Urine should not be seen as a useless excretion product. Doping experts know, as do clinical microbiologists. In two recently published studies zillions of urine cultures were drained from computer systems and linked to primary care data, yielding very interesting findings. One study from Israel quantified the effects of direct and indirect fluoroquinolone use on antibiotic resistance in E. coli, see also our comments to that study. The second comes from the UK, the country that has an ambition to reduce Gram-negative bacterial bloodstream infection rates by 50%, because of increasing BSI rates. This study may provide both the reason for the problem and the direction to meet that ambition.
The study in short: they analysed 312.896 UTI episodes, that were categorized upon the timing of antibiotic prescription by the GP: Immediate (n=271.070), deferred (n=19.292) or none (n=22.534). Then they quantified the proportion of patients developing BSI (<60 days of UTI) which was 0,2% (n=479) among those with immediate antibiotics and 2.2% (n=413) and 2.9% (n=647) for those with deferred and no antibiotics, respectively. Control of confounders yielded odds ratio for BSI of 7.12 (6.22-8.14) and 8.08 (7.12-9.16) for deferred and no antibiotics, compared to immediate antibiotics. Actually, adjusted hazard ratios for mortality at day 60 after UTI were 1.16 (1.06-1.27) and 2.18 (2.04-2.33) for deferred and no antibiotics, compared to immediate antibiotics.
The signal is clear: early antibiotics for UTI prevent subsequent BSI and even death. And if immediate antibiotics would have reduced the incidence of BSI to 0.2% it would have prevented – in this cohort – 976 episodes of BSI, being 63% of all BSI. Yet, that would also extend lives and thus increase likelihood of other UTIs (that should then be treated immediately). These benefits would come at a price: around 8% more antibiotic prescriptions among subjects with UTI.
So why were elderly (average age of the cohort was 76.9 years) not treated with antibiotics for UTI? The authors state: ”It could be patient or doctor choice, but it is also possible that antimicrobial stewardship programmes and quality premium payments are encouraging a culture of more judicious antibiotic use. Public Health England recently reported a 13.2% reduction in antibiotic prescribing in primary care between 2013 and 2017.”
There are a few caveats: This remains to be a retrospective study, and although considerable adjustment for confounding was performed, you will never be able to fully adjust. And there is confounding, as can be seen by the differences in crude and adjusted odds and hazard ratios.
But even then: this study “puts the finger at the painfull spot” (Dutch expression). Antibiotic stewardship is not by definition safe. It is crucial to determine safety when we admit to our desire to withhold antibiotics as much as possible in order to save them for the future.
Antibiotics do more than causing resistance.
The accompanying editorial said more or less the same, but nicer.