Extensively drug-resistant gram-negative bacteria harbouring dual resistance to carbapenems and colistin represent a critical global health threat. A total of 929 population-representative Enterobacter isolates were systematically collected from 29 hospitals across four regions of Taiwan between 2010 and 2020. Forty-one isolates (4.4%) were nonsusceptible to carbapenems and underwent whole-genome sequencing, resistance gene profiling, plasmid analysis, and antimicrobial susceptibility testing (AST). Among them, 35 isolates (85.4%) exhibited dual resistance to carbapenems and colistin; however, only half (17/35) were detectable by standard phenotypic AST. Colistin resistance was primarily mediated by activation of the chromosomal arnBCADTEF operon, which was frequently inducible and often undetected by standard testing, rather than by mcr-9 or mcr-10. A conserved IncHI2 plasmid carrying blaIMP-8 and mcr-9 persisted and circulated across Enterobacter species for over a decade. Species-specific resistance patterns were observed: E. roggenkampii typically exhibited colistin resistance despite lacking carbapenemases, whereas E. hormaechei commonly carried blaIMP-8 and occasionally lacked the arn operon. Both species exhibited comparable imipenem nonsusceptibility, complicating therapeutic decision-making. The convergence of carbapenem and colistin resistance in a substantial proportion of Enterobacter isolates at the population level makes this genus an emerging priority for hospital infection control and antimicrobial resistance surveillance. These findings underscore the urgent need for improved diagnostics, strengthened antimicrobial resistance surveillance, and optimized treatment strategies.

RATIONALE:Recent empirical research suggests that isoniazid may lead to a risk reduction of incident tuberculosis (TB) among close TB contacts of someone with multidrug-resistant TB (MDR-TB). OBJECTIVES:To evaluate the association between isoniazid TB preventive treatment (TPT), compared to no treatment, upon incident TB in household contacts of MDR-TB cases using a large global consortium of TB contact tracing studies. METHODS:We conducted a systematic review and individual-participant meta-analysis among observational studies of household contact tracing studies. Participants were included if they were exposed to someone with MDR-TB and were given either 6 months of isoniazid TPT or no TPT. Our primary outcome was incident TB in contacts exposed to TB. We derived adjusted hazard ratios (aHRs) using mixed-effects, multivariable survival regression models with study-level random effects. The effectiveness of isoniazid TPT against incident TB was estimated through propensity score matching. MEASUREMENTS AND MAIN RESULTS:We included participant-level data from 6668 contacts exposed to MDR-TB from 17 countries. The effectiveness of isoniazid TPT against incident TB in contacts of MDR-TB was 57% (aHR, 0.43 [95% CI, 0.26-0.71]) and did not appreciably change with adjustment for additional potential confounders. The reduction in incident TB was marginally greater among child (<20 years old) contacts (aHR, 0.51 [95% CI, 0.28-0.92) compared to adult contacts (aHR, 0.69 [95% CI, 0.22-2.20]). The reduction in incidence was 73% (aHR, 0.27 [95% CI, 0.11-0.70]) in the first year of follow-up; effectiveness dropped to 60% (aHR, 0.40 [95% CI, 0.15-1.06]) from 12 to 23 months of follow-up and was nonsignificant after 2 years (28% effectiveness; aHR, 0.72 [95% CI, 0.33-1.54]). CONCLUSIONS:Among >6500 contacts of MDR-TB, isoniazid TPT was highly effective in preventing incident TB. The reduction was greatest in high-burden countries and waned after 2 years of follow-up.

