Reviewβ-Lactam plus aminoglycoside or fluoroquinolone combination versus β-lactam monotherapy for Pseudomonas aeruginosa infections: A meta-analysis
Introduction
Pseudomonas aeruginosa is among the leading causes of infections in hospitalised and immunocompromised patients and is associated with significant morbidity and mortality [1], [2]. It has been suggested that a combination of antibiotics might be more effective than monotherapy at least for severe infections, and combination therapy with a β-lactam plus an aminoglycoside or a fluoroquinolone has been proposed in the guidelines of several medical associations [3]. Findings of in vitro studies suggested that synergism was accomplished against P. aeruginosa strains when two drugs that target a different or even the same bacterial mechanism are combined [4], [5]. Similar studies suggested that development of resistance is prevented by combination antibiotic regimens [6], [7]. Furthermore, in an era of increasing antibiotic resistance, adequate empirical treatment is more likely with the use of a combination of antibiotics.
Several efforts have been made through meta-analyses of randomised controlled trials (RCTs) to investigate whether combination antibiotic therapy was associated with better clinical outcomes than monotherapy. However, these meta-analyses either included a small number of patients with P. aeruginosa infections, or a variety of antibiotic classes were compared in the treatment arms of the included studies [8], [9], [10], [11]. We aimed to review systematically and to synthesise the published evidence with the methodology of meta-analysis in order to examine whether combination antibiotic therapy of β-lactam with either aminoglycoside or fluoroquinolone was associated with more favourable clinical outcomes compared with β-lactam monotherapy in patients with P. aeruginosa infections.
Section snippets
Literature search
A systematic search was performed in the PubMed and Scopus databases until April 2012. The following search term was applied: ‘(pseudomonas OR aeruginosa) AND (combination OR monotherapy) AND (mortality OR outcome)’. The bibliographies of relevant studies were also hand-searched to identify additional potentially eligible studies. Articles published in languages other than English, German, French, Spanish, Italian or Greek were not evaluated. Unpublished studies presented at scientific
Results
Fig. 1 shows the process used for article selection. Nineteen articles from those retrieved from the literature search were included [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]. A total of 8675 patients were enrolled, of whom 1721 had P. aeruginosa infections. Table 1 shows the reason for exclusion of RCTs from the meta-analysis.
Table 2 shows the characteristics of the 19 selected studies and their outcomes. Eight studies
Discussion
The published available evidence suggests that the combination of a β-lactam with an aminoglycoside or fluoroquinolone does not result in a survival benefit in patients with P. aeruginosa infections compared with β-lactam monotherapy. Most of the studies reported on mortality of patients receiving definitive treatment. Fewer data regarding empirical treatment were available. In addition, all but one of the studies that provided data on mortality were non-randomised, and none of those that
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