Drug Fever

A 2-year-old girl presented with high-grade fever for 4 days and abdominal pain with vomiting for 2 days. There was no history of respiratory or genitourinary symptoms. She had no known drug allergies. There was a history of urinary tract infection (UTI) twice in the past which was treated with intravenous ceftriaxone followed by oral cefixime. Her micturating cystourethrogram and dimercaptosuccinic acid scans were normal. On physical examination, she was uncomfortable and ill-looking. Her body temperature was 101.2 °F, pulse rate was 90 bpm, and blood pressure was 92/70 mmHg. On examination of the abdomen, there was right lumbar tenderness. All other systems were normal on examination. The initial laboratory reports revealed a hemoglobin level of 11.4 g/dL, total leucocyte cell count (TLC) of 18,900/cmm with 74% neutrophils, platelet count of 2.3 lacs/cmm, erythrocyte sedimentation rate of 34 mm/h, and C-reactive protein level of 65 mg/L. The child’s electrolytes were within the normal range, and renal and liver function tests were normal. Urine routine examination revealed 18 pus cells per high power field. A diagnosis of upper urinary tract infection was made. A catheter urine sample was sent for culture. An abdominal ultrasound revealed enlarged kidneys with a hypoechoic parenchyma and loss of the normal corticomedullary differentiation. The child was started on IV piperacillin–tazobactam. Over the next 72 h, the abdominal pain and vomiting subsided, the fever became low grade, and the child became playful. Her urine grew extended-spectrum beta-lactamase producing Klebsiella pneumoniae. IV piperacillin–tazobactam was continued with a plan to switch over to oral antibiotics once the child was asymptomatic. On day 6 of antibiotics, high-grade fever spikes restarted with a maximum temperature of 102.2 °F. On re-examination, there was no thrombophlebitis or any other focus of infection. The child was re-investigated. The complete blood count showed a total leukocyte count of 8460 cells/cmm with 54% neutrophils and a normal eosinophil count. Repeat ultrasonography of the kidneys, ureters, and bladder didn’t show any complications. Urinalysis and serum procalcitonin levels were normal. Repeat blood and urine cultures were sterile. Intermittent fever persisted, but she continued to remain playful and active and improve clinically. There was no rash or eosinophilia. It was observed that her pulse rate was between 82 and 94 bpm even during fever spikes. The possibility of drug fever (DF) was considered, and piperacillin/tazobactam was discontinued. The temperature normalized within 48 h with no further fever spikes. The antibiotic course was completed with oral trimethoprim–sulfamethoxazole (TMP-SMZ). The child was referred to the nephrologist for evaluation of recurrent UTI.