Antistaphylococcal penicillins versus cephalosporins for definitive treatment of meticillin-susceptible Staphylococcus aureus bacteraemia: A systematic review and meta-analysis

https://doi.org/10.1016/j.ijantimicag.2014.09.002Get rights and content

Highlights

  • Data from 1643 patients studied mainly retrospectively were included.

  • Unadjusted 30-day mortality was lower in patients treated with ASPs than in those treated with cephalosporins (RR 0.62, 95% CI 0.40–0.98).

  • Propensity score adjusted 30-day mortality was not different in patients receiving ASPs or cephalosporins (0.75, 0.41–1.39).

  • Both unadjusted (0.85, 0.54–1.32) and adjusted (1.42, 0.22–9.06) 90-day mortality were not different between patients receiving ASPs or cephalosporins.

  • Limited data regarding adverse events, development of resistance and recurrences were available.

  • Specific data regarding primary or secondary, community-acquired, healthcare-associated or nosocomial MSSA bacteraemia were not available. Several ASPs and cephalosporins were compared.

Abstract

The objective of this study was to assess the comparative effectiveness and safety of antistaphylococcal penicillins (ASPs) and cephalosporins for the definitive treatment of patients with meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. PubMed and Scopus electronic databases were searched up to December 2013. All-cause mortality was the primary outcome of interest. A meta-analysis of unadjusted and adjusted data was performed. Seven articles (1643 patients) were included; all but one were retrospective studies, and three of them employed propensity score matching. The studies enrolled primarily adults hospitalised in medical wards for primary or secondary community-acquired, healthcare-associated or nosocomial MSSA bacteraemia. Several ASPs and cephalosporins were compared. Unadjusted 30-day mortality was lower in patients treated with ASPs than in those treated with cephalosporins [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.40–0.98]. Propensity score-adjusted 30-day mortality was not different in patients receiving ASPs or cephalosporins (RR = 0.75, 95% CI 0.41–1.39). Substantial heterogeneity and publication bias were found in these analyses. Both unadjusted (RR = 0.85, 95% CI 0.54–1.32) and adjusted (RR = 1.42, 95% CI 0.22–9.06) 90-day mortality did not differ between patients receiving ASPs or cephalosporins. Limited data regarding adverse events, development of resistance and recurrence were available. In conclusion, the limited available published data derive from retrospective studies and show that there appears to be no statistically significant difference in mortality between ASPs and cephalosporins for the treatment of MSSA bacteraemia.

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.

Section snippets

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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