Clinical Microbiology and Infection

Rationale: Infections due to Extended-spectrum {beta}-lactamases-producing Enterobacterales (ESBL-PE) require empirical treatment with carbapenems. ESBL-PE carriage is considered as a risk factor for ESBL-PE involvement during ICU infection. Our aim was to determine factors that may predict the actual involvement of ESBL-PE. Methods: A two-periods bicentric ambispective study including ICU ESBL-PE carriers patients from April 2011 to January 2019. All ESBL-PE carriers who developed an infection were analyzed. Results: 6112 patients and 4902 patients were screened during the two periods. 384 and 232 ESBL-PE carriers were identified. Total number of infectious episodes were 146 and 114, respectively. A total of 144 pneumonias, 42 urinary tract infection and 45 digestive infections were studied. An ESBL-PE was involved in 35 (24.3%) episodes of pneumonia, and 44 (37.9%) of extra-pulmonary infections. The most frequent ESBL-PE involved were K. pneumoniae, E. cloacae and E. coli. Similar species and phenotypes were present in colonisation and infection in 29 (82.8%) of pneumonia and in 40 (90.9%) of extra-respiratory infection. Multivariate analysis identified Klebsiella pneumonia or Enterobacter cloacae carriage as risk factor for ESBL-PE involvement in pneumonia and E. coli carriage and detection of ESBL-PE carriage before ICU admission as protective factors. Conclusion: In our study an ESBL-PE involvement is infrequent in pneumonia. A known carriage before ICU admission and E. coli carriage are factors associated with the absence of ESBL-PE un the episode of respiratory infection. A confirmation of our findings could lead to a reduction in the empirical use of carbapenems in this population.

Background: Patients with chronic hepatitis B (CHB) may have an increased risk of severe COVID-19. Tenofovir has been hypothesized to confer protection against severe disease, but evidence is inconclusive. We evaluated the risk of severe COVID-19 among CHB patients treated with tenofovir compared with other nucleos(t)ide analogues (NAs). Methods and findings: In this nationwide, registry-based cohort study, we included all adults with CHB and laboratory-confirmed COVID-19 in Sweden between February 2020 and July 2022. Data from national health and socioeconomic registers were linked using unique personal identification numbers (PINs). Patients with HIV, hepatitis C, or hepatitis D coinfection were excluded. Exposure was defined as tenofovir versus other NA therapy. The primary outcome was severe COVID-19, defined as hospitalization >2 days or death within 30 days of diagnosis. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI), controlling for age, sex, comorbidities, vaccination, socioeconomic status, and region of birth. Among 5,877 CHB patients with COVID-19, 672 were receiving NA therapy (437 tenofovir, 235 other NAs). Severe COVID-19 occurred in 8.0% of tenofovir-treated patients and 14.5% of those receiving other NAs (unadjusted OR 0.52; 95% CI, 0.31-0.85). After adjustment, the association was attenuated and no longer significant (aOR 0.72; 95% CI, 0.39-1.31). Older age, comorbidities, and unvaccinated status were strongly associated with severe disease. Conclusions: The apparent protective effect of tenofovir against severe COVID-19 in unadjusted analyses was largely explained by confounding factors. The risk of severe disease was primarily driven by age, comorbidities, and vaccination status. Prevention of severe COVID-19 in patients with CHB should instead focus on vaccination and management of comorbidities.

