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@@antibiotic Ettarippt
@@antibiotic Ettarippt
@@antibiotic Ettarippt
31 million US cases/year
AAPA Chapter Lecture Series Supported by an educational grant from Aventis Pharmaceuticals, a member of the sanofi-aventis group
1 Garau J, et al. Clin Microb Infect. 1998;4(suppl 2):S51-S58 2 Bishai WR. Otolaryngol Head Neck Surg. 2002;127: S3-S9 3 Ball P, Make B. Chest. 1998;113:199S-204S 4 Colice GL, et al. Chest. 2004;125:2140-2145 5 Hall MJ, Owings MF. 2000. Advance Data From Vital Health Statistics. June 19, 2002, 329:1-20.
Dyslipidemia Health Maintenance Diabetes Pain management Allergic disorders Hypertension Respiratory/ENT infections Musculoskeletal disorders/injuries
1,000,000 5,000,000 9,000,000 13,000,000 17,000,000 21,000,000 25,000,000
Streptococcus pneumoniae
Streptococcus pneumoniae
Sinusitis
Acute Bronchitis
1 File TM Jr. Lancet. 2003;362:1991-2001; 2American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754; 3 Guthrie R. Chest. 2001;120:2021-2034; 4Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130: 1-45; 5Bartlett JG, et al. Clin Infect Dis. 2000;31:347-382
Haemophilus influenzae
S pneumoniae 15%25%1 20%43%2 20%60%3 H influenzae 30%59%1 22%35%2 3%10%3 3%22%1 2%10%2 1%2%4 M catarrhalis S pyogenes 3%7%2 0%8%2 3%5%4 S aureus 1%6%4 Mycoplasma spp 2%8%4 Legionella spp 4%6%4 Chlamydophila spp
1. Guthrie R. Chest. 2001;120:20212034; 2. Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:145; 3. American Thoracic Society. Am J Respir Crit Care Med. 2001;163:17301754; 4. Bartlett JG, Mundy LM. N Engl J Med. 1995;333:16181624.
An important pathogen in RTIs causing 1 3%10% CAP 30%59% AECB2 22%35% ABRS3 Over 30% -lactamase positive4
Haemophilus influenzae
1 American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754.; 2Guthrie R. Chest. 2001;120:20212034; 3Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:1-45; 4Hoban DJ, et al. Clin Infect Dis. 2001;32(suppl 2):S81-S93
Moraxella catarrhalis
Moraxella catarrhalis
An important pathogen in RTIs causing: 1%2% CAP1 3%22% AECB2 2%10% ABRS3 Over 90% lactamase positive4
1 3
Mycoplasma pneumoniae
May be a factor in 30% 40% of CAP cases1 Often undetected because of poor diagnostic tools1 IDSA and ATS treatment guidelines for CAP include the importance of atypical coverage2,3
Bartlett JG, Mundy LM. N Engl J Med. 1995;333:1618-1624; 2Guthrie R. Chest. 2001;120:2021-2034; 3Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:1-45; 4Hoban DJ, et al. Clin Infect Dis. 2001;32(suppl 2):S81-S93.
Thibodeau KP, Viera AJ. Am Fam Physician. 2004;69:1699-1706; 2Bernstein JM. Chest. 1999;115:9S-13S; American Thoracic Society. Am J Respir Crit Care Med. 2001;163:1730-1754.
% Resistance
30
Penicillin Azithromycin Levofloxacin
20
10
0
a 19 92 -1 99 3 b, c g h h h 99 2 d, e e, f 19 98 -1 99 9 20 00 -2 00 1 19 94 -1 20 01 -2 00 2 19 96 -1 99 7 19 99 -2 00 0 19 91 -1 19 94 99 5 h
*Mortality rates depend on pathogen: P aeruginosa mortality was 61.1%, but that organism was isolated in only 18 cases; C psittaci mortality was 0 and was isolated in 32 cases.
