Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov 12;10(6):e02384-19.
doi: 10.1128/mBio.02384-19.

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

Affiliations

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

Andreu Coello Pelegrin et al. mBio. .

Erratum in

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 (blaGES-5, blaVIM-2-8, and blaIMP-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.

Keywords: Indonesia; Pseudomonas aeruginosa; infection control; intensive care units; microbial drug resistance; single nucleotide polymorphism.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Multilocus sequence type of genotype-corrected CNPA. Sequence types are displayed in the abscissa axis. The ordinate axis indicates the number of genotype-corrected isolates.
FIG 2
FIG 2
(A) Antimicrobial resistance heat map of 130 isolates of carbapenem-nonsusceptible P. aeruginosa (CNPA). The x axis contains only AMR determinants that were variably present in the CNPA collection. The following AMR determinants are not displayed because they were present in all isolates: APH(3′)-IIb (aminoglycoside resistance); blaOXA-50 (β-lactam resistance); fosA (fosfomycin resistance); bcr-1 (bicyclomycin resistance); arnA and basS (polymyxin resistance); catB (chloramphenicol resistance); pmpM (multidrug and toxic compound extrusion [MATE] transporter); emrE (small multidrug resistance efflux pump); crpP (quinolone resistance); mexA-mexB-oprM plus mexR, nalC, and nalD plus cpxR plus ArmR (resistance-nodulation-cell division [RND] efflux pump plus mexAB repressors plus mexAB activator plus mexR inhibitor); mexC-mexD-oprJ plus NfxB (RND efflux pump plus mexCD-oprJ repressor); mexE-mexF-oprN plus mexT plus mexS (RND efflux pump plus mexEF activator plus mexT suppressor); mexG-mexH-mexI-opmD plus soxR (RND efflux pump plus transcriptional activator); mexJ-mexK-opmH plus mexL (RND efflux pump plus mexJK repressor); mexM-mexN-oprM (RND efflux pump); mexP-mexQ-opmE (RND efflux pump); mexV-mexW-oprM (RND efflux pump); muxA-muxB-muxC-opmB (RND efflux pump); triA-triB-triC-opmH (RND efflux pump); mexY plus mexZ (RND efflux pump component plus mexXY transcriptional regulator). (B) Bar plots showing the relation between the MIC of imipenem, meropenem, ciprofloxacin, and amikacin (subplots 1 to 4) and their related resistance genes found among the CNPA according to the literature. Vertical red dashed lines mark the EUCAST 2019 resistance breakpoints.
FIG 3
FIG 3
(Top image) Receiving operator characteristics curve. The area under the curve value is represented at the right corner of the image. (Bottom image) Cumulative distribution analysis showing the effects of variations in the cutoff SNP values on sensitivity (blue line), specificity (red line), and the positive likelihood ratio (green line). A vertical dashed black line shows the threshold corresponding to 5 SNP. A zoomed image of the first 100 cutoffs is displayed inside a box.
FIG 4
FIG 4
(A) Potential transmission events (PTEs) and (B) acquisition events (AEVs) from known sources during the study period. The boxes consisting of dashed lines represent the two intensive care units, during the preintervention and postintervention phases (panels on the left and right, respectively). Environmental sources of CNPA are depicted by green-colored sinks. Dashed lines represent transmissions (both PTEs and AEVs) between the two study phases; note that such transmissions have been registered as belonging to the postintervention phase.

References

    1. Strateva T, Yordanov D. 2009. Pseudomonas aeruginosa—a phenomenon of bacterial resistance. J Med Microbiol 58:1133–1148. doi:10.1099/jmm.0.009142-0. - DOI - PubMed
    1. Labarca JA, Salles MJC, Seas C, Guzmán-Blanco M. 2016. Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii in the nosocomial setting in Latin America. Crit Rev Microbiol 42:276–292. doi:10.3109/1040841X.2014.940494. - DOI - PubMed
    1. Klockgether J, Cramer N, Wiehlmann L, Davenport CF, Tümmler B. 13 July 2011, posting date Pseudomonas aeruginosa genomic structure and diversity. Front Microbiol doi:10.3389/fmicb.2011.00150. - DOI - PMC - PubMed
    1. European Centre for Disease Prevention and Control. 2018. Surveillance of antimicrobial resistance in Europe 2017. Annual report of the European Antimicrobial Resistance Network (EARS-Net). https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobi....
    1. Miyoshi-Akiyama T, Tada T, Ohmagari N, Viet Hung N, Tharavichitkul P, Pokhrel BM, Gniadkowski M, Shimojima M, Kirikae T. 2017. Emergence and spread of epidemic multidrug-resistant Pseudomonas aeruginosa. Genome Biol Evol 9:3238–3245. doi:10.1093/gbe/evx243. - DOI - PMC - PubMed

Publication types

MeSH terms