A multinational, preregistered cohort study of β-lactam/β-lactamase inhibitor combinations for treatment of bloodstream infections due to extended-spectrum-β-lactamase-producing enterobacteriaceae
Journal
Antimicrobial Agents and Chemotherapy
Journal Volume
60
Journal Issue
7
Pages
4159-4169
Date Issued
2016
Author(s)
Guti?rrez-Guti?rrez B.
P?rez-Galera S.
Salamanca E.
De Cueto M.
Calbo E.
Almirante B.
Viale P.
Oliver A.
Pintado V.
Gasch O.
Mart?nez-Mart?nez L.
Pitout J.
Akova M.
Pe?a C.
Molina J.
Hern?ndez A.
Venditti M.
Prim N.
Orig?en J.
Bou G.
Tacconelli E.
Tumbarello M.
Hamprecht A.
Giamarellou H.
Almela M.
P?rez F.
Schwaber M.J.
Bermejo J.
Lowman W.
Mora-Rillo M.
Natera C.
Souli M.
Bonomo R.A.
Carmeli Y.
Paterson D.L.
Pascual A.
Rodr?guez-Ba?o J.
G?lvez J.
Del Toro M.D.
Retamar P.
Falcone M.
Russo A.
Daikos G.
Karaiskos I.
Trecarichi E.M.
Losito A.R.
Garc?a-V?zquez E.
G?mez J.
Roilides E.
Iosifidis E.
Doi Y.
Tuon F.F.
Navarro F.
Mirelis B.
San Juan R.
Fern?ndez-Ruiz M.
Larrosa N.
Puig M.
Cisneros J.M.
Gonz?lez V.
Rucci V.
Ruiz De Gopegui E.
Marinescu C.I.
Fari?as M.C.
Cano M.E.
Gozalo M.
Pa?o-Pardo J.R.
Navarro-San Francisco C.
G?mez-Zorrilla S.
Tubau F.
Pournaras S.
Tsakris A.
Zarkotou O.
Azap ?.K.
Antoniadou A.
Poulakou G.
Virmani D.
Torre-Cisneros J.
P?rez-Nadales E.
Gracia-Ahulfinger I.
Helvaci ?.
Sahin A.O.
Cant?n R.
Ruiz P.
Bartoletti M.
Giannella M.
Riemenschneider F.
Badia C.
Xercavins M.
Fontanals D.
Jov? E.
REIPI/ESGBIS/INCREMENT Group
Abstract
The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.) Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
SDGs
Other Subjects
amoxicillin plus clavulanic acid; beta lactam antibiotic; beta lactamase inhibitor; carbapenem derivative; doripenem; ertapenem; imipenem; meropenem; piperacillin plus tazobactam; sultamicillin; antiinfective agent; beta lactam; beta lactamase; beta lactamase inhibitor; carbapenem derivative; adult; aged; Article; bloodstream infection; carbapenemase producing Enterobacteriaceae; cohort analysis; controlled study; drug efficacy; extended spectrum beta lactamase producing Enterobacteriaceae; female; human; in vitro study; major clinical study; male; monotherapy; mortality rate; multicenter study; observational method; outcome variable; priority journal; retrospective study; bacteremia; drug effects; Enterobacteriaceae; enzymology; Kaplan Meier method; metabolism; microbiology; middle aged; mortality; multivariate analysis; odds ratio; pathogenicity; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Enterobacteriaceae; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Retrospective Studies
Type
journal article