Antibiotic Failure: Not Only a Hospital Phenomenon


The public tends to think of antibiotic resistance as a problem that largely affects patients in hospitals, say researchers from Cardiff University, University of Oxford, and Pharmatelligence, all in the United Kingdom (UK); and Abbott Healthcare Products in the Netherlands. Unfortunately, they note, so do many primary care practitioners, even though recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism.

As the researchers’ study of 22 years of primary care prescribing in the UK makes clear, antibiotic resistance is a primary care problem, too. During that time, > 1 in 10 of the initial antibiotic monotherapies they studied failed.

Using data on 58 million antibiotic prescriptions from the Clinical Practice Research Datalink, a database derived from nearly 700 primary care practices in the UK, the researchers analyzed almost 11 million first-time monotherapy episodes for 4 indications: upper respiratory tract infections (URTIs), lower respiratory tract infections, skin and soft tissue infections, and acute otitis media. Of all antibiotic prescriptions, 98% were monotherapy.

Over time, the proportion of infections treated with antibiotics changed. The greatest increase was in the smallest class, acute otitis media, which rose from 63% in 1991 to 83% in 2012. The proportion of URTIs treated with antibiotics dropped from 59% in 1991 to 55% in 2012.

The most commonly prescribed antibiotics were amoxicillin (42% of infections), followed by phenoxymethylpenicillin (penicillin-V) (95% for URTIs) and flucloxacillin (97% for skin and soft tissue infections).

The treatment failure rate rose from 13.9% in 1991 to 15.4% in 2012, with some “notably high levels of failure,” the researchers say. They cite trimethoprim’s overall failure rate of 37% (increasing from 24.7% in 1991 to 55.9% in 2012) when used to treat URTIs. Failure rates for cephalosporins also increased “markedly.” By contrast, failure rates for macrolides across the 4 infection classes remained largely stable. In 2012, the antibiotics with the lowest failure rates were penicillin-V for URTIs, and lymecycline and oxytetracycline for skin and soft tissue infections.

The rise in antibiotic failures was less prominent for the most frequently prescribed antibiotics and those recommended for first-line treatment, such as amoxicillin, clarithromycin, and erythromycin. The more striking increases were seen in antibiotics not usually recommended as first-line treatments for the infection classes in the study, such as cephalosporins. Those drugs, however, might have been prescribed for more severely ill and frail patients who had recently been prescribed a first-line drug or who were already resistant to a drug, the researchers say.

Most of the increase in failures dated from 2000, the researchers say, when community antibiotic prescribing, which had been falling in the late 1990s, plateaued, and then once again began rising.

Their findings could represent a phenomenon that will resolve, or might be an “early indication of a more dramatic and worrying process,” the researchers caution. The finding that 1 in 10 initial antibiotic treatments in primary care fails represents a “considerable burden” on patients and the health care system. They suggest that primary care physicians can play a central role in helping to contain rises in antibiotic treatment failures by managing patient expectations and carefully considering whether each prescription is justified.

Currie CJ, Berni E, Jenkins-Jones S, et al. BMJ. 2014;349:g5493.
doi: 10.1136/bmj.g5493.

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