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.