Issue: Newsletter 8 | November 1, 2025
| Citation of Articles | PICO | Main Results | Risk of Bias |
|---|---|---|---|
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Burdet C, Saïdani N, Dupieux C, Lemaignen A, Canouï E, Surgers L, et al. Cloxacillin versus cefazolin for meticillin-susceptible Staphylococcus aureus bacteraemia (CloCeBa): a prospective, open-label, multicentre, non-inferiority, randomised clinical trial. Lancet. 2025 Oct 17; doi:10.1016/S0140-6736(25)01624-1
• Editorial commentary: Kao CM, Fritz SA. Treatment of MSSA bacteraemia: a call for a personalised approach. Lancet. 2025 Oct 17; doi:10.1016/S0140-6736(25)01844-6 |
P: 292 adults (mean age 62.7 years; 74% male) with methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia (without CNS infection or intravascular implant) recruited from 21 hospitals in France. I: Cefazolin 25–50 mg/kg IV every 8 hours for 7 days (followed by investigator’s choice; total ≥14 days). C: Cloxacillin 25–50 mg/kg IV every 4–6 hours for 7 days (followed by investigator’s choice; total ≥14 days). O: Composite primary outcome of sterile blood cultures at day 3 (day 5 for endocarditis), survival, and clinical success at day 90; safety outcomes including serious adverse events and acute kidney injury. |
Cefazolin achieved non-inferior efficacy to cloxacillin for the composite primary endpoint (75% vs 74%; treatment difference –1%, 95% CI –11 to 9; p = 0.012). Serious adverse events were significantly fewer with cefazolin (15% vs 27%; p = 0.010), and acute kidney injury occurred far less often (1% vs 12%; p = 0.0002). These findings indicate cefazolin provides comparable clinical effectiveness with improved safety and tolerability. | Moderate risk: Open-label design may introduce performance and detection bias, although objective microbiological and mortality endpoints reduce this risk. Randomization and stratification by centre and infection source enhance internal validity. Exclusion of ~7% post-randomization and investigator-selected continuation therapy may introduce minor attrition and performance bias. Overall, evidence reliability is good with limited blinding-related concerns. |
| Haidara FC, Adubra L, Abdou M, Alber D, Ashorn U, Cheung YB, et al. Mass administration of azithromycin to infants in Mali to reduce mortality. N Engl J Med. 2025 Oct 15;393:1498–1508. doi:10.1056/NEJMoa2504644 |
P: 149,090 infants aged 1–11 months from 1151 villages in Mali, West Africa (82,600 person-years of follow-up). I: (1) Twice-yearly azithromycin (20 mg/kg orally at two quarterly visits from Jan–Jun, placebo Jul–Dec); (2) Quarterly azithromycin (20 mg/kg every 3 months). C: Placebo every 3 months. O: Primary—death within 3 months after eligibility confirmation; Secondary—adverse events and mortality among untreated children aged 12–59 months. |
Mortality rates were similar across groups: 11.9 deaths per 1000 person-years (control), 11.8 (twice-yearly azithromycin; incidence rate ratio [IRR] 1.00, 95% CI 0.83–1.19), and 11.3 (quarterly azithromycin; IRR 0.93, 95% CI 0.75–1.15). No significant mortality reduction was observed with either dosing schedule. Adverse events were rare and comparable among groups. Mortality among older, untreated children did not differ by group. Overall, azithromycin mass administration did not lower infant or child mortality. | Low risk: Large, cluster-randomized design with village-level randomization and high follow-up completeness strengthens validity. Blinding of intervention (placebo-controlled) minimizes performance and detection bias. Objective mortality outcomes reduce measurement bias. Potential minor bias from unequal cluster allocation (3:4:2 ratio) and community-level confounders, but overall robust and generalizable evidence. |
| Ayele H, Jo J, Begum K, Hu C, Le TM, Alam MJ, et al. A randomized phase 1 study investigating gut microbiome changes with moxifloxacin vs. oral vancomycin: implications for Clostridioides difficile risk. J Infect Dis. 2025 Oct 13;jiaf512. doi:10.1093/infdis/jiaf512 |
P: Healthy adult volunteers (aged 18–40) in a phase 1 non-blinded randomized trial comparing moxifloxacin to vancomycin; exact number of participants not clearly stated in the abstract. I: Moxifloxacin for 10 days. C: Vancomycin for 10 days. O: Microbiome (16S rRNA sequencing) and bile acid metabolomic changes. |
Moxifloxacin caused minimal overall microbial disruption but did induce transient reduction in Clostridiales and secondary bile acids (Day 0 to Day 7). Vancomycin caused more marked and prolonged disruption: increased Proteobacteria, decreased Clostridiales, and longer suppression of secondary bile acids. These findings suggest a shorter window of gut vulnerability with moxifloxacin relative to vancomycin. | Moderate risk: Lack of blinding (open label), healthy volunteer sample limiting applicability to patient populations, and unclear sample size undermine external validity. Use of objective microbiome/metabolome outcomes strengthens internal validity but small size likely limits generalizability. |
| Mingchay P, Kawkitinarong K, Torvorapanit P, Ohata PJ, Suwanpimolkul G, et al. Effectiveness of nebulized bronchodilator–enhanced sputum induction in Thai patients with presumed pulmonary tuberculosis: a randomized controlled trial (NeB-TB Trial). Clin Infect Dis. 2025 Oct 23; doi:10.1093/cid/ciaf580 |
P: 204 adults with presumed pulmonary TB and negative Xpert MTB/RIF Ultra results or inadequate sputum production, enrolled at King Chulalongkorn Memorial Hospital, Thailand. I: Bronchodilator-enhanced sputum induction (nebulized bronchodilator plus 3% hypertonic saline). C: Conventional sputum induction (3% hypertonic saline alone). O: Primary—TB diagnosis by Xpert MTB/RIF assay; Secondary—mycobacterial culture positivity, need for bronchoscopy, adverse events, time to treatment initiation. |
