Suspected drug reaction with piperacillin/tazobactam, in a premature infant

Abstract

Drug-induced reactions are not well described in paediatric literature, less so in the newborn [1]. Piperacillin/tazobactam is a combination of an extended-spectrum penicillin, piperacillin and the α-lactamase inhibitor tazobactam commonly marketed by Wyeth (Maidenhead, UK) under the trade name Tazocin® or Zosyn®[2]. This broad spectrum antibiotic is used by neonatalogists to treat sepsis as a second- or third-line antibiotic. There are no reported data of skin reactions as a result of piperacillin/tazobactam in neonatal literature [3, 4]. In adults, the most commonly reported adverse events in clinical trials of piperacillin/tazobactam plus an aminoglycoside have included diarrhoea (17.6%), fever (2.7%), vomiting (2.7%), urinary tract infection (2.7%) and rash (2.3%). Piperacillin/tazobactam, like other penicillins, can also cause reversible agranulocytosis [2, 5]. A 27 + 4-week male infant weighing 0.936 kg was born vaginally to a 16-year-old primigravida following onset of premature labour. There was no evidence of chorioamnionitis. The baby was transferred ex utero to our Neonatal Intensive Care Unit soon after delivery. One dose of steroid had been given 6 h before the delivery and one dose of curosurf at birth. His Apgar score at 5 min was 8. He was extubated on the second day onto continuous positive airway pressure. He developed a septic illness when he was 26 days old and required re-ventilation. He was started on piperacillin/tazobactam (90 mg kg−1 12 hourly) and gentamycin 4 mg kg−1 once a day, as previous skin swabs had grown lactose fermenting coliforms. After his first two doses of piperacillin/tazobactam the baby developed a peeling exanthema mainly involving his hands and soles of his feet, which later spread to involve the rest of his body to a lesser degree. The piperacillin/tazobactam was stopped in favour of meropenem after 48 h because of the possibility that this was a drug reaction. No staphylococcus was isolated from any skin or blood cultures. During this episode, his blood pressure was stable and no inotropes were needed. At the same time, he developed a coagulopathy associated with neutropenia and thrombocytopenia managed with transfusions of platelets, blood and plasma. After stopping the piperacillin/tazobactam, the skin condition improved over the following week; he developed generalized exfoliation revealing normal underlying skin. Drug reactions are rarely described in the neonatal literature. In adult literature, piperacillin/tazobactam has been described to cause a dermatological reaction. We report a case of a 27-week infant who was treated with piperacillin/tazobactam for a septic episode, following which he developed a severe exanthema and agranulocytosis. Although staphylococcal scalded skin was a differential diagnosis in our patient, we failed to isolate any staphylococcus from blood or surface (including nose) swabs. It is important to consider drug reactions in neonatology where the use of antibiotics is rife. As there are scant safety and efficacy data for use of many drugs used in neonatology, there is a need to be suspicious of skin reactions in neonates, as these may be due to drugs. We would encourage neonatologists to consider adverse drug reactions and report them in order to gain more information on this topic.