Background The World Health Organization (WHO) recommends 4-month treatment for children with non-severe pulmonary tuberculosis, outlining eligibility criteria for settings with and without chest X-ray (CXR). We evaluated the diagnostic accuracy of the WHO eligibility criteria in settings without CXR (WHO-criteria) and developed clinical scores to support disease classification. Methods Using data from an individual participant dataset (IPD; Decide TB) of children with confirmed/unconfirmed tuberculosis from four diagnostic studies (RaPaed-TB, Umoya, TB-Speed HIV, TB-Speed Decentralisation), we assessed the diagnostic accuracy of the WHO-criteria (with/without bacteriological testing) using expert CXR interpretation as a reference. We developed two multivariable logistic regression models with (Score 1) and without (Score 2) bacteriological testing, converted coefficients into integer scores with a threshold of >10 corresponding to a sensitivity [≥]70%. Results Of 2,383 children in the Decide TB-IPD, 633 (26.6%) met the eligibility criteria for a 4-month regimen, of whom 116 (18.3%) had radiologically severe disease. With and without bacteriological testing, the WHO-criteria had sensitivities of 30.1% (95%CI: 20.3%-40.2%) and 21.7% (95%CI: 10.4%-34.5%), and specificities of 83.4% (95%CI: 80.2%-86.4%) and 81.9% (95%CI: 78.8%-84.9%), respectively. Score 1 and Score 2 had sensitivities of 41.1% (95%CI: 32.4%-49.5%) and 30.9% (95%CI: 22.6%-40.4%), and specificities of 77.3% (95%CI: 73.6%-80.8%) and 83.0% (95%CI: 79.5%-86.3%) respectively. Using WHO-criteria, 91/116 (78.4%) and 105/116 (90.5%) of children were at risk of undertreatment, compared to 68/116 (58.6%) and 80/116 (68.9%) when using developed scores. Conclusions Developed scores demonstrated better sensitivity than WHO-criteria, however, performance remains suboptimal. Implementing shorter antituberculosis regimens without CXR remains challenging in children.

Purpose: Central nervous system tuberculosis (CNS TB) presenting with vasculitis or arachnoiditis causes significant morbidity and mortality. The purpose of this study was to characterise the clinical spectrum and outcomes of patients diagnosed with TB arachnoiditis and TB-associated CNS vasculitis Methods A retrospective study was conducted between October 2020 and September 2023, screening patients admitted with suspected CNS TB to a tertiary care hospital. Patients diagnosed with proliferative arachnoiditis, and TB-associated CNS vasculitis were recruited. Their clinical details, follow-up records, and outcomes were assessed. Results Among 318 patients admitted with suspected CNS TB, 87 patients had complications, with follow-up data available for 69 patients. Vasculitis, spinal arachnoiditis (SA), and optochiasmatic arachnoiditis (OCA) was diagnosed in 66 (76%), 41 (47%), and 26 (30%) patients respectively. Median duration of follow-up was 490 days. Median mRS at discharge was 4. 18 (69%) OCA patients and 14 (35%) SA patients received pulse methylprednisolone. Intrathecal hyaluronidase was administered in 14 patients and thalidomide was given to 9 patients. 30 (46%) patients with vasculitis were treated with aspirin. 69 patients completed follow-up, 49% died. Among the remaining, 88.6% had improvement with treatment with a median mRS of 2 (1-3). Among patients with OCA, 3(23.1%) showed complete improvement with a median improvement of 3 points on Likert scale. In the SA patients, 19 (55.9%, 34) patients were alive on follow-up, with a median mRS of 1. Aspirin use was not associated with better mRS or survival in patients with vasculitis. A multivariable Cox proportional model showed age at diagnosis to be the only predictor of mortality (HR 1.04, 95% CI (1.01- 1.08), p =0.012). Conclusions TB arachnoiditis and CNS vasculitis are severe complications of CNS TB, and management remains a challenge. The poor therapeutic response to intrathecal hyaluronidase, thalidomide, and aspirin highlights need for further larger prospective trials and search for alternative agents.

Background: Multidrug-resistant tuberculosis (MDR-TB) remains a significant public health threat in low- and middle-income countries, including Cameroon. This systematic review and meta-analysis aimed to determine the pooled prevalence of MDR-TB and other specific anti-tuberculosis drug resistance patterns, as well as to identify factors associated with drug-resistant tuberculosis in Cameroon. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, Embase, Cochrane Library, and African Journals Online. Additional studies were identified through Google Scholar and reference list screening. Observational studies (cross-sectional, cohort, and case-control) reporting drug resistance among bacteriologically confirmed tuberculosis patients in Cameroon were eligible. Joanna Briggs Institute critical appraisal tools were used to critically assessed the study quality. Pooled prevalence estimates were calculated using random-effects meta-analysis. Subgroup analyses and meta-regression explored sources of heterogeneity. A p-value 0.05 was considered statistically significant. Results: Twenty-eight studies conducted between 1995 and 2022 were included. The pooled prevalence of MDR-TB was 5.2% (95% CI: 2.7-9.6; 21 studies; n = 7,515), with significantly higher acquired resistance (11.6%; 95% CI: 6.3-20.3) than initial resistance (2.0%; 95% CI: 1.1-3.5). The highest pooled MDR-TB prevalence was observed in the most recent studies (38.8%; 95% CI: 33.7-44.2), and the lowest in 2015-2019 (2.7%; 95% CI: 0.4-15.2). Any resistance to anti-tuberculosis drugs was 16.0% (95% CI: 10.3-23.9; 28 studies; n = 9,931), and rifampicin resistance was 4.6% (95% CI: 2.4-8.6; 25 studies; n = 8,728). Monoresistance was highest for streptomycin (6.4%; 95% CI: 3.7-10.8) and isoniazid (4.7%; 95% CI: 3.0-7.4). Previous tuberculosis infection was the strongest predictor of drug resistance (OR = 3.9; 95% CI: 1.8-8.4), followed by alcohol consumption (OR = 1.8; 95% CI: 1.2-2.7) and history of incarceration (OR = 1.7; 95% CI: 1.1-2.6). High heterogeneity was observed across most of the pooled estimates. Conclusions: Drug-resistant tuberculosis, particularly MDR-TB, poses a substantial burden in Cameroon, with acquired resistance significantly exceeding initial resistance. Previous tuberculosis infection, alcohol use, and incarceration are key modifiable risk factors. These findings underscore the urgent need to strengthen routine drug susceptibility testing, scale up rapid molecular diagnostics, enhance treatment adherence strategies, and implement targeted interventions for high-risk populations.

BackgroundOutbreaks of fluconazole-resistant Candida parapsilosis have recently emerged worldwide. In Spain, this phenomenon has been reported since 2020, mainly involving isolates from different clones harbouring the Y132F mutation at Erg11. MethodsWe analysed the expansion of fluconazole resistant C. parapsilosis strains within the national antifungal resistance surveillance program. Genetic clustering and relationships were assessed using microsatellite typing and whole genome sequencing. FindingsWe identified the expansion of three distinct clones carrying the Y132F mutation. Additionally, there was an increase in strains harbouring the G458S mutation, most of which belonged to a clonal complex, although other less prevalent clones were also detected. G458S isolates showed higher resistance to azoles than Y132F strains, particularly to voriconazole and isavuconazole. This increased resistance was associated with mutations in the Tac1 transcriptional regulator and duplication of a chromosomal region containing Tac1 and Erg11. One G458S isolate without mutation at Tac1 exhibited lower MIC values. Furthermore, two isolates carried the K143R mutation, and a distinct group of resistant strains without detectable ERG11 mutations was also identified. Resistant cases were detected across 31 hospitals in 12 autonomous regions. InterpretationOur findings indicate a concerning nationwide expansion of antifungal-resistant C. parapsilosis in Spain, involving multiple resistance mechanisms and clonal lineages, with implications for antifungal treatment and infection control strategies.

Antimicrobial resistance constitutes a major threat to global public health. Among emerging extensively drug-resistant bacteria (eXDR), carbapenemase-producing Enterobacteriaceae (CPE) expose hospitals to outbreaks through rapid dissemination, and to therapeutic limitations. Through a mixed epidemiological-qualitative methods study, we report the most extensive CPE carriage outbreak known to date in France, which occurred at Hopital Europeen Marseille (HEM) between January and June 2025. By the end of November 2024, the admission of an index patient returning from Senegal carrying an NDM-producing Escherichia coli led to an extensive transmission, despite adherence to national screen and isolate guidelines. More than 7,500 rectal screening tests evidenced 481 CPE carriers (including 343 NDM, 129 OXA-48-like and 9 other CPE), and 14 vancomycin-resistant Enterococcus faecium carriers. This major outbreak conducted to a phenomenal involvement of clinical, technical and administrative teams within the institution. It highlighted operational limitations in current screening, cohorting and biocleaning strategies in the context of hospital-wide outbreak. We describe the outbreak trajectory, the control measures implemented and provide a structured synthesis of lessons learned across organisational, scientific and policy domains.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [≤]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.

Background: Blood culture-negative infective endocarditis (BCNIE) poses a significant diagnostic challenge. This study evaluated a multimodal diagnostic algorithm combining serological and molecular methods at the Argentine National Reference Laboratory. Methods: A prospective analysis was conducted on 53 consecutive patients with suspected BCNIE referred between January 2019 and December 2024. The diagnostic workflow included indirect immunofluorescence for Bartonella spp. and Coxiella burnetii, species-specific PCR for Bartonella spp. and Tropheryma whipplei, and broad-range 16S rRNA PCR with Sanger sequencing on available blood and valvular tissue specimens. Results: An etiological diagnosis was established in 17 of 53 patients (32.1%). Bartonella spp. was the predominant pathogen (47.1%; 8/17), followed by T. whipplei (35.3%; 6/17) and Streptococcus spp. (17.6%; 3/17). All Bartonella cases were initially detected via serology, with molecular confirmation achieved exclusively through valvular tissue analysis. Conclusions: Implementing a standardized multimodal diagnostic algorithm significantly enhances etiological yields in BCNIE. The findings emphasize the complementary value of frontline serology and targeted molecular testing, highlighting that simultaneous submission of serum, blood, and valvular tissue is essential for optimal diagnosis.

Colombia has been internationally recognised as a paradigmatic case of vaccine confidence crisis since the 2014 Carmen de Bolivar event, and national HPV vaccination coverage remains far below the World Health Organization 2030 target. Most published evidence focuses on female adolescents and on cervical cancer; the perception of the HPV vaccine in university-age populations of both sexes--and across the broader spectrum of HPV-attributable disease--remains comparatively understudied. We aimed to describe the influence of biopsychosocial determinants on HPV vaccine perception among university students of both sexes in Cucuta, Norte de Santander, Colombia. We conducted a cross-sectional study with a mixed quantitative-qualitative approach in 2024 among four universities (Universidad de Santander, Universidad Francisco de Paula Santander, Universidad de Pamplona and Universidad Libre; combined enrolment 21,033 students). Using convenience sampling stratified by institution, 750 actively enrolled undergraduate students of both sexes (18-60 years) completed a structured online questionnaire adapted from previously validated instruments. The instrument captured sociodemographic information, HPV knowledge and HPV vaccine perception. Data were analysed using Students t-test, one-way analysis of variance, Tukey post-hoc tests, effect sizes and 95% confidence intervals, with a 0.05 significance threshold. Of 750 respondents, 54.2% were women, 61.3% were under 20 years of age, and 75.1% attended public universities. HPV knowledge was high in 39.2%, intermediate in 42.4% and low in 18.4%; women and students aged 26 years or older displayed higher knowledge. Although 91.2% had heard of HPV and 82.5% knew that both sexes could acquire it, recognition of clinical manifestations and complications was uneven: cervical cancer 51.7%, penile cancer 30.5%, vaginal warts 45.9% and warts in the penis, larynx, anus or rectum 34.0%. Vaccine-specific knowledge was low in 77.1%, with men disproportionately represented (85.9% versus 69.5% in women). Overall positive perception of HPV vaccination was 66.6%, slightly higher in women (68.8%) than men (63.9%), in students aged 26 years or older (70.1%) and in students from private universities (68.1% versus 65.9%). Inferential analysis identified sex (Cohens d = -0.357), type of university (d = 0.189) and HPV knowledge (partial eta-squared = 0.096) as the only significant determinants. Age, socioeconomic stratum, age at sexual debut and vaccine-specific knowledge did not reach meaningful significance. HPV vaccine perception was predominantly positive but conditioned by three biopsychosocial determinants, with HPV knowledge as the primary driver. The persistent gender gap reflects historical anchoring of HPV messaging in cervical disease and female-targeted campaigns. Public-health strategies should adopt comprehensive, gender-inclusive educational interventions that explicitly visibilise non-cervical HPV-related cancers and address both sexes from a common evidence base.

