clove and Enterobacteriaceae-Infections

Data regarding the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in neonates at the community level are scarce in low-income and middle-income countries (LMICs), where the burden of neonatal sepsis is high.Our study aims at identifying and quantifying the role of the different routes of ESBL-PE transmission for neonates, which are still undefined in the community in LMICs.. In a semirural community in Madagascar, 60 mothers and their neonates will be recruited at delivery, during which a maternal stool sample and meconium of the newborn will be collected. Home visits will be planned the day of the delivery and next at days 3, 7, 14, 21 and 28. Stool samples from the newborn, the mother and every other household member will be collected at each visit, as well as samples from the environment in contact with the newborn (food, surfaces and objects). Sociodemographic data and factors which might drive ESBL-PE acquisition will also be collected.We will analyse the isolated ESBL-PE using DNA sequencing methods to characterise clones, resistance genes and plasmids of ESBL-PE. To analyse these data globally, we will develop novel analytical approaches combining mathematical modelling and statistics. Finally, mathematical simulations will be performed to test different strategies of control of ESBL-PE transmission to neonates.In complement, we will conduct an anthropological investigation to understand local environments and practices that would contribute to neonatal ESBL-PE acquisition. In-depth interviews with members of 16 households will be conducted and 4 mother-newborn pairs will be followed by a participants' observations methodology.. The study was approved by the ethical committee in Madagascar and by the institutional review board of Institut Pasteur, Paris, France.Findings will be reported to participating families, collaborators and local government; presented at national and international conferences and disseminated by peer-review publications.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cohort Studies; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Infant, Newborn; Madagascar

The diffusion of extended-spectrum beta-lactamase (E-ESBL)-producing Enterobacteriaceae is a major concern worldwide, especially in low-income countries, where they may lead to therapeutic failures. In hospitals, where colonization is the highest, E-ESBL transmission is poorly understood, limiting the possibility of establishing effective control measures. We assessed E-ESBL-acquisition routes in a neonatalogy ward in Madagascar. Individuals from a neonatology ward were longitudinally followed-up (August 2014-March 2015). Newborns' family members' and health-care workers (HCWs) were stool-sampled and tested for E-ESBL colonization weekly. Several hypothetical acquisition routes of newborns-e.g. direct contact with family members and HCWs and indirect contact with other newborns through environmental contamination, colonization pressure, or transient hand carriage-were examined and compared using mathematical modeling and Bayesian inference. In our results, high E-ESBL acquisition rates were found, reaching > 70% for newborns, > 55% for family members, and > 75% for HCWs. Modeling analyses indicated transmission sources for newborn colonization to be species dependent. Health-care workers' route were selected for

Topics: Anti-Bacterial Agents; beta-Lactamases; Carrier State; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Health Personnel; Humans; Infant, Newborn; Madagascar; Models, Biological; Monte Carlo Method; Nurseries, Hospital; Parents

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.

Topics: Adult; beta-Lactamases; Child, Preschool; Cohort Studies; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Incidence; Infant; Infant, Low Birth Weight; Infant, Newborn; Klebsiella pneumoniae; Madagascar; Male; Multivariate Analysis; Pregnancy; Proportional Hazards Models; Risk Factors; Young Adult

We investigated the molecular mechanism of ß-lactam resistance in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterial strains isolated in neonatal units of different hospitals in Anatnanarivo, Madagascar.. Bacteria were identified by standard biochemical methods, disc diffusion antibiograms and Etest. Resistance genes were sought by PCR. Strains were characterized by Rep-PCR (Diversilab), plasmid analysis and rep-typing.. From April 2012 to March 2013, 29 ESBL-producing E. cloacae and 15 K. pneumoniae were isolated from blood culture (n = 32) or gastric samples (n = 12) performed at day 0 or 2 from 39/303 newborns suspected of early neonatal infection. These infants were treated with expanded spectrum cephalosporins, due to lack of carbapenems, leading to a high mortality rate (45 %). Isolates recovered were all, but 4, multidrug resistant, particularly to fluoroquinolones (FQ) except for 21 E. cloacae isolates. Isolates produced TEM-1 and CTX-M-15 ß-lactamases and their genes were located on several self-transferable plasmids of variable sizes sizes that could not be linked to a major plasmid incompatibility group. E. cloacae isolates belonged to 6 Rep-types among which two counted for 11 isolates each. The FQ resistant E. cloacae isolates belonged to one clone, whereas the FQ susceptible E. cloacae isolates belonged to four clones. The K. pneumoniae isolates belonged to 9 Rep-types among which one included five isolates.. This study is the first molecular characterization of ESBL-producing isolates from neonatology units in Madagascar, a country with limited epidemiological data. It revealed an important multi-clonal dissemination of CTX-M-15-producing isolates reflecting both the high community carriage and the very early nosocomial contamination of the neonates.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Newborn, Diseases; Infant, Postmature; Infant, Premature; Klebsiella Infections; Klebsiella pneumoniae; Madagascar; Male; Microbial Sensitivity Tests; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA

The spread of extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-PE) in low-income countries, where the burden of neonatal sepsis is high, may have a serious impact on neonatal mortality rates. Given the potential for mother-to-child transmission of multiresistant bacteria, this study investigated the ESBL-PE rectal colonization among pregnant women at delivery in the community in Madagascar and estimated a prevalence of 18.5% (95% confidence interval, 14.5% to 22.6%). One strain of Klebsiella pneumoniae isolated was also a New Delhi metallo-β-lactamase-1 (NDM-1) producer.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infant, Newborn; Madagascar; Pregnancy; Young Adult

Topics: Antitubercular Agents; Brain Abscess; Brain Neoplasms; Combined Modality Therapy; Diagnosis, Differential; Enterobacter cloacae; Enterobacteriaceae Infections; Epilepsy, Tonic-Clonic; Frontal Lobe; Humans; Madagascar; Male; Neuroimaging; Peritonitis, Tuberculous; Superinfection; Surgical Wound Infection; Tuberculoma, Intracranial; Tuberculosis, Pleural; Tuberculosis, Pulmonary; Young Adult

We investigated the molecular characteristics of multidrug-resistant, extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolated in community settings and in hospitals in Antananarivo, Madagascar.. Forty-nine E. coli, K. pneumoniae, K. oxytoca and E. cloacae ESBL-producing isolates were studied. In antimicrobial susceptibility analyses, many of the isolates exhibited resistance to aminoglycosides, fluoroquinolones and trimethoprim-sulfamethoxazole. Gene amplification analysis and sequencing revealed that 75.5% (n=37) of the isolates harbored blaCTX-M-15 and 38.7% (n=19) harbored blaSHV-12. The non-ESBLs resistance genes detected were blaTEM-1, blaOXA-1, aac(6')-Ib,aac(6')-Ib-cr, tetA, sul-1, sul-2, qnrA, qnrB and catB-3. We found dfrA and aadA gene cassettes in the class 1 integron variable regions of the isolates, and the combination of dfrA17-aadA5 to be the most prevalent. All blaCTX-M-15 positive isolates also contained the ISEcp1 insertion element. Conjugation and transformation experiments indicated that 70.3% of the antibiotic resistance genes resided on plasmids. Through a PCR based replicon typing method, plasmids carrying the blaSHV-12 or blaCTX-M-15 genes were assigned to either the IncFII replicon type or, rarely, to the HI2 replicon type. All isolates were subtyped by the rep-PCR and ERIC-PCR methods.Phylogenetic grouping and virulence genotyping of the E. coli isolates revealed that most of them belonged to group A1. One isolate assigned to group B2 harbored blaCTX-M-15 and five virulence genes (traT, fyuA, iutA, iha and sfa) and was related to the O25b-ST131 clone.. Our results highlight the dissemination of multidrug resistant Enterobacteriaceae isolates in Antananarivo. These findings underline the need for a rational use of antibiotic and for appropriate methods of screening ESBL in routine laboratories in Antananarivo.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cluster Analysis; Community-Acquired Infections; Conjugation, Genetic; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Humans; Integrons; Madagascar; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Typing; Phylogeny; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA; Transformation, Bacterial

The purpose of this study was to evaluate the incidence of acquired resistance to antibiotics in Madagascar. Testing was carried out on total of 1267 strains of medically significant bacteria isolated from specimens sent to the Pasteur Institute of Madagascar in Antananarivo between October 1997 and October 1998. Antibiograms were performed using the diffusion technique on gel media with antibiotic disks. Results were read according to the criteria of the Antibiogram Committee of the French Society of Microbiology. Preliminary findings documented a high incidence of resistance to widely available, low-price antibiotics including penicillin G and tetracycline for which 84 p. 100 and 65 p. 100 of Staphylococcus aureus respectively demonstrated resistance; tetracyclin to which 80 p. 100 of streptococcus were resistant; and ampicillin, cotrimoxazole, and phenicoles to which 60 p. 100, 60 p. 100 and 28 p. 100 of Escherichia coli respectively and 77 p. 100, 83 p. 100, and 71 p. 100 of Shigella sp. respectively were resistant. Second-line antibiotics including penicillin M, macrolides, nalidixic acid, and nitrofuranes were still relatively active, thus providing an effective alternative. Newly developed antibiotics such as fluoroquinolones and third-generation cephalosporines were highly effective but a few resistant strains were observed. Although not representative of Madagascar as a whole, the findings of this preliminary study indicate that acquired resistance must be taken into account in designing simplified decision charts for front-line laboratories, that appropriate information must be made available to health care workers, and that further testing is needed to monitor the evolution of antibiotic resistance.

Topics: Bacterial Infections; Decision Support Techniques; Drug Resistance, Microbial; Enterobacteriaceae Infections; Enterococcus faecalis; Gram-Positive Bacterial Infections; Humans; Incidence; Madagascar; Patient Selection; Population Surveillance; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus agalactiae