Adapted from Fine MJ, et al. JAMA. 1996;275:134-141.
a Thornsberry et al, Suppl. Infect. Med. 1993, 93:15-24; Thornsberry et al, AAC 1999, 43:2612-2623; bBarry et al, AAC 1994, 38:2419-2425; cBarry & Fuchs, AAC 1995, 39:238-240; dGruneberg et al, DMID 1996, 25:169-181; e(Invasive isolates tested with erythromycin) Gay et al JID 2000, 182:1417-24; fDoern et al, AAC 1996, 40:1208-1213; g Thornsberry et al, DMID 1997, 29:249-257; hKarlowsky et al CID 2003, 36:963-70
Penicillin-resistant 35 30 Macrolide-resistant
(MIC 2 mg/L)
Percentage
NE 27%
1 Spika JS, et al. J Infect Dis. 1991;163:1273-1278. 2Jorgensen JH, et al. Antimicrob Agents Chemother. 1990;34:2075-2080. 3 Doern GV, et al. Antimicrob Agents Chemother. 2001;45:1721-1729. 4Doern GV, Brown SD. J Infect. 2004;48:56-65. 5Doern GV, et al. Antimicrob Agents Chemother. 1996;40:1208-1213. 6Doern GV, et al. Emerg Infect Dis. 1999;5:757-765.
Southwest 20%
4 % 3 2 1 0
1995 1996 1997
OFL-Nonsusceptible Isolates: Persons <18 Y OFL-Nonsusceptible Isolates: Persons 18 Y LFX-Nonsusceptible Isolates: Persons 18 Y
12 10 8 Rate* 6 4 2 0
1864 Years <18 Years 1993 1994 1995 1996 1997 1998 65 Years
1998
1999
Year
*Per 100 persons
Year
Streptococcus pneumoniae in US
FQ Prescriptions per 1000 people 6 Percent FQ - resistant 5 4 3 2 1 0 1988-89 1994-95 1997-98 1999-00 2001-02 2002-03
497 45 1527 30 1601 34 1531 33 1925 45 1974 44
Fluoroquinolone-resistant
120 100 80 60 40 20
Isolates Centers
Percent of isolates
% Sensitive (NCCLS)
100 98.2 97.1 89.6 70 70 70
Has rapidly resulted in a shift away from S. pneumo to H. Influenzae in selected populations, diseases AAP, IDSA, ATS, WHO, etc.
High dose, short-course antibiotic therapies Appropriate-spectrum antibiotics without collateral damage
NCCLS now is known as the National Clinical and Laboratories Standards Institute
Age Recent exposure to antibiotics Exposure to Day Care Immunologic status Socioeconomic status Local geographic factors Recent hospitalization
Wise R. A review of the mechanisms of action and resistance of antimicrobial agents. Can Respir J 1999;6(SupplA):A20-2.
Relative risk of infection with macrolide resistant pneumococci, by prior antibiotic use, TIBDN
40 35 30 25 20 15 10 5 0 Unknown No prior AB Prior AB - Prior AB Prior ? not MAC Macrolide
Cross sectional study of 303 adults/children with S. pneumo bacteremia 33 PNSP; 270 PS or PISP Risk factors for PNSP:
RTI in previous 12 mo - OR 5.0 (1.6-15.6) -lactam in previous 6 mo - OR 10.9 (2.4-49.9) Stay in high risk area OR 5.8 (1.8-19.3)
> 1 Risk factor - PPV 21%; NPV 99% for PNSP bacteremia
Ruhe et al; Clin Inf Dis 2004; 38: 508-14
Relative risk of infection with FQ resistant pneumococci, by prior antibiotic use, TIBDN
Percent ciprofloxacin resistant 20 18 16 14 12 10 8 6 4 2 0 Unknown No prior AB Prior AB - Prior AB ? not FQ Prior FQ
P value
.002 .006 .02 <.001 <.001
Inappropriate therapy with worse outcomes Treatment failures: Outpatient failure commonly results in inpatient treatment Inpatient failure results in prolonged hospitalization
Increased difficulty with placement in extended care facilities Need for isolation precautions with a negatively impacted quality of patient care
Increased mortality with S pneumoniae with penicillin MICs >2.0 g/mL or >4.0 g/mL and a statistically significant increase in complications13 High likelihood of failure to prevent S pneumoniae bacteremia with macrolide therapy for CAP caused by macrolide-resistant strains46
1. Feikin DR, et al. Am J Public Health. 2000;90:223229. 2. Metlay JP, et al. Clin Infect Dis. 2000;30:520527. 3. Klepser ME, et al. Pharmacotherapy. 2003;23:349359. 4. Kelley MA, et al. Clin Infect Dis. 2000;31:10081011. 5. Lonks JR, et al. 2002;35:556564. 6. Iannini PB, et al. Presented at: Infectious Diseases Society of America 2004 Annual Meeting. September 30 October 3, 2004, Boston, Ma.
