Infectious Diseases and Therapy最新文献

Introduction: Outpatient parenteral antimicrobial therapy (OPAT) enables effective infection management outside hospital settings, offering clinical and economic benefits. While widely adopted internationally, its implementation in Italy remains fragmented. This study aimed to systematically map the use of OPAT in Italy to identify research and policy priorities.

Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews guidelines. The protocol was registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/GX8S6 ) in August 2025. Searches were performed across PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus. Eligible studies included primary research on OPAT in Italy, with no restrictions on publication date or language. Data extraction focused on study characteristics, OPAT indications, antimicrobial agents, delivery models, and outcomes.

Results: Twenty-three studies were included, mostly observational and single-center, published between 2000 and 2025. OPAT was primarily delivered at home or in infusion centers. The most frequent indications were infections of bone and joint, skin and soft tissue, and the respiratory tract. Ceftriaxone was the most used antimicrobial. Delivery was mainly intravenous, often via elastomeric pumps and peripheral or central venous access. Reported outcomes were generally favorable, with cure or improvement rates exceeding 90% in several studies. Adverse events were infrequent, mostly associated with drug reactions or catheter-related complications. Patient satisfaction was consistently high. Economic evaluations were limited but suggested cost savings primarily driven by reductions in hospital stays.

Conclusions: OPAT is feasible and increasingly used in Italy, but remains inconsistently implemented across regions. Broader adoption would benefit from national guidance, standardized protocols, and integrated stewardship frameworks. Future research should address comparative and cost-effectiveness, as well as equitable access, to support systematic scale-up aligned with national health priorities on antimicrobial resistance and community-based care.

Introduction: Fecal microbiota, live-jslm (RBL) is the first single-dose, microbiota-based product approved by the US Food and Drug Administration and Health Canada to prevent recurrent Clostridioides difficile infection (rCDI) following standard-of-care antibiotics. The phase 3 PUNCH CD3-OLS study enrolled participants with numerous comorbidities and permitted inclusion of participants hospitalized due to rCDI. The safety and efficacy of RBL were evaluated in this subgroup analysis of hospitalized participants from PUNCH CD3-OLS.

Methods: The hospitalization subgroup included participants hospitalized for rCDI within 90 days prior to RBL administration. Participants received a single dose of RBL 24-72 h after