Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric Escherichia coli of Cattle

Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric Escherichia coli (E. coli) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric E. coli could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

From incipient island arc to doubly-vergent orogen: A review of geodynamic models and sedimentary basin-fills of southern Central America

Southern Central America is a Late Mesozoic/Cenozoic island arc that evolved in response to the subduction of the Farallón Plate beneath the Caribbean Plate in the Late Cretaceous and, from the Oligocene, the Cocos and Nazca Plates. Southern Central America is one of the best studied convergent margins in the world. The aim of this paper is to review the sedimentary and structural evolution of arc-related sedimentary basins in southern Central America, and to show how the arc developed from a pre-extensional intra-oceanic island arc into a doubly-vergent, subduction orogen. The Cenozoic sedimentary history of southern Central America is placed into the plate tectonic context of existing Caribbean Plate models. From regional basin analysis, the evolution of the southern Central American island arc is subdivided into three phases: (i) non-extensional stage during the Campanian; (ii) extensional phase during the Maastrichtian-Oligocene with rapid basin subsidence and deposition of arc-related, clastic sediments; and (iii) doubly-vergent, compressional arc phase along the 280 km long southern Costa Rican arc segment related to either oblique subduction of the Nazca plate, west-to-east passage of the Nazca–Cocos–Caribbean triple junction, or the subduction of rough oceanic crust of the Cocos Plate. The Pleistocene subduction of the Cocos Ridge contributed to the contraction but was not the primary driver. The architecture of the arc-related sedimentary basin-fills has been controlled by four factors: (i) subsidence caused by tectonic mechanisms, linked to the angle and morphology of the incoming plate, as shown by the fact that subduction of aseismic ridges and slab segments with rough crust were important drivers for subduction erosion, controlling the shape of forearc and trench-slope basins, the lifespan of sedimentary basins, and the subsidence and uplift patterns; (ii) subsidence caused by slab rollback and resulting trench retreat; (iii) eustatic sea-level changes; and (iv) sediment dispersal systems