Vet Clin Equine 21 (2005) 627–649

Diagnosis and Treatment

of Septic Arthritis
Alison J. Morton, DVM, MSpVM
Department of Large Animal Sciences, University of Florida
College of Veterinary Medicine, Box 100136, Gainesville, FL 32610, USA

Septic arthritis (SA) is a common orthopedic condition presented to

equine veterinarians. Because SA is a potentially life-threatening condition,
any horse suspected of having an infected or contaminated joint should be
considered an emergency patient and warrants immediate attention. Suc-
cessful treatment of SA in horses involves several critical goals. These
goals can be broadly categorized as follows: (1) immediate and accurate
recognition of the condition, (2) complete diagnostic examinations, (3)
thorough elimination of infection, (4) prompt reduction of inflammation
and pain, and (5) timely return to function. This article briefly reviews
the pathophysiology, outlines diagnostics, describes treatment options
and prognostics, and discusses current research in diagnosis and treatment
of SA.

Etiology
Joint infection in horses most commonly results from synovial contami-
nation via wounds, hematogenous spread, and iatrogenic introduction after
intra-articular injection or surgical intervention [1–3]. Less commonly, SA
may result from local extension of a periarticular infection or idiopathically
[1–3]. The principal potentiating factors for establishing infection after inoc-
ulation are considered to be the presence of foreign material or devitalized
tissue, the nature and number of contaminating organisms, and immuno-
logic compromise [1].
SA occurs in foals and mature horses [3]. In neonates, the risk of joint
infection is greatest during the first 30 days of life [2,4], and partial or

E-mail address: mortona@mail.vetmed.ufl.edu

0749-0739/05/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.cveq.2005.08.001 vetequine.theclinics.com
628 MORTON

complete failure of passive transfer of immunoglobins is the principal pre-

disposing cause [1,2,4–6]. The resulting immunocompromise increases sus-
ceptibility to the development of pneumonia, diarrhea, and umbilical
infections, which can lead to bacteremia [1,2,4–6]. The joints and their adja-
cent tissues are preferred sites where bacteria may settle, especially in foals
younger than 6 months of age, likely because of low local blood flow and
corresponding low oxygen tension in the tissues within and surrounding
the joints [3,5]. Often, more than one joint is affected, and gram-negative bac-
teria (Escherichia coli, Salmonella, Pseudomonas, Enterobacter, Acinetobacter,
Proteus, Klebsiella, and Citrobacter spp) are commonly the cause [1,3,7].
Involvement of more than one joint is common in foals and is seen in
approximately 50% of foals with SA; it is much less common in adult horses
and has only been reported to occur in 1.5% of cases [2,8].
In adult horses, SA is more commonly a result of wounds or iatrogenic
introduction of microorganisms [3,9]. With wounds, a variety of bacteria
(gram-positive and gram-negative) can be expected, whereas Staphylococcus
aureus and other staphylococci are the usual isolates found in iatrogenic SA
[2,3,8]. Staphylococci are pathogens for human beings and animals. Human
isolates of S aureus and other staphylococci, unlike animal isolates, are fre-
quently resistant to the penicillinase-resistant penicillins and are referred to
as methicillin (oxacillin)-resistant S aureus (MRSA). MRSA emerged in the
1980s as a major clinical and epidemiologic pathogen in human hospitals
[10], and over recent years, MRSA infections in horses and other animals
have been increasingly identified [10–13]. Although no reports of MRSA in-
fection have been made in equine SA, other types of MRSA infections in
horses have been identified, and SA caused by MRSA has been reported
in a dog [10–12]. If no cause can be identified in the adult horse, it is likely
a result of hematogenous spread, and gram-positive bacteria are the more
likely cause [8].
Certain intra-articular medications, including corticosteroids and poly-
sulfated glycosaminoglycans, have been associated with a higher risk for de-
velopment of SA because of their potential to decrease normal synovial
defenses [2,14]. Adult Standardbred horses and horses that receive an
intra-articular injection are also reportedly at a higher risk for the develop-
ment of SA [2,15].

Pathophysiology
Diarthrodial joints are closed spaces with a mesenchymal synovial lin-
ing that produces and maintains a selective physical, cellular, and bio-
chemical environment [1]. The normal synovial membrane is capable of
controlling a large inoculation of microorganisms and preventing their
proliferation and colonization [2]. The size of the inoculum required
to overcome the synovial defenses is determined by the individual
 SEPTIC ARTHRITIS 629

microorganism’s virulence and pathogenicity [1,2]. SA occurs when the sy-

novial membrane or synovial fluid is inoculated with bacteria or other mi-
croorganisms that overcome these defense mechanisms, colonize, and
establish an infection within the joint space [2]. After colonization of the
synovium, there is release of a variety of enzymes, free radicals, and other
inflammatory mediators, which initiate a marked synovial inflammatory
response [1–3].
Microorganisms and foreign material contain a variety of antigens that
incite the immediate and delayed immunologic responses that contribute
to the inflammatory process. Certain microorganisms are more likely to pro-
duce delayed reactions, but with most clinical cases of SA, the predominant
response is immediate and dramatic. This immediate immune response
results when the microorganisms and debris are recognized by the host as
foreign and inflammatory cells, predominantly neutrophils, are rapidly re-
cruited to the site in an attempt to eliminate the infection [2,16,17]. In this
attempt, the neutrophils phagocytize microorganisms and release many de-
structive substances, including enzymes like collagenases and lysozymes,
free radicals, and cytokines like interleukin (IL)-1 and tumor necrosis factor
(TNF) [2,18]. Concurrent with neutrophil influx, many inflammatory medi-
ators enter the joint as a result of the disruption of the blood-synovial bar-
rier, and activation of the plasmin, kinin, coagulation, and fibrinolytic
pathways occurs [2]. This cascade of events amplifies the inflammation
and activates synoviocytes and chondrocytes. Activation of synoviocytes,
chondrocytes, neutrophils, and macrophages results in derangement of nor-
mal cell metabolism, reduced proteoglycan production, and release of a
variety of matrix metalloproteinases (MMPs) [2,18,19]. The MMPs are
a family of homologous zinc endopeptidases that are essential for normal
cartilage matrix turnover but also play a key role in the degradation of car-
tilage matrix that is central to many pathologic conditions of joints, includ-
ing SA [19–21].
In addition to the massive inflammatory process, the physical effects of
the resulting joint effusion, accumulation of fibrin, and alterations in carti-
lage biomechanics contribute to the disease process [2]. High intra-articular
pressure results from the excessive accumulation of fluid and results in pain,
reduced blood flow to the synovium and joint capsule, and ischemia of the
neighboring physes [2,22]. With SA an excessive amount of fibrin is pro-
duced, and if not removed, this fibrin can remain in the joint for many
weeks. The accumulation of fibrin often results in formation of an intrasy-
novial fibrinocellular conglomerate, or pannus [1,23]. The pannus spans the
joint and covers and traps devitalized tissue, foreign material, and bacteria.
It acts as a nidus for continued infection and is rich in inflammatory cells
that perpetuate the destructive inflammatory cycle. Because the pannus
acts as a physical barrier to the synovium, it prevents membrane diffusion,
compromising intrasynovial nutrition and access for circulating antimicro-
bial drugs [1,2].
630 MORTON

Diagnosis
History and physical examination
A complete history should be obtained and physical examination per-
formed on every horse suspected of having SA. History of a recent wound
or traumatic event, joint injection, joint or periarticular surgery, systemic ill-
ness, or immunocompromise is often reported and provides important
insight into the duration of possible infection and into the probable type
of infecting microorganism(s) involved [2]. Typically, horses with SA are
markedly lame. The lameness may have initially been less severe but is gen-
erally rapidly progressive and may quickly become non-weight bearing.
Lameness may be less severe if examination is performed close to onset of
the infection, if the affected joint is open and draining, if the joint has recently
been injected with corticosteroid medication, or if analgesic treatment has
been given [2]. Vital parameters are often within normal limits. If pain is
severe, elevated heart and respiratory rates may be present. Occasionally,
horses and, more often, foals are febrile. Marked joint effusion, periartic-
ular heat and swelling, and marked sensitivity to palpation and manipula-
tion are usually observed. Wounds or other evidence of trauma may be
identified near or distant to the affected joint. In foals, diarrhea, umbilical
infection, pneumonia, or other systemic illness is commonly present.

