Selection and co-selection of antibiotic resistances amongEscherichia coliby antibiotic use in primary care: an ecological analysis

Abstract

The majority of studies that link antibiotic usage and resistance focus on simple associations between the resistance against a specific antibiotic and the use of that specific antibiotic. However, the relationship between antibiotic use and resistance is more complex. Here we evaluate which antibiotics, including those mainly prescribed for respiratory tract infections, are associated with increased resistance among Escherichia coli isolated from urinary samples.Monthly primary care prescribing data were obtained from National Health Service (NHS) Digital. Positive E. coli records from urine samples in English primary care (n=888,207) between April 2014 and January 2016 were obtained from the Second Generation Surveillance System. Elastic net regularization was used to evaluate associations between prescribing of different antibiotic groups and resistance against amoxicillin, cephalexin, ciprofloxacin, co-amoxiclav and nitrofurantoin at the clinical commissioning group (CCG) level. England is divided into 209 CCGs, with each NHS practice prolonging to one CCG.Amoxicillin prescribing (measured in DDD/ 1000 inhabitants / day) was positively associated with amoxicillin (RR 1.03, 95% CI 1.01 – 1.04) and ciprofloxacin (RR 1.09, 95% CI 1.04 – 1.17) resistance. In contrast, nitrofurantoin prescribing was associated with lower levels of resistance to amoxicillin (RR 0.92, 95% CI 0.84 – 0.97). CCGs with higher levels of trimethoprim prescribing also had higher levels of ciprofloxacin resistance (RR 1.34, 95% CI 1.10 – 1.59).Amoxicillin, which is mainly (and often unnecessarily) prescribed for respiratory tract infections is associated with increased resistance against various antibiotics among E. coli causing urinary tract infections. Our findings suggest that when predicting the potential impact of interventions on antibiotic resistances it is important to account for use of other antibiotics, including those typically used for other indications.Author summaryAntibiotic resistance is increasingly recognised as a threat to modern healthcare. Effective antibiotics are crucial for treatment of serious bacterial infections and are necessary to avoid that complicated surgical procedures and chemotherapy becoming life-threatening. Antibiotic use is one of the main drivers of antibiotic resistance. The majority of antibiotic prescriptions are prescribed in primary care, however, a large proportion of these antibiotic prescriptions are unnecessary. Understanding which antibiotics are causing antibiotic resistance to what extent is needed to prevent under- or over-investment in interventions lowering use of specific antibiotics, such as rapid diagnostic tests for respiratory tract infection.We have statistically evaluated which antibiotics are associated with higher and lower levels of antibiotic resistance against common antibiotics among Escherichia coli bacteria sampled from the urinary tract by comparing antibiotic prescribing and resistance in different geographical areas in England. Our model shows that amoxicillin, the most commonly used antibiotic in England and mainly used for respiratory tract infections, is associated with increased resistance against several other antibiotics among bacteria causing urinary tract infections. The methods used in this study, that overcome several of the limitations of previous studies, can be used to explore the complex relationships between antibiotic use and antibiotic resistance in other settings.

Effect of antibiotic stewardship interventions in primary care on antimicrobial resistance of Escherichia coli bacteraemia in England (2013–18): a quasi-experimental, ecological, data linkage study

“… 36 One study by Pouwels and colleagues noted that the use of specific antibiotics, such as levofloxacin, for E coli urinary tract infections is associated with resistance to other antibiotics used for other indications, such as ciprofloxacin, leading to co-selection of antibiotic resistance E coli isolates. 40 One of the most likely reasons for the unhindered resistance despite decreases in antibiotic prescribing is the accumulation of mutations conferring resistance to antibiotics and acquired antibiotic resistance genes within the bacterial populations. 41 Collignon and colleagues suggested that transmission of antibiotic-resistant genes was likely to be the most dominant contributor to antibiotic resistance, implying that resistance might continue despite a restriction of prescribing.…”

Uso ambulatorio de cefalosporinas en una población colombiana: estudio de prescripción-indicación

“…Cefalexina y cefradina para el manejo de infecciones del tracto respiratorio superior y de vías urinarias no complicadas presentaron una menor proporción de uso, probablemente por ser un manejo alternativo en estas indicaciones 14,18 . El uso de antimicrobianos que son útiles en varias indicaciones podría incrementar el riesgo de www.revinf.cl Antimicrobianos aparición de cepas resistentes, como se ha mostrado para amoxicilina o cotrimoxazol 32 . Dado que las cefalosporinas se pueden emplear en múltiples patologías, se debería limitar su uso en indicaciones en las cuales no sean tratamiento de primera línea, con el fin de protegerlas como recurso, evitando el desarrollo de resistencia bacteriana y desenlaces adversos.…”

Overuse of antibiotics: Can viral vaccinations help stem the tide?

“…While, for example, lower levels of amoxicillin prescribing in primary care are associated with lower levels of resistance against amoxicillin and trimethoprim among urinary specimens, 5 this does not necessarily result in a reduction in resistance against antibiotics that are almost exclusively used in the hospital setting 3 . Moreover, within England, the reported number of macrolide‐resistant BSI for Gram‐positive bacteria increased between 2014 and 2018, even though prescribing for macrolides decreased in both hospitals and primary care 3 .…”