely on empiric data and anecdotal information when using antibiotics in these ani- ‘mals. It is therefore not surprising that antibiotic treatment failure occurs in these patients, as the very basics of ‘antibiotic administration are unknown, Antibiotic therapy is nonetheless a challenge in small mammals. Veteri- narians need to have extensive knowl- edge of the biology of the patient and the pharmacology of the antibiotic they are using, An appropriate antibiotic can potentially save the life of e small mam- ‘mal, but inappropriate use will kill a rabbit or a rodent. The principles of antibiotic use in dogs and cats apply similarly to small mammals. However, when discussing small mammals and antibiotics, it is important to make a distinction be- tween ferrets and other small mammals kept as pets (.e, rabbits and rodents). Ferrets react to antibiotics and infections. like dogs and cats. On the other hand, there are fewer safe antibiotics for use in rabbits and rodents than in dogs andBACTERIAL INFECTIONS AND ANTIBIOTIC THERAPY IN SMALL MAMMALS TABLE 1 QUESTIONS TO CONSIDER BEFORE BEGINNING EMPIRIC ANTIBIOTIC BUC RYN GR NES LURE IU esy that antibiotic? W's the antibiotic safe to use in rabbits and rodents? cats. For example, amoxicilin, a benign drug in most ani- mals, can cause a fatal enterotoxemia in rabbits and rodents. Ideally, before antibiotic administration, a cul- ture and minimum data base should be obtained and the antibiotic chosen based on those results. Empiric antibiotic treatment should be instituted if a culture can- not be obtained or before results are known. Whenever antibiotics are used empirically, four-quadrant coverage should be considered. To accomplish this, drugs that are effective against aerobic, anaerobic, gram-positive, and gram-negative organisms should be chosen. Questions to consider before beginning empiric antibiotic treat- ment in small mammals are found in Table 1. Identifying the Organ System Involved Before an anti chosen, itis important to identity the organ system involved. This can be challenging in rab- bits and rodents and may not be appar- ent ifthe site of infection is primary or secondary. For example, jaw abscesses in rabbits are common, yet very few jaw abscesses are caused by puncture ‘wounds to the face. Jaw abscesses are frequently due to organisms that travel from other sites. One must consider the location of the other sites and, there- fore, the other organ systems involved. ‘Treating a jaw abscess without recog- nizing that the condition is an isolated event will probably lead to antibiotic treatment failure. BBYarovutirtet mod Paicme erence bacterial diseas roe tearen tenure TeTTU EOP Pilar tcc ers Sn treatment length, Puy nuteaag Brits (en Acute or Chronic Disease? In rabbits and rodents, one must determine whether the bacterial disease is the result of an acute infection for an acute manifestation of @ chronic infection. For example, a pet rabbit exhibits signs of “snuffles” at 3 years of age. Is this because the rabbit recently devel- oped upper respiratory bacterial disease or because a chronic pasteurellosis infection is only now becoming apparent? Another example is a guinea pig that has been a pet for 1 year and suddenly develops bacterial pneumonia Is this because it recently developed lower respiratory disease or because a chronic vita infection is only now becoming apparent with secondary bacter- | pneumonia? Determination of acute or chronic bac- terial disease is imperative, as this dictates prognosis, treatment length, and choice of antibiotic. Most Likely Pathogen at Infection Site In rabbits, it is common to attribute all infections to Pasteurella multocida. Although many diseases can be traced to this organism, numerous species of bacteria are cultured routinely from rabbits. Before culture results are known, a Gram’s stain of the infected area should be obtained to potentially identify the organ- ism. Some selected bacterial species known to infect rabbits and rodents include pathogenic species of Staphylococcus, Streptococcus, Bordetella, Klebsiella, Proteus, Pseudomonas, Listeria, Actinomyces, and Actinobacillus. Use the Best Antibiotic The best antibiotic to use is based not ‘only on the spectrum of activity of the jotic but also on the safety of that antibiotic in rabbits and rodents. An antibiotic that has the least likelihood of inciting gastrointestinal disease is recommended (Table 2). Some of the drugs include the fluoro- quinolones, trimethoprim-sulfa, chlo- ramphenicol, aminoglycosides, and metronidazole. Antibiotics that are intermediate in their ability to incite gastrointestinal disease include par- enteral penicilin, oral or injectable cephalosporins, tetracycline, and ery- thromycin. Antibiotics that are highly likely to cause gastrointestinal disease include amoxi lin, clin- damycin, and lincomycin. These antibi- safer20 Supp! Compend Contin Educ Pract Vet Vol. 20, No. (A), 1998 ANTIMICROBIAL THERAPY IN EXOTICS TABLE 2 ANTIBIOTIC USE IN RABBITS AND RODENTS IN RELATION TO THE GASTROINTESTINAL TRACT Least Likely to Incluce Dysbiosis Chloramphenicol (generic) Fluoroquinolones (Bayt, Beyer) Metronidazole (Flagyl, Searle) ‘Timethoprim-sulfa (Bactrim™ Pediatric ‘Suspension, Roche) otics are most likely to cause dysbiosis of the gastroin- testinal tract. They suppress the normal gastrointestinal flora by allowing other flora to proliferate, which leads to deleterious changes. The abnormal flora changes the PH, which in turn increases volatile fatty acid produc- tion, thereby further suppressing the growth of normal bacteria. Eventually, enteritis develops and ultimately the production of toxins from Clostridium spiroforme {iota toxins) leads to enterotoxemia. Antibiotic-induced enteritis and enterotoxemia should be treated aggressively to save the patient, and the antibiotic should be discontinued. Some recom- mend the use of metronidazole at 20 mg/kg ql2h to decrease the amount of Clostridium. Intravenous or sub- cutaneous fluids should be given, as should nutritional supplementation with high-fiber foods. Some advocate using cholestyramine to prevent death from the iota tox- ins, This has been shown experimental- |y to work by theoretically binding bac- terial toxins at a suggested dose of 2 8/20 ml of water q24h by gavage. Amount of Antibiotic Needed at Site of Infection The amount of antibiotic needed at the infected site is difficult to determine in rabbits and rodents because of the formation of caseous pus and the walled-off abscesses that are impenetra- ble to many antibiotics. Clearly, abscess- es are best treated by combining antibi- ‘tic therapy with wound debridement ‘and daily flushing, which increase the chance of successful therapy. Intermediate in Ability to Induce Dysbiosis ‘Aminoglycosides (Amikacin C™, Phoenix) Cephalosporins (Anc Erythromycin (generic) Parenteral pencilin (Pen-G, Phoenix) Wm Tetracycine (genetic) The subcutaneous un icomo ge rivel Ce Prin ects (oue the most frequently used Rone meena) a _ administration in vo Most Likely to Induice Dysbiosis *, SmithKline Beecham) lm Amoxicillin (generic) 1m Ampicilin (generic) 1H Gindamycin (generic) Lincomyein (generic) Dose and Route of Administratio The dose and route of administration for most antibi- otics in rabbits and rodents are based on clinical expe- rience. Exatic animal formularies list dose ranges, dose frequency, treatment length, and methods of adminis- tration. in rabbits and rodents, the stress of administra- tion should be considered when determining the route. Combination antibiotic and steroid preparations should not be given or applied to rabbits or rodents. Antibiotic ‘administration in the drinking water rarely allows the drug to reach effective serum concentrations. if the drinking water develops an undesirable taste from the antibiotic, the patient may stop drinking and dehydrate. Antibiotic administration in small mammals includes the parenteral, enteral, and topical routes. Parenteral routes include intramuscular, subcutaneous, intraper- toneal, intravenous, or intraosseous routes. The intra- muscular route is rarely used for an extended period of time in small mam- mals because of their size. Their rela- Sy tively small muscle mass limits the ‘areas for multiple drug injections. The intravenous of intraosseous routes are reserved primatily for the most severe cases of bacterial disease, The subcuta- neous route of antibiotic administration is the most frequently used parenteral route of administration in small mam- ‘mals, The enteral route is used exten- sively, especially with antibiotics admin- istered at home. Antibiotics are given by syringe or in the food. It is difficult to administer antibiotics in pill form to most smallBACTERIAL INFECTIONS AND ANTIBIOTIC THERAPY IN SMALL MAMMALS. BU2.) Bae) COMMONLY USED ANTIBIOTICS IN SMALL MAMMALS’ ‘Aminoglycosides (Amikacin C%, Phoenii) WV q2ah Metronidazole (Flagyl, Searle) 20 mg/kg PO q12-24h mammals. Rabbits may take medication mixed in jams or jellies. The topical route of drug administration should be used for superficial infections in small mam- mals. This should be done cautiously, especially if the topical antibiotic ingredient has the potential to cause dysbiosis if ingested by the patient. Antibiotic Safety in Rabbits and Rodents Finally, it must be determined whether the chosen antibiotic is safe to use in rabbits and rodents, Not all rabbits or rodents develop gastrointestinal disease from the more dangerous a , and not all small mam- mals die from antibiotic-induced gastrointestinal dis- ease. However, the risk of disease can be greatly less- ened when the appropriate treatment is selected. Guidelines for antibiotic use are easier to follow in ferrets than in the other common small mammal patients. Ferrets, since they are carnivores, have a gas- {rointestinal system more similar to dogs and cats than to rabbits and rodents. Usually, antibiotics that are safe to use in dogs and cats are likewise safe in ferrets. No antibiotic pharmacokinetic studies have been per- formed in ferrets, so drug dose, treatment length, and frequency are based on clinical experience and extrap- lated from other species. n ferrets, the most appropri- ate antibiotic based on culture results can be used with- ut regard to serious gastrointestinal upset. Specific Antibiotics Used in Small Mammals ‘The ideal antibiotic to use in small mammals is eas- ‘Amikacin: 8-16 mg/kg IM oF Because of the isk of nephrotoxicity in small mammals tse with discretion; may be a poor choice for many rabbit end rodent infections because of poor penetration to abscessed areas Use for anaerobic infections ily administered, bactericidal, and does not cause gas- trointestinal disease. Common antibiotics used in small mammals (Table 3) are discussed below. Fluoroquinolones The most commonly used dass of drugs in small mammals are the fluoroquinolones. This antibiotic ‘group is safe, can be given orally, and is effective against Pasteurella and other serious gram-negative infections. Enrofloxacin, a veterinary quinolone with more docu- ‘mented use in small mammals than any other quinolone, is used at a dosage of 10 to 20 mg/kg IM, SC, or PO qi2h, Penicillin such as penicillin should be used with caution in rabbits and rodents. Oral penicilin is associ- ated with gastrointestinal disease in these species. Injectable penicilin is safer to use and is recommended at 40,000 to 80,000 U/kg IM. Trimethoprim-Sufa Drugs Trimethoprim-sulfa drugs are commonly used in small mammals and appear to be safe. These drugs can be given at 30 mg/kg PO ql2h. Caution is recom- mended in patients with urinary tract disease, ‘Aminoglycosides Because aminoglycosides are potentially nephrotox- ic in small mammals, this class of drugs should be used 2Loe £ a = 8 or 22. Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3(A) 1998 with discretion. Also, these antibiotics poorly penetrate abscessed areas and may be a poor choice for many rabbit and rodent infections. Amikacin can be used at a dose of 8 to 16 mg/kg IM or IV q2ah. Metronidazole Metronidazole is used for anaerobic infections at a dose of 20 mg/kg PO q12-24h. The incidence of anaer- bic infections in small mammals is unknown. Pulse Therapy ‘Anew concept in drug administration is called pulse therapy. This type of treatment involves once-a-day drug administration rather than multiple, daily dosing. Drags that are effective in pulse therapy have a “postantibiot- ic effect” these drugs are still effective even after their concentrations decrease. Also, drugs that are used for pulse therapy have their best effect at a high dose for a limited time. This is opposed to the classes of drugs that are more effective at a steady state. Penicilins are more ANTIMICROBIAL THERAPY IN EXOTICS effective at steady-state concentrations. Fluoroquino- ‘glycosides are more effective in pulse therapy. Pulse therapy is ideally suited for small mam- mals. Drug administration can be challenging and stressful to these patients. Once-a-day administration i therefore advantageous. For this reason, selection of a fluoroquinolone antibiotic in small mammals is a ratio- nal choice based on safety, spectrum of activity, and once-a-day administration ones and ar References |. Harkness J, Wagner JE (eds): The Biology and Medicine of Rabbits and Rodents, ed 4, Philadelphia, Lea & Febiger, 1995, 2. bilyer EV, Quesenbeny KE (eds): Ferrets, Rabbits, ond Rodents: Clinical Medicine and Surgery. Philadelphia, WA Saunders, 1997. 