Prescribing antibacterial drugs to treat likely viral infections Using improper diagnostic criteria in clinical decision making for infections that likely have viral etiologies Providing broad-spectrum agents when narrowspectrum agents are most suitable Prescribing antibiotics at improper doses or for improper durations
Antibiotic modifying enzymes (e.g., penicillin resistance in S aureus) Target site alterations (e.g., methicillin resistance in S Aureus) Permeability barriers (e.g., vancomycin tolerance in VISA) Efflux pumps (e.g., erythromycin resistance in S pneumoniae)
overuse? not completing antibiotic course? incorrect antibiotic choice? organisms genetic adaptability?
Treat bacterial infections only Tailor the spectrum of coverage to likely pathogens Do not over-treat with shotgun therapies Prevent emergence of resistant organisms
Use of very broad spectrum antibiotics is causing development of resistant gram-negative enteric pathogens1,3
Collateral damage
1 3
Doern GV, Brown SD. J Infect. 2004;48:56-65; 2Johnson DM, et al. Diagn Microbiol Infect Dis. 2003;47:373-376; Ball P, et al. J Antimicrob Chemother. 2002;49:31-40.
PE abnormality? No
Yes
High risk
No Acute Bronchitis
makes
pneumonia unlikely
Elderly Immunosuppressed
Adapted from Gonzales R, Sande MA. Ann Int Med. 2000;133:981-991. Martinez, Comp Ther (in review)
*
-0.5 -0.3 -0.1 0 0.1 0.3
*DL pooled risk difference= -0.0167 (95% CI = -0.0591 to 0.0256)
Favors Antibiotic
CTS: "antibiotics should only be considered for use in patients with purulent exacerbations1 GOLD: "Antibiotics are only effectivewith worsening dyspnea and cough also have increased sputum volume and purulence2 ATS/ERS: "May be initiated in patients with altered sputum characteristics3 NICE: "Antibiotics should be used to treat exacerbations of COPD associated with a history of more purulent sputum4
0.5
0.5
1.0
1.5
1 Balter, et al. Can Respir J. 2003;10(suppl B):3B-32B; 2Global Initiative for Chronic Obstructive Lung Disease. Executive Summary 2004; 3Celli BR, et al. Eur Respir J. 2004;23:932-946; 4National Institute for Clinical Excellence. Clinical Guideline 12, February 2004.
Effect Size
Sore Throat Fever Worsening of symptoms at 57d in pts with ABS complicating a viral URTI
Seasonal prevalence of ABRS correlates with common cold 0.5%2% of common colds complicated by ABRS infection 87% of patients with viral respiratory infections (common colds) have sinus cavity inflammation
Gwaltney et al. N Engl J Med 1994;330:2530. Pitkaranta et al. J Clin Microbiol 1997;35:17913.
Viral URI
Gwaltney. Clin Infect Dis 1996;23:120925. Osguthorpe et al. Med Clin North Am 1999;83:2741.
Management of ABRS
Discolored nasal drainage, nasal congestion, facial pain (viz. upper teeth pain)
Sx worsening after 4 days, Sx persisting > 7 days (adults), > 10 days (children) YES NO Probably viral and no antibiotic is warranted. Rx decongestants, rest, hydration call if symptoms worsen or if persists > 10 days
Symptoms worsening after 4 days, persistence of major symptom 10d, or symptoms out of proportion to typical VRI
Switch class from prior antibiotic and consider: High dose amox/clav Moxifloxacin Consider ENT referral for endoscopic culture NO
Can afford to wait 48 hours to switch therapy because of impending complication, comorbidity
YES
Amoxicillin High potency cephalosporin: cefdinir, cefpodoxime, cefuroxime Clarithyromycin Doxycycline TMP/SMX Telithromycin
Major Factors Discolored Nasal / Post-nasal drainage Nasal obstruction / congestion Facial pain / pressure Cough not due to asthma (in children) Hyposmia / anosmia
Minor Factors Fever Cough Fatigue Maxillary dental pain Ear fullness/pressure Headache
Adapted from Lanza DC et al. Otolaryngol Head Neck Surg. 1997;117(suppl):S1-S7. SAHP. Otolaryngol Head Neck Surg. 2004;130:1-45.
