CONICET | Buscador de Institutos y Recursos Humanos

INTRODUCTION:Since the discovery of penicillin in 19281 it have scheduled millions of beta-lactam treatments and saved an incalculable number of lives thanks to them. However, adverse reactions of these antibiotics they are a negligible cause of morbidity and mortality. He example best known for its severity are the anaphylactic reactions to beta-lactams that were described in 1946, already during the first years of its clinical use. That same year, the first case of neutropenia was described. by beta-lactams. Although the neutropenia caused by beta-lactams it is a well documented side effect in the medical literature, in recent years there has been less articles dedicated to this topic and there are no recent references that review this topic. So, on a Medline search, It is only few reports article, one related to cefepime, four articles that refer to the beta-lactam neutropenia, one article refers to Piperacillin neutropenia and one that refers to agranulocytosis by antibiotics in general. But nevertheless, the not negligible frequency of neutropenia and the frequency of beta lactams use in clinical practice suggest that it is a relevant problem in certain populations.Few studies have been conducted to describe epidemiology and risk factors. We also describe a Case series of 4 patients of piperacillin-tazobactam (PTZ) induced neutropenia.OBJECTIVE:To describe 4 cases of neutropenia linked to the use of tazobactam piperacillin, show its characteristics and indicate possible risk factors.METHODS:The clinical cases were registered in 2 assistance centers in the Autonomous City of Buenos Aires (Argentina). For the literature review, standard search strategies were used in Medline through https://www.ncbi.nlm.nih.gov/pubmed/ site. The strategies were based on the use of MESH terms (("Leukopenia"[Majr]) AND "beta-Lactams"[Mesh]) CASES - RESULTS:Case 1: A 35-year-old male with a double J catheter placed in the ureter was diagnosed with pyelonephritis and receives prolonged treatment with PTZ. He developed febrile neutropenia on day 20 of treatment. All other causes were ruled out. Serology for HIV, hepatitis, CMV, EBV, and other infectious causes were negative. The treatment was stopped on day 28 with positive de challenge. Case 2: A 32-year-old woman without significant clinical history started treatment with PTZ for renal abscesses. After 18 days she develops febrile neutropenia. The hematology evaluation ruled out other causes and suggested downloading pharmacological causes. Treatment was stopped on day 22 with positive de challenge.Case 3: 62-year-old man with urinary infection receives PTZ during 10 days. seven days after ending treatment, he was presents intra hospital pneumonia and received PTZ, presenting febrile neutropenia on the eighth day of treatment. Positive de challenge was observed on day 10.Case 4: A 72-year-old man with sepsis received subsequently ceftriaxone, ampicillin-sulbactam and PTZ. On the seventh day of PTZ he develops neutropenia, with positive de challenge two days later.DISCUSSION:Neutropenia has been described as an adverse reaction of almost all beta-lactams. Several articles have reported cases, as well as some reviews have analyzed this reaction. PTZ is indicated as one of the antibiotics that presents neutropenia with greater frequency. Common epidemiological characteristics include: -It usually appears after treatments with more 10 days -Related with high dose antibiotic-its incidence increases with the cumulative dose -It is often preceded by fever or rash that serve as alarm signals. -It usually lasts less than 10 days, and exceptionally entails Infectious complications or death. -Between all beta-lactams, the publications in recent years have focused on the neutropenia caused by piperacillin-tazobactam or by cefepime, demonstrating that the incidence of neutropenia during prolonged treatments with them is high.Proposed risk factors include: prolonged treatment (> 10 days), sequential use of antibiotics, young age, existence of liver disease, and concomitant use of myelotoxic factors. Important measures for early detection include the use of periodic hemograms and clinical examination (detecting fever, rash).Clinical trials with these antibiotics had not detected this complication, because in these Trials, treatments were less than 2 weeks.In the development of new beta-lactams it must have considered the possible occurrence of neutropenia during prolonged intravenous treatments.