Reviewed by: Rebekah Moehring, MD, MPH, FIDSA, FSHEA; Duke University, Durham, NC
Stewards rejoice! Two new randomized controlled trials were published this month supporting the “Shorter is Better” mantra. And yes, Dr. Brad Spellberg already has his table updated.
The Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children (SCOUT-CAP) randomized controlled trial has several things to get excited about. First, it’s a rarity to get a high-quality randomized trial in a pediatric population around antibiotics (thank you NIH ARLG!) This was a double blind, placebo-controlled trial of 380 children randomized to 5- vs. 10-day duration of antibiotics in outpatient community-acquired pneumonia. Second, this trial used the novel desirability of outcome ranking response adjusted for days of antibiotics (DOOR/RADAR) methodology for the primary outcome, comparing an ordinal composite clinical outcome of the treatment groups ranked by days of antibiotics. The result showed 69% (95% CI, 63-75) probability of a more desirable RADAR for the 5-day strategy. Third, this RCT had a secondary outcome focused specifically on antibiotic resistance. Among 171 participants, investigators collected throat swabs on day 19-25 to measure the “resistome” among oral flora, counting up antibiotic resistance genes per prokaryotic cell (RGPC). RGPC was measured for all resistance genes and for beta-lactamases in particular; both were lower in the short course group. Hard to know if these median differences actually lead to clinically relevant future risks of drug-resistant infections for the individual or wider community. But still – it’s nice to have something quantifiable to suggest we reduce selection for resistance genes when we use short courses. Regardless, it’s time to get those implementation tools updated. This is the third RCT to support short course for pediatric CAP (SAFER and CAP-IT).
Shorter is Better cite #2 this month comes from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial investigators. Tumor resection and reconstruction surgeries are among the most high-risk and complex orthopedic procedures – often involving large implants, radiated soft tissues, perioperative chemotherapy, and comorbidities that put patients at high risk of surgical site infection. Addressing the “but my patients are special” rationales for using prolonged antibiotics in this group is tough, but this RCT could help. PARITY investigators at 48 sites in 12 different countries enrolled 611 patients randomized to 1 vs. 5 days of IV cefazolin or cefuroxime post-operatively, with the 1-day group receiving saline infusions as placebo on days 2-5. Surgical site infection over 1-year follow up was not different between arms (15% for 5 days vs. 16.7% for 1 day). Antibiotic adverse events were uncommon (15 vs. 5 events), but 3 times higher in the 5-day group (hazard ratio, 3.24; 95% CI, 1.17-8.98). Most were due to C. difficile (11 vs. 4). Too bad we didn’t have a comparison group with only intra-operative dosing (ending antibiotics when incision closed) instead of the full 24-hours in orthopedic surgeries, but this is a great place to start!
References
Williams DJ, Creech CB, Walter EB, et al. Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial. JAMA Pediatr. Published online January 18, 2022. doi:10.1001/jamapediatrics.2021.5547
The Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) Investigators. Comparison of Prophylactic Intravenous Antibiotic Regimens After Endoprosthetic Reconstruction for Lower Extremity Bone Tumors: A Randomized Clinical Trial. JAMA Oncol. Published online January 06, 2022. doi:10.1001/jamaoncol.2021.6628