Elias Dahdouh | Universidad Complutense de Madrid (original) (raw)

Papers by Elias Dahdouh

Frontiers in cellular and infection microbiology, May 16, 2024

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent t... more Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficultto-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and wholegenome sequencing was performed. Antibiotic resistance and virulenceassociated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were bla OXA-48 (45.6%), bla VIM-1 (23.3%), bla NDM-1 (7.8%), bla KPC-3 (6.7%), and bla NDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven Frontiers in Cellular and Infection Microbiology frontiersin.org 01

Frontiers in Microbiology, Mar 23, 2018

Currently, antimicrobial resistance is one of the most prominent public health issues. In fact, t... more Currently, antimicrobial resistance is one of the most prominent public health issues. In fact, there is increasing evidence that animals constitute a reservoir of antimicrobial resistance. In collaboration with the Lebanese Ministry of Agriculture, the aim of this study was to determine the prevalence of intestinal carriage of multi-drug-resistant Gram-negative Bacilli in poultry farms at the national level. Between August and December 2015, 981 fecal swabs were obtained from 49 poultry farms distributed across Lebanon. The swabs were subcultured on MacConkey agar supplemented with cefotaxime (2 µg/ml). Isolated strains were identified using MALDI-TOF mass spectrometry. Multilocus sequence typing analysis was performed for Escherichia coli. Phenotypic detection of extended spectrum β-lactamases (ESBL) and AmpC production was performed using double disk synergy and the ampC disk test, respectively. β-lactamase encoding genes bla CTX−M , bla TEM , bla SHV , bla FOX , bla MOX , bla EBC , bla ACC , bla DHA , and bla CMY using PCR amplification. Out of 981 fecal swabs obtained, 203 (20.6%) showed bacterial growth on the selective medium. Of the 235 strains isolated, 217 were identified as E. coli (92%), eight as Klebsiella pneumoniae (3%), three as Proteus mirabilis (1%) and three as Enterobacter cloacae (1%). MLST analysis of E. coli isolates showed the presence of ST156, ST5470, ST354, ST155, and ST3224. The phenotypic tests revealed that 43.5, 28.5, and 20.5% of the strains were ampC, ESBL, and ampC/ESBL producers, respectively. The putative TEM gene was detected in 83% of the isolates, SHV in 20%, CTX-M in 53% and CMY ampC β-lactamase gene in 65%. Our study showed that chicken farms in Lebanon are reservoirs of ESBL and AmpC producing Gram-negative bacilli. The level of antibiotic consumption in the Lebanese veterinary medicine should be evaluated. Future studies should focus on the risk factors associated with the acquisition of multi-drug-resistant organisms in farm animals in Lebanon.

ISRN Infectious Diseases (Online), Jul 17, 2013

Several studies have reported the isolation of resistant Gram-Negative Bacilli in Lebanon. Howeve... more Several studies have reported the isolation of resistant Gram-Negative Bacilli in Lebanon. However, those studies are new and scarce as compared to worldwide data and mostly restricted to single center studies. In this review, we attempt to provide a reliable and comprehensive report describing the current situation and providing prospects for bacterial resistance in Lebanon. Several studies have shown that Extended Spectrum-Lactamase-producing E. coli and K. pneumoniae strains are being increasingly reported. Moreover, 2.15% of E. coli and 7.84% of K. pneumoniae isolates have shown carbapenem resistance and up to 30% of isolated E. coli strains were found to be Multi-Drug Resistant. Molecular studies showed that the most widespread-Lactamases in Lebanon are of the CTX-M-15 and SHV types. In addition, K. pneumoniae strains producing metallo-Lactamase and Klebsiella pneumoniae Carbapenemase have been reported. Resistant Pseudomonas aeruginosa and Acinetobacter baumannii caused several nosocomial infections and some Acinetobacter baumannii strains were found to produce OXA-58 type ESBL. e few data addressing the rate of antibiotic consumption in Lebanon show a high rate of antibiotic misuse and abuse. In conclusion, there is a need for antibiotic stewardship programs and additional studies that go beyond the scope of single-center studies in Lebanon.

