An editorial notes that when interpreting these results, doctors must be careful not to be overly influenced by an attractive and plausible underlying pathophysiologic mechanism (hyperkalemia) for sudden death, as the researchers had no data on serum potassium concentrations in participants. In addition, despite extensive efforts by the authors to control for measured confounders, the possibility that unmeasured and residual confounding contributed to the observed association, cannot be excluded. However it applauds the researchers for highlighting this potential drug interaction and calls for further replication studies and sensitivity analyses to be conducted to confirm these preliminary results, enhance validity, and reduce uncertainties around interpretation. In the meantime, the results of this one study cannot be definitive and in the absence of higher quality evidence, it suggests several approaches:
• prescribe alternative antibiotics for uncomplicated community acquired infections in patients taking renin-angiotensin system blockers (RASBs) or;• as co-trimoxazole is an established antibiotic with a broad spectrum of activity and is well tolerated, continue prescribing it with RASBs but monitor potassium concentrations until either drug is stopped; or • wait for other confirmatory studies before modifying practice.