Factors Influencing Time to Vancomycin-Induced Clearance of Nonendocarditis Methicillin-Resistant Staphylococcus aureus Bacteremia: Role of Platelet Microbicidal Protein Killing and agr Genotypes

• Published in: The Journal of infectious diseases Vol. 201; no. 2; pp. 233 - 240
• Main Authors: Moise, Pamela A., Forrest, Alan, Bayer, Arnold S., Xiong, Yan Q., Yeaman, Michael R., Sakoulas, George
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.01.2010; University of Chicago Press; Oxford University Press
• Subjects: Aged; Aged, 80 and over; Anti-Bacterial Agents - pharmacology; Bacteremia; Bacteremia - drug therapy; Bacteremia - microbiology; BACTERIA; Bacterial diseases; Bacterial Proteins - genetics; Bacterial sepsis; Bacteriology; beta-Thromboglobulin - physiology; Biological and medical sciences; Cubism; Endocarditis; Female; Fundamental and applied biological sciences. Psychology; Genotype; Genotypes; Human bacterial diseases; Humans; Infections; Infectious diseases; Kaplan-Meier Estimate; Male; Medical sciences; Methicillin resistant staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Microbial Sensitivity Tests; Microbiology; Middle Aged; Miscellaneous; Penicillin-Binding Proteins; Platelets; Staphylococcus aureus; Trans-Activators - genetics; Vancomycin - pharmacology; Peptides; Genotype; Clearance; Vancomycin; Bacteremia; Protein; Infection; Antibiotic; Platelet; Glycopeptide; Polypeptide; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Antibacterial agent; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/649429

Background. Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated the interrelationship of these factors with time to clearance of MRSA bacteremia during vancomycin therapy in patients without endocarditis. Methods. Vancomycin minimum inhibitory concentration and in vitro killing, agr function (δ-hemolysin activity), agr group, SCCmec type, and survival in tPMP-1 killing assays were determined for 29 MRSA bacteremia isolates. Results. Increased resistance to tPMP-1 killing was observed with agr group III MRSA (P = .025) and MRSA with reduced or absent agr function (P = .023). The median time to clearance of MRSA bacteremia was earlier for agr group III (3 days) versus group I (10.5 days) or II (15 days) (P = .001). In multivariate analysis, agr group II, reduced tPMP-1 killing in vitro, and prior vancomycin exposure were significant independent predictors of longer MRSA bacteremia duration. Conclusions. Specific genotypic, phenotypic, and clinical parameters appear to correlate with persistent MRSA bacteremia. The interrelationship of these and other factors probably contributes to vancomycin-mediated clearance of MRSA bacteremia.