title: 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.affiliation: First Department of Respiratory Medicine - Intensive Care Unit, University of Athens, Sotiria Chest Diseases and General Hospital, 152 Mesogeion Avenue, 115 27 Athens, Greece. Electronic address: kostis_pontikis@yahoo.gr.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Pontikis
authors.affiliation: Sixth Department of Internal Medicine, Hygeia Hospital, 4 Erythrou Stavrou Street, 151 23 Marousi, Athens, Greece.
authors.forename: Ilias
authors.initials: I
authors.lastname: Karaiskos
authors.affiliation: Intensive Care Unit, Hospital of Arta, Lofos Peranthis, 471 00 Arta, Greece.
authors.forename: Styliani
authors.initials: S
authors.lastname: Bastani
authors.affiliation: Second Department of Intensive Care Medicine, University of Athens, Attikon Hospital, 1 Rimini Street, 124 62 Chaidari, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.affiliation: Intensive Care Unit, University Hospital of Ioannina, Stavros Niarchou Avenue, 455 00 Ioannina, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Kalogirou
authors.affiliation: Intensive Care Unit, Konstantopoulio Hospital, 3-5 Agias Olgas Street, 142 33 Nea Ionia, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Katsiari
authors.affiliation: Fourth Department of Internal Medicine, University of Athens, Attikon Hospital, 1 Rimini Street, 124 62 Chaidari, Athens, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Oikonomou
authors.affiliation: Fourth Department of Internal Medicine, University of Athens, Attikon Hospital, 1 Rimini Street, 124 62 Chaidari, Athens, Greece.
authors.forename: Garyphallia
authors.initials: G
authors.lastname: Poulakou
authors.affiliation: Infectious Diseases Department, Hippokration Hospital, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.affiliation: Sixth Department of Internal Medicine, Hygeia Hospital, 4 Erythrou Stavrou Street, 151 23 Marousi, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000378:metabolism*; D003091:Colistin / Q000009:adverse effects / Q000627:therapeutic use; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005578:Fosfomycin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification; D000078304:Tigecycline; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005578:Fosfomycin; D000078304:Tigecycline; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline; D003091:Colistin
keywords: Critically ill; Fosfomycin; Klebsiella; PDR; Pseudomonas; XDR