Neutropenia Associated with Cloxacillin and Other Semisynthetic Penicillins in Children

Abstract

Five children treated with high dose of semisynthetic penicillin for three to four weeks developed neutropenia (< 1.5 × 10 9 /L). All patients were on cloxaxillin. In addition, three patients received ampicillin, and one received piperacillin therapy for the same duration. All patients developed neutropenia 15 to 23 days following therapy and resolved 8 to 95 days after discontinuation of the penicillin. One patient developed serious perianal necrotizing fascitis as a complication of neutropenia. The red blood cell count and platelets were normal in all patients. Bone marrow aspiration performed on two patients revealed a maturation arrest of the granulocyte precursor. A complete cell count and differential should be monitored during high dose penicillin therapy. Neutropenia in adults is a rare but well recognized complication of high dose therapy with penicillin and its semisynthetic derivatives (nafcillin, oxacillin, cloxacillin, ampicillin, carbenicillin, piperacillin, methicillin and ticarcillin [1][2][3][4][5][6][7][8][9].Not all the penicillins noted have been reported to cause neutropenia in children. There has been only one report of cloxacillin induced neutropenia in the pediatric age group [10]. Furthermore, this paper emphasizes the possible additive effects of more than one penicillin. Patients and MethodsCloxacillin alone or administered in conjunction with other semisynthetic penicillins, was implicated as the cause of neutropenia in five children seen at King Saud University and the Security Forces Hospital in Riyadh, Saudi Arabia over a nine-month period.All patients received a prolonged (mean 28 days) high dosage (45 to 126 gm/m 2 ) of cloxacillin alone or in conjunction with other semisynthetic penicillins. At the time of diagnosis complete blood count (CBC) and differential was obtained and weekly thereafter. At,the onset of neutropenia a CBC was obtained twice weekly until complete recovery was documented. All patients were followed up (mean follow-up time six months) and in none of the patients did neutropenia recur. Other causes of neutropenia were excluded and neutrophil anti-bodies were negative in cases I, II, III and IV.With the exception of case III, who was on aspirin prior to and throughout the course of illness, none of the patients were on any other medications. No patients were rechallenged with the offending medication. Case 1A two-year-old Saudi girl was admitted with a ten day history of fever and limp. Bone aspirate and pus obtained from a surgical drainage confirmed the clinical diagnosis of staphylococcal osteomyelitis. On admission, the white blood cell count (WBC) was 19.8 ×