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Among a subset of cases randomly selected for review, Pseudomonas sp. was a rare cause of IAI, but anti-pseudomonal antibiotics were commonly prescribed empirically. We observed a large increase in cefepime utilization for IAI during a TZP shortage that was not warranted based on the observed frequency of identification of Pseudomonas sp. as the causative organism in IAI, suggesting a need to revisit national guideline recommendations.Chlamydia trachomatis is a strict intracellular bacterium that causes sexually transmitted infections and eye infections that can lead to life-long sequelae. Treatment options are limited to broad-spectrum antibiotics that disturb the commensal flora and contribute to selection of antibiotic-resistant bacteria. Hence, development of novel drugs that specifically target C. trachomatis would be beneficial. 2-pyridone amides are potent and specific inhibitors of Chlamydia infectivity. The first generation compound KSK120, inhibits the developmental cycle of Chlamydia resulting in reduced infectivity of progeny bacteria. Here, we show that the improved, highly potent second-generation 2-pyridone amide KSK213 allowed normal growth and development of C. trachomatis and the effect was only observable upon re-infection of new cells. Progeny elementary bodies (EBs) produced in the presence of KSK213 were unable to activate transcription of essential genes in early development and did not differentiate into the replicative form, the reticulate body (RB). The effect was specific to C. trachomatis since KSK213 was inactive in the closely related animal pathogen C. muridarum and in C. caviae The molecular target of KSK213 may thus be different in C. trachomatis or non-essential in C. muridarum and C. caviae Resistance to KSK213 was mediated by a combination of amino acid substitutions in both DEAD/DEAH RNA helicase and RNAse III, which may indicate inhibition of the transcriptional machinery as the mode of action. 2-pyridone amides provide a novel antibacterial strategy and starting points for development of highly specific drugs for C. trachomatis infections.Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin resistant Staphylococcus aureus in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in S. aureus following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that fusC carriage confers resistance to FA, and mupA carriage confers high-level resistance to mupirocin in multiple S. aureus genetic backgrounds. https://www.selleckchem.com/products/baf312-siponimod.html In vitro experiments demonstrated that carriage of fusC and mupA confer a competitive advantage in the presence of sub-inhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonisation model to show that clinically relevant concentrations of topical antibiotics can co-select for presence of unrelated antimicrobial resistance determinants, such as mecA, blaZ, and qacA, in fusC or mupA harbouring S. aureus These findings provide valuable insights on the role of acquired FA or mupirocin resistance in co-selecting for broader antibiotic resistance in S. aureus, prompting greater need for judicious use of topical antibiotics.Two novel ISCR1-associated dfr genes, dfrA42 and dfrA43, were identified from trimethoprim (TMP)-resistant Proteus strains and were shown to confer high level TMP resistance (MIC ≥ 1024 mg/L) when cloned into Escherichia coli These genes were hosted by complex class 1 integrons suggesting their potentials for dissemination. Analysis of enzymatic parameters and TMP affinity were performed, suggesting that the mechanism of TMP resistance for these novel DHFRs is the reduction of binding with TMP.The MAST® Carba PAcE test is a colorimetric test used to detect carbapenemase-producing Gram-negative bacilli from cultured colonies. The performances of this test were compared to β-CARBA™, Carba NP test and RAPIDEC® CARBA NP tests using a collection of 280 characterized isolates. Sensitivity and specificity of the MAST® Carba PAcE test were 79.8% (95%IC 73.3%-85.1%) and 98.9% (95%IC 92.9%-99.9%). The MAST® Carba PAcE sensitivity was the lowest mainly due to interpretation difficulties (particularly OXA-48-like).The COVID-19 pandemic has had many ramifications on healthcare delivery and practice. As part of this, utilising biomarkers to risk stratify patients has become increasingly popular. During the COVID-19 pandemic the use of D-dimer has increased due to the evidence of COVID-19 induced thrombo-embolic disease. We evaluated the use of D-dimer on all hospital admissions during the peak of the pandemic and evaluated its sensitivity in diagnosing pulmonary embolic disease (PE). Patients without COVID-19 infection were as likely to have evidence of PE as their COVID-positive counterparts. However, the sensitivity of a D-dimer was higher in COVID-positive patients at a lower D-dimer level (>1,500 μg/L, sensitivity 81%, specificity 70%) than in those without clinical, immunological or radiological evidence of COVID-19 infection (D-dimer >2,000 μg/L, sensitivity 80%, specificity 76%). These data suggest higher D-dimer thresholds should be considered for the exclusion of pulmonary emboli.The value of vitamin D supplementation in the treatment or prevention of various conditions is often viewed with scepticism as a result of contradictory results of randomised trials. It is now becoming apparent that there is a pattern to these inconsistencies. A recent large trial has shown that high-dose intermittent bolus vitamin D therapy is ineffective at preventing rickets - the condition that is most unequivocally caused by vitamin D deficiency. There is a plausible biological explanation since high-dose bolus replacement induces long-term expression of the catabolic enzyme 24-hydroxylase and fibroblast growth factor 23, both of which have vitamin D inactivating effects. Meta-analyses of vitamin D supplementation in prevention of acute respiratory infection and trials in tuberculosis and other conditions also support efficacy of low dose daily maintenance rather than intermittent bolus dosing. This is particularly relevant during the current COVID-19 pandemic given the well-documented associations between COVID-19 risk and vitamin D deficiency.
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