Frontiers in Cellular and Infection Microbiology, May 2, 2023

Introduction: Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat... more Introduction: Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients. Methods: RLs of bla CTX-M-1-Family , bla OXA-1 , bla OXA-48 and bla VIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients' demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates. Results and discussion: 76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for bla OXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, noncarbapenem b-lactams, and glycopeptides were statistically associated with testing negative for bla CTX-M-1-Family and bla OXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant Frontiers in Cellular and Infection Microbiology frontiersin.org 01

Microbiology Spectrum

In this study, we track the relative intestinal loads of antibiotic resistance genes among pediat... more In this study, we track the relative intestinal loads of antibiotic resistance genes among pediatric liver transplant patients and determine the relationship between this load, antibiotic consumption, and infections caused by antibiotic-resistant organisms. We demonstrate that the consumption of broad spectrum antibiotics increase this load and decrease the gut microbial diversity among these patients.

International Journal of Molecular Sciences

The EPIC consortium brings together experts from a wide range of fields that include clinical, mo... more The EPIC consortium brings together experts from a wide range of fields that include clinical, molecular and basic microbiology, infectious diseases, computational biology and chemistry, drug discovery and design, bioinformatics, biochemistry, biophysics, pharmacology, toxicology, veterinary sciences, environmental sciences, and epidemiology. The main question to be answered by the EPIC alliance is the following: “What is the best approach for data mining on carbapenemase inhibitors and how to translate this data into experiments?” From this forum, we propose that the scientific community think up new strategies to be followed for the discovery of new carbapenemase inhibitors, so that this process is efficient and capable of providing results in the shortest possible time and within acceptable time and economic costs.

Microbial Genomics

The population structure of a set of OXA-48-producing Klebsiella pneumoniae isolates belonging to... more The population structure of a set of OXA-48-producing Klebsiella pneumoniae isolates belonging to sequence type 11 (ST11 Kp-OXA) and obtained from two hospitals in Madrid in the period from 2012 to 2015 was studied by genome sequencing. Overall, 97 ST11 Kp-OXA isolates were sequenced and their population structure and demography were studied by Bayesian phylodynamic analysis using core-genome SNVs. In total, 92 isolates were from Hospital La Paz, 57 of them from two selected units. The remaining five isolates were from different units of Hospital Doce de Octubre. Altogether, 96 out of the 97 ST11 Kp-OXA isolates could be ascribed to a single lineage that evolved into three sublineages. Demographic inference showed an expansion of the ST11 Kp-OXA in the first half of 2013 in agreement with the registered incidences. Dated phylogeny showed transmission clusters within hospital wards, between wards and between hospitals. The ST11 Kp-OXA outbreak in Hospital La Paz was largely due to th...

Clinical Microbiology and Infection

Archives of Disease in Childhood

ObjectivesTo evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR... more ObjectivesTo evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children.DesignCross-sectional multicentre diagnostic study.SettingStudy nested in a prospective, observational cohort (EPICO-AEP) performed between February and March 2021 including 10 hospitals in Spain.PatientsChildren from 0 to 18 years with symptoms compatible with Covid-19 of ≤5 days of duration were included. Two NPS samples (Ag-RDT and RT-PCR) and one OSS sample for RT-PCR were collected.Main outcomePerformance of Ag-RDT and RT-PCR on NPS and RT-PCR on OSS sample for SARS-CoV-2.Results1174 children were included, aged 3.8 years (IQR 1.7–9.0); 73/1174 (6.2%) patients tested positive by at least one of the techniques. Sensitivity and specificity of OSS RT-PCR were 72.1% (95% CI 59.7 to 81.9) and 99.6% (95% CI 99 to 99.9), respectively, versus 61.8% (95% CI 49.1 to 73) a...

