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Underestimation of vancomycin and teicoplanin MICs by broth microdilution leads to underdetection of glycopeptide-intermediate isolates of Staphylococcus aureus.

ABSTRACT: Broth microdilution was compared with tube macrodilution and a simplified population analysis agar method for evaluating vancomycin and teicoplanin MICs and detecting glycopeptide-intermediate isolates of Staphylococcus aureus. Modal vancomycin and teicoplanin MICs recorded by tube macrodilution and the agar plate assay, which both used inocula of 10(6) CFU, were significantly higher (2 microg/ml) against a panel of borderline glycopeptide-susceptible and glycopeptide-intermediate methicillin-resistant S. aureus (MRSA) bloodstream isolates compared to broth microdilution (1 microg/ml). Vancomycin and teicoplanin MIC distributions by tube macrodilution and agar testing were also markedly different from those evaluated by broth microdilution. The 20-fold-lower inoculum size used for broth microdilution compared to macrodilution and agar MIC assays explained in part, but not entirely, the systematic trend toward lower vancomycin and teicoplanin MICs by microdilution compared to other methods. Broth microdilution assay led to underdetection of the vancomycin-intermediate S. aureus (VISA) phenotype, yielding only three VISA isolates, for which vancomycin MICs were 4 microg/ml compared to 8 and 19 VISA isolates detected by macrodilution and agar testing, respectively. While macrodilution and agar testing detected 7 and 22 isolates with elevated teicoplanin MICs (8 microg/ml), respectively, broth microdilution failed to detect such isolates. Detection rates of isolates with elevated vancomycin and teicoplanin MICs by macrodilution and agar testing assays were higher at 48 h than at 24 h. In conclusion, the sensitivity of broth microdilution MIC testing is questionable for reliable detection and epidemiological surveys of glycopeptide-intermediate resistance in S. aureus isolates.

SUBMITTER: Vaudaux P

PROVIDER: S-EPMC2934981 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Vancomycin, the first line antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, is often administered inappropriately when MIC is greater than 2 µg/mL, including 'susceptible' strains. This study assessed the discordance of vancomycin minimum inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus (MRSA). Methods:In total, 229 MRSA isolates from blood cultures collected between 2009 and 2015 at a tertiary hospital in Taiwan were examined. The MICs of vancomycin were measured using Vitek 2, E-test, and standard broth microdilution at the level of 2 µg/mL. Results:The geometric mean of the MICs of hospital-acquired MRSA was higher than that of community-acquired MRSA (P < 0.001), with the exact agreement rates (with broth microdilution) at 2 µg/mL being 53.6% in Vitek 2 and 86.7% in E-test. Overall, E-test (98.1%) had more categorical accordance than did Vitek 2 (94.0%; P = 0.026). Vitek 2 had a tendency to overestimate MRSA in high-MIC isolates, whereas E-test inclined underestimation in low-MIC isolates. Surprisingly, the discordance rates of MRSA vancomycin MICs were higher in hospital-acquired isolates (13.3%-17.0%) than in community-acquired isolates (6.2%-7.0%). Conclusion:The Infectious Diseases Society of America recommends the use of alternative antimicrobial agents when vancomycin MIC is ? 2 µg/mL; in this study, only 53.6% of the isolates tested using Vitek 2 showed a high MIC in the broth microdilution method. Accurate identification of the resistance profile is a key component of antimicrobial stewardship programs. Therefore, to reduce inappropriate antibiotic use and mitigate the emergence of resistant strains, we recommend using complementary tests such as E-test or Broth microdilution to verify the MIC before administering second-line antibiotics. Strengths:(1) We compared the categorical agreement between different methods measuring MRSA MICs level. (2) Physicians should incorporate this information and consider a complementary test to verify the appropriateness of the decision of shifting vancomycin to second-line antibiotic treatment to improve patients' prognosis. (3) MRSA-vancomycin MICs at a cutoff of 2 µg/mL obtained using Vitek II exhibited a higher sensitivity level and negative predictive value than those obtained using E-test in the prediction of categorical agreement with standard broth microdilution. Limitation:(1) Our research was based on a single hospital-based study. (2) The MRSA strains in this study were stored for more than 12 months after isolation. (3) We did not collect information on clinical prognosis.

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Underestimation of vancomycin and teicoplanin MICs by broth microdilution leads to underdetection of glycopeptide-intermediate isolates of Staphylococcus aureus.

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