Peripheral blood analyses

In horses suspected of having SA, blood should be collected for a com-
plete blood cell (CBC) count and biochemical profile. In adult horses, the
CBC count and biochemical profile are usually unremarkable. Mild hyper-
fibrinogenemia and a ‘‘high normal’’ white blood cell (WBC) count with
mild neutrophilia are the most common findings [8,15,17]. In foals, moder-
ate to marked leukocytosis characterized predominantly as neutrophilia and
hyperfibrinogenemia is typically reported. If evidence of systemic disease is
present in adult horses or foals, blood culture samples should be taken and
submitted for aerobic and anaerobic cultures and microbial sensitivities.

Synovial fluid analyses

Synovial fluid collection is paramount in establishing a diagnosis and
properly directing therapy of SA in horses. Synovial fluid should be col-
lected for analysis using strict aseptic technique. Arthrocentesis should be
performed distant to any areas of potentially infected tissue (eg, abrasions,
wounds, cellulitis) to prevent potential inoculation of uninfected synovial
tissues with infectious agents. After aseptic preparation, fluid should be col-
lected and transferred into plain (red-top) and ethylenediamine tetra-acetic
acid (EDTA; purple-top) blood collection tubes. To obtain the best growth
from equine synovial fluid, blood culture bottles should be used for aerobic
 SEPTIC ARTHRITIS 631

and anaerobic microbial cultures. Blood culture bottles contain ideal media
for growth of most microorganisms, allow for a larger volume of synovial
fluid to be used, dilute and contain inhibitors of antimicrobial drugs, lyse
cells, and are easy and convenient to use [2,17,24].
If attempts at direct arthrocentesis are unsuccessful, sterile physiologic
fluid, such as 0.9% saline or lactated Ringer’s solution, can be injected
into the joint to facilitate collection. Because the fluid used to facilitate sam-
ple collection dilutes the sample, results of synovial fluid analyses are af-
fected. Urea concentration in synovial fluid of normal and septic joints
closely mirrors concentration in serum; therefore, urea concentrations in
the synovial fluid and serum collected simultaneously can provide a means
for more accurately calculating the amount of resultant synovial fluid dilu-
tion if fluid distention is necessary [25].
Conventional synovial fluid analysis and cytology should be performed.
The appearance of the synovial fluid is evaluated by visual inspection. Nor-
mal synovial fluid is pale yellow and clear. The presence of opacity and floc-
culent material in a synovial fluid sample indicates synovitis [23]. The severe
synovitis associated with SA results in a serofibrinopurulent sample, and the
fluid is often bloody secondary to hemorrhage from the markedly inflamed
synovial membrane [23]. The volume of fluid is usually increased in infected
joints but depends on the stage of disease and the amount of fibrin present
[23]. If the joint has an open wound and it is actively draining, this may be
difficult to assess and makes collection of a sample more challenging. Even
when the amount of fluid is markedly increased, collection may be difficult
because of the interference from inflamed synovial tissues and fibrinous ma-
terial within the joint. Normal synovial fluid does not contain clotting fac-
tors and therefore does not clot [23]; however, synovial fluid from septic
joints does clot, and the size of the clot is proportional to the degree of
synovitis [23].
Normal synovial fluid total protein is generally accepted as less than or
equal to 2 g/dL [23,26]. Total protein concentration increases with SA
and often rises above 4 g/dL, although it varies according to the duration
of infection and may be lower earlier in the disease process [2,8,17,23,27].
The WBC count of normal equine synovial fluid is less than 200 cells/mL
[23,26,28]. Neutrophils, lymphocytes, and large mononuclear cells are pres-
ent in normal fluid, but the neutrophils account for less than 10% of the
population of WBCs [2,23]. In equine SA, WBC counts in synovial fluid
are usually greater than 30,000 cells/mL and can often approach and exceed
100,000 cells/mL [2,8,15,17,23,29]. If the affected joint has recently been in-
jected with corticosteroid medication, the WBC count may be much lower,
especially during the initial onset. The WBC count of septic joint fluid is pre-
dominantly composed of neutrophils, which usually account for greater
than 80% of the total WBC population [2,8,15,17,29]. The neutrophils
may have toxic changes but are often healthy in appearance [23]. Bacteria
may be identified but are only reported to be seen in 25% of cases
632 MORTON

[2,8,17,23]. The synovial fluid WBC count at the time of admission has been
shown to correlate directly with ultimate survival of horses with SA [30].
Viscosity is directly related to the hyaluronan content of synovial fluid [28].
Synovial fluid viscosity decreases with SA. Practically, viscosity can be esti-
mated by watching the fluid drop from a syringe or by separating a drop be-
tween the examiner’s thumb and index finger [23]. Normal fluid strings from
a syringe from 5 to 7 cm, or from 1.5 to 5 cm between fingers, before breaking
[23]. Mucinous precipitate quality (MPQ) or mucin clotting is poor in syno-
vial fluid from infected joints. MPQ is evaluated by adding 2% acetic acid to
synovial fluid and assessing the characteristics of the precipitate formed [23].
The pH of normal synovial fluid reflects the pH of serum and is 7.3 in
healthy joints. In human beings and dogs, extremely low pH values develop
in SA [29,31,32]. The pH of synovial fluid of horses decreased significantly
within 12 hours of S aureus joint infection and ranged from 6.2 to 6.9 up to
9 days after infection in one study [29]. Intrasynovial lactate concentrations
increase with inflammation and infection secondary to anaerobic glycolysis
of synoviocytes and neutrophils [29]. The normal lactate concentration of
equine synovial fluid is slightly greater than that of serum and ranges be-
tween 1.25 and 2.8 mmol/L [29]. In an experimental model of S aureus
SA, lactate concentrations increased markedly within the first 24 hours of
joint infection, ranging from 6.9 to 11.9 mmol/L, and were significantly
higher than normal for 8 days after infection [29]. In addition, after manifesta-
tion of clinical signs, the lactate concentration was greater than 4.9 mmol/L
in 66% of the infected joints [29]. In SA in human beings and horses, serum
and synovial fluid glucose difference (SSGD) has been used as a diagnostic
aid [29,33,34]. Normally, the glucose concentration of synovial fluid closely
parallels or is slightly lower than that of serum. Increased glycolytic activity
in synovial cells and neutrophils as well as glucose consumption by bacteria
results in a reduction of synovial fluid glucose concentration [29,35]. SSGD of
1.3 to 2.2 mmol/L has been considered diagnostic for SA in people [29,33].
In 83% of horses with SA in one study, SSGD exceeded 2.2 mmol/L [29]. Sy-
novial fluid pH, lactate, and glucose can be easily and inexpensively measured
using various colorimetric analysis products, including direct visual compar-
ison using ‘‘dip sticks’’ or portable glucometer and other spectrophotometric
units commercially available.
MMP-2 and MMP-9 have been widely investigated for use as biologic
markers of cartilage degradation in human beings, horses, and other species
[19–21]. Activities of pro- (latent) and active forms of MMP-2 and MMP-9
are analyzed using gelatin zymography, a technique that is not routinely
available for commercial use and is restricted to research laboratories. In-
creased MMP-9 activity has been identified in the synovial fluid of cattle
with SA [19]. Elevations of pro-forms of MMP-2 and MMP-9 have been
shown in the synovial fluid of horses with SA, although the level of the ac-
tive form of MMP-2 was not different between the normal and septic joints
[36]. The level of the active form of MMP-9 was also elevated in septic joints
 SEPTIC ARTHRITIS 633

of horses and was directly proportional to the synovial fluid WBC count
throughout the course of the disease [36]. The ratio of pro-MMP-9 to
pro-MMP-2 was significantly different in normal, untreated septic, and trea-
ted septic joints of horses in another similar study [30]. The pro-MMP-9–
to–pro-MMP-2 ratio at the time of admission was shown to be related to
ultimate survival [30]. In another study, septic joints had significantly higher
concentrations of pro- and active MMP-9 compared with all other catego-
ries of joint disease and normal joints examined [37]. Elevations of other en-
zymes, such as alkaline phosphatase (ALP), aspartate amino transferase
(AST), and lactate dehydrogenase (LDH), have been correlated with the se-
verity of experimentally induced synovitides, but no specificity for the use of
these enzymes in the diagnosis, treatment, or prognosis of equine SA has
been established [38]. As demand for and use of these and other assays in-
crease, the availability of these tests should follow and may prove important
in the evaluation, treatment, and prognosis of horses with SA.
Polymerase chain reaction (PCR) of bacterial nucleic acid sequences is
used extensively in human cases of SA to identify obscure bacteria or bac-
teria that are difficult to culture, such as Mycoplasma spp [39]. Some veter-
inary research and clinical laboratories are currently using PCR similarly for
identification of microorganisms such as Salmonella and Rhodococcus spp,
but usefulness in diagnosis of equine SA has not been evaluated. Gas-liquid
chromatography of synovial fluid has also been shown to be useful in iden-
tifying a specific causative diagnosis of SA in human beings [23]. Preliminary
work in the horse has identified specific peaks characteristic for particular
bacteria, but this technique has not achieved routine use [40].

