Biology subjects

MacFadden, D. R.

Publications and source records attributed to MacFadden, D. R..

4 recordsLinked to original sources

bioRxiv2018

Rates of increase of antibiotic resistance and ambient temperature in Europe: a cross-national analysis of 28 countries between 2000-2016

BackgroundWidely recognized as a major public health threat globally, the rapid increase of antibiotic resistance in bacteria could soon render our most effective method to combat infections obsolete. Factors influencing the burden of resistance in human populations remain poorly described, though temperature is known to play an important role in mechanisms at the bacterial level.\n\nMethodsWe performed an ecologic analysis of country level antibiotic resistance prevalence in 3 common bacterial pathogens across 28 countries in Europe, and used multivariable models to evaluate associations with minimum temperature and other predictors over a 17-year period (2000-2016). We quantified the effects of minimum temperature, population density, and antibiotic consumption on the rate of change of antibiotic resistance across geographies.\n\nFindingsFor three common bacterial pathogens and four classes of antibiotics, we found evidence of a long-term effect of ambient minimum temperature on rates of increase of antibiotic resistance across 28 countries in Europe between 2000-2016. Specifically, we show that across all antibiotic classes for the pathogens E. coli and K. pneumoniae, European countries with 10{degrees}C warmer ambient temperatures have experienced more rapid increases in antibiotic resistance over the 17-year period, ranging between 0.33%/year (95% CI 0.2, 0.5) and 1.2%/year (0.4, 1.9), even after accounting for recognized drivers of resistance including antibiotic consumption and population density. We found a decreasing relationship for S. aureus and methicillin of -0.4%/year (95% CI -0.7, 0.0), reflecting widespread declines in MRSA across Europe over the study period.\n\nInterpretationAmbient temperature may be an important modulator of the rate of change of antibiotic resistance. Our findings suggest that rising temperatures globally may hasten the spread of resistance and complicate efforts to mitigate it.\n\nFundingCanadian Institutes of Health Research Fellowship (D.R.M.).

epidemiology↗

bioRxiv2018

Lineage calling can identify antibiotic resistant clones within minutes

Surveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empiric antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could impact patient treatment and outcomes. Here we present a method called genomic neighbor typing for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both S. pneumoniae and N. gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in determination of resistance within ten minutes (sens/spec 91%/100% for S. pneumoniae and 81%/100% N. gonorrhoeae from isolates with a representative database) of sequencing starting, and for clinical metagenomic sputum samples (75%/100% for S. pneumoniae), within four hours of sample collection. This flexible approach has wide application to pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.

bioinformatics↗

bioRxiv2018

Antimicrobial resistance prevalence and rates of hospitalization with septicemia in the diagnosis in adults in different US states

ObjectivesRates of hospitalization with sepsis/septicemia and associated mortality in the US have risen significantly during the last two decades. Antibiotic resistance may contribute to the rates of sepsis-related outcomes through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. However, there is limited information about the relation between prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes. MethodsFor different age groups of adults (18-49y,50-64y,65-74y,75-84y,85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014 and rates of hospitalization with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) reported to the Healthcare Cost and Utilization Project (HCUP), as well as rates of mortality with sepsis (ICD-10 codes A40-41.xx present on death certificate). ResultsAmong the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones in E. coli had the strongest association with septicemia hospitalization rates for individuals aged over 50y, and with sepsis mortality rates for individuals aged 18-84y. A number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults were also found. ConclusionsOur findings, as well as our related work on the relation between antibiotic use and sepsis rates support the association between resistance to/use of certain antibiotics and rates of sepsis-related outcomes, suggesting the potential utility of antibiotic replacement.

epidemiology↗

bioRxiv2018

Trends in outpatient antibiotic prescribing practice among US older adults, 2011-2015: an observational study

Structured abstractO_ST_ABSObjectiveC_ST_ABSTo identify temporal trends in outpatient antibiotic use and antibiotic prescribing practice among older adults.\n\nDesignObservational study using United States Medicare administrative claims during 2011-2015. Trends in antibiotic use were estimated using multivariable regression adjusting for beneficiaries demographic and clinical covariates.\n\nSettingMedicare.\n\nParticipants4.6 million Medicare beneficiaries from a nationwide, 20% sample of fee-forservice Medicare beneficiaries [≥]65 years old.\n\nMain outcome measurementsOverall rates of antibiotic prescription claims, rates of appropriate and inappropriate prescribing, rates for each of the most frequently prescribed antibiotics, and rates of antibiotic claims associated with specific diagnoses.\n\nResultsAntibiotic claims fell from 1362.2 to 1361.6 claims per 1,000 beneficiaries per year during 2011-2015, an overall 0.2% decrease (95% CI 0.07-0.32). Inappropriate antibiotic claims fell from 552 to 533 claims per 1,000 beneficiaries, a 4.1% decrease (CI 3.9-4.3). Individual antibiotics had heterogeneous changes in use. For example, azithromycin claims per beneficiary decreased by 18.4% (CI 18.2-18.7) while levofloxacin claims increased by 28.1% (CI 27.5-28.6). Azithromycin use associated with each of the potentially appropriate and inappropriate respiratory diagnoses we considered decreased, while levofloxacin use associated with each of those diagnoses increased.\n\nConclusionAmong US Medicare beneficiaries, overall antibiotic use and inappropriate use declined modestly, but individual drugs experienced divergent changes in use. Trends in drug use across indications were stronger than trends in use for individual indications, suggesting that guidelines and concerns about antibiotic resistance were not major drivers of change in antibiotic use.

epidemiology↗