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abril 6, 2021

Evolution and genomic insight into methicillin-resistant Staphylococcus aureus ST9 in China

CONCLUSIONS: Host exchange and regional transmission of ST9 have occurred between pigs and humans. Pig rearing and trading might have favoured gene exchanges between ST9 isolates. Resistance genes, obtained from the environment and other isolates, were stably integrated into the chromosomal DNA. The abundance of resistance genes among ST9 is likely attributed to the extensive use of antimicrobial agents in livestock. Phages are present in the genomes of ST9 and may play a role in the rapid…

DOSAGE INDIVIDUALIZATION OF LINEZOLID: PRECISION DOSING OF LINEZOLID TO OPTIMISE EFFICACY AND MINIMISE TOXICITY

High interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualised dosing.A retrospective pharmacokinetic analysis was performed using data from 338…

Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species

Invasive yeast infections represent a major global public health issue and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically-resistant species. We here report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species…

Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance

Candida auris is globally recognized as an opportunistic fungal pathogen of high concern, due to its extensive multidrug resistance (MDR). Still, molecular mechanisms of MDR are largely unexplored. This is the first account of genome-wide evolution of MDR in C. auris obtained through serial in vitro exposure to azoles, polyenes, and echinocandins. We show the stepwise accumulation of copy number variations and novel mutations in genes both known and unknown in antifungal drug resistance….

In vitro Susceptibility of Multidrug-Resistant Pseudomonas aeruginosa following Treatment-emergent Resistance to Ceftolozane-tazobactam

We compared the in vitro susceptibility of multidrug-resistant Pseudomonas aeruginosa isolates collected before and after treatment-emergent resistance to ceftolozane-tazobactam. Median baseline and post-exposure ceftolozane-tazobactam MICs were 2 and 64 μg/mL, respectively. Whole-genome sequencing identified treatment-emergent mutations in ampC among 79% (11/14) of paired isolates. AmpC mutations were associated with cross-resistance to ceftazidime-avibactam, but increased susceptibility to…

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update

Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents…

Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis

Rifampicin-resistant/multidrug-resistant (RR/MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis (TB) are serious public health problem in Kazakhstan. In 2012 and 2013, stringent regulatory authorities approved the first new TB drugs in fifty years, bedaquiline and delamanid, offering hope for more effective and less toxic MDR-TB treatment. The endTB Observational Study is a multi-country study that enrolled patients receiving a bedaquiline- or delamanid-containing regimen for…

Sorry for the delay

Patients affected by tuberculosis should be adequately treated. Those who are diagnosed early in the course of the disease have a better chance for a successful outcome than patients where the diagnosis of tuberculosis is delayed. We have been invited to comment on an article accepted for publication in CMI that addresses delays in the diagnosis of tuberculosis in China and we are discussing different mechanisms leading to delayed or inadequate tuberculosis treatments.