Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies

Matthew E. Falagas (1, 2, 3) , Antonia C. Kastoris (1) , Drosos E. Karageorgopoulos (1) , Petros I. Rafailidis (1, 2)

1 Alfa Institute of Biomedical Sciences (AIBS)
2 Department of Medicine
3 Department of Medicine

The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR isolates was ≥90% and 50–90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR and 0/31 MDR spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a β-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR endocarditis. In six clinical studies, 33 patients with MDR . infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR . infections. Further research is needed to clarify the potential utility of this agent.

Mots clés: Bacterial drug resistance; Microbial sensitivity tests; Drug combinations; Cystic fibrosis; Pneumonia; Metallo-β-lactamases

Matthew E. Falagas, Antonia C. Kastoris, Drosos E. Karageorgopoulos, Petros I. Rafailidis. Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies. International Journal of Antimicrobial Agents, 2009, 34 (2), pp.111. ⟨10.1016/j.ijantimicag.2009.03.009⟩. ⟨hal-00556337⟩