Synovial membrane biopsy

Biopsy of synovial membrane can be performed readily during arthro-
scopic exploration of a joint. Histologic changes seen in the synovium
of horses with SA include a neutrophilic and lymphoplasmacytic infiltrate,
edema, vasodilation, villus hypertrophy, fibrin accumulation, and formation
of granulation tissue [17,27]. Often, histology cannot differentiate between
infected and noninfected joints unless microorganisms are identified [27],
but with use of special staining and molecular biologic techniques, more ob-
scure forms of equine synovitides, such as immune-mediated arthropathies,
may be recognized. Biopsy may not provide much additional diagnostic infor-
mation over synovial fluid analyses in the horse with SA but can increase the
chance of obtaining a positive microbial culture result [5]. Culture of synovial
fluid yields better results than culture of synovial membrane, although syno-
vial fluid culture is negative in almost half of the infected joints cultured
[27]. Culturing synovial fluid and synovial membrane increased the number
of positive cultures to 70% in previously treated infected equine joints in
one study; hence, submitting both synovial fluid and synovial membrane in-
creases the likelihood of identification of the causative microorganism [17].
634 MORTON

Imaging
Radiographs of the affected joint or joints should be performed as part of
routine diagnostics of SA in horses. Radiographs are used to evaluate the
possibility and degree of bone involvement. Bone involvement may include
osteitis, osteomyelitis, physitis, osteoarthritis, or fracture that communicates
or is related to the affected joint. Osteomyelitis and physitis are common in
foals, whereas they are uncommon in adult horses [5,6]. Radiographic evi-
dence of osteoarthritic changes secondary to SA can take weeks to months
to be seen [2]; therefore, films should be obtained as close to the time of in-
jury as possible and repeated if necessary. Contrast radiography, such as fis-
tulograms and contrast arthrography, can be used to help determine
communication of a wound with a neighboring joint or can help to identify
cartilaginous defects not seen on routine radiographs. Cartilage or bone
involvement negatively influences the prognosis and necessitates more ag-
gressive surgical treatment, including removal or stabilization of fracture
fragments and debridement of unhealthy cartilage, bone, and surrounding
tissues, as well as potentially requiring multiple surgical procedures.
Ultrasonography can be useful in the diagnosis of SA in horses. Ultraso-
nography can be used for evaluation of communication of a wound with
a nearby joint, to determine the degree of effusion of the affected joint, to
assess the nature of the synovial fluid, to evaluate the integrity of parts of
the articular cartilage, to identify potential foreign bodies not readily seen
radiographically, and to assess the degree of inflammation of the synovium
subjectively. Ultrasonography is useful in joints that are not as easily as-
sessed by physical examination or radiography, such as the shoulder and
hip [2]. In addition, ultrasonography can be used for guiding arthrocentesis
for collection of synovial fluid for analyses.
Radionuclide imaging, or nuclear scintigraphy, has also been used
extensively in human patients to help in the differential diagnosis between
infected and aseptic osteoarticular diseases [41]. 67Gallium, 99mtechnetium
(Tc)-radiolabeled polyclonal IgG, 99mTc-nanocolloids, and 99mTc-methylene
diphosphonate (MDP) have all been reported for potential use in SA but
show low specificity for infection because they accumulate in areas of non-
specific inflammation as well as in areas of infection [41–43]. Specificity
ranging from 60% to 80% has been shown when 67Gallium and 99mTc-
MDP scintigraphy has been coupled [42]. 111In-labeled or 99mTc-labeled au-
tologous leukocytes have been shown to be more accurate in diagnosing SA
in human beings, especially when associated with labeled colloids or when
late 24-hour images are obtained. Using these leukocyte labeling techniques,
sensitivities between 75% and 100% and specificities between 73% and
100% have been reported [44,45]. 99mTc-ciprofloxacin scintigraphy is de-
signed to differentiate infection from sterile inflammation by specifically
binding to live bacteria with a specificity of 85% to 96% [46,47]. Limited
evaluations of scintigraphic techniques have been performed in the equine
 SEPTIC ARTHRITIS 635

patient with SA. 99mTc-labeled autologous leukocytes have been reported to

be successful in identifying infectious processes in a few individual cases in
foals and mature horses [14,48]. 99mTc-labeled autologous leukocytes and
other scintigraphic techniques may be valuable for the diagnosis of more
obscure cases of SA in horses that are not readily diagnosed by routine di-
agnostics or for evaluating whether treatment has successfully eliminated
infection.
Computed tomography (CT) and magnetic resonance imaging (MRI) are
becoming increasingly available and affordable for the diagnosis of muscu-
loskeletal problems in equine patients. CT and MRI provide superior detail
of bone and soft tissues, respectively, over other conventional equine imag-
ing techniques. Little data currently exist on use of MRI and CT for diag-
nosis of SA in horses; however, this is expected to change as the use and
availability of these modalities increase.

Treatment
Antimicrobial therapies
In horses suspected of having SA, systemic broad-spectrum antimicrobial
therapy should be instituted immediately after synovial fluid has been col-
lected for culture and other diagnostic tests. Broad-spectrum antimicrobial
coverage is recommended, regardless of the cause of SA. The initial choice
of antimicrobial agents may be guided based on the underlying cause of the
infection (eg, wound, iatrogenic) and the desirable characteristics of the an-
timicrobial agent. Desirable characteristics of the antimicrobial agent(s) in-
clude good susceptibility of common infective agents, bactericidal activity,
ability to reach therapeutic levels in synovial tissues and bone, good po-
tency, minimal toxicity and side effects to the patient, and affordability.
Most of the systemically administered antibiotics that have been evaluated
in horses have been shown to be present and active in infected joints, al-
though the maximum synovial concentrations and the time to maximum
concentration often lag behind plasma or serum concentrations [2,16,17].
Because the availability of suitable and affordable antimicrobial agents is
more limited for equine patients, a few combinations are commonly used
for initial broad-spectrum therapy. The most commonly used antibiotics
for gram-positive coverage include penicillin (potassium, sodium, or pro-
caine), sodium ampicillin, or a cephalosporin (ceftiofur, cefazolin, or cefo-
taxime). For gram-negative coverage, an aminoglycoside (gentamicin or
amikacin) or a fluoroquinolone (enrofloxacin or ciprofloxacin) is often se-
lected. If Bacteroides spp or another anaerobic microorganism is suspected,
metronidazole may also be included. Table 1 lists dosages and routes of ad-
ministration of some of the more commonly used antimicrobials [49–52].
Once microbial culture and sensitivity results are available, antimicrobial
therapy should be directed based on results. If no positive growth is
636 MORTON

Table 1
Spectrum of activity and doses for commonly used equine antimicrobials
Antimicrobial Bacterial spectrum Dosage
Amikacin Gram-negative (Escherichia Adult: 8–10 mg/kg IM or IV q24h
coli, Klebsiella spp, Proteus Foals: 20–25 mg/kg IM or IV q24h
spp, Enterobacter spp, Intra-articular: 250–500 mg/d per
Pseudomonas spp) joint
Staphylococcus spp
Ampicillin Gram-positive (except 10–20 mg/kg IM or IV q6–8h
b-lactamase producing 25–40 mg/kg IM or IV q6–8h
[eg, Staphylococcus aureus]) (anaerobic or refractory infections)
Most gram-positive anaerobes
(Clostridium spp)
Some aerobic and anaerobic
gram-negative (E coli,
Klebsiella spp, Enterobacter
spp, Proteus spp, Shigella
spp)
Azithromycin Rhodococcus equi Foals: 10 mg/kg PO q24h for 4–7
days, then q48h for 21 days
Cefazolin Gram-positive (including 10–20 mg/kg IV or IM q6–8h
penicillin-resistant Intra-articular: 500 mg/d per joint
Staphylococcus spp)
Some gram-negative (E coli,
Klebsiella spp, Enterobacter
spp)
Ceftiofur Gram-positive 2.2 mg/kg IV or IM q12h
E coli and Proteus spp 11 mg/kg/d (refractory infections)
Intra-articular: 500 mg/d per joint
Chloramphenicol Broad spectrum (Bacteroides 35–50 mg/kg PO q6–8h
spp, Bordatella spp, 25–50 mg/kg IV or IM q6–8h
Chlamydia spp,
Enterobacteriaceae,
Hemophilus spp, Pasteurella
spp, Mycoplasma spp,
Rickettsiae, Salmonella spp,
Staphylococcus spp, most
anaerobes, some protozoa)
Clarithromycin R equi Foals: 7.5 mg/kg PO q12h
Streptococcus zooepidemicus
Doxycycline Actinomyces spp, Ehrlichia 10 mg/kg PO q12h
spp, Leptospira spp, 20 mg/kg PO q24h
Borrelia spp, Toxoplasma
spp, Brucella spp,
Hemobartonella spp, some
anaerobes
Enrofloxacin Gram-negative 5 mg/kg IM or IV q24h
7.5–10 mg/kg PO q24h
 SEPTIC ARTHRITIS 637

