Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Chinese hospitals

Objective: The aim of this study was to investigate the molecular epidemiology and carbapenem resistance mechanisms of Pseudomonas aeruginosa isolated from patients with burns in Azerbaijan, Iran. Method: Pseudomonas aeruginosa was isolated from 38 patients with burns. Disk diffusion and agar dilution methods were used to determine antibiotic susceptibility patterns. The overproduction of AmpC β-lactamase and efflux pumps were detected by phenotypic methods. The presence of carbapenemase-encoding genes was detected by multiplex polymerase chain reaction (PCR). Expression of the OprD gene and MexAB efflux pumps were also evaluated with real-time PCR. Random amplified polymorphic DNA typing (RAPD-PCR) was used for genotyping of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Results: Minimum inhibitory concentration (MIC) assays demonstrated high levels of resistance to all classes of antibiotics except colistin and polymyxin B. The initial screening by carbapenem disks indicated 24 isolates (63.15%) as CRPA. Different mechanisms of carbapenem resistance were observed, including carbapenemase production (8.4%), overexpression of AmpC (25%) and decreased expression of OprD (75%). The overexpression of MexAB efflux pumps was detected in 19 (79.1%) isolates by phenotypic assay or real-time PCR. The resistance to carbapenem was multifactorial in most cases (58.3%). The RAPD genotyping revealed different patterns with nine clusters. Conclusion: According to our results, the prevalence of CRPA is at an alarming level. Our results did not demonstrate an epidemic clone. The most common mechanism of carbapenem resistance was decreased expression of OprD. Therefore, we suggest a reconsideration in the management of CRPA infections of patients in our burn care hospital in Azerbaijan, Iran.

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Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00574-09 ◽

2009 ◽

Vol 53 (11) ◽

pp. 4783-4788 ◽

Cited By ~ 169

Author(s):

José-Manuel Rodríguez-Martínez ◽

Laurent Poirel ◽

Patrice Nordmann

Keyword(s):

Pseudomonas Aeruginosa ◽

Membrane Protein ◽

Molecular Epidemiology ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Mechanisms Of Resistance ◽

Genes Encoding ◽

Imipenem Resistance

ABSTRACT The contributions of different mechanisms of resistance to carbapenems among a collection of imipenem- and meropenem-nonsusceptible Pseudomonas aeruginosa isolates were investigated. This screening included the recently reported extended-spectrum cephalosporinases (ESACs) weakly hydrolyzing carbapenems. Eighty-seven percent of the studied isolates were resistant to imipenem. Genes encoding metallo-β-lactamases or carbapenem-hydrolyzing oxacillinases were not identified. The main mechanism associated with imipenem resistance was the loss of outer membrane protein OprD. Identification of overexpressed ESACs and loss of OprD were observed for 65% of the isolates, all being fully resistant to imipenem. Resistance to meropenem was observed in 78% of the isolates, with all but one also being resistant to imipenem. Overexpression of the MexAB-OprM, MexXY-OprM, or MexCD-OprJ efflux systems was observed in 60% of the isolates, suggesting the contribution of efflux mechanisms in resistance to meropenem. The loss of porin OprD and the overproduction of ESACs were observed in 100% and 92% of the meropenem-resistant isolates, respectively. P. aeruginosa can very often accumulate different resistance mechanisms, including ESAC production, leading to carbapenem resistance.

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High incidence of MDR and XDR Pseudomonas aeruginosa isolates obtained from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz030 ◽

2019 ◽

Vol 74 (5) ◽

pp. 1244-1252 ◽

Cited By ~ 16

Author(s):

Astrid Pérez ◽

Eva Gato ◽

José Pérez-Llarena ◽

Felipe Fernández-Cuenca ◽

María José Gude ◽

...

Keyword(s):

Clinical Trial ◽

Pseudomonas Aeruginosa ◽

Molecular Epidemiology ◽

Carbapenem Resistance ◽

Clonal Diversity ◽

Resistance Mechanisms ◽

Ventilator Associated Pneumonia ◽

Restriction Patterns ◽

High Incidence ◽

Tof Ms

Abstract Objectives To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial. Methods Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST. Results Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235. Conclusions MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.

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Molecular epidemiology of Pseudomonas Aeruginosa

Frontiers in Bioscience ◽

10.2741/speert ◽

2002 ◽

Vol 7 (1-3) ◽

pp. e354 ◽

Cited By ~ 20

Author(s):

David, P. Speert

Keyword(s):

Pseudomonas Aeruginosa ◽

Molecular Epidemiology

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Occurrence of Plasmid-Mediated carbapenem Resistance genes among Pseudomonas aeruginosa isolated from clinical and hospital environmental samples in Al –Nasseryia city, Iraq.

