Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Andrea J Zimmer; Erica Stohs; Jane Meza; Christopher Arnold; John W Baddley; Pranatharthi Chandrasekar; Zeinab El Boghdadly; Carlos A Gomez; Eileen K Maziarz; Jose G Montoya; Steven Pergam; Kenneth V Rolston; Michael J Satlin; Gowri Satyanarayana; Shmuel Shoham; Lynne Strasfeld; Randy Taplitz; Thomas J Walsh; Jo-Anne H Young; Yuning Zhang; Alison G Freifeld

doi:10.1093/ofid/ofac240

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Open Forum Infect Dis. 2022 May 18;9(7):ofac240. doi: 10.1093/ofid/ofac240. eCollection 2022 Jul.

Authors

Andrea J Zimmer¹, Erica Stohs¹, Jane Meza², Christopher Arnold³, John W Baddley⁴, Pranatharthi Chandrasekar⁵, Zeinab El Boghdadly⁶, Carlos A Gomez⁷, Eileen K Maziarz⁸, Jose G Montoya⁹, Steven Pergam¹⁰, Kenneth V Rolston¹¹, Michael J Satlin¹², Gowri Satyanarayana¹³, Shmuel Shoham¹⁴, Lynne Strasfeld¹⁵, Randy Taplitz¹⁶, Thomas J Walsh¹², Jo-Anne H Young¹⁷, Yuning Zhang¹, Alison G Freifeld¹

Affiliations

¹ University of Nebraska College of Medicine, Omaha, Nebraska, USA.
² University of Nebraska College of Public Health, Omaha, Nebraska, USA.
³ University of Virginia, Charlottesville, Virginia, USA.
⁴ University of Maryland, Baltimore, Maryland, USA.
⁵ Wayne State University, Detroit, Michigan, USA.
⁶ Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
⁷ University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁸ Duke University Medical Center, Durham, North Carolina, USA.
⁹ The Dr. Jack S. Remington Laboratory for Specialty Diagnostics at the Palo Alto Medical Foundation, Palo Alto, California, USA.
¹⁰ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
¹¹ University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹² Weill Cornell Medicine of Cornell University, New York, New York, USA.
¹³ Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁴ Johns Hopkins University, Baltimore, Maryland, USA.
¹⁵ Oregon Health & Science University, Portland, Oregon, USA.
¹⁶ COH National Medical Center, Duarte, California, USA.
¹⁷ University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.

Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.

Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall.

Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Keywords: bacteremia following chemotherapy; bacteremia in cancer patients; bloodstream infections; empirical antibiotics; febrile neutropenia.