Adjuvant β-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-analysis

Abstract

Infections due to methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB) seriously threaten public health due to poor outcomes and high mortality. The objective of this study is to perform a systematic review and meta-analysis of the current evidence on adjuvant β-lactam (BL) therapy combined with vancomycin (VAN) or daptomycin (DAP) for MRSAB. PubMed, Embase and Cochrane Library were systematically searched for publications reporting clinical outcomes of BLs+VAN or BLs+DAP for adult patients with MRSAB through April 5, 2020. Meta-analysis techniques were applied using random-effects modelling. Three randomized controlled trials and 12 retrospective cohort studies were identified, totalling 2594 patients. Combination treatment significantly reduced the risk of clinical failure [lsqb]risk ratio (RR)=0.80, 95% confidence interval (CI) 0.66–0.96; P=0.02, I2=39%[rsqb], bacteraemia recurrence (RR=0.66, 95% CI 0.50–0.86; P=0.002, I2=0%), and persistent bacteraemia (RR=0.65, 95% CI 0.55–0.76; P<0.00001, I2=0%) and shortened the duration of bacteraemia [lsqb]standardized mean difference(SMD)= –0.37, 95% CI –0.48 to –0.25; P<0.00001, I2=0%[rsqb]. There was no significant difference in the risk of crude mortality, nephrotoxicity, or thrombocytopenia between groups. Notably, combination treatment might non-significantly increase the risk of C. difficile infection (CDI) (RR=2.13, 95% CI 0.98–4.63; P=0.06, I2=0%). Subgroup analysis suggested that DAP+BLs could reduce crude mortality (RR=0.53,95% CI 0.28–0.98; P=0.04,I2=0%).The meta-analysis suggested that although combination therapy with BLs could improve some microbial outcomes, it could not reduce crude mortality but might increase the risk of CDI and should be applied very cautiously. Regarding mortality reduction, the combination of DAP+cephalosporins appears more promising.

Daptomycin versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection with or without Endocarditis: A Systematic Review and Meta-Analysis

“…A recent meta-analysis of 15 studies (3 RCTs) on 2594 patients investigating the role of adjuvant beta-lactam therapy failed to demonstrate an overall benefit on mortality of combination regimens compared with DAP or VAN alone (relative risk 1.14. 95% CI 0.92–1.57), although a positive effect was apparent regarding clinical failure, recurrence or persistence of bacteremia, as well as on death rate when considering the small subgroup (three studies) of patients receiving DAP plus beta-lactam [ 40 ]. The association between DAP and a beta-lactam agent is intriguing since it might help to circumvent the emergence of strains non-susceptible to DAP and the emergence of resistance to host cationic antimicrobial peptides; by a so-called “see-saw” effect mechanism, MRSA strains might gain improved susceptibility to beta-lactams [ 41 ].…”

A Systematic Review of Intracellular Microorganisms within Acanthamoeba to Understand Potential Impact for Infection

“…A final score was assigned to each study after consensus between the reviewers. NOS scores can vary from 0 to 9, and studies, with an average score of ≥6 were included for this review ( Table S1 ) [ 133 ]. A meta-analysis of the studies was not performed due to a high level of heterogeneity.…”

The Effect of Combination Therapy on Mortality and Adverse Events in Patients with Staphylococcus aureus Bacteraemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…Improved outcomes for patients with SAB have been sought through efforts to enhance antimicrobial efficacy by using combination antimicrobial therapy. In a previous meta-analysis of β-lactams combined with aminoglycosides, rifampicin combined with standard regimens for the treatment of SAB, β-lactams combined with vancomycin, or daptomycin in the treatment of MRSAB, it was suggested that combination therapy cannot significantly reduce the mortality of patients compared with that for monotherapy [ 17 , 18 , 36 ]. The above three meta-analyses are consistent with our results; however, owing to the poor quality and heterogeneity of the studies included in these meta-analyses, convincing clinical data are sparse.…”

“…Several efforts have been made through meta-analyses to investigate whether combination antibiotic therapy is associated with better clinical outcomes than monotherapy. However, these meta-analyses either included a small number of patients with S. aureus infections or most of the included studies were non-RCTs with large heterogeneity that affected the reliability of the results [17][18][19]. We aimed to systematically review and synthesize the published RCTs via meta-analysis methodology to examine whether combination antibiotic therapy was associated with more favourable clinical outcomes than monotherapy in patients with SAB.…”