Heterogeneity of Carbapenem Resistance Mechanisms among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study

© Copyright 2017, Mary Ann Liebert, Inc. 2017. Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23 and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial

Expression and Roles of Antimicrobial Peptides in Innate Defense of Airway Mucosa: Potential Implication in Cystic Fibrosis

© Copyright © 2020 Geitani, Moubareck, Xu, Karam Sarkis and Touqui. The treatment of respiratory infections is associated with the dissemination of antibiotic resistance in the community and clinical settings. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides (AMPs), the central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. Most AMPs are epithelium-derived and play a key role in host defense at mucosal surfaces. They are classified on the basis of their structure and amino acid motifs. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils, in particular, contribute to AMP synthesis. The relevance of AMPs for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Of note, AMPs are active against bacterial strains that are resistant to conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of AMPs. In this review, we focus on studies related to direct bactericidal effects of AMPs and their potential clinical applications with a particular focus on cystic fibrosis

Surveillance of carbapenem non-susceptible gram negative strains and characterization of carbapenemases of classes A, B and D in a Lebanese hospital

© 2015, Lebanese Order of Physicians. All rights reserved. The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest® for metallo-β-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize β-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS1999; four Acinetobacter baumannii harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P. aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes

Could Gut Modulation through Probiotic Supplementation Be Beneficial in Autism Spectrum Disorder?

Evidence is mounting to a possible link between autism spectrum disorder (ASD) and gut microbiota through the well-known gut-brain axis. Numerous mechanisms have been suggested including bacterial metabolites that could involve in chemokines, antimicrobial peptides, or neuropeptides production. Hence, numerous studies reported dysbiosis in autistic patients. Antibiotic courses are known to more or less improve neurobehavioral symptoms; however, it could lead to side effects. Modulation of the gut microbiota using pro- and/or prebiotics is therefore an appealing way of treatment. Fecal microbiota transfer is suggested to be an alternative new approach that could be promising. The aim of our chapter will be first to briefly review the current data concerning the possible role of the gut microbiota and its mechanisms in ASD and second to review the interest and limits of the pre- and probiotic supplementations in ASD treatment. Lastly, we will discuss on the potential interest of the microbiota transfer in ASD

Individual variations in intestinal microbiota were higher in preterm infants with necrotising enterocolitis than healthy controls

International audienc

Assessment of the performance of CHROMagar KPC and Xpert Carba-R assay for the detection of carbapenem-resistant bacteria in rectal swabs: First comparative study from Abu Dhabi, United Arab Emirates

© 2019 International Society for Antimicrobial Chemotherapy Objectives: The objective of this study was to evaluate the performance of CHROMagar™ KPC compared with Xpert® Carba-R assay for the detection of carbapenem-resistant bacterial isolates from rectal swabs. Methods: Rectal swabs were obtained from patients admitted to Cleveland Clinic Abu Dhabi (United Arab Emirates) over a period of 7 months and were screened for carbapenem resistance by either culture on CHROMagar KPC or carbapenemase production using the Xpert Carba-R molecular method. Further testing for carbapenem susceptibility of isolates recovered from CHROMagar KPC was performed using VITEK®2. Results: A total of 1813 rectal swabs were screened, of which 61 (3.4%) were positive for carbapenem resistance by either one or both methods. Both methods were equally efficient in detecting carbapenem resistance in 37/61 swabs (60.7%), mostly positive for Klebsiella pneumoniae (22 isolates), of which 40.9% (9/22) carried blaOXA-48-like and blaNDM. Xpert Carba-R assay detected 12 additional swabs with negative CHROMagar KPC culture and revealed additional carbapenemase-producing organisms carrying blaOXA-48-like and/or blaNDM. CHROMagar KPC recovered organisms in nine swabs not detected by the genotypic method, 44.4% of which were K. pneumoniae. Three swabs yielded false-positive results (carbapenem-susceptible organisms) by both methods. Sensitivity and specificity were, respectively, 75.4% and 99.8% for CHROMagar KPC and 80% and 99.8% for Xpert Carba-R. Conclusion: This comparative study of CHROMagar KPC versus Xpert Carba-R in rectal swabs showed a slightly higher sensitivity for the PCR-based method. Whilst CHROMagar KPC provides a less expensive screening method, Xpert Carba-R may be more accurate and faster

