Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria

• Published in: International journal of antimicrobial agents 2014-01, Vol.43 (1), p.52-59
• Main Authors: Pontikis, Konstantinos, Karaiskos, Ilias, Bastani, Styliani, Dimopoulos, George, Kalogirou, Michalis, Katsiari, Maria, Oikonomou, Angelos, Poulakou, Garyphallia, Roilides, Emmanuel, Giamarellou, Helen
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Bacterial Proteins - secretion; beta-Lactamases - secretion; Colistin - adverse effects; Colistin - therapeutic use; Critical Illness; Critically ill; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination - adverse effects; Drug Therapy, Combination - methods; Female; Fosfomycin; Fosfomycin - adverse effects; Fosfomycin - therapeutic use; Humans; Infectious Disease; Intensive Care Units; Klebsiella; Klebsiella Infections - drug therapy; Klebsiella Infections - microbiology; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - enzymology; Klebsiella pneumoniae - isolation & purification; Male; Middle Aged; Minocycline - adverse effects; Minocycline - analogs & derivatives; Minocycline - therapeutic use; PDR; Prospective Studies; Pseudomonas; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - enzymology; Pseudomonas aeruginosa - isolation & purification; Pseudomonas Infections - drug therapy; Pseudomonas Infections - microbiology; Treatment Outcome; XDR
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2013.09.010

Abstract Fosfomycin is active in vitro against extensively drug-resistant (XDR) and pandrug-resistant (PDR) Pseudomonas aeruginosa and Klebsiella pneumoniae carbapenemase-producing strains; however, the in vivo effectiveness against such pathogens is almost unknown. A multicentre, observational, prospective case-series study was performed in 11 ICUs. All consecutive fosfomycin-treated patients suffering from XDR or PDR fosfomycin-susceptible, microbiologically documented infections were recorded. Clinical and microbiological outcomes were assessed. A safety analysis was performed. In total, 68 patients received fosfomycin during the study period, 48 of whom were considered suitable for effectiveness analysis based on predefined criteria. Bacteraemia and ventilator-associated pneumonia were the main infections. Carbapenemase-producing K. pneumoniae and P. aeruginosa were isolated in 41 and 17 cases, respectively. All isolates exhibited an XDR or PDR profile, being fosfomycin-susceptible by definition. Fosfomycin was administered intravenously at a median dose of 24 g/day for a median of 14 days, mainly in combination with colistin or tigecycline. Clinical outcome at Day 14 was successful in 54.2% of patients, whilst failure, indeterminate outcome and superinfection were documented in 33.3%, 6.3% and 6.3%, respectively. All-cause mortality at Day 28 was 37.5%. Bacterial eradication was observed in 56.3% of cases. Fosfomycin resistance developed in three cases. The main adverse event was reversible hypokalaemia. In conclusion, fosfomycin could have a place in the armamentarium against XDR and PDR Gram-negative infections in the critically ill. Resistance development during therapy, which has been a matter of concern in previous studies, did not occur frequently. The necessity of combination with other antibiotics requires further investigation.