Search

Objectives: To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources., Methods: A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR)., Results: Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae , Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases., Conclusions: These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Objectives: Carbapenemase-producing Enterobacterales (CPE) are high priority targets of global antimicrobial surveillance. Herein, we determined the colonization rate of CPE on admission to intensive care units in Vientiane, Lao PDR in August-September 2019., Methods: Data regarding clinical conditions, infection control, and antibiotic usage were collected during admission. Rectal swab samples (n = 137) collected during admission were inoculated to selective chromogenic agars, followed by confirmatory tests for extended-spectrum beta-lactamases and carbapenemases. All CPE isolates were sequenced on Illumina (HiSeq2500), reads assembled using SPAdes 3.13, and the draft genomes used to query a database (https://www.genomicepidemiology.org) for resistome, plasmid replicons, and sequence types (ST). Optical DNA mapping (ODM) was used to characterize plasmids and to determine location of resistance genes. Minimum spanning tree was generated using the Bacterial Isolate Genome Sequence database (BIGSdb) and annotated using iTOL., Result: From 47 Enterobacterales isolated on selective agars, K. pneumoniae (25/47) and E. coli (12/47) were the most prevalent species, followed by K aerogenes (2/47), K. variicola (1/47), and K. oxytoca (1/47). The overall prevalence of ESBLs was 51.0%; E. coli 83.3% (10/12) and Klebsiella spp. 41.3% (12/29). Twenty percent of the K. pneumoniae (5/25) isolates were carbapenem-resistant, and 4/5 contained the blaNDM-1 gene. All blaNDM-1 isolates belonged to ST147 and were indistinguishable with cgMLST. ODM showed that the blaNDM-1 gene was located on identical plasmids in all isolates., Conclusion: The prevalence of ESBL-producing Enterobacterales was high, while carbapenemases were less common. However, the detection of clonal dissemination of blaNDM-1-producing K. pneumoniae isolates in one of the intensive care units calls for vigilance. Stringent infection prevention and antimicrobial stewardship strategies are highly important measures., Competing Interests: No Authors have competing interest.

Within 8 months, 3 children from 1 family in northern Vietnam died from melioidosis. Burkholderia pseudomallei of the same sequence type, 541, was isolated from clinical samples, borehole water, and garden and rice field soil. Boreholes should be properly constructed and maintained to avoid B. pseudomallei contamination.

Objectives: The carbapenemase-encoding gene bla NDM-1 has been reported in Vietnam during the last 10 years, and bla NDM -producing Enterobacteriaceae are now silently and rapidly spreading. A key factor behind dissemination of bla NDM-1 is plasmids, mobile genetic elements that commonly carry antibiotic resistance genes and spread via conjugation. The diversity of bla NDM-1 -encoding plasmids from neonates at a large Vietnamese hospital was characterized in this study., Methods: 18 fecal Klebsiella pneumoniae and Klebsiella quasipneumoniae isolates collected from 16 neonates at a large pediatric hospital in Vietnam were studied using optical DNA mapping (ODM) and next-generation sequencing (NGS). Plasmids carrying the bla NDM-1 gene were identified by combining ODM with Cas9 restriction. The plasmids in the isolates were compared to investigate whether the same plasmid was present in different patients., Results: Although the same plasmid was found in some isolates, ODM confirmed that there were at least 10 different plasmids encoding bla NDM-1 among the 18 isolates, thus indicating wide plasmid diversity. The ODM results concur with the NGS data. Interestingly, some isolates had two distinct plasmids encoding bla NDM-1 that could be readily identified with ODM. The coexistence of different plasmids carrying the same bla NDM-1 gene in a single isolate has rarely been reported, probably because of limitations in plasmid characterization techniques., Conclusions: The plasmids encoding the bla NDM-1 gene in this study cohort were diverse and may represent a similar picture in Vietnamese society. The study highlights important aspects of the usefulness of ODM for plasmid analysis., Competing Interests: Competing Interests None to declare., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among patients at hospitals in LMICs, with increased risk of hospital-acquired infections., Methods: We isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from faecal samples collected in 2017 from patients at admission and discharge at a Vietnamese neonatal intensive care unit (NICU). 126 CRKP were whole-genome sequenced. The phylogenetic relationship between the isolates and between clinical CRKP isolates collected in 2012-2018 at the same hospital were investigated., Results: NDM-type carbapenemase-(61%) and KPC-2-encoding genes (41%) were the most common carbapenem resistance genes observed among the admission and discharge isolates. Most isolates (56%) belonged to three distinct clonal clusters of ST15, carrying bla KPC-2 , bla NDM-1 and bla NDM-4 , respectively. Each cluster also comprised clinical isolates from blood collected at the study hospital. The most dominant ST15 clone was shown to be related to isolates collected from the same hospital as far back as in 2012., Conclusions: Highly resistant CRKP were found colonising admission and discharge patients at a Vietnamese NICU, emphasising the importance of continued monitoring. Whole-genome sequencing revealed a population of CRKP consisting mostly of ST15 isolates in three clonally related clusters, each related to blood isolates collected from the same hospital. Furthermore, clinical isolates collected from previous years (dating back to 2012) were shown to likely be clonally descended from ST15 isolates in the largest cluster, suggesting a successful hospital strain which can colonise inpatients., (© 2021. The Author(s).)

