Major topics explored in the top-ranked ID articles of 2013 include the use of cefepime for gram-negative infections due to AmpC or extended-spectrum β-lactamase-producing Enterobacteriaceae, optimizing antibiotic therapy through the use of extended- or continuous-infusion regimens, the use of the oral integrase inhibitor dolutegravir to combat HIV disease, and new approaches to treatment of Clostridium difficile infection and enterococcal endocarditis.
With the vast number of articles published each year, it is difficult to remain up-to-date on current, significant ID pharmacotherapy publications. This review of significant publications in 2014 may be helpful by lessening this burden.
Background
Bezlotoxumab is a fully human monoclonal antibody that binds and neutralizes Clostridioides difficile toxin B. Administration of bezlotoxumab along with standard of care antibiotic (SoC) treatment of C. difficile infections (CDI) is associated with lower rates of CDI recurrence (rCDI). We aimed to determine the real-world incidence of rCDI in patients with cancer within 12 weeks after receiving bezlotoxumab.
Methods
This is a retrospective, single-center, descriptive study of patients with cancer that received bezlotoxumab from Jan 2018 through Oct 2021 at a large cancer center. rCDI was defined as a clinical illness associated with a positive stool nucleic acid amplification test with or without a confirmatory toxin assay for which CDI SoC was prescribed.
Results
A total of 131 patients were included in the study (median age of 63 years, 47% male, 77% Caucasian, 21% ICU admission), with 31% having one or more CDI episodes ≤ 6 months prior to receiving bezlotoxumab. The most common primary cancer type was leukemia (36%) followed by a solid organ tumor (35%), lymphoma (21%), and myeloma (8%). Cytotoxic chemotherapy or immune checkpoint inhibitors were prescribed within 6 months in 78% of cases and 60% of patients were given antibiotics not related to CDI. Fidaxomicin was most frequently administered as SoC (56%), followed by oral vancomycin (44%) with or without intravenous metronidazole. Within 12 weeks following bezlotoxumab treatment, rCDI occurred in 14 (10.7%, 95% Cl 5.4% to 16.0%) patients. Using univariate analysis, patients with rCDI were more likely to have received levofloxacin before and during bezlotoxumab treatment (86% versus 47%; OR 6.76, 95% CI 1.45 - 31.56, p=0.009).
Conclusion
In this real-world study, the rate of rCDI following use of bezlotoxumab during SoC antibiotics was comparable to that seen in clinical trials. Use of levofloxacin as prophylaxis for prolonged neutropenia in hematologic malignancies was associated with significantly higher rates of rCDI in patients that received bezlotoxumab. Our study suggests that neutropenia and antibiotic induced dysbiosis are risk factors for rCDI despite bezlotoxumab administration.
Disclosures
Pablo C. Okhuysen, MD, AstraZeneca: Stocks/Bonds|Beam Therapeutics: Stocks/Bonds|Biontech: Stocks/Bonds|Deinove: Grant/Research Support|Ferring: Advisor/Consultant|Glaxo Smith Kleine: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Melinta: Grant/Research Support|Merck Sharp & Dohme Corp: Grant/Research Support|Moderna: Stocks/Bonds|Napo Pharmaceuticals: Advisor/Consultant|Napo Pharmaceuticals: Grant/Research Support|Novavax: Stocks/Bonds|Pfizer: Stocks/Bonds|Summit: Advisor/Consultant|Summit: Grant/Research Support.
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