• Luka Bielen, Robert Likić, Viktorija Erdeljić, Ivana Mareković, Nataša Firis, Marijana Grgić-Medić, Ana Godan, Ivan Tomić, Blaženka Hunjak, Alemka Markotić, Danijela Bejuk, Vladimira Tičić, Silvana Balzar, and Branka Bedenić.
• Robert Likić, University Hospital Center Zagreb, Department of Internal Medicine, Unit of Clinical Pharmacology, Kispaticeva 12, 10000 Zagreb, Croatia, robert.likic@mef.hr.
• Croat. Med. J. 2018 Apr 30; 59 (2): 56-64.

AimTo determine in vitro susceptibility of multiresistant bacterial isolates to fosfomycin.MethodsIn this prospective in vitro study (local non-random sample, level of evidence 3), 288 consecutively collected multiresistant bacterial isolates from seven medical centers in Croatia were tested from February 2014 until October 2016 for susceptibility to fosfomycin and other antibiotics according to Clinical and Laboratory Standards Institute methodology. Susceptibility to fosfomycin was determined by agar dilution method, while disc diffusion was performed for in vitro testing of other antibiotics. Polymerase chain reaction and sequencing were performed for the majority of extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and carbapenem-resistant isolates.ResultsThe majority of 288 multiresistant bacterial isolates (82.6%) were susceptible to fosfomycin. The 236 multiresistant Gram-negative isolates showed excellent susceptibility to fosfomycin. Susceptibility rates were as follows: Escherichia coli ESBL 97%, K. pneumoniae ESBL 80%, Enterobacter species 85.7%, Citrobacter freundii 100%, Proteus mirabilis 93%, and Pseudomonas aeruginosa 60%. Of the 52 multiresistant Gram-positive isolates, methicillin-resistant Staphylococcus aureus showed excellent susceptibility to fosfomycin (94.4%) and vancomycin-resistant enterococcus showed low susceptibility to fosfomycin (31%). Polymerase chain reaction analysis of 36/50 ESBL-producing K. pneumoniae isolates showed that majority of isolates had CTX-M-15 beta lactamase (27/36) preceded by ISEcp insertion sequence. All carbapenem-resistant Enterobacter and Citrobacter isolates had blaVIM-1 metallo-beta-lactamase gene.ConclusionWith the best in vitro activity among the tested antibiotics, fosfomycin could be an effective treatment option for infections caused by multiresistant Gram-negative and Gram-positive bacterial strains in the hospital setting.

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