TheScientificWorldJournal, 2014

The aim of this study was to determine the usefulness of the MPC of carbapenems against clinical ... more The aim of this study was to determine the usefulness of the MPC of carbapenems against clinical isolates of Pseudomonas spp. and Acinetobacter spp. and to assess its possible relationship with mechanisms of resistance. Detection of the mechanisms of resistance was performed using Antibiotic Susceptibility Testing, Double Disk Synergy, disk antagonism, addition of NaCl to the medium, addition of PBA or EDTA to Carbapenem disks, addition of PBA to Cefoxitin disks, and CCCP test for 10 Pseudomonas spp. and Acinetobacter baumannii strains. The MIC and MPC were determined using the broth macrodilution and plate dilution methods, respectively. Four Acinetobacter baumannii strains produced MBL. Two of them produced Oxacillinase and one produced ESBL. Two Pseudomonas spp. isolates produced both KPC and MBL. The resistant Acinetobacter spp. and Pseudomonas spp. strains had higher MPC values than susceptible ones. However, the Mutant Selection Window was found to be dependent on the degree o...

Indian Journal of Forensic Medicine & Toxicology, 2019

Frontiers in Cellular and Infection Microbiology, 2017

Microbial drug resistance (Larchmont, N.Y.), Jan 26, 2017

Extended-spectrum beta-lactamases (ESBL) and carbapenemase-producing organisms pose severe proble... more Extended-spectrum beta-lactamases (ESBL) and carbapenemase-producing organisms pose severe problems for hospitalized patients. In the absence of efficient sanitation and sewage disposal, the risks for transmission of hospital organisms into the community are high. Our objectives were to study the occurrence and mechanisms of resistance of multidrug-resistant gram-negative bacilli in two Lebanese hospital sewage treatment plants. Wastewater samples were collected, filtered, and cultivated on MacConckey+cefotaxime agars. ESBL, AmpC, metallo-β-lactamases (MBL), and Klebsiella pneumoniae Carbapenemases (KPC) production were phenotypically detected using plain Mueller Hinton agar plates, and plates impregnated with 5 mM EDTA, 10 mg/mL phenyl boronic acid, and 250 μg/mL cloxacillin (embedded). Temocillin discs were used for the presumptive detection of OXAs. ESBL, carbapenemase, outer membrane protein F (OMPF), and outer membrane protein C (OMPC) genes were detected using polymerase chain...

International Journal of Antimicrobial Agents, 2017

Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug resistance among A. ... more Acinetobacter baumannii is a highly versatile nosocomial pathogen. Multidrug resistance among A. baumannii isolates led to the use of colistin, subsequently giving rise to colistin-resistant strains. In this study, the genetic and phenotypic profiles of two colistin-resistant A. baumannii isolates were investigated. Two A. baumannii isolates were obtained from Patient 1 (C071 and C440) and three isolates were obtained from Patient 2 (C080, C314 and C428). Susceptibility profiles were determined by VITEK2 and Etest. Clonality was determined by RAPD analysis and trilocus multiplex PCR. The pmrCAB operon was sequenced and common carbapenemase genes were screened for by PCR. Doubling times, haemolysis, surface motility, biofilm formation, siderophore production and proteolytic activity were phenotypically determined. Finally, whole-genome sequencing was performed for all five isolates. Isolates C440 and C428 were resistant to colistin and were clonally identical to their sensitive counterparts. The cause of colistin resistance was traced to the previously described P233S mutation in pmrB of C440 and to a novel ΔI19 mutation in pmrB of C428. blaand blafrom the strains of Patients 1 and 2, respectively, were also detected. C440 had attenuated proteolytic activity and was positive for siderophore production compared with C071. No difference in in vitro virulence was detected between isolates C080, C314 and C428. In conclusion, one common and one novel mutation were encountered in pmrB from two distinct colistin-resistant A. baumannii isolates. These mutations caused colistin resistance during therapy in two distinct clones, and only one of them had altered in vitro virulence.

