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
Maternal preconceptional cytomegalovirus (CMV) immunity does not protect the fetus from acquiring congenital CMV infection (cCMV). Nonprimary infections due to recurrence of latent infections or reinfection with new virus strains during pregnancy can result in fetal infection. Because the prevalence of cCMV increases with increasing maternal CMV seroprevalence, the vast majority of the cases of cCMV throughout the world follow nonprimary maternal infections and is more common in individuals of lower socioeconomic background. Horizontal exposures to persons shedding virus in bodily secretions (young children, sexual activity, household crowding, low income) probably increase the risk of acquisition of an exogenous nonprimary CMV infection and fetal transmission. In addition, more frequent acquisition of new antibody reactivities in transmitter mothers suggest that maternal reinfection by new viral strains could be a major source of congenital infection in such populations. However, the exact frequency of CMV nonprimary infection in seroimmune women during pregnancy and the rate of intrauterine transmission in these women are yet to be defined. Usually, the birth prevalence of cCMV is high (≥7:1000) in highly seropositive populations. There is increasing evidence that the frequency and severity of the clinical and laboratory abnormalities in infants with congenital CMV infection born to mothers with nonprimary CMV infection are similar to infants born after a primary maternal infection. This is particularly true for sensorineural hearing loss, which contributes to one third of all early-onset hearing loss in seropositive populations. This brief overview will discuss the need for more research to better clarify the natural history of cCMV in highly seropositive populations, which, in almost all populations, remains incompletely defined.