Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2013 Elsevier B.V. and the International Society of Chemotherapy.
Συγγραφείς:
Pontikis, K.
Karaiskos, I.
Bastani, S.
Dimopoulos, G.
Kalogirou, M.
Katsiari, M.
Oikonomou, A.
Poulakou, G.
Roilides, E.
Giamarellou, H.
Περιοδικό:
International Journal of Antimicrobial Agents
Λέξεις-κλειδιά:
carbapenemase; colistin; fosfomycin; tigecycline, adult; antibiotic resistance; article; bacteremia; bacterial clearance; bacterial strain; bacterium isolate; case study; cause of death; clinical article; critically ill patient; diarrhea; drug safety; drug withdrawal; female; human; hypokalemia; intensive care unit; Klebsiella infection; Klebsiella pneumoniae; male; middle aged; multicenter study; nephrotoxicity; neutropenia; nonhuman; observational study; outcome assessment; priority journal; prospective study; Pseudomonas aeruginosa; Pseudomonas infection; rash; thrombocytopenia; treatment outcome; ventilator associated pneumonia, Critically ill; Fosfomycin; Klebsiella; PDR; Pseudomonas; XDR, Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Minocycline; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections; Treatment Outcome
DOI:
10.1016/j.ijantimicag.2013.09.010
