Acute neutropenia induced by antibiotics: systematic review of case reports

The potentially life-threatening side effect of acute neutropenia is rarely associated with antibiotic use. Information about rare side effects of drugs is usually abstracted from case reports as experimental studies are ethically questionable. Thus, systemic reviews of published case reports could be an option to summarize available evidence about manifestation and treatment options of this condition. Aim of our review was to detect the most common antibiotics associated with AN, as well as severity of this side effect, chosen treatment strategy and outcome. We extracted data about patient demographics, suspected antibiotic, duration of treatment before onset of AN, stage of AN (mild, moderate, or severe), used treatment and duration of recovery, through a search of databases (MEDLINE 1968-2020) and identification of published case reports.  Overall 83 cases were included. The majority of cases were concerning antibiotics from beta-lactam or glycopeptide groups with Ceftaroline and Vancomycine being the two most commonly described drugs. Neutropenia developed after a median 21 days of treatment and in most cases, it was classified as severe with absolute neutrophil count below 500 cells/mm3 (85.5%). In 51.8% of cases the suspected antibiotic was discontinued, in 37.4% of cases it was substituted for another agent. Neutropenia was resolved after a median six days. Only three case reports mentioned death because of neutropenia. The use of granulocyte colony-stimulating growth factors shortened the duration of neutropenia and improved outcome for patients' health. Neutropenia induced by antibiotics remains rarely reported side-effect. Long-term and high-dose treatment regimens by beta-lactam or glycopeptide antibiotics expose a higher risk for development of AN, thus regular full blood counts are advised during therapy.