Bronchodilator-enhanced induction significantly increased TB detection (30.1% vs 17.8%; RR 1.68, 95% CI 1.01–2.80; NND 4 vs 6), showed a trend toward higher culture positivity (RR 1.49, 95% CI 0.93–2.41), reduced need for bronchoscopy (RR 0.41, 95% CI 0.15–1.12), fewer adverse events, and fewer induction attempts. Time to treatment initiation was significantly shorter (median 4.5 vs 14 days; p < 0.01). Subgroup analysis indicated pronounced benefit among outpatients (RR 1.86, 95% CI 1.00–3.48). | Low-to-moderate risk: Randomized design reduces selection bias; objective primary outcome (Xpert MTB/RIF) limits detection bias. Open-label intervention could introduce performance bias, but effects on lab-based outcomes are minimal. Single-center study and short follow-up may limit generalizability. Adequate sample size and balanced groups strengthen internal validity. |
| McCann N, Vicentine MP, Ebrahimi N, Greenland M, Angus B, Collins AM, et al. Safety, efficacy, and immunogenicity of a Salmonella Paratyphi A vaccine. N Engl J Med. 2025 Oct 29;393(17):1704–14. doi:10.1056/NEJMoa2502992 |
P: 72 healthy U.K. adults (median age 32 years; 46% women) enrolled in a controlled human infection model for Salmonella Paratyphi A infection. I: Two oral doses of live attenuated S. Paratyphi A vaccine (CVD 1902), 14 days apart C: Placebo O: S. Paratyphi A infection within 14 days after oral challenge; safety; immunogenicity |
CVD 1902 vaccine significantly reduced S. Paratyphi A infection rates compared to placebo (21% vs 75%; P<0.001), corresponding to 73% vaccine efficacy (95% CI, 46–86) in the intention-to-treat analysis and 69% (95% CI, 42–84) per-protocol. The vaccine induced strong serum IgG and IgA O-antigen responses, absent in placebo recipients. Adverse event profiles were similar between groups, with no vaccine-related serious adverse events. | Low risk: The randomized, double-blind, placebo-controlled design minimizes selection and performance bias. Controlled challenge and full follow-up strengthen validity. However, use of a small, healthy adult sample and artificial challenge model may limit generalizability to broader, real-world populations. |
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Lucinde RK, Gathuri H, Mwaniki P, Orindi B, Otieno EO, Mwakio S, et al. A pragmatic trial of glucocorticoids for community-acquired pneumonia. N Engl J Med. 2025 Oct 29; doi:10.1056/NEJMoa2507100
• Editorial: Kwizera A, Dünser MW. Glucocorticoids for pneumonia in Africa — old therapy, new context. N Engl J Med. 2025 Oct 29; doi:10.1056/NEJMe2514533 |
P: 2180 adults (median age 53 years; 46% women) hospitalized with community-acquired pneumonia (CAP) in 18 public hospitals in Kenya I: Oral low-dose glucocorticoids for 10 days plus standard care C: Standard care for CAP O: Death from any cause at 30 days after enrollment |
Adjunctive oral low-dose glucocorticoids for 10 days reduced 30-day all-cause mortality compared with standard care alone (22.6% vs 26.0%; HR 0.84, 95% CI 0.73–0.97, P=0.02). Adverse and serious adverse events occurred at similar frequencies between groups, with only 0.5% experiencing glucocorticoid-related serious events. The findings suggest mortality benefit without increased safety risk in a low-resource setting. | Moderate risk: The pragmatic, open-label design could introduce performance and detection bias. However, large sample size, randomization, and consistent outcome assessment strengthen validity. Lack of blinding and variable care standards across 18 hospitals may limit internal control and generalizability. |
| The SuDDICU Investigators for the Australia and New Zealand Intensive Care Society Clinical Trials Group and the Canadian Critical Care Trials Group. Selective decontamination of the digestive tract during ventilation in the ICU. N Engl J Med. 2025 Oct 29; doi:10.1056/NEJMoa2506398 |
P: 9289 critically ill adults undergoing mechanical ventilation in 26 ICUs in Australia and Canada (plus 10,711 for ecological assessment). I: Selective decontamination of the digestive tract (SDD) with topical oral and gastric antimicrobials during ventilation plus 4 days of intravenous antibiotics. C: Standard ICU care without SDD. O: In-hospital death within 90 days; secondary outcomes included bloodstream infections, antibiotic resistance, adverse events, and days alive and free of ventilation or hospitalization. |
SDD did not significantly reduce in-hospital mortality at 90 days compared with standard care (27.9% vs 29.5%; OR 0.93, 95% CI 0.84–1.05, P=0.27). It reduced new bloodstream infections (4.9% vs 6.8%) and antibiotic-resistant organism cultures (16.8% vs 26.8%), but non-inferiority for ecological resistance outcomes was not confirmed. Adverse and serious adverse events were rare and comparable between groups. Overall, SDD improved some microbiologic outcomes but failed to show a mortality benefit. | Low-to-moderate risk: The cluster-randomized, multicenter design strengthened validity and reduced contamination bias. The open-label approach could introduce performance bias, and differing infection-control standards may have affected consistency. Non-inferiority ecological analyses limit interpretation of resistance findings. High sample size and standardized outcome assessment reduce attrition and detection bias. |
Wu W, Tan J. Nasal leech. N Engl J Med. 2025 Oct 25;393:e28. doi:10.1056/NEJMicm2509569
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