zithromax and Agranulocytosis

Topics: Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Azithromycin; Granulocyte Colony-Stimulating Factor; Humans; Male; Neutropenia; Pneumonia, Mycoplasma; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Azithromycin (AZM) is widely used for respiratory tract infections and otitis media because of its activity against Haemophilus influenzae and atypical pathogens, and its ease of administration. Although leukopenia is the one of the most frequent AZM-related laboratory abnormalities in children, agranulocytosis has not been reported in adults. Here, we present the case of an 81-year-old man with agranulocytosis following AZM-treatment for acute otitis media. He developed febrile neutropenia and granulocyte colony-stimulating factor and cefepim were administered. All his symptoms and absolute neutrophil counts were recovered within 7 days after admission. Physicians must be vigilant in identifying drug-induced neutropenia in AZM-treated patients because early detection can decrease the severity and prevent mortality.

Topics: Acute Disease; Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Azithromycin; Humans; Male; Otitis Media

Azithromycin has been shown to preferentially distribute to infection loci. Due to the potential contribution of phagocytes as transporters of drug to these sites, there has been some concern that immunosuppression of the cellular arm of the host defence system would greatly reduce the delivery of azithromycin to sites of infection and hence impair efficacy. Therefore, we evaluated the pharmacokinetics and pharmacodynamics of azithromycin in a Staphylococcus aureus intramuscular infection model in normal and immunosuppressed mice, employing therapeutic and prophylactic regimens. Immunosuppression was induced by daily doses of cyclophosphamide that culminated in leucopenia with an underlying granulocytopenic condition, with circulating peripheral granulocytes numbering from < or = 0.1-0.3 x 10(9)/L. Azithromycin tissue levels were not reduced in infection loci in granulocytopenic mice but moderate increases in Cmax and AUC values were observed, relative to similar tissues from normal mice. The tissue half-life of azithromycin in infected tissues in a therapeutic mode (75 h) was three-fold longer than in a prophylactic mode (25 h); this correlated with the degree of inflammation (therapy was withheld until inflammation was evident; i.e., prophylaxis reduced inflammation). Histological examination of infected tissues from normal and leucopenic mice was indistinguishable despite a 70%-85% reduction in circulating granulocytes. Compared with untreated infected controls, bactericidal activity was noted following prophylaxis with azithromycin and bacteraemia was suppressed in mice receiving azithromycin therapeutically. In summary, these data indicate that azithromycin delivery and efficacy in a moderately immunosuppressed animal model are unimpaired.

Topics: Agranulocytosis; Animals; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Bacteremia; Colony Count, Microbial; Cyclophosphamide; Half-Life; Immunosuppression Therapy; Immunosuppressive Agents; Leukocyte Count; Leukopenia; Male; Mice; Muscle, Skeletal; Staphylococcal Infections; Staphylococcus aureus