3. Brown SE, Rosenthal KL (eds): Self Assessment Colour Review of Small Mammals. London, Manson, 1997. 4, Allen DG, Pringle JK, Smith O: Handbook of Veterinary Drugs. Philadelphia, 38 Lippincott, 1993. 5. Carpenter JW, Mashima’TY, Rupiper Dl: Exotic Animal Formulary. Manbattan, KS, Greystone Publications, 1996.Supp! Compend Contin Educ Pract Vet Vol. 20, No. 5(A) 1998 Common Bacterial Disease and Antibiotic Therapy in Reptiles Douglas R. Mader, MS, DVM. Diplomate ABVP (Companion Animal) Pet Health Services Big Pine Key, Florida acterial diseases, as a group, ate one of the B= causes of morbidity and mortality in rep les. Many of these diseases can be treated suc- cessfully if recognized in time. Infectious disease is almost always secondary to immunosuppression in rep- tiles and is often associated with the stress of captivity. Management and husbandry disorders are often at the root of the problem. Gram-negative bacteria are the most ‘common bacterial pathogens associat- ed with infectious disease. Gram-posi- tive bacteria are frequently isolated as normal inhabitants in reptiles and are only rarely implicated in disease Salmonella spp., ubiquitous reptilian bacteria, have been cultured from more than 90% of selected reptile colonies, and understanding their significance can be problematic. Anaerobes and pathogenic fungi may also be impor- tant components of reptilian pathology. Gram-negative etatret wetness most common etacoehl Gattuso) (roe r toe maa tan) Fi astotene tect brie gual (oon sp 23 Sampling Techniques General Considerations Proper specimen collection is the key to identifying a pathogen. Improperly collected samples may lead to erroneous results and an inappropriate choice of an antimicrobial. Although culture swabs are the most commonly used tool for sample collection, they are poorly absorbent and provide only minimal support for the survival and transport of microbes from the hospital to the clinical laboratory. ‘Swabs are most effective when premoistened with sterile saline before sampling the affected area. (Some ‘swabs can be moistened inside their transport tube pri- or to using.) After careful “swabbing” of the infected site, the inoculated swab should be placed back into its transport tube and allowed to remain at room temper- ature for 15 to 20 minutes prior to refrigeration. Nasol/ Oral Cavity Sampling discharges from the nasal or oral cavities are not recommended. These specimens contain inflammatory exudates that have passed through ‘anatomic locations known to be colonized with normal flora. As a result, cultures often reveal a mixed growth of bacteria, leading to misinterpretation of the true pathogen(s). ‘A common “bad” practice in exotic animal medicine has been to culture both the oral cavity and the cloaca, ‘alled a “combo culture” This practice is used as a screening tool, and, although easy to perform, it does not always provide specific information regarding bac- terial pathogens. Oral cavity flora is a reflection of envi- ronmental bacteria. Although the actual pathogen might be included in the culture sample, it is possibly lost by a myriad of other incidental microorganisms. A similar problem is encountered when the cloacal region is cultured randomly. Site-specific bacterial sampling is preferable to random sampling. For ‘example, snakes with infectious stom- atitis (mouth rot) benefit from appro- priate antimicrobial therapy based on proper bacterial isolation. However, col- lecting a useful specimen can be diffi- ‘alt. Agein, another common practice (although not a good one) is to swab the affected gingiva with a culturette in the hope of identifying the pathogen. A en collected by this technique will yield various oral cavity and envi-24 Supp! Compend Contin Educ Pract Vet Vol. 20, No. 3(A), 1998 Figure !—Severe case of infectious stomatitis ina snake, Culturing from deep within the offeced site, as opposed to sampling fram superficll gingival tissues, will result In @ more accurate assessment ofthe bacteria involved, ronmental flora. Gram-negative bacteria are commonly isolated, but their significance is nebulous at best. A better technique isto prepare the area with alcohol and inject a small amount of sterile, nonbactericidal saline (0.05-0.1 mi) into the site of the lesion. After the area is massaged, the region should be aspirated. A culture of the aspirate will be more rewarding, microbiological- ly, than a random sampling of the surface (Figure 1). Cloacal cultures may be useful in patients with diar- thea or other gastrointestinal signs. Proper diagnostics such as fecal examinations for ova and parasites, includ- ing protozoal pathogens, should always be done before bacterial cultures. Just as with oral cavity cultures, inter- pretation of the culture results can be confusing because many different bacteria are normally present. Respiratory Tract Proper sampling is imperative in patients displaying respiratory signs. Random culturing of the saliva or of tra- cheal exudate within the oral cavity is nondiagnostic. If time and cost restraints are imposed, the preferable sam- pling site is located high within the choanal slit. Because this site is juxtaposed to the opening of the glottis, a significant pathogen is more likely to be isolated, A preferable technique would be to perform a tracheal wash. An appropri- ately sized, sterile, red-rubber catheter inserted transelottally and directed into the lung. Sterile saline (approxi- mately 1 of the patient's body weight) is infused through the catheter, The patient is then gently inverted, Proper sampling is Puntos a coe tl reptilian patients Cis eyaters Bestel m ars cs ANTIMICROBIAL THERAPY IN EXOTICS rolled side to side, or in some way rocked to allow mix- ing and washing of the saline within the lung. After this is accomplished, as much fluid as possible is with- drawn. itis not uncommon to retrieve only a small por- tion of the infused saline. Any remaining fluid is readily absorbed through the lungs. Occasionally, in cases of severe pneumonia, quantities greater than the amount infused will be retrieved. The collected fluid can be used for both cytologic examination and bacterial culture and sensitivity testing. Miscellaneous Sampling Open abscesses should be debrided and samples taken from deep within the lesion, preferably from the lining or capsule. Closed abscesses are sampled by aspirating material using sterile technique. Cystic and Vesicular fluid are cultured in a similar manner. Blood cultures are warranted if septicemia is suspect- ed. The skin should be disinfected with alcohol and air-dried for 30 seconds. Both aerobic and anaerobic cultures can be done from a minimum sample size of 05 to 1.0 ml of blood using a pediatric ysis-centrifuga- tion tube. Reptilian urine is not sterile. Although clinicians are encouraged to perform urinalysis as part of their standard data bases, culture and sensitivity are not indicated. Interpreting Culture Results Culture results should be correlated with the response to treatment. Therapeutics can be fine-tuned based on the isolate and sensitivity data. Two areas of the culture results must be evaluated: (1) the quantita- tive results and (2) the minimum inhibitory concentra- tion (MIC) patterns. Laboratory culture results are useful when reported in ‘quantitative terms. Quantitation is used to differentiate the normal flora from the pathogens. This is especially true in reptilian clinical microbiology because gram- negative bacteria are normally part of that indigenous flora. Sometimes heavy growth of a bacteria, which is normally present in smaller numbers, isthe only indication that a bacterial infection is the cause of disease. Gram-negative bacteria are part of the resident flora in snakes, but during illness (e.g., pneumonia) the number of these bacteria rises significantly. This may be reported by the laboratory cul-COMMON BACTERIAL DISEASE AND ANTIBIOTIC THERAPY IN REPTILES ture as moderate to heavy growth and is useful in determining whether an organism should be considered a pathogen. A common organism found in low numbers may not be the cause ‘of an infection. A common organism found in large numbers in a sick reptile ‘may be important. The clinician should request that bac- terial sensitivity results be reported as MICS in addition to the traditional infor- ‘mation on sensitivity and resistance to antibiotics. The MIC is a quantitative measurement of the concentration of antibiotic in the patient's serum neces- sary to inhibit the growth of the bacte- si tia without The antibiotic disc diffusion method is an older method of determining antibiotic sensitivity and is based on human clinical data. This method does not indicate the degree of susceptibility that the cultured bacteria has to differ- ent antibiotics. Ifthe clinician knows the serum con- centration range of an antibiotic that corresponds to the dosage used, MIC data can be bet- ter utilized and the drug dosed more rationally. Thus, the use of MIC data allows the clinician to not only select a sensitive antibiotic, but specifically, the most sensitive one. MIC results are reported as an actual number. If the number is low for a certain antibiotic, a comparatively low concentration of that antibiotic is needed to inhibit bacterial growth; therefore, the antibiotic may be a good choice for treatment. If the number is high for a certain antibiotic, it may be impossible to achieve the necessary serum concentration needed to inhibit growth of the bacteria. The highest achievable concen- tration of an antibiotic in a patient is independent of culture results and depends on the volume of distribu- tion and clearance time of the antibiotic in the patient. The benefit of using MIC results is that the clinician can tailor the dosage of the antibiotic to the sensi of the specific pathogen without generalizing treat- ment rationale to a type of bacteria. An antibiotic with an MIC thatis relatively low in the sensitivity range may be effective at a lower dosage than if the MIC were higher. A result of “sensitive” does not indicate the WUNalotsmos sta U(@m crite Peat etrartatars rooney can tailor the dosage of the antibiotic to the Site moat specific pathogen generalizing restate ranula Free maa ons Letaros te data allows a dinician to avoid pre- scribing an antibiotic in the high end of the dosage range when a smaller dosage might be as effective. This is important when using potentially toxic drugs such as the aminoglycosides. For example, Proteus penneri is cub ‘tured from an abscess in a box turtle. The (MIC for amikacin is less than 0.5 pg/ml, and the MIC for gentamicin is 8 pg/ml Both would be reported as sensitive according to the older system, but ‘amikacin is shown to be the better choice when based on MIC values. Pseudomonas aeruginosa is cultured from a bite wound in a snake and a bite wound in an iguana. Piperacillin is teported as sensitive in both cases. However, the MIC for piperacilin for the Pseudomonas infection in the snake is less than 8 g/ml, and the MIC for piperacillin for the Pseudomonas infec- tion in the iguana is 16 g/ml. From these MIC data, the bacteria cultured from the snake are clearly more sensitive to the effects of piperacilin, and a lower dosage can be used. Within an expected MIC range of an antibiotic, a smaller number is more desirable than a larg- er number. In a situation where MIC data for two drugs are the same, the antibiotic choice should be for the drug that is less expensive, easier to administet, and less toxic. Interpreting “No Growth” Sample Results ‘A number of factors explain why a “no growth” occurs in a sample collected from an obviously infected site. A recent study of the bacterial flora of ill reptiles revealed that approximately 50% of cultured specimens yielded anaerobic bacteria. This could account for labo- ratory results of “no growth” if anaerobic culture is not requested. "No growth’ reports also occur as a result of submit ‘ting an inoculated swab on which the bacteria die before arriving at the laboratory for plating. if a sample is taken from an aggressive infection, itis possible to actually collect too much bacteria. When this happens, bacteria grow so fast in the transport tube that they actually outgrow their food supply and die. Other pos- sibilities indude prolonged storage, overheating of the specimen, inappropriate or outdated culture media, and laboratory error. RH Tia ley!Reptiles’ 26 Suppl Compend Contin Educ Pract Vet Vol. 2, No. 3A), 1998 Figure 2—Pseudomonas