ReviewFosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies
Introduction
In an era of extensive bacterial drug resistance, especially among non-fermenting Gram-negative species such as Pseudomonas aeruginosa and Acinetobacter baumannii [1], emphasis should be given not only to the development of new drugs but also to the re-evaluation of older and ‘forgotten’ drugs [2], [3], [4]. Fosfomycin is a drug representing the latter category, discovered almost 40 years ago. It inhibits bacterial cell wall biosynthesis by inactivating the UDP-N-acetyl-glucosamine-3-o-enolpyruvultransferase [5].
The oral form of this broad-spectrum antibiotic [6] has principally been used in the treatment of uncomplicated urinary tract infections (UTIs) in the USA, the UK and other countries. However, the intravenous form has been used for indications beyond UTIs in only a few countries such as Germany, France, Spain and Japan [7]. Recent data suggest that it may be considered as an alternative in the treatment of Gram-negative and Gram-positive infections other than of UTIs [7], [8].
Thus, we sought to evaluate human and animal studies that examined the clinical effectiveness and/or microbiological activity of fosfomycin against multidrug-resistant (MDR), extensively drug-resistant (XDR) or pandrug-resistant (PDR) non-fermenting Gram-negative bacilli.
Section snippets
Literature search
We systematically searched PubMed, Scopus and the Cochrane Library databases up to January 2009. The keywords used were (fosfomycin OR phosphomycin OR phosphonomycin) AND (drug resistance OR Pseudomonas OR Acinetobacter OR Stenotrophomonas OR Burkholderia). Bibliographies of relevant articles were also hand-searched.
Study selection
Studies were selected if they included microbiological, animal experimental or clinical data on the effect of fosfomycin against MDR non-fermenting Gram-negative pathogens such as
Results
The process of study selection is depicted as a flow diagram in Fig. 1. A total of 30 studies published between 1985 and 2008 were included in the review [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. Twenty-three of these are microbiological studies on the activity of fosfomycin against clinical isolates of MDR non-fermenting Gram-negative bacteria [8], [9], [10],
Discussion
The main finding of our review is that fosfomycin may play a role in the treatment of infections caused by MDR P. aeruginosa. One has to acknowledge that relatively few studies have examined the clinical or microbiological effects of fosfomycin on infections due to MDR non-fermenting Gram-negative bacilli. Interestingly, the great majority of relevant studies regard P. aeruginosa, whilst there is a dearth of relevant data for MDR A. baumannii, Burkholderia spp. and Stenotrophomonas spp.
The
Conclusions
Fosfomycin could potentially be considered in the treatment of infections caused by MDR P. aeruginosa if established therapeutic options are not available. An appreciable number of studies have documented good antimicrobial activity of fosfomycin against MDR P. aeruginosa isolates, which is difficult to quantitate given the lack of universally accepted specific species-related susceptibility breakpoints. The antimicrobial activity of fosfomycin against MDR P. aeruginosa may also be enhanced in
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