Introduction: Adverse drug reactions (ADRs) represent a significant challenge in tuberculosis (TB) treatment, affecting adherence and outcomes. International clinical standards for ADR management exist, yet their direct implementation in high-TB-prevalence countries is hindered by differences in healthcare system capacity, infrastructure, and policy. A high TB-burden country requires contextually adapted standards to guide clinical practice effectively.

Aims: This study aimed to adapt the International Clinical Standards for Adverse Effects Management in TB Treatment to a national healthcare context through structured expert consensus. The adapted standards were evaluated for their relevance and feasibility of implementation across healthcare tiers.

Methods: A modified Delphi survey was conducted from June to September 2025. Eighty-five TB-related experts from clinical, academic, and policymaking backgrounds with at least four years of TB management experience from both hospital and community health centers were invited to participate. Eight international standards comprising 62 statements were rated across two rounds for relevance and implementation feasibility, with consensus defined as ≥70% agreement and an interquartile range of ≤1.

Results: Fifty-nine experts completed the survey. In the first round, 32 of 62 items (51.6%) reached consensus (IQR<1.00), covering counseling, core psychological and pharmacological management, ADR resumption protocols, and health worker training and reporting. Twenty-seven items (43.5%) required revision, primarily those concerning laboratory monitoring, referral coordination, and cross-level feasibility, while three items (4.8%) were excluded (IQR>1.00). After second-round revisions, 64 of 71 items (90.1%) reached consensus (IQR<1.00). The finalized framework comprises eight clinical standards mapped across community-based care and hospital settings within a tiered healthcare system.

Conclusions: International ADR management standards were successfully adapted to a national healthcare context through rigorous expert consensus. The resulting framework is contextually relevant and implementable across healthcare tiers, providing a practical foundation for strengthening pharmacovigilance and improving TB treatment outcomes nationwide.

Keywords: Adverse drug reactions, Delphi method, tuberculosis

Introduction: Persistent colonisation of carbapenem-resistant Enterobacteriaceae (CRE), which are resistant to most antibiotic classes and to carbapenems, may increase the risk of untreatable infections.

Aims: To identify risk factors for extended CRE colonisation.

Methods:
Setting: We collected data from the Hong Kong Hospital Authority (HA) electronic health records (EHRs). Patients aged >18, tested between 01/01/2017-30/06/2023 were included. CRE laboratory tests used genotypic (polymerase chain reaction) or phenotypic (antimicrobial susceptibility test) methods.
Design/Exposure: Patients with positive CRE tests were case; negative tests were controls. Repeated CRE colonisation detected during certain duration was categorized into short-term (0-3 months), prolonged (4-6 months), and persistent (6-12 months). Risk factors included healthcare resources utilisation, co-morbidities, medication exposure in the past year.
Statistical analysis: We matched each duration of case and controls in 1:3 ratio by a propensity score of CRE infection, adjusting sex, age, and CRE onset year-month. Conditional logistic regression was used to calculate the odds ratio (OR) at 95% confidence interval (CI). We conducted backward model selection by computing Akaike information criteria.

Results: Out of 441,426 episodes from 439,394 patients who received ≥1 CRE test, 4,638 episodes (1.05%) had ≥1 CRE positive result. They were further grouped into short-term (N=3,146, 0.71%), prolonged (N=750, 0.17%), persistent (N=742, 0.17%)
History of renal disease and number of antibiotic types prescribed in the past year were associated with elevated risk of CRE extended colonisation.
[Renal: Short-term OR 2.04 (95% CI 1.42-2.95); Prolonged 3.56(1.57-8.08); Persistent 5.45(2.24-13.29);
Number of antibiotic types: Short-term OR 1.18(1.16-1.2); Prolonged 1.22(1.18-1.26); Persistent 1.32 (1.25-1.39)].

Conclusions: Patients with renal disease and those prescribed multiple antibiotics in the past year are at heightened risk for persistent CRE colonization, likely due to increased susceptibility and slower clearance of infections.
Keywords: antimicrobial resistance, Carbapenem-resistant Enterobacteriaceae, hospital surveillance, antibiotics use, test-negative design

Introduction: Direct-acting antivirals (DAAs) have transformed the management of chronic hepatitis C virus (HCV) infection, achieving high cure rates in routine clinical practice. However, a subset of patients infected with genotype 3 HCV continue to experience treatment failure. Identifying factors associated with non-response is essential for optimizing treatment strategies and supporting disease elimination efforts.

