Screening for Candida auris in patients admitted to eight intensive care units in England, 2017 to 2018

Background Candida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment.     

Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells

There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies     

Linkage,recombination and mutation rate analyses of 16 X-chromosomal STR loci in Sri Lankan Sinhalese pedigrees

International Journal of Legal Medicine - This study investigated genetic linkage, recombination fractions and mutation rates of 16 X chromosomal short tandem repeat (X-STR) markers using a...     

Optimizing antibiotic prescribing: collective approaches to managing a common-pool resource

BackgroundAntimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way.ObjectivesWe aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma.SourcesWe conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas.ContentThe social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms.ImplicationsWe conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development.     

Dental plaque biofilm in oral health and disease

Dental plaque is an archetypical biofilm composed of a complex microbial community. It is the aetiological agent for major dental diseases such as dental caries and periodontal disease. The clinical picture of these dental diseases is a net result of the cross-talk between the pathogenic dental plaque biofilm and the host tissue response. In the healthy state, both plaque biofilm and adjacent tissues maintain a delicate balance, establishing a harmonious relationship between the two. However, changes occur during the disease process that transform this 'healthy' dental plaque into a 'pathogenic' biofilm. Recent advances in molecular microbiology have improved the understanding of dental plaque biofilm and produced numerous clinical benefits. Therefore, it is imperative that clinicians keep abreast with these new developments in the field of dentistry. Better understanding of the molecular mechanisms behind dental diseases will facilitate the development of novel therapeutic strategies to establish a 'healthy dental plaque biofilm' by modulating both host and microbial factors. In this review, the present authors aim to summarise the current knowledge on dental plaque as a microbial biofilm and its properties in oral health and disease.     

Oral microflora in infants delivered vaginally and by caesarean section

BACKGROUND. Early in life, vaginally delivered infants exhibit a different composition of the gut flora compared with infants delivered by caesarean section (C-section); however, it is unclear whether this also applies to the oral cavity. AIM. To investigate and compare the oral microbial profile between infants delivered vaginally and by C-section. DESIGN. This is a cross-sectional case-control study. Eighty-four infants delivered either vaginally (n = 42) or by C-section (n = 42) were randomly selected from the 2009 birth cohort at the County Hospital in Halmstad, Sweden. Medically compromised and premature children (<32 weeks) were excluded. The mean age was 8.25 months (range 6-10 months), and parents were asked to complete a questionnaire on socioeconomic factors, lifestyle, and hygiene habits. Saliva was collected and analysed using checkerboard DNA-DNA hybridization. RESULTS. A higher prevalence of salivary Streptococcus salivarius, Lactobacillus curvata, Lactobacillus salivarius, and Lactobacuillus casei was detected in infants delivered vaginally (P < 0.05). The caries-associated bacteria Streptococcus mutans and Streptococcus sobrinus were detected in 63% and 59% of all children, respectively. CONCLUSION. A significantly higher prevalence of certain strains of health-related streptococci and lactobacilli was found in vaginally delivered infants compared with infants delivered by C-section. The possible long-term effects on oral health need to be further investigated.