OBJECTIVES:Evidence on the effectiveness of antiviral therapy in preventing influenza-related severe illness and hospitalization among children remains limited. We hypothesized that early administration of antiviral therapy within 48 hours of symptom onset would significantly reduce the risk of subsequent influenza-related severe illness and hospitalization. METHODS:This multicenter, age- and season-matched, retrospective case-control study included all pediatric outpatients with laboratory-confirmed influenza who sought care at the participating hospitals between 2020 and 2023. Cases were defined as children subsequently hospitalized or deceased because of influenza and were matched to nonhospitalized controls by date of initial visit and age strata. The effectiveness of early antiviral therapy (initiated within 48 hours of symptom onset, compared with delayed or no use) was estimated using conditional logistic regression. Subgroup analyses were performed for children aged 5 years or younger and older than 5 years. RESULTS:Among 1492 children (354 cases and 1138 controls; mean age, 7.1 years), early antiviral therapy was associated with an 81% lower risk of hospitalization overall (adjusted odds ratio [aOR], 0.19; 95% CI, 0.14-0.27), with similar protection among children aged 5 years or younger (aOR, 0.19; 95% CI, 0.12-0.31) and older than 5 years (aOR, 0.15; 95% CI, 0.09-0.25). The effect remained robust across sensitivity analyses by antiviral agent, with E-values up to 10.0 (range, 9.47-19.49 across subgroups). CONCLUSIONS:Early antiviral therapy in pediatric outpatients with influenza substantially reduces the risk of subsequent severe illness and hospitalization, supporting prompt initiation of treatment in this population.

Men who have sex with men (MSM) with HIV are disproportionately affected by persistent human papillomavirus (HPV) infections and related anogenital cancers. No controlled trial has evaluated the efficacy of the nonavalent HPV vaccine (9vHPV) in this population. This prospective, controlled cohort study offered eligible MSM with HIV a 3-dose 9vHPV series and followed both the vaccinated group (vaccinees) and the unvaccinated group (controls). Anal specimens were collected for HPV genotyping, cytology, and microbiota profiling. The primary outcomes were the clearance and incidence of 9vHPV-covered HPV types. Baseline vaccine-type HPV prevalence was 41.0% in vaccinees (n = 39; median age, 33 y; median CD4, 682/μl) and 39.3% in controls (n = 56; median age, 35 y; median CD4, 679/μl) (P = .865). At month 3, 75.0% of vaccinees with prevalent HPV infection had cleared at least one genotype, and 85.7% of those with abnormal baseline cytology experienced regression. However, clearance rates (per 1000 person-months) were 46.3 (vaccine type) and 56.0 (non-vaccine type) in vaccinees versus 64.1 and 91.8 in controls (P = .456 and 0.371). HPV incidence was 19.5 (vaccine type) and 15.1 (non-vaccine type) in vaccinees versus 12.4 and 12.4 in controls (P = .378 and 0.710). 9vHPV vaccination was not associated with enhanced clearance (aHR, 0.27; 95% CI, 0.11-0.68) or decreased incidence of vaccine-type HPV (aHR, 0.44; 95% CI, 0.11-1.82). No significant differences were observed in anal dysplasia regression or anal microbiota composition over 12 months. Given the lack of short-term secondary benefit and persistence of HPV incidence, MSM with HIV require continued routine anal cancer screening.

The recent surge in spillover events of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b to humans and mammals in North America has raised urgent pandemic concerns. Human H5N1 vaccines are unavailable in most countries. We synthesized data from ferret challenge trials to evaluate whether widely available seasonal influenza vaccines confer cross-protection against lethal H5N1 infection. We systematically searched PubMed, Embase, and Web of Science for ferret studies of lethal H5N1 challenge published up to 5 July 2025 (PROSPERO #CRD42024520346). Random-effects meta-analyses were conducted to compare vaccine efficacy (VE) of seasonal influenza vaccines and H5N1 vaccines against H5N1-related mortality. Seroprotection was defined as a neutralizing antibody titre of ≥1:40. We identified 35 studies (157 trials). Seasonal influenza vaccines without N1 did not confer significant cross-protection (five trials; VE 14.8%, 95% CI -3.6 to 30.0). In contrast, VE was 73% for N1-containing seasonal influenza vaccines (19 trials; 95% CI 54-84) and 77% for H5N1 vaccines overall (133 trials; 95% CI 72-82) (p = 0.52). The VE of N1-containing seasonal influenza vaccines was modestly lower than that of H5N1 vaccines with seroprotection (88%; 66 trials; 95% CI 84-91; p = 0.009), but comparable to H5N1 vaccines that did not achieve seroprotection (63%; 67 trials; 95% CI 52-71; p = 0.29). The VE of seasonal influenza vaccines against H5N1 was robust across sensitivity analyses, with no evidence of publication bias (p = 0.99). Seasonal influenza vaccines significantly reduce H5N1-associated mortality in ferret trials, suggesting the cross-protection potential of currently available vaccines. Human studies are warranted.

