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The ratio of pre-dialysis vancomycin trough serum concentration to minimum inhibitory concentration is associated with treatment outcomes in methicillin-resistant Staphylococcus aureus bacteremia.

ABSTRACT: Vancomycin is a standard treatment for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, and its efficacy is closely linked to the recommended serum trough concentration of 15-20 mg/L. However, it is unknown how the pre-dialysis trough serum concentration (Cpre-HD) correlates with MRSA eradication in renal failure patients undergoing intermittent hemodialysis (HD).To evaluate the relationship between Cpre-HD and the treatment outcomes in this population.A retrospective study was conducted to enroll renal failure patients undergoing HD who had received vancomycin treatment for MRSA bacteremia during January 2013 to June 2016. Treatment failure was defined as persistent bacteremia after ≥ 7 days of vancomycin therapy or recurrent MRSA infection within 30 days. Patient characteristics, vancomycin dosing regimen, Cpre-HD, vancomycin minimum inhibitory concentration (MIC), and subsequent culture data were reviewed. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point of Cpre-HD.42 patients were enrolled and 64% had treatment failure. Although there were no significant differences in demographics or Cpre-HD between the two groups, Cpre-HD/MIC was significantly higher in the success group than that in the failure group (22.80±10.90 vs. 14.94±6.11, p = 0.019). The area under the ROC curve was 0.74, while the sensitivity, specificity, positive predictive value, and negative predictive value were 67%, 78%, 62.5%, and 81%, respectively, at the optimal Cpre-HD/MIC of ≧ 18.6.Cpre-HD/MIC was associated with vancomycin treatment outcome in MRSA bacteremia, and targeting to achieve a Cpre-HD/MIC of ≧ 18.6 may improve treatment outcomes in renal failure patients who are on intermittent HD.

SUBMITTER: Fu CF

PROVIDER: S-EPMC5837094 | 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.

Project description:BACKGROUND:Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. METHODS/DESIGN:The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment.The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. DISCUSSION:If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. TRIAL REGISTRATION:The trial is listed on clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013).

Project description:ObjectiveThe use of the vancomycin minimum inhibitory concentration (MIC) as a prognostic predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) has been debated in the last decade. We performed a systematic review and meta-analysis to investigate whether an elevated vancomycin MIC is associated with a worse prognosis for patients with MSSA bacteraemia.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were searched from inception to December 2019.Eligibility criteriaRandomised controlled trials or observational studies were considered eligible if they provided clinical outcomes of patients with MSSA bacteraemia, stratified by vancomycin MIC.Data synthesisPrimary outcome was mortality. Secondary outcomes included septic thrombophlebitis, persistent bacteraemia and complicated bacteraemia. Pooled ORs and 95% CIs were calculated. Subgroup analyses included the susceptibility testing method.ResultsFifteen observational studies were included. Bacteraemia due to MSSA isolates with high vancomycin MICs was associated with higher mortality than isolates with low MICs (OR 1.44; 95% CI 1.12 to 1.84; I2=40.3%). Additionally, significantly greater septic thrombophlebitis (OR 3.16; 95% CI 1.11 to 9.00; I2=58.6%) and a trend towards more persistent bacteraemia (OR 1.79; 95% CI 0.97 to 3.31; I2=0%) were observed in patients with high vancomycin MICs than in patients with low MICs. Differences in complicated bacteraemia were not significant. Similar findings were obtained in subgroup analyses using Etest. However, significant differences in outcomes were not observed between the high and low vancomycin MICs detected using broth microdilution.ConclusionThe available data suggest an association between elevated vancomycin MICs detected using Etest and adverse clinical outcomes for patients with MSSA bacteraemia. Future studies should validate these findings and explore the potential mechanisms.Prospero registration numberCRD42018090547.

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The ratio of pre-dialysis vancomycin trough serum concentration to minimum inhibitory concentration is associated with treatment outcomes in methicillin-resistant Staphylococcus aureus bacteremia.

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