Grand Round 178 http://infection.thelancet.com Vol 6 March 2006 Introduction Co-trimoxazole (trimethoprim-sulfamethoxazole) is one of the most commonly prescribed antimicrobial agents in clinical practice. It is a first-line agent for the treatment of urinary tract infections, uncomplicated sinusitis, and acute exacerbations of chronic bronchitis. 1–5 It is also first-line therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS. 6 Although co-trimoxazole is well tolerated in most patients, many adverse events related to its use have been described, ranging from mild gastrointestinal intolerance to life-threatening complications including neutropenia, Stevens–Johnson syndrome, and aseptic meningitis. 1,7–11 Although not commonly reported, hypoglycaemia has also been described as a complication of treatment with co-trimoxazole. Co-trimoxazole-induced hypoglycaemia may be severe, resulting in a decreased level of consciousness and seizure activity. 12–14 We report a case of severe and protracted hypoglycaemia complicated by seizure that was associated with the use of co-trimoxazole for the treatment of P carinii pneumonia in a patient with AIDS. We also review the indications for use, dosage regimens, clinical features, predisposing factors, and management of 13 previously reported cases of co- trimoxazole-induced hypoglycaemia. Case presentation In July 2004, a 46-year-old man was admitted to hospital with a new diagnosis of AIDS complicated by a bloodstream and meningeal infection caused by Cryptococcus neoformans. His CD4 cell count at the time of AIDS diagnosis was 59 cells per L. Computed tomography (CT) scan of the thorax also revealed ground-glass opacities in the upper lobes and perihilar regions bilaterally, raising the suspicion of opportunisitic infection. A subsequent broncheoalveolar lavage was positive by immunofluoresence for P carinii, providing a concurrent diagnosis of P carinii pneumonia. Treatment of his cryptococcal disease was initiated with intravenous amphotericin B (0·7 mg/kg per day) followed by fluconazole (400 mg orally every day). For P carinii pneumonia, therapy was instituted with co-trimoxazole at a dose of 1280 mg trimethoprim/ 6400 mg sulfamethoxazole orally daily. The patient was stabilised and discharged home. 11 days after discharge, the patient was brought to the emergency department for evaluation of an alteration in his level of consciousness accompanied by falls. At this time, the patient had received 18 days of co-trimoxazole. There was no prior history of hypoglycaemia or diabetes mellitus and he denied the use of medications other than those prescribed for the treatment of his opportunistic infections. The patient had no history of alcohol abuse, intravenous drug use, or liver disease. On examination, a fluctuating level of consciousness was observed. There were no focal neurological deficits. The initial plasma glucose measurement was 43·2 mg/dL. Despite administration of two intravenous boluses of 50 mL of a 50% glucose solution, hypoglycaemia persisted and within 30 minutes of arrival, he experienced a generalised tonic clonic seizure. A plasma glucose measurement at that time was 28.8 mg/dL. His serum creatinine was 1·97 mg/dL, with a calculated creatinine clearance of 46 mL/min. All of his medications were discontinued. Ongoing hypoglycaemia necessitated admission to the intensive care unit for the administration of a continuous infusion of a 50% glucose solution. After 30 hours of admission, the glucose infusion was decreased to a 10% solution and was eventually discontinued. Despite aggressive glucose support, the plasma glucose concentration did not exceed 90 mg/dL during the first 24 hours of admission. Further investigations revealed an inappropriately normal serum insulin level of 0·83 g/L (normal, 0.3–1.5 g/L) at a time when his plasma glucose concentration was 70·2 mg/dL and he was receiving intravenous glucose to maintain this plasma concentration. A baseline cortisol Lancet Infect Dis 2006; 6: 178–82 ELS is at the University of Toronto, Toronto, Canada; AK is at the Wilson Centre for Research in Education and the Division of General Internal Medicine, Sunnybrook and Women’s Health Sciences Centre, Universirt of Toronto; and WLG is at the Divisions of Infectious Diseases and General Internal Medicine, University Health Network, University of Toronto. Correspondence to: Dr Wayne L Gold, Toronto General Hospital, 200 Elizabeth Street, 13EN-213, Toronto, Ontario, Canada, M5G 2C4. Tel +1 416 340 4410; fax +1 416 340 3357; wayne.gold@uhn.on.ca Elizabeth L Strevel, Ayelet Kuper, Wayne L Gold Co-trimoxazole (trimethoprim-sulfamethoxazole) is a commonly prescribed antimicrobial agent. Although it is well tolerated in most patients, serious adverse events related to its use have been described. Hypoglycaemia is a rare but potentially life-threatening complication of therapy. We describe a case of refractory hypoglycaemia complicated by seizure associated with co-trimoxazole for the treatment of Pneumocystis carinii pneumonia in a patient with AIDS. We also review 13 previously reported cases of co-trimoxazole-induced hypoglycaemia. Among this patient population, renal insufficiency was the most prevalent predisposing risk factor (93%). The mean daily dose of co-trimoxazole was 4·5 double strength (160 mg trimethoprim/800 mg sulfamethoxazole) tablets per day. Serum insulin levels were raised or inappropriately normal in 88% of cases in which they were measured, suggesting a sulfonylurea-like effect of co-trimoxazole as the mechanism of hypoglycaemia. All cases required intravenous glucose administration, and 43% experienced protracted (12 hours) hypoglycaemia. Dosage adjustments should be made when prescribing co-trimoxazole to patients with renal dysfunction. Severe and protracted hypoglycaemia associated with co-trimoxazole use