Home > Newsletter Archive > Bacterial and Fungal Infections Newsletter
Issue: Newsletter 7 | October 15, 2025
| Citation of Articles | PICO | Main Results | Risk of Bias |
|---|---|---|---|
| Paterson DL, Sulaiman H, Liu PY, Chatfield MD, Yilmaz M, Salmuna ZN, et al. Cefiderocol versus standard therapy for hospital-acquired and health-care-associated Gram-negative bacterial bloodstream infection (the GAME CHANGER trial): an open-label, parallel-group, randomised trial. Lancet Infect Dis. 2025 Oct 7; doi:10.1016/S1473-3099(25)00469-4 |
P: 504 adults with health-care-associated or hospital-acquired Gram-negative bloodstream infection (127 [25%] with carbapenem-resistant organisms) across 17 tertiary hospitals in 6 countries. I: Cefiderocol 2 g IV every 8 hours. C: Standard-of-care antibiotics chosen by clinicians. O: All-cause mortality at 14 days (primary); safety and adverse events (secondary). |
Cefiderocol was non-inferior to standard therapy for 14-day mortality (8% vs 7%; absolute risk difference 1%, 95% CI –3 to 6). Among carbapenem-resistant cases, mortality was 14% vs 10% (difference 5%, 95% CI –7 to 16), showing no superiority. Five serious adverse events related to cefiderocol (delirium, stupor, rigors, abnormal liver chemistry, rash) all resolved. Overall, cefiderocol was effective and safe but offered no mortality advantage over standard care. | Moderate risk: The open-label design could introduce performance or detection bias, though objective primary outcome (mortality) limits impact. Randomization with stratification by region and comorbidity strengthens internal validity. Minor attrition (9 excluded post-randomization) and clinician-selected comparators may introduce variability. Low event rates in subgroups reduce precision of treatment effect estimates. |
| Wang Z, Chen S, Poon J, Han SC, Ye D, Yu F, et al. A hybrid chatbot to promote pneumococcal vaccination among older adults: a randomized clinical trial. JAMA Netw Open. 2025 Oct 8;8(10):e2535813. doi:10.1001/jamanetworkopen.2025.35813 |
P: 374 Hong Kong residents aged ≥65 years (57% female; mean age 69.6 years) with no prior pneumococcal vaccination, recruited via random telephone calls. I: Hybrid chatbot with a rule-based component delivering stage-of-change–tailored interventions and an AI natural language processing component providing real-time answers, delivered at months 0, 1, 2, and 3. C: Chatbot-delivered standard online intervention (video link without real-time Q&A). O: Primary—validated pneumococcal vaccination uptake at 12 months; Secondary—stage of change score at 12 months and session completion rate. |
The hybrid chatbot significantly increased validated pneumococcal vaccination uptake compared with the standard online intervention (29.4% vs 18.7%; P = .01). Mean stage-of-change score was higher (2.2 vs 1.9; P = .02), and more participants completed at least one intervention session (79.7% vs 57.8%; P < .001). Overall, the hybrid chatbot demonstrated greater engagement and effectiveness in promoting vaccination among older adults. | Moderate risk: Partial masking may introduce performance bias, as participants knew which intervention they received. Self-reported outcomes validated by researchers reduce detection bias. Randomization and balanced groups support internal validity, though recruitment via telephone and limited geographic scope may affect generalizability. Attrition and engagement differences could influence outcome estimates. |
|
Verbakel JY, Burvenich R, D’hulster E, De Rop L, Van den Bruel A, Anthierens S, et al. A clinical decision tool including a decision tree, point-of-care testing of CRP, and safety-netting advice to guide antibiotic prescribing in acutely ill children in primary care in Belgium (ARON): a pragmatic, cluster-randomised, controlled trial. Lancet. 2025 Sep 25; doi:10.1016/S0140-6736(25)01239-5
• Editorial Commentary: Hay AD, Brown E. Reducing just-in-case primary care antibiotic prescribing in children. Lancet. 2025 Sep 25; doi:10.1016/S0140-6736(25)01336-4 |