Table 1 (continued )
Antimicrobial Bacterial spectrum Dosage
Erythromycin R equi Foals only:
Erythromycin estolate: 25 mg/kg
PO q6–8h
Erythromycin phosphate: 37.5 mg/kg
PO q12h
Erythromycin gluceptate: 5 mg/kg
IV q4–6h
Gentamicin Gram-negative (E coli, Adult: 4.4–6.6 mg/kg IV or IM q24h
Klebsiella spp, Proteus spp, Foal: (!2 weeks) 12–14 mg/kg IV or
Enterobacter spp, IM q24h
Pseudomonas spp) Intra-articular: 150–500 mg/d per
Staphylococcus spp joint
Metronidazole Anaerobes (including 10–20 mg/kg PO q6–8h
Bacteroides fragilis)
Giardia spp
Penicillin G Gram-positive (except Sodium or potassium penicillin:
b-lactamase producing 22,000–44,000 U/kg IV q6–8h
[eg, S aureus]) Procaine penicillin: 22,000–44,000
Most anaerobes U/kg IM q12h
Rifampin Broad spectrum Adults: 10 mg/kg PO q24h
R equi Foals: 7.5 mg/kg PO q12h, for
R equi, use with a macrolide
or azalide
Ticarcillin Extended penicillin, including 44 mg/kg IV or IM q6–8h
gram-positive (coagulase-
positive Staphylococcus
spp, S aureus,
Enterococcus spp,
Streptococcus spp)
gram-negative (Klebsiella
pneumoniae, Proteus
mirabilis and vulgaris,
E coli, Enterobacter
aerogenes, Serratia
marcescens, Pseudomonas
aeruginosa, and B fragilis)
Trimethoprim- Broad spectrum 20–30 mg/kg PO q12–24h
sulfamethoxazole No anaerobes
Vancomycin Gram-positive, including most 4.3–7.5 mg/kg IV q8h
methicillin-resistant strains
Abbreviations: IM, intramuscular; IV, intravenous; PO, per os; q, every.

obtained from culture, broad-spectrum therapy should be continued until

clinical signs of SA have resolved and synovial fluid parameters have nor-
malized. If no improvement is seen within a reasonable amount of time
(72 hours) despite appropriate therapy, diagnostics may need to be repeated,
including culture; antimicrobial therapy may need to be re-evaluated; and
additional surgical intervention may be warranted.
638 MORTON

An increasing number of MRSA isolates from human infections are re-

sistant to most of the commonly used antimicrobials, including aminoglyco-
sides, macrolides, fluoroquinolones, chloramphenicol, and tetracycline [10].
In addition, human MRSA strains should be considered to be resistant to all
cephalosporins, cephems, carbapenems, and other b-lactams (eg, ampicillin-
sublactam, amoxicillin-clavulanic acid, ticarcillin-clavulanic acid) regardless
of the in vitro test results obtained [10]. Increasing evidence documents
that there is interspecies transmission of MRSA and methicillin-resistant
S intermedius (MRSI) between human beings and horses as well as other an-
imals [10,53–56]. It is likely that the same resistant patterns seen with human
strains can be predicted to develop or exist in equine resistant staphylococ-
cal infections. Currently, in the treatment of human resistant infections, the
oxazolidinone, linezolid, is active against MRSA and glycopeptide-resistant
enterococci (GRE), but resistant organisms and treatment failures have
been reported [57]. Use of the streptogramin combinations quinupristin-dal-
bavancin or pristinamycin affords activity against MRSA and GRE, but the
first is limited by the slow infusion of a large volume [57,58]. Numerous in-
vestigations of new antimicrobial agents, such as the new glycopeptides or-
tavancin and dalbavancin, the glycolipodepsipeptide ramoplanin, and the
tetracyclines tigecycline and BAY73-7388, show promising results, but there
are concerns, based on existing antibiotics, that resistance may develop
quickly to these new compounds [57]. The most promising antibiotic on
the horizon is the novel lipopeptide daptomycin. Daptomycin has a uni-
que mechanism of action, displays rapid concentration-dependent killing,
and is bactericidal even during the stationary phase of growth; in addition,
resistant strains are difficult to generate in vivo [57,59]. None of these
compounds have been evaluated for use yet in horses but may become valu-
able for treatment of multiresistant infections in the future.
Many techniques and products now exist to deliver higher concentrations
of antimicrobial agents locally to infected joints than can be safely achieved
by systemic administration. These therapies should be used to augment
rather than to replace systemic antimicrobial therapy. The most simple of
these therapies is direct intra-articular administration of antimicrobial
agents. Direct intra-articular administration of gentamicin at a dose of
150 mg provides much higher synovial concentrations (1000-fold) compared
with systemic administration of 6.6 mg/kg every 24 hours and retains higher
than minimal inhibitory concentration (MIC) for many common equine
bacterial pathogens for longer than 24 hours after injection [52]. Aminogly-
cosides, including amikacin (250 mg) and gentamicin (150 mg), as well as
other antimicrobial drugs may be injected daily into infected equine joints
[52]. Intra-articular injection of antimicrobials induces a mild synovitis, al-
though it is generally accepted that the synovitis is much less detrimental
than the septic process and that the benefits outweigh any risks.
A variety of infusion systems are available that can be attached to cath-
eters or drains, which are placed and maintained in joints to provide
 SEPTIC ARTHRITIS 639

a constant infusion of antimicrobial agents. These systems theoretically al-

low one-time placement, avoiding daily arthrocentesis. Continuous infusion
of gentamicin in the tarsocrural joint of horses has been shown to deliver
significantly higher synovial concentrations than when administered
systemically at 6.6 mg/kg intravenously once daily and maintains concentra-
tions well above MIC for most of the common equine pathogens in the sy-
novial fluid, synovial membrane, joint capsule, subchondral bone, and other
periarticular tissues, without significant harm to the joint and surrounding
tissues [60,61]. Drains and catheters should be used with extreme care,
and heparinized systems should be avoided. Heparin has been shown to po-
tentiate the growth of Staphylococcus organisms, and indwelling units can
provide a route for further contamination of the joint [62].
Several antibiotic-impregnated delivery systems are also available for lo-
cal delivery of high concentrations of different antibiotics and can be placed
in or in close proximity to equine joints. The material composition of these
delivery systems dictates characteristics, such as rate of antibiotic release,
biocompatibility, and biodegradability. The most commonly used material
used to treat equine patients is polymethylmethacrylate (PMMA). PMMA
is an inexpensive, nonbiodegradable, high-density plastic formed by mixing
a fluid monomer and powdered polymer [63]. Antibiotic(s) can be added
separately to this mixture before it hardens and then molded into beads
or cylinders [63]. The antibiotics are released from the PMMA in a bimodal
manner, with rapid release of approximately 5% of the drug within 24 to 48
hours, followed by slow release, which may continue for years [63]. Many
antibiotics, including penicillins, amikacin, gentamicin, cephalosporins, clin-
damycin, lincomycin, and vancomycin, have been shown to elute from
PMMA [63,64]. The beads eventually become encapsulated within fibrous
tissue, although they may still release therapeutic levels of antibiotics within
2 to 3 mm of the surrounding area [63]. PMMA beads placed in joints
should be placed in non–weight-bearing areas and stabilized to prevent
movement and subsequent articular cartilage damage. The beads, especially
if placed in periarticular tissues, theoretically do not need to be removed if
they are not interfering with joint function, although it is the author’s expe-
rience that removal of the beads is necessary to prevent ongoing localized
inflammation and because these beads can harbor infection in some cases.
Many effective biodegradable materials, including collagen-based deliv-
ery systems, chitosan, hydroxyapatite, and various types of beads and mi-
crospheres, are now available to deliver high concentrations of antibiotics
locally at the site of infection [64–69]. These systems have many advantages
over PMMA delivery systems, including more rapid and constant release of
higher concentrations of antibiotic, improved biocompatibility, and the fact
that these materials are biodegradable [64–69]. Because resistance of bacte-
ria to aminoglycosides is relative, depending only on the concentration and
elimination time of the antibiotic by bacterial enzymatic inactivation, the
prolonged rapid release of high concentrations of these and similar
640 MORTON

