Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis

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Time to switch from CLSI to EUCAST? a Southeast Asian perspective

Despite the importance of antimicrobial susceptibility testing (AST) to clinical management of infection and to antimicrobial resistance (AMR) surveillance, methodologies and breakpoints of the two most commonly used systems worldwide, CLSI and EUCAST, are far from harmonized. Most laboratories in resource-constrained settings such as Southeast Asia, including our own, currently follow CLSI disk diffusion AST guidelines. Many aspects of the EUCAST system, not least the freely available nature of all output, are likely to be attractive to laboratories in our setting, but published reports of the practical differences between CLSI and EUCAST methodologies are lacking. Our manuscript highlights key differences between CLSI and EUCAST disk diffusion AST methodologies, and the practical implications of adopting EUCAST guidelines in our laboratory network. We discuss potential barriers to adoption of EUCAST guidelines in resource-Clinical Microbiology and Infection constrained settings including difficulties in obtaining horse blood for media supplementation and the need for an MIC method for AST of N. gonorrhoeae. We highlight the need for a globally harmonized AST system that is practical and freely available, and we hope this commentary will be useful for laboratories considering switching between CLSI and EUCAST

Impact of CLSI and EUCAST breakpoint discrepancies on reporting of antimicrobial susceptibility and AMR surveillance

We investigated the impact of breakpoint discrepancies between CLSI and EUCAST on susceptibility interpretation of clinical isolates at the Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos and performed a literature search to compare our findings to published reports. Zone diameters for first-line antimicrobial agents tested against non-duplicate clinical isolates of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in 2017 were interpreted separately using EUCAST 2018 and CLSI 2018 breakpoints and greement measured. Applying EUCAST instead of CLSI breakpoints to 428 E. coli, 208 K. pneumoniae and 78 P. aeruginosa isolates would have increased rates of ciprofloxacin resistance (59.1% vs 46.5% in E. coli, 37.5% vs 13.9% in K. pneumoniae, 28.2% vs 10.3% in P. aeruginosa) and amoxicillinclavulanic acid resistance (52.3% vs 19.9% in E. coli, 35.6% vs 22.1% in K. pneumoniae). Our results are supported by a literature search which identified 20 articles whose main objective was comparing susceptibility interpretation between CLSI and EUCAST. 19/20 articles reported significant discrepancies in one or more pathogen-antimicrobial combinations, nearly always due to a reduction in susceptibility rates and/or increase in resistance rates when applying more restrictive EUCAST breakpoints. We conclude that breakpoint discrepancies between CLSI and EUCAST have a significant impact on susceptibility interpretation of clinical isolates and AMR surveillance initiatives, and highlight the need for globally harmonized clinical breakpoints

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia.

BACKGROUND: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations

Leptospirosis, melioidosis, and rickettsioses in the vicious circle of neglect.

The global priorities in the field of infectious diseases are constantly changing. While emerging viral infections have regularly dominated public health attention, which has only intensified after the COVID-19 pandemic, numerous bacterial diseases have previously caused, and continue to cause, significant morbidity and mortality-deserving equal attention. Three potentially life-threatening endemic bacterial diseases (leptospirosis, melioidosis, and rickettsioses) are a huge public health concern especially in low- and middle-income countries. Despite their continued threat, these diseases do not receive proportionate attention from global health organizations and are not even included on the WHO list of neglected tropical diseases (NTDs). This, in turn, has led to a vicious circle of neglect with continued, yet conceivably preventable, hospitalizations and deaths each year especially in the vulnerable population. This is a call from a group of multi-institutional experts on the urgent need to directly address the circle of neglect and raise support in terms of funding, research, surveillance, diagnostics, and therapeutics to alleviate the burden of these 3 diseases.fals

Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans

Cryptococcus neoformans (C. neoformans var. grubii) is an environmentally acquired pathogen causing 181,000 HIV-associated deaths each year. We sequenced 699 isolates, primarily C. neoformans from HIV-infected patients, from 5 countries in Asia and Africa. The phylogeny of C. neoformans reveals a recent exponential population expansion, consistent with the increase in the number of susceptible hosts. In our study population, this expansion has been driven by three sub-clades of the C. neoformans VNIa lineage; VNIa-4, VNIa-5 and VNIa-93. These three sub-clades account for 91% of clinical isolates sequenced in our study. Combining the genome data with clinical information, we find that the VNIa-93 sub-clade, the most common sub-clade in Uganda and Malawi, was associated with better outcomes than VNIa-4 and VNIa-5, which predominate in Southeast Asia. This study lays the foundation for further work investigating the dominance of VNIa-4, VNIa-5 and VNIa-93 and the association between lineage and clinical phenotype

Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data.

BACKGROUND: There is a pressing need to understand better the extent and distribution of antimicrobial resistance on a global scale, to inform development of effective interventions. Collation of datasets for meta-analysis, mathematical modelling and temporo-spatial analysis is hampered by the considerable variability in clinical sampling, variable quality in laboratory practice and inconsistencies in antimicrobial susceptibility testing and reporting. METHODS: The Microbiology Investigation Criteria for Reporting Objectively (MICRO) checklist was developed by an international working group of clinical and laboratory microbiologists, infectious disease physicians, epidemiologists and mathematical modellers. RESULTS: In keeping with the STROBE checklist, but applicable to all study designs, MICRO defines items to be included in reports of studies involving human clinical microbiology data. It provides a concise and comprehensive reference for clinicians, researchers, reviewers and journals working on, critically appraising, and publishing clinical microbiology datasets. CONCLUSIONS: Implementation of the MICRO checklist will enhance the quality and scientific reporting of clinical microbiology data, increasing data utility and comparability to improve surveillance, grade data quality, facilitate meta-analyses and inform policy and interventions from local to global levels