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: a cross-sectional study

Abstract

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 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 as either underlying or contributing causes of death on a death certificate in different age groups of US adults; E. coli as well as MSSA bacteremia in England) per unit of antibiotic prescribing (defined as the rate of outcome divided by the rate of outpatient 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. 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. Additionally, multivariable analysis for the US data has 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 the corresponding age groups. 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. Those results, as well as the related epidemiological data suggest that replacement of certain antibiotics, particularly penicillins in the treatment of certain syndromes should be considered for reducing the rates of outcomes related to severe bacterial infections.

Rise in mortality involving poisoning by medicaments other than narcotics, including poisoning by psychotropic drugs in different age/racial groups in the US

“…Our results, as well as other work, e.g. [19][20][21][22][23][24]26,27] support the need for a comprehensive evaluation of the impact of prescribing/misuse of various medications on health, including mortality outcomes.…”

“…Those results, as well as earlier studies showing associations between medication use and health-related and mortality outcomes (e.g. [19][20][21][22][23][24]26,27]), including for deaths that do not have poisoning listed on a death certificate further support the need for a comprehensive evaluation of the impact of prescribing and misuse of various medications on health and mortality outcomes in different population groups, as well as the related guidance regarding the use of those medications. Additionally, such analyses may help elucidate the role of medication use/misuse in the long-term decline in life expectancy in Non-Hispanic whites compared to other major racial groups in the US [1].…”

“…A number of studies, including meta-analyses, suggest elevated risks for mortality, including sudden cardiac death (SCD) associated with the use of various psychotropic drugs (both antipsychotics and antidepressants), as well as certain sedative-hypnotic drugs (benzodiazepines) [19][20][21][22][23][24], though firmly establishing causal links in such studies can be challenging [25]. For the case of antibiotics, recent work suggests an association between prescribing rates for certain antibiotics, particularly penicillins in the elderly, and mortality and hospitalization rates for sepsis/septicemia [26,27], with that association presumably being mediated by antimicrobial resistance [28]. Further work is needed to gain a more comprehensive understanding of the effect of prescribing and misuse of different medications on health-related, including mortality outcomes in different age/racial groups.…”

“…[19][20][21][22][23][24] have suggested elevated risks for mortality and other health-related outcomes associated with the use of psychotropic medications (both antipsychotic medications and antidepressants) and sedative-hypnotic medications (particularly benzodiazepines). Recent work suggests associations between rates of prescribing for penicillins, and rates of mortality and hospitalization for septicemia/sepsis in older adults [26,27]. Additionally, rates of consumption of certain medications, particularly psychotropic drugs, sedative-hypnotic medications and antibiotics in Non-Hispanic whites are higher than in other major racial groups (save for Native Americans) [10][11][12][13][14][15][16][17][18], and those differences may have an effect on health-related, including mortality outcomes [19][20][21][22][23][24]26,27].…”

Rise in mortality involving poisoning by medicaments other than narcotics, including poisoning by psychotropic drugs in different age/racial groups in the US

“…A number of studies, including meta-analyses, suggest elevated risks for mortality, including sudden cardiac death (SCD) associated with the use of various psychotropic drugs (both antipsychotics and antidepressants), as well as certain sedative-hypnotic drugs (benzodiazepines) [19–24], though firmly establishing causal links in such studies can be challenging [25]. For the case of antibiotics, recent work suggests an association between prescribing rates for certain antibiotics, particularly penicillins in the elderly, and mortality and hospitalization rates for sepsis/septicemia [26,27], with that association presumably being mediated by antimicrobial resistance [28]. Further work is needed to gain a more comprehensive understanding of the effect of prescribing and misuse of different medications on health-related, including mortality outcomes in different age/racial groups.…”