Most cited article - PubMed ID 29353076
First report of an Escherichia coli from Lebanon carrying an OXA-181 carbapenemase resistance determinant
INTRODUCTION: In the battle against multidrug-resistant bacterial infections, ceftazidime- avibactam (CZA) stands as a pivotal defense, particularly against carbapenemresistant (CR) Gram-negative pathogens. However, the rise in resistance against this drug poses a significant threat to its effectiveness, highlighting the critical need for in-depth studies about its resistance mechanisms. METHODS: This research focuses on the genomic characterization of CR- and CZA-resistant Escherichia coli (n=26) and Klebsiella pneumoniae (n=34) strains, harboring the blaNDM and/or blaOXA-48-like genes, at a major Lebanese tertiary care medical center, using whole genome sequencing (WGS). RESULTS: Our findings revealed a notable prevalence of blaNDM in all K. pneumoniae strains isolates, with 27 of these also harboring blaOXA-48. On the other hand, E. coli strains predominantly carried the blaNDM-5 gene. Whole genome sequencing (WGS) identified a predominance of ST383 among K. pneumoniae strains, which possessed a multi-replicon IncFIB-IncHI1B plasmid harboring the blaNDM-5. Additionally, various Inc group plasmids in K. pneumoniae across multiple sequence types were found to carry the blaNDM. Similarly, diverse STs of E. coli were observed to carry blaNDM-5 on different plasmids. DISCUSSION: The study underscores NDM carbapenemases as a paramount resistance mechanism in Lebanon,jeopardizing critical last-resort treatments. It also illuminates the role of varied sequence types and mobile genetic elements in the spread of NDM resistance,stressing the urgent need for strategies to mitigate this threat, especially in nosocomial infections.
- Keywords
- Escherichia coli, Klebsiella pneumoniae, ST383, blaNDM-5, carbapenem resistance,
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Azabicyclo Compounds * pharmacology MeSH
- Bacterial Proteins genetics metabolism MeSH
- beta-Lactamases * genetics metabolism MeSH
- Ceftazidime * pharmacology MeSH
- Tertiary Care Centers MeSH
- Carbapenem-Resistant Enterobacteriaceae genetics drug effects isolation & purification MeSH
- Escherichia coli * genetics drug effects MeSH
- Drug Combinations * MeSH
- Genome, Bacterial MeSH
- Carbapenems * pharmacology MeSH
- Klebsiella pneumoniae * genetics drug effects MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial * genetics MeSH
- Plasmids genetics MeSH
- Gene Transfer, Horizontal MeSH
- Whole Genome Sequencing * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Lebanon MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- avibactam, ceftazidime drug combination MeSH Browser
- Azabicyclo Compounds * MeSH
- Bacterial Proteins MeSH
- beta lactamase NDM-5, E coli MeSH Browser
- beta-Lactamases * MeSH
- Ceftazidime * MeSH
- Drug Combinations * MeSH
- Carbapenems * MeSH
Enterobacter spp. and Klebsiella aerogenes are rod-shaped Gram-negative opportunistic pathogens. This study aimed at the molecular and genomic characterization of multidrug resistant Enterobacter spp. and K. aerogenes isolates recovered from hospitalized patients in a tertiary care hospital in Lebanon. A total of 59 Enterobacter spp. clinical isolates consisting of 41 carbapenem-resistant and 18 susceptible by Etest were included in this study. Genotypic identification through whole-genome sequencing (WGS) was performed and confirmed in silico. Resistance and plasmid profiles were studied using ResFinder4.0 and Plasmid-Finder2.1. Multilocus sequence typing (MLST) was used to determine the isolates' clonality. Using the average nucleotide identity (ANI) we identified and confirmed that 47 (80%) isolates were E. hormaechei, 11 (18%) were Klebsiella aerogenes and 1 (2%) was an E. cloacae. Carbapenem-resistance was detected among 41 isolates all showing an MIC90 of ≥ 32 μg/mL for ertapenem, imipenem, and meropenem. blaNDM-1 (58.5%), blaACT-16 (54%), and blaOXA-1 (54%) were the most common detected β-lactamases, while blaCTX-M-15 (68%) was the main detected extended-spectrum β-lactamase (ESBL) encoding gene. Chromosomal ampC, carbapenemase encoding genes, and porin modifications were among the detected carbapenem resistance determinants. The carbapenemase encoding genes were linked to three well-defined plasmid Inc groups, IncFII/IncFIB, IncX3, and IncL. MLST typing revealed the diversity within the studied isolates, with ST114 being the most common among the studied E. hormaechei.: The spread of carbapenem-resistant isolates in clinical settings in Lebanon is a serious challenge. Screening and continuous monitoring through WGS analysis could effectively limit the dissemination of drug-resistant isolates in hospitalized patients. IMPORTANCE Drug resistance is an increasing global public health threat that involves most disease-causing organisms and antimicrobial drugs. Drug-resistant organisms spread in health care settings, and resistance to multiple drugs is common. Our study demonstrated the mechanisms leading to resistance against the last resort antimicrobial agents among members of the Enterobacteriaceae family. The spread of carbapenem-resistant bacteria in clinical settings is a serious challenge. Screening and continuous monitoring could effectively limit the dissemination of drug-resistant isolates in hospitalized patients.
