In this episode, I’ll discuss 7 vs 14 days of antibiotic therapy for gram-negative bacteremia.
A 14-day duration of therapy to treat gram-negative bacteremia has been a common recommendation, but some recent randomized trials have suggested that a 7-day duration is noninferior to 14. A group of authors has published in JAMA a systematic review and noninferiority meta-analysis to combine data from a large new trial with those identified in a 2022 meta-analysis.
The meta-analysis included data from 4 randomized trials and nearly 4000 patients, all of whom were hospitalized at the time of gram-negative bacteremia and were given 7 or 14 days of antibiotic therapy. The primary outcome was 90-day all-cause mortality. The authors performed an intention-to-treat analysis and a per-protocol analysis that excluded about 15% of the patients. In the intent to treat analysis, numerically fewer patients died by day 90 from any cause in the 7 day group, however this difference was not statistically significant and demonstrated a nearly 98% chance of noninferiority. Results were similar in the per-protocol analysis, with the chance of noninferiority being 95%.
The authors concluded:
In this systematic review and meta-analysis of patients with Gram-negative bloodstream infections and adequate source control, 7 days of antibiotic therapy had a high probability of being noninferior to 14 days. These findings support a shorter duration of antibiotic therapy for appropriately selected patients like those in the included RCTs.
Several things should be noted about this meta-analysis before applying it to practice. First, all patients included in the study had adequate source control, so these results can only apply to such patients. Patients who were immunocompromised were not well-represented in the 4 trials that made up this meta-analysis, and most patients had a urinary source of infection. Furthermore, over 90% of the infections were caused by Enterobacterales bacteria. There is a small trial not yet completed of 300 patients looking at the same outcome in patients with pseudomonas bacteremia that should help determine whether this shortened duration strategy can be applied to other pathogens.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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