From treating UTI to agranulocytosis

The growing problem of antibacterial resistance has resulted in increased interest in fosfomycin, especially its parenteral formulation. It is a broad-spectrum antibiotic with both in vivo and in vitro activity against a wide range of bacteria, including MDR and XDR bacteria. Due to its high tissue penetration, fosfomycin may be used in a broad range of tissues and targets, including the CNS, soft tissue, bone, lungs, and abscess fluid. The most commonly reported adverse effects are hypokalemia and hypernatremia. We describe a case of agranulocytosis in a young patient with chronic kidney disease, a rarely described side effect that may be fatal. A 21-year-old woman was a freshly diagnosed case of end-stage renal disease during workup for complaints of generalized body weakness, reduced appetite, and hypertension. She was started on hemodialysis. During the course of her hospital stay, she developed features of urinary tract infection, urine routine and microscopy revealed leucocyte esterase 3+ and nitrites 3+ and microscopy showed numerous pus cells. The blood culture was sterile. The urine culture was positive for Klebsiella pneumoniae ssp pneumoniae (MDRO) and was sensitive to only fosfomycin. Oral fosfomycin was started; however, she developed multiple episodes of nausea and vomiting after taking the first oral dose. Therefore, she was started on 4 g of injectable fosfomycin, followed by 2 g of fosfomycin twice a day. She was found to have leukopenia, with her total leucocyte counts decreasing from 13500/cumm to 4100/cumm and then further to 2100 cells/cumm in two consecutive days of administration of injectable fosfomycin. On the third day, the counts further decreased to 1700/cumm, with an absolute neutrophil count of 493 cells/μ. In view of suspected fosfomycin-induced leukopenia, the injectable drug was stopped. The total leucocyte counts were repeated after two days of stopping fosfomycin. The repeated leucocyte counts were normal. To our knowledge, this is the first paper reporting on agranulocytosis induced by fosfomycin in chronic kidney disease patients and the fourth paper to date. This paper provides the second detailed description of a case. Cytotoxic chemotherapy can cause predictable and dose-related decreases in neutrophil counts. Neutropenia secondary to other medications tends to be an idiosyncratic reaction either as an immune-mediated reaction or because of direct myeloid cell line damage. This effect has been associated with a variety of medications. Literature data are scarce. A summary of product characteristics revealed that only a few cases of transient neutropenia and agranulocytosis have been reported. Parenteral fosfomycin is often used in patients receiving other medications, so it is rarely the only suspect. In our patient, there was a sudden decrease in the neutrophil count after two days of treatment with injectable fosfomycin, indicating that it is the causative agent. The counts normalized after stopping the drug.