aeruginosa pneumonia in @ boa con~ strictor. Note the posturing in the corner of the cage, whichis not ‘uncommon in snakes with pneumonia, Microorganisms Gram-Positive Isolates Most gram-positive bacteria are not considered path- ‘ogenic in reptiles. They are common inhabitants, espe- Gally of the skin. However, some gram-positive bacteria can cause disease. Coagulase-positive staphylococci are usually patho- genic. The production of coagulase and pathogenicity ‘has a 95% correlation. Treatment should be considered in any reptile showing clinical signs that has had coag- ulase-positive staphylococci cultured from its lesion, Streptococci ate grouped by their ability to hemolyze blood agar. The two main types of hemolysis are alpha and beta. Over 90% of beta-hemolytic streptococci are pathogenic; therefore, treatment should be considered in patients with this type. All gram-positive bacteria have the potential to be pathogenic, especially in a compromised animal. ‘Treatment should be considered when the patient is not responding to therapy for gram-negative bacteria or when an infection is present but no gram-negative bac- teria are cultured. if coagulase-positive staphylococci ot beta-hemolytic streptococci are cultured, treatment, as directed by MIC results, should be cor red. Gram-Negative Isolates Most species of Salmonella spp. and Salmonella ari- zonae (formerly Arizona arizonae) are considered path- genic. Many reptiles harbor these organisms as part of their normal flora, and interpreting their presence can ANTIMICROBIAL THERAPY IN EXOTICS Figure 3—"Blster disease,” or vesicular dermatitis, ina red-talled ‘boa constrictor caused by Aeromonas sp. This bacterium may be carried from snake to snake by the mite Ophionyssus natricis. be difficult. Animals affected (as opposed to merely car- rying the organism) with Salmonella bacteria usually do not show clinical signs but rather may present as poor doers or die acutely. One overt clinical sign noticed by the author is a weeping, crusting, vesicular dermatitis in both lizards and snakes. These bacteria have public health importance because of their zoonotic potential Pseudomonas spp., especially P. aeruginosa, are ‘commonly found as part of the normal flora in the oral cavity and intestinal tracts of reptiles. As such, they are often considered opportunistic pathogens. Poor hus- bandry, including suboptimal environmental tempera- ture and malnutrition, can predispose reptiles to Pseudomonas infections. Pseudomonas spp. are fre- quently isolated from lesions associated with ulcerative stomatitis, pneumonia, dermatitis, and septicemia (Figure 2). Healthy reptiles from which Pseudomonas spp. are cultured in light numbers from the oral cavity ‘r gastrointestinal tract probably need not be treated. Aeromonas spp. are associated with pneumonia, lesions of the oral cavity, cutaneous lesions, and sep- ticemia (Figure 3). The snake mite Ophionyssus natricis is a vector of this bacteria. Aeromonas spp. isolated from healthy animals in small numbers may be part of the normal flora. However, treatment should be consi ered if growth is significant or ifthe organism is present in patients with clinical signs. Serratia spp. ate part of the normal flora of the oral cavity in reptiles. These organisms are commonly isolat- ed from cutaneous lesions and appear to be introduced by traumatic events, such as bite wounds. Cutaneous infection with Serratia spp. typically causes caseated abscesses that require surgical curettage and antibiotic therapy for resolution, Providencia spp. are commonly isolated from the oralCOMMON BACTERIAL DISEASE AND ANTIBIOTIC THERAPY IN REPTILES cavity of healthy snakes and are believed to be oppor- tunistic pathogens. Treatment is considered if the Patient has a poor clinical status. Klebsiella spp., especially K. pneumoniae, ate com- monly associated with pneumonia and hypopyon. The author has also isolated Klebsiella from osteomyelitis lesions in iguanas and snakes (Figure 4). These organ: isms are considered normal flora by some clinicians. When isolated from clinically ill reptiles, the patient should be treated. ‘Mycobacterium spp. are ubiquitous in the environ- ment. Potentially pathogenic species in reptile patients include M. marinum, M. chelonei, and M. thamnopheos. Although commonly isolated from cutaneous lesions, mycobacteria can also cause systemic illness accompa- niied by nonspecific signs such as anorexia, lethargy, and wasting, Acid-fast organisms are readily identified in skin scrapings or by biopsy (Figure 5). No successful treatment of infection with Mycobacterium spp. has been reported, and these organisms may have some zoonotic potential. Euthanasia of clinically affected ani- mals may be an option worth discussing with the client. Anaerobic Bacteria A study of the bacterial flora of ill reptiles revealed that approximately 50% of all cultured specimens yield- ced anaerobic bacteria. Bacteroides spp. are the most common obligative anaerobes isolated from reptiles. These facts should play a part when empirically select- ing antibiotics Antibiotic Therapy in Reptiles {As previously discussed, most bacterial pathogens of reptiles are gram-negative organisms. Common isolates include Pseudomonas spp., Aeromonas spp., Klebsiella spp., and Salmonella spp. To date, very few pharmaco- kinetic studies have been published in reptiles and with only a limited number of antibiotics. Many factors must be considered when choosing an antibiotic, The results of microbiologic culture and sen- sitivity testing, the species being treated, physical con- dition of the patient, frequency of administration, cost of the therapy, owner compliance, and other factors are all important. The veterinary clinician must have a thorough under standing of reptile physiology and biology prior to admin- istering medications. Since all reptiles are ectotherms and their metabolism is temperature dependent, they will often react unpredictably to the same drug in different set- tings. A good working knowledge of the more common species of reptiles and their life histories and peculiarities will help prevent potential disasters during therapy. Several publications list the drugs that have been eval aeal 28. Suppl Compend Contin Educ Pract Vet Vol. 2, No, (A) 1998 ANTIMICROBIAL THERAPY IN EXOTICS OU-S)B cal COMMON BACTERIAL ISOLATES, PATHOGENICITY, AND RECOMMENDED ANTIBIOTICS IN REPTILES* Bacterial Isolate Acinetobacter Actinobacilus Aeromonas Bacteroides Citeobacterfreundit Clostridium Connebacterium Edwardsiella Enterobacter lebsiell ‘Micrococcus Morganello ‘Mycobacterium Pasteurella Proteus Staphylococcus (coagulase-positive) Stophylococcus ulase-negative) Streptococcus (alpha-hemol (beta hemolyti Pathogenicity + He He +H Not pathogenic Not pathogenic Not pathogenic Recommended Antibiotic Aminoglycoside (Amikacin C2 uoroguinolone (Baytril", Bayer) ‘Aminoglycoside (Amikacin C™, Phoenix) Fiuoroquinolone (Bayt, Bayes) Aminoglycoside (Amikacin C™, Phoenix) Penicilin (Pfizespen"-AS Aqueous, Rosrig) Cephalosporin (Ancef, SmithKline Beecher) Metronidazole (Fagyl' Tablets, Searle) ‘Aminoglycoside (Amikacin C™, Phoenix) Fluoroquinolone (2aytil, Bayer) Penicilin (Pfizerpen®-AS Aqueous, Roerig) Cephalosporin (Ancef", SmithKline Beech Metronidazole (Flagyl Tablets, Seale) pi cept clin (Pfizerpen*-AS Aqueous, Roerig) ialosporin (Ancef*, SmithKline Beecha ‘Aminogiycoside (Amikacin C™, hen). ‘Arninogiycoside (Amikat Fuaroquinolone (Bayt nC, Phoenia) " Boyer) ‘Aminogiycoside (Amikacin , Phoenix) Fluoroquinolone (Baytil’, Boyer Aminoglycoside (Amikacin C™, Phoenin) F Cep) quinolone (Baytril’, Bayer) losporin (Ancef*, SmithKline Beecham) ‘Aminoglycoside (Amikacin C™, Phoenix) Fluoroquinolone (Baytil, Bayer) Tieatment not recommended Fluorac inolone (Bayt, Bayer) Fluoroquinolone (Baytil, Bayer) ‘Aminoglycoside (Amikacin C™, Phoenix) ‘Aminoglycoside (Amikacin ™, Phoer iment questionable ‘Aminoglycoside (Amikacin C™, Phoenix) Fluoroquinolone (Baytil, Bayer) Cephalosporin (Ancef, SmithKline Beecham) None needed ed Fluoroquinolone (Baytil*, Bayer) ees of pathogenicity "Modified from Rosenthal KL, Meder DM: Microbiology. in Mader OR epiile Medicine ond Surgery. Philadelphia, WE Saunders, 1996,COMMON BACTERIAL DISEASE AND ANTIBIOTIC THERAPY IN REPTILES 29 TABLE 2 TEN STEPS FOR RATIONAL ANTIMICROBIAL U 1. Initalassessment-Always perforin 4 proper thorough physical examination, including evaluation of the letion and hydratio jon plays otic choice due to catabolic odu Joacal) temperature. ter fluids as needed sample collection Blood (CBC/serum pro en cultures (lung f masses, ee, fluids Determine method of administiation (oral, systemic, topical). Coordinate your choice with owner exper 6. Choice of crug-Gener versus combination therapy (see below). Adjustment of dosages (c dehydration renal function, bacterial cut ity re 8. Proper follow-up and patient. monitoring progress checks, uric acid measurements) : ime, enrofloxaci 9. Ail renal patients), cefta sulla TABLE 3 COMMON ANTIMICROBIALS USED IN REPTILIAN PRACTICE Drug Species mika Alligator Tortoise Snake cin C™, Phoenix) (Fortax*, Glaxo) Sea turtle Chloramphenicol Snake (Chloromycetin’ Sodium Succinate, Parke Davis) Doxycycline Tortoise iw |) (ibramycin’, Ptizer) ~— Envofloxacin all IM, PO Bayt, Bayer) Hermann’s tortoise IM : opher tortoise | Star torts Green iguar Aligator Snake Po. ets, Searle) uated pharmacokinetically, as well as those drugs com- monly used empirically in practice. Attempting to list al of those drugs here is beyond the scope of this article. However, itis prudent to offer some guidelines for ratio- nal antimicrobial therapy (Tables 1 through 3; Figure 6). Dose (ng/kg) Interval (br) 96 18 Caligir initial Mader et al 19 n 2 Lawrence etal, R Stamper et 2-12 Bush et (species Clark et a dependent) 50 initial Spétte etal, 1991 Mader, 1996 10 Spire et a, 19 5 erart et al, 199 “ 5 Raphael et al, 1994 Maxwell & Jac 07 Helmick et a : 20 Kolmstetter et al, 1997 0028 fetal, 1991 24 (fist two doses); Jacobson, 198 Gen Before treatment is initiated, the patient should be given a thorough examination, including a complete blood count (CBC) and serum profile (with a uric acid measurement) to assess hydration status. Dehydrated Corie | = Q Oy ce 30 Supp! Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998 Figure 6—Some wounds, such as this rodent bite, are considered emergencies and may require combination drug therapy with anib!~ coves such as amikacin and metrondazot or hyperuricemic patients should be properly rehydrat- ed prior to initiating therapy. Rarely will cases need more than 1 to 2 days to determine appropriate hydra- tion prior to treatment. However, if for some reason treatment must begin immediately, it would behoove the practitioner to choose a nonnephrotoxic drug. Another important consideration is the ambient tem- perature of the reptile’s environment (Figure 7). Pharmacokinetic studies have shown that an increase in ambient temperature tends to increase both the vol- lume of distribution and body clearance of the drug. A decrease in ambient temperature with a resultant decrease in body clearance could potentially allow a buildup in concentration of the drug such that it might reach toxic levels if dosing is not decreased accordingly. It has also been pointed out that when reptile pathogens are treated at higher temperatures, the MIC needed to achieve effective treatment significantly decreases. This allows for 2 lower dose of antibiotic to be given, another positive factor when dealing with potentially nephrotoxic drugs. Most researchers feel that it is best to treat sick rep- tiles near the higher end of their preferred optimum temperature zone (POTZ). Not only is it beneficial for reasons already mentioned, but elevated ambient tem- peratures have been shown to stimulate the host's immune system and aid in fighting disease in other ways already discussed When selecting the appropriate antibiotic, clinicians should consider the status of the host's immune sys- tem. In critically ill or immunocompromised reptiles, bactericidal (rather than bacteriostatic) antibiotics are preferable. In cases of gram-negative sepsis, especially with Pseudomonas infections, the reptile patient is often severely immunocompromised. In many cases, the animals are ill because they have ANTIMICROBIAL THERAPY IN EXOTICS Figure 7—Variables such as species, ambient temperature, and route of administration al affect antibiotic doses. ti imperative to select appropriate drags and dosages when treating diferent rep tan species. been immunocompromised due to improper husbandry conditions, which is most commonly caused by being maintained at suboptimal environmental temperatures. ‘Methods of Antibiotic Administration ‘There has been much controversy over the use of oral antibiotics in reptiles. From the purely academic stand- point, only two pharmacokinetic studies have ever been done on the use of oral antibiotics in reptiles. Most of the information on oral dosing