Issue: Newsletter 12 | January 15, 2026
| Citation of Articles | PICO | Main Results | Risk of Bias |
|---|---|---|---|
| Meya DB, Cresswell FV, Dai B, Engen N, Naidoo K, Ganiem AR, et al. Trial of high-dose oral rifampin in adults with tuberculous meningitis. N Engl J Med. 2025 Dec 17; doi:10.1056/NEJMoa2502866 |
P: 499 adults with definite or probable tuberculous meningitis (60.9% HIV-positive) from Indonesia, South Africa, and Uganda I: High-dose oral rifampin (total 35 mg/kg/day) plus standard antituberculous therapy for 8 weeks C: Standard-dose rifampin (10 mg/kg/day) plus standard antituberculous therapy O: All-cause mortality at 6 months |
In the intention-to-treat population, 6-month mortality did not differ significantly between groups, with deaths occurring in 44.6% of participants in the high-dose rifampin group and 40.7% in the standard-dose group (hazard ratio 1.17, 95% CI 0.89–1.54; P=0.25). Among those who died, median time to death was shorter in the high-dose group (13 days, IQR 4–39) compared with the standard-dose group (24 days, IQR 6–56). Drug-induced liver injury occurred more frequently with high-dose rifampin (8.0% vs 4.4%), although no deaths were attributed to liver injury. Overall, high-dose rifampin did not improve survival and was associated with higher hepatotoxicity. | Low to moderate risk: The double-blind, randomized, placebo-controlled design minimizes selection, performance, and detection bias. Intention-to-treat analysis and multicenter enrollment strengthen internal validity and generalizability. However, high overall mortality and potential heterogeneity across countries and HIV status may dilute treatment effects. Short-term follow-up for the primary outcome and limited power for subgroup analyses may affect precision. |
|
Luckey A, Balasegaram M, Barbee LA, Batteiger TA, Broadhurst H, Cohen SE, et al. Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial. Lancet. 2026 Jan 10; doi:10.1016/S0140-6736(25)01953-1
• Editorial Commentary: Workowski KA. Zoliflodacin shows benefit as an oral treatment for uncomplicated gonorrhoea. Lancet. 2026 Jan 10; doi:10.1016/S0140-6736(25)02331-1 |
P: 930 patients aged ≥12 years with suspected uncomplicated urogenital gonorrhoea from 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (88% male at birth; 55% Black or African American, 31% Asian, 12% White) I: Single oral dose of zoliflodacin 3 g C: Single intramuscular dose of ceftriaxone 500 mg plus oral azithromycin 1 g O: Microbiological cure at test-of-cure (day 6 ±2) |
Microbiological cure at TOC was 90.9% (460/506; 95% CI 88.1–93.3) for zoliflodacin and 96.2% (229/238; 95% CI 92.9–98.3) for ceftriaxone plus azithromycin. The estimated difference was 5.3% (95% CI 1.4–8.6), meeting the prespecified non-inferiority margin of <12%. Zoliflodacin was generally well tolerated, with mostly mild to moderate adverse events, including headache (10%), neutropenia (7%), and leukopenia (4%). Adverse events were similar in the comparator group, with injection site pain (12%), neutropenia (8%), and diarrhoea (7%). No serious adverse events were reported. | Moderate risk: Open-label design could introduce performance or detection bias, although laboratory staff were blinded to treatment assignment. Large multinational sample and randomization strengthen internal validity. High follow-up and clear microbiological endpoints minimize attrition and measurement bias. Non-inferiority margin selection and imbalance in group sizes (2:1 randomization) may influence interpretation. |
|
Lagrand RS, Sabelis LWES, Gramberg MCTT, Ahmad M, van den Bosch AJF, Brekelmans W, et al. Bone biopsy not superior to ulcer bed biopsy guided antibacterial therapy on remission of diabetic foot osteomyelitis: a randomized controlled trial. Clin Infect Dis. 2025 Dec 15; doi:10.1093/cid/ciaf684
• Editorial Commentary: Senneville EM, Lipsky BA. Do we need a bone biopsy for managing diabetic foot osteomyelitis? Clin Infect Dis. 2025 Dec 23; doi:10.1093/cid/ciaf685 |
P: 84 adults with diabetic foot osteomyelitis (DFO) undergoing both percutaneous bone and ulcer bed biopsies I: Antibiotic therapy guided by percutaneous bone biopsy cultures C: Antibiotic therapy guided by ulcer bed biopsy cultures O: DFO remission at 12 months |
