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by Nancy Walsh

Primary care patients prescribed an antibiotic for a urinary tract or respiratory infection consistently developed resistance to that antibiotic lasting as long as one year, a British meta-analysis revealed.

In five studies that included 14,348 patients treated for urinary tract infections, within one month of receiving an antibiotic an individual patient’s odds ratio having a resistant pathogen was 4.40 (95% CI 3.78 to 5.12), according to Céire Costelloe, PhD, of the University of Bristol, and colleagues.

By 12 months, a “small but important residual association” remained (OR 1.33, 95% CI 1.15 to 1.53), the researchers reported online in BMJ.

In seven studies of various respiratory pathogens that included 2,605 patients, the odds ratio for resistance within two months of exposure was 2.37 (95% CI 1.42 to 3.95), and remained at 2.37 at 12 months (95% CI 1.25 to 4.50).

However, patients in studies who were not exposed to antibiotics had a pooled odds ratio of 0.08 for resistance in the first two months.

Among the 24 studies of antibiotic prescribing reviewed for the meta-analysis, evidence was also found for a dose-response relation for two commonly prescribed first line antibiotics in primary care, amoxicillin and trimethoprim.

One of the most threatening problems faced by worldwide healthcare services is the increasing prevalence of antimicrobial resistance, but there are many barriers to the appropriate and limited use of antibiotics, including the perception among clinicians and patients that the risk is limited or theoretical.

This erroneous perception may relate, at least in part, to the fact that some studies have examined the association of antibiotic overuse and resistance at the population level, but not at the individual, level.

“Consequently for clinicians, whose primary concern is the unwell individual, the impact of antimicrobial use on the prevalence of societal resistance may not be an important consideration,” they wrote.

Costelloe and colleagues undertook the meta-analysis of studies examining antibiotic resistance among individual patients to highlight the effect of antibiotic prescribing on emergent resistance on the individual level.

Escherichia coli was the organism seen in all of the studies of antibiotic resistance among urinary tract bacteria. In these studies, the drugs involved included nalidixic acid in addition to trimethoprim and amoxicillin.

Bacterium found in the studies of resistance among respiratory pathogens included strains of Streptococci and Haemophilus, and the drugs involved included amoxicillin, azithromycin, and clarithromycin.

One prospective study evaluated resistance to respiratory tract streptococci at multiple specific time points. The pooled odds ratios were:

* At one week, 12.22 (95% CI 6.76 to 22.10)

* At two weeks, 7.70 (95% CI 3.63 to 16.34

* At one month, 6.08 (95% CI 2.76 to 13.39)

* At two months, 3.61 (95% CI 2.18 to 5.97)

* At six months, 2.16 (95% CI 1.30 to 3.61)

That study provided strong evidence of a time trend for resistance to macrolides (β coefficient −0.25, 95% CI −0.39 to −0.11, P=0.004), according to the researchers.

In discussing their findings, Costelloe and colleagues explained that resistance is not simply a characteristic of the pathogen, but also affects the individual because plasmids and integrons can be transferred from invading bacteria to commensal organisms.

“And because both transmission of commensal organisms between individuals and antibiotic prescribing in the community remain frequent events, even a transient effect of antibiotic use on the carriage of resistant organisms by an individual could have a major impact on the endemic level of resistance in the population,” they cautioned.

The likelihood that resistant bacteria would be isolated from a patient was related to the number or duration of antibiotic courses prescribed in the previous 12 months; the more courses or doses of a drug, the more likely resistant bacteria would be found.

They concluded that the fewest courses of antibiotics should be used in primary care, and if patients are treated and develop another infection within a year, consideration should be given to choosing a different antibiotic for that infection.

The researchers noted some positive publication bias in the urinary tract infection studies, but they were unable to assess publication bias in the respiratory tract studies.

In an accompanying health systems perspective analysis, Chantal M. Morel, PhD, and Elias Mossialos, PhD, of the London School of Economics and Political Science, addressed how financial incentives might help persuade pharmaceutical companies to develop more new antibiotics.

“Incentives to develop new antibiotics should be designed with some early funding to ignite interest and appropriate rewards for the high risks of research and development,” Morel and Mossialos wrote.

They added that such actions should be accompanied by efforts to dismantle incentive structures that lead to overuse of antibiotics.

An editorial that also accompanied the meta-analysis further addressed future needs in combating infectious disease.

“Much more can be done to bolster diagnostics and surveillance of resistance patterns, reduce demand from patients for unnecessary antibiotics, and help standardize optimal dosing regimens and treatment times,” stated Anthony D. So, MD, of Duke University in Durham, N.C., and colleagues.

The United States and the European Union have established a task force on antimicrobial resistance to improve the therapeutic use of antibiotics in the medical and veterinary communities, to prevent drug-resistant infections, and to help move more new drugs to the market.

“The EU-US Transatlantic Task Force must rise to this complex challenge and define its solution in global terms. Nothing less than the future of medicine, from organ transplants to chemotherapy, is at stake, and there will be no second chances,” So and colleagues warned.

Nancy Walsh is a MedPage Today contributing writer.

Originally published in MedPage Today. Visit MedPageToday.com for more infectious disease news.