- Keywords
- ESBL, Enterobacter, Klebsiella aerogenes, multidrug resistance, β-lactamases,
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Bacterial Proteins genetics MeSH
- beta-Lactamases genetics MeSH
- Enterobacter aerogenes * genetics MeSH
- Enterobacter genetics MeSH
- Carbapenems pharmacology MeSH
- Klebsiella pneumoniae genetics MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Multilocus Sequence Typing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Lebanon MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- Bacterial Proteins MeSH
- beta-Lactamases MeSH
- Carbapenems MeSH
Aim of this study was to genetically characterize two carbapenemase-producing Escherichia coli strains obtained from a pediatric patient affected by diarrhea, expressing OXA-181 and/or NDM-5 type enzymes. The above microorganisms were collected in the same Desenzano hospital (Northern Italy) where the bla NDM- 5 gene was detected for the first time in Italy 3 years ago. One strain (5P), belonged to sequence type ST405/ST477 (according to Pasture/Oxford schemes) and serotype O102:H6. It was characterized by a 130562 bp multi-replicon plasmid IncFII/IncFIA/IncFIB (pVSI_NDM-5) enclosing two main antibiotic resistance islands: (i) ARI-I, 10030 bp in size, carried genes coding for β-lactam- (bla OXA- 1, bla CTX-M- 15), fluoroquinolone/aminoglycoside- (aac(6')-lb-cr) and phenicol- resistance (catB3), (ii) ARI-II, 15326 bp in size, carried genes coding for sulfonamide- (sul1), β-lactam- (bla NDM- 5, bla TEM- 1 B), phenicol- (catB3), trimethoprim- (dfrA17), antiseptic- (qacEΔ1), and aminoglycoside- (aadA5, rmtB) resistance. The other isolate (5M), belonged to sequence type ST2659/ST759 and serotype O50/02:H18, and carried four plasmids: a 153866 bp multi-replicon IncFII/IncFIA/IncFIB (pISV_IncFII_NDM-5), an 89866 bp IncI1 plasmid, a 51480 bp IncX3 plasmid (pISV_IncX3_OXA181), and a 41143 bp IncI plasmid (pISV_IncI_CMY-42). pISV_IncFII_NDM-5 carried two main antibiotic resistance islands: (i) ARI-III, 12220 bp in size, carried genes coding for β-lactam- (bla OXA- 1), fluoroquinolone/aminoglycoside- (aac(6')-lb-cr), tetracycline- (tet(B)) and phenicol- resistance (catB3, catA1), and ii) ARI-IV, 26527 bp in size, carried determinants coding for macrolide- (erm(B), mph(A)), sulfonamide- (sul1), beta-lactam- (bla NDM- 5, bla TEM- 1 B), trimethoprim- (dfrA14, dfrA12), antiseptic- (qacEΔ1), and aminoglycoside- resistance (aadA5). pISV_IncI_CMY-42 harbored the bla CMY- 42 gene coding for beta-lactam resistance, pISV_IncX3_OXA181 harbored genes encoding fluoroquinolone- (qnrS1) and beta-lactams- resistance (bla OXA- 181). In conclusion, the detection of two different NDM-5 E. coli strains from a pediatric patient with a history of travel to the Far East countries strongly highlight an increasing trend and risk of importation from such areas.