comes from dinical experience. Because of the inherent problems of ectothermy, there is a question regarding how well antibiotics are absorbed. Until proven otherwise, all animals should be kept at their POTZ when enteral antibiotics are pre scribed. The POTZ will vary among species, and clini- cians must be sure to research the proper POTZ require ments for the species they are treating. There are two common methods for administering oral antibiotics. if the patient is still feeding, the anti otic can be mixed with the food or injected into the dead prey and fed to the animal. Gavaging, or stomach tubing, is a second technique used to administer oral medications. Although the academic jury may be out regarding the efficacy of enteral antibiotics, the author can attest to over 10 years of experience, with literally thousands of patients, that oral antibiotics used in appropriate cases work extremely well. Topical Antibiotic Therapy ‘As well as oral dosing of systemic antibiotics, it is not uncommon to actually treat the oral cavity itself. This may be done in cases of severe infectious stomatitisCOMMON BACTERIAL DISEASE AND ANTIBIOTIC THERAPY IN REPTILES Figure 8—Enrofloacin if administered via intramuscular injec tions has the potentil to case sterile abscesses a the injection sites, as is seen in ths reculated python. where the oral cavity is abscessed. Since the vascularity to an abscessed oral cavity is usually compromised, antibiotics given systemically may not be able to reach adequate therapeutic levels in the infected tissues. Aminoglycoside antibiotics have decreased activity in anaerobic or acidic environments. Silvadene® (Hoechst Marion Roussel) is a soft, white, water-miscible cream containing the antimicrobial agent silver sulfadiazine. This bacter effective against a broad range of both gram-positive ‘and gram-negative bacteria, including Pseudomonas ‘eruginosa, as well as some types of yeast. Silvadene” cream is easily applied with a cotton-tipped swab or other applicator. A dressing is not necessary unless the treated area is in a location where the cream may be rubbed of by the patient. Otherwise, the cream will last for 2 to 3 days before a new application is required. Silvadene* cream can be safely applied directly to the mucous membranes in the oral cavity with no untoward side effects idal cream is Injectable Antibiotic Therapy Injectable antibiotics are probably the best form for assuring proper delivery of the drug. However, the author firmly believes that if injectable antibiotics are requited, their use should be restricted to the hospital environment. Antibiotics are either injected intramuscularly (Figure 8) of, less commonly, subcutaneously. The intravenous route of administration is often limited by the availabili- ty of venous access. The size and the species being treat- ed will determine whether or not intravenous infusion is possible (Figure 9). Reptiles have an anatomic variation known as the Figure 9—incravenous access is valuable for both fluid therapy ‘and in cases where venous acess is necessary for intravenous antbi- ‘otic therapy in serious gram-negative sepsis renal portal system, Blood leaving the tail and pelvic limbs passes through the kidneys before returning to the heart. Recent studies in water turtles and box tur- tles have demonstrated that this has a significant effect cn antibiotics cleared from the body via tubular secre tion, such as carbenicilin, but had no effect on those drugs eliminated by glomerular filtration, such as gen- tamicin, Antibiotics that are either cleared by the kidney or are potentially nephrotoxic should not be administered in the hindlimbs or tal. The renal portal system can be avoided by making all injections in the cranial half of the body. {An important consideration when selecting an antibi- lic is its ability to penetrate the target tissue site. For example, in patients with severe infectious stomatitis, the vascular supply may be compromised to the oral cavity inthe area of the lesions, which, in turn, may pre- vent good penetration of the antibiotic to the site of infection, ‘Another method of ensuring adequate antibiotic lev- els to the affected tissue is to calculate the total sys- temic dose, draw it into a syringe, and then add an equal volume of bacteriostatic water to dilute it to half concentration. Three-fourths of the dose should be injected intramuscularly and the remaining quarter dose injected directly into the region of the mouth where the infection is present. If more than one loca tion in the mouth needs to be injected, itis recom- mended that a new needle be used to prevent seeding of bacteria from one site to another. Fiuid Therapy Because reptiles are uricotelic (ie, they excrete uric32. Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998 Figure 10—Cauton should be used when administering poteria!~ Iy toxic medications in dehydrated patients. The pericardium around this snake heart is filed with tophi as a result of aminoglycoside induced gout acid as the end product of protein metabolism), they are readily susceptible to visceral gout. f the patient is dehydrated or develops renal pathology due to treat- ment with nephrotoxic drugs, the insoluble uric acid forms microcrystals called "tophi” on the serosal sur- faces and within tissues, such as the heart, lungs, liver, and kidneys (Figure 10) Visceral gout can be prevented by utilizing proper drug dosages, evaluating the patient's hydration status, and monitoring blood uric acid levels throughout thera- Py. Blood uric acid levels should be rechecked 1 to 2 ‘weeks after the treatment is finished. The patient should be supplemented with physiolog- ic fluids at 15 to 25 ml/kg on the days it receives antibi- otic treatment. The fluids can be given orally, intra- coelomically, or subcutaneously in the lateral sinus, which is located at the junction between the epaxial musculature and the Conclusion Very few studies have been conducted on the phar- ‘macokinetics of antibiotics in reptiles. To date, only two drug studies have been performed in lizards, and one of those was a toxicity evaluation. Fortunately, with the increasing popularity of pet rep- tiles and the concomitant increase in their worth to the pet trade, more research is being carried out worldwide. Suggested Readings ‘ustwich P, Keymer |: Fungi and actinomycetes, in Cooper J, Jackson OF (eds): Diseases of the Reptilia. San Diego, Academic Press, 1981, pp 195-231 Beck K, Loomis IM Lewbar G, eta: Preliminary comparison of plasma concentrations of gentamicin injected into the ca- nial and caudal mb musculature of the Eastern box turtle (Ferrapene carolina carolina).J Zo0 Wildl Med 26:265-268, 1995. Bush M, Smeller JM, Carache P, etal: Preliminary study of ANTIMICROBIAL THERAPY IN EXOTICS antibiotics in snakes. Proceedings of the American Association of Zoo Veterinarians, 1976, p50. Caligiuri RL, Kolias GY, Jacobson ER, etal: The effects of ambi- ent temperature on amikacin pharmacokinetics in gopher tortoises. J Vet Pharmacol Ther 13:282-291, 1990. CChiodini 8, Sundberg J: Salmonellosis in reptiles: A review. Am 1 Epidemiol 113(5):494~499, 1981 ‘lark CH, Rogers ED, Mitton JL; Plasma concentrations of chlor- “amphenicol in snakes. Am J Vet Res 46:2654~2657, 1985, Cooper J: Bacteria, in Cooper JE, Jackson OF (eds): Diseases ‘of the Reptiia. ‘San Diego, Academic Press, 1981, pp 165-191 Draper C5, Walker RD, Lawler HE: Patterns of oral bacterial infection in captive snakes. JAVMA 179:1223~1226, 1981 Harvey R, Price T: Salmonella isolation from reptilian faeces: A discussion of appropriate cultural techniques. J Hygiene 91(1):25-32, 1983, Helmick KE, Papich MG, Viet KA, et al: Preliminary kinetics of single dose intravenously administered enrofloxacin and onytetracyline in the American alligator (Alligator missssip- jensis). Proceedings of the American Association of 200 Veterinarians, 1997, p 27 Hilf M, Swainson 0, Wagner R, et al: Pharmacokinetics of Piperaclin in blood pythons (Python curtus) and in vitro evaluation of efficacy against aerobic gram-negative bacte- tia.J Zoo Wild! Med 22:199-203, 1991 Hilf M, Wagner R, Yu V:A prospective study of upper airway flo- rain healthy boid snakes and snakes with pneumonia. ! 200 Wildl Med 21(3):318-325, 1990. Hodge MK: The effect of acclimation temperature on genta- micin nephrotoxicity in the Florida broad banded water snake (Natrix fasciata). Proceedings of the American Assocation of Zoo Veterinarians, 1978, p 226 Holt PE: Drugs and dosages, in Cooper JE, Jackson OF (eds): Diseases of the Reptilia. Sen Diego, Academic Press, 1981, pp 551-581 Holz P, Barker IK, Conlon PO, et al: The reptilian renal portal system and its eifects on drug kinetics. Proceedings of the ‘American Association of Zoo Veterinarians, 1994, pp 95-96. Jacobson ER: Biology and Diseases of Reptiles. Laboratory ‘Animal Medicine. New York, Academic Press, 1984, pp 449-476, Jacobson ER: Gentamicinelated visceral gout in two boid snakes. Vet Med Small Anim Cin 71:361, 1976. Jacobson ER: Necrotizing mycotic dermatitis in snakes: Clinical and pathologic features JAVMA 177(9):838-84, 1960. Jacobson ER: Reptiles. Vet Clin North Am Small Anim Pract 17):1203-1225, 1987 Jacobson ER: Use of chemotherapeutics in reptie medicine, in Jacobson ER, Kollas GV (eds): Exotic Animas. New York, Churchill Livingstone, 1988, pp 35-48. Jacobson ER, Brown MP, Chung M, etal Serum concentration and disposition kinetics of gentamicin and amikacin in juve rile American alligators. J Zoo Anim Med 19:188-194, 1968, Jang 5, Hirsh D: Identity of Bacteroides isolates and previously named Bacteroides spp. in clinical specimens of animal or- gin. Am J Vet Res 52(5):738-741, 1991 Keymer I: Diseases ofthe chelonians: (2) Necropsy survey of terrapins and turtles. Vet Rec 103:577-582, 1978. Kluger Mi, Ringler DH, Anver MR: Fever and survival, Science 188:166-168, 1975. Kolmstetter CM, Frazier, Cox’, etal: Metronidazole phorma- cokinetics in yellow rats snakes (Elaphe obsoleta quadrivi- tata). Proceedings of the American Associaton of Zoo Veterinarians, 1997, p 26 Lappin PB, Dunstan RV: Difficult dermatologic diagnosis. JAV- ‘MA 200(6):785-786, 1992.COMMON BACTERIAL DISEASE AND ANTIBIOTIC THERAPY IN REPTILES Lawrence K, Muggleton PW, Needham JR: Preliminary study on. the use of ceftazidime, @ broad spectrum cephalosporin aniibiatc, in snakes. Res Vet Sci 36:16-20, 1984, Mader DR: Antibiotic therapy in reptile medicine, in Frye FL (ed): Biomedical and Surgical Aspects of Captive Reptile Husbandry, ed 2, vol 2. Melbourne, FL, Krieger Publishing, 1990, pp 621-684, Mader DR (ed): Reptile Medicine and Surgery. Philadelphia, WB Saunders, 1996, pp 466-472. ‘Mader DR, Conzeiman GM, Baggot JD: Effects of ambient tem- perature on the halflife and dosage regimen of amikacin in the gopher snake. JAVA 187:1134, 1985. ‘Maxwell LK, Jacobson ER: Preliminary single dose pharmaco kinetics of enrofloxacin after oral and intramuscular admin- istration in green iguanas (iguana iguana). Proceedings of the American Association of Zoo Veterinarians, 1997, p 25. ‘MigakiG, Jacobson E, Casey H: Fungal diseases in reptiles, in Hoff G, Frye F, Jacobson E (eds): Diseases of Amphibians cand Reptiles. New York, Plenum Press, 1984, pp 183-204. ‘Montali Ri, Bush M, Smellers JM: The pathology of nephrotox- icity of gentamicin in snakes, Vet Patho! 16:108-115, 1979. Needham J: Miciobiology and laboratory techniques, in ‘Cooper JE, Jackson OF (eds): Diseases of the Reptilia. San Diego, Academic Press, 1981, pp 93-134. Paisley 1, Lauer BA: Pediatic blood cultures. Clin Lab Med 14(1):17-30, 1994. Plowman C, Montali , Phillips Let al: Septicemia and chron- ic abscesses in iguanas (Cyclura comuta and iguana igua- 1na) associated with a Neisseria species. J Zoo Anim Med 18(2-3):86-95, 1987, Prezant RM, Isaza |, Jacobson ER: Plasma concentrations and. disposition kinetics of enrofloxacin in gopher tortoises (Gopherus ployphemmus).J Z00 Wild! Med 25:82-67, 1994. Raphael BL, Papich M, Cook RA: Pharmacokinetics of enrofloxacin after a single intramuscular injection in Indian star tortoises (Geochelone elegans). J Zoo Wild! Med 25:88-94, 1994, Reddaciff G, Cunningham M, Hartley W: Systemic infection with a yeast-like organism in captive banded rock rat tlesnakes (Crotalus lepidus klauberi). J Wild! Dis 29(1):145-149, 1993, Rosenthal KL, Mader DR: Microbiology, in Mader DR (ed): Reptile Medicine and Surgery. Philadelphia, WB Saunders, 1996, pp 117-125, Ross R: The Bacterial Disease of Reptiles. The Institute for Herpetological Research. 