Prevalence of the carbapenem-heteroresistant phenotype among ESBL-producing Escherichia coli and Klebsiella pneumoniae clinical isolates

Author(s):  
Karen Tan ◽  
James Nguyen ◽  
Kevin Nguyen ◽  
Holly K Huse ◽  
Paul H Nieberg ◽  
...  

Abstract Objectives Carbapenem-heteroresistant (cHR) Enterobacteriaceae strains have been reported worldwide; however, the prevalence among clinical ESBL-producing Enterobacteriaceae isolates obtained from patients with repeated hospital admissions remains largely unknown. Methods Heteroresistance was screened by disc diffusion and confirmed by a modified population analysis profiling (PAP) method against ertapenem, imipenem, meropenem and ceftolozane/tazobactam. MIC testing was performed by broth microdilution against carbapenems and a panel of agents with potential activity against ESBL-producing strains. Results One hundred and seventy-three ESBL-producing meropenem-susceptible Escherichia coli and Klebsiella pneumoniae isolates were selected for testing. A total of 519 bacteria/carbapenem combinations were screened by disc diffusion; 84 combinations were identified as cHR. Modified PAP confirmed 70 bacteria/carbapenem combinations as heteroresistant; most (63%, 44/70) confirmed cHR colonies grew within the ertapenem zone of inhibition, followed by imipenem (30%, 21/70), then meropenem (7%, 5/70). In total, one-third of the unique patient isolates (32%, 55/173) were identified as being heteroresistant to at least one carbapenem; of those patients, 16% (9/55) had a carbapenem-non-susceptible isolate on subsequent visits. Only two cHR isolates screened positive for ceftolozane/tazobactam heteroresistance (1%, 2/173), of which one was confirmed heteroresistant by modified PAP. cHR isolates were more likely to be collected from a non-urinary source (e.g. respiratory) compared with non-cHR isolates (31% versus 19%, P = 0.02). MIC distributions of all tested antibiotic agents did not differ between non-cHR and cHR isolates. Conclusions Our findings raise concerns for the continued use of carbapenems as first-line therapy for ESBL infections and for the potential selection for strains with full carbapenem resistance.

2019 ◽  
Vol 66 (3) ◽  
pp. 367-376
Author(s):  
Namita Jaggi ◽  
Nirupama Chatterjee ◽  
Vyoma Singh ◽  
Santosh Kumar Giri ◽  
Priyambada Dwivedi ◽  
...  

2014 ◽  
Vol 63 (3) ◽  
pp. 367-370 ◽  
Author(s):  
Shougang Kuai ◽  
Haifeng Shao ◽  
Lihua Huang ◽  
Hao Pei ◽  
Zhonghua Lu ◽  
...  

This study was conducted to analyse the presence of a plasmid-mediated carbapenem resistance mechanism in a clinical Enterobacter aerogenes isolate from a patient from Jiangsu province, People’s Republic of China. PCR and sequencing confirmed that the isolate harboured Klebsiella pneumoniae carbapenemase (KPC)-2, DHA-1 and TEM-1 β-lactamase genes. Both the KPC-2 and DHA-1 genes were transferred to Escherichia coli C600 by transconjugation, and Southern blotting confirmed that these two genes were located on the same plasmid, which was of approximately 56 kb in size. The Enterobacter aerogenes isolate was resistant to carbapenems and other tested antimicrobial agents. The Escherichia coli transconjugant showed reduced susceptibility but not resistance to carbapenems and other β-lactams, indicating the presence of another, possibly permeability-related, resistance mechanism in the clinical isolate.


2008 ◽  
Vol 52 (6) ◽  
pp. 2014-2018 ◽  
Author(s):  
Jia Chang Cai ◽  
Hong Wei Zhou ◽  
Rong Zhang ◽  
Gong-Xiang Chen

ABSTRACT Twenty-one Serratia marcescens, ten Klebsiella pneumoniae, and one Escherichia coli isolate with carbapenem resistance or reduced carbapenem susceptibility were recovered from intensive care units (ICUs) in our hospital. Enterobacterial repetitive intergenic consensus-PCR and pulsed-field gel electrophoresis demonstrated that all the S. marcescens isolates belonged to a clonal strain and the 10 K. pneumoniae isolates were indistinguishable or closely related to each other. The MICs of imipenem, meropenem, and ertapenem for all isolates were 2 to 8 μg/ml, except for K. pneumoniae K10 (MICs of 128, 256, and >256 μg/ml). Isoelectric focusing, PCRs, and DNA sequencing indicated that all S. marcescens isolates produced KPC-2 and a β-lactamase with a pI of 6.5. All K. pneumoniae isolates produced TEM-1, KPC-2, CTX-M-14, and a β-lactamase with a pI of 7.3. The E. coli E1 isolate produced KPC-2, CTX-M-15, and a β-lactamase with a pI of 7.3. Conjugation studies with E. coli (EC600) resulted in the transfer of reduced carbapenem susceptibility compared to that of the original isolates, and only the bla KPC-2 gene was detected in E. coli transconjugants. Plasmid restriction analysis showed identical restriction patterns among all E. coli transconjugants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ompK35/36 gene sequence analysis of outer membrane proteins revealed that K. pneumoniae K10 failed to express OmpK36, because of insertional inactivation by an insertion sequence ISEcp1. All these results indicate that KPC-2-producing S. marcescens, K. pneumoniae, and E. coli isolates emerged in ICUs in our hospital. KPC-2 combined with porin deficiency results in high-level carbapenem resistance in K. pneumoniae. The same bla KPC-2-encoding plasmid was spread among the three different genera.


