Neutrophils play a critical role in the innate immune system by protecting the body against bacterial, fungal, and other infectious agents. The absolute neutrophil count (ANC), typically ranging from 2,500 to 6,000 cells/µL in healthy individuals, is a key laboratory parameter used to assess immune competence. Neutropenia, defined as an ANC below 1,500 cells/µL, is categorized into mild, moderate, and severe forms based on the degree of reduction. Although neutropenia can result from various etiologies such as infections, immune-mediated disorders, and bone marrow suppression, drug-induced neutropenia remains an important clinical concern. Idiosyncratic drug-induced neutropenia (IDIN), a rare but potentially life-threatening adverse reaction, has an estimated incidence of 2–15 cases per million annually in the United States. Despite its rarity, IDIN accounts for a significant proportion of severe neutropenia cases and is associated with increased morbidity and mortality, particularly among elderly patients and those with comorbid conditions such as renal disease, sepsis, or shock. Among implicated medications, anti-infective agents—especially beta-lactam antibiotics—are frequently reported contributors. These include penicillin derivatives, cephalosporins, carbapenems, and monobactams, collectively accounting for nearly half of antibiotic-associated IDIN cases. Cephalosporins, in particular, have been increasingly linked to hematologic adverse effects, including neutropenia, over several decades of clinical observation. Evidence suggests that third-generation cephalosporins contribute substantially to severe neutropenia among beta-lactam antibiotics. Although the precise mechanisms underlying IDIN remain poorly understood, proposed pathways include immune-mediated destruction of neutrophils and direct bone marrow toxicity. Given the widespread use of cephalosporins in clinical practice, understanding their potential to induce neutropenia is essential for improving patient safety. Early recognition, routine monitoring of ANC in high-risk patients, and prompt discontinuation of the offending agent are crucial strategies in mitigating adverse outcomes. This review highlights the epidemiology, risk factors, and clinical implications of cephalosporin-associated neutropenia, emphasizing the need for heightened clinical vigilance and further research into its underlying mechanisms.
Anderson Michael James Carter (Mon,) studied this question.