scholarly journals Colistin Heteroresistance among Extended Spectrum β-lactamases-Producing Klebsiella pneumoniae

2020 ◽  
Vol 8 (9) ◽  
pp. 1279
Author(s):  
Felipe Morales-León ◽  
Celia A. Lima ◽  
Gerardo González-Rocha ◽  
Andrés Opazo-Capurro ◽  
Helia Bello-Toledo
Keyword(s):  
Klebsiella Pneumoniae ◽  
Population Analysis ◽  
Global Regulator ◽  
Extended Spectrum ◽  
Regulatory Systems ◽  
Two Component ◽  
Pap Method ◽  
Susceptibility Tests ◽  
Sequence Types ◽  
First Descriptions

Colistin-heteroresistant (CST-HR) Enterobacterales isolates have been identified recently, challenging the clinical laboratories since routine susceptibility tests fail to detect this phenotype. In this work we describe the first CST-HR phenotype in extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolates in South America. Additionally, we determine the genomic mechanisms of colistin heteroresistance in these strains. The CST-HR phenotype was analyzed by the population analysis profile (PAP) method, and mutations associated with this phenotype were determined by whole-genome sequencing (WGS) and the local BLAST+ DB tool. As a result, 8/60 isolates were classified as CST-HR according to the PAP method. From WGS, we determined that the CST-HR isolates belong to three different Sequence Types (STs) and four K-loci: ST11 (KL15 and KL81), ST25 (KL2), and ST1161 (KL19). We identified diverse mutations in the two-component regulatory systems PmrAB and PhoPQ, as well as a disruption of the mgrB global regulator mediated by IS1-like and IS-5-like elements, which could confer resistance to CST in CST-HR and ESBL-producing isolates. These are the first descriptions in Chile of CST-HR in ESBL-producing K. pneumoniae isolates. The emergence of these isolates could have a major impact on the effectiveness of colistin as a “last resort” against these isolates, thus jeopardizing current antibiotic alternatives; therefore, it is important to consider the epidemiology of the CST-HR phenotype.

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

2020 ◽  
Author(s):  
Karen Tan ◽  
James Nguyen ◽  
Kevin Nguyen ◽  
Holly K Huse ◽  
Paul H Nieberg ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Hospital Admissions ◽  
Population Analysis ◽  
Carbapenem Resistance ◽  
Disc Diffusion ◽  
First Line Therapy ◽  
Potential Activity ◽  
Pap Method ◽  
Antibiotic Agents

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.

scholarly journals Colistin Heteroresistance in Klebsiella Pneumoniae Isolates and Diverse Mutations of PmrAB and PhoPQ in Resistant Subpopulations

2019 ◽  
Vol 8 (9) ◽  
pp. 1444 ◽  
Author(s):  
Hae Suk Cheong ◽  
So Yeon Kim ◽  
Yu Mi Wi ◽  
Kyong Ran Peck ◽  
Kwan Soo Ko
Keyword(s):  
Klebsiella Pneumoniae ◽  
Population Analysis ◽  
Test Strip ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Disk Diffusion ◽  
Regulatory Systems ◽  
Disk Diffusion Testing ◽  
Time Kill

Heteroresistance may pose a threat to the prognosis of patients following colistin treatment. We investigated colistin heteroresistance in Klebsiella pneumoniae isolates from South Korea. Among 252 K. pneumoniae blood isolates, 231 were susceptible to polymyxins. Heteroresistance to colistin was determined using population analysis profiles, disk diffusion assays, and E-test strip tests for the susceptible isolates. As a result, we identified three colistin-heteroresistant K. pneumoniae isolates belonging to separate clones (ST11, ST461, and ST3217) by multilocus sequence typing analysis. Two colistin-resistant subpopulations were selected from each heteroresistant isolate in either disk diffusion testing or E-testing. Two resistant subpopulations from the same isolate exhibited different amino acid substitutions in the two-component regulatory systems PmrAB and PhoPQ. An in vitro time–kill assay showed that meropenem combined with colistin had a 1× minimum inhibitory concentration bactericidal effect against a multidrug-resistant, colistin-heteroresistant isolate.

scholarly journals Comparative Population Analysis of Klebsiella pneumoniae Strains with Extended-Spectrum β-Lactamases Colonizing Patients in Rehabilitation Centers in Four Countries

2013 ◽  
Vol 57 (4) ◽  
pp. 1992-1997 ◽  
Author(s):  
A. Baraniak ◽  
R. Izdebski ◽  
J. Fiett ◽  
E. Sadowy ◽  
A. Adler ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Klebsiella Pneumoniae ◽  
Population Analysis ◽  
International Project ◽  
High Genetic Diversity ◽  
Content Type ◽  
Rehabilitation Centers ◽  
Extended Spectrum ◽  
Comparative Population

ABSTRACTThe international project MOSAR was conducted in five rehabilitation centers; patients were screened for rectal carriage of extended-spectrum β-lactamase (ESBL)-producing members of theEnterobacteriaceae. Among 229Klebsiella pneumoniaeisolates, four clonal groups (CG) or complexes (CC) prevailed: CG17 in France, CG101 in Italy, CG15 in Spain, and CC147 in Israel. ESBLs, mainly CTX-Ms, were produced by 226 isolates; three isolates expressed AmpC-like cephalosporinases. High genetic diversity ofK. pneumoniaepopulations was observed, with specific characteristics at each center.

scholarly journals Outbreak of bloodstream infection with extendedspectrum ß-lactamase-producing Klebsiella pneumoniae at a Teaching Hospital

