Presentation on theme: "Relationship of biocide use to antibiotic resistance Stuart B. Levy, M.D. Tufts University School of Medicine Alliance for the Prudent Use of Antibiotics."— Presentation transcript:
Relationship of biocide use to antibiotic resistance Stuart B. Levy, M.D. Tufts University School of Medicine Alliance for the Prudent Use of Antibiotics
It’s A Question of Residues Non-residues ? Triclosan QACs Triclocarban Bleach Peroxides Alcohols Residues
Cross- and Co- Resistance (Biocides and antibiotics) Target mutations Multidrug efflux systems Plasmids & transposons
Inhibitors of Enoyl reductase (fabI, inhA) TriclosanDiazaborine Isoniazid
Mutations in InhA confer triclosan resistance in Mycobacterium smegmatis Strain Selected InhA Relative MIC on* mutation (in 7H9 medium) Triclosan Isoniazid mc 2 155 (wt) -- none 1.0 1.0 MT 1 TRC M161V 6.3 8.5 MT 9 TRC M103T 6.3 1.2 MT 17 TRC A124V 5.8 2.0 mc 2 651 INH S94A 6.322.0 mc 2 155 -- none 6.3 >64 (p::inhA) *TRC = triclosan, INH = isoniazid McMurry et al, AAC 43:711, 1999.
Efflux as a Common Mechanism of Biocide and Antibiotic Resistance
mar acrAB antibiotics organic solvents pine oils bile salts triclosan chloroxylenol quaternary amines chlorhexidine
Biocide resistance and antibiotic resistance: Regulators and efflux pumps Biocide Inducer/SubstrateAffected proteinsDrugs QACs, chlorhexidine, triclosan Morita et al JAC: 51:991 (2003) NfxB MexCD-OprJ (P. aeruginosa) Multiple antibiotics Triclosan Schweizer et al AAC 42:394 (1998) Schweizer FEMS Microb Lett 202:1 (2001) MexAB-OprM MexJK (P. aeruginosa) Multiple antibiotics
Genetic linkage of resistance to QACs and to ß-lactam antibiotics in staphylococci Sidhu et al MDR 7:363 (2001) Sidhu et al AAC 46:2797 (2002)
DECREASED DRUG SUSCEPTIBILITY DRUG RESISTANCE Penicillin resistant S. pneumoniae Fluoroquinolone resistant E.coli Vancomycin resistant S. aureus
0 10 20 30 40 50 60 0.03120.06250.12500.25000.5000 1.02.04.0 Triclosan MIC (ug/ml) % of total isolates S. aureus N=43 S. capitis N=42 S. epidermidis N=73 S. warneri N=155 Triclosan Susceptibility (Staphylococcus) A. Aiello et al. Antimicrob. Agnts. Chemother. 48:2973-2979, 2004. Household hand isolates
Triclosan Susceptibility Klebsiella pneumoniae (N = 69) 0 5 10 15 20 25 30 35 0.03120.06250.12500.25000.5000 1.02.04.08.0 16.032.0 Triclosan MIC (ug/ml) % of total isolates Household hand isolates A. Aiello et al. Antimicrob. Agnts. Chemother. 48:2973-2979, 2004.
S. Langsrud et al. Appl. Microb. 140:321 (2003) Antibiotic Susceptibility of Benzalkonium Chloride selected mutants
Figure 2. Proportion of study participants with >1 bacterial species resistant to an antimicrobial agent on their hands. In the group that used antibacterial products, 82 and 105 hand samples were available at baseline and at year-end, respectively. In the group that used nonantibacterial products (i.e., plain soap), 82 and 96 hand samples were available at baseline and at year-end, respectively. Aiello, et al. Emerg Inf Dis 11:1565, 2005. Antibiotic Resistance and Hand Soaps
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