Antibiotic resistance is common Only prescribe antibiotic therapy when appropriate Use a antibiotic targeted to likely pathogensand nothing else! New treatment options should minimize resistant pathogens
Broad-spectrum antibiotics may cause development of resistance in key enteric gram-negative pathogens Development of resistance in other pathogens limits available treatment options A tailored-spectrum antibiotic in the treatment of RTIs may help prevent collateral damage
1 Paterson DL. Clin Infect Dis. 2004;38(suppl 4):S341-S345.
Tailored Coverage
1 Barman Balfour JA, Figgitt DP. Drugs. 2001;61:815-829; 2Lonks JR, et al. Clin Infect Dis. 2002; 35:556-564; 3Gleason PP. Pharmacotherapy. 2002;22:2s-11s; 4Neuhauser MM, et al. JAMA. 2003;289:885-888.
The majority of RTIs are caused by three major pathogens: S pneumoniae, H influenzae, and M These major pathogens exhibit high antibiotic resistance levels; these levels are increasing Atypical pathogens have a significant mortality burden, especially in CAP Use of very broad spectrum antibiotics selects for resistance among non-respiratory bacteria, resulting in collateral damage
catarrhalis
Tailored coverage of common pathogens involved in AECB, ABRS, and mild to moderate CAP without collateral enteric gram-negative damage Low potential to induce macrolide type (ermB) resistance in vitro Rapid bactericidal activity against S pneumoniae in vitro Worldwide patient experience with more than 10 million prescriptions Convenient once-daily dosing
CH3
Ribosome Domain II Domain V
Chronic bronchitis?
Yes
No antibiotics necessary
Uncomplicated
Disease severity?*
Complicated
Telithromycin
Active smoker?
CH3
Telithromycin maintains binding to domain V despite methylation
Domain V
Complicated
Macrolide Fluoroquinolone
Uncomplicated
Recent ABX
Macrolide Doxycycline
1. Heffelfinger JD et al. Arch Intern Med. 2000;160:1399. 3. Niederman MS et al. Am J Respir Crit Care Med. 2001;163:1730.
2. Bartlett JG et al. Clin Infect Dis. 2000;31:347-82. 4. Mandell LA et al. Clin Infect Dis. 2003; 37:1405.
1. Heffelfinger JD et al. Arch Intern Med. 2000;160:1399. 3. Niederman MS et al. Am J Respir Crit Care Med. 2001;163:1730.
2. Bartlett JG et al. Clin Infect Dis. 2000;31:347-82. 4. Mandell LA et al. Clin Infect Dis. 2003; 37:1405.
Case Study
8882 Isolates
0.2
0.4
0.6
MIC 90 (g/mL)
0.8
1.0
1.2
Increasing Potency AUC0-24/MIC90: gemifloxacin=330; moxifloxacin=192; gatifloxacin=69; levofloxacin=48. AUC data from manufacturers product prescribing information.
Jacobs MR, et al. J Antimicrob Chemother 2003;52:229-246.
62-year-old man with a longstanding history of Class II COPD He presents with a complaint of just feeling bad He is usually managed on tiotropium bromide (Spiriva) q.d. and salmeterol (Serevent) b.i.d. PMhX is significant for dyslipidemia (rosouvastatin [Crestor] 10 mg q.d.) and HTN (lisinopril [Zestril] 10 mg q.d.)
Yesterday he began his usual routine of going out for newspaper, breakfast, coffee, but upon returning home he had to sit and rest for an extended period of time to catch his breath As the day progressed, he felt increasingly fatigued, and his daily cough worsened and developed an increased sputum Otherwise, he says everything is fine and specifically denies other symptoms when questioned
On PE he appears older than his stated age, sitting on exam table in NAD but fatigued; 5 6, 140 lbs. V/S: Temp 100.2o F oral, P 104, RR 24, 140/96 mmHg, SaO2 92% RA Cardiac: Tachy, + S1/S2, RRR, M/G/R, S3/S4 Pulm: Diminished BS bilat, scant upper airway rhonchi GI: Benign Ext: Pale, hair growth, cool, DP +1 B/L, edema
10
Amoxicillin-Clavulanate misses atypical pathogens Azithromycin high resistance rate Levofloxacin broad spectrum with significant collateral damage Telithromycin tailored spectrum providing appropriate empiric coverage
Prevent or at least slow the emergence of antimicrobial resistance Optimize selection, duration, and dose of antibiotic selections Reduce mortality and morbidity Reduce length of stay/time off from ADLs Reduce global healthcare expenditures Reduce adverse drug events
Dont treat non-bacterial infections or noninfectious diseases with antibiotics Dont prolong duration beyond what is needed Avoid prophylactic antibiotics unless the benefit has been demonstrated When given the choice, opt for bactericidal not bacteristatic antibiotics Use the narrowest spectrum agent available
11