Knight, G. M. | bioRxiv Science

bioRxiv2017

The relative fitness of drug resistant Mycobacterium tuberculosis: a modelling study of household transmission in Lima, Peru

The relative fitness of drug resistant versus susceptible bacteria in an environment dictates resistance prevalence. Estimates for the relative fitness of resistant Mycobacterium tuberculosis (Mtb) strains are highly heterogeneous and mostly derived from in-vitro experiments. Measuring fitness in the field allows us to determine how the environment influences resistance spread.\n\nWe designed a household structured, stochastic mathematical model to estimate the fitness costs associated with multi-drug resistance (MDR) carriage in Mtb in Lima, Peru between 2010-2013. By fitting the model to data from a large prospective cohort study of TB disease in household contacts we estimated the fitness, relative to susceptible strains with a fitness of 1, of MDR-Mtb to be 0.33 (95% credible interval: 0.17-0.54) or 0.39 (0.26-0.58), if only transmission or progression to disease, respectively, was affected. The relative fitness of MDR-Mtb increased to 0.57 (0.43-0.73) when the fitness cost influenced both transmission and progression to disease equally.\n\nWe found the average relative fitness of MDR-Mtb circulating within households in Lima, Peru between 2010-2013 to be significantly lower than concurrent susceptible-Mtb. If these fitness levels do not change, then existing TB control programmes are likely to keep MDR-TB prevalence at current levels in Lima, Peru.

epidemiology↗

bioRxiv2017

A National Estimate of the Health and Cost Burden of Escherichia coli Bacteraemia in the Hospital Setting: The Importance of Antibiotic Resistance.

BackgroundAntibiotic resistance poses a threat to public health and a burden to healthcare systems. Escherichia coli causes more bacteraemia cases in England than any other bacterial species, these infections, in part due to their high incidence, also pose a significant antibiotic resistance burden. The main aim of this study was to estimate the impact of E. coli bacteraemia on patient in-hospital mortality and length of stay. Secondarily, this study also aimed to estimate the effect of antibiotic resistance on these outcomes.\n\nMethods and FindingsCase patients were adult E. coli bacteraemia patients infected between July 2011 and June 2012, as reported in an English national mandatory surveillance database, with susceptibility data taken from a national laboratory surveillance database. Control patients were all non-case, adult patients with an English hospital admission record. Case and control patient characteristics and admission information were taken from NHS Digital Datasets. Resistance was defined as non-susceptible and intermediate isolates, whilst susceptible was defined as susceptible and non-tested isolates. Time to in-hospital mortality and discharge was investigated through Cox proportional hazards models. To acquire estimates of excess length of stay, multistate models were constructed, with a unit bed day cost applied to estimate cost burden. The total number of case and control hospital spells was 14,051 and 8,919,275 respectively. Acquisition of E. coli bacteraemia was associated with a statistically significant increased daily risk of in-hospital mortality, especially for the first eight days of someones hospital admission [Hazard Ratio = 2.77 (95% confidence interval; 2.61-2.94)]. Antibiotic resistance did not seem to significantly increase this risk further, though did significantly reduce risk of experiencing a discharge event (dead or alive). E.coli bacteraemia was estimated to cost {pound}14,340,900 over the study period (rounded to the nearest {pound}100), with resistance associated with excess costs per infection of {pound}220 - {pound}420 dependent on resistance type, for those where a significant impact was found (rounded to the nearest {pound}10).\n\nConclusionsE. coli bacteraemia places a significant burden on patient health and on the hospital sector in England. Resistance is an important factor on length of stay with regards to such infections.

epidemiology↗