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.

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 24g/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.

• Authors: Konstantinos Pontikis, Ilias Karaiskos, Styliani Bastani, George Dimopoulos, Michalis Kalogirou, Maria Katsiari, Angelos Oikonomou, Garyphallia Poulakou, Emmanuel Roilides, Helen Giamarellou
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 43 Issue 1 Pg. 52-9 (Jan 2014) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 24183799 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Fosfomycin
• Tigecycline
• beta-Lactamases
• carbapenemase
• Minocycline
• Colistin

Topics

• Administration, Intravenous
• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Bacterial Proteins (metabolism)
• Colistin (adverse effects, therapeutic use)
• Critical Illness
• Drug Resistance, Multiple, Bacterial
• Drug Therapy, Combination (adverse effects, methods)
• Female
• Fosfomycin (adverse effects, therapeutic use)
• Humans
• Intensive Care Units
• Klebsiella Infections (drug therapy, microbiology)
• Klebsiella pneumoniae (drug effects, enzymology, isolation & purification)
• Male
• Middle Aged
• Minocycline (adverse effects, analogs & derivatives, therapeutic use)
• Prospective Studies
• Pseudomonas Infections (drug therapy, microbiology)
• Pseudomonas aeruginosa (drug effects, enzymology, isolation & purification)
• Tigecycline
• Treatment Outcome
• beta-Lactamases (metabolism)