Case Presentation: A 52-year-old male with a history of type 2 diabetes mellitus, peripheral neuropathy, hypertension, hyperlipidemia, sleep apnea, and osteomyelitis of the right great toe presented to the hospital with a 3-day history of fever and chills. Of note, patient had been admitted 3 weeks prior with a complaint of a right foot ulcer, which was diagnosed as right foot osteomyelitis. Bone biopsy at the time showed Streptococcus agalactiae and Prevotella bivia on culture, which was treated with surgical debridement. The patient was prescribed piperacillin/tazobactam for 6 weeks.On exam, the patient was febrile with a fever of 38.9 ˚C, and his vitals included a heart rate of 100 bpm with a blood pressure of 128/74 mmHg. His skin was warm to touch without any rash, and his right foot ulcer appeared to be healing without any purulence or erythema. Laboratory results included a white blood cell (WBC) count of 1,400 per microliter with 28% bands, platelet count of 82,000 per microliter, and red blood cell (RBC) count of 4 million cells per microliter. The patient had an LDH of 3,342 U/L. Respiratory viral panel PCR including COVID-19 were negative, and blood and urine cultures had no growth. Chest x-ray, CT chest/ abdomen/ pelvis revealed no source of infection. X-ray and MRI of the right foot suggested severe osteomyelitis and cellulitis, however the foot appeared normal clinically. Antibiotics were changed to Ciprofloxacin and Daptomycin under the suspicion that the patient had developed drug-induced fever and pancytopenia from piperacillin/tazobactam infusion. Two days after starting on Ciprofloxacin and Daptomycin, the patient’s fever resolved, and his CBC counts improved. Patient was discharged on 6 weeks of the prescribed antibiotics and was followed as an outpatient.
Discussion: Piperacillin/tazobactam is an extended spectrum penicillin with broad-spectrum bacterial coverage used to treat multiple infections and remains the treatment of choice for moderate to severe diabetes-related foot infections. Some of the commonly noted side effects of piperacillin/tazobactam include diarrhea, constipation, headache, nausea, vomiting and skin rash. The rare side effects occurring in less than 1% of the patients, include fever and reversible pancytopenia, which are known to be dose and duration dependent. Pipercillin/ tazobactam is generally believed to affect the CBC through an immune-mediated process or bone marrow suppression. Most patients improve or recover within a week of discontinuation of pipercillin/tazobactam. Our patient’s elevated LDH likely suggested an immune reaction causing hemolysis as the likely cause of the patient’s pancytopenia and fever.
Conclusions: While piperacillin/tazobactam is generally well tolerated and serious adverse reactions are rare, hospitalists need to be aware of these reactions including fever and pancytopenia. With early recognition of a drug reaction, prompt discontinuation of pipercillin tazobactam can lead to improved patient outcomes and prevent unnecessary patient workup.