The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study

Muneerah M Aleissa; Isabel H Gonzalez-Bocco; Sara Zekery-Saad; David W Kubiak; Eric M Zhang; Jessie Signorelli; Sarah P Hammond; Amir M Mohareb; Marlise R Luskin; Jennifer Manne-Goehler; Francisco M Marty

doi:10.1093/ofid/ofac306

The Relationship Between Antibiotic Agent and Mortality in Patients With Febrile Neutropenia due to Staphylococcal Bloodstream Infection: A Multicenter Cohort Study

Open Forum Infect Dis. 2022 Jun 20;9(8):ofac306. doi: 10.1093/ofid/ofac306. eCollection 2022 Aug.

Affiliations

¹ Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
³ Department of Pharmacy, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Division of Infectious Diseases, Massachusetts General Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is a common cause of bloodstream infection (BSI) in patients with febrile neutropenia, but treatment practices vary, and guidelines are not clear on the optimal regimen.

Methods: We conducted a multicenter retrospective cohort study of MSSA BSI in febrile neutropenia. We divided patients into 3 treatment groups: (1) broad-spectrum beta-lactams (ie, piperacillin-tazobactam, cefepime, meropenem); (2) narrow-spectrum beta-lactams (ie, cefazolin, oxacillin, nafcillin); and (3) combination beta-lactams (ie, both narrow- and broad-spectrum). We used multivariable logistic regression to compare 60-day mortality and bacteremia recurrence while adjusting for potential confounders.

Results: We identified 889 patients with MSSA BSI, 128 of whom had neutropenia at the time of the index culture: median age 56 (interquartile range, 43-65) years and 76 (59%) male. Of those, 56 (44%) received broad-spectrum beta-lactams, 30 (23%) received narrow-spectrum beta-lactams, and 42 (33%) received combination therapy. After adjusting for covariates, including disease severity, combination therapy was associated with a significantly higher odds for 60-day all-cause mortality compared with broad spectrum beta-lactams (adjusted odds ratio [aOR], 3.39; 95% confidence interval [CI], 1.29-8.89; P = .013) and compared with narrow spectrum beta-lactams, although the latter was not statistically significant (aOR, 3.30; 95% CI, .80-13.61; P = .071).

Conclusions: Use of combination beta-lactam therapy in patients with MSSA BSI and febrile neutropenia is associated with a higher mortality compared with treatment with broad-spectrum beta-lactam after adjusting for potential confounders. Patients in this study who transitioned to narrow-spectrum beta-lactam antibiotics did not have worse clinical outcomes compared with those who continued broad-spectrum beta-lactam therapy.

Keywords: Staphylococcus aureus; beta-lactams; bloodstream infections; febrile neutropenia.