1984. Sedgwick CJ, Pokras MA: Extrapolating rational drug doses and treatment periods by allometric scaling. Proceedings of the American Animal Hospital Association, S5th Annual ‘Meeting, 1988, pp 156-157, ‘Sporle H, Gabel T, Schldger B: Blood levels of some antinfec- tives in the Heimann’s tortoise (Testudo herman), in the 4th International Colloquium on Pathology and Medicine of Reptiles and Amphibians. Abst, Bad Nauheim, Germany, 1991 ‘Stamper MA, Papich M, Lewbart Get al: Single dose pharma cokinetics of ceftazidime in loggerhead sea turtles (Caretta coretta). Proceedings of the American Association of Zoo Veterinarians, 1997, p 16. Stewart J: Anaerobic bacterial infections in reptiles. Zoo Wild ‘Med 21:180-184, 1980. Wallach 1, Boever W: Diseases of Exotic Animals: Medical and ‘Surgical Menagement Philadelphia, WB Saunders, 1983, pp 978-1047 33Birds, ji elatess) ‘Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998: Common Bacterial Infections and Antibiotic Use in Companion Birds Keven Flammer, DVM Diplomate ABV? (Avian Practice) Deoartmet of Companion Animal and Special Species Medicine College of Verinary Medicine North Carolina State Univessy Rakigt, Nort Carolina acterial diseases are among the most common B= al problems reported in companion birds (psittacines, canaries, and finch- 5). Primary infections occur, but sec- ondary infections due to poor hus- bandry and immunosuppression are more common. Poor husbandry can expose birds to a large number of potentially infectious organisms from other birds and environmental sources. Birds may become immunosuppressed due to malnutrition, stress, medication, for concurrent diseases. Because sec- ondary problems are so common, it is important to identify and eliminate the underlying cause of the bacterial infec- tion in addition to determining appro- priate antibiotic treatment. Many species of bacteria can poten- tially cause disease in companion birds, I ETA cane bacteria can Pacosteel bares disease in Ceerireret em tat but a limited Pot trae (erunitont by reported. but a limited number are commonly reported. This manuscript emphasizes clinical aspects of common infections as well as the selection of an antimicrobial treatment regimen for use in companion birds. Table 1 lists the most commonly reported bacterial diseases. Table 2 lists uncommon bacteria, Excellent reviews offer more comprehensive information, including data on less common infectious organisms! and on organisms commonly causing disease at specific anatomic loca- tions.” Diagnosis Bacterial infections are best diagnosed by a combina- tion of culture and cytology, Culture is needed to iden- tify and quantitate potential pathogens and to deter- mine their antimicrobial susceptibility. Culture has limitations and will fail to demonstrate the presence of pathogens that do not grow on conventional media (eg, Chlamydia, mycobacteria, megabacteria, and anaerobes) or bacteria that are present in low numbers ‘or intermittently shed (e.g., Salmonella). Cytology can aid in identifying bacteria that are difficult to grow, but ‘organisms must be present in large numbers.* Smears of feces, feather pulp, or other clinical samples should be stained with Gram’s stain (Figure 1) to characterize microbial flora and with a hematologic stain to char- acterize cellular responses such as inflammation. A Ziehl-Neelsen stain can be used to identify acid-fast bacteria. Samples can be easily collected from the choana, crop, and cloaca (Figure 2) with moistened ‘swabs. More invasive samples can be collected from the trachea with the patient under anesthesia (Figure 3). Surgery or endoscopy (Figure 4) is needed to collect samples from the periorbital sinuses and internal organs (eg, liver, air sac biopsies, or kid- rneys).* Culture Sites and Normal Flora Normal alimentary tract flora is important to identify because it can be cultured from many sites. In psittacines and many passerines, normal alimenta- ry tract flora is composed of anaerobes and gram-positive bacteria“* The ‘normal anaerobic flora is poorly charac- terized. Normal aerobic rods include Lactobacillus, Corynebacterium, and Bacillus. Normal aerobic cocci include nonhemolytic Streptococcus, Micrococ- 4COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS 35 BLN) Bo OMMONLY REPORTED BACTERIAL, SES IN COMPANION BIRDS ‘Moderately Common Bacterial Diseases I Other Enterobacteriaceae (eg, Salmonella, Citrobacter, Proteus, Serratia) © Staphylococcus aureus Enterococcus faecalis (in canaries) Important but Infrequent Bacterial Diseases 1 Bordetella mt Mycobacteria mt Mogabacteria § Pasteurella multocida ‘cus, and many Staphylococcus species, with the excep- tion of Staphylococcus aureus. Not all species of bacte- via are found in every culture, and cultures that lack aer- bic growth can occur in normal birds. Gram-negative bacteria are generally considered to be abnormal, but their isolation is not necessarily an indication for treat- ment. The host may tolerate small numbers, and certain strains of Escherichia coli and Enterobacter may be harmless. £. coli is frequently isolated from healthy cockatoos. Canaries and finches often have sparse nor- mal flora. ‘Common culture sites and normal flora are listed in Table 3. Cultures from the nares are not recommended, 1s contaminant organisms can be isolated from the rim Figure |—Feca! smear from a bird with yeost and gram-negative bacteria asing Gram’s stain, TABLE 2 UNCOMMONLY REPORTED BACTERIAL DISEASES IN (OMPANION BIRDS . . 1m Streptococcus (hemolytic) Yersinia of the nares and complicate diagnosis. Very fresh feces can be used for culture, but cloacal cultures are pre ferred. Gram-Negative Bacteria Enterobacteriaceae This group includes . coli, Klebsiella, Enterobacter, Salmonella, Proteus, Citrobacter, Yersinia, Serratia, and ‘others. Most species grow on conventional media. Pathogenicity varies greatly among different species and strains of these bacteria. Clinical signs of disease are similar for the various species of bacteria and depend on pathogenicity of the agent, site of infection, and condi- tion of the host (Figures 5 through 7). Many members of this group of bacteria are commonly found in the envi- ronment, and some are considered autochthonous flora of mammals and other birds. Contaminated food, water, and infected bitds are common sources of infection. Figure 2—Colection of « cloacal culture from a macaw. Cultures from the cloaca recover flora fom the urinary, repreductve, and digestive tracts.Figure 2—Collection of a cloacal culture from a macaw. Cultures from the cloaca recover flora from the urinary, reproductive, and digestive tracts.‘36 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1998 ANTIMICROBIAL THERAPY IN EXOTICS Figure 3—Trachea! wsh in an anestheted bue-fronted Amaron Figure 4—Loparoscopy is used to collec cultures fom internal part ongans TABLE 3 COMMON CULTURE SITES AND NORMAL FLORA IN COMPANION BIRDS Crop cultures can be collected with a moistened swab or by gavage. Indications for crop cytol ogy and cultures include regurgitation and crop stasis. Normal alimentary tac flora i usualy present, The presence of small numbers of gram-negative bacteria may be due to transient Organisms in food that have no clinical significance. The choana receives flora from the upper respiratory system and the oral cavity. Indications for sampling include thinitis and periorbital sinusitis. Samples from this site should be collected with a small alginate swab directed toward the rostral-most portion of the sift Swabs collected from the caudal sit are often contaminated with flora from the oral cavity. Periorbital sinus Sinusitis and chronic rhinitis are indications for sampling ths site. Samples can be collected sur- ically or by gently flushing saline with a needle and syringe. The normal sinus should be sterile ‘a contain small numbers of normal alimentary tract flora, Conjunctiva Samples can be collected with a moistened swab or spatula, indications for sampling include Conjunctivitis and epiphora. Normal cultures are usually sterile, but small numbers of Staphylococcus epidermidis, alpha-hemolytic Streptococcus, and Corynebacterium can be isolat- ed from normal birds? a Birds) Trachea ‘Samples can be collected with the patient under anesthesia by introducing a swab protected by a sterile sleeve through the glottis or by conducting a tracheal wash. Indications for sampling include chronic cough or inspiratory dyspnea, Normal samples are usually sterile; small numbers of Streptococeus are occasionally isolated Internal organs The lungs can be sampled by flushing and aspirating a small amount of saline introduced via a sterile tracheal tube. Air sacs, liver, kidney, spleen, and other organs are best sampled via ‘endoscopy. Samples from internal organs should be sterile. Occasionally small numbers of nor mal alimentary tract flora are isolated. s 3 c iss 4 3COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS Figure 5—Mating hyacinth macows. Breeding bird shouldbe ro ely cultured prior to the reeding season to ident subclinical righ be passed nesting. E coli, Enterobacter, and Klebsiella are common di ‘ease agents in companion birds. Isolation of small numbers may not be clinically significant. Enterobacter is a common seed contaminant that seldom causes nical infection, except in compromised hosts. E. coli strains can vary from innocuous to highly pathogenic, but no in vitro methods are available to identity non- pathogenic strains. Klebsiella is a common food and environmental contaminant that can cause serious infections in compromised hosts or when present in large numbers. Klebsiella is protected by a capsule; therefore, longer treatment periods may be required for elimination from the host. Infection by other members of this group is less com- mon. Proteus is usually found in unsanitary environ- ments and infects compromised hosts. Citrobacter is uncommon in psittacines but is a common cause of septicemia in weaver finches and waxbills. Salmonella, Yersinia, and Serratia are generally considered patho- genic, so isolation of even small numbers of these gen- ‘era may be significant. Salmonella is shed intermittent- ly and may require special enrichment media (e. selenite broth and/or briliant green agar) to enhance growth. Salmonella infections in psittacine birds are rel- atively uncommon, but outbreaks can cause wide- spread mortality. Yersinia pseudotuberculosis infections ‘are common in Europe but infrequent in the United States. Toucans, aracaris, and barbets are considered highly susceptible. Occasional reports of Serratia infec- tions in psittacine birds have been reported. The susceptibility of the Enterobacteriaceae to antibi- ties varies with both the species and strain of the organism; therefore, susceptibility tests for specific iso- lates are necessary. Most isolates are susceptible to the fluoroquinolones, aminoglycosides, advanced-genera- Is lethargl anorexic, and has fuffed fea ig in-a nesting hyacinth macaw due t0 a in ed by Klebsiella pneumoniae and yeas. Stunted birds often have poor feathering and a body that is small in relation to the head site. tion beta-lactam antibiotics, and_trimethoprim-sulfa drug combinations. Resistance to tetracyclines, chlor- amphenicol, early generation beta-lactam antibiotics (eg, ampicillin, cephalexin), and the macrolides is common. if empiric treatment is needed before sus- ceptibility tests are available, enrofloxacin is a good first- choice antibiot Pseudomonas aeruginosa Pseudomonas aeruginosa commonly causes respira- tory, alimentary, and wound infections (Figure 8). It grows on conventional media. Pseudomonas is not usu- ally highly pathogenic, but systemic infections can occur in compromised birds. It is found in moist environments ‘and can contaminate garden hoses, faucets, and auto- matic watering systems. Comcob bedding and fruits and vegetables may also become contaminated. Birds usual ly acquire infections from environmental sources, although bird-to-bird transmission of respiratory and ali-KS ac} ix & 4 3 38. Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3A) 1998 ANTIMICROBIAL THERAPY IN EXOTICS Figure 8—Sinusitis in @ Mexican red-headed Amazon parrot caused by a resistant strain of Pseudomonas aeruginosa. mentary tract infection occurs. Pseudomonas aerugi- 1nosa is often resistant to conventional antibiotics; there- fore, aminoglycosides, advanced-generation beta-lactam antibiotics (e.g, piperacillin or cefotaxime), and the fluoroquinolones may be needed for treatment. Aminoglycoside therapy combined with an advanced- ‘generation beta-lactam may be needed to treat resistant. strains, Strains that are resistant to all available antibi- oties are occasionally encountered in avian medicine. Bordetella avium Bordetella avium is a more recently recognized pathogen of psittacine birds.” It is primarily associated with upper respiratory infections in psittacines and is one of the causes of “lock-jaw” in nestling cockatiels. It grows on conventional media, but the colonies are tiny and may be overlooked or overgrown by gram-negative bacteria and yeast. Treatment is most effective if started very early in the disease process; however, treatment failures are common, and birds with resolving clinical signs may still shed the organism. In several outbreaks of temporomandibular rigidity in cockatiels, isolates of Bordetella were susceptible to numerous antibiotics in vitro but treatment was not successful.