Inhibitory and Bactericidal Activities of Daptomycin, Vancomycin, and Teicoplanin against Methicillin-Resistant Staphylococcus aureus Isolates Collected from 1985 to 2007

Abstract

The inhibitory and bactericidal activities of daptomycin, vancomycin, and teicoplanin against a collection of 479 methicillin-resistant Staphylococcus aureus isolates were assessed. The isolates were collected from U.S. and European hospitals from 1985 to 2007 and were primarily from blood and abscess cultures. The MICs and minimum bactericidal concentrations (MBCs) of the three agents were determined, and the MBC/MIC ratios were calculated to determine the presence or absence of tolerance. Tolerance was defined as an MBC/MIC ratio of >32 or an MBC/MIC ratio of >16 when the MBC was greater than or equal to the breakpoint for resistance. Tolerance to vancomycin and teicoplanin was observed in 6.1% and 18.8% of the strains, respectively. Tolerance to daptomycin was not observed.Although vancomycin and teicoplanin are the standard therapies for staphylococcal bacteremia, tolerance to vancomycin and teicoplanin has been demonstrated in both coagulasenegative staphylococci and Staphylococcus aureus as well as in various Streptococcus species (2,3,7,10,13,15,20,21,23,25). Daptomycin, a lipopeptide antibiotic, has been demonstrated to have rapid bactericidal activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and tolerance to this drug has not been demonstrated (2,9,10,19,21,24,26,28).The issue of antibiotic tolerance is a complicated one. Some studies have suggested that infections caused by tolerant strains may be more difficult to treat, especially when they cause complicated infections such as endocarditis, meningitis, or osteomyelitis or cause infections in immunocompromised patients (7,8,14,15,16,18,20,22,23,25). Other investigators' expert analyses do not agree that there is proof of a correlation between tolerant strains and treatment failures or that bactericidal activity is required for the treatment of serious MRSA infections (17,25,26,27,28). Controversy concerning the appropriate methods for the determination of tolerance in clinical isolates and in the practicality of testing isolates for tolerance in the clinical laboratory also exists.This study looked at MRSA isolates obtained primarily from blood and abscess cultures collected between 1985 and 2007. The main purpose of the study was to determine the in vitro inhibitory and bactericidal activities and the level of tolerance to the three drugs observed by standardized MIC and minimum bactericidal concentration (MBC) tests (4,5,19).(This study was presented in part at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 17 to 20 September 2007.) MATERIALS AND METHODS Microorganisms.A collection of 479 MRSA isolates, primarily from blood and abscess sources of infection, collected from U.S. and European hospitals between 1985 and 2007 were tested. The isolates were unique and nonconsecutive and were collected for a variety of studies. All of the strains were susceptible to daptomycin, vancomycin, and teicoplanin and resistant to oxacillin by previous MIC testing. Vancomy...

Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

“…All S. aureus isolates tested so far demonstrate an MBC/MIC ratio of 1 or 2, indicating rapid bactericidal activity of DAP (43)(44)(45). The DAP MBC/MIC ratios varied among the four VGS strains in this study (from 4 to 16) and were higher than the values seen with S. aureus.…”

Bactericidal activity of daptomycin versus vancomycin in the presence of human albumin against vancomycin-susceptible but tolerant methicillin-resistant Staphylococcus aureus (MRSA) with daptomycin minimum inhibitory concentrations of 1–2μg/mL

“…If the compromise of bactericidal activity by tolerance has clinical implications, then the magnitude of the tolerance problem should be measured. Whilst some studies set at 15% vancomycin tolerance in wild-type MRSA [8], a recent study reported rates of 18%, 6.1% and 0% to teicoplanin, vancomycin and daptomycin, respectively [9].…”

“…The most frequent resistance phenotype is the heterogeneous vancomycin-intermediate-resistant S. aureus (hVISA), ranging from 0% to 50% in different studies, followed by homoresistant vancomycin-intermediate S. aureus (VISA) (10% of all vancomycin-intermediate-resistant isolates) and with inappreciable spread of vancomycin-resistant S. aureus (VRSA) strains [2][3][4][5][6][7]. Vancomycin tolerance is defined as a minimum bactericidal concentration:minimum inhibitory concentration (MBC:MIC) ratio of ≥32 or an MBC:MIC ratio ≥16 with an MBC value in the resistant range [8,9] and it can be assumed that 100% of VISA and VRSA, 74% of hVISA and 15% of wild-type MRSA are tolerant to this antibiotic 0924-8579/$ -see front matter © 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.…”

Investigation of Daptomycin Activity Against Methicillin Resistant Staphylococci Isolated from Clinical Samples

“…(24) yaptıkları çalışmada daptomisin, vankomisin ve teikoplanin için MİK ve minimum bakterisidal konsantrasyon oranlarını kıyaslamışlar ve en etkin antibiyotiğin daptomisin olduğu sonucuna varmışlardır.…”