Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type
ABSTRACT The bactericidal activity of quinupristin-dalfopristin was assessed by time-kill experiments against Staphylococcus aureus strains with characterized phenotypes and genotypes of MLS(B) resistance. A set of laboratory strains composed of isogenic pairs of S. aureus RN4220 derivatives containing or not the erm(A), erm(B) or erm(C) genes constitutively expressed and of 13 clinical isolates containing these genes inducibly or constitutively expressed were studied. Three of the clinical isolates with erm(B) or erm(A) genes had an unusual inducible MLS(B) cross resistance. The early bactericidal activity of quinupristin-dalfopristin was altered against strains expressing constitutive quinupristin resistance regardless of the erm(A), erm(B) or erm(C) type of gene. We conclude that the bactericidal activity of quinupristin-dalfopristin against staphylococci was dependent on the activity of quinupristin rather than on the erm genotype of the strain.
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ABSTRACT: Treatment of chronic or recurrent Staphylococcus aureus infections may require using antibiotics with activity against intracellular multiresistant organisms. Quinupristin/dalfopristin (3:7) has been examined in this context. Quinupristin and dalfopristin were used separately or mixed. Strains used were: (i) methicillin-susceptible and -resistant S. aureus (MSSA and MRSA); (ii) one vat(B) MSSA and msr(A/B) MRSA; (iii) erm(A)+ [MSSA, MRSA, vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA)]; and (iv) one erm(A/B)+ cfr+ MRSA resistant to quinupristin, dalfopristin and their combination. Assessment of activity was determined by: (i) MICs (CLSI method); and (ii) concentration-response curves in broth and after phagocytosis by THP-1 macrophages, with descriptors of the model (Emin) and the pharmacodynamic response [maximal relative efficacy (Emax), relative potency (EC50) and apparent static concentration (Cstatic)]. erm(A)-positive strains were all susceptible to quinupristin/dalfopristin (except strain CM05), with MICs not adversely influenced by acid pH or by the MRSA, VISA or VRSA character of the strain. In concentration-response experiments, quinupristin/dalfopristin showed similar patterns for all strains (except strain CM05), with a >3 log10 cfu decrease in broth and a 1.3 [erm(A) strain] to 2.6 [fully susceptible, vat(B) and msr(A/B) strains] log10 cfu decrease for intracellular bacteria at the maximal extracellular concentration tested (25 mg/L). Maximal extracellular and intracellular activity was obtained for a quinupristin/dalfopristin ratio of 3:7. For strain CM05, quinupristin/dalfopristin was static in all conditions. Based on historical comparisons with rifampicin, fluoroquinolones, lipoglycopeptides and other antistaphylococcal drugs with a large accumulation in eukaryotic cells, quinupristin/dalfopristin appears to be one of the most active antibiotics against intracellular S. aureus studied in this model so far, largely irrespective of its resistance phenotype.Journal of Antimicrobial Chemotherapy 04/2010; 65(6):1228-36. DOI:10.1093/jac/dkq110 · 5.44 Impact Factor
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ABSTRACT: Although remarkable advances in the development of antibacterial agents for infections caused by Staphylococcus aureus began in the 1940s, treatment of this pathogen is still a challenge for clinicians. The emergence of S aureus strains with resistance to penicillin and methicillin in 1948 and 1961 and the recent reports of vancomycin-resistant strains indicate that the battle against this versatile pathogen is not yet over. This review discusses the newly developed antimicrobial agents, mechanisms of action, in-vitro studies, and emerging trends in S aureus resistance to these antibacterial agents. The availability of linezolid in intravenous and oral form is an advantage for the treatment of pneumonia and skin and soft tissue infection. Daptomycin is recommended for the treatment of deep-seated infections, such as endocarditis or osteomyelitis caused by methicillin-resistant S aureus. Tigecycline is a promising antibacterial agent in cases of complicated intra-abdominal infections and complicated skin infections in adults. Novel cephalosporins, quinolones, and conjugate vaccines are currently being developed. Rational antimicrobial usage along with effective infection control measures are required to avert the rapid emergence of resistant strains of S aureus to these new agents.Wounds: a compendium of clinical research and practice 01/2006; 18(5):129-146. · 0.70 Impact Factor
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ABSTRACT: The aim of this study was to investigate the erythromycin resistance patterns of Enterococci sp. present in cow milk. A total 110 erythromycin resistant Enterococci were isolated from milk samples; E. faecalis (n=101), E. avium (n=7), and E. durans (n=2). The minimum inhibitory concentration of erythromycin against 110 Enterococci were determined. The 66.3% of Entercocci (n=73) showed high level resistance ( mg/ml). Among 110 isolates, 86.3% (n=95) showed phenotype and 13.6% (n=15) showed The aim of this study was to investigate the erythromycin resistance patterns of Enterococci sp. present in cow milk. A total 110 erythromycin resistant Enterococci were isolated from milk samples; E. faecalis (n=101), E. avium (n=7), and E. durans (n=2). The minimum inhibitory concentration of erythromycin against 110 Enterococci were determined. The 66.3% of Entercocci (n=73) showed high level resistance ( mg/ml). Among 110 isolates, 86.3% (n=95) showed phenotype and 13.6% (n=15) showed phenotype. All of isolates have erm(B) determinant, 75.45% (n=83) have mef(A) an efflux system determinant. The majority of Enetrcococci isolated from raw milk samples in northern area of Gyeonggi-Do showed high level of resistance to erythromycin.Korean Journal of Microbiology 01/2010; 46(2).