®” Management techniques including removal of potential adult carriers, isolation of sick birds, and careful cleaning and disin- {ection of the aviary and nursery are necessary to con- trol this problem, Pasteurella multocida Pasteurella multocida is a gram-negative rod with characteristic bi-polar staining. Infection is rare in com- anion birds, except for those attacked by mammals, especially cats. Inoculation of Pasteurella following a ‘at bite can result in @ rapid septicemia and death. For Figure 9—Dermaitis in the axilla of a cockatel. Avian dermati~ tis is often complicated by Staphylococcus aureus. Figure !0—Feather loss in a green-winged macaw. Feather pick ing and Joss are usually due to behavioral or viral ceuses but may be complicated by a bacterial foliults. this reason, cat bites are usually treated as an avian emergency and prophylactic antibiotic treatment with a parenteral drug is immediately started if there is a chance of skin penetration. Pasteurella is susceptible to many antibiotics. Gram-Positive Bacteria Gram-positive bacterial infections are much less com- mon than gram-negative infections in psittacine birds. Of the gram-positive bacteria, Staphylococcus aureus is most commonly linked with disease in psittacines. En- terococcus faecalis infections are common in canaries and finches. Most Staphylococcus species isolated from birds are considered normal flora. Staphylococcus aureus is con- sidered to be potentially pathogenic and is most com- monly involved in skin and wound infections (Figures 9 and 10). Septicemia and respiratory, joint, neurologic, and umbilical infections also occur. Antimicrobial sus- ceptibilty varies and should be confirmed with a sus-COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS Figure ll—Hepatc granulomas caused by Mycobacterium avi- ceptbilty test. Early generation beta-lactams, aminogly- cosides, fluoroquinolones, and trimethoprim-sulfa are potentially effective. ‘A number of Streptococcus species are also part of the normal alimentary tract flora. Pathogenicity markers are lacking for avian Streptococcus, but it is believed that hemolytic strains may be more pathogenic. Pathogenic species have been associated with respira- tory disease, joint lesions, endocarditis, and omphalits. Streptococcus may be resistant to numerous antibiotics, including fluoroquinolones and the aminoglycosides. Susceptibility testing is necessary to guide drug selec- tion Enterococcus faecalis (formerly known as Strepto- coccus faecalis) is a common cause of persistent tra- cheitis and respiratory infections in canaries and finch- ¢s." Infection can be very difficult to eliminate. Often, antimicrobial therapy provides temporary relief but clin- ical signs recur. In a colony, isolating affected individu- als and repeatedly treating the flock helps to control infection. Improved hygiene may also help. Other Significant Bacterial Infections ‘Mycobacteria Mycobacteria are acid-fast bacteria that require special media and long growth periods for isolation. A number of species can potentially infect birds, including Mycobacterium avium, M. bovis, M. genavense, and, rarely, M. tuberculosis M. and M. 4genavense cause the majority of avian infections. Avian mycobacterial infec- avium testy mits Mycobacterium species should be Hfelsetatateet) infected birds to PIC ree nett tea date Eres a0 8 Fito tntrar co tions are not commonly passed to humans, but precau- tions should be taken to prevent exposure to young, old, and immunosuppressed people. Infections are most commonly reported in older finches, Amazon parrots, and parakeets of the genus Brotogeris (e.g, grey-cheeked)." Mycobacteria cause chronic debiltation; the most common clinical signs are wasting, poor feathering, and inactivity. Most birds will have a marked leukocytosis. Infection usually begins in the intestine and later spreads to other organs, espe- cially the liver and spleen. Skin and bone marrow lesions are also common. Three types of lesions are seen: (1) the tubercular form where classic granulomas may form in various tissues (Figure 11), (2) the nontu- berculous form where there is diffuse infiltration of var- ious organs but no granuloma formation, and (3) the paratuberculous form with the most prominent lesions confined to the intestinal tract. Avian mycobacterial lesions may be confused with tumors and other lesions; therefore, impression smears should be routinely col- lected from any abnormal mass for acid-fast staining. Mycobacterial infections are diagnosed by demon- strating acid-fast organisms by culture or staining in feces, organ biopsies, or histopathologic sections. Newer methods using radiometric culturing and DNA probe tests may provide more reliable results. Antemortem diagnosis can be difficult; repeated testing of fecal samples or hepatic biopsy is recommended. if possible, the Mycobacterium species should be identi- fied to aid in assessing the zoonotic risk of the infection. Euthanasia is usually recommended to reduce expo- sure to humans and other birds. Treatment using pro- longed administration of a cocktail of drugs has been successful but requires extreme diligence on the part of the owner to accomplish the treatment. Birds with the nontuberculous form have the greatest chance of success; those with large granulomas will sel- dom respond. The occurrence of Mycobacterium infection in a collection of birds causes great concem to the bird owner because itis difficult to determine how far the infection has spread. There can be a long delay between exposure and the onset of identifiable signs—up to 18 months in the author's experience. Following exposure, birds in direct con- tact with the contaminated area should be isolated for approximately 2 years. 9oA Q oy S BS = i oy _ ei 40 Supp! Compend Contin Educ Pract Vet Vel. 20, No. 3(A), 1998 Figure 12—Merican red-teaded Amazon partot in a heated oxy gen cage. Supportive core is important when managing microbial The aviary should be cleaned and disinfected with a tuberculocidal disinfectant, and all exposed organic material (eg, perches, nest boxes) should be discard- ed, Birds can be screened for disease by monitoring bodyweight, complete blood counts, and acid-fast stains of feces approximately every 2 to 3 months. ill birds should be isolated and tested with hepatic biopsy. Megabacteria Megabacteria are very large (20 to 50 jum) gram-pos- itive rods." They are difficult to grow but can be isolat- ed on blood agar in an environment enriched with 10% carbon dioxide. investigators that megabactetia are a normal component of the upper alimentary tract flora that causes opportunistic infections.® Megabacterial infections are most ‘common in finches, budgerigars, and other small psittacines, but infections have been reported in the larger psittacines and other avian species. Clinical signs include weightloss, regur- gitation, passage of whole seeds in the droppings, and diarrhea. Debilitated birds often suffer secondary infections and eventually die. The bacteria cause proventricular and ventricular disease, induding dilatation, increased mucus secretion, decreased luminal acidity, and softening of the koilin layer. Diagnosis is most reliably made at necropsy, where the organism can be demonstrated in histopathologic sam- Some believe The goal of EVitslyrstamttocyeg SCMcom ciate tty effective drug otro ie ene ta itor fuccas(n act period sufficient to aid the host in Glitters ta ANTIMICROBIAL THERAPY IN EXOTICS ples or smears of the proventricular mucosa using Gram’s stain, Antemortem diagnosis is more difficult, as ical signs are similar to proventricular dilatation dis- ease. The large rods can be found on fecal smears, but shedding of the organism may be intermittent. Radio- graphs or fluoroscopy may demonstrate proventricular dilatation and a characteristic hourglass constriction between the proventriculus and ventriculus." Treatment of patients with megabacterial disease is stil being investigated. Reports of in vitro antibiotic sus- ceptiblity are conflicting, and antibiotic treatment is seldom successful. Better success has been achieved by acidifying the drinking water and treating with antifun- gal agents. Oral amphotericin B and nystatin have been effective in small birds." Antibiotic Use in Companion Birds ‘As previously discussed, bacterial diseases are com- ‘mon in companion birds (parrots, canaries, and finch- es), and rational selection of the antibiotic chosen for treatment can improve success of treatment. Birds are often presented at an advanced stage of disease; there- fore, antimicrobial therapy must be maximized early in the disease process. Drugs do not act alone—a func- tional immune system is required to clear the bird of infection. Supportive care such as stress reduction and fluid, nutritional, and thermal support are very impor- tant when managing avian cases (Figure 12). It is also important to find and eliminate the source of infection and improve conditions that may con- tribute to secondary infections. General Considerations The goal of antibiotic therapy is to ‘maintain effective drug concentrations at the site of infection for a period suf- ficient to aid the host in eliminating the bacteria. Its difficult to establish thera- peutic drug concentrations in birds because they excrete many drugs rapid- 'y and repeated drug administration is stressful. The ideal therapeutic regimen establishes therapeutic concentrations with low toxicity and low frequency of | administration. Several reviews provide comprehensive information on avian antimicrobial therapy.'©? The factors described below should be considered when selecting an antibiotic.COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS Collect diagnostic samples be- fore starting treatment. Samples should be collected for cytology, culture, and serology before start ing treatment to avoid confusion in interpreting results. If you must treat empirically, ‘make an educated guess of what you want to treat. If a bird is markedly ill, it may be necessary to start treatment before the results of culture and susceptibility tests are known. Knowledge of the common microbial diseases will help guide both diagnostic and therapeutic decisions. n psittacine birds, infections by gram-negative bacteria (Enterobacteriaceae and Pseudomonas), Chlamydia psittaci, and yeast (Candida) are common and should be considered in the diferential diagnosis of any sick bicd. The following pathogens are less common: gram-positive bac- teria (eg, Staphylococcus aureus), ‘Mycobacterium avium, and Asper- gillas. In canaries and finches, gram-positive bacterial infections are more commonly encountered than in psittacines. Table 4 pro- vides guidelines for treatment if susceptibility results are unknown. Measure the susceptibility pat- tem of the target organisms. The “Se antimicrobial susceptibility of com- tot mon bacterial isolates can be mea- ‘sured by either Kitby-Bauer or min- imum inhibitory concentration (MIC) tests. Results from a Kirby- Bauer test can be misleading when applied to birds (Figure 13). The citeria for deciding whether an isolate is susceptible are based on drug concentrations that can be achieved with a standardized dosing regimen in humans (or small animals tis not always possible to achieve sim- ilar concentrations in birds. MIC data provide quantitative information that can be very useful when develo treatment regimens for resistant organisms. Consider whether immediate antimicrobial action is required. Marked ill or septicemic birds will benefit from a bactericidal drug administered intramuscularly Organism idemenas bes eater tate TREATMENT GUIDELIN! sceptblty is highly verible, TABLE 4 5 FOR AVIAN MICROBIAL DISEASE WITH UNKNOWN SUSCEPTIBILITY RE: Treatment Fluoroquinolones (ee Aminoglycasides Late-generation betatactams Trimethaprim-sulfa combin: joxacin [Bayti”, Bayer) Fluoroquingtones ( Aminoglycosides cin [Baytil, Bayer)) Aminoglycosides luoroquinolones ( Advanced-generation ‘enrofloxacin [Bayti”, Bayer]) lactams Amikacin of tobramycin and cefotaxime combination Amikacin or tobramycin and piperacillin combination ‘Amikacin or tobramycin and enrofloxacin combination Many antibiotics effective Early generation betalactams (eg. cephalexin) Metron Nystatin Ketoconazole uconazole nes, and advanced Combination therapy with amikacin or tobramycin and cefotaxime, or intravenously. Enrofloxacin is a good choice for ‘empiric therapy of a suspected gram-negative bacterial infection. Consider how the drug should be delivered and how frequently it can be dosed. Dosing the drug is stressful for both the owner and patient. The treatment regimen should require as little bird handling as possi- ble. Some birds will initially accept oral dosing but later refuse it. Small volumes are usually easier to dose than larger volumes, so availability of a concentrated oral for- mulation is helpful. Make sure the owner can accom- 41a 2 rs) ies) 42. Supp! Compend Contin Educ Pract Vet Vol. 20, No. 3(A), 