In low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0–13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns.

BackgroundThe present study aimed to perform a deep phenotypic and genotypic analysis of 15 clinical carbapenem-resistant Acinetobacter baumannii (CRAb) strains isolated in Madagascar between 2008 and 2016 from diverse sources.MethodsCRAb isolates collected from the Clinical Biology Centre of the Institut Pasteur of Madagascar, from the neonatal unit of Antananarivo military hospital, and from intensive care units of Mahajanga Androva and Antananarivo Joseph Ravoahangy Andrianavalona (HJRA) hospitals were subjected to susceptibility testing. Whole-genome sequencing allowed us to assess the presence of antibiotic-resistance determinants, insertion sequences, integrons, genomic islands and potential virulence factors in all strains. The structure of the carO porin gene and deduced protein (CarO) were also assessed in CRAb isolates.ResultsAll isolates were found to be multidrug-resistant strains. Antibiotic-resistance genes against six classes of antimicrobial agents were described. The four carbapenem-resistance genes: blaOXA-51 like, blaOXA-23, blaOXA-24, and blaOXA-58 genes were detected in 100, 53.3, 13.3, and 6.6% of the isolates, respectively. Additionally, an ISAba1 located upstream of blaOXA-23 and blaADC-like genes was observed in 53.3 and 66.7% of isolates, respectively. Further, Tn2006 and Tn2008 were found associated to the ISAba1-blaOXA-23 structure. An 8051-bp mobilizable plasmid harbouring the blaOXA-24 gene was isolated in two strains. In addition, 46.7% of isolates were positive for class 1 integrons. Overall, five sequences types (STs), with predominantly ST2, were detected. Several virulence genes were found in the CRAb isolates, among which two genes, epsA and ptk, responsible for the capsule-positive phenotype, were involved in A. baumannii pathogenesis.ConclusionsThis study revealed the presence of high-level carbapenem resistance in A. baumannii with the first description of OXA-24 and OXA-58 carbapenemases in Madagascar. This highlights the importance of better monitoring and controlling CRAb in Madagascan hospitals to avoid their spread.Electronic supplementary materialThe online version of this article (10.1186/s13756-019-0491-9) contains supplementary material, which is available to authorized users.

2AbstractThe antimicrobial resistance ofNeisseria gonorrhoeato all classes of current available antibiotics is a global concern. National surveillance programmes monitoring the susceptibility profiles ofNeisseria gonorrhoeaehardly exist in resource constraint settings. Therefore, little is known about the antimicrobial susceptibility profile and associated genetic resistance mechanisms ofN. gonorrhoeaein Madagascar. We report susceptibility data ofN. gonorrhoeaeisolates obtained by the medical laboratory of the Institut Pasteur de Madagascar, from 2014 -2020. In addition, we present data on the antimicrobial resistance mechanisms and antimicrobial resistance profile of a subset of isolates (N=46), including all isolates available of 2020. Over the study period, ceftriaxone resistant isolates exceeding the threshold of 5% in 2017 and 2020, were reported. Of the subset of re-tested isolates, all were found susceptible to ceftriaxone, azithromycin, and spectinomycin. Conversely, all isolates were resistant to ciprofloxacin and the majority was also resistant to penicillin and tetracycline. None of the isolates carried the mosaicpenAgene and chromosomal mutations associated to the antibiotic resistance ingyrA, parC, penA, ponA, porBandmtrRgenes were detected. The high rate of resistance to Penicillin and Tetracycline is explained by the presence of β-lactamaseblaTEMandtetMgenes, respectively, a plasmid mediated resistance. We found a high number of circulating multilocus sequence types. Almost half of them were new types, and one of them was among the four most predominant sequence types. Our report provides a detailed dataset obtained through phenotypic and genotypic methods which will serve as baseline for future surveillance ofN. gonorrhoeaein our setting, and Madagascar.1.5RepositoriesThis Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the Accession BioProject PRJNA929018.3Impact statementNeisseria gonorrhoeaeis becoming increasingly resistant to all classes of antibiotics available for infections treatment.Resource constraint settings encounter difficulties in implementing surveillance of the antimicrobial susceptibility ofN. gonorrhoeae. We report here antimicrobial susceptibility results from gonorrhoea among patients consulting a medical laboratory in Antananarivo, Madagascar in 2014–2020. We used whole-genome sequencing to identify resistance mechanisms in a subset of isolates including all viable isolates of 2020.We report multilocus sequence types and discuss phenotypes and genotypes according to the phylogenetic analysis of the isolates. The susceptibility results are the first in a decade to be reported. We set the baseline to study further the evolution and transmission ofN. gonorrhoeaeresistance mechanisms and genotypes in general. Our report will enable improving surveillance ofNeisseria gonorrhoeaein Madagascar and Africa.Overall, it will contribute to the global, regional, and national surveillance ofN. gonorrhoeae. In addition, it may set a benchmark for implementation in other settings facing barriers implementing phenotypic resistance surveillance ofN. gonorrhoeae.4Data summaryThe source code of the Tormes pipeline used in this study is also available on Github:https://github.com/nmquijada/tormes.The SRA sequences have been deposited in the NCBI SRA database under accession numbers SRR23260223 and SRR23260193.The genome assemblies can be accessed using the accession numbers: SAMN32949360 - SAMN32949405.The MLST genes of all isolates can be accessed through this link:https://doi.org/10.5281/zenodo.7581537The Perl scripts used for a quality filtering of the assemblies which is to remove small contigs can be accessed through the following link:https://github.com/Alainnoah/Remove-Small-Contigs-Draft-Assemblies.Genomic analysis with metadata in Pathogenwatch could be accessed with this link:https://pathogen.watch/collection/f7t4wjtjlybh-mdgwhofaA visualization of genomic epidemiology of our isolates with Microreact can be accessed with this link:https://microreact.org/project/7FADQYwhm5h1zJyJTynM6R-unnamed-projectA supplementary material in an Excel sheet summarizing the lists of plasmids used for alignment (Table S1), the statistics of the sequences (Table S2), and the minimum inhibitory concentration values ofN. gonorrhoeaeisolates and their antimicrobial resistance genetic mechanisms (Table S3) is available through this link:https://doi.org/10.6084/m9.figshare.21973511