Aims: To identify real-world predictors of treatment failure among patients with genotype 3 HCV receiving DAA-based therapy. To evaluate the impact of demographic and clinical factors on sustained virological response.

Methods: A multicenter prospective cohort study was conducted among 2000 genotype 3 HCV-infected patients treated with sofosbuvir plus daclatasvir with or without ribavirin or sofosbuvir/velpatasvir with or without ribavirin. Clinical, demographic, and laboratory data were collected from patient records. Sustained virological response at 12 weeks post-treatment was assessed. Multivariable logistic regression was used to identify independent predictors of treatment failure.

Results: Overall sustained virological response was achieved in 95.5% of patients. Response rates at 12 weeks were comparable between sofosbuvir plus daclatasvir (94.4%) and sofosbuvir/velpatasvir (94.7%). Treatment failure was more common among older patients and those with cirrhosis. Age greater than 60 years was independently associated with treatment failure (OR 4.46; 95% CI 2.35–8.46; p<0.001). Cirrhosis was the strongest predictor of non-response (OR 53.91; 95% CI 26.49–109.60; p<0.001). Cirrhotic patients receiving sofosbuvir/velpatasvir plus ribavirin achieved higher response rates than those receiving sofosbuvir plus daclatasvir plus ribavirin (88% vs 83%). Both regimens were well tolerated; skin rash and oral ulcers occurred more frequently with sofosbuvir plus daclatasvir.

Conclusions: DAA-based therapy achieved high effectiveness among genotype 3 HCV patients. Advanced age and cirrhosis were the primary predictors of treatment failure. Early diagnosis and treatment before progression to advanced liver disease may improve treatment outcomes and support HCV elimination programs.

Keywords: Hepatitis C; Drug effectiveness; Pharmacoepidemiology; Safety Outcomes

Introduction. Despite the substantial global burden of Clostridioides difficile infection (CDI) and its close relationship with antibiotic exposure, evidence remains limited.
Aims. We aimed to characterize antibiotic-associated CDI by assessing drug- and age-specific signal patterns, and geographic and temporal variations.
Methods. This study used the United States Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate antibiotic-associated CDI. Antibiotics were classified by pharmacological class, and CDI events were defined by the Medical Dictionary for Regulatory Activities. CDI event signals were identified using disproportionality analyses with the information component (IC) and reporting odds ratio (ROR), along with corresponding 95% confidence intervals (CIs). We also assess the WHO-regional burden of CDI between 1990 and 2023, using data from the Global Burden of Disease Study 2023. Burden of CDI was assessed using disability-adjusted life years (DALYs) and age-standardized DALY rates (ASDRs) per 100,000, with 95% uncertainty intervals (UIs).
Results. Among 19,346,526 FAERS reports, 2464 antibiotic-associated CDI cases were identified, 43.55% in males. Antibiotic-associated CDI showed a disproportionality signal overall (IC, 3.17 [IC0.25, 3.10]; ROR, 10.56 [95% CI, 10.11-11.02]). The strongest signals were observed for penicillin combinations and carbapenems, while clindamycin showed the greatest individual level signal (IC, 4.85 [IC0.25, 4.64]; ROR, 32.63 [95% CI, 28.76-37.02]). Signals increased with and peaked among adults aged ≥80 years. The Region of the Americas surpassed Europe around 1997 in ASDR and around 2000 in absolute DALY counts, recording the highest regional burden by 2023, with an ASDR of 10.69 (95% UI 9.49-12.20) per 100,000.
Discussion. Antibiotic-associated CDI showed drug-specific signals and peaked among adults aged ≥80 years, whereas WHO-regional estimates indicated a geographically uneven, rising global burden. Our findings underscore the need for risk-stratified antibiotic stewardship, diagnostic vigilance in older adults, and specific surveillance and strategies.
Keywords. Clostridioides difficile infection, antibiotics, DALY

Introduction: Staphylococcus aureus is a common commensal bacterium causing opportunistic infections particularly in immunocompromised children. Antimicrobial resistance (AMR) limits treatment options, elevating disease severity and facilitating caregiver-to-child household transmission through close interactions.

