Prescribing of different antibiotics, rates of sepsis-related mortality and bacteremia in the US and England, and the utility of antibiotic replacement vs. reduction in prescribing

Background Antibiotic use contributes to the rates of bacteremia, sepsis and associated mortality, particularly through lack of clearance of resistant infections following antibiotic treatment. At the same time, there is limited information on the effects of prescribing of some antibiotics vs. others on the rates of outcomes related to severe bacterial infections.

Methods We looked at associations (univariate, as well as multivariable for the US data) between the proportions (state-specific in the US, Clinical Commissioning Group (CCG)-specific in England) of different antibiotic types/classes among all prescribed antibiotics in the outpatient setting (oral antibiotics in the US), and rates of outcomes (mortality with sepsis, ICD-10 codes A40-41 present on the death certificate in different age groups of US adults, and E. coli and MSSA bacteremia in England) per unit of antibiotic prescribing (defined as the rate of outcome divided by the rate of prescribing of all antibiotics).

Results In the US, prescribing of penicillins was associated with rates of mortality with sepsis for persons aged 75-84y and 85+y between 2014-2015, while multivariable analyses also shown an association between the percent of individuals aged 50-64y lacking health insurance, as well as the percent of individuals aged 65-84y who are African-American and rates of mortality with sepsis. In England, prescribing of penicillins other than amoxicillin/co-amoxiclav was associated with rates of both MSSA and E. coli bacteremia for the period between financial years 2014/15 through 2017/18.

Conclusions Our results suggest that prescribing of penicillins is associated with rates of E. coli and MSSA bacteremia in England, and rates of mortality with sepsis in older US adults, which agrees with our earlier findings. Those results, as well as the related epidemiological data suggest that replacement of certain antibiotics, particularly penicillins should be considered for reducing the rates of outcomes related to severe bacterial infections.