Higher Hospital Admissions Among Patients With Repeat Antibiotic Use

Previous research has established that individuals who are prescribed many courses of antibiotics can develop antimicrobial resistance. Investigators of a new study in BMC Medicine evaluated whether frequent antibiotic use is associated with reduced infection-related hospital admissions. The investigators found that repeated courses of antibiotics may have limited benefit and be linked with adverse outcomes.

The study team used data from the Clinical Practice Research Databank and the Secure Anonymized Information Linkage database, 2 United Kingdom based electronic health record collections. Data from 1.8 million patients were included in the analysis.

The primary outcome was hospital admission with an infection-related complication in the 30 or 182 days after an antibiotic prescription.

The study population consisted of patients in the electronic health records prescribed a systemic antibiotic by a primary care provider from January 2000 through December 2017. The study population was restricted to patients with at least 3 years of previous history in the electronic health records to evaluate long term effects.

The Clinical Practice Research Databank yielded 11.5 million antibiotic prescriptions. The smaller Wales-based Secure Anonymized Information Linkage database contained 3.7 million.

In the Clinical Practice Research Databank, 5.1 million antibiotic prescriptions took place after a recent record of an upper respiratory infection, lower respiratory tract infection, urinary tract infection, otitis media, and externa. Another 2.0 million had a recent record of another infection, and 4.3 million had no indication recorded.

Patients in the Clinical Practice Research Databank were given 7.1 antibiotic prescriptions on average in the 3 years prior. In the Secure Anonymized Information Linkage database, patients received an average of 6.6 antibiotics in the 3 years prior.

In the Clinical Practice Research Databank, 56.9% of antibiotic prescriptions were for patients with 3+ prescriptions in the 3 years before and 18.9% were for patients with 9+ previous prescriptions.

The most common antibiotic prescribed was amoxicillin, but use decreased among patients with higher past antibiotic use. Those patients were more likely to receive prescriptions for clarithromycin, nitrofurantoin, and cephalexin.

Hospital admissions peaked in all prior-exposure categories shortly after antibiotic initiation. However, for patients with limited past antibiotic use, rates quickly and substantially dropped over time. On the other hand, patients with frequent past antibiotic use saw less reductions with rates remaining high over the following 6 months.

“In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90—1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14–1.81] in the days 4–30 after and 3.22 [95% CI 2.29–4.53] in the 3–6 months after,” study authors wrote.

The investigators suggested several explanations for the patterns they observed including that there are immunocompromised patients and patients colonized with resistant bacteria. Though, there could be a casual factor involving gut microbiota.

“The intestinal commensal microbiota provides colonization resistance against pathogens. It may be possible that antibiotics cause dysbiosis (perturbations of the intestinal microbiota), contributing to the loss of colonization resistance followed by an increment of the resistome in the intestinal microbiota,” the study authors proposed.

The investigators concluded by arguing that there is little evidence in the literature for the effectiveness of repeat antibiotic use in primary care, that dysbiosis may lead to adverse outcomes over time, and that antimicrobial stewardship interventions should target patients with frequent antibiotic use.

A December 2019 study examining antibiotic prescriptions indications in the United States among a nationally representative sample found that 57% of antibiotic prescriptions were for appropriate indications, 25% inappropriate indications, and 18% had neither appropriate nor inappropriate documentation. That leaves up to 43% of prescriptions potentially inappropriate.

Health disparities can also lead to appropriate antibiotic prescriptions that would not be needed if patients had access to routine care. A study found many Medicaid patients wind up at the emergency department for dental care that may not have been necessary if they’d had a dentist, leading to antibiotic and opioid prescriptions.