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BackgroundDiagnostic microbiological capabilities remain a challenge in low- and middle-income countries resulting in major gaps. The global antimicrobial resistance burden has necessitated use of appropriate prescribing to curb the menace. This study highlights the process used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making.MethodsThis retrospective cross-sectional descriptive study used 3 years of cumulative data at the Medical Research Council Unit The Gambia from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardised methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines.ResultsA total of 14776 non-duplicate samples (blood cultures n=4382, urines n=4914, other miscellaneous swabs and aspirates n=2821 and n=390 respectively, sputa n=334, stools n=1463, CSF 353 and other samples n= 119) were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n= 315) S. aureus (n=232), and K. pneumoniae (n=96) were the leading cause of disease Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase resistance was present in 23% (71/315) vs 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%.ConclusionThis antibiogram has confirmed susceptibility to commonly used antimicrobials was higher for E. coli than K. pneumoniae with high ESBL resistance warranting surveillance. An alternative aminoglycoside with better sensitivity such as amikacin might be relevant although this was not tested and that cloxacillin remains a drug of choice for the Staphylococci.

BackgroundExtended spectrum beta-lactamases-producing (ESBL-P) and/or carbapenem-resistant (CR) Klebsiella pneumoniae have severely restricted available treatment options in healthcare settings in Vietnam. Understanding the diversity and transmission mechanisms of ESBL- and carbapenemase-encoding K. pneumoniae is important in both hospital and community settings for patient management.MethodsWe conducted a 6-month prospective cohort study of 69 Intensive care unit (ICU) patients from two hospitals in Hanoi, Vietnam. Longitudinally collected samples from patients and the ICU environment were cultured on selective media, and 357 K. pneumoniae colonies were whole genome sequenced. We performed phylogenetic analyses, and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K. pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K. pneumoniae.FindingsDespite being geographically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. Many patients carried the same resistant K. pneumoniae clone from admission to discharge. 45.9% of total isolates carried both ESBL- and carbapenemase-encoding genes, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM-1 in 46. 6% of samples from the globally successful ST15 lineage.InterpretationThese results highlight the high prevalence of ESBL-positive carbapenem-resistant K. pneumoniae in Vietnamese ICUs. Through studying K. pneumoniae ST15 in detail, we illustrated how important resistance genes are coalescing in stains carried broadly by patients entering the two hospitals directly or through referral.FundingThis study was supported by the Medical Research Council Newton Fund, United Kingdom (grant MR/N029399/1); the Ministry of Science and Technology, Vietnam (grant HNQT/SPÐP/04.16); This research was funded in whole by the Wellcome Trust (grant 206194). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

BackgroundVietnam has high rates of antimicrobial resistance (AMR) but limited capacity for genomic surveillance. This study used whole genome sequencing (WGS) to examine the prevalence and transmission of three key AMR pathogens in two intensive care units in Hanoi, Vietnam.MethodsA prospective surveillance study of all adults admitted to intensive care units (ICUs) at the National Hospital for Tropical Diseases (NHTD) and Bach Mai Hospital (BMH) was conducted between June 2017 and January 2018. Clinical and environmental samples were cultured on selective media, characterised using MALDI TOF MS, and illumina sequenced. Phylogenies based on the de novo assemblies (SPAdes) were constructed using Mafft (PARsnp), Gubbins and RAxML. Resistance genes were detected using Abricate against the NCBI database.Findings3,153 Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A. baumannii (global clone [GC]2, sequence types [ST]2, ST571) and K. pneumoniae (ST15, ST16, ST656, ST11, ST147) isolates. Colonisation was most common with E. coli (88.9%) followed by K. pneumoniae (62.4%). Of the E. coli, 91% carried a blaCTX-M variant, while 81% of K. pneumoniae isolates carried blaNDM (54%) and/or blaKPC (45%). Transmission analysis using single nucleotide polymorphisms (SNPs) identified 167 clusters involving 251 (68%) patients, in some cases involving patients from both ICUs. There were no significant differences between the lineages or AMR genes recovered between the two ICUs.InterpretationThis study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission prior to ICU admission in other healthcare settings or in the community.FundingThis work was funded by the Medical Research Council Newton Fund, United Kingdom; the Ministry of Science and Technology, Vietnam; and the Wellcome Trust, United Kingdom.Research in contextEvidence before this studyGlobally, antimicrobial resistance (AMR) is projected to cause 10 million deaths annually by 2050. Ninety percent of these deaths are expected to occur in low- and middle-income countries (LMICs), but attributing morbidity and mortality to AMR is difficult in the absence of comprehensive data. Whilst efforts have been made to improve AMR surveillance in these settings, this is often hampered by limited expertise, laboratory infrastructure and financial resources.Added value of this studyThis is the largest prospective surveillance study of three key AMR pathogens (E. coli, K. pneumoniae and A. baumannii) conducted in critical care settings in Vietnam. Sampling was restricted to patients who were colonised or infected with extended spectrum beta-lactamase (ESBL) producing and/or carbapenem-resistant organisms. Colonisation with more than one organism was very common, with multidrug-resistant (MDR) E. coli being predominant in stool samples. A small number of predominant lineages were identified for K. pneumoniae and A. baumannii, while the E. coli isolates were highly genetically diverse. A large number of genomic clusters were identified within the two ICUs, some of which spanned both ICUs. There were no significant differences between lineages or AMR genes between the two ICUs.Implications of all the available evidenceThis study found high rates of colonisation and infection with three key AMR pathogens in adults admitted to two Vietnamese ICUs. Whilst transmission was common within ICUs the finding of similar lineages and AMR genes in both ICUs suggests that dissemination of AMR occurs prior to ICU admission, either in referral hospitals or in community settings prior to hospital admission. Strategies to tackle AMR in Vietnam will need to account for this by extending surveillance more widely across hospital and community settings.

BackgroundMany nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to COVID-19 infection, progression to symptoms, likelihood of severe disease and survival. The pandemic has fostered many nutrition-related theories, sometimes backed by a biased interpretation of evidence.ObjectivesTo provide a systematic review of the latest evidence on how malnutrition across all its forms (under- and over-nutrition and micronutrient status) may influence both susceptibility to, and progression and severity of, COVID-19.MethodsWe synthesised information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity and diabetes; protein-energy malnutrition; anaemia; vitamins A, C, D, and E; poly-unsaturated fatty acids; iron; selenium; zinc; anti-oxidants, and nutritional support. For each section we provide: a) a landscape review of pertinent material; b) a systematic search of the literature in PubMed and EMBASE databases, including a systematic search of a wide range of pre-print servers; and c) a screen of six clinical trial registries. Two reviewers were assigned per section for data extraction. All original research was considered, without restriction to study design, and included if it covered: 1) SARS-CoV-2, MERS-CoV or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16thMay and 11thAugust, 2020. PROSPERO registration CRD42020186194.ResultsAcross the 13 searches, a total of 2732 articles from PubMed and EMBASE, 4164 articles from the pre-print servers, and 433 trials were returned. A total of 288 published articles and 278 pre-print articles were taken to full text screening. In the final narrative synthesis, we cover 22 published articles, 39 pre-print articles and 79 trials. The review highlights a range of mechanistic and observational evidence to highlight the role nutrition can play in susceptibility and progression of COVID-19. However, to date, there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited.ConclusionsTo date there is no conclusive evidence supporting adoption of novel nutritional therapies. However, given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. There is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.