RESUMO
Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
Assuntos
Acinetobacter baumannii , Antibacterianos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sepse Neonatal , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Sepse Neonatal/microbiologia , Sepse Neonatal/tratamento farmacológico , Recém-Nascido , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/genética , Amicacina/farmacologia , Amicacina/uso terapêutico , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Países em Desenvolvimento , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
OBJECTIVES: The study aimed to compare the developmental outcome of very low birth weight infants with a group of normal-term controls in a tertiary hospital in sub-Saharan Africa. DESIGN: A group of 105 very low birth weight infants were assessed at a mean age of 17.6 months (95% CI 16.7 to 18.6) using the Bayley Scales of Infant Development, Third Edition, and compared with a group of normal-term controls at the same mean age. RESULTS: Seven of the study infants (7%) had developmental delay (a score below 70), compared with none in the control group (p=0.04). Three of the seven study infants were delayed on all three subscales, one of whom had cerebral palsy. A further 34% of the study infants were 'at risk' of developmental delay (a score below 85). There was no difference in the mean composite score between the study group and controls for the cognitive (p=0.56), motor (p=0.57) or language (p=0.66) subscales. There was no difference in mean composite scores on all subscales between infants who were appropriate for gestational age and those who were small for gestational age. Cognitive and motor scores remained stable in paired assessments of study infants before and after 1 year of age; language scores decreased significantly (p<0.001). Mechanical ventilation was the only risk factor significantly associated with a cognitive score below 85 in study infants. CONCLUSION: Very low birth weight infants in sub-Saharan Africa are at risk of developmental delay and require long-term neurodevelopmental follow-up.