Antibiotic treatment failure in four common infections in UK primary care 1991-2012: longitudinal analysis

What's labelled Cochrane contains not always Cochrane

The publication of Craig J Currie et al. from the Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, UK, and Global Epidemiology, Pharmatelligence, Cardiff, UK, is not so intelligent as it wants to be.

1. Conclusions like "from 1991 to 2012, more than one in 10 first line antibiotic monotherapies for the selected infections were associated with treatment failure" mean in the publications reality that in 22 years of observation only 13.9 to 15.4 percent of antibiotic treatment failed. In the meantime 86.1 to 84.6 percent of the antibiotic treatment obviously succeeded instead.

2. When "overall failure rates increased by 12% over this period..." of 22 years this is an annual increase of 0.545 percent only.

In my opinion most of the British GP and Family Doctors did right with their targeting antibiotic treatment from 1991 until 2012. Nearly constant failure rates from 13.9 to 15.4 percent over such a long period instead of augmenting antibiotic resistance, increasing allergies e. g. against penicillin and amoxicillin, ß-lactamase active germs, less effectiveness of older antibiotics e.g. trimethoprim and tetracycline, non indicated ciprofloxacin therapy, and new multi-resistant germs like MRSA or others should be taken into consideration.

This seems to be a very undifferentiated BMJ-publication caricaturing the former idea of critical Cochrane investigation.

This phenomenal analysis must be a first, and deserves congratulations.

Analysing GP records is hugely difficult, and GPRD goes to great lengths to secure accurate reliable data, with mitigation of bias.

The authors expected to see a general rise in ‘treatment failure’, no doubt in anticipation of rising antibiotic resistance. But the study revealed unexpected results, not easy to explain. Standard trusty amoxicillin appears to have remained reliable throughout the decades ! Whilst Trimethoprim, Ciprofloxacin and Cefalexin are increasingly failing. The authors suggest this may be because of inappropriate off-guideline usage, which would explain their initial failure-rate back in the 1990s. But how does it explain the steady deterioration vis-à-vis amoxicillin ?

Maybe there is an unrecognised bias resulting from the definition of ‘monotherapy’ and ‘treatment failure’? Only episodes of ‘monotherapy’ are examined, whereby the initial antibiotic is the first in a 30-day period, and no other antibiotic should have been given within 30 days. But then the definition of ‘failure’ includes patients given another antibiotic within 30 days, lumped together with other criteria, which may represent very different things. Surely there should be no one with a second antibiotic within 30 days of the first, since that was an exclusion criterion ? To my mind, a switch of antibiotic within the period of illness under observation (2-15 days), should be the better indicator of a GP thinking that treatment has failed.

Given that the really significant ‘failures’ relate to hospital admissions for lower respiratory infections, it would be useful if the authors followed up with a detailed analysis of this subset, with a more refined definition of failure. I suggest something akin to that used by Hess et al., in their reference 14:

“ defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. “

There is a wealth of information here ready to answer many more questions. An especially useful tool would be an ‘antibiotic failure’ monitoring system, telling us when our ‘first-line’ schedules need updating !

Well done, Currie et al, and GPRD !

Reference
Hess G, Hill JW, Raut MK, Fisher AC, Mody S, Schein JR, et al. Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: results from a claims analysis. Adv Ther2010;27:743-55.