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: 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. · 0.54 Impact Factor
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ABSTRACT: The antibacterial activity of XRP2868, a new oral streptogramin composed of a combination of RPR132552 (streptogramin A) and RPR202868 (streptogramin B), was evaluated against a collection of clinical gram-positive isolates with characterized phenotypes and genotypes of streptogramin resistance. The effects of genes for resistance to streptogramin A or B on the activity of XRP2868 and its components were also tested by cloning these genes individually or in various combinations in gram-positive recipient strains susceptible to quinupristin-dalfopristin. The species tested included Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae, and other species of streptococci. XRP2868 was generally fourfold more potent than quinupristin-dalfopristin against S. aureus, E. faecium, and streptococci and had activity against E. faecalis (MICs = 0.25 to 1 microg/ml). XRP2868 appeared to be affected by the same mechanisms of resistance as those to quinupristin-dalfopristin. Nevertheless, the strong activity of factor A of the oral streptogramin enabled the combination to be very potent against streptogramin-susceptible staphylococci, streptococci, and E. faecium (MICs = 0.03 to 0.25 microg/ml) and to retain low MICs against the strains harboring a mechanism of resistance to factor A or factor B of the streptogramin. However, the combination of mechanisms of resistance to factors A and B caused an increase in the MICs of XRP2868, which reached 1 to 4 mug/ml. As with the other streptogramins, there was a reduction in the bactericidal effect of XRPR2868 when the staphylococcal strains acquired a constitutively expressed erm gene.Antimicrobial Agents and Chemotherapy 02/2006; 50(1):237-42. DOI:10.1128/AAC.50.1.237-242.2006 · 4.48 Impact Factor
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ABSTRACT: In recent years, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen in children without established risk factors, and its prevalence in the United States is increasing. Although many CA-MRSA infections are mild, primarily involving the skin and soft tissues, the organism can cause serious, invasive, and life-threatening infections. To provide a comprehensive review of the epidemiology, clinical features, therapy, and prevention of CA-MRSA infections in children, we performed MEDLINE (1966-January 2006) and Cochrane Library searches, and reviewed abstracts for relevance to S. aureus infections. Only articles pertaining to CA-MRSA infections in pediatrics were closely examined. As a genetically distinct pathogen, CA-MRSA is generally susceptible to multiple non-beta-lactam antimicrobials. The optimal treatment for CA-MRSA infections in pediatric patients has not been well studied. Common antibiotics used include clindamycin, trimethoprim-sulfamethoxazole, vancomycin, and rifampin. Rational empiric antimicrobial therapy for infections caused by S. aureus requires consideration of the possibility of methicillin resistance. The local prevalence and susceptibilities of CA-MRSA, severity of infection, and individual risk factors should be considered in selecting treatment.Pharmacotherapy 01/2007; 26(12):1758-70. DOI:10.1592/phco.26.12.1758 · 2.66 Impact Factor