Dataset Information

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

ABSTRACT: Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible Pseudomonas aeruginosa (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmission dynamics of CNPA strains and to characterize their resistome. We found that the number of CNPA transmissions and acquisitions by patients was highly variable over time but that, overall, the rates were not significantly reduced by the intervention. Environmental sources were involved in these transmissions and acquisitions. Four high-risk international CNPA clones (ST235, ST823, ST357, and ST446) dominated, but the distribution of these clones changed significantly after the intervention was implemented. Using resistome analysis, carbapenem resistance was explained by the presence of various carbapenemase-encoding genes (bla GES-5, bla VIM-2-8, and bla IMP-1-7-43) and by mutations within the porin OprD. Our results reveal for the first time the dynamics of P. aeruginosa antimicrobial resistance (AMR) profiles in Indonesia and additionally show the utility of WGS in combination with clinical data to evaluate the impact of an infection control intervention. (This study has been registered at www.trialregister.nl under registration no. NTR5541).IMPORTANCE In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between ICUs, before and after an infection control intervention. Our data show the importance of the broad dissemination of the internationally recognized CNPA clones, the relevance of environmental reservoirs, and the mixed effects of the implemented intervention; it led to a profound change in the clonal make-up of CNPA, but it did not reduce the patients' risk of CNPA acquisitions. Thus, CNPA epidemiology in Indonesian ICUs is part of a global expansion of multiple CNPA clones that remains difficult to control by infection prevention measures.

SUBMITTER: Pelegrin AC

PROVIDER: S-EPMC6851282 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

Pelegrin Andreu Coello AC Saharman Yulia Rosa YR Griffon Aurélien A Palmieri Mattia M Mirande Caroline C Karuniawati Anis A Sedono Rudyanto R Aditianingsih Dita D Goessens Wil H F WHF van Belkum Alex A Verbrugh Henri A HA Klaassen Corné H W CHW Severin Juliëtte A JA

mBio 20191112 6

Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible <i>Pseudomonas aeruginosa</i> (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmiss ...[more]

PMID: 31719179

Similar Datasets

Project description:Background:Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex have emerged worldwide, but the epidemiology in Indonesian hospitals has not been studied. Methods:A prospective observational study was performed on the intensive care units (ICUs) of the national referral hospital in Jakarta-Indonesia, in 2013 and 2014. All consecutive adult patients admitted and hospitalized for >48 h in ICUs were included. Basic and clinical data at admission were recorded. Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex from clinical cultures and standardized screening were included. Environmental niches and healthcare workers (HCWs) were also screened. PCR was used to detect carbapenemase genes, and Raman spectroscopy as well as multilocus sequence typing (MLST) for typing. Results:Of 412 included patients, 69 (16.7%) carried carbapenem-nonsusceptible A. baumannii-calcoaceticus complex on admission, and 89 (25.9%) became positive during ICU stay. The acquisition rate was 43 per 1000 patient-days at risk. Six isolates were cultured from environment and one from a HCW. Acquisition of carbapenem-nonsusceptible A. baumannii-calcoaceticus complex was associated with longer ICU stay (median interquartile range [IQR]: 11 days [5-18], adjusted hazard ratio [aHR]: 2.56 [99% confidence interval (CI):1.76-3.70]), but not with mortality (adjusted odds ratio: 1.59 [99%CI: 0.74-3.40] at the chosen level of significance). The blaOXA-23-like gene was detected in 292/318 (91.8%) isolates, including isolates from the environment and HCW. Typing revealed five major clusters. Sequence types (ST)195, ST208, ST218, ST642 as well as new STs were found. The dominant clone consisted of isolates from patients and environment throughout the study period. Conclusions:Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex are endemic in this setting. Prevention requires source control and limiting transmission of strains. Trial registration:The study was retrospectively registered at www.trialregister.nl (No:5541). Candidate number: 23,527, NTR number: NTR5541, Date registered NTR: 22nd December 2015.

Project description:This study established the in vitro activity of ceftolozane/tazobactam (C/T) and its genotypic resistance mechanisms by whole-genome sequencing (WGS) in 195 carbapenem-nonsusceptible Pseudomonas aeruginosa (CNSPA) clinical isolates recovered from Singapore between 2009 and 2020. C/T susceptibility rates were low, at 37.9%. Cross-resistance to ceftazidime/avibactam was observed, although susceptibility to the agent was slightly higher, at 41.0%. Whole-genome sequencing revealed that C/T resistance was largely mediated by the presence of horizontally acquired ?-lactamases, especially metallo-?-lactamases. These were primarily disseminated in well-recognized high-risk clones belonging to sequence types (ST) 235, 308, and 179. C/T resistance was also observed in several non-carbapenemase-producing isolates, in which resistance was likely mediated by ?-lactamases and, to a smaller extent, mutations in AmpC-related genes. There was no obvious mechanism of resistance observed in five isolates. The high C/T resistance highlights the limited utility of the agent as an empirical agent in our setting. Knowledge of local molecular epidemiology is crucial in determining the potential of therapy with novel agents.IMPORTANCE Pseudomonas aeruginosa infection is one of the most difficult health care-associated infections to treat due to the ability of the organism to acquire a multitude of resistance mechanisms and express the multidrug resistance phenotype. Ceftolozane/tazobactam (C/T), a novel ?-lactam/?-lactamase inhibitor combination, addresses an unmet medical need in patients with these multidrug-resistant P. aeruginosa infections. Our findings demonstrate geographical variation in C/T susceptibility owing to the distinct local molecular epidemiology. This study adds on to the growing knowledge of C/T resistance, particularly mutational resistance, and will aid in the design of future ?-lactams and ?-lactamase inhibitors. WGS proved to be a useful tool to understand the P. aeruginosa resistome and its contribution to emerging resistance in novel antimicrobial agents.

Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) are emerging worldwide. In South America, clinical isolates presenting such a phenotype usually do not belong to the globally distributed international clone 2 (IC2). The majority of these isolates are also resistant to multiple other antimicrobials and are often designated extremely drug-resistant (XDR). The aim of this study was to characterize the resistance mechanisms presented by 18 carbapenem-resistant A. baumannii isolates from five different Brazilian hospitals. Species identification was determined by rpoB sequencing, and antimicrobial susceptibility was determined by broth microdilution. Isolates were submitted to whole genome sequencing using Illumina platform and genetic similarity was determined by PFGE, MLST, and cgMLST. Genome analysis was used to identify intrinsic and acquired resistance determinants, including mutations in the AdeRSABC efflux system and in outer membrane proteins (OMPs). All isolates were identified as A. baumannii and grouped into 4 pulsotypes by PFGE, which belonged to clonal complexes (CC) 15 Pas /103 Ox (n = 4) and 79 Pas /113 Ox (n = 14), corresponding to IC4 and IC5, respectively. High MIC values to carbapenems, broad-spectrum cephalosporins, amikacin, and ciprofloxacin were observed in all isolates, while MICs of ampicillin/sulbactam, gentamicin, and tigecycline varied among the isolates. Minocycline was the most active antimicrobial agent tested. Moreover, 12 isolates (66.7%) were considered resistant to polymyxins. Besides intrinsic OXA-51 and ADC variants, all isolates harbored an acquired carbapenem-hydrolyzing class D ?-lactamase (CHDL) encoding gene, either bla OXA- 23 or bla OXA- 72. A diversity of aminoglycoside modifying enzymes and resistance determinants to other antimicrobial classes were found, as well as mutations in gyrA and parC. Non-synonymous mutations have also been identified in the AdeRSABC efflux system and in most OMPs, but they were considered natural polymorphisms. Moreover, resistance to polymyxins among isolates belonging to IC5 were associated to non-synonymous mutations in pmrB, but no known polymyxin resistance mechanism was identified in isolates belonging to IC4. In conclusion, A. baumannii clinical isolates belonging to South America's major clones present a myriad of antimicrobial resistance determinants. Special attention should be paid to natural polymorphisms observed in each clonal lineage, especially regarding non-synonymous mutations in constitutive genes associated with distinct resistance phenotypes.

Project description:The uptake of evidence-based therapies in the intensive care environment is suboptimal, particularly in limited-resource countries. Checklists, daily goal assessments, and clinician prompts may improve compliance with best practice processes of care and, in turn, improve clinical outcomes. However, the available evidence on the effectiveness of checklists is unreliable and inconclusive, and the mechanisms are poorly understood. We aim to evaluate whether the use of a multifaceted quality improvement intervention, including the use of a checklist and the definition of daily care goals during multidisciplinary daily rounds and clinician prompts, can improve the in-hospital mortality of patients admitted to intensive care units (ICUs). Our secondary objectives are to assess the effects of the study intervention on specific processes of care, clinical outcomes, and the safety culture and to determine which factors (the processes of care and/or safety culture) mediate the effect of the study intervention on mortality.This is a cluster randomized trial involving 118 ICUs in Brazil conducted in two phases. In the observational preparatory phase, we collect baseline data on processes of care and clinical outcomes from 60 consecutive patients with lengths of ICU stay longer than 48 h and apply the Safety Attitudes Questionnaire (SAQ) to 75% or more of the health care staff in each ICU. In the randomized phase, we assign ICUs to the experimental or control arm and repeat data collection. Experimental arm ICUs receive the multifaceted quality improvement intervention, including a checklist and definition of daily care goals during daily multidisciplinary rounds, clinician prompting, and feedback on rates of adherence to selected care processes. Control arm ICUs maintain usual care. The primary outcome is in-hospital mortality, truncated at 60 days. Secondary outcomes include the rates of adherence to appropriate care processes, rates of other clinical outcomes, and scores on the SAQ domains. Analysis follows the intention-to-treat principle, and the primary outcome is analyzed using mixed effects logistic regression.This is a large scale, pragmatic cluster-randomized trial evaluating whether a multifaceted quality improvement intervention, including checklists applied during the multidisciplinary daily rounds and clinician prompting, can improve the adoption of proven therapies and decrease the mortality of critically ill patients. If this study finds that the intervention reduces mortality, it may be widely adopted in intensive care units, even those in limited-resource settings.ClinicalTrials.gov NCT01785966.

Dataset Information

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

Publications

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets