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

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 (BSI) in U.S. cancer patients, it is unclear if current guidelines remain relevant. Methods In a cross-sectional study, fourteen U.S. cancer centers prospectively identified BSIs in high-risk FN patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results Among 389 organsims 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. Conclusion In accordance with U.S. 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.

Antimicrobials in patients with hematologic malignancies and recipients of hematopoietic cell transplantation and other cellular therapies

“…as most infections remain susceptible to the anti-pseudomonal beta-lactams. 28,29 Access to rapid diagnostic platforms that identify pathogen and resistance markers allow clinicians to respond earlier and transition to these agents when necessary. Local antibiograms play a critical role in determining the role of these therapeutics in the management of this vulnerable population.…”

“…Newer broad spectrum agents (e.g., ceftazidime‐avibactam, cefiderocol), designed to target carbapenem resistant Enterobacterales, have largely replaced more toxic agents like the polymyxins. While it may be enticing to consider these agents as first line in the immunocompromised patient, they have not been shown to be better empirically, as most infections remain susceptible to the anti‐pseudomonal beta‐lactams 28,29 . Access to rapid diagnostic platforms that identify pathogen and resistance markers allow clinicians to respond earlier and transition to these agents when necessary.…”

Global impact of antibacterial resistance in patients with hematologic malignancies and hematopoietic cell transplant recipients

“…Enterobacterales comprise the majority of Gram-negative BSIs during chemotherapy-induced neutropenia. [11][12][13] Unfortunately, FQ resistance has become increasingly common in Enterobacterales in the United States. 14 In a recent multicenter study, 22% of urinary Escherichia coli isolates from ambulatory patients were FQ-R and 28% of isolates from hospitalized patients were FQ-R. 15 A high prevalence of FQ-R E has also been observed among patients with hematologic malignancies and HCT recipients.…”

“…14 In a recent multicenter study, 22% of urinary Escherichia coli isolates from ambulatory patients were FQ-R and 28% of isolates from hospitalized patients were FQ-R. 15 A high prevalence of FQ-R E has also been observed among patients with hematologic malignancies and HCT recipients. A multicenter US study of BSIs during fever and neutropenia found that 53% of Enterobacterales bloodstream isolates were FQ-R. 13 FQ-R E are also common in other countries. A multicenter Italian study of 342 BSIs due to E. coli in patients with hematologic malignancies found that 70% of isolates were resistant to FQs.…”

“…24,25 In a US multicenter study of BSIs that occurred during fever and neutropenia, 72% of VGS bloodstream isolates were resistant to levofloxacin. 13 Moreover, the prevalence of oropharyngeal colonization with FQ-R VGS may increase after the initiation of FQ prophylaxis. 26…”