Remission at 12 months was 31.4% (95% CI 18.1–48.7) in the bone biopsy group and 39.4% (95% CI 24.2–57.0) in the ulcer bed biopsy group. The relative risk of not achieving remission in the bone biopsy group was 1.13 (95% CI 0.80–1.60) in ITT analyses and 1.12–1.18 in per-protocol analyses, indicating no significant difference between groups. In 85.9% of cases, antibiotics chosen from one sample effectively covered bacteria from the other sample, which may explain the similar clinical outcomes. | Moderate risk: The randomized design reduces selection bias, and blinding of outcome assessors helps limit detection bias; however, clinicians and patients were likely not blinded, introducing potential performance bias. The small sample size and wide confidence intervals limit statistical power and precision. The multicenter setting improves generalizability, but variability in antibiotic selection and clinical management may influence outcomes. Adherence to antibiotic regimens was not reported, which could affect the observed treatment effect. |
| Zhang L, Peng M, Zhang H, Xiang C, Ai Y, Kong Y, et al. Oral acetaminophen and postoperative delirium in noncardiac surgical older patients requiring intensive care unit admission: a pragmatic randomized controlled trial. J Intensive Med. 2025 Dec 26; doi:10.1016/j.jointm.2025.10.005 |
P: 164 noncardiac surgical patients aged ≥65 years admitted to ICU at Xiangya Hospital (median age 74.8 years, IQR 62–91) I: Oral acetaminophen 500 mg every 8 h for the first 48 h after ICU admission C: Intravenous sufentanil 3.0 μg/h for the first 48 h after ICU admission O: Postoperative delirium (POD) on days 1–5, assessed by the Confusion Assessment Method |
POD occurred in 11.0% (9/82) of patients in the acetaminophen group and 17.1% (14/82) in the sufentanil group. Oral acetaminophen did not significantly reduce POD risk (risk ratio 0.6; 95% CI 0.3–1.4; P=0.262). There were no differences in the cumulative incidence of POD over postoperative days 1–5 (log-rank P=0.270) or in secondary outcomes including pain scores, ICU/hospital length of stay, 28-day mortality, gastrointestinal complications, quality of life, or cognitive function. | Moderate risk: Open-label design may introduce performance and detection bias, particularly for subjective outcomes like delirium. Single-center setting limits generalizability. Sample size is modest, limiting power to detect small differences. Blinded assessment of delirium was not specified, which may affect outcome measurement. |
| An M, et al. An mHealth (Mobile Health) intervention for smoking cessation in people with tuberculosis: a cluster randomized clinical trial. JAMA. 2025 Dec 22; doi:10.1001/jama.2025.22836 |
P: 1080 adults with drug-sensitive pulmonary tuberculosis who smoked daily (mean age 48.7 years; >96% male) attending rural TB clinics in Bangladesh and Pakistan I: Mobile health (mHealth) text message program providing motivational and behavioral support daily for 2 months, then monthly for 4 months C: Usual care with written tobacco cessation information O: Continuous tobacco abstinence at 6 months, verified by carbon monoxide breath test |
Continuous abstinence at 6 months was 41.7% (300/720) in the mHealth group versus 15.3% (55/360) in usual care. Self-reported point abstinence was higher in the mHealth group at 9 weeks (49.0% vs 20.8%) and at 6 months (55.6% vs 22.8%). TB treatment adherence and success rates were similar between groups. Mortality was lower in the mHealth group (3.5%) compared with usual care (7.5%). Overall, the mHealth program substantially improved tobacco cessation in TB patients. | Moderate risk: Cluster-randomized, open-label design may introduce performance and detection bias. High proportion of male participants limits generalizability. Lack of long-term follow-up beyond 6 months and absence of an attention control group may influence outcome assessment. Message comprehension among participants with lower education levels could affect intervention fidelity. Multisite rural setting improves external validity. |
| Leitner DR, Walsh SR, Suzuki M, Desjardins M, Hannaford A, Sherman AC, et al. Safety and immunogenicity of PanChol, a single-dose live-attenuated oral cholera vaccine: results from a phase 1a, double-blind, randomised, placebo-controlled trial. Lancet Infect Dis. 2026 Jan 7. doi:10.1016/S1473-3099(25)00682-6 |
P: 57 healthy adults aged 18–55 years without prior cholera infection or vaccination (47% male; median age 30.6 years) I: Single oral dose of live-attenuated PanChol vaccine (various doses; randomized module used 2×10⁷ CFU or 2×10⁸ CFU) C: Oral placebo (matching diluent) O: Safety (solicited, unsolicited, serious adverse events) and vibriocidal antibody seroconversion to Inaba and Ogawa serotypes at day 14 |