Background. The 2024 international reference standard for urinary tract infection (UTI) research scores four domains - symptoms and signs, systemic criteria, pyuria, and culture - to classify samples as No UTI, Possible UTI, Probable UTI, or Definite UTI. It explicitly identifies spinal cord injury (SCI) as a condition of impaired symptom perception, and states that catheter-associated UTI requires a separate standard. We applied it to verified-asymptomatic samples from adults with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury or disease (SCI/D) who use intermittent catheterization (IC), to test whether it can identify UTI likelihood in this population. Methods. The reference standard was applied to 224 samples from 99 adults with NLUTD due to SCI/D using IC, all verified asymptomatic by the Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter (USQNB-IC) at sampling and for 72 hours prior. Because no participant was febrile and no blood markers are drawn in this population, the systemic-criteria domain scored zero for every sample; the reported classifications are therefore a floor. Pyuria was scored under conservative and inclusive interpretations of categorical urinary white blood cell (WBC) bins. Results. Under conservative interpretation, 40.2% of samples were classified No UTI, 21.9% Possible UTI, and 37.9% Probable UTI; under inclusive interpretation, 11.6% No UTI, 38.4% Possible UTI, and 50.0% Probable UTI. No sample reached Definite UTI - a structural consequence of the empty systemic domain. Conclusions. The consensus reference standard classifies 38-50% of fully asymptomatic NLUTD-IC samples as Probable UTI, a floor estimate that could only rise if blood markers were available. This confirms the 2024 framework's own prediction that a separate standard is needed for populations with altered symptom expression and baseline-positive urinary markers.

Background: Q fever, caused by Coxiella burnetii, is a zoonosis with significant public health implications. Spain has the highest number of cases in the European Union/European Economic Area, but the clinical and hospitalization burdens remain poorly characterized. This study described the epidemiology, demographic and clinical characteristics, and geographical distribution of hospitalized Q fever patients in Spain from 2016 to 2023. Methods: We conducted a nationwide, retrospective study using the Spanish Minimum Basic Data Set for Hospitalization (MBDS-H). All hospital admissions with an ICD-10-CM code for Q fever (A78) between 2016 and 2023 were included. We analyzed demographic data, comorbidities, complications, length of stay, intensive care unit (ICU) admission, and mortality. We calculated hospitalization rates per 100,000 population. Temporal trends were assessed using Poisson regression. Results: We identified 3,358 hospitalizations for Q fever, representing an overall hospitalization rate of 0.89 per 100,000 population. The median patient age was 56 years (interquartile range [IQR] 42-70), and the cohort was predominantly male (72%). The median hospital length of stay was 9 days (IQR 6-15), and 8.3% required ICU admission. The overall mortality rate was 2.4%. The most common complication was pneumonia (32%). Significant upward trends were observed over the study period for patient age, hypertension, and acute heart failure (p<0.05). Geographical analysis revealed the highest hospitalization rates in the Canary Islands (2.33), La Rioja (2.16), and the Balearic Islands (1.93). Conclusion: This study highlights the hospitalization burden due to Q fever in Spain. The risk of hospitalization increases with age and the presence of predisposing conditions. The marked regional heterogeneity and high frequency of complications such as pneumonia underscore the need for enhanced surveillance and a strengthened One Health approach to control this zoonosis.

Background: Localized skin and soft tissue infections may need systemic antibacterials, but local inflammation can delay symptom recovery. We evaluated whether topical fresh Taraxacum mongolicum wet dressing added to ceftriaxone was associated with short-term benefit in selected clinically stable adults. Methods: In this single-center, assessor-blinded, three-arm randomized trial, 180 adults aged 18-74 years were randomized 1:1:1 to topical T. mongolicum plus intravenous ceftriaxone, topical T. mongolicum alone, or ceftriaxone alone for 7 days. The primary outcome was day-7 clinical response assessed by blinded independent assessors using prespecified global clinical improvement criteria. Analyses followed the intention-to-treat principle; sensitivity analyses assessed robustness. Results: Day-7 clinical response rates were 91.67% (55/60), 76.67% (46/60), and 68.33% (41/60) in the combined, T. mongolicum, and ceftriaxone groups, respectively (overall P = 0.006). Compared with ceftriaxone alone, combined therapy had a higher response rate (risk difference, 23.3 percentage points; 95% CI, 9.6 to 37.0; risk ratio, 1.34; 95% CI, 1.11 to 1.62). Sensitivity analyses were directionally consistent. Secondary outcomes and bacterial clearance favored the combined group. No serious adverse events were reported. Conclusions: In selected clinically stable adults with localized skin and soft tissue infections, adjunctive topical fresh T. mongolicum plus ceftriaxone was associated with improved short-term outcomes compared with ceftriaxone alone. Findings require cautious interpretation because this was a single-center, partially blinded trial without a placebo dressing control. The dressing should not replace antibiotics, drainage, or urgent care when indicated. Trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR2026000549.

Background Current molecular diagnostics for Mycobacterium tuberculosis (MTB) require complex nucleic acid extraction procedures and laboratory infrastructure, limiting their use as point-of-care (POC) tests in resource-limited settings. To address these barriers, we developed an extraction-free one-pot CRISPR assay for rapid detection of MTB directly from minimally processed sputum specimens. Methods The assay integrates ambient-temperature chemical lysis, recombinase polymerase amplification, and CRISPR-Cas12a detection within a single closed-tube workflow. A conserved region of the MTB-specific IS6110 insertion sequence was targeted for detection. Analytical performance was evaluated using serially diluted MTB genomic DNA standards, followed by clinical validation using 100 archived sputum specimens, including 50 MTB-positive samples and 50 MTB-negative controls. Results The extraction-free assay detected MTB genomic DNA within 30 minutes and achieved an analytical limit of detection of 100 copies per reaction. In clinical validation, the assay correctly identified 48 of 50 MTB-positive specimens and 49 of 50 MTB-negative specimens, yielding 96.0% sensitivity and 98.0% specificity. Conclusions This study demonstrates the feasibility of extraction-free one-pot CRISPR-Cas12a detection of MTB directly from sputum specimens. By eliminating conventional nucleic acid extraction while maintaining high analytical sensitivity and diagnostic performance, the platform may facilitate future development of rapid molecular diagnostics for POC and resource-limited settings.

Background Nontuberculous mycobacteria (NTM) are clinically important pathogens but often weakly positioned within health systems, with unclear institutional ownership, variable notification arrangements, and limited surveillance visibility. Methods We conducted a multilingual online survey among programme-facing national and subnational mycobacterial stakeholders from November to December 2025. Using an adaptive hierarchical recruitment strategy, we targeted 217 countries and jurisdictions. One response per programme was requested. We assessed institutionalisation, notification, agenda maturity, thematic discussion priorities, and barriers to action. We also derived relative policy momentum from three urgency domains (diagnostics, clinical management, and surveillance) using within-WHO region hierarchical clustering. Findings were used to develop a heuristic roadmap for staged NTM governance and system visibility. Results We received 193 programme-level responses, including from subnational jurisdictions, representing 171 of 217 targeted countries (78.8% jurisdictional coverage). NTM institutionalisation status was heterogeneous: 34% reported NTM integration within the NTP, while 37% expressed intents to institutionalise within the NTP in nearest future. Mandatory notification was reported by 21% of programme units, voluntary notification by 10%, and notification under consideration by 24%. NTM appeared to enter policy discussions along a gradient, with clinical management and diagnostics attracting earlier attention than surveillance, training needs, and financing. Globally, pulmonary NTM was discussed more frequently than extrapulmonary disease. Across WHO regions, policy momentum clustering separated programmes into higher and lower profiles, with surveillance consistently being the weakest domain. Financing and lack of epidemiological data were identified as the most actionable barriers. There was broad support for TB-NTM surveillance integration. Conclusions NTM governance is heterogeneous and frequently weakly anchored globally. The findings do not support a single universal institutional model; rather, existing mycobacterial platforms may provide pragmatic starting points for improving programme visibility, coordination, and reporting. The proposed heuristic roadmap outlines staged governance options according to burden, capacity, and institutional context.

Background and Aims The optimal treatment for first episodes and first recurrences of Clostridioides difficile infections (CDI) is unknown and there is emerging evidence for pulse and taper (P-T) regimens. Therefore, we sought to estimate the relative efficacy of treatment options. Methods MEDLINE and CENTRAL were searched from database inception to May 21, 2025 and unpublished conference abstracts were searched from recent infectious disease conferences. RCTs on the treatment of first episodes or first recurrences of CDI comparing fixed-dose or P-T regimens of fidaxomicin or vancomycin were included. The primary and secondary outcomes were 40- and 56-day CDI recurrence, respectively. A random-effects network meta-analysis on the risk ratio (RR) scale was conducted using a standard regimen (10-14 days) of vancomycin as the comparator. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results 8 RCTs were included comprising a total of 2181 patients. For 40-day recurrence, fidaxomicin P-T had the highest probability of ranking best (RR=0.10, 95%Confidence Interval [95%CI]=0.10-0.49, SUCRA=1.00), followed by vancomycin P-T (RR=0.49, 95%CI=0.32-0.76, SUCRA=0.61), fixed-dose fidaxomicin (RR=0.61, 95%CI=0.49-0.76, SUCRA=0.39), and, finally, fixed-dose of vancomycin (SUCRA=0.00). The treatments ranked in the same order for 56-day recurrence, though only 3 RCTs reported on this timepoint. Conclusion Vancomycin P-T, fidaxomicin P-T, and fixed-dose fidaxomicin were all superior to a fixed-dose vancomycin. Head-to-head comparative effectiveness RCTs are needed to quantify their relative effect sizes of and impact on long-term prevention of recurrent CDI.

Abstract Introduction. Culture data guide orthopedic-infection management, yet the organism spectrum, resistance, and no-growth fraction are reported inconsistently and mostly within proprietary registries. We characterized these in a public, reproducible dataset. Methods. Retrospective cross-sectional study using MIMIC-IV version 3.1, a de-identified single-center US database. Episodes with an International Classification of Diseases diagnosis of prosthetic joint infection (PJI) or native osteomyelitis were identified; organism-spectrum and no-growth analyses were restricted to the 46% with at least one deep musculoskeletal culture (tissue or bone, synovial or joint fluid, implant sonication), so the benchmark describes culture-sampled, not all, coded episodes. Proportions carry exact 95% CIs; variation was tested by logistic regression with Benjamini-Hochberg control, and an out-of-fold logistic model quantified how well no-growth was anticipated by structured data. Results. Of 7697 episodes (median age, 60 years; 35.5% female), 1089 were PJI, 5715 native osteomyelitis, and 893 other device infection. Among 7700 deep specimens (3560 episodes; 2603 patients), 35.7% showed no growth (patient-clustered 95% CI, 34.0%-37.3%). The fraction was higher in PJI than osteomyelitis (48.6% vs 26.6%) but rose with sampling intensity (24.5% to 50.7%), indicating differential ascertainment. S. aureus led (32.5%; 43.3% methicillin-resistant), and PJI was less often polymicrobial than osteomyelitis (adjusted OR, 0.44). No-growth was weakly anticipated by structured data (out-of-fold AUROC, 0.63). Conclusions. About one-third of deep specimens from code-defined orthopedic infection showed no growth. This specimen-level fraction differs from a criterion-confirmed culture-negative-infection rate and depends on sampling intensity; it is released as a re-runnable benchmark on identical open data, not a transferable rate.