BACKGROUND:Necrotizing fasciitis (NF) is a fulminant soft-tissue infection with high in-hospital mortality. Although NF is traditionally classified into types I-IV by microbiology, emerging data - particularly from East Asia - suggest that monomicrobial Gram-negative (mono-GNB) NF is epidemiologically and prognostically distinct. This systematic review and meta-analysis aimed to quantify global subtype distributions and in-hospital mortality, with a focus on mono-GNB NF. METHODS:We searched PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library from inception to 1 September 2023, for eligible studies reporting NF microbiology. Included cases were classified as polymicrobial, monomicrobial Gram-positive, mono-GNB, culture-negative, or other pathogen-related. The primary outcomes were the pooled proportion of mono-GNB NF cases and the associated in-hospital mortality. We used random-effects models to estimate pooled proportions and mortality rates, and we conducted subgroup analyses by time period (before 2000 vs. from 2000 onward) and the six World Health Organization (WHO) regions. RESULTS:A total of 142 studies encompassing 6740 patients were included. Globally, the pooled proportion of mono-GNB NF increased from 12% before 2000 to 18% from 2000 onward (P = 0.03). Between-study heterogeneity was substantial (I2 > 95%). The proportion of mono-GNB cases was highest in the WHO regions of the Western Pacific, South-East Asia, and Africa. Among NF subtypes, mono-GNB NF exhibited the highest in-hospital mortality (28% before 2000 vs. 22% from 2000 onward; P = 0.70). Between-study heterogeneity was moderate (I2 = 41%). CONCLUSION:The rising proportion and persistently high in-hospital mortality of mono-GNB NF support its recognition as a distinct NF subtype and warrant reconsideration of the conventional NF classifications. In high-prevalence regions, empiric antimicrobial regimens should include prompt Gram-negative coverage to complement surgical debridement, while sustained epidemiological surveillance remains essential.

Background Evidence on the impact of active case finding (ACF) on tuberculosis (TB) incidence remains limited. We assessed incidence trends and case characteristics following the 2006 integration of annual community-wide chest-radiography-based ACF with the national directly observed treatment, short-course (DOTS) programme in Taiwan’s mountainous Indigenous regions (MIRs). Methods Population-level data were obtained from the national surveillance database, and individual-level data were sourced from the case-management system. We analysed log-linear trends in TB incidence (notification rates) using an exponential decay model, and compared MIRs with metropolitan regions and flatland Indigenous regions (FIRs), where the same DOTS programme was implemented without annual community-wide ACF. We compared ACF-detected and symptom-driven cases for characteristics consistent with earlier detection. Findings TB incidence in MIRs showed a sustained exponential decline from 292·9 per 100 000 in 2005 to 86·9 per 100 000 in 2022 (R²=0·94, p<0·001). The estimated log-linear rate of decline was 38·9% (16·7% to 61·2%) steeper than that in metropolitan regions (log-incidence slopes –0·0297 vs –0·0214), whereas no significant difference was observed between FIRs and metropolitan regions. The faster decline in MIRs was concentrated among individuals aged <40 years, whereas the rate of decline did not differ among individuals aged 40–59 years or ≥60 years. MIR cases (n=1141) were substantially more likely to be detected through ACF than non-MIR cases (n=14 507; 26·1% vs 3·2%; p<0·001). Compared with symptom-driven MIR cases (n=587), annual community-wide ACF-detected MIR cases (n=231) were less likely to have smear-positive, culture-positive sputum results at diagnosis (46·8% vs 55·7%; p=0·021) or cavitation on initial chest radiography (14·2% vs 22·0%; p=0·013). Interpretation Annual community-wide ACF integrated into DOTS in Taiwan’s high-incidence MIRs was associated with a sustained, faster decline in TB incidence over 17 years, concentrated among individuals aged <40 years, and with case characteristics consistent with earlier detection. Funding​None.