2020 ◽  
Author(s):  
Samuel Lipworth ◽  
Karina-Doris Vihta ◽  
Kevin K Chau ◽  
James Kavanagh ◽  
Timothy Davies ◽  
...  

The incidence of bloodstream infections (BSIs) caused by Enterobacteriaceae (e.g. Escherichia coli, Klebsiella pneumoniae) continues to increase globally and the threat of untreatable disease is substantial1. Prophylactic vaccines represent an alternative approach to combating antimicrobial resistance (AMR) by reducing antibiotic usage and preventing infections caused by AMR-associated strains. To investigate their potential utility, we performed in silico serotyping on 4035 E. coli/K. pneumoniae BSI from population-level surveillance in Oxfordshire (2008-2018) in addition to 3678 isolates from previous studies. Most infections, including those associated with AMR, were caused by isolates with a small subset of O-antigens, with no evidence that the proportion of BSIs caused by these changed significantly over time. O-antigen targeted vaccines might therefore be useful in reducing the significant morbidity and mortality2 associated with BSIs. Vaccines may also have a role in preventing the spread of carbapenem resistance genes into common serotypes associated with community-onset disease.


2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.


1982 ◽  
Vol 3 (3) ◽  
pp. 230-237 ◽  
Author(s):  
Patrick R. Murray ◽  
Jacquelyn R. Zeitinger ◽  
Donald J. Krogstad

AbstractWe retested 2,181 bacteria-antibiotic combinations with the Kirby-Bauer disc-diffusion technique and found interpretive changes with 120 (5.5%). Most changes (101 of 120) were single steps (i.e. from R to I, I to R or S, or S to I). Of the 19 remaining, 10 of them were from R to Sand nine from S to R. These changes were significantly more frequent for combinations with zone diameters clustered near interpretive breakpoints (within 2mm) than for other combinations, and there was a linear relationship between decreased reproducibility and increased clustering near interpretive breakpoints.Based on an analysis of all susceptibility testing results performed in 1978, combinations most commonly clustered near interpretive breakpoints included: Ampicillin with Klebsiella pneumoniae; erythromycin with enterococci; chloramphenicol with Serratia marcescens; gentamicin with Pseudomonas aeruginosa and enterocci; and tetracycline with Enterobacter spp., Escherichia coli, and K. pneumoniae.


Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1551
Author(s):  
Uthaibhorn Singkham-in ◽  
Netchanok Muhummudaree ◽  
Tanittha Chatsuwan

Carbapenem-resistant Klebsiella pneumoniae has globally emerged as an urgent threat leading to the limitation for treatment. K. pneumoniae carrying blaOXA-48, which plays a broad magnitude of carbapenem susceptibility, is widely concerned. This study aimed to characterize related carbapenem resistance mechanisms and forage for new antibiotic combinations to combat blaOXA-48-carrying K. pneumoniae. Among nine isolates, there were two major clones and a singleton identified by ERIC-PCR. Most isolates were resistant to ertapenem (MIC range: 2–>256 mg/L), but two isolates were susceptible to imipenem and meropenem (MIC range: 0.5–1 mg/L). All blaOXA-48-carrying plasmids conferred carbapenem resistance in Escherichia coli transformants. Two ertapenem-susceptible isolates carried both outer membrane proteins (OMPs), OmpK35 and OmpK36. Lack of at least an OMP was present in imipenem-resistant isolates. We evaluated the in vitro activity of an overlooked antibiotic, azithromycin, in combination with other antibiotics. Remarkably, azithromycin exhibited synergism with colistin and fosfomycin by 88.89% and 77.78%, respectively. Bacterial regrowth occurred after exposure to colistin or azithromycin alone. Interestingly, most isolates were killed, reaching synergism by this combination. In conclusion, the combination of azithromycin and colistin may be an alternative strategy in dealing with blaOXA-48-carrying K. pneumoniae infection during a recent shortage of newly effective antibiotic development.


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