Introduction
Neutropenia is characterized as a decrease in the absolute neutrophil count, categorized as mild (1000–1500/μL), moderate (500–1000/μL), or severe (< 500/μL) [1]. The most severe form, called agranulocytosis, is a life-threating condition in which the patient becomes highly susceptible to infectious diseases and shows a mortality rate of 10–20% [2]. Agranulocytosis can be caused by a wide range of medications, including clozapine [3] and antibiotics [1], and infection control becomes particularly difficult in patients with antibiotic-induced agranulocytosis. Furthermore, in patients who continue to have a fever, it is necessary to switch to another antibiotic and add concomitant treatment with granulocyte-colony-stimulating factor [4]. Accordingly, there is an urgent need to identify antibiotics that have a low risk of inducing agranulocytosis.
Although the mechanisms of antibiotic-induced agranulocytosis remain unknown, Weitzman and Stossel [5] speculated that antibiotic-induced agranulocytosis may be caused by opsonizing antineutrophil antibodies, i.e., an IgG or IgM immune-mediated hypersensitivity reaction. However, because agranulocytosis is a rare adverse event (AE) [6], it is difficult to collect a sufficient number of samples to conduct clinical studies. Recently, spontaneous reporting systems (SRSs) have been shown to be useful for detection of rare AEs and have been used as primary tools in postmarketing surveillance. In Japan, individual AEs are collected by healthcare workers at the Pharmaceuticals and Medical Devices Agency (PMDA). The Japanese Adverse Drug Event Report (JADER) database, which is available online, was established in April 2004 by the PMDA and reflects the realities of clinical practice [7]. Thus, data mining using the JADER database can be used as a screening tool for antibiotic-induced agranulocytosis.
In this study, we evaluated the expression profiles of antibiotic-induced agranulocytosis using the JADER database.