2015 ◽  
Vol 34 (3) ◽  
pp. 230-232
Author(s):  
NP Senanayake ◽  
L Karunanayake
Keyword(s):  
Blood Culture ◽  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Neonatal Intensive Care ◽  
Clinical Laboratory ◽  
Blood Stream Infection ◽  
Blood Stream ◽  
Extended Spectrum ◽  
Susceptibility Tests ◽  
Rational Use Of Antibiotics

Introduction: Klebsiella pneumoniae (K. pneumoniae) is an important hospital-acquired pathogen causing severe infections in neonatal units. Several outbreaks of infection caused by multi-drug-resistant K. pneumoniae isolates have been widely reported among neonates. The aim is to investigate an outbreak of blood stream infection caused by Extended-Spectrum ß-Lactamases (ESBL) producing K.pneumoniae in a Neonatal Intensive Care Unit (NICU) at Teaching Hospital Kandy, Sri Lanka. Materials and Methods: Blood culture samples were collected from the neonates on admission to the NICU and 2 to 3 days later on clinical suspicion of blood stream infection. The blood culture samples were processed according to the standard methods and the antibiotic susceptibility tests were carried out as per Clinical Laboratory Standards Institute (CLSI) guidelines. Results: Of the 140 blood cultures 36 were identified as Extended-Spectrum ß-Lactamases (ESBL) producing K.pneumoniae. All the isolates were susceptible to ciprofloxacin, amikacin, netilmicin, imipenem and meropenem. Twenty eight of the 36 patients responded to treatment with a combination of amikacin and meropenem. Conclusion: ESBL producing K.pneumoniae was responsible for this outbreak at the NICU. Knowing the susceptibility patterns of clinical isolates will allow the rational use of antibiotics, which is important in the treatment of infections with multi-drugresistant bacteria. J Nepal Paediatr Soc 2014;34(3):230-232 DOI: http://dx.doi.org/10.3126/jnps.v34i3.10459

scholarly journals Detection in two hospitals of transferable ceftazidime-avibactam resistance in Klebsiella pneumoniae due to a novel VEB β-lactamase variant with a Lys234Arg substitution, Greece, 2019

2020 ◽  
Vol 25 (2) ◽  
Author(s):  
E. Voulgari ◽  
S.D. Kotsakis ◽  
P. Giannopoulou ◽  
E. Perivolioti ◽  
L.S. Tzouvelekis ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Conjugal Transfer ◽  
Extended Spectrum ◽  
Greek Hospitals ◽  
Sequence Types

Two ceftazidime-avibactam (CAZ-AVI)-resistant Klebsiella pneumoniae carbapenemase (KPC)-positive K. pneumoniae strains, including one pandrug resistant, were isolated in 2019 from two Greek hospitals. The strains were sequence types (ST)s 258 and 147 and both harboured similar self-transmissible IncA/C2 plasmids encoding a novel Lys234Arg variant of the Vietnamese extended-spectrum β-lactamase (VEB)-1, not inhibited by AVI (VEB-25). Conjugal transfer of VEB-25-encoding plasmids to Escherichia coli yielded CAZ-AVI-resistant clones, supporting that VEB-25 is directly linked to the derived phenotype.

scholarly journals Effects of the Global Regulator CsrA on the BarA/UvrY Two-Component Signaling System

2014 ◽  
Vol 197 (5) ◽  
pp. 983-991 ◽  
Author(s):  
Martha I. Camacho ◽  
Adrian F. Alvarez ◽  
Ricardo Gonzalez Chavez ◽  
Tony Romeo ◽  
Enrique Merino ◽  
...  
Keyword(s):  
Small Rnas ◽  
Feedback Loop ◽  
Kinase Activity ◽  
Rna Binding ◽  
Response Regulator ◽  
Global Regulator ◽  
Regulatory Systems ◽  
Two Component ◽  
Two Component Signal Transduction ◽  
Cognate Response Regulator

The hybrid sensor kinase BarA and its cognate response regulator UvrY, members of the two-component signal transduction family, activate transcription of CsrB and CsrC noncoding RNAs. These two small RNAs act by sequestering the RNA binding protein CsrA, which posttranscriptionally regulates translation and/or stability of its target mRNAs. Here, we provide evidence that CsrA positively affects, although indirectly,uvrYexpression, at both the transcriptional and translational levels. We also demonstrate that CsrA is required for properly switching BarA from its phosphatase to its kinase activity. Thus, the existence of a feedback loop mechanism that involves the Csr and BarA/UvrY global regulatory systems is exposed.

scholarly journals Sequence Types 235, 111, and 132 Predominate among Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates in Croatia

2014 ◽  
Vol 58 (10) ◽  
pp. 6277-6283 ◽  
Author(s):  
Marija Guzvinec ◽  
Radosław Izdebski ◽  
Iva Butic ◽  
Marko Jelic ◽  
Maja Abram ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Analysis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Content Type ◽  
Extended Spectrum ◽  
Sequence Types

ABSTRACTA population analysis of 103 multidrug-resistantPseudomonas aeruginosaisolates from Croatian hospitals was performed. Twelve sequence types (STs) were identified, with a predominance of international clones ST235 (serotype O11 [41%]), ST111 (serotype O12 [15%]), and ST132 (serotype O6 [11%]). Overexpression of the natural AmpC cephalosporinase was common (42%), but only a few ST235 or ST111 isolates produced VIM-1 or VIM-2 metallo-β-lactamases or PER-1 or GES-7 extended-spectrum β-lactamases.

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