1998 Figure 13—Routine interpretation of the dsc diffusion antimicro~ bial suscepiblty te may be misleading in birds, Isolates are clar~ sified as susceptible based on the antibiotic concentrations that can be maincained in human; similar concentrations may not be achier= able in birds. plish the treatment recommendations and check to ver- ify compliance. Consider conditions at the site of infection. ‘Abscesses and granulomas are dificult to treat because reduced blood supply, debris, pH, and low oxygen ten- sion may interfere with the action of some antibiotics. Abscesses should be surgically debulked. Flushing the nares with saline removes mucus and aids in the treat- ment of upper respiratory infections. Lipophilic drugs and increased drug concentrations are needed to pen- etrate these sites, Consider potential toxic side effects, especially in ANTIMICROBIAL THERAPY IN EXOTICS relation to the patient's current physiologic condition and possible combined effects if more than one drug is used, Table 5 lists potential toxic side effects of several ‘commonly used agents. Monitor or treat the patient for secondary infec- tions. Many of the drugs used in avian medicine reduce normal alimentary tract flora. Treated birds are more prone to secondary infections by resistant bacteria, ‘yeast, and aspergillosis. Regardless of the site of infec- tion, the cloaca should be cultured and treatment for potential pathogens included in the therapeutic plan. The owner should maximize nutrition, maximize hus- bandry to reduce exposure to environmental patho- gens, and minimize stress to reduce the impact on the immune system. Monitoring fecal Gram’s stains or pro- phylactic treatment with antifungal drugs is recom- mended when treating nestling birds. Antibiotics NOT Commonly Used in Companion Avian Medicine Penicillin, tetracycline, and erythromycin are seldom used in avian medicine because microbial resistance is common. Kanamycin and streptomycin are consid- ered too toxic for use in birds. Chloramphenicol is rarely used because there are more efficacious drugs and con- tact with this drug can cause adverse reactions in humans. Antibioties requi tration are seldom used because of the difficulty of ‘administration. i intravenous-only adminis- TABLE 5 POTENTIAL TOXIC SIDE EFFECTS OF ANTIBIOTICS USED IN COMPANION BIRDS Nephrotoricty is commonly reported in companion ‘dysfunction and ototoxicity are potential complications. — Betalactams Toxic reactions are rarely reported. Idiosyncratic reactions (eg, anaphylaxis and . anemia) have been anecdotally reported. Endotoxin release is @ potential problem e iflarge numbers of gram-negative bacteria ate killed ‘Timethoprim-sulfa combinations Gi upset and regurgitation are commonly reported, especially in macaws. The sul- {fa component can be nephrotoxic in dehydrated animals. Doxycycline Hepatic toxicity occurs in birds treated with excessive doses.COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS 3 MVLNS) Bone) COMMONLY USED ANTIBIOTICS IN COMPANION BIRDS | Drug/Spectrum Starting Dosages. Dosing Comments Other Comments | Enrofloxacin 15 mg/kg IM oF ‘Most infections in Oral administration is Enrotloxacin (Bayt, Bayes) is Po Bib psittacines ond passerines well tolerated; IM highly active against most garr- administration causes ‘negate bacteria resistance 15 mg/kg IM or Highly susceptible bacteria __ritation at the site of ‘orimonly reported for PO once daily (eg, MIC <0.03 pgimi) injection Pseuidemanas aeruginosa at ower doses and occasionally 15 mg/kg IM or ‘Senegal parrats for E col, Klebsiella, and Po BiD-TiD Acinetobacter, acinity is moderate ‘against Staphylococaus sp. and 05 t0.05 mg/ml Highly susceptible bacteria limited against Streptococcus sp; in drinking water (MIC-<0.1 ug/ml) ino activity against anaerobes Penicillin 100-200 mg/kg _—_use higher doses and more __Penicilins have relatively ‘Ampicilin and amoxicilin are PO or IMthvee to frequent administration low toxicity an advantage effective against many gram- six times daily with severe infections and when treating patients postive bacteria and anaerobes more resistant organisms with compromised renal but few gram-negative bacteria; ‘ot hepatic function; 2 later-generation pericilins Little research completed major disadvantage is the Gicarcilin, piperacillin) have to direct dosage guidelines. frequency of enhanced activity against gram- administration require negative baceria, including to maintain effe Pseudomonas, but are avalable concentrations jn parenteral formulations only ephalosporins 50-100 mg/kg PO Use higher doses and more __Cephalosporins have First-generation products OF IM thiee to six frequent administration relatively low tc (cephalothin, cephalexin) are times deily with severe infections and advantage when treating effective against many gram. ore resistant organisms patients with Positive and some gram-negative rapranases eri bacteria; most second- and third Little research complet repatic Function; a major ‘generation cephalosporins to direct dosage guidel disadvar demonstrate enhanced gram- negative but reduced gram- positive bacterial activity to maintain effective centrations Aminoglycosides 5-10 mg/kg/day Excellent activity against most sram-negative bacteria and 20-30 mg/kg/day Amikacin Staphylococcus; poor activity ‘against most Streptococcus, anaerobes, and sites with low ‘oxygen tension; tobramycin most active against Pseudomonas; aminoglycosides synergistic wth those betalactam antibiotics and ‘amikacin is the least toxic possibly the fluoroquinolones sntamicin, tobramycin hydrated patients and th renal disease ‘Trimethoprim-sutfamethoxazole 16 mg/kg of Dose is empirically Probably bacteriostatic at Good efficacy against many trimethoprim with but often successful doses used in birds; may ‘gram-positive and gram-negative 80 mg of not be the best choice for etal pathogens, with the sulfamethoxazole Po BID ption some strains of E.coli Klebsiella are resistant ator (continued)? > 2 = iS 3 i 6. oy eu 44 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 3(A) 1998 ANTIMICROBIAL THERAPY IN EXOTICS TABLE 6 (continued) ‘Drug/Spectrum Starting Dosages Tetracyclines Chlortetracyeine: Used primariy to treat 196 in diet chlamyydiosis in companion birds; some actvity against other bacteria, but therapeutic drug Doxycycline: concentrations difficult to 25-50 mg/kg/day achieve; treatment of PO chlamydiosis requires 45 days of treatment and can be difficult, consult references for further Doxyeyclne: 75-100 mg/kg IM every 5-7 days Liquamycin 14-200" Prize long-acting onytetracydine: 50-75 mg/kg SQ every 2-3 days lindamycin Active against gram-positive and anaerobic bacteria 100 mg/kg SID 0 mg/kg BID g TID tics Commonly Used in Companion Avian Medicine It is important to note that drug doses in birds are poorly established. The doses listed in this section are ‘general recommendations; safety and efficacy will vary. Commonly used antibiotics in companion birds are list ed in Table 6. Enrofloxacin Enrofloxacin is a fluoroquinolone antimicrobial drug.” It is bactericidal, widely distributed, and excreted primarily through renal tubular secretion and glomeru- lar filtration. Enrofloxacin is partially metabolized by the liver to ciprofloxacin, an equipotent metabolite. Oral administration is well tolerated; intramuscular adminis- tration causes irritation at the site of injection. Articular defects in growing animals and inducement of seizures in seizure-prone animals have been reported in mam- mals but not in psittacine “Dosing Comments Other Comments Ausable in commercial pellets or can be added to mash diet May be poorly accepted Macaws and cockatoos should receive the low end of the dosage range: doses poorly established for some birds ‘May couse regurgitation; ‘monitor closely for hepatic toxicity Use only formulations that have been tested in birds Good information to Buide dosing of Vibravens® (Pfizer) doses for other products poorly established; all injectable products cause intation oF necrosis at the site of injection Goffin’s cockatoos, blue and gold macaws; doses not established in other species Causes iritation at the site of injection; use caution with multiple injections; inject between shoulder blades to ‘minimize complications | Dose developed for pigeons Most olten used to treat osteomyelitis caused by anaerobic bacteria Empirically derived dose used in psittacines and raptors Enrofloracin is highly active against most gram-nega- tive bacteria, although resistance is commonly reported for Pseudomonas aeruginosa at lower doses and occa- sionally reported for E.coli, Klebsiella, and Acinetobacter. Resistance develops slowly and is believed to occur only by chromosomal mutation. Enrofloxacin has moderate activity against Staphylococcus, poor activity against most Streptococcus and Enterococcus, and no activity against anaerobes. thas been used to treat chlamydiosis and in the author's experience will ameliorate clinical signs but ‘not necessarily eliminate the infection. Doses of 15 mg/kg IM or PO twice daily maintains effective drug concentrations in most of the psittacine species that have been tested® Senegal parrots required thrice daily dosing for moderately resistant ‘organisms. For highly susceptible bacterial infections (MIC <0.03 g/ml) in most parrots, once daily dosing may be adequate. Intramuscular injection act vesCOMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS greater peak concentrations and can be used to initiate treatment in severely ill birds. The intramuscular formu- lation causes irritation at the site of injection, so this route should not be used for repeated administration. The intramuscular formulation, however, can be given orally. Enrofloxacin dosed at 0.3 to 0.5 mg/ml in drink- ing water can be used to treat highly susceptible bacte- tia (MIC <0.1 g/m.” Enrofloxacin is an extraordinary drug. tt is highly active against gram-negative bacteria and effective with ‘once or twice daily dosing. It is one of the few anti otics that is effective when administered via the drink- ing water; however, the MIC of the organism must be known since lower plasma concentrations are achieved than with other routes of administration. Disadvantages include relative inactivity against many Streptococcus and all anaerobes. itis unpalatable, and some birds will refuse oral administration. Placing the drug in a flavored vehicle or fruit juice may help. Correctly using and dos- ing enrofloxacin is imperative if resistance is to be avoided. Penicilins and Cephalosporins (Beta-Lactam Antibiotics) ‘The penicillins and cephalosporins are beta-lactam antibiotics and share similar pharmacology.” They are bactericidal and widely distributed to the extracellular space but poorly penetrate the cerebrospinal fluid. Renal excretion is rapid, and they are considered less toxic than other antibiotics, although allergic reactions (anaphylaxis) can ‘occur. Beta-lactams have reduced effi- cacy in the presence of overwhelming numbers of organisms (‘inoculum effect’). They also cause the release of endotoxin after killing bacteria, a theo- retic disadvantage when treating gram- negative bacterial sepsis. The spectrum and route of adminis- tration of the effective against many gram-positive but few gram-negative organisms and ‘are available in oral and injectable for- Pvt rmulations. Later-generation per such as ticacilin and piperacillin have enhanced activity against gram-negative bacteria, including Pseudomonas, but ate available in parenteral formulations only. Cephalosporins also differ in spec- incu oetar et Hel bMetathis against gram- ioe bvem ace ee can be dosed once ary Cr en be ritel is one of the few Tete tea effective when Preritrcicocstaae} faitote tate etter coo trum and are classified into first, second, and third-gen- eration products First-generation products such as cephalothin and cephalexin are effective against many gram-positive and some gram-negative bacteria In gen- eral, second- and third-generation cephalosporins demonstrate enhanced gram-negative bacterial activity but reduced activity against gram-positive bacteria, The third-generation product cefotaxime has been widely used to treat Pseudomonas infections and, unlike other cephalosporins, achieves therapeutic concentrations in the central nervous system. Early generation penicilins are appropriate only for treating infections caused by highly susceptible patho- gens. First-generation cephalosporins have better gram- negative activity but are primarily used to treat gram- positive bacteria, especially susceptible strains of ‘Staphylococcus aureus. The advanced-generation peni- cillins and cephalosporins have an excellent gram- negative spectrum. Beta-lactams have relatively low tox- icity, an advantage when treating patients with compro- mised renal or hepatic function. A major disadvantage is the frequency of administration required to maintain effective concentrations. Limited dosing studies suggest that the penicillins should be