Clesrovimab and nirsevimab are long-acting monoclonal antibodies used to prevent respiratory syncytial virus (RSV) disease in infants, but waning protection in the first year of life is incompletely characterised. We applied a published Bayesian inference framework to clesrovimab and pooled nirsevimab trial data to estimate time-varying efficacy against medically attended RSV lower respiratory tract infection (LRTI) and RSV-associated hospitalisation, accounting for differences in placebo-arm event timing between trials. Estimated clesrovimab efficacy declined from 60.7% (95% CrI: 46.3-72.6) shortly after dosing to 38.3% (8.6-52.9) at six months against medically attended RSV LRTI, and from 87.1% (71.2-96.2) to 49.6% (10.4-70.7) against RSV-associated hospitalisation. For nirsevimab, corresponding estimates declined from 86.9% (75.4-95.0) to 53.8% (27.4-69.7) against LRTI, and from 77.5% (52.6-91.8) to 49.7% (15.7-68.3) against hospitalisation. After accounting for differences in RSV exposure timing and LRTI endpoint definitions between trials, we found no evidence of a difference in efficacy or waning between clesrovimab and nirsevimab.

Background: Monitoring Pseudomonas aeruginosa (P. aeruginosa) infection in people with cystic fibrosis (pwCF) is essential for early detection, targeted treatment, and prevention of chronification. Sputum culture is the current standard, yet many patients, particularly those receiving CFTR modulator therapy, struggle to expectorate sputum. Microbial aerosols from the respiratory tract offer a non-invasive alternative. This proof-of-principle study assessed the accuracy and feasibility of the AveloMask, a novel breath aerosol collection kit paired with qPCR detection. Methods: Adult pwCF and bronchiectasis patients attending routine monitoring visits and healthy controls were enrolled in a cross-sectional study. Participants wore the mask for 30 minutes, followed by 20 instructed coughs. Mask filters were tested with a triplex qPCR assay targeting P. aeruginosa specific ecfX and gyrB, and human RPP30 as an endogenous control. Accuracy was evaluated using a composite reference standard (sputum culture and PCR). Results: Of 25 patients enrolled, 23 were included in the analyses. Sensitivity was 12/19 (63.2%) for breath qPCR versus 15/19 (78.9%) for sputum culture. Breath qPCR missed 5 cases detected by sputum culture but detected 2 sputum culture-negative/qPCR-positive cases. Specificity of breath qPCR was 100% in 4 patients and 15 healthy controls. RPP30 was detected in all mask samples. AveloMask was perceived as easy to use, with many patients preferring it over sputum collection. Discussion: Mask-based breath collection demonstrated promising diagnostic accuracy for detection of P. aeruginosa. Breath sampling may complement or partially substitute sputum-based diagnostics, especially in patients unable to expectorate. Further studies are needed to define its clinical role.

Importance: Pharmacological targeting of host mechanisms that limit sepsis-induced organ dysfunction represents a new therapeutic approach. Preclinical studies showed that low-dose epirubicin enhances tissue damage control and attenuates sepsis severity independently of pathogen burden, thereby promoting disease tolerance to infection. Yet epirubicin can cause myelotoxicity when used in cancer therapy. Objective: To investigate whether low-dose epirubicin can safely be administered to patients with sepsis and septic shock. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial conducted in five German University hospitals. Patients with sepsis, defined by Sepsis-3 criteria, were eligible within 48 hours after diagnosis. The first patient was enrolled on October 19, 2022, and the last follow-up was conducted on May 21, 2025. Interventions: Eligible patients were randomized in a 4:1 ratio to receive either placebo or low-dose epirubicin in addition to standard care. There were three consecutive phases. Patients in the epirubicin group received a single dose of epirubicin (either 3.75 mg/m2, 7.5 mg/m2 or 15 mg/m2, depending on study phase). Main Outcomes and Measures: The primary endpoint of the trial was the 14-day myelotoxicity. Secondary and explorative outcomes included 90-day mortality, the degree of organ dysfunction as assessed by SOFA score, PK/PD modelling and cytokine release. Results: Of 854 patients assessed for eligibility, 32 were randomized and 31 were included in the primary analysis population. Six participants received placebo, nine participants received 3.75 mg/m2, nine received 7.5 mg/m2 and eight individuals received 15 mg/m2 epirubicin, respectively. There was no myelotoxicity in any group. Mortality at 90 days and SOFA-scores were not significantly different between groups. Two of 39 SAEs in the epirubicin group were assessed by the investigators as possibly related to epirubicin, Conclusions and Relevance Among patients with sepsis and septic shock, low dose epirubicin was not associated with increased myelotoxicity.