A large study of electronic health records in the United Kingdom has found a link between the number of antibiotic prescriptions and the risk of infection-related hospitalization.
The study, published today in BMC Medicine, found that patients with more antibiotic prescriptions had a higher risk of infection-related hospital admissions over time, with the risk increasing along with the number of prescriptions. Patients who had received more than nine antibiotic courses in the previous 3 years were found to be more than twice as likely to be admitted to the hospital with an infection within 3 to 6 months as those who'd received one course of antibiotics or fewer.
The authors of the study say the findings indicate that repeated prescribing of antibiotics, a common practice in UK primary care offices, has limited clinical benefit and could be increasing the risk of adverse outcomes.
Risk rises with number of prescriptions
For the population-based cohort study, researchers from the University of Manchester and Public Health England analyzed health records from two databases covering primary care practices in England and Wales—the Clinical Practice Research Databank (CPRD) and Secure Anonymized Information Linkage (SAIL) databases.
The study population consisted of more than 2 million patients prescribed an antibiotic from 2000 through 2017 for common infections, such as upper and lower respiratory tract infections, urinary tract infections, and ear infections. The analysis was restricted to patients with at least 3 years of history in the databases.
The primary outcome analyzed was hospital admission with infection-related complication that occurred in the 6 months after an antibiotic prescription. The researchers divided the patients into five groups based on the number of antibiotic prescriptions received in the previous three years: 0 to 1, 2, 3 to 4, 5 to 8, and 9 or more.
Overall, repeated antibiotic use was frequent, with patients in both databases on average receiving seven antibiotic prescriptions in the previous 3 years. Incidence of hospitalization linked to an infection was highest within the first 3 days after a prescription, and hospitalization rates were similar among all groups.
The adjusted incidence rate ratio (IRR) among CPRD patients was 0.90 (95% confidence interval [CI], 0.77 to 1.04) when comparing infection-related hospitalization after 3 days in patients with the most previous antibiotic use (9 or more prescriptions) compared with those with the least. In both databases, most hospitalizations were for lower respiratory tract infections and pneumonia.
As time went on, infection-related hospitalization decreased, but much less so for patients with more frequent prior antibiotic use, who showed a sustained higher risk of hospitalization over time compared with the lowest-use group. The associated risk was highest in those who'd received 9 or more antibiotics in the previous 3 years. Within 4 to 30 days after a prescription, the rates of hospitalization were more than 50% higher (adjusted IRR, 1.52; 95% CI, 1.34 to 1.72). Differences were even larger in the 3 to 6 months after a prescription (adjusted IRR, 2.26; 95% CI, 1.92 to 2.67).
The results were broadly similar in patients from the SAIL database, and were also similar when the analysis looked at patients with and without comorbidity.
Frequent antibiotics don't help, may hurt
The researchers say it's unclear what exactly is behind the association between increased hospitalization risk and more frequent antibiotic use, but they offer a few potential explanations. For one, the results could be affected by patients who are immunocompromised and as a result suffer more infections, or have been colonized with resistant bacteria from previous hospitalizations.
In addition, frequent antibiotic use could be causing increased resistance, resulting in infections that are harder to treat and require hospitalization.
But another possibility—one that's been suggested in previous research—is that frequent antibiotic use could be disrupting the balance of bacteria in the gut (the intestinal microbiota) in ways that enable colonization with resistant pathogens or make patients more susceptible to infections caused by those pathogens. The researchers acknowledge, however, that their study does not provide direct evidence to support this hypothesis, and that further work is needed to test it.
While that question remains unanswered, the researchers conclude that what's clear from this study and previous studies is that there is little evidence that frequent and repeated antibiotic use for common infections is actually clinically effective.
"In conclusion, there is little evidence in the literature for the clinical effectiveness of repeated antibiotic use in primary care although [it] is common practice," they wrote. "Antimicrobial stewardship interventions should target these patients with high use of antibiotics but apparently limited value."
