Evaluation of a Risk-guided Strategy for Empiric Carbapenem Use in Febrile Neutropenia.
Int J Antimicrob Agents. 2018 May 08;:
Authors: Khoo AL, Zhao YJ, Teng M, Ying D, Jin J, Chee YL, Poon LM, Lim SE, Koh LP, Chng WJ, Lim BP, Hsu LY, Ann Chai LY
Febrile neutropenia (FN) is associated with substantial morbidity and necessitate empiric broad spectrum antibiotic treatment. We evaluated a risk-guided FN management strategy using empiric piperacillin-tazobactam and carbapenem in a prospective cohort study. The analysis involved 723 FN episodes in hospitalised adult patients, including those with severe sepsis or prior infection/colonisation with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Propensity score matching analysis was used to adjust for baseline differences between treatment groups and produced 267 matched pairs. The primary outcome was all-cause mortality. The secondary outcomes were incidence of drug-resistant Gram-negative (including ESBL-producing bacteria), other and Gram-positive isolates, invasive pulmonary aspergillosis (IPA) and their associated mortality. There was no difference in mortality between empiric carbapenem and piperacillin-tazobactam (18/267 (6.7%) vs 14/267 (5.2%), p=0.466). We observed higher incidences of drug-resistant Gram-negative isolates (77/267 (28.8%) vs 26/267 (9.7%), p<0.001) including ESBL-producing bacteria (57/267 (21.4%) vs 16/267 (6.0%), p<0.001) in carbapenem-treated episodes where its use lowered mortality. The mortality rates for ESBL-positive infections were 5.3% (3/57) and 25% (4/16) (p=0.037); and drug-resistant Gram-negative infections, 6.5% (5/77) and 23.1% (6/26) (p=0.018) in piperacillin-tazobactam- and carbapenem- treated episodes respectively. More IPA were observed with carbapenem (16/267 (6.0%) vs 6/267 (2.3%), p=0.029). Antifungal prophylaxis reduced the risk of death (odds ratio 0.39, 95% confidence interval 0.17 to 0.87, p=0.017). Risk-guided carbapenem prescribing in FN rightly identified cases prone to drug-resistant Gram-negative infections and reduced the mortality in these episodes.
PMID: 29751120 [PubMed - as supplied by publisher]