A Review of β-Lactam-Associated Neutropenia and Implications for Cross-reactivity

Objective: To review the incidence, management, and current understanding of the pathophysiology of beta-lactam-induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative beta-lactam in the setting of this reaction. Data Sources: A literature analysis using the PubMed and Ovid search engines (July 1968 to October 2020) was performed using the search terms neutropenia, leukopenia, beta-lactam, nonchemotherapy, agranulocytosis, and G-CSF (granulocyte colony-stimulating factor). Study Selection and Data Extraction: The included Englishlanguage studies evaluated the incidence, mechanism, and/or management of beta-lactam-induced neutropenia in pediatric or adult patients. Data Synthesis: Drug-induced neutropenia is a well-documented adverse reaction of beta-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy. However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction. Both direct toxic and immune-mediated mechanisms have been implicated. Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative beta-lactam. Relevance to Patient Care and Clinical Practice: Given the frequency of use and superiority of beta-lactams over alternative therapy for several infectious disease states, practical recommendations are needed on the management and safe use of beta-lactams following beta-lactam-induced neutropenia. Conclusion: Future use of ss-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following ss-lactam-induced neutropenia and may be considered when indicated, with close laboratory monitoring.