Análise de reações adversas a antimicrobianos em crianças hospitalizadas

Abstract

Introduction. Adverse drug reactions (ADRs) especially affect hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs for health systems. Antimicrobials are often involved in these reactions due to the frequency and consequences of their use. Thus, investigating ADRs related to antimicrobials in children can help to improve understanding of the factors involved, as well as help in the development of appropriate strategies to contribute to the safety of these patients. Aim. To analyze ADRs to antimicrobials in hospitalized children. Methods. The study was carried out in two stages. In step 01, a prospective multicenter cohort study was carried out in 5 public hospitals for 6 months. Children aged 0 to 11 years and 11 months who remained hospitalized for more than 48 hours and used prescribed antimicrobials for more than 24 hours were included. To analyze the causality and preventability of ADRs, the validated Portuguese versions of the Liverpool causality and preventability tools were used. This study was approved by the Human Research Ethics Committee (CEP: SE:2,801,684; CE:3,027,780; RJ:3,264,238; DF:4,273,903; RGS: 3,782,762). Results. In stage 01, a total of 1,020 patients met the inclusion criteria. Of these, 152 patients had 183 suspected ADRs. The majority of reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Regarding causality, severity and preventability, the majority were classified as probable (58.5%), moderate (61.1%) and inevitable (56.2%), respectively. Our findings showed that ADRs were associated with increased length of stay (P < 0.001), increased time on therapy (P < 0.015), increased days of therapy (P = 0.038) and increased number of antimicrobials prescribed per patient (P < 0.001). In relation to stage 02, 30 articles met the inclusion criteria. Skin reactions were the main serious clinical manifestations presented in most articles 19/30, with emphasis on erythema multiforme (71 cases), Stevens-Johnson syndrome (72 cases) and toxic epidermal necrolysis (22 cases). The main classes of antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the main outcomes found, 30% (9/30) of the articles mentioned at least one death and 46.7% (14/30) of the studies reported an increase in hospitalization time, the need for intensive therapy and/or transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication replacement or prescription of specific medication for the symptomatology. Conclusion. The incidence of ADR in hospitalized children exposed to antimicrobials was 14.9%. Its occurrence was classified as probable, moderate in severity and inevitable. ADRs were significantly influenced by length of stay and the number of antimicrobials prescribed per patient. In the systematic review, the majority of moderate and severe ADRs were cutaneous reactions with an emphasis on erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. The main classes involved were penicillins, cephalosporins and sulfonamides, and in relation to antimicrobials, the highest number of ADRs was reported for vancomycin, amoxicillin and amoxicillin with clavulanate. 30% of articles reported at least one death related to a moderate or severe ADR caused by antimicrobials.