administered at 100 to 200 mg/kg three to six times daily" and the cephalo- sporins at 50 to 100 mg/kg three to six times daily.” Higher doses and more frequent administration are especially important when treating severe infections. Aninogiycosides ‘The aminoglycoside antibiotics are bactericidal, and those used in avian medicine include gentamicin, mycin, and amikacin.” They are not absorbed from the gastrointestinal tract and must be administered parenteral- Iy2® Aminoglycosides are confined to the extracellular space and poorly pen- etrate the eye and cerebrospinal fluid. Excretion is almost exclusively by glomerular filtration. Aminoglycosides are not active against anaerobes nor are they active against facultative anaer- obes at sites with low oxygen tension (eg, large abscesses). Activity is reduced in proteinaceous environ- ments such as abscesses and exudates. ‘Aminoglycosides are relatively toxic when compared to other antibiotics.” Nephrotonicity, ototoxicity, and neuro- tobra- 4546 Suppl Compend Contin Educ Pract Vet Vol. 20, No. 5(A), 1998 muscular synaptic dysfunction (with rapid intravenous infusion) are potential complications. Nephrotoxicity is relatively common in treated birds but usually resolves if the drug is dosed appropriately and for a short dura- tion. Aminoglycoside therapy should be limited to 7 days and used with caution in dehydrated patients or those with compromised renal function. Because of potential toxicity, only gentamicin, tobramycin, and amikacin are routinely used in com- anion avian medicine. Amikacin is considered to be the least toxic and is the aminoglycoside of choice. Gentamicin can be used to reduce expense and to treat amikacin-resistant organisms. Tobramycin is especially active against Pseudomonas. These drugs have excel- lent activity against most gram-negative bacteria and Staphylococcus. Aminoglycosides have poor activity against most Streptococcus, anaerobes, and sites with low oxygen tension. They are synergistic with beta-lac- tam antibiotics and possibly the fluoroquinolones. Advantages of aminoglycoside use include once to twice daily administration and excellent activity against ‘gram-negative bacteria, Disadvantages include poten- tial nephrotoxicity and the need for par- enteral administration. Kinetic studies fof gentamicin® and amikacin™ recom- mended dosing at two to three times day. New information indicates that the same total daily dose administered once daily may be as effective as split- ing it into multiple daily doses.” Gentamicin and tobramycin canbe dosed at 5 to 10 mg/kg/day and amikacin at 20 to 30 mg/kg/day. Trimethoprim—Sulfonamide Combinations Combining trimethoprim with @ sul- fonamide causes synergistic interfer- fence with microbial folic acid synthe- sis This combination is probably bacteriostatic at the doses used in birds. Tissue penetration is good, and excretion is primarily renal. This combi- nation has good efficacy against many gram-positive and gram-negative bac- terial pathogens, with the exception of Pseudomonas. Timethoprim-sulfonamide combi- nations are usually well tolerated but may cause gastrointestinal upset and regurgitation after oral dosing, especial- PeUiitius ova (Co therapy should be limited to 7 days PYOmice Matta caution in PLC a ton Dut Meeurcon ttc renal function; amikacin is oes seeacoors fae oyatoe(e and is the elites nicest ie nt (ead ANTIMICROBIAL THERAPY IN EXOTICS ly in macaws, This can be reduced by giving less drug or adding the drug to food, Sulfonamides can cause kid- ney damage in dehydrated birds, and injectable prod- ucts may cause irritation and necrosis at the site of injection. Many other side effects (eg, rashes, photo- sensitization, arthritis, and hepatic disorders) have been reported in mammals but not in birds. Pharmacokinetic studies have not been performed in psittacine birds, but empiric doses of 16 mg/kg of trimethoprim with 80 mg of sulfamethoxazole given twice daily have been clini- cally successful. A combination of trimethoprim-sul- famethoxazole is most commonly used in birds. jethoprim-sulfamethoxazole is an. excellent broad-spectrum bacteriostatic drug. It is often used for oral treatment of gram-negative bacterial infections, especially in nestling birds. Disadvantages include the relatively large volume that must be dosed, the occur- rence of regurgitation in some birds, and the potential for nephrotoxicity in dehydrated birds. Tetracyclines Tetracyclines are bacteriostatic, lipophilic, and widely distributed to tissue. Injectable formu- lations are available but cause necrosi at the site of injection. Oral absorption is reduced in the presence of cations such as calcium or magnesium. The route of excretion varies. Prolonged treatment may have catabolic and immunosuppressive effects, reduce normal gut flora, and render the animal ‘more susceptible to opportunistic infec- CO ere ors In companion avian medicine, tetra- gyclines are primarily used to treat chlamydiosis. Most other bacterial infections are resistant at plasma con- centrations (0.5 to 2 g/ml) that can be achieved in birds. Doxycycline is the most commonly used tetracycline because it is more lipid soluble, readily absorbed after oral administration, and has a prolonged elimination half-life. Treatment of chlamydiosis is com- plex because long treatment periods (60 to 45 days) are necessary to clear birds of infection. injectable, oral, food- based, and water-based treatment reg- imens have been used with varying degrees of success and complications.COMMON BACTERIAL INFECTIONS AND ANTIBIOTIC USE IN COMPANION BIRDS Reviews covering treatment of chlamy- diosis are available.*3* Macrolides ‘The macrolides are bacteriostatic and active against gram-positive bacteria and anaerobic bacteria." Oral absorp- tion is good in mammals; few pharma- cokinetic studies have been done in birds. Macrolides are well distributed to tissues and eliminated primarily by hepatic metabolism. Toxicity is usually limited to gastrointestinal irritation and vomiting. Clindamycin is the most use- ful drug in birds; erythromycin and tylosin are seldom used. New macro- lides (azithromycin and clarithromycin) show prolonged tissue half-lives in oth- er species but have not been investigat- cd in birds. ‘Advantages of clindamycin. include good activity against gram-positive and anaerobic bacteria. There are no phar- macokinetic studies to guide dosing psittacines, but 100 mg/kg given once daily is recommended for pigeons.” References 1. Gerlach H: Bacteria in Ritchie BW, Harson G), Harrison LR (eds): Avian Medicine: Principals and Application. Lake ‘Worth, FL, Wingers Publishing, 1994, pp 948-983. 2. ReavillD: Bacterial diseases, in Rosskopf W, Woerpel RW (eds): Diseases of Cage and Aviary Birds. Baltimore, Willams & Wikins, 1996, pp 596-612. 3. Dortestein Git: Bacteriology, in Altman RB, Cubb St, Dorrestein GM, Quesenberry K (eds): Avian Medicine and Surgery Philadelphia, WS Saunders, 1997, pp 255-200. 4, Campbell TW: Avian Hematology and Cytology. Ames, IA, lowa State University Press, 1968. 5. Tayior M: Endoscopic examination and biopsy techniques, in Ritchie BM, Harison Gi, Harrison LR (eds): Avion Medicine: Principals and Application. Lake Worth, FL, Wingers Publishing, 1994, pp 327-354 6, Bangert RL, Cho BR, Widders PR, ea A survey of aerobic bacteria and fungi in the feces of healthy psitacine birds. Avion Dis 32:46-52, 1988, 1L. Bowman TA, Jacobson ER: Cloacal flora of clinically normal captive psitacine birds. J Zo0 Anim Med 1181-85, 1980. 8. Flammer k, Drewes LA: Species-related differences in the incidence of gram negative bacteria (slated from the cloaca of psitacne birds. Avian Dis 32:79-83, 1988. 9. Wolf ED, Amats K, Olsen J: Survey of conjunctiva flora in the eye of clinically normal captive exotic birds. JAVIMA 185:1252-1235, 1985 10. Clubb SL: Outbreaks of bordetelloss in psittacines and stiches. Proceedings of the Association of Avian Veterinarians, 1994, pp 63-68. 11. Desriese LA, Uytebroek E, DueatelleR, etal: Tacheits due Davee lttom cats most commonly Tce mearevo va ttets cs ee Leferttoe ane d lipid soluble, Pacer ibe locog eral Fcmuc| administration, and Ete w nce tentsaet Clrtertecony half-life. 19, 20. 2. 2 23, 24, 25, 26. 2, to Enterococcus faecalis infection in canaries. J Assoc Avian Vet 2:113-116, 1990. 12, Van Der Heyden N: Mycobacteriosis, in Rosskopf Wl, Woerpel RW (eds) Diseases of Cage and Aviary Birds Baltimore, Wiliams & Wilkins, 1996, pp 596-612. 15, Ungerechts N: Radiographic signs of proventricular infection with “megabac- teria” J Assoc Avian Vet 4:203, 1990, 14, Filippich Li: Parker MG: Megabacteria and preventricular/ventricular disease in psitacines and passerines. Proceedings ff the Association of Avian Veterinar: jans, 1994, pp 287-291. 15, Filippich L, Peny RA: Drug tials against megabacteria in budgerigars (Melo- psittacus undulatus). Aust Vet Pract 2:184-189, 1993, 16, Dortestein GM: Metabolism, pharmacol- ‘gy, and therapy, in Altman R, Clubb Sl, Dorrestein GM, Quesenberry K (eds): ‘Avian Medicine and Surgery. Phila- delphia, WB Saunders, 1997, pp 659-670. 17, Tully TN: Formulary, in Altman R, Club SL, Dorrestein GM, Quesenberry K (eds): Avian Medicine and Surgery Philadelphia, WB Saunders, 1997, pp 671-688. 18, Rosskopf WI, Woerpel RW: Practical avian therapeutics with dosages of com- monly used drugs, in Rosskopf W, Woerpel RWW (eds): Diseases of Cage ‘and Aviary Birds. Baltimore, Wiliams & Wikins, 1996, pp 255-259, Carpenter JW, Mashima TY, Rupiper DJ: Exotic Animal Formulary. Manhattan, KS, Greystone Publications, 1996, Lumelj JT: Psittacine antimicrobial therapy, in Antimicrabial therapy in caged birds and exotic pets Proceedings ofthe North American Veterinary Conference, 1995, pp 38-48. Flammer K: Antimicrobial therapy, in Ritchie BWW, Har'son G, Hamison LR (eds): Avian Medicine: Principles and Application, Lake Worth, FL, Wingers Publishing, 1994, pp 434-456, Quesenberry KE: Avian antimicrobial therapeutics, in Jacobson ER, Kollias GV (eds): Exotic Animals/ Contemporary issues in Small Animal Practice 9:177-207, 1988. ‘Sheet M: Concentrations of active ingredient in the serum and tissues after parenteral administration of Baytri. Vet ‘Med Rev 2:104-119, 1987. Fammer K, Aucoin OP, Whitt DA: Intramuscular and oral disposition of enrofloxacin in Afican grey parrots follow- ing single and multiple doses. Vet Pharmacol Ther 14:359-366, 1991 Dorrestein GM: Enrofloxacin in pet avian and exotic ani- mal therapy. Proceedings of the First International Baytil ‘Symposium, 1992, pp 63-71 Flammer K: Update on the clinical pharmacology of select- ‘ed antimicrobial drugs in psittacine birds. Proceedings of the Association of Avian Veterinarians, 1995, pp 1316. Flammer k, Aucoin DP, Whitt DA, Prus SA: Plasma concen: trations of enrofloxacin in African grey parrats treated with medicated water. Avian Dis 34:1017-1022, 1990, 4748 Supp! Compend Contin Educ Pract Vet Vol. 20, No. 3A), 1996 28, 2, 30, 3 32 3. Mandell Gl, Sande MA: Peniclins, cephalosporins, and other beta lactam antibiotics, in Gilman AG, et al (eds): The Pharmacological Basis of Therapeutics. New York, Pergamon Press, 1990, pp 1065-1097. Ensley PK, Janssen DL: A preliminary study comparing the pharmacokinetics of ampicilin given orally and intramus- culary to paittacines. Z00 Anim Med 12:42-#7, 1981. Mandell GL, Sande MA: The aminoglycosides, in Gilman AG, et al (eds): The Pharmacological Basis of Therapeutics. New York, Pergamon Press, 1990, pp 1098-1116. Flammer Ket al: Adverse effects of gentamicin in scarlet macaws and rose breasted cockatoos. Am J Vet Res 50:404~407, 1990. Gronwall R, Brown MP, Clubb SA: Pharmacokinetics of amikacin in Aftican grey parrots. Am J Vet Res 50:250-252, 1989. ‘Munckhof WW), Grayson L, Turidge JD: A meta-analysis of studies on the safety and efficacy of aminoglycosides giu- en either once daily ot as divided doses. J Antimicrob Chemother 37:645-663, 1996. Bushby SRM: Sulfonamide and trimethoprim combina- 35, 36. 3 38. 39, 40. ANTIMICROBIAL THERAPY IN EXOTICS tions. JAVMA 176:1049-1060, 1980. Romwary A. Honay MS: On the pharmacokinetics of sulphonamide trimethoprim combination orally in geese. ‘Acta Vet Acad Sci Hung 26:173-179, 1976. Mandell Gl, Sande MA: Tetracyclines, chloramphenicol, erythromycin, and miscellaneous antibacterial agents, in Gilman AG, et al (eds): The Pharmacological Basis of Therapeutics. New York, Pergamon Press, 1990, pp 17-1148, Flammer K: Chlamydia, in Altman R, Clubb SL, Dorrestein GM, Quesenberry K (eds): Avian Medicine ond Surgery. Philadelphia, WB Saunders, 1997, pp 364-379. Fudge AM: Avian chlamydiosis, in Rosskopf VW, Woerpel RW (eds): Diseases of Cage and Aviary Birds, Baltimore, Williams & Wilkins, 1996, pp 572-585. Burrows GE: Phatmacology of macrolides, lincomycins, ‘and spectinomycin, JAVMA 176:1072~1077, 1980. Ritchie BV, Hartison GJ: Formulary, in Ritchie Bw, Hartison Gy, Hartison LR (eds): Avian Medicine: Principles and Application. Lake Wort, FL, Wingers Publishing, 1994, pp 457-458,