antibiotics increases the efficacy and decreases the risk of inducing resistant
bacteria [70]. The major advantages of biodegradable materials are that they
do not require an additional surgical procedure for removal, are associated
with less inflammation than PMMA, and allow gradual filling of healing tis-
sue at their site of placement [67,69,70].
Collagen-based delivery systems are available in membrane and sponge
forms impregnated with gentamicin or without antibiotic for impregnation
with the desired antibiotic [65,70–72]. The rate of resorption of collagen de-
vices depends on vascularization at the site of implantation and can range
from approximately 1 week to a couple of months [71]. The rate of release
of antibiotic is hence related to blood flow. When compared with PMMA in
one study, collagen sponges released a 15-fold greater concentration of gen-
tamicin into wounds 24 hours after implantation [73]. Collagen-based deliv-
ery systems have the additional advantageous characteristic of providing
hemostasis, which can minimize postoperative effusion in the joint [70]. In
eight horses with traumatically induced synovial sepsis treated with arthro-
scopic or tenoscopic lavage followed by implantation of a gentamicin-
impregnated collagen sponge, seven were treated successfully and were
sound after treatment [71]. Gentamicin-impregnated collagen sponges in
combination with arthroscopic lavage were shown to treat two cases of cat-
tle with SA of a radiocarpal joint successfully in one study and 86% of cases
of cattle with chronic SA in another study [70,72].
Use of antibiotic-impregnated hydroxyapatite, chitosan, and various bio-
degradable beads and microspheres has not been reported in clinical cases of
SA in horses or other animals but has been successfully employed to treat
select infections in human patients [74,75]. In addition to delivering high
concentrations of antibiotics locally, antibiotic-impregnated hydroxyapatite
and polylactide microspheres combined with bioactive glass are osteocon-
ductive and, in some cases, osteoinductive and can also be used as filler
for bone defects [66]. Teicoplanin-incorporated polylactide-co-glycolide
(PLGA) microspheres were shown to deliver synovial concentrations of tei-
coplanin that exceeded the MIC of the test organism effectively for at least
2 weeks when implanted into the femoral condyles of rabbits [76]. Micro-
spheres provide the additional advantage that they are small and can be in-
jected into small spaces. These delivery systems may prove useful for
treating SA in horses in the future, especially when associated with bony de-
fects or small joint spaces, such as those of the distal tarsus.
In human beings, isolated limb perfusion (ILP), isolated limb infusion
(ILF), or isolated retrograde injection (IRI) is used to deliver high concen-
trations of cytotoxic or antimicrobial agents locally while avoiding the
effects and risks of systemic administration [77–79]. ILP uses an extracorpo-
real delivery circuit that delivers the treatment agent intra-arterially to the
isolated limb (via tourniquet). During perfusion, the blood is oxygenated,
and before the tourniquet is removed, the limb is ‘‘washed out,’’ removing
the perfusate and blood and replacing it with low-molecular-weight dextran
 SEPTIC ARTHRITIS 641

[78]. ILF is similar to ILP, but the circuit is technically simpler and does not
involve oxygenation of the blood [79]. Both methods have been shown to
treat melanoma and diabetic ulcers effectively, but the ILF method has
the advantage of lower cost and ease of application [77–79]. IRI is also
used with some success in human beings and involves tourniquet isolation
of the limb and injection of agent in a high volume of fluid into a distal
vein. During IRI, the blood is not circulated through a circuit and the
limb is not washed out after treatment [79]. In treating equine patients, re-
gional intravenous and intraosseous limb perfusions are also effective meth-
ods for delivering higher concentrations of antibiotics to synovial tissues.
These procedures are akin to the IRI technique used in human beings. In
each, a tourniquet is placed proximal to the affected joint and left in place
for 30 minutes after antibiotic infusion has begun. With intravenous perfu-
sion, a distal vein is aseptically catheterized and the desired antibiotic is di-
luted with a higher volume (depending on the location and size of the area to
be treated) of sterile physiologic fluid and is slowly injected. Intraosseous
perfusion requires aseptic drilling of a small strategically placed unicortical
hole in a bone proximal or distal to the joint and placing an intraosseous
bone port through which antibiotics can be administered into the medullary
cavity [80]. When compared, the two techniques successfully delivered peak
concentrations of amikacin in the distal interphalangeal, metacarpophalan-
geal, and digital flexor tendon sheath 5 to 50 times that of recommended
peak serum concentrations for therapeutic efficacy when a tourniquet was
placed just distal to the carpus, although the peak concentration of amikacin
was significantly higher for the distal interphalangeal joint with the regional
intravenous technique [80].

Surgical treatment
Physical removal of bacteria, inflammatory products, devitalized tissue,
and other debris is as important, if not more so, than antimicrobial therapy.
Many techniques have been described to establish drainage and treat SA
in horses, including synovial aspiration [3,6], distention-irrigation [3,6],
through-and-through lavage [1,3,6], use of drains [1,2,16], open surgery
[1,2,8], and arthroscopy [1,2,81].
In human beings, arthroscopy is considered to offer several advantages
over other treatments, including improved visualization, identification of
foreign material and infected or devitalized tissue, and access to a larger
area of synovial surfaces [1,82–84]. Arthroscopic debridement has dramati-
cally reduced the rate of complications and mortality associated with the
treatment of SA [82]. Arthroscopic examination and debridement allows
efficient evaluation, debridement, and decompression with minimal morbid-
ity; a reduced period of hospitalization; and maximal functional recovery
compared with other treatments [1,82–84]. Prognosis and therapeutic
642 MORTON

consequences are influenced by arthroscopic staging of the joint at initial

examination [82,83]. Joints are staged based on macroscopic appearance
according the criteria described by Stutz and colleagues [82]. A single
arthroscopic debridement and lavage, along with systemic antibiotic ther-
apy, was sufficient in 96% of stage I, 48% of stage II, and 25% of stage
III infected joints in one study [82]. Additional arthroscopic debridement
and lavage procedures were successful in treating all except 5% of stage II
and 16% of stage III infections, in which open debridement with synovec-
tomy was required to eliminate infection [83]. The mean interval between
the first and second procedures was 3 days and between the second and third
procedure was 6 days [82]. Arthroscopic debridement and lavage have been
shown to be insufficient to treat stage IV infection, and open revision is rec-
ommended [82].
Arthroscopic debridement and lavage have been shown to improve the
prognosis for survival and to prevent loss of use in horses with contaminated
and infected joints [1,81]. Survival rates of 89% to 100% and return to pre-
operative level of performance in 81% to 89% of cases have been reported in
recent studies [1,81]. Horses in these studies received shorter courses of sys-
temic antimicrobial drugs and were hospitalized for shorter periods [1,81].
Horses with marked pannus, osteochondral pathologic findings, or osteomy-
elitis were more likely not to survive [1]. Partial synovectomy can be per-
formed during arthroscopic debridement and has been shown to treat SA
effectively in horses [2,85]. Although partial synovectomy allows debride-
ment of ‘‘trapped’’ fibrin and cells that can harbor infection, care should
be taken not to perform excessive removal of tissue, because the syno-
vium provides the vital defense mechanisms and nutrients to the joint [2].
In cases in which infection has been resolved or in open traumatic
wounds where significant joint destruction has occurred, surgical arthrodesis
may be performed to eliminate pain secondary to joint motion [86]. For
most joints, this is a salvage procedure, and horses may become ‘‘pasture’’
or ‘‘breeding’’ sound. Treatment of overwhelming joint infection by massive
cancellous bone grafting has been described as a salvage procedure for horses
valued for breeding [87].

Additional therapies
Intra-articular administration of sodium hyaluronate after joint lavage
has been shown to be more beneficial than joint lavage alone in an S aureus
model of SA. Sodium hyaluronate–treated joints showed a significant reduc-
tion in lameness, joint circumference, synovial fluid protein concentra-
tion, and synovial WBC concentration. The synovial membrane of the
treated joints contained less cellular infiltrate and less granulation tissue
formation and had a more normal structural appearance than untreated
joints [9].
 SEPTIC ARTHRITIS 643

Pain management is often just as important as controlling and eliminat-

ing infection. Successful surgical and antimicrobial therapies often improve
comfort, but additional therapy is usually warranted. Uncontrolled severe
lameness can result in potentially life-threatening complications, such as
laminitis and cecal impaction.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely
used therapeutic agents to help control the pain and inflammation associ-
ated with SA in horses. The most commonly employed NSAIDs include
phenylbutazone and flunixin meglumine. Phenylbutazone and flunixin me-
glumine are nonselective cyclooxygenase (COX) inhibitors, and their use
can be associated with risks of gastrointestinal and renal toxicity. These
risks are much greater in the face of dehydration. Horses receiving NSAID
therapy should be closely monitored for signs of dehydration and toxicity,
including decreased albumin and total protein concentrations, colic, gastro-
intestinal (gingival or gastric) mucosal ulceration, diarrhea, and proteinuria.
Recently, COX-2–selective inhibitors have become available for use in horses
and may potentially decrease the risk of gastrointestinal toxicosis asso-
ciated with the use of traditional nonselective NSAIDs [88]. Significant
decreases in the synovial WBC and COX-2–elaborated prostanoids have
been documented in treatment of a lipopolysaccharide model of equine syno-
vitis with etodolac, a COX-2 preferential NSAID [88].
Severe hind limb lameness can be managed well with epidural analgesia.
Opioids, a2-adrenergic agonists, local anesthetics, and combinations of these
drugs have all been described as effective analgesic agents [89]. The effects of
epidural morphine (0.2 mg/kg) may be prolonged by combining detomidine
(30 mg/kg) and may provide effective analgesia for several hours in the horse
[89]. Other effective methods of providing additional analgesia to horses in-
clude continuous rate infusion (CRI) of lidocaine [90] or opioids, such as bu-
torphanol [91], and transdermal administration of opioids, such as fentanyl,
[92] or topically applied NSAIDs, such as diclofenac [93].
Infected joints should be kept protected with a sterile bandage to prevent
external contamination of surgical sites or wounds and to provide compres-
sion to help control and eliminate associated swelling. Initially, bandages
should be changed daily and necessary wound care and joint therapies per-
formed simultaneously until infection has resolved and wounds or surgical
sites have healed. Strict stall rest should also be maintained during this pe-
riod. Once infection and synovitis have resolved and wounds and surgical
sites have healed, controlled exercise and physical therapy, including passive
range-of-motion exercises, should be gradually introduced.

Other future potential therapies

Many therapeutic strategies are being investigated for the potential treat-
ment of osteoarthritis. The aim of many of these novel therapies is to
644 MORTON

antagonize the activity of proinflammatory cytokines and prevent their cat-

abolic effects. Strategies used include the administration of anticytokine
antibodies or soluble cytokine receptor proteins, ex vivo gene transfer, ret-
rovirus-induced expression of IL-1 receptor antagonists, and adenovirus-
mediated expression of IL-4 and IL-10 [94]. Other strategies are focused
on stimulating anabolic activity in an attempt to enhance cartilage repair.
The most promising of these strategies is gene-mediated therapy. Gene
therapy involves the transfer of specific genetic base sequences that encode
for the production of specific proteins. Genes are transferred via ‘‘vectors’’,
most commonly viri, that carry the therapeutic genes to target cells. Gene
therapy may be used to insert a normal gene to replace a nonfunctional
gene, to swap an abnormal gene with a normal gene, to repair an abnormal
gene, or to up- or down-regulate the expression of a particular gene. For
example, in laboratory studies, gene therapy has been successful in pro-
moting cartilage repair through stimulation of proteoglycan synthesis in
rat cartilage explants and restoration of equine cartilage matrix by cotrans-
duction of genes promoting the production of insulin-like growth factor-I
(IGF-1) and IL-1 receptor antagonist protein [94,95]. Although this re-
search is far from clinical application and is designed to target the treat-
ment of osteoarthritis, it is reasonable to assume that when these
therapies become clinically available, they may play an important role in
preventing cartilage damage and promoting cartilage repair in equine SA
as well.
Immunomodulatory therapy is another advancing field of research di-
rected at the treatment of infectious, inflammatory, neoplastic, and im-
munodeficiency diseases. Trends in immunomodulatory therapy include,
but are not limited to, development of vaccines against infectious agents,
administration of recombinant cytokines to augment antifungal therapies,
conjugation of antigen with immunostimulatory oligonucleotides to cre-
ate potent immunogens to treat infection and neoplasia, and transfer of
specific genes to prevent lymphocyte apoptosis during sepsis [96–99].
These therapies may provide an additional way to treat infectious
processes, such as SA, successfully in equine patients, especially in im-
munocompromised patients or patients with infection with unusual
microorganisms.
Tissue plasminogen activator (tPA), streptokinase, and urokinase are fi-
brinolytic agents that are primarily used to dissolve vascular thrombi [100].
These fibrinolytic agents have been successfully used as adjuvant therapy for
the treatment of pleural empyema in human patients [100]. Their fibrinolytic
action breaks up the fibrinous debris and allows more effective drainage of
fluid [100]. None of these agents have been evaluated for use in treating SA
in human beings or animals, but these agents may provide a method for
more effective debridement of fibrinous debris in septic joints provided
they do not produce significant harm to the articular cartilage and other sy-
novial structures.
 SEPTIC ARTHRITIS 645

Summary
Although the prognosis of SA in horses was initially described as guarded
[6,9,15] to poor [5], more recently, with earlier intervention and more aggres-
sive surgical treatment, the prognosis has been described as good [2,3,8] to
very good [1,81]. The main causes of failure of treatment still include the in-
ability to eliminate the causative agent and the inability to disrupt the de-
structive inflammatory cycle [2,3]. Early recognition, thorough diagnostic
examinations, and aggressive therapy are critical to overcome these failures
and to prevent loss of use or life of affected horses. With continued research,
new diagnostic modalities and therapeutic regimens should help to improve
decision-making processes and outcomes for treatment of SA in horses.

References
[1] Wright I, Smith M, Humphrey D, et al. Endoscopic surgery in the treatment of contami-
nated and infected synovial cavities. Equine Vet J 2003;35:613–9.
[2] Bertone A. Infectious arthritis. In: McIlwraith C, Trotter G, editors. Joint disease in the
horse. 1st edition. Philadelphia: WB Saunders; 1996. p. 397–409.
[3] Meijer M, van Weeren P, Rijkenhuizen A. Clinical experiences of treating septic arthritis in
the equine by repeated joint lavage: a series of 39 cases. J Am Vet Med Assoc 2000;47:
351–65.
[4] Cohen N. Causes of and farm management factors associated with disease and death in
foals. J Am Vet Med Assoc 1994;204:1644–51.
[5] Firth E. Current concepts of infectious polyarthritis in foals. Equine Vet J 1983;15:5–9.
[6] Martens R, Auer J, Carter G. Equine pediatrics: septic arthritis and osteomyelitis. J Am Vet
Med Assoc 1986;188:582–5.
[7] Brewer B, Koterba A. Bacterial isolates and susceptibility patterns in foals in a neonatal
intensive care unit. Compend Contin Educ Pract Vet Equine Pract 1990;12:1773–80.
[8] Schneider R, Bramlage L, Moore R. A retrospective study of 192 horses affected with septic
arthritis/tenosynovitis. Equine Vet J 1992;24:436–46.
[9] Bruisie R, Sullins K, White N, et al. Evaluation of sodium hyaluronate therapy in induced
septic arthritis in the horse. Equine Vet J Suppl 1992;11:18–23.
[10] Seguin J, Walker R, Caron J, et al. Methicillin-resistant Staphylococcus aureus outbreak in
a veterinary teaching hospital: potential human-to-animal transmission. J Clin Microbiol
1999;37:1459–63.
[11] Owen M, Moores A, Coe R. Management of MRSA septic arthritis in a dog using genta-
micin-impregnated collagen sponges. J Small Anim Pract 2004;45:609–12.
[12] Hartmann F, Trostle S, Klohnen A. Isolation of methicillin-resistant Staphylococcus au-
reus from a postoperative wound infection in a horse. J Am Vet Med Assoc 1997;211:590–2.
[13] Weese J, Archambault M, Willey B, et al. Methicillin-resistant Staphylococcus aureus in
horses and horse personnel, 2000–2002. Emerg Infect Dis 2005;11:430–5.
[14] Hardy J. Septic arthritis in the foal. In: Large Animal Proceedings of the Ninth Annual
Symposium of the American College of Veterinary Surgeons. Rockville (MD): American
College of Veterinary Surgeons; 1999. p. 63–6.
[15] LaPointe J, Laverty S, La Voie J. Septic arthritis in 15 Standardbred race horses after intra-
articular injection. Equine Vet J 1992;24:430–4.
[16] Bertone A, McIlwraith C. A review of current concepts in the therapy of infectious arthritis
in the horse. In: Proceedings of the 32nd Annual Conference of the American Association
of Equine Practitioners. Lexington (KY): American Association of Equine Practitioners;
1987. p. 323–39.
646 MORTON

