what intervention on the use or dosing of antibiotics work to decrease resistance ?
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What intervention on the use or dosing of antibiotics work to decrease resistance ?. Jan. 18, 2007 Sung-Ching Pan. Antibiotics control strategies. Agriculture use. Mutation prevention dose. Combination therapy. Conan MacDougall and Ron E. Polk, CLINICAL MICROBIOLOGY REVIEWS, 2005. - PowerPoint PPT PresentationTRANSCRIPT
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What intervention on the use or dosing of antibiotics work to
decrease resistance?
Jan. 18, 2007Sung-Ching Pan
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Antibiotics control strategies
Conan MacDougall and Ron E. Polk, CLINICAL MICROBIOLOGY REVIEWS, 2005
Mutation prevention
dose
Agriculture use
Combination therapy
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Antibiotics control
• Relationship between antibiotics usage and resistance– Ecological study
• Penicillin use and penicillin resistant S. pneumononas (PRSP)
• Antibiotics use (3rd cephalosporin, macrolide and fluroquilolone) and MRSA
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Antibiotics control
• Relationship between antibiotics usage and resistance– Individual study
Antibiotic Departmental consumptionb Prior specific antibioticc Prior treatment with any other antibioticc
Gentamicin 1.03 (0.70–1.50) 2.12 (1.29–3.48) 1.81 (1.40–2.33)
Amikacin 1.80 (1.00–3.24) 2.40 (1.31–4.40) 1.31 (1.49–2.20)
Cefuroxime 1.12 (1.01–1.23) 3.24 (1.97–5.34) 2.77 (1.99–3.87)
Ceftazidime 1.45 (1.19–1.76) 3.88 (1.89–7.97) 1.55 (1.18–2.04)
Ciprofloxacind 1.06 (0.57–1.97) 4.05 (2.00–8.21) 1.27 (0.62–2.70)
Leibovici et al. J Antimicrob Chem, 2001
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Antibiotics control
• Relationship between antibiotics usage and resistance- Temporal sequence?– Intervention-change– Discontinue intervention-reverse
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Education campaignHELENA SEPPALA, et al. NEJM 1997
InterventionIn the
end1991
*Physicians were reached mainly through the Finnish Medical Journal and lectures at national and local meetings for general practitioners.
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Limitations
• Ecological study, hard to control confounding
• After the intervention stop, what will happen?
• The problem of this strategy: Decrease use of macrolide, but increase use of other antibiotics, other resistance?– “the total rate of use of antimicrobial agents re
mained unchanged”
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Education campaign (hospital/individual level)
• Some researches study the behavior change of antibiotics prescription after education campaign
• Education campaign- antibiotics resistance?
• Publication bias?• Combination with other infection control
strategies
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Restriction of usageWhite AC, CID, 1997
• Prior authorization– Ben Taub General Hospital is a 575-bed urban teachi
ng hospital in Houston.– Enforcement of the prior-authorization requirement be
gan on 1 January 1994.– Intravenous amikacin, ceftazidime, ciprofloxacin, fluco
nazole, ofloxacin, and ticarcillin/clavulanate.– Faculty of the Infectious Diseases Service, Departme
nt of Medicine, were available 24 hours a day to provide antibiotic approval
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Restriction of usageWhite AC, CID, 1997
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• Limitation:– Before –after study– Other intervention? in-service programs for surgical ICU staff on
hand washing in November 1993 and July and August 1994.
• Need staffs support
Restriction of usageWhite AC, CID, 1997
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997
• Switch of empirical for nosocomial pneumonia in ICU from ceftazidime to ciproxin
• Primary outcome: – incidence of ventilator-associated pneumo
nia (VAP)– nosocomial bacteremia
• Study design: – before(6 months) Vs. after (6 months)
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Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997
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Single switchKollef MH, et al. AMm J Respir Crit Care Med, 1997
• Before-after design• Ceftazidime related drug resistance chang
e did not clarified– Ceftazidime resistant P. aeruginosa– ESBL K. pneumonia or E.coli
• Problem with this strategy:– How about drug resistance to ciproxin?
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Routine cyclingRaymond DP, et al. Crit Care Med 2001
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Routine cycling
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Routine cycling
Agent A Agent A Agent AAgent B Agent B Agent B
Time
Resistance
Limitation:
1. Short follow up time
2. Different patients population in the before-after setting
Ciproxin Tazocin carbapenem cefepime
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Routine cycling
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Combination therapy
• β-lactams+ aminoglycoside:– Pseudomonas
• Carbapemen+aminoglycoside– MDR Acinectobacter baumanii
• Work for therapeutic goal, but for resistance?
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Combination therapy El Amari EB, et al. CID 2001
• Case-control study • Influence of previous exp
osure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates
• piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides
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Combination therapy (meta-analysis of RCT)Bliziotis IA, CID 2005
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Mutation prevention dose• Control use in agriculture
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Concentration dependent Vs. Time dependent
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The emergence of resistance
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Mutation prevention concentration
• Describes the antibacterial concentration that inhibits the growth of the least-susceptible, single step mutant;
• The MIC of the least susceptible organism• There is a low likelihood for spontaneous
mutant formation at or above the MPC.
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Mutation prevention concentration
• Limitation on clinical use– MPCs differ among th
e various fluoroquinolones against different pathogens
– the MPC for each antibacterial agent is dependent on the genotypic profile of the organism.
KD2138: parC
KD2139: gyrA
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Antibiotics control
• Education campaign• Restriction of usage• Single switch/ antibiotics cycling• Combination therapy• Pk/Pd, Mutation prevention dose• Control use in agriculture
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Agriculture use regulation
Antibiotics
resistance
Animal pathogen
Human pathogen
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Study designRamsay CE, J. Antimicrob. Chemother, 2003
• Review of 306 studies of interventions to improve antimicrobial prescribing in hospitals, 70% did not meet the minimum criteria of the Cochrane Collaboration’s Effective Practice and Organization of Care Group.
• The most commonly excluded studies were those using uncontrolled before- and-after designs (46%) or inadequate interrupted time series analysis (24%).
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Study design
• Interrupted time series with segmented regression: a method of analysis applied to before-and-after quasi-experimental study designs
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Study design
• Mathematic modeling:– While a long-term follow up is needed for
before-and-after quasi-experimental study designs
– Control confounding
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