Frontiers in cellular and infection microbiology, 2016

Introduction:Acinetobacter baumannii is a nosocomial pathogen that usually affects critically ill... more Introduction:Acinetobacter baumannii is a nosocomial pathogen that usually affects critically ill patients. High mortality rates have been associated with MDR A. baumannii infections. Carbapenem resistance among these isolates is increasing worldwide and is associated with certain International Clones (ICs) and oxacillinases (OXAs). Moreover, this organism possesses a wide range of virulence factors, whose expression is not yet fully understood. In this study, clinical A. baumannii isolates are characterized in terms of antibiotic resistance, mechanisms of carbapenem resistance, clonality, and virulence. Materials and Methods:A. baumannii clinical isolates (n = 90) where obtained from a tertiary care center in Beirut, Lebanon. API 20NE strips in addition to the amplification of blaOXA-51-like were used for identification. Antibiotic susceptibility testing by disk diffusion was then performed in addition to PCRs for the detection of the most commonly disseminated carbapenemases. Clon...

PLOS ONE, 2017

Introduction Acinetobacter baumannii is a nosocomial pathogen that is showing increasing rates of... more Introduction Acinetobacter baumannii is a nosocomial pathogen that is showing increasing rates of carbapenem resistance. Multi-Drug Resistant (MDR) International Clones (ICs), associated with certain oxacillinases, are being reported globally. This organism also harbors numerous virulence determinants. In this study, we aim at characterizing A. baumannii isolated from a Spanish hospital in terms of antimicrobial susceptibility, clonality, carbapenemase genes harbored, and virulence determinants expressed. Materials and methods Fifty nine clinical bloodstream isolates were obtained from 2009 until 2013. Antimicrobial Susceptibility Testing was performed according to the CLSI guidelines. PFGE and tri-locus PCR typing were then performed in order to determine local and international clonality. PCRs for the detection of common carbapenemases were also performed. Production of hemolysis, biofilms, siderophores, surface motility, and proteolysis were determined phenotypically. Doubling times for selected strains were also calculated. Finally, statistical analysis for detecting associations between these factors was conducted. Results and discussion Carbapenem non-susceptibility was 84.75%, suggesting the immediate need for intervention. PFGE showed the distribution of the majority of the isolates among 7 clusters. Although all three ICs were detected, IC II was predominant at 71.19%. bla OXA-24-like was the most prevalent carbapenemase (62.71%), followed by bla OXA-58-like (13.56%), and bla OXA-23-like (11.86%). Strains pertaining to IC II, and those harboring bla OXA-24-like , were positively associated with α-hemolysis, production of strong biofilms, and siderophore production. Harboring bla OXA-23-like and bla OXA-58-like was associated with attenuated virulence. These

Acinetobacter baumannii is a highly versatile nosocomial pathogen that is implicated in several n... more Acinetobacter baumannii is a highly versatile nosocomial pathogen that is implicated in several nosocomial infections among critically ill patients and results in high mortality rates. These infections include ventilator associated pneumonia, bloodstream infections, urinary tract infections, and burn wound infections. Multi-Drug Resistant (MDR), and especially Carbapenem Resistant Acinetobacter baumannii (CRAB) isolates are also sharply increasing in frequency, forcing clinicians to revert to the use of colistin. This organism has numerous intrinsic resistance mechanisms, virulence determinants, and an elastic genome that allows it to acquire resistance to almost all antimicrobial agents rather easily. The acquisition of oxacillinases (OXAs) is one of the most common mechanisms of acquiring carbapenem resistance. Moreover, some clinically important International Clones (ICs) with MDR profiles are disseminated all over the world. A. baumannii is known to differentially express virule...

Acinetobacter baumannii is a pathogen implicated in infecting critically ill patients. CRAB isola... more Acinetobacter baumannii is a pathogen implicated in infecting critically ill patients. CRAB isolates are increasing in frequency worldwide, forcing clinicians to use colistin. A. baumannii has numerous intrinsic resistance mechanisms, virulence determinants, and can acquire resistance to almost all antibiotics. OXAs among clinically significant ICs are the most common cause of carbapenem resistance. A. baumannii can differentially express virulence determinants and the cause of this is not extensively investigated. In this Doctoral Thesis, the relationship between clonality, virulence, and antimicrobial resistance is investigated in two sets of isolates obtained from hospitals from Spain and Lebanon. Our aim is providing clinicians and infection control specialists with tools that could be used to improve therapy and limit the spread of CRAB isolates; and to better understand the interaction between virulence and antibiotic resistance. Fifty nine clinical A. baumannii isolates were ...