Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in intensive care units of the national referral hospital in Jakarta, Indonesia

Yulia Rosa Saharman, Anis Karuniawati, Rudyanto Sedono, Dita Aditianingsih, Pratiwi Sudarmono, Wil H F Goessens, Corné H W Klaassen, Henri A Verbrugh, Juliëtte A Severin, Yulia Rosa Saharman, Anis Karuniawati, Rudyanto Sedono, Dita Aditianingsih, Pratiwi Sudarmono, Wil H F Goessens, Corné H W Klaassen, Henri A Verbrugh, Juliëtte A Severin

Abstract

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.

Keywords: Acinetobacter baumannii-calcoaceticus complex; Antimicrobial resistance; Carbapenemase; Carbapenems; Indonesia; Intensive care unit.

Conflict of interest statement

The Ethics Committee of the Faculty of Medicine, Universitas Indonesia, approved the research on 17th September 2012, No: 561/PT02.FK/ETIK/2012, (No: 757/UN2.F1/ETIK/X/2014). A Material Transfer Agreement (MTA) was reviewed and approved by the Director of National Institute Research and Development, Ministry of Health (No: LB.02.01/I.9.4/8500/2013). Written informed consent was obtained using a form that was approved by the Ethics Committee Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo General Hospital. A signature and the date of signature was put on the form by the study subjects or their guardians and by the person who conducted the informed consent discussion and two witnesess. The signature confirmed that the consent was based on information that had been understood including publication.Yulia Rosa Saharman 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 Department of Medical Microbiology and Infectious Diseases, Erasmus MC in Rotterdam, The Netherlands. Preliminary results of this study were presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2014 in Washington, DC (poster C-1477). All authors report no conflict of interest relevant to this article.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Acquisition of carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in ICUs. Note: The solid line represents the cumulative percentage of patients by first day of culture being positive for carbapenem-nonsusceptible A. baumannii-calcoaceticus complex during ICU stay. In total, data from 89 patients are included in this figure. The median acquisition day (day 7, 60% of patients positive) is shown as well
Fig. 2
Fig. 2
Cumulative percentage of length of stay for patients according to their carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex status. Note: Lengths of stay (days) represent total days patients were hospitalized in the ICU. The red line represents patients that were always carbapenem-nonsusceptible A. baumannii-calcoaceticus complex negative during their ICU stay. The blue line represents patients already carbapenem-nonsusceptible A. baumannii-calcoaceticus complex positive on the day of admission. The green line represents patients that were carbapenem-nonsusceptible A. baumannii-calcoaceticus complex positive only at the time of discharge and the black line represents patients that became positive for carbapenem-nonsusceptible A. baumannii-calcoaceticus complex during their ICU stay before the day of discharge. P value: comparison between patients that became positive with carbapenem-nonsusceptible A. baumannii-calcoaceticus complex before the day of discharge and the other groups
Fig. 3
Fig. 3
Survival analysis of ICU patients according to their carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex status. Note: Survival of patients with carbapenem-nonsusceptible A. baumannii-calcoaceticus complex acquired during their ICU stay (blue line) compared with the survival of patients that remained negative for carbapenem-nonsusceptible A. baumannii-calcoaceticus complex in their screening and clinical cultures (green line)
Fig. 4
Fig. 4
Persistence of Raman clones of carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex in two ICUs of Dr. Cipto Mangunkusomo General Hospital, Jakarta, Indonesia. Note: Endemic curves of the five biggest clusters of carbapenem-nonsusceptible A. baumannii-calcoaceticus complex in each ICU, April–October 2013 and April–August 2014. The dark blue bars represent cluster CIPTO-30. The red bars represent CIPTO-31. The green bars represent CIPTO-45. The yellow bars represent CIPTO-46 and the light blue bars represent CIPTO-48. The x-axis indicates time of the study (by week). The y-axis indicates number of isolates

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