Establishment and development of the intestinal microbiota of preterm infants in a Lebanese tertiary hospital

© 2016 The Authors The establishment and development of the intestinal microbiota is known to be associated with profound short- and long-term effects on the health of full-term infants (FTI), but studies are just starting for preterm infants (PTI). The data also mostly come from western countries and little information is available for the Middle East. Here, we determined the composition and dynamics of the intestinal microbiota during the first month of life for PTI (n = 66) and FTI (n = 17) in Lebanon. Fecal samples were collected weekly and analyzed by quantitative PCR (q-PCR) and temporal temperature gradient gel electrophoresis (TTGE). We observed differences in the establishment and composition of the intestinal microbiota between the two groups. q-PCR showed that PTI were more highly colonized by Staphylococcus than FTI in the first three weeks of life; whereas FTI were more highly colonized by Clostridium clusters I and XI. At one month of life, PTI were mainly colonized by facultative anaerobes and a few strict anaerobes, such as Clostridium cluster I and Bifidobacterium. The type of feeding and antibiotic treatments significantly affected intestinal colonization. TTGE revealed low species diversity in both groups and high inter-individual variability in PTI. Our findings show that PTI had altered intestinal colonization with a higher occurrence of potential pathogens (Enterobacter, Clostridium sp) than FTI. This suggests the need for intervention strategies for PTI to modulate their intestinal microbiota and promote their health

Role of outer membrane permeability, efflux mechanism, and carbapenemases in carbapenem-nonsusceptible Pseudomonas aeruginosa from Dubai hospitals: Results of the first cross-sectional survey

© 2019 The Authors Objectives: Carbapenem resistance in Pseudomonas aeruginosa is growing and results from variable mechanisms. The objectives of the current study were to investigate mechanisms of carbapenem resistance and genetic relatedness of P. aeruginosa isolates recovered in Dubai hospitals. Methods: From June 2015 through June 2016, carbapenem-nonsusceptible P. aeruginosa were collected from 4 hospitals in Dubai, and subjected to antimicrobial susceptibility testing, molecular investigation of carbapenemases by PCR-sequencing, analysis of outer membrane porin OprD2 and multidrug efflux channel MexAB-OprM levels by qPCR, and fingerprinting by ERIC-PCR. Results: Out of 1969 P. aeruginosa isolated during the study period, 471 (23.9%) showed reduced carbapenem susceptibility. Of these, 37 were analyzed and 32% of them produced VIM-type metallo-β-lactamases, including VIM-2, VIM-30, VIM-31, and VIM-42, while GES-5 and GES-9 co-existed with VIM in 5.4% of isolates. Outer membrane impermeability was observed in 73% of isolates and 75.6% displayed overproduced MexAB-OprM. ERIC-PCR revealed one large clone including most carbapenemase-producing isolates indicating clonal dissemination. Conclusion: This is the first study on carbapenem-nonsusceptible P. aeruginosa from Dubai, incriminating VIM production as well as outer membrane permeability and efflux systems as resistance mechanisms. Further studies on carbapenem-nonsusceptible P. aeruginosa in Dubai are warranted for containment of such health hazard

Investigating Pneumonia Etiology Among Refugees and the Lebanese population (PEARL): A study protocol

Background: Community-acquired pneumonia (CAP), a leading cause of mortality, mainly affects children in developing countries. The harsh circumstances experienced by refugees include various factors associated with respiratory pathogen transmission, and clinical progression of CAP. Consequently, the etiology of CAP in humanitarian crisis situations may differ to that of settled populations, which would impact appropriate case management. Therefore, the Pneumonia Etiology Among Refugees and the Lebanese population (PEARL) study was initiated with the objective of identifying the causal pathogenic microorganisms in the respiratory tract of children and adults from both the refugee and host country population presenting with signs of CAP during a humanitarian crisis. Methods: PEARL, a prospective, multicentric, case-control study, will be conducted at four primary healthcare facilities in Tripoli and the Bekaa valley over 15 months (including two high-transmission seasons/winters). Sociodemographic and medical data, and biological samples will be collected from at least 600 CAP cases and 600 controls. Nasopharyngeal swabs, sputum, urine and blood samples will be analyzed at five clinical pathology laboratories in Lebanon to identify the bacterial and viral etiological agents of CAP. Transcriptomic profiling of host le