[17] Bertone A, McIlwraith C, Jones R. Comparison of various treatments for experimentally

induced equine infectious arthritis. Am J Vet Res 1987;48:519–29.
[18] Palmer J, Bertone A. Joint structure, biochemistry, and biochemical disequilibrium in sy-
novitis and equine joint disease. Equine Vet J 1994;26:263–77.
[19] Arican M, Coughlin A, Clegg P, et al. Matrix metalloproteinases 2 and 9 activity in bovine
synovial fluids. J Am Vet Med Assoc 2000;47:449–56.
[20] Jouglin M, Robert C, Valette J, et al. Metalloproteinases and tumor necrosis factor-alpha
activities in synovial fluids of horses: correlation with articular cartilage alterations. Vet Res
2000;31:507–15.
[21] Brama P, Tekoppele J, van Weeren P, et al. Matrix metalloproteinase activity in equine
synovial fluid: influence of age, osteoarthritis, and osteochondrosis. Ann Rheum Dis
1998;57:697–9.
[22] Hardy J, Bertone A, Muir W. Joint pressure influences synovial tissue blood flow as deter-
mined by colored microspheres. J Appl Physiol 1996;80:1225–32.
[23] McIlwraith C, Billinghurst R, Frisbie D. Current and future diagnostic means to better
characterize osteoarthritis in the horse-routine synovial fluid analysis and synovial fluid
and serum markers. In: Proceedings of the 47th Annual Conference of the American Asso-
ciation of Equine Practitioners. Lexington (KY): American Association of Equine Practi-
tioners; 2001. p. 171–9.
[24] Montgomery R, Long I, Milton J. Comparison of aerobic culturette, synovial membrane
biopsy, and blood culture medium in detection of canine bacterial arthritis. Vet Surg
1989;18:300–3.
[25] Gough M, Munroe G, Mayhew I. Urea as a measure of dilution of equine synovial fluid.
Equine Vet J 2002;34:76–9.
[26] Van Pelt R. Interpretation of synovial fluid findings in the horse. J Am Vet Med Assoc 1974;
165:91–5.
[27] Madison J, Sommer M, Spencer P. Relations among synovial membrane histopathologic
findings, synovial fluid cytologic findings, and bacterial culture results in horses with sus-
pected infectious arthritis: 64 cases (1979–1987). J Am Vet Med Assoc 1991;198:1655–61.
[28] Persson L. On the synovia in horses. Acta Vet Scand 1971;35:3–77.
[29] Tulamo R, Bramlage L, Gabel A. Sequential clinical and synovial fluid changes associated
with acute infectious arthritis in the horse. Equine Vet J 1989;21:325–31.
[30] Kidd J, Barr A, Tarlton J. Matrix metalloproteinases 2 and 9 and white blood cell count at
referral as indicators of survival in horses with septic arthritis. In: Proceedings of the 43rd
Congress of the British Equine Veterinary Association. 2004. p. 297.
[31] Sawyer D. Synovial fluid analysis of canine joints. J Am Vet Med Assoc 1963;143:609–12.
[32] Ward T, Steigbiegel R. Acidosis of the synovial fluid correlates with synovial fluid leukocy-
tosis. Am J Med 1978;64:933–6.
[33] Krey P, Bailen D. Synovial fluid leukocytosis, a study of extremes. Am J Med 1977;67:
436–42.
[34] Van Pelt R. Monoarticular idiopathic septic arthritis in horses. J Am Vet Med Assoc 1971;
158:1658–73.
[35] Roberts J, McLees B, Kerby G. Pathways of glucose metabolism in rheumatoid and non-
rheumatoid synovial membrane. J Lab Clin Med 1967;70:503–11.
[36] Kidd J, Tarlton J, Barr A. A longitudinal and cross-sectional study of synovial fluid
matrix metalloproteinases 2 and 9 and white blood cell count in septic arthritis in horses.
In: Proceedings of the 43rd Congress of the British Equine Veterinary Association 2004.
p. 296.
[37] Trumble T, Trotter G, Oxford J, et al. Synovial fluid gelatinase concentrations and matrix
metalloproteinase and cytokine expression in naturally occurring joint disease in horses.
Am J Vet Res 2001;62:1467–77.
[38] McIlwraith C. Experimentally induced arthritis of the equine carpus: clinical determina-
tions. J Am Vet Med Assoc 1979;40:11–20.
 SEPTIC ARTHRITIS 647

[39] Titov A, Vyshnevskaya E, Mazurenko S, et al. Use of polymerase chain reaction to diag-
nose tuberculous arthritis from joint tissues and synovial fluid. Arch Pathol Lab Med
2004;128:205–9.
[40] Koch D. Management of infectious arthritis in the horse. Compend Contin Educ Pract Vet
1979;1(Suppl):S45.
[41] Sarda L, Cremieux A, Lebellec Y, et al. In ability of 99mTc-ciprofloxacin scintigraphy to
discriminate between septic and sterile osteoarticular diseases. J Nucl Med 2003;44:920–6.
[42] Palestro C. The current role of gallium imaging in infection. Semin Nucl Med 1994;24:
128–41.
[43] Ang E, Sandram F, Goh A, et al. 99mTc-polyclonal IgG and 99mTc-nanocolloid scans in or-
thopaedics: a comparison with conventional bone scan. Nucl Med Commun 1993;14:
419–32.
[44] Schauwecker D, Park H, Mock B. Evaluation of complicating osteomyelitis with 99mTc-
MDP, 111In-granulocytes, and 67Ga-citrate. J Nucl Med 1984;25:849–53.
[45] McCarthy K, Velchik M, Alavi A, et al. Indium-111-labeled white blood cells in the detec-
tion of osteomyelitis complicated by a pre-existing condition. J Nucl Med 1988;29:1015–21.
[46] Sonmezoglu K, Sonmezoglu M, Halac M. Usefulness of 99mTc-ciprofloxacin (Infecton)
scan in the diagnosis of chronic orthopedic infections: comparative study with 99mTc-
HMPAO leukocyte scintigraphy. J Nucl Med 2001;42:567–74.
[47] Yapar Z, Kibar M, Yapar A, et al. The efficacy of 99mTc-ciprofloxacin (Infecton) imaging
in suspected orthopaedic infection: a comparison with sequential bone/gallium imaging.
Eur J Nucl Med 2001;28:822–30.
[48] Koblik P, Lofstedt J, Jakowski R, et al. Use of 111 In-labeled autologous leukocytes to im-
age an abdominal abscess in a horse. J Am Vet Med Assoc 1985;186:1319–22.
[49] Thompson J. In: Formulary of the pharmacy, University of Florida Veterinary Medical
Teaching Hospital. Jacksonville (FL): University of Florida; 2004. p. 8–144.
[50] Allen D, Pringle J, Smith D, et al. Common dosages for large animal. In: Smith M, Geyer A,
editors. Handbook of veterinary drugs. Philadelphia: JB Lippincott; 1993. p. 294–495.
[51] Walmsley J. Local delivery systems for the treatment of septic arthritis. In: Proceedings of
First World Veterinary Congress. Munich; 2002. p. 209.
[52] Lloyd K, Stover S, Pascoe J, et al. Synovial fluid pH, cytologic characteristics, and genta-
micin concentration after intra-articular administration of the drug in an experimental
model of infectious arthritis in horses. Am J Vet Res 1990;51:1363–8.
[53] Weese J, Rousseau J, Traub-Dargatz J, et al. Community-associated methicillin-resistant
Staphylococcus aureus in horses and humans who work with horses. J Am Vet Med Assoc
2005;226:580–3.
[54] Gortel K, Campbell K, Kakoma I, et al. Methicillin resistance among staphylococci iso-
lated from dogs. Am J Vet Res 1999;60:1526–30.
[55] Kania S, Williamson N, Frank L, et al. Methicillin resistance of staphylococci isolated from
the skin of dogs with pyoderma. Am J Vet Res 2004;65:1265–86.
[56] Guardabassi L, Loeber M, Jacobson A. Transmission of multiple antimicrobial-resistant
Staphylococcus intermedius between dogs affected by deep pyoderma and their owners.
Vet Microbiol 2004;98:23–7.
[57] Shah P. The need for new therapeutic agents: what is the pipeline? Clin Microbiol Infect
2005;(11Suppl):36–46.
[58] Ng J, Gosbell I. Successful oral pristinamycin therapy for osteoarticular infections due to
methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus spp. J Anti-
microb Chemother 2005;55:1008–12.
[59] Richter S, Kealey D, Murray C, et al. The in vitro activity of daptomycin against Staphy-
lococcus aureus and Enterococcus species. J Antimicrob Chemother 2003;52:123–7.
[60] Lescun T, Adams S, Wu C, et al. Effects of continuous intra-articular infusion of gentami-
cin on synovial membrane and articular cartilage in the tarsocrural joint of horses. Am J Vet
Res 2002;63:683–7.
648 MORTON

