LAUSR

A one-year-old girl with a medical history of haemorrhagic enteritis was treated with fosfomycin, administered orally. After 5 days of treatment, the infant developed severe acute kidney injury, and was referred to our hospital for renal replacement therapy. On admission, she presented with a mild maculopapular rash on her body, and slight oedema of her face. The laboratory examination results were as follows: white blood cells 20.0 × 10/L with 0% eosinophils, urea nitrogen 52.8 mmol/L, creatinine 703.7 μmol/L, and bicarbonate 10.4 mmol/L. On the day of admission, she commenced renal replacement therapy in the form of peritoneal dialysis. The patient achieved clinical recovery, and renal function improved with eventual discontinuation of dialysis on hospital day 8. An open renal biopsy was performed on hospital day 36 to access for acute kidney injury. Histopathological examination revealed diffuse tubulitis associated with patchy inflammatory cell infiltrates including eosinophils (Fig. 1). In addition, the drug lymphocyte stimulation test for fosfomycin revealed a stimulation index of 477% (normal: under 180%). On the basis of these findings, it was suggested that fosfomycin was the offending drug for the acute interstitial nephritis (AIN). Fosfomycin has been generally recognized as a welltolerated drug, and hypersensitivity reactions are extremely rare in the clinical setting of fosfomycin use. In addition, fosfomycin has been reported to have unique immunomodulatory activities associated with high-tolerance, such as suppression of IgE-mediated histamine release from peripheral blood basophils. Recently, some cases of anaphylaxis evoked by fosfomycin have been reported. Each case demonstrated evidence of hypersensitivity on various examinations, including the challenge test, skin test and basophil activation test, although, to our knowledge, severe renal toxicity, including AIN has never been reported previously. Herein, we have presented the first biopsy-proven case of AIN caused by fosfomycin administration. Clinicians should be aware of the possibility that fosfomycin, which is generally considered to be a well-tolerated antibiotic, can cause severe AIN via an allergic mechanism.