Inhibitory Activities of 11 Antimicrobial Agents and Bactericidal Activities of Vancomycin and Daptomycin against Invasive Methicillin-Resistant Staphylococcus aureus Isolates Obtained from 1999 through 2006

Abstract

We assessed MICs and minimal bactericidal concentrations of vancomycin, daptomycin, and nine other antimicrobials against methicillin-resistant Staphylococcus aureus isolates obtained from 1999 through 2006. No vancomycin, daptomycin, or linezolid resistance was observed. Clindamycin, gentamicin, and ciprofloxacin resistance decreased significantly. No tolerance to vancomycin or daptomycin was observed, nor was MIC creep seen.The increasing prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been accompanied by debate over the effectiveness of vancomycin, perhaps due to diminished inhibitory or bactericidal activity that may have occurred in recent years. Some recent studies have differed with respect to the stability of vancomycin MICs over time (5,8,9,18,21). An earlier study from University of Texas Health Science Center and University Hospital indicated that the activity of vancomycin against MRSA did not change between the years 1987 and 1999, during a period of increasing resistance to other drug classes (e.g., macrolides, lincosamides, and fluoroquinolones) (9).The presence and/or significance of antimicrobial tolerance remains an area of controversy (15,20). Vancomycin tolerance was not related to outcome in an animal model of S. aureus endocarditis (20). However, reduced bactericidal activity of vancomycin (using a high-inoculum method) correlated with worse outcome in bacteremic patients treated with vancomycin (15).The purpose of this study was to assess the inhibitory and bactericidal activities of vancomycin and daptomycin and inhibitory activities of nine other commonly used antimicrobial agents against isolates of MRSA recovered from bacteremic patients at a university hospital during an 8-year period from 1999 through 2006.The first 30 MRSA isolates recovered from bacteremic patients each year were retrieved from the frozen isolate bank of the University Hospital Microbiology Laboratory during the years 1999 through 2006. Vancomycin troughs have been carefully monitored for approximately the last 2 years of the study period. These strains represented the first isolate recovered from each patient (not posttherapy), had been stored in skim milk at Ϫ70°C since isolation, and had been subcultured a minimum of two times.Isolates were tested by the CLSI (formerly NCCLS) broth microdilution procedure (3); the test medium was cation-adjusted Mueller-Hinton broth. Panels incorporated 1/2-log 2 dilutions of vancomycin (range of concentrations, 0.12 to 8 g/ ml). Also incorporated were standard dilutions of daptomycin (0.12 to 8 g/ml, with 50 g/ml calcium added to each daptomycin well), linezolid (0.06 to 16 g/ml), erythromycin (0.06 to 64 g/ml), clindamycin (0.03 to 16 g/ml), doxycycline (0.06 to 16 g/ml), minocycline (0.06 to 16 g/ml), trimethoprim-sulfamethoxazole (0.03 to 8 g/ml), gentamicin (0.06 to 8 g/ml), rifampin (0.25 to 8 g/ml), and ciprofloxacin (0.06 to 16 g/ ml). Microdilution panels were incubated at 35°C in air for 20 to 22 h prior to visual determinat...

Vancomycin MICs for Staphylococcus aureus Vary by Detection Method and Have Subtly Increased in a Pediatric Population Since 2005

“…Steinkraus et al, using Etest, found an increase in the percentage of MRSA isolates from blood cultures between 2001 and 2005 (16). This is in contrast to reports of stable vancomycin MICs over similar periods of time as revealed by BMD (1,7,9). These studies indicate that vancomycin susceptibility results are highly dependent on methodology and perhaps isolate source.…”

Vancomycin Susceptibility Trends and Prevalence of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus in Clinical Methicillin-Resistant S. aureus Isolates

“…Several studies have reported elevated vancomycin MICs in MRSA isolates where the MICs are at the upper end of the susceptibility range (18, 27, 38, 40-43, 50, 52). However, not all medical institutions are reporting an increase in vancomycin MICs (1,11,20,33). One study measured vancomycin MICs in MRSA isolates collected from 2002 to 2006 from nine different U.S. medical centers using a reference broth microdilution assay with a broad range of precise incremental dilutions (39).…”

“…Most of the isolates had a MIC of 1.5 g/ml, causing the Etest results to be more elevated than the results of the other two assays. Etest also measures the MIC for a larger proportion of bacteria at ϳ10 8 CFU than the broth microdilution assays at ϳ10 4 CFU, making Etest more sensitive in detecting resistant mutants and MIC increases (11,33,43).…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…The term vancomycin "MIC creep" is now frequently used (101,276,333,374). This phenomenon has been demonstrated at a number of centers in the United States over recent years by using Etest or vancomycin broth MIC (289,333,374), while at another location in the United States, no change in vancomycin MIC was detected between 1999 and 2006 (117). In France, increases in glycopeptide MICs (predominately teicoplanin) were observed over a 20-year period (276), while in Spain, the testing of over 3,000 clinical isolates by broth microdilution between 2002 and 2006 found no change in vancomycin MICs at one institution (6).…”