Background Respiratory syncytial virus (RSV) is increasingly recognized as a cause of severe respiratory illness in adults, especially the elderly and those with comorbidities. However, data on outcomes and risk factors for severe disease in this population remain limited. Methods We retrospectively analyzed 123 adult patients diagnosed with RSV infection at a tertiary center in Taiwan from 2015 to 2023. Clinical characteristics, laboratory data, detection of other pathogens, clinical course and outcome were reviewed. Multivariable logistic regression identified risk factors for severe RSV infection, including ICU admission and 30-day mortality. Results The mean age was 55.7 years; 50% were aged ≥60 years and 13% were ≥75 years. ICU admission occurred in 17%, with significant associations to viral coinfection and elevated C-reactive protein (CRP). Thirty-day mortality was 13%, and overall in-hospital mortality was 18%, all among patients with comorbidities. Independent predictors of 30-day mortality included late elderly (aOR 24.2, p = 0.03), high CRP > 11.5 mg/dL (aOR 16.4, p = 0.005) and thrombocytopenia < 34,103/μL (aOR 11.4, p = 0.01). Conclusion Advanced age (≥75 years), high CRP, and severe thrombocytopenia are key predictors of mortality in adults RSV patients. These findings highlight the need for targeted prevention strategies, including vaccination, in high-risk populations.

Objectives Despite the availability of rapid tuberculosis (TB) nucleic acid amplification (NAA) testing, prevention of TB transmission within healthcare facilities remains a challenge due to ongoing difficulties in promptly isolating infectious TB cases upon hospitalization. Methods We reviewed all hospitalized sputum culture-positive TB patients who were not immediately placed in airborne isolation before anti-TB treatment at a high caseload medical center in Taiwan during 2016-2019, and applied root cause analysis to systematically identify structural barriers to prompt isolation. Results Among 235 cases, 95 (40.4%) had non-suggestive chest radiography (CXR) findings (Category 1), 62 (26.4%) had suggestive findings but sputum testing was delayed (≥3 days; Category 2), and 78 (33.2%) had timely sputum testing but delayed positive results (Category 3,). In Category 1, 52.6% later developed typical CXR findings. In Category 2, 72.6% had misread CXRs and 27.4% had delayed review. In Category 3 (65.4% had sputum result turnaround time >3 days), TB-NAA test was not done in 24 (30.8%) patients (1 smear-positive and 23 smear-negative). Of the 13 false-negative TB-NAA cases, only one had repeat NAA testing. Conclusions Prompt isolation requires clinical alertness, accurate CXR interpretations, frontline TB-NAA, and repeat testing when suspicion persists despite negative results.

To understand the extent of SARS-CoV-2 transmission and immunity during Taiwan's first major COVID-19 outbreak in 2021, we conducted a seroepidemiological investigation using blood donor specimens. A total of 5000 residual blood samples were randomly selected from donors aged 17-65 years across six geographic regions during April 25-July 3 (week 17-week 26), 2021. This time period spanned from the beginning of the surge to six weeks after its peak. Serologic testing using Roche Elecsys® assays measured antibodies against nucleocapsid (N) and spike (S) proteins. Infection-induced seropositivity, defined as having both anti-N and anti-S antibodies, was detected in only one individual (0.02%, 95% confidence interval (CI): 0-0.06%). Blood having only anti-S antibody, indicating vaccine-induced immunity, was observed in 5.2% of samples (95% CI: 4.6-5.8%). The findings suggest that SARS-CoV-2 infection prevalence remained low in the community at the time, with seropositivity primarily reflecting early stages of vaccine rollout. This study demonstrates the value of blood donor-based serosurveillance for estimating infection and vaccine-induced immunity, and informs future policy for public health monitoring.

