Antistaphylococcal penicillins versus cephalosporins for definitive treatment of meticillin-susceptible Staphylococcus aureus bacteraemia: A systematic review and meta-analysis
Introduction
Studies performed worldwide have shown that Staphylococcus aureus is among the leading pathogens causing bacteraemia [1], [2], [3]. The incidence both of hospital- and community-acquired S. aureus bacteraemia (SAB) has risen during the past decades owing to frequent use of intravascular devices, larger numbers of immunocompromised patients and an increased number of surgical procedures [1], [2], [3]. Despite improvements in healthcare services and antimicrobial drug treatment, mortality rates remain high. In particular, it has been estimated that the death rate for infections due to meticillin-resistant S. aureus (MRSA) is 34.2%, whilst that for meticillin-susceptible S. aureus (MSSA) is 25% [4].
Although SAB remains a common infection associated with significant morbidity and mortality, limited clinical data exist for optimal antibiotic therapy, especially regarding MSSA bacteraemia. Historically, antistaphylococcal penicillins (ASPs), e.g. oxacillin, nafcillin, cloxacillin, dicloxacillin and flucloxacillin, were considered to be the treatment of choice for SAB caused by penicillin-resistant strains, whilst cephalosporins were considered an alternative option. However, the comparative clinical effectiveness of β-lactams against MSSA bacteraemia has not been clearly estimated.
In the absence of randomised controlled trials (efficacy studies), the selection of antimicrobial agents for MSSA bacteraemia was based on local availability of antibiotics, clinical experience and in vitro studies. Experimental studies indicated that ASPs are superior to cephalosporins and are more bactericidal [5], [6]. Recently, experimental studies demonstrated the high inoculum effect among clinical isolates of MSSA with cefazolin treatment, suggesting a possible cause of cefazolin treatment failure reported in case reports and animal models [5], [7]. To our knowledge, few studies that assessed the comparative effectiveness and safety of β-lactams for the treatment of MSSA bacteraemia have been published. Hence, in this systematic review, we evaluated the effectiveness and safety of ASPs compared with cephalosporins.
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Literature search
With the aim of collecting data about the treatment of MSSA bacteraemia, a search of the literature was performed using the Scopus and PubMed electronic databases up to December 2013. A review protocol was not done. Two of the authors (KZV and KNA) searched the literature independently. The search term applied in both databases was: ‘(staphylococcus aureus) AND (meticillin-sensitive OR meticillin-susceptible OR MSSA) AND (bacteremia OR septicemia OR blood stream infection)’. Any article written
Results
Fig. 1 summarises the selection process of articles eligible for inclusion in the systematic review and meta-analysis. After a thorough search of electronic databases, 575 and 476 articles were identified and screened in PubMed and Scopus, respectively, from which 44 full-text articles were assessed for eligibility, among which 7 were selected for the meta-analysis [8], [9], [10], [11], [12], [13], [14]. The rest of the retrieved studies were excluded because of ineligible outcomes. The
Discussion
Currently, there are limited published data regarding the optimal definitive treatment for MSSA bacteraemia. This systematic review and meta-analysis showed that although unadjusted 30-day mortality was lower in patients treated with ASP compared with those treated with cephalosporins (in declining order, the majority of data are for cefuroxime and cefazolin), the analysis of propensity score-adjusted data showed no difference between the compared groups of antibiotics. In two of the studies
Acknowledgments
The authors would like to thank Dr M. Paul, Dr D.J. Livorsi and Dr M.L. Schweizer for providing the requested data.
Funding: No funding sources.
Competing interests: MEF has participated on advisory boards of Achaogen, Astellas, AstraZeneca, Bayer and Pfizer, has received lecture honoraria from Angelini, Astellas, AstraZeneca, Glenmark, Merck and Novartis, and has received research support from Angelini, Astellas and Rokitan. All other authors declare no competing interests.
Ethical approval: Not
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