Objectives: We performed a One Health surveillance in Hanoi-a region with a high-density human population and livestock production, and a recognized hotspot of animal-associated antimicrobial resistance (AMR)-to study the contribution of bla CTX-M -carrying Escherichia coli and plasmids from food-animal sources in causing human community-acquired urinary tract infections (CA-UTIs)., Methods: During 2014-2015, 9090 samples were collected from CA-UTI patients (urine, n = 8564), pigs/chickens from farms and slaughterhouses (faeces, carcasses, n = 448), and from the slaughterhouse environment (surface swabs, water, n = 78). E. coli was identified in 2084 samples. Extended-spectrum β-lactamase (ESBL) production was confirmed in 235 and bla CTX-M in 198 strains by PCR with short-read plasmid sequencing. Fourteen strains were long-read sequenced to enable plasmid reconstruction., Results: The majority of the ESBL-producing E. coli strains harboured bla CTX-M (n = 198/235, 84%). High clonal diversity (48 sequence types, STs) and distinct, dominant STs in human sources (ST1193, n = 38/137; ST131, n = 30/137) and non-human sources (ST155, n = 25/61) indicated lack of clonal transmission between habitats. Eight bla CTX-M variants were identified; five were present in at least two sample sources. Human and food-animal strains did not show similar plasmids carrying shared bla CTX-M genes. However, IS6 elements flanking ISEcp1-bla CTX-M -orf477/IS903B structures were common across habitats., Conclusions: In this study, animal-associated bla CTX-M E. coli strains or bla CTX-M plasmids were not direct sources of CA-UTIs or ESBL resistance in humans, respectively, suggesting evolutionary bottlenecks to their adaptation to a new host species. Presence of common IS6 elements flanking bla CTX-M variants in different plasmid backbones, however, highlighted the potential of these transposable elements for AMR transmission either within or across habitats., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICU's) at the Vietnamese National Children's Hospital., Method: CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status., Results: CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR - 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD., Conclusion: Admission CRE screening and cohort care in pediatric ICU's significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay., (© 2021. The Author(s).)

Background: Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae ., Methods: In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015., Results: Aside from the carbapenem resistance gene bla KPC-2 , which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone., Conclusions: The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones., Competing Interests: Competing interestsThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s). 2019.)

Background: Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC)., Methods: A point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome., Results: A total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n = 805), Escherichia coli (n = 682) and Enterobacter spp. (n = 61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2% per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU, CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5·5, P < 0·01) with CRE colonisation and HAI on admission., Conclusion: These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antibiotic resistance (ABR) is an increasing burden for global health. The prevalence of ABR in Southeast Asia is among the highest worldwide, especially in relation to hospital-acquired infections (HAI) in intensive care units (ICU). However, little is known about morbidity and mortality attributable to ABR in neonates., Aim: This study aimed to assess mortality and the length of hospitalization attributable to ABR in gram-negative bacteria (GNB) causing HAI in a Vietnamese neonatal ICU (NICU)., Methods: We conducted a prospective cohort study (n = 296) in a NICU in Hanoi, Vietnam, from March 2016 to October 2017. Patients isolated with HAI caused by GNB were included. The exposure was resistance to multiple antibiotic classes, the two outcomes were mortality and length of hospital stay (LOS). Data were analysed using two regression models, controlling for confounders and effect modifiers such as co-morbidities, time at risk, severity of illness, sex, age, and birthweight., Results: The overall case fatality rate was 44.3% and the 30 days mortality rate after infection was 31.8%. For every additional resistance to an antibiotic class, the odds of a fatal outcome increased by 27% and LOS increased by 2.1 days. These results were statistically significant (p < 0.05)., Conclusion: ABR was identified as a significant risk factor for adverse outcomes in neonates with HAI. These findings are generally in line with previous research in children and adults. However, heterogeneous study designs, the neglect of important confounders and varying definitions of ABR impair the validity, reliability, and comparability of results., Competing Interests: The authors have declared that no competing interests exist.

Resistance among Klebsiella pneumoniae to the last-resort antibiotics carbapenems and colistin is increasing worldwide. In this study, whole-genome sequencing was used to determine the colistin resistance mechanisms in clinical isolates of carbapenem- and colistin-resistant K. pneumoniae from Vietnam. Alterations in the regulatory gene mgrB, via mutations and insertion sequence transpositions, were found in 30 of 31 isolates, emphasising the importance of this resistance mechanism in colistin-resistant K. pneumoniae., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)