Exploring the relationship between primary care antibiotic prescribing for urinary tract infections, Escherichia coli bacteraemia incidence and antimicrobial resistance: an ecological study

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states

“…In a study of cases of E. coli bacteremia in England, urogenital infection had been treated in 310/891 (34.8%) cases in the 4 weeks preceding bacteremia and this sub-population differed very significantly in its antibiotic resistances [13], suggesting treatment failure due to presence of antibiotic resistance prior to the onset of bacteremia. Antibiotic use is one important driver of the prevalence of antibiotic resistance [14][15][16][17][18][19] and thus may contribute to sepsis incidence.…”

“…Antibiotic use has been implicated as a cause of resistance not only to the drug class used, but to other drugs. For example, fluoroquinolone use was found to be associated with methicillinresistant S. aureus (MRSA) infections [20][21][22][23], with some of those infections leading to sepsis outcomes, while amoxicillin use was found to be associated with trimethoprim resistance in Enterobacteriaceae [14], with trimethoprim-resistant urinary tract infections (UTIs) leading to bacteremia outcomes [15]. While causality is not conclusively proven in these studies, it is plausible given the fact that resistance to different drug classes tends to cluster in bacterial populations, leading to the phenomenon of co-selection [24,25].…”

“…Earlier work has shown a relationship, including spatial correlations between the rates of antibiotic consumption and prevalence of antibiotic resistance, e.g. [14][15][16][17][18][19]. At the same time, there is limited information on the relationship between levels of prescribing for different antibiotic types/classes, and rates of sepsis hospitalization.…”

Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states

“…For example, prevalence of resistance to certain antimicrobials, including ciprofloxacin and trimethoprim, was found to be significantly higher in bacteremia outcomes associated with urinary tract infections (UTIs) than in the population of patients with UTIs in England [10], suggesting treatment failure to be an important factor behind the volume of UTI-associated bacteremia. Another study documented an association between trimethoprim resistance, trimethoprim use in UTI treatment and subsequent UTI-related bacteremia in England [12], whereas association between amoxicillin use in England and prevalence of trimethoprim resistance (likely modulated by the high rates of cross-resistance) was shown in [13]. The latter represents an example of how resistance to/use of one antibiotic affects the prevalence of other resistance phenotypes, or pathogenic organisms, with additional examples being the relation between fluoroquinolone use/resistance and (i) methicillin-resistant staphylococcus aureus (MRSA) infections [14,15]; (ii) extended-spectrum beta-lactamese (ESBL) producing infections [16,17]; (iii) Clostridium difficile (C. difficile) infections [18].…”

“…Our results support the need for (i) examing the utility of replacement of certain antibiotics by certain others in the treatment of different syndromes for reducing the rates of severe outcomes associated with bacterial infections; (ii) enhancing antibiotic stewardship (including the use of fluoroquinolones), both in the inpatient and the outpatient settings; (iii) stepping up efforts for preventing acquisition of antibiotic-resistant bacteria (particularly E. coli in the elderly) [39]. Additionally, the relation between antibiotic resistance as well as antibiotic use and the rates of severe bacterial infections, including sepsis, as well as the associated mortality outcomes [9][10][11][12]19,20], and the limited options for antibiotic replacement support the need for new antibiotics. This need may not be fulfilled through the current system of antibiotic development/production, and additional incentives for antibacterial research and development are worth considering [40].…”