Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review

ABSTRACT Background Technologies and life support management have enhanced the survival of preterm infants. The immune system of newborns is immature, which contributes to the occurrence of healthcare-associated infections. The overlap of several conditions with neonatal sepsis and the difficulty of diagnosis and laboratory confirmation during this period result in a tendency to over-treat neonatal sepsis. The use of antimicrobial agents is a risk factor for multidrug-resistant bacterial infections. This work aimed to perform a systematic review of the relationship between inadequate use of antimicrobial agents and increase in neonatal sepsis related to healthcare assistance, due to bacterial resistance. Methods Our population, exposition, comparison, outcome and study type was as follows: P: hospitalized neonates with sepsis diagnosis, E: inappropriate use of antimicrobial agents, C: adequate use of antimicrobial agents or no indication of infection, O: resistant bacterial infection, and S: original studies. We performed searches in the PubMed, Scopus, Virtual Health Library (Scielo, LILACS, and MEDLINE), and Embase without limits on time, language, and the references of the articles found. Fourteen studies were included and assessed using the Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle, and the Strengthening the Reporting of Observacional Studies in Epidemiology methodologies. Results All studies found were observational and started with a low-quality evidence level in the Grading of Recommendations, Assessment, Development, and Evaluation. Conclusions Despite their low-quality evidence, the studies demonstrated the association between inadequate use of antimicrobial agents and increase of neonatal resistant bacterial healthcare-associated infections in neonatal units. However, there is significant difficulty in conducting high-quality studies in this population due to ethical issues tied to randomized trials. Therefore, new studies should be encouraged to recommend adequate treatment of newborns without increasing the risk of healthcare-associated infections by multidrug-resistant bacteria.

Empirical antimicrobial therapy for late-onset sepsis in a neonatal unit with high prevalence of coagulase-negative Staphylococcus / Terapia antimicrobiana empírica para sepse tardia na unidade neonatal com alta prevalência de Staphylococcus coagulase negativo

Abstract Objective: The aim of this study was to compare two different empiric treatments for late-onset neonatal sepsis, vancomycin and oxacillin, in a neonatal intensive care unit with a high prevalence of coagulase-negative Staphylococcus. Methods: A cross-sectional study was conducted in an neonatal intensive care unit from 2011 to 2014. Data from the medical records of at-risk newborns were collected daily. Infections were defined according to the National Health Surveillance Agency criteria. Data analysis was performed using an internal program. Results: There was a significant reduction in the number of Staphylococcus aureus infections (p = 0.008), without endocarditis, meningitis, or lower respiratory tract infection, as well as a reduction in the frequency of deaths related to S. aureus infection. There were no significant changes in the incidence of Gram-negative bacterial or fungal infections. An increase in coagulase-negative Staphylococcus infections was observed (p = 0.022). However, there was no measured increase in related morbidity and mortality. There was a reduction in the median number of days of treatment with oxacillin from 11.5 to 6 days (p < 0.001) and an increase of one day in the median number of days of treatment with vancomycin (p = 0.046). Conclusions: Modification of the empiric treatment regimen for neonatal late-onset sepsis with use of oxacillin showed a significant reduction in S. aureus infections, as well as a reduction in the frequency of infections with major organ system involvement and mortality due to infection with this microorganism. As a result, oxacillin can be considered as an effective treatment for late-onset sepsis, making it possible to avoid broad-spectrum antibiotics.

Resumo Objetivo Comparar dois períodos com diferentes esquemas empíricos para tratamento de sepse neonatal tardia, incluindo vancomicina ou oxacilina respectivamente, em unidade neonatal de referência com alta prevalência de Staphylococcus coagulase negativo. Métodos Estudo transversal, feito em unidade neonatal de referência, de 2011 a 2014. Os dados foram coletados diariamente por vigilância ativa em prontuário de recém-nascidos de risco. As infecções foram notificadas conforme critérios definidos pela Agência Nacional de Vigilância Sanitária. O banco de dados e a análise foram feitos em programa interno. Resultados Ocorreu redução significativa da notificação de infecções por Staphylococcus aureus (p = 0,008), sem notificações de endocardite, meningite e infecções de vias aéreas inferiores, além de redução na frequência de óbitos pelo microrganismo e sem alteração significativa nas incidências de infecções por bactérias Gram negativas e fungos. Houve aumento de infecções S. aureus coagulase negativo (p = 0,022), mas sem aumento de morbidade e mortalidade. Ocorreu redução na mediana do tempo de uso de oxacilina, de 11,5 para 6 dias (p < 0,001), com aumento de mediana de um dia de uso de vancomicina (p = 0,046). Conclusões A modificação do esquema empírico com uso de oxacilina revelou redução significativa das infecções por S. aureus, além da redução na frequência de infecção de foco profundo e mortalidade pelo microrganismo. Considera-se que oxacilina pode ser usada como esquema de tratamento de sepse neonatal tardia para se evitar o uso de antibióticos de largo espectro.