Emergence of colistin resistance in Pseudomonas aeruginosa ST235 clone in South Korea

Wi, Yu Mi; Choi, Ji-Young; Lee, Ji-Young; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon; Ko, Kwan Soo

doi:10.1016/j.ijantimicag.2017.01.023

Cited by 36 publications

(30 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the production of carbapenemases, mainly Ambler class B metallo-␤-lactamases (MBLs), is noteworthy in P. aeruginosa as a mechanism of carbapenem resistance (4), the presence of non-carbapenemase-mediated carbapenem resistance is far more common (5)(6)(7). Loss of outer membrane porin D (OprD) function in conjunction with another mechanism, such as overexpression of ampC or overexpression of efflux pumps, is the major determinant of resistance to carbapenems (5)(6)(7).…”

mentioning

confidence: 99%

Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms

Greenwood‐Quaintance

Schuetz

et al. 2018

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Although carbapenems are effective for treating serious multidrug-resistant infections, carbapenem-resistant (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemase-producing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168-172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for ,, ,, , and by PCR. In the prior study, expression of ,, and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 non-carbapenemase-producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillin-tazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased and increased expression (5.1% versus 25.6%, = 0.025, and 4.3% versus 34.8%, = 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased and increased expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.

show abstract

mentioning

confidence: 99%

Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms

Greenwood‐Quaintance

Schuetz

et al. 2018

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…[6][7][8] The emergence MDR P. aeruginosa that are resistant to carbapenems, aminoglycosides and fluoroquinolones was followed by reports of colistin-only sensitive isolates 9 and, more recently, of colistin resistance in carbapenem nonsusceptible isolates. 10 All have a major impact on medical practice due to the few remaining treatment options. Interestingly, these reports coincide with multi-locus sequence type (ST) 235, [9][10][11] the predominant global epidemic clone.…”

Section: Introductionmentioning

confidence: 99%

“…10 All have a major impact on medical practice due to the few remaining treatment options. Interestingly, these reports coincide with multi-locus sequence type (ST) 235, [9][10][11] the predominant global epidemic clone. Several metalloβ-lactamase (MBL) genes have been identified in ST235 P. aeruginosa isolates from Asian countries, namely VIM and IMP, and usually associated with integrons carrying multiple resistance determinants.…”

Section: Introductionmentioning

confidence: 99%

Genomic Surveillance ofPseudomonas aeruginosain the Philippines from 2013-2014

Chilam

Argimón²,

Limas

et al. 2020

Preprint

View full text Add to dashboard Cite

Pseudomonas aeruginosa is an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized.We sequenced the whole genomes of 176 P. aeruginosa isolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-β-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population of P. aeruginosa in the Philippines was diverse, with clonal expansions of XDR genomes belonging to multilocus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, including blaVIM-2, with differences in gene composition and synteny to other P. aeruginosa class 1 integrons described before.We produced the first comprehensive genomic survey of P. aeruginosa in the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.

show abstract

“…In the periplasm, an overproduced AmpC cephalosporinase can inactivate a broad range of β‐lactam antibiotics while the Mex‐Opr family of RND efflux pumps removes antibiotics from the periplasm, inner membrane, and cytosol (Wolter, Black, Lister, & Hanson, ). The carbapenems (doripenem, meropenem, and imipenem) in addition to colistin are considered last resort antibiotics for the treatment of P. aeruginosa infections (Manohar, Babu, Bozdogan, & Ramesh, ; Wi et al, ). However, mutations that result in truncations in OprD have been associated with imipenem resistance, and when coupled with increased expression of genes encoding the MexAB‐OprM efflux pump lead to decreased susceptibility to meropenem and doripenem (Wolter et al, ).…”

Section: Introductionmentioning

confidence: 99%

lptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa

et al. 2019

View full text Add to dashboard Cite

PurposeIn the lungs of cystic fibrosis patients, Pseudomonas aeruginosa is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a P. aeruginosa clinical isolate, PA34.MethodsPA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid‐log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem‐resistant colonies hypersusceptible to non‐carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT‐rtPCR and OprD production by SDS‐PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem‐resistant clinical isolates hypersusceptible to non‐carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ‐Emerald stain.ResultsIsogenic mutants showed 4‐ to 8‐fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (≥4‐fold MIC decrease) to aminoglycosides, fluoroquinolones, and non‐carbapenem β‐lactams. Expression of ampC or mex‐opr efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non‐synonymous mutations in LptF or LptG were observed in 6/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.ConclusionEvaluation of hypersusceptible mutants identified the association between lptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.

show abstract

Emergence of colistin resistance in Pseudomonas aeruginosa ST235 clone in South Korea

Cited by 36 publications

References 17 publications

Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms

Activity of Ceftolozane-Tazobactam against Carbapenem-Resistant, Non-Carbapenemase-Producing Pseudomonas aeruginosa and Associated Resistance Mechanisms

Genomic Surveillance ofPseudomonas aeruginosain the Philippines from 2013-2014

lptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa

Contact Info

Product

Resources

About