First-line antibiotic resistance may have increased 12% over 2 decades

More than 1 in 10 first-line antibiotic monotherapies for 4 common infections had treatment failure, an overall increase of 12% from 1991 to 2012, an industry-funded study found.

Researchers conducted a longitudinal analysis of data from nearly 700 primary care practices and 14 million people in the U.K. to determine failure rates for first-line antibiotics used for upper and lower respiratory tract infections, skin and soft-tissue infections, and acute otitis media, as well as how the rates changed from 1991 to 2012.

From 58 million antibiotic prescriptions, researchers reviewed 10,967,607 monotherapy episodes for the 4 indications: 4,236,574 (38.6%) for upper respiratory tract infections; 3,148,947 (28.7%) for lower respiratory tract infections; 2,568,230 (23.4%) for skin and soft-tissue infections; and 1,013,856 (9.2%) for acute otitis media.

Results appeared online Sept. 23 at The BMJ. The study was funded by Abbott Healthcare Products, and co-authors from the company helped design the study and suggested editorial changes.

Probable antibiotic treatment failures were identified by the patient having switched to an alternative antibiotic within 30 days of treatment (94.4%) or having been referred to a specialist or specialist clinic (4.6%). In 1991, the overall failure rate was 13.9%: 12% for upper respiratory tract infections, 16.9% for lower respiratory tract infections, 12.8% for skin and soft-tissue infections, and 13.9% for acute otitis media. By 2012, the overall failure rate was 15.4%, a 12% increase compared with 1991; the highest rate was seen in lower respiratory tract infections.

Failure rates were below 20% for most commonly prescribed antibiotics: amoxicillin, phenoxymethylpenicillin (penicillin V), and flucloxacillin. However, when used to treat upper respiratory tract infections (56,474 infections), trimethoprim had an overall failure rate of 37.2%, increasing from 24.7% in 1991-1995 to 55.9% in 2008-2012. Failure rates of cephalosporins for lower respiratory tract infections increased markedly, the researchers noted. For example, rates for cephalexin rose from 22% in 1991-1995 to 30.8% in 2008-2012, and rates for ciprofloxacin rose from 22.3% in 1991-1995 to 30.8% in 2008-2012. In contrast, failure rates for flucloxacillin to treat skin and soft-tissue infections did not rise, even though prescribing increased.

Failure rates for macrolides across the 4 types of infections remained largely stable. In 2012, the antibiotics with the lowest failure rates for upper respiratory tract infections were phenoxymethylpenicillin (9.4%) and amoxicillin (12.2%). For lower respiratory tract infections, the lowest failure rates were for amoxicillin (18.8%) and clarithromycin (19.2%). For skin and soft-tissue infections, the lowest rates were for lymecycline (5.8%) and oxytetracycline (7.2%). For acute otitis media, the lowest failure rates were for amoxicillin (10.3%) and erythromycin (13.4%).

The researchers noted that, given the lack of new antibiotic classes on the horizon, increases in failure rates are troubling because of the considerable burden they place on patients and the health care system. They wrote, “Our data suggest that primary care physicians could play a central role in helping to contain rises in antibiotic treatment failure by managing patients' expectations and carefully considering whether each prescription is justified; once the decision is made to prescribe an antibiotic, the choice should follow current guidelines regarding first line drugs.”