TY - JOUR
T1 - High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units
T2 - Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level
AU - Pelegrin, Andreu Coello
AU - Saharman, Yulia Rosa
AU - Griffon, Aurélien
AU - Palmieri, Mattia
AU - Mirande, Caroline
AU - Karuniawati, Anis
AU - Sedono, Rudyanto
AU - Aditianingsih, Dita
AU - Goessens, Wil H.F.
AU - van Belkum, Alex
AU - Verbrugh, Henri A.
AU - Klaassen, Corné H.W.
AU - Severin, Juliëtte A.
N1 - Funding Information:
A material transfer agreement (MTA) (no. LB.02.01/I.9.4/8500/2013) was reviewed and approved by the Director of National Institute of Research and Development, Ministry of Health, Indonesia.
Funding Information:
Y.R.S. is an awardee of the DIKTI-NESO Scholarship by The Directorate General of Higher Education of Indonesia Ministry of Research, Technology and Higher Education of the Republic of Indonesia, and of the Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
Funding Information:
A.C.P. and M.P. received funding from the European Union’s Horizon 2020 research and innovation program New Diagnostics for Infectious Diseases (ND4ID) under Marie Skłodowska-Curie grant agreement no. 675412.
Funding Information:
We thank the staff of the Department of Anesthesia and Intensive Care, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, for their commitment and cooperation. Y.R.S. is an awardee of the DIKTI-NESO Scholarship by The Directorate General of Higher Education of Indonesia Ministry of Research, Technology and Higher Education of the Republic of Indonesia, and of the Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands. A.C.P. and M.P. received funding from the European Union?s Horizon 2020 research and innovation program New Diagnostics for Infectious Diseases (ND4ID) under Marie Sk?odowska-Curie grant agreement no. 675412. A.C.P., M.P., C.M., A.G., and A.V.B. are employees of bioM?rieux, a company developing, marketing, and selling tests in the infectious disease domain. The company had no influence on the design and execution of the clinical study and did not influence the choice of the diagnostic tools used during the clinical study. The opinions expressed in the manuscript are ours and do not necessarily reflect company policies. A material transfer agreement (MTA) (no. LB.02.01/I.9.4/8500/2013) was reviewed and approved by the Director of National Institute of Research and Development, Ministry of Health, Indonesia.
Publisher Copyright:
© 2019 Pelegrin et al.
PY - 2019/11/12
Y1 - 2019/11/12
N2 - 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, ST375, 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.
AB - 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, ST375, 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.
KW - Indonesia
KW - infection control
KW - intensive care units
KW - microbial drug resistance
KW - Pseudomonas aeruginosa
KW - single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85074898767&partnerID=8YFLogxK
U2 - 10.1128/mBio.02384-19
DO - 10.1128/mBio.02384-19
M3 - Article
C2 - 31719179
AN - SCOPUS:85074898767
SN - 2161-2129
VL - 10
JO - mBio
JF - mBio
IS - 6
M1 - e02384-19
ER -