PanChol was well tolerated across all doses, with mostly mild and transient solicited adverse events. Solicited adverse events occurred in 69% of PanChol recipients versus 38% of placebo recipients; diarrhoea was the most common event (39% vs 38%, respectively), predominantly mild. No serious or vaccine-related grade >2 adverse events were observed. Vibriocidal seroconversion to both Inaba and Ogawa serotypes occurred in 100% of vaccine recipients who received ≥10⁵ CFU and had samples available beyond day 7, demonstrating strong immunogenicity across a 100,000-fold dose range. | Moderate risk: The randomized, double-blind, placebo-controlled design in the dose-expansion module strengthens internal validity, but the small sample size and phase 1 nature limit precision and generalizability. Earlier dose-escalation phases were open-label, introducing potential performance and detection bias for safety outcomes. Short follow-up and use of immunogenicity rather than clinical efficacy outcomes also limit inference. |
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Livorsi DJ, Thompson AM, Green MS, Hoelscher AC, Chu KK, Neuner E, et al. Prospective audit and feedback by antibiotic stewardship teams to reduce antibiotic overuse at hospital discharge: a stepped-wedge cluster-randomized clinical trial. JAMA Netw Open. 2026 Jan 9;9(1):e2549655. doi:10.1001/jamanetworkopen.2025.49655
• Editorial Commentary: Szymczak JE, Vaughn VM, Hersh AL. Improving discharge antibiotic use via prospective audit and feedback—the importance of contextual variation. JAMA Netw Open. 2026 Jan 9;9(1):e2549620. doi:10.1001/jamanetworkopen.2025.49620 |
P: 21,842 hospital admissions across 10 hospitals with antibiotic stewardship programs (median age 66 years; 61.3% male) I: Discharge-focused prospective audit and feedback, including dissemination of oral antibiotic step-down guidelines and AS team review of patients anticipated to discharge within 48 hours C: Usual care during baseline period without discharge-focused audit and feedback O: Primary: postdischarge antibiotic use (frequency and duration); Secondary: inpatient antibiotic use, length of stay, 30-day readmission, and optimal antibiotic prescribing at discharge |
The intervention did not reduce the proportion of patients prescribed antibiotics at discharge (21.8% vs 21.9%; OR 0.94, 95% CI 0.84–1.05) nor postdischarge antibiotic duration (7.6 vs 7.1 days; mean difference 0.02 days, 95% CI −0.50 to 0.53). There were no significant differences in inpatient antibiotic duration, length of stay, or 30-day readmission. However, among a manually reviewed subset of patients with selected uncomplicated infections, optimal antibiotic prescribing at discharge improved during the intervention period (58.8% vs 46.2%; OR 1.61, 95% CI 1.08–2.40). | Moderate risk: The stepped-wedge cluster-randomized design strengthens causal inference, but the per-protocol analysis may introduce selection bias. Only a subset of cases underwent manual review for optimal prescribing, limiting generalizability of that outcome. Partial uptake of audit feedback (approximately one-quarter of audited cases) may have diluted the intervention effect. Lack of blinding could introduce performance bias, though objective prescribing outcomes reduce detection bias. |
| Warren BG, Graves AM, Fils-Aime G, Barrett A, Mamikunian I, Gunsch C, et al. Efficacy of a foamed disinfectant in reducing pathogen contamination in renovated inpatient in-room sinks: a randomized controlled trial. Infect Control Hosp Epidemiol. 2026 Jan;47(1):13–19. doi:10.1017/ice.2025.10318 |
P: 30 in-room sinks in a newly renovated hospital unit (15 intervention, 15 control) I: Hydrogen peroxide/peracetic acid foamed disinfectant applied to sink drains three times weekly C: Standard daily surface cleaning O: Sink conversion events (first detection of ≥1 epidemiologically important pathogen [Pseudomonas aeruginosa, Stenotrophomonas spp., Acinetobacter spp., ESBL-producing or carbapenem-resistant Enterobacterales]) |
Nearly all sinks (29/30) experienced an SCE during the 35-week study. Only 44 (9%) samples from intervention sinks were positive for EIPs versus 270 (47%) from control sinks (p < 0.00001). EIPs were recovered from 4% versus 24% of P-traps and 4% versus 39% of tail pipes; sink top/handle contamination was rare and similar (3% vs 4%). Acinetobacter spp. and Stenotrophomonas spp. were most frequent. Intervention sinks had delayed time to SCE (p = 0.0001). | Moderate risk: Blinding was not possible due to the nature of the intervention, which could introduce performance bias. High-frequency sampling and objective microbiologic outcomes reduce detection bias. Small sample size (30 sinks) limits generalizability. Frequent storage of items in sinks (93% observations) could confound contamination risk. |
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