LAUSR

To the Editor: Piperacillin–tazobactam is a commonly prescribed broadspectrum antibiotic especially in inpatient settings for polymicrobial coverage. It is a penicillin and a beta-lactamase inhibitor combination. It has coverage against gramnegative bacteria including pseudomonas and anaerobes. It is relatively well-tolerated and the most common side effects include various gastrointestinal symptoms including diarrhea, constipation, nausea, vomiting, and abdominal pain. Rarer complications include injection site reactions, thrombophlebitis, fever, insomnia, and headaches. Very rarely it can cause bone marrow suppression. This can be in the form of pancytopenia, but bicytopenia and thrombocytopenia have also been reported. Here, we describe the case of a young man who developed bicytopenia after being started on a course of piperacillin–tazobactam for lower extremity cellulitis. His white cell count and platelet count recovered after discontinuation of piperacillin– tazobactam and he made a successful recovery. A 25-year-old male patient presented with fever along with pain and swelling in his left foot. On physical examination, the patient was febrile with a temperature of 102 °F and was tachycardiac with a pulse of 110 beats per minute. His left foot was red swollen, warm, and tender to touch. Laboratory studies showed a raised white cell count of 15 3 103/mL and a quantitative c-reactive protein of 150 mg/L. His platelet count was 250 3 103/mL. The patient was diagnosed with sepsis secondary to cellulitis of the left foot and admitted for further management. The patient was started on Tazobactam– piperacillin combination empirically for the treatment of sepsis and, at a dose of 4.5 gram via the intravenous route every 8 hours. The patient responded well to this medication and his sepsis resolved by the next day. However, repeat labs at 72 hours showed a fall in white cell count down to 2.7 3 10.3/mL and platelet count to 108 3 103/mL. The leukopenia was primarily neutropenia with an absolute neutrophil count of 890 cells/mm3. The patient was subsequently worked up for his bicytopenia. His Hepatitis B, C, and HIV serology were negative. His prothrombin time, partial thromboplastin time, chemistry panel including liver function test, renal function tests, and serum electrolytes were normal. Dengue and malarial parasite tests were also negative. Ultrasound abdomen was normal with no evidence of hepatosplenomegaly. His blood and urine samples were sent for culture and sensitivity. Meanwhile, the Patient’s medication list was reviewed. Tazobactam–piperacillin was the only drug in his medication list that could have possibly caused the bicytopenia. Hence, the Tazobactam–piperacillin was stopped. The patient’s temperature record was kept and his blood counts were repeated on alternate days. Blood and urine cultures came to be negative and follow-up labs showed complete blood count with normalized white blood cell and platelets counts. Because all other causes of neutropenia and thrombocytopenia were ruled out and his repeated complete blood count report after stopping Tazobactam–piperacillin showed an increase in the cells counts, Tazobactam–piperacillin was believed to be the culprit for the transient bicytopenia. Naranjo scale for a possible drug side effect was applied and the patient score came out to be 7, which suggested the bicytopenia as a probable drug adverse reaction of Tazobactam–piperacillin. Neutropenia and thrombocytopenia are rare adverse side effects of Tazobactam–Piperacillin. The exact mechanism of this adverse event is not fully understood but may be immune-mediated, or secondary to a direct toxic effect of this medication on the bone marrow.1 A review of the literature reported 4 prior cases reported, and these have been summarized in Table 1.1–4 An analysis of these shows that it has been reported at different age groups, with no predilection for a particular age group. Two of the prior patients were treated for pneumonia and 2 for skin infections like in our case. The time of onset of this side effect varies from days to weeks, although it was reported within hours in a patient on re-exposure.3 Two of the prior studies reported bicytopenia with neutropenia and thrombocytopenia.1,4 The other study reported a fall in only one cell line. All the patients reported a successful recovery in cell lines on the discontinuation of the medication. The average time to recover was 2–3 days. All the patients were managed with discontinuation of Tazobactam–piperacillin, whereas one patient was also treated with high-dose steroids.1 American Journal of Therapeutics 0, 1–2 (2020)