[61] Lescun T, Ward M, Adams S. Synovial tissue gentamicin concentration during continuous
infusion of the tarsocrural joint in horses. In: Proceedings of the 32nd Annual Conference
of the Veterinary Orthopedic Society. Okemos (MI): Veterinary Orthopedic Society; 2005.
p. 34.
[62] Fortier L. Joint lavage, articular debridement and synovectomy techniquesdnew develop-
ments. In: Proceedings of First World Veterinary Congress. Munich; 2002. p. 81.
[63] Sayegh A, Moore R. Polymethylmethacrylate beads for treating orthopedic infections.
Compend Contin Educ Pract Vet Equine Pract 2003;25:788–92.
[64] Ethell M, Bennett R, Brown M, et al. In vitro elution of gentamicin, amikacin, and ceftiofur
from polymethylmethacrylate and hydroxyapatite cement. Vet Surg 2000;29:375–82.
[65] Prior D. Localised drug delivery via collagen-based biodegradable matrices. In: The drug
delivery companies report. Autumn/winter, 2004. PharmaVentures; 2004. p. 39–42.
[66] Koort J, Makinen T, Suokas E, et al. Efficacy of ciprofloxacin-releasing bioabsorbable os-
teoconductive bone defect filler for treatment of experimental osteomyelitis due to Staphy-
lococcus aureus. Antimicrob Agents Chemother 2005;49:1502–8.
[67] Liu S, Ueng S, Chan E, et al. In vitro elution of vancomycin from biodegradable beads.
J Biomed Mater Res 1999;48:613–20.
[68] Habib M, Onyilofor S, Ebube N, et al. Preparation and characterization of ofloxacin micro-
spheres for the eradication of bone associated bacterial biofilm. J Microencapsul 1999;16:
27–37.
[69] Ambrose C, Gogola G, Clyburn T, et al. Antibiotic microspheres: preliminary testing for
potential treatment of osteomyelitis. Clin Orthop 2003;415:279–85.
[70] Hirsbrunner G, Steiner A. Treatment of infectious arthritis of the radiocarpal joint of cattle
with gentamicin-impregnated collagen sponges. Vet Rec 1998;142:399–402.
[71] Summerhays G. Treatment of traumatically induced synovial sepsis in horses with gentami-
cin impregnated collagen sponges. Vet Rec 2000;147:184–8.
[72] Steiner A, Hirsbrunner G, Miserez R, et al. Arthroscopic lavage and implantation of gen-
tamicin-impregnated collagen sponges for treatment of chronic septic arthritis in cattle. Vet
Comp Orthop Traumatol 1999;12:64–9.
[73] Letsch R, Rosenthal E, Joka T. A comparative study of two local antibiotic carriers in
the treatment of osteomyelitis of long bones. In: Stemberger A, Ascherl R, Lechner F,
et al, editors. Collagen as a drug carrier: some applications in surgery. London: Franklin
Scientific Projects; 1991. p. 109–13.
[74] Aksungur P, Sungur A, Unal S, et al. Chitosan delivery systems for the treatment of oral
mucositis: in vitro and in vivo studies. J Cont Release 2004;98:269–79.
[75] Buranapanitkit B, Srinilta V, Oungbho K, et al. The efficacy of a hydroxyapatite composite
as a biodegradable antibiotic delivery system. Clin Orthop 2004;424:244–52.
[76] Atilla B, Calis S, Yenice I, et al. Controlled delivery of teicoplanin from an intraarticular
biodegradable microparticulate system; in vitro/in vivo evaluation. In: Proceedings of First
World Veterinary Congress. Munich; 2002. p. 53.
[77] Mian R, Henderson M, Speakman D, et al. Isolated limb infusion for melanoma: a simple
alternative to isolated limb perfusion. Can J Surg 2001;44:189–92.
[78] Schaadt J, Crowley R, Miller D, et al. Isolated limb perfusion: a literature review. J Am Soc
Extracorporeal Tech 2002;34:120–43.
[79] Thompson J, Kam P, Waugh R, et al. Isolated limb infusion with cytotoxic agents: a simple
alternative to isolated limb perfusion. Semin Surg Oncol 1998;14:238–47.
[80] Butt T, Bailey J, Dowling P, et al. Comparison of 2 techniques for regional antibiotic de-
livery to the equine forelimb: intraosseous perfusion vs. intravenous perfusion. Can Vet J
2001;42:617–22.
[81] ter Braake F. Direct endoscopic approach improves prognosis of septic-synovitis in the
horse. Tijdschr Diergeneeskd 2002;127:444–9.
[82] Stutz G, Kuster M, Kleinstuck F. Arthroscopic management of septic arthritis: stages of
infection and results. Knee Surg Sports Traumatol Arthrosc 2000;8:270–4.
 SEPTIC ARTHRITIS 649

[83] Vispo Seara J, Barthel T, Schmitz H, et al. Arthroscopic treatment of septic joints: prognos-
tic factors. Arch Orthop Trauma Surg 2002;122:204–11.
[84] Polahofer G, Hassenpflug J, Peterson W. Arthroscopic treatment of septic arthritis in a pa-
tient with posterior stabilized total knee arthroplasty. Arthrosc J Arthrosc Relat Surg 2004;
20:311–3.
[85] Bertone A, Davis D, Cox H, et al. Arthrotomy versus arthroscopy and partial synovectomy
for treatment of experimentally induced infectious arthritis in horses. Am J Vet Res 1992;
53:585–91.
[86] Groom L, Gaughan E, Lillich J, et al. Arthrodesis of the proximal interphalangeal joint
affected with septic arthritis in 8 horses. Can Vet J 2000;41:117–23.
[87] Bramlage L. Treatment of overwhelming joint infections by massive cancellous bone graft-
ing. In: Lecture abstracts of the AO ASIF Advanced Techniques in Equine Fracture Man-
agement. 2005.
[88] Morton A, Campbell N, Gayle J, et al. Preferential and non-selective cyclooxygenase inhib-
itors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci 2005;
78:189–92.
[89] Goodrich L, Nixon A, Fubini S, et al. Epidural morphine and detomidine decreases post-
operative hind limb lameness in horses after bilateral stifle arthroscopy. Vet Surg 2002;31:
232–9.
[90] Robertson S, Sanchez L, Merritt A, et al. Effect of systemic lidocaine on visceral and
somatic nociception in conscious horses. Equine Vet J 2005;37:122–7.
[91] Sellon D, Roberts M, Blikslager A, et al. Effects of continuous rate infusion of butorphanol
on physiologic outcome variables in horses after celiotomy. J Vet Intern Med 2004;18:
555–63.
[92] Thomasy S, Slovis N, Maxwell L, et al. Transdermal fentanyl combined with nonsteroidal
anti-inflammatory drugs for analgesia in horses. J Vet Intern Med 2004;18:461–2.
[93] Lynn R, Hepler D, Kelch W, et al. Double-blinded placebo-controlled clinical field trial to
evaluate the safety and efficacy of topically applied 1% diclofenac liposomal cream for the
relief of lameness. Vet Ther 2004;5:128–38.
[94] Venkatesan N, Barre L, Benani A, et al. Stimulation of proteoglycan synthesis by glucur-
onosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc Natl Acad Sci
USA 2004;101:18087–92.
[95] Nixon A, Haupt J, Frisbie D, et al. Gene-mediated restoration of cartilage matrix by com-
bination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy. Gene Ther
2005;12:177–86.
[96] Dalloul R, Lillehoj H. Recent advances in immunomodulation and vaccination strategies
against coccidiosis. Avian Dis 2005;49:1–8.
[97] Ray A, Anand S. Recent trends in antifungal therapy: focus on systemic mycoses. Indian J
Chest Dis Allied Sci 2000;42:357–66.
[98] Datta S, Cho H, Takabayashi K, et al. Antigen-immunostimulatory oligonucleotides
conjugates: mechanisms and applications. Immunol Rev 2004;199:217–26.
[99] Bommhardt U, Chang K, Swanson P, et al. Akt decreases lymphocytes apoptosis and
improves survival in sepsis. J Immunol 2004;172:7583–91.
[100] Ray L, Berkenbosch J, Russo P, et al. Tissue plasminogen activator as an adjuvant therapy
for pleural empyema in pediatric patients. J Intensive Care Med 2004;19:44–50.