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.sp2.568 ◽

2020 ◽

Vol 12 (sp2) ◽

Keyword(s):

Pseudomonas Aeruginosa ◽

Resistance Genes ◽

Environmental Samples ◽

Carbapenem Resistance

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Faculty Opinions recommendation of Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.729280945.793541414 ◽

2018 ◽

Author(s):

Adam Hill ◽

Kate Regan

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Molecular Epidemiology

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Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

Nature Communications ◽

10.1038/s41467-021-22814-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rachel Wheatley ◽

Julio Diaz Caballero ◽

Natalia Kapel ◽

Fien H. R. de Winter ◽

Pramod Jangir ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

Rapid Evolution ◽

Carbapenem Resistance ◽

Host Immunity ◽

High Definition ◽

Loss Of Resistance ◽

Pseudomonas Aeruginosa Infection ◽

Second Wave

AbstractIt is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

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Prevalence of metallo-β-lactamase genes among Pseudomonas aeruginosa isolated from various clinical samples in China

Journal of Laboratory Medicine ◽

10.1515/labmed-2019-0162 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Wei Wang ◽

Xiaoya Wang

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Susceptibility ◽

Ethylenediaminetetraacetic Acid ◽

Carbapenem Resistance ◽

Opportunistic Pathogen ◽

Detection Methods ◽

Clinical Samples ◽

Routine Practice ◽

Carbapenem Resistant ◽

High Prevalence

AbstractBackgroundPseudomonas aeruginosa is an opportunistic pathogen which is associated with nosocomial infections and causes various diseases including urinary tract infection, pneumonia, soft-tissue infection and sepsis. The emergence of P. aeruginosa-acquired metallo-β-lactamase (MBL) is most worrisome and poses a serious threat during treatment and infection control. The objective of this study was to identify antibiotic susceptibility, phenotypic detection of MBL production and to determine the prevalence of MBL genes in carbapenem-resistant P. aeruginosa isolated from different clinical samples.MethodsA total of 329 non-duplicate P. aeruginosa isolated from various clinical samples from two hospitals in China between September 2017 and March 2019 were included in this study. Phenotypic detection of MBL was performed by the combined detection method using imipenem and imipenem-ethylenediaminetetraacetic acid (EDTA) discs. MBL-encoding genes including blaVIM-1, blaVIM-2, blaIMP-1, blaIMP-2, blaSPM-1, blaSIM, blaNDM-1 and blaGIM were detected by polymerase chain reaction (PCR).ResultsOf the 329 P. aeruginosa, majority of the isolates were resistant to imipenem (77.5%) followed by meropenem (64.7%). Of the 270 P. aeruginosa isolates tested, 149 (55.2%) isolates were found to be positive for MBL detection. Of the different samples, 57.8% (n = 26) of P. aeruginosa isolated from blood were found to be positive for MBL production. Of the various MBL genes, blaIMP-1 (28.2%) was the most predominant gene detected followed by blaVIM-2 (18.8%), blaVIM-1 (16.1%), blaNDM-1 (9.4%), blaIMP-2 (6.7%), blaSIM (6.0%), blaSPM-1 (4.0%) and blaGIM (1.3%) genes.ConclusionsThe high resistance of P. aeruginosa toward imipenem and meropenem and the high prevalence of blaIMP-1 and blaVIM-2 set the alarm on the increasing, perhaps the increased, carbapenem resistance. In addition to routine antibiotic susceptibility testings, our results emphasize the importance of both the phenotypic and genotypic MBL detection methods in routine practice for early detection of carbapenem resistance and to prevent further dissemination of this resistant pathogen.

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Complete Sequence of pOZ176, a 500-Kilobase IncP-2 Plasmid Encoding IMP-9-Mediated Carbapenem Resistance, from Outbreak Isolate Pseudomonas aeruginosa 96

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00423-13 ◽

2013 ◽

Vol 57 (8) ◽

pp. 3775-3782 ◽

Cited By ~ 48

Author(s):

Jianhui Xiong ◽

David C. Alexander ◽

Jennifer H. Ma ◽

Maxime Déraspe ◽

Donald E. Low ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Carbapenem Resistance ◽

Complete Sequence ◽

Open Reading Frames ◽

Content Type ◽

Conserved Sequence ◽

Carbapenem Resistant ◽

Class 1 ◽

Usage Analysis ◽

Type 3

ABSTRACTPseudomonas aeruginosa96 (PA96) was isolated during a multicenter surveillance study in Guangzhou, China, in 2000. Whole-genome sequencing of this outbreak strain facilitated analysis of its IncP-2 carbapenem-resistant plasmid, pOZ176. The plasmid had a length of 500,839 bp and an average percent G+C content of 57%. Of the 618 predicted open reading frames, 65% encode hypothetical proteins. The pOZ176 backbone is not closely related to any plasmids thus far sequenced, but some similarity to pQBR103 ofPseudomonas fluorescensSBW25 was observed. Two multiresistant class 1 integrons and several insertion sequences were identified. TheblaIMP-9-carrying integron containedaacA4→blaIMP-9→aacA4, flanked upstream by Tn21 tnpMRAand downstream by a completetnioperon of Tn402and amermodule, named Tn6016. The second integron carriedaacA4→catB8a→blaOXA-10and was flanked by Tn1403-liketnpRAand asul1-type 3′ conserved sequence (3′-CS), named Tn6217. Other features include three resistance genes similar to those of Tn5, a tellurite resistance operon, and twopiloperons. The replication and maintenance systems exhibit similarity to a genomic island ofRalstonia solanacearumGM1000. Codon usage analysis suggests the recent acquisition ofblaIMP-9. The origins of the integrons on pOZ176 indicated separate horizontal gene transfer events driven by antibiotic selection. The novel mosaic structure of pOZ176 suggests that it is derived from environmental bacteria.

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