Dataset Information

The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal.

ABSTRACT: Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed by the disk diffusion method. Antibiotic-resistance genes for class A beta-lactamases, carbapenemases, and plasmid resistance to colistin resistance (mcr-1-8) were screened by RT-PCR. (2) Results: The 240 enterobacteria were composed of: Escherichia coli (60.83%), Klebsiella pneumoniae (21.67%), Enterobacter cloacae (13.75%), Citrobacter freundii (2.08%), Serratia marcescens (0.83%), Klebsiella aerogenes (0.42%), and Proteus mirabilis (0.42%). Class A beta-lactamase genes were found in 229 isolates (70.41% bla_TEM, 37.5% bla_SHV, 83.75% bla_CTX-A, and 0.42% bla_CTX-B). The carbapenemase genes bla_OXA-48 and bla_NDM were found in 25 isolates, including 14 isolates with bla_OXA-48, 13 isolates with bla_NDM, and 2 isolates with both genes simultaneously. The mcr-8 gene was found in one isolate of E. cloacae. (3) Conclusions: The epidemiology of antibiotic-resistance genes in enterobacteria in Senegal shows the emergence of CPEs. This phenomenon is worrying, and rigorous surveillance is necessary to avoid further spread.

SUBMITTER: Sarr H

PROVIDER: S-EPMC10459028 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal.

Sarr Habibou H Niang Aissatou Ahmet AA Diop Amadou A Mediannikov Oleg O Zerrouki Hanane H Diene Seydina M SM Lo Seynabou S Dia Mouhamadou Lamine ML Sow Ahmad Iyane AI Fenollar Florence F Rolain Jean-Marc JM Hadjadj Linda L

Pathogens (Basel, Switzerland) 20230726 8

Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed b ...[more]

PMID: 37623934

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Project description:BackgroundWith an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.MethodsPatients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.ResultsTwenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.ConclusionsColistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Project description:In recent years, extended ESBL and carbapenemase producing Gram negative bacteria have become widespread in hospitals, community settings and the environment. This has been triggered by the few therapeutic options left when infections with these multi-drug resistant organisms occur. The emergence of resistance to colistin, the last therapeutic option against carbapenem-resistant bacteria, worsened the situation. Recently, animals were regarded as potent antimicrobial reservoir and a possible source of infection to humans. Enteric Gram negative bacteria in animals can be easily transmitted to humans by direct contact or indirectly through the handling and consumption of undercooked/uncooked animal products. In the Mediterranean basin, little is known about the current overall epidemiology of multi-drug resistant bacteria in livestock, companion, and domestic animals. This review describes the current epidemiology of ESBL, carbapenemase producers and colistin resistant bacteria of animal origin in this region of the world. The CTX-M group 1 seems to prevail in animals in this area, followed by SHV-12 and CTX-M group 9. The dissemination of carbapenemase producers and colistin resistance remains low. Isolated multi-drug resistant bacteria were often co-resistant to non-beta-lactam antibiotics, frequently used in veterinary medicine as treatment, growth promoters, prophylaxis and in human medicine for therapeutic purposes. Antibiotics used in veterinary medicine in this area include mainly tetracycline, aminoglycosides, fluoroquinolones, and polymyxins. Indeed, it appears that the emergence of ESBL and carbapenemase producers in animals is not related to the use of beta-lactam antibiotics but is, rather, due to the co-selective pressure applied by the over usage of non-beta-lactams. The level of antibiotic consumption in animals should be, therefore, re-considered in the Mediterranean area especially in North Africa and western Asia where no accurate data are available about the level of antibiotic consumption in animals.

Project description:BackgroundPneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.MethodsThe OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure.ResultsBetween 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively.ConclusionsCombination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Project description:The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant Klebsiella pneumoniae isolates from Pakistan. These clinical isolates represented five sequence types: ST11 (n = 3 isolates), ST14 (n = 3), ST15 (n = 1), ST101 (n = 2), and ST307 (n = 1). Resistance profiles against 25 clinically-relevant antimicrobials were determined by broth microdilution; resistant phenotypes were observed for at least 15 of the 25 antibiotics tested in all isolates except one. Specifically, 8/10 isolates were carbapenem-resistant and 7/10 isolates were colistin-resistant. The blaNDM-1 and blaOXA-48 carbapenemase genes were present in 7/10 and 5/10 isolates, respectively; including 2 isolates carrying both genes. No plasmid-mediated determinants for colistin resistance (e.g. mcr) were detected, but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were observed. A blaOXA-48-carrying IncL/M-type plasmid was found in all blaOXA-48-positive isolates. The application of WGS to molecular epidemiology and surveillance studies, as exemplified here, will provide both a more complete understanding of the global distribution of MDR isolates and a robust surveillance tool useful for detecting emerging threats to public health.

Dataset Information

The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal.

Publications

The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal.

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