P: 6,750 children aged 6 months–12 years with acute illness in ambulatory care across 171 Belgian general practitioner and community paediatrician practices. I: Clinical decision tool incorporating validated decision tree, guided point-of-care CRP testing, and safety-netting advice. C: Usual care without CRP point-of-care testing or decision tool. O: Antibiotic prescribing at index consultation (superiority); recovery time, additional testing, follow-up visits, and antibiotic prescribing after consultation (non-inferiority); safety outcomes. |
The clinical decision tool significantly reduced antibiotic prescribing at the index consultation (16% vs 22%; adjusted OR 0.72, 95% CI 0.55–0.94; p=0.017). Recovery time (mean difference –0.1 day, 95% CI –0.5 to 0.3), additional testing (aARR 2.0%, –1.7 to 5.0), follow-up visits (aARR 2.8%, –0.9 to 6.1), and antibiotic prescribing after the consultation (aARR 2.4%, 0.2–4.2) were all non-inferior. Serious adverse events occurred in 1% of intervention vs 2% of control patients, with none related to study procedures. No deaths occurred. | Moderate risk: The cluster-randomised, unblinded design could introduce performance and detection bias. However, randomisation at the practice level and adjustment for age and clustering enhance internal validity. Large sample size and balanced allocation strengthen generalisability, though lack of blinding may have influenced prescribing behaviour and parent–clinician interactions. Attrition bias was minimal with full follow-up reporting. |
| Dudeja S, Saini SS, Sundaram V, Dutta S, Sachdeva N, Kumar P. Early hydrocortisone versus placebo in neonatal shock: a double-blind randomized controlled trial. J Perinatol. 2025 Feb 2025;45:342–9. doi:10.1038/s41372-025-02222-3 |
P: 84 neonates with fluid-refractory shock (median gestational age 30.3 weeks, median birth weight 1148 g). I: Early hydrocortisone initiated along with vasoactive therapy. C: Saline placebo alongside vasoactive therapy. O: All-cause mortality at 14 days; duration of vasoactive drugs; vasoactive-inotrope scores; adverse effects; medium-term complications. |
14-day all-cause mortality was similar between early hydrocortisone and placebo groups (OR 0.53, 95% CI 0.19–1.52). Duration of vasoactive drug use, vasoactive-inotrope scores, incidence of hydrocortisone-related adverse effects, and medium-term complications were comparable between the two groups. Early hydrocortisone did not significantly reduce mortality in neonates with fluid-refractory shock. | Moderate risk: The study was randomized but likely unblinded once catecholamine-resistant shock occurred, allowing crossover to open-label hydrocortisone, which may introduce performance and detection bias. Small sample size limits statistical power and generalizability. Outcome reporting appears complete, reducing attrition bias. |
| Tikkinen KAO, Najafabadi BT, Hajebrahimi S, Tondroanamag F, Mikkola A, Horsti S, et al. A Multicenter Randomized Controlled Trial of Antimicrobial Prophylaxis to Prevent Urinary Tract Infections after Shockwave Lithotripsy for Urolithiasis: The APPEAL Trial. Eur Urol. 2025 Sep 24; doi:10.1016/j.eururo.2025.08.019 |
P: 1694 adults (median age 50 years; 30% female) undergoing shockwave lithotripsy for kidney (74%) or ureteral (26%) stones. I: Single pre-procedure dose of ciprofloxacin. C: Placebo. O: Composite of bacteriuria or symptomatic UTI after SWL; secondary outcomes: pyelonephritis and urosepsis. |
Antibiotic prophylaxis reduced post-SWL pyelonephritis (0% vs 1.2%, RR 0.05, 95% CI 0.003–0.93) but not the composite of bacteriuria or symptomatic UTI (2.7% vs 3.9%, RR 0.68, 95% CI 0.41–1.15). Symptomatic UTI occurred less frequently with ciprofloxacin (1.3% vs 2.7%, RR 0.49, 95% CI 0.19–1.23), though not statistically significant. No urosepsis or serious adverse events were reported. Overall benefit was small in absolute terms. | Low-to-moderate risk: Blinded, multicenter design minimizes performance and detection bias. Large sample size and prespecified outcomes strengthen validity. However, low event rates limit statistical power for secondary outcomes, and exclusion of 28 patients post-randomization may introduce minor attrition bias. |
Copyright © ADVANCE-ID. All rights reserved.
ADVANCE-ID
Saw Swee Hock School of Public Health
National University of Singapore
Tahir Foundation Building
National University of Singapore
12 Science Drive 2, #10-01, Singapore 117549
+65 6516 4988