Aims: To investigate the epidemiology and risk factors associated with S.aureus carriages and corresponding AMR status in Hong Kong children, adolescents and their caregiver.

Methods: Children (aged 0-18years) and caregiver were recruited at Hong Kong Children’s Hospital. Nasal swabs were collected to screen S.aureus carriage, alongside demographic and antibiotic-history questionnaire. Bacteria identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). AST on isolates involved 10 antibiotics based on local epidemiology and CLSI-guidelines utilizing disc diffusion. Cases included children with S.aureus carriage; controls were those without. Resistance subgroup analysis compare carriers with ≥1 antibiotic resistance against fully susceptible non-carriers. Risk factors were determined via logistic regression optimized by bidirectional stepwise Akaike Information Criterion (AIC) selection.

Results: Among 293 analyzed child-caregiver pairs (children: mean age 7.4 years, 57.8% male), 80 children (27.3%) were cases, and 213 (72.7%) non-carrier controls. Child isolates exhibited highest resistance to penicillin (63.7%); doxycycline (11.3%); azithromycin (10%) and oxacillin (5%; Methicillin-resistant Staphylococcus aureus indicator). Significant risk factors for S.aureus carriage in child was S.aureus carriage in caregiver (OR:2.06, 95%CI:1.06-3.97). In subgroup analysis, 75% of children carriers exhibited ≥1 antibiotic resistance. Caregiver ≥1 antibiotic resistance carriage was identified as significant risk factor for children ≥1 antibiotic resistance carriage (OR:9.60, 95%CI:1.03–98.30).

Conclusions: Prevalence of S.aureus and MRSA carriage were similar to previously documented providing reassuring evidence that carriage is well managed. Close contacts, such as children and caregivers, exhibited a strong association with resistance carriage. However, a high prevalence of antibiotics resistance was observed. While phenotypic risk factor associated with resistance carriage were absent, further microscopic epidemiological investigations are warranted.

Keywords: Antimicrobial resistance, Methicillin-Resistant Staphylococcus aureus, Antibiotic Stewardship

Introduction: Denosumab is often discontinued, and its rapidly reversible biologic effects may alter the risk of infection after treatment. However, this post-discontinuation risk remains unclear.
Aims: To compare the risk of serious infections after discontinuation of denosumab compared to zoledronic acid (ZA) among patients with osteoporosis using nationwide claims data
Methods: Using the Korean National Health Insurance Service database, we conducted a retrospective cohort study. Individuals aged more than 65 years with osteoporosis were eligible, and initiators of denosumab or ZA between October 1, 2017 and December 31, 2023, and subsequently discontinued their drug were included. Patients with chronic kidney disease in the year before initiation, overlapping use of both drugs, or missing data were excluded. Denosumab discontinuers were matched 1:1 to ZA discontinuers using propensity scores derived from age, sex, insurance type, Charlson Comorbidity Index, fracture history, hospital days, and treatment duration. Treatment duration was calculated using episodes constructed using a 60-day grace period. Serious infection was defined as hospitalization with ICD 10 codes for pneumonia, urinary tract infection (UTI), tuberculosis, cellulitis/erysipelas, and infective endocarditis (IE). Patients were followed from the end of drug coverage until the serious infection, initiation of new osteoporosis medication, death, or 31 December 2024. Cox proportional hazards models in matched cohort estimated hazard ratios (HR) with 95% confidence intervals (CIs).
Results: Among 405,776 new users (340,447 denosumab; 65,329 ZA), 65,329 matched pairs were included. The denosumab discontinuation was not associated with a higher risk of serious infection compared to ZA discontinuation. The adjusted HR for pneumonia was 1.02 (CI 0.99–1.05), UTI 0.94 (CI 0.86–1.04), tuberculosis 1.03 (CI 0.99–1.06), cellulitis/erysipelas 1.03 (CI 1.00–1.06), and IE 1.03 (CI 1.00–1.06).
Conclusions: Among older adults with osteoporosis, denosumab discontinuation was not associated with higher risks of serious infection compared with ZA discontinuation.

Keywords: Denosumab. Zoledronic acid, Serious infection