Time to intestinal clearance of carbapenemase-producing Enterobacterales in hospital patients: a longitudinal retrospective observational cohort study.

BACKGROUND: Intestinal clearance of carbapenemase-producing Enterobacterales (CPE-IC) is a cornerstone to discontinue isolation precautions for CPE patients in hospitals. This study aimed to evaluate the time to spontaneous CPE-IC and identify its potential associated risk factors. METHODS: This retrospective cohort study was carried out between January 2018 and September 2020 on all patients in a 3200-bed teaching referral hospital with confirmed CPE intestinal carriage. CPE-IC was defined as at least three consecutive CPE-negative rectal swab cultures without a subsequent positive result. A survival analysis was performed to determine the median time to CPE-IC. A multivariate Cox model was implemented to explore the factors associated with CPE-IC. RESULTS: A total of 110 patients were positives for CPE, of whom 27 (24.5%) achieved CPE-IC. Median time to CPE-IC was 698 days. Univariate analysis showed that female sex (P=0.046), multiple CPE-species in index cultures (P=0.005), Escherichia coli or Klebsiella spp. (P=0.001 and P=0.028, respectively) were significantly associated with the time to CPE-IC. Multivariate analysis highlighted that identification of E. coli carbapenemase-producing or CPEs harbouring ESBL genes in index culture extended the median time to CPE-IC, respectively (adjusted hazard ratio (aHR) = 0.13 (95% confidence interval: 0.04-0.45]; P=0.001 and aHR = 0.34 (95% confidence interval: 0.12-0.90); P=0.031). CONCLUSION: Intestinal decolonization of CPE can take several months to years to occur. Carbapenemase-producing E. coli are likely to play a key role in delaying intestinal decolonization, probably through horizontal gene transfer between species. Therefore, discontinuation of isolation precautions in CPE-patients should be considered with caution.

Methoxpropamine (MXPr) in powder, urine and hair samples: Analytical characterization and metabolite identification of a new threat.

Methoxpropamine (MXPr) is an arylcyclohexylamine dissociative drug with structural similarities with 3-MeO-PCE, ketamine and deschloroketamine. MXPr was identified for the first time in Europe in October 2019 in Denmark and is considered a new psychoactive substance. We undertook the molecular identification and characterization of MXPr in urine, hair and powder samples. We used a combination of several analytical methods: liquid-state nuclear magnetic resonance (NMR), infra-red spectroscopy (IR) and liquid chromatography high-resolution mass spectrometry (LC-HRMS). The second objective was to explore the metabolism of MXPr in silico and in vitro. To detect characteristic metabolites that prove MXPr consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS). A software algorithm (Unifi®) was used to predict in silico biotransformations of MXPr. Three metabolites were identified in the in vitro studies including N-despropyl(nor)MXPr, O-desmethyl MXPr and dihydroMXPr. Most of these phase II metabolites were confirmed to be present in urine and hair samples collected from an MXPr consumer. This is the first report of the identification of MXPr in France with analytical findings. This study highlights the challenge of identifying new psychoactive substances (NPS) when they are missing from compound libraries and if a standard is not available. The use of various complementary analytical methods combined with HRMS offers a promising approach for the molecular characterization of NPS.