Clinical impact of endemic NDM-producing Klebsiella pneumoniae in intensive care units of the national referral hospital in Jakarta, Indonesia

OBJECTIVE: A prospective observational study was performed to assess the epidemiology and clinical impact of carbapenem-non-susceptible Klebsiella pneumoniae (CNKP) in intensive care units (ICUs) of the national referral hospital in Jakarta, Indonesia. MATERIALS/METHODS: Adult patients consecutively hospitalized for > 48 h in two ICUs of the national referral hospital were included from April until October 2013 and from April until August 2014. K. pneumoniae from clinical cultures and standardized screening of rectum and throat on admission, discharge and weekly if hospitalized > 7 days were collected. Environmental niches and healthcare workers (HCWs) were also screened. Susceptibility was determined phenotypically and the presence of carbapenemase genes by PCR. Raman spectroscopy as well as multiple-locus variable number tandem repeat analysis (MLVA) were used for typing. RESULTS: Twenty-two out of 412 (5.3%) patients carried CNKP on admission and 37/390 (9.5%) acquired CNKP during ICU stay. The acquisition rate was 24.7/1000 patient-days at risk. One out of 31 (3.2%) environmental isolates was a CNKP. None of the HCWs carried CNKP. Acquisition of CNKP was associated with longer ICU stay (adjusted Hazard Ratio: 2.32 [CI99: 1.35-3.68]). ICU survival was lower among patients with CNKP compared to patients with carbapenem-susceptible K. pneumoniae (aHR 2.57, p = 0.005). Ninety-six of the 100 (96%) CNKP isolates carried a carbapenemase gene, predominantly blaNDM. Raman typing revealed three major clusters among 48 Raman types identified, whereas MLVA distinguished six major clusters among a total of 30 different genotypes. CONCLUSIONS: NDM-producing CNKP are introduced into these ICUs and some strains expand clonally among patients and the environment, resulting in endemic CNKP. CNKP acquisition was associated with prolonged ICU stay and may affect ICU survival. TRIAL REGISTRATION: The study was registered at Netherlands Trial Register http://www.trialregister.nl. Candidate number: 23527, NTR number: NTR5541, NL number: NL5425 (https://www.trialregister.nl/trial/5424), Retrospectively registered: NTR: 22 December 2015

Epidemiology and characterisation of carbapenem-non-susceptible Pseudomonas aeruginosa in a large intensive care unit in Jakarta, Indonesia

The aim of this study was to describe the epidemiology and clinical impact of carbapenem-non-susceptible Pseudomonas aeruginosa (CNPA) in intensive care units (ICUs) of the national refer

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units

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

Tocilizumab as a Treatment for ‘Cytokine Storm Syndrome’ in COVID-19: A Case Report

Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases of COVID-19. This case report describes a case of a 53-year-old male patient who has been diagnosed with COVID-19. Further evaluation in this patient showed that there was a marked increase in IL-6 level in blood accompanied with hyperferritinemia, which was in accordance with the characteristic of cytokine storm syndrome. Patient was treated with tocilizumab, a monoclonal antibody and is an antagonist to IL-6 receptor. The binding between tocilizumab and IL-6 receptors effectively inhibit and manage cytokine storm syndrome. Although this case report reported the efficacy of tocilizumab in managing cytokine storm syndrome, tocilizumab has several adverse effects requiring close monitoring. Further clinical randomized control trial is required to evaluate the efficacy and safety of tocilizumab administration in participants with various clinical characteristics and greater number of subjects.