Background/purpose Milestone framework has been implemented in residency training to facilitate the residents’ assessment worldwide. We aim to evaluate the effectiveness of longitudinal milestones developed by Taiwan Society of Internal Medicine and compare the milestone ratings between the first-year resident (R1) program and the second-year post-graduate year (PGY2) program in Taiwan. Methods A multicenter observational cohort study was conducted, enrolling 153 first-year residents (107 R1 and 46 PGY2) in 2020 at six medical centers. The study tracked improvements in 22 sub-competencies over three years. The correlation between final milestone ratings and medical specialty board examination scores was analyzed. Results Of the 153 first-year residents recruited (107 R1 and 46 PGY2), 125 residents (100 R1 and 25 PGY2) completed three years of continuous milestone evaluations. Significant improvements in all 22 sub-competencies were found during the training of residents (all P < 0.001). Generally, there were no differences of milestone ratings in each year between R1 and PGY2 groups, except one sub-competency of practice-based learning and improvement (PBLI) had significant lower ratings in PGY2 group. A significant correlation was found between final milestone ratings and medical specialty board examination scores, particularly in the domains of Patient Care (P = 0.036), Systems-Based Practice (P = 0.024), and Professionalism (P = 0.041). Conclusion We demonstrate that milestone ratings effectively support the educational objectives of internal medicine residency in Taiwan. No major differences were found between the two residency programs. Final milestone ratings correlated with board exam performance, reinforcing the framework's validity.

Background The 2022 global mpox epidemic declined before modified Vaccinia Ankara–Bavarian Nordic (MVA-BN) vaccines were widely deployed, contributing to the perception that transmission was self-limiting within a small high-risk population. This may have delayed global vaccine allocation and weakened responses to the resurgence that has disproportionately affected Africa since 2024. The reasons for the 2022 decline remain uncertain, and prior studies have reported widely divergent estimates of vaccination impact. We systematically reviewed and meta-analysed the evolving transmissibility of mpox clades and the effects of interventions.Methods We searched GenBank, PubMed and Embase through 18 May 2025, for mpox virus sequences, reproduction number (R) estimates and modelling studies evaluating intervention effectiveness. Two reviewers independently assessed eligibility, extracted data and evaluated risk of bias using a validated tool. Random-effects meta-analyses were performed.Results Fifty-two studies reporting R estimates and 40 studies evaluating intervention effectiveness met eligibility criteria. For clade I mpox, pooled R increased from 0.71 (95% CI 0.26 to 1.17) during 1970–2017 to 1.23 (1.12–1.33) for subclades Ib/Ia after 2023 (p=0.0303). For clade II mpox, pooled R was 1.11 (0.90–1.32) during 2017–2021 and increased to 2.66 (2.31–3.00) for subclade IIb in 2022–2023 (p<0.0001). During the 2022 subclade IIb outbreak, empirical modelling studies estimated that behaviour change and vaccination together were associated with a substantial reduction in mpox cases (55%, 95% CI 37 to 73; I²=81.2%), although effect sizes varied across settings according to the extent of behaviour change and the timing and coverage of vaccine rollout.Conclusions Behaviour change and vaccination likely played important roles in the decline of the 2022 mpox epidemic in many studied settings. Given the stepwise increase in human-to-human transmissibility associated with the emergence of new subclades, effective mpox epidemic control requires proactive, rapid and equitable vaccine rollout supported by culturally tailored risk communication.PROSPERO registration number CRD420250653072.

​Background: Symptomatic outpatients with COVID-19 and other respiratory infections present similarly, yet triage decisions often precede RT-PCR results. SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) provide immediate results and preferentially detect high viral burden. We assessed whether Ag-RDT positivity at presentation identifies patients who subsequently develop severe COVID-19. Methods: We conducted a multicentre cohort study of 36,020 symptomatic outpatients who underwent same-day Ag-RDT and RT-PCR testing at four Taiwanese sites from May to October 2021. Participants with RT-PCR-confirmed infection were prospectively monitored for 14 days; records of all participants were reviewed for repeat testing and clinical events, and the participating hospital system was the sole tertiary-care provider serving the study catchment area. Severe COVID-19 was defined as RT-PCR-confirmed SARS-CoV-2 infection followed within 14 days by invasive mechanical ventilation or in-hospital death. We evaluated triage and diagnostic performance and prognostic associations adjusted for the age-adjusted Charlson Comorbidity Index among confirmed patients. Findings: Among 36,020 participants, 306 (0·8%) were Ag-RDT positive, 254 (0·7%) were RT-PCR positive, and 36 (0·1%) developed severe COVID-19. All confirmed infections were detected at index testing; no severe event followed a negative index RT-PCR in available records. Ag-RDT positivity identified severe COVID-19 with 80·6% sensitivity (95% CI 64·0–91·8), 99·2% specificity (99·1–99·3), 9·5% positive predictive value (6·4–13·3), and 99·98% negative predictive value (99·96–99·99). Diagnostic sensitivity and specificity were 63·8% (57·5–69·7) and 99·6% (99·5–99·7). Among patients with confirmed COVID-19, Ag-RDT-positive participants had lower Ct values (median 19·5 vs 30·9; p<0·001) and a greater risk of severe disease (17·9% vs 7·6%); the ACCI-adjusted odds ratio was 2·90 (1·15–7·31). Interpretation: Point-of-care Ag-RDT positivity identified most subsequent severe COVID-19 events despite moderate diagnostic sensitivity. It may support immediate triage before RT-PCR results, but prospective contemporary validation is required.

The COVID-19 pandemic and associated nonpharmaceutical interventions (NPIs) profoundly disrupted the transmission dynamics of respiratory viruses worldwide. However, the long-term impact on multiple respiratory pathogens, particularly in Taiwan, remains unclear. We conducted an interrupted time series analysis using negative binomial regression to assess monthly trends of five respiratory viruses—adenovirus, enterovirus, influenza, parainfluenza virus (PIV) and respiratory syncytial virus (RSV)—on the basis of data collected from three tertiary medical centers in Taiwan (2015–2023). The study period was divided into three phases: pre-COVID-19 (2015–2019), during COVID-19 (2020–2022), and post-COVID-19 (2023). Negative binomial regression with seasonal adjustment and lag variables was used to assess virus-specific trends. Percentage changes in case numbers were calculated. A total of 60,368 virus cases were identified. During the COVID-19 period, significant decreases in the number of adenovirus (-31.6

BACKGROUND:The necessity of pre-exposure prophylaxis (PrEP) for ending the global AIDS epidemic by 2030 remains controversial. In Taiwan, the HIV epidemic predominantly affects young, sexually active men who have sex with men (MSM). This study aimed to model the impact and cost-effectiveness of a high-coverage oral emtricitabine/tenofovir PrEP program in Taiwan from an HIV elimination perspective. METHODS:We applied stochastic and risk/age-structured deterministic modeling to assess the impact of PrEP scale-up on the basic reproduction number (R0) and the trajectory of the HIV epidemic in Taiwan, respectively. Both models were parameterized using the national HIV registry and cascade data. Cost-effectiveness was evaluated from a societal perspective. RESULTS:Here we show that an intensive HIV test-and-treat strategy targeting HIV-positive individuals alone would substantially decrease HIV transmission but is not sufficient to eliminate the HIV epidemic among MSM at the estimated mixing level. In contrast, a PrEP program covering 50% of young, sexually active, high-risk, HIV-negative MSM would suppress HIV's R0 below 1, facilitating its elimination. It would also reduce HIV incidence to levels below the World Health Organization's HIV elimination threshold (1/1000 person-years) by 2030 and is highly cost-saving, yielding a benefit-cost ratio of 7.16. The program's effectiveness and cost-effectiveness remain robust even under conditions of risk compensation (i.e., no condom use among PrEP users), imperfect adherence (75%), or low-level emtricitabine/tenofovir resistance (1%). CONCLUSION:Our findings strongly support scaling up PrEP for young, sexually active, high-risk, HIV-negative MSM as a critical strategy to end the HIV epidemic in Taiwan and globally.

BACKGROUND:The efficacy of molnupiravir for COVID-19 treatment remains controversial due to substantial heterogeneity in dosage and study settings across randomised controlled trials (RCTs). METHOD:We systematically searched Medline, PubMed, Embase, and the Cochrane Register of Clinical Trials up to February 3, 2025, for RCTs and real-world studies evaluating molnupiravir 800 mg twice daily as an early treatment for COVID-19 to prevent mortality and hospitalisation in high-risk adult outpatients. The primary outcomes were all-cause mortality and all-cause hospitalisation. Random-effects models were used to estimate pooled effect sizes. RESULTS:Thirty-four studies were included, comprising 30,345 participants from 11 RCTs and 1,581,737 participants from 23 cohort studies. Molnupiravir reduced mortality risk by 55 %-65 % at 28 days (RCTs: risk ratio [RR] 0.35; 95 % CI 0.12-0.98, I2 0 %; cohort studies: RR 0.45; 95 % CI 0.27-0.73, I2 91 %). This benefit persisted at 3 months (RR 0.47; 95 % CI 0.23-0.95, I2 93 %) and 6 months (RR 0.62; 95 % CI 0.52-0.74, I2 0 %). The effectiveness in preventing 28-day hospitalisation varied by participants' mean age in both RCTs (35-45 vs. 45-57 years: RR 0.55; 95 % CI 0.36-0.84 vs. 1.06; 95 % CI 0.81-1.39, subgroup difference P = 0.01) and cohort studies (62-74 vs. 75-85 years: RR 0.88; 95 % CI 0.77-1.01 vs. 0.56; 95 % CI 0.44-0.72, subgroup difference P < 0.01). CONCLUSIONS:Molnupiravir significantly reduces the risk of mortality. It also lowers the risk of hospitalisation in the oldest group (mean age ≥75 years) but not in younger groups (mean age 45-74 years).

BACKGROUND:Hemodialysis (HD) patients with nasal Staphylococcus aureus carriage are at an increased risk of S. aureus infection. PURPOSE:This study investigated the incidence of S. aureus bacteremia and associated mortality in HD patients receiving active screening and decolonization (ASD) program for nasal S. aureus carrier in a teaching hospital HD unit. METHODS:The ASD program was divided into five stages: 1: preintervention, 2: preparation, 3: intervention, 4: interruption, and 5: reintervention. Nasal screening was conducted every 3 months in stages 3 and 5. Patients colonized with S. aureus received decolonization with mupirocin to the nares and 4 % chlorhexidine gluconate body wash. S. aureus bacteremia and mortality were assessed. Whole-genome sequencing was conducted on S. aureus isolate in stage 3. RESULTS:In preintervention stage, the bacteremia incidence and mortality rate were 7.8 and 3.1 cases per 100 patient-years(PY). In the intervention stage, the incidence rate decreased to 1 case per 100 PY without mortality. In the reintervention stage, the incidence and mortality rates were 2.1 and 0.6 cases per 100 PY. The rates in stages 3, 4, and 5 were significantly lower than those in preintervention stage (p < 0.05). Genomic analysis of S. aureus isolates from stage 3 revealed genetically diversity. High-level mupirocin-resistant S. aureus isolates carrying mupA-bearing plasmids were identified. CONCLUSIONS:ASD programs for S. aureus carrier may improve clinical outcomes in HD units. However, mupirocin resistance may emerge after decolonization, indicating a need for ongoing monitoring and alternative decolonization strategies.

Background: An argument against COVID-19 vaccine boosters is that immune imprinting may impair immune responses to new SARS-CoV-2 variants, as some epidemiological studies found a paradoxical increase in Omicron variant infections correlated with the number of prior pre-Omicron vaccine doses. However, substantial variability between studies has left the true impact of boosters uncertain, warranting further investigation. Methods: We systematically reviewed available data and applied meta-regression to identify sources of heterogeneity among studies that examined the impact of pre-Omicron COVID-19 vaccine boosters—compared with primary vaccination series without boosters—on the risk of Omicron variant infections and severe diseases. Results: We screened 1703 articles and included 35 eligible studies. Heterogeneities in the impact of pre-Omicron boosters on the risk of Omicron infections and severe diseases are attributable to differences in time after boosters, age, and vaccine products (meta-regression R2: 70.4 % and 67.7 %, respectively). During the first month post-vaccination, pre-Omicron mRNA boosters decrease—rather than increase—the risk of Omicron infections and severe diseases by 58 % (95 % CI: 54 %–62 %) and 80 % (95 % CI: 68 %–87 %). This effectiveness declines to 9 % (95 % CI: 7 %–23 %) and 55 % (95 % CI: 49 %–60 %) by the sixth and fifth month, respectively. The certainty for evidence is moderate for protection against infections and high for protection against severe diseases. Conclusion: Our findings refute the immune imprinting hypothesis that COVID-19 boosters impair immunity against new SARS-CoV-2 variants and support current recommendations to stay protected through updated booster vaccination once or twice a year.