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Interventions to treat methicillin-susceptible Staphylococcus aureus bacteremia: many methodological concerns.

ABSTRACT: The aim of this letter was to point out some methodological concerns about an article written by Shi et al. and published in the journal. There is an increasing trend in the isolation of Methicillin-susceptible Staphylococcus aureus bacteremia and a variety of questions regarding the best therapy to treat this condition. These concerns might lead to selection, publication and information bias that prevent the generalization and application of these results in our clinical practice.

SUBMITTER: Garcia-Perdomo HA

PROVIDER: S-EPMC6815029 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Interventions to treat methicillin-susceptible Staphylococcus aureus bacteremia: many methodological concerns.

García-Perdomo Herney Andrés HA Toro Maldonado Jessica Fernanda JF

BMC infectious diseases 20191025 1

The aim of this letter was to point out some methodological concerns about an article written by Shi et al. and published in the journal. There is an increasing trend in the isolation of Methicillin-susceptible Staphylococcus aureus bacteremia and a variety of questions regarding the best therapy to treat this condition. These concerns might lead to selection, publication and information bias that prevent the generalization and application of these results in our clinical practice. ...[more]

PMID: 31653196

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Project description:Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Project description:Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.

Project description:Several studies have shown that patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) have worse outcomes than those with bacteremia caused by methicillin-susceptible S. aureus (MSSA). However, only a limited number of studies have stratified the MRSA isolates into healthcare-associated (HA-) and community-associated (CA-) MRSA strains in such a comparison. This three-year retrospective cohort study, enrolling adult patients with nosocomial S. aureus bacteremia (SAB), was designed to investigate whether CA-MRSA and/or HA-MRSA strains were associated with different outcomes in comparison to MSSA in such a setting. The drug susceptibilities and staphylococcal cassette chromosome mec (SCCmec) types were determined for all of the causative isolates available. The MRSA bacteremia was further categorized into those caused by CA-MRSA strains (CA-MRSA-S bacteremia) when the causative isolates carried the type IV or V SCCmec element, those caused by HA-MRSA strains (HA-MRSA-S bacteremia) when the isolates carried the type I, II, or III SCCmec element, or unclassified MRSA bacteremia when the isolates were not available. The relevant demographic, clinical, and laboratory data were collected by reviewing the patients' charts. The primary outcome was all-cause in-hospital mortality. A total of 353 patients were studied. The overall in-hospital mortality rate was 32.6%, with 23.3% in MSSA, 30.5% in CA-MRSA-S, 47.5% in HA-MRSA-S, and 35.3% in unclassified MRSA bacteremia, respectively. The multivariate analysis showed that HA-MRSA-S, but not CA-MRSA-S, bacteremia was associated with a significantly worse outcome compared with MSSA. The other risk factors independently associated with all-cause in-hospital mortality included the Charlson co-morbidity index, septic shock, thrombocytopenia, and persistent bacteremia. Resistance to linezolid and daptomycin was found among the MRSA isolates. The present study showed that bacteremia caused by HA-MRSA-S, but not CA-MRSA-S, was an independent risk factor for all-cause in-hospital mortality in patients with nosocomial SAB. Continuous monitoring regarding the susceptibilities of MRSA to linezolid and daptomycin is necessary.

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Interventions to treat methicillin-susceptible Staphylococcus aureus bacteremia: many methodological concerns.

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Interventions to treat methicillin-susceptible Staphylococcus aureus bacteremia: many methodological concerns.

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