An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n=20) or clindamycin-rifampicin combination therapy (n=19). Patients received continuous IV clindamycin infusion for 2-6weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2weeks of oral treatment. https://www.selleckchem.com/products/hada-hydrochloride.html The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf=Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p<0.001) and its median AUC was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p<0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively. The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion. The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion. Studies on coronavirus disease 2019 (COVID-19) have mainly focused on hospitalized patients or those with severe disease. We aim to assess the clinical characteristics, outcomes and factors associated with hospital admission or death in adult outpatients with COVID-19. This is a prospective cohort of outpatients with suspected or confirmed COVID-19, registered in the Covidom telesurveillance solution for home monitoring of patients with COVID-19 in the Greater Paris area, from March to August 2020. The primary outcome was clinical worsening, defined as hospitalization or death within 1month after symptom onset. Among 43103 patients, mean age was 42.9years (SD 14.3years); 93.0% (n=40081) of patients were <65years old and 61.9% (n=26688) were women. Of these 43103 patients, 67.5% (n=29104) completed a medical questionnaire on co-morbidities and symptoms. The main reported co-morbidities were asthma (12.8%; n=3685), hypertension (12.3%; n=3546) and diabetes (4.8%; n=1385). A small proportion of all eligible patients (4.1%, 95% CI 3.9-4.2; 1751/43103) experienced clinical worsening. The rate of hospitalization was 4.0% (95% CI 3.8%-4.2%; n=1728) and 0.1% (95% CI 0.1%-0.2%; n=64) died. Factors associated with clinical worsening were male sex, older age, obesity and co-morbidities such as chronic renal disease or cancer under treatment. Probability of worsening was reduced with anosmia/ageusia. Clinical worsening was rare among outpatients. Male sex, older age and co-morbidities such as chronic renal disease, active cancers or obesity were independently associated with clinical worsening. However, our cohort may include patients younger and healthier than the general population. Clinical worsening was rare among outpatients. Male sex, older age and co-morbidities such as chronic renal disease, active cancers or obesity were independently associated with clinical worsening. However, our cohort may include patients younger and healthier than the general population. Ceftazidime-avibactam (CZA) and cefiderocol are recently commercialized molecules active against highly drug-resistant bacteria, including carbapenem-resistant members of the Enterobacteriaceae. Mutants resistant to CZA have been described, notably in Klebsiella pneumoniae carbapenemase (KPC) producers. Considering the structural similarities between ceftazidime and cefiderocol, we hypothesized that resistance to CZA in KPC-producing members of the Enterobacterales may lead to cross-resistance to cefiderocol. CZA-resistant mutants from three clinical isolates of the Enterobacterales carrying either bla or bla were selected invitro. Mutants with increased MIC to CZA compared to the ancestral allele were cloned in a pBR322 plasmid and expressed in Escherichia coli TOP10. We evaluated the impact of these mutations on cefiderocol MICs and minimal bactericidal concentrations (MBCs), and we assessed the impact of bacterial inoculum size on cefiderocol MICs. We used 37 KPC mutants with increased CZA MICs. suggesting that precautions should be taken when treating infections with a suspected high inoculum. mcr-9.1 is a newly described mobile colistin resistance gene. We have noted its presence in multiple species of carbapenem-resistant Enterobacterales (CRE) from our institution. We aimed to determine the clinical features, genomic context and phenotypic impact of mcr-9.1 carriage in a series of patients between 2010 and 2019. We identified 32 patients with mcr-9.1-carrying CRE isolates (mCRE) and collected demographic, antimicrobial exposure and infection data. Whole-genome sequencing (including short and long reads) was performed on 32 isolates. We assessed sequence similarity of mcr-9.1-harbouring plasmids, then compared our findings with plasmids for which sequence data were publicly available. There was no colistin exposure in patients prior to isolation of mCRE. mcr-9.1 was identified on IncHI2 plasmids across four different bacterial species and was co-located with bla in 23/30 plasmids studied. mCRE isolates did not demonstrate phenotypic colistin resistance, either at baseline or following sublethal colistin exposure, thus showing that mcr-9.