ABSTRACT
BACKGROUND: Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. Colonisation prevalence data in Cambodia are lacking. The aim of this study was to determine gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated socio-demographic risk factors; and to characterise relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS). RESULTS: Faeces and questionnaire data were obtained from individuals < 16 years in north-western Cambodia, 2012. WGS of cultured ESC-R-EC/KP was performed (Illumina). Maximum likelihood phylogenies were used to characterise relatedness of isolates; ESC-R-associated resistance genes and their genetic contexts were identified from de novo assemblies using BLASTn and automated/manual annotation. 82/148 (55%) of children/adolescents were ESC-R-EC/KP colonised; 12/148 (8%) were co-colonised with both species. Independent risk factors for colonisation were hospitalisation (OR: 3.12, 95% CI [1.52-6.38]) and intestinal parasites (OR: 3.11 [1.29-7.51]); school attendance conferred decreased risk (OR: 0.44 [0.21-0.92]. ESC-R strains were diverse; the commonest ESC-R mechanisms were blaCTX-M 1 and 9 sub-family variants. Structures flanking these genes were highly variable, and for blaCTX-M-15, - 55 and - 27 frequently involved IS26. Chromosomal blaCTX-M integration was common in E. coli. CONCLUSIONS: Gastrointestinal ESC-R-EC/KP colonisation is widespread in Cambodian children/adolescents; hospital admission and intestinal parasites are independent risk factors. The genetic contexts of blaCTX-M are highly mosaic, consistent with rapid horizontal exchange. Chromosomal integration of blaCTX-M may result in stable propagation in these community-associated pathogens.
Subject(s)
Carrier State/epidemiology , Cephalosporins/pharmacology , Drug Resistance, Bacterial , Escherichia coli Infections/epidemiology , Gastrointestinal Tract/microbiology , Klebsiella Infections/epidemiology , Adolescent , Anti-Bacterial Agents/pharmacology , Cambodia/epidemiology , Carrier State/microbiology , Child , Child, Preschool , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli/pathogenicity , Female , Gastrointestinal Tract/parasitology , Hospitalization , Humans , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/pathogenicity , Male , Parasitic Diseases/epidemiology , Parasitic Diseases/microbiology , Prevalence , Risk Factors , Surveys and Questionnaires , Whole Genome SequencingABSTRACT
BACKGROUND: Re-intubation and re-operation may occasionally be required after neuromuscular block (NMB) reversal. This study evaluated block onset times of a second dose of rocuronium (1.2 mg kg(-1)) after sugammadex reversal of rocuronium 0.6 mg kg(-1). METHODS: In this open-label study of healthy anaesthetized volunteers, subjects received rocuronium 0.6 mg kg(-1), were antagonized at 1-2 post-tetanic counts with sugammadex 4.0 mg kg(-1), and received rocuronium 1.2 mg kg(-1) at 5, 7.5, 10, 15, 20, 22.5, 25, 27.5, 30, 45, or 60 min after sugammadex. Spontaneous recovery occurred after repeat rocuronium dose. Primary endpoints were the onset time of maximal block (time to lowest T(1) value reached) and the clinical duration of block (until T(1)=25%) after repeat rocuronium dose. RESULTS: Sixteen subjects were included. For subjects receiving rocuronium 1.2 mg kg(-1) 5 min after sugammadex (n=6), mean (sd) onset time (to T(1)=0) was 3.06 (0.97) min; range, 1.92-4.72 min. For repeat dose time points ≥25 min (n=5), mean onset was faster (1.73 min) than for repeat doses <25 min (3.09 min) after sugammadex. The duration of block ranged from 17.7 min (rocuronium 5 min after sugammadex) to 46 min (repeat dose at 45 min). Mean duration was 24.8 min for repeat dosing <25 min vs 38.2 min for repeat doses ≥25 min. CONCLUSIONS: Rapid re-onset of NMB occurred after repeat dose of rocuronium 1.2 mg kg(-1) as early as 5 min after sugammadex in healthy volunteers. Re-onset of block took longer if second rocuronium dose was <25 min after sugammadex. The duration of action of second rocuronium dose increased with later repeat dose time points.
Subject(s)
Androstanols/administration & dosage , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/administration & dosage , gamma-Cyclodextrins/pharmacology , Adolescent , Adult , Androstanols/antagonists & inhibitors , Androstanols/pharmacology , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Models, Biological , Neuromuscular Blockade/methods , Neuromuscular Junction/physiology , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Neuromuscular Nondepolarizing Agents/pharmacology , Pilot Projects , Rocuronium , Sugammadex , Young AdultABSTRACT
The Thunderdome-party was a mass gathering of 14000 young people. Many of them were under influence of drugs (amphetamine and ecstasy (MDMA)). The organization of on-site emergency medical assistance was essential in order to avoid overload at the local emergency department and to avoid a disequilibrium of the local emergency medical system, the 'call 100' system in Belgium. The benefit of a prehospital medical team at the event is illustrated by the description of the population treated on-site. Toxicological screening of blood and urine was not necessary to safely treat drug intoxication during the Thunderdome-party.
