Empiric piperacillin-tazobactam versus carbapenem in febrile neutropenia : increased incidence of invasive pulmonary aspergillosis

Louis Yi Ann Chai*1

Author address: 

1 National University Health System, Singapore


Background: Febrile neutropenia (FN) is a common complication in cancer patients receiving
myelosuppressive chemotherapy and pose a mortality risk. Empiric broad spectrum antimicrobial
therapy can be life-saving. Piperacillin-tazobactam and carbapenems are commonly employed in
these instances. The objective was to compare the clinical outcomes of piperacillin-tazobactam and
carbapenems as empiric therapy in oncology and haematology patients with febrile neutropenia.
Material/methods: In a retrospective analysis, we compared the effects of empiric piperacillintazobactam
versus carbapenems in the management of febrile neutropenia. We constructed a logistic
regression model to estimate a propensity score for each patient’s probability of receiving a treatment
given pre-treatment characteristics. The propensity score model was estimated using the following
variables: age, gender, ethnicity, underlying condition, stem cell transplant recipient, multinational
association for supportive care in cancer (MASCC) score and antimicrobial prophylaxis. The outcomes
of interest were death, incidence of drug-resistant gram-negative organism, gram-positive organism
and invasive pulmonary aspergillosis, length of treatment and hospitalisation.
Results: There were 353 and 370 patients receiving piperacillin-tazobactam and carbapenem
respectively before matching, and 234 patients in each group after matching. The all-cause mortality
was 6% (43/723) There was no significant difference in the incidence of death for both the matched
(4.3% vs 6.8%, p = 0.226) and unmatched (5.1% vs 6.8%, p = 0.346) cohorts.
There was a higher incidence of invasive pulmonary aspergillosis in both the matched (2.6% vs 6.8%,
p = 0.029) and unmatched (2.0% vs 8.4%, p = 0.000) cohorts. In the unmatched cohort, there were
higher incidences of culture results positive for extended-spectrum beta-lactamase (ESBL)- producing
(5.8% vs 23.2%, p = 0.000) and drug-resistant gram-negative organisms in the carbapenem group
(9.9% vs 30.8%, p = 0.000). However, those receiving piperacillin-tazobactam were more likely to
succumb when confronted with such organisms (20.7% vs 7.0%, p = 0.084). There were few grampositive
organisms (overall <1%) and no difference was found in both group. These differences were
not significant in the matched cohort. There were no significant differences in the length of
hospitalisation (median: 20 vs 24 days, p = 0.926) and antibiotic treatment (median: 10 vs 10 days, p =
Conclusions: In a cohort of oncology and haematology patients, a higher incidence of invasive
pulmonary aspergillosis was observed in patients receiving empiric carbapenem therapy for febrile
neutropenia. This was observed despite using propensity score matching to adjust for confounders
presented by the two treatment group in terms of age, risk of FN complications and stem cell
transplant recipient.


abstract No: 


Full conference title: 

27th European Congress of Clinical Microbiology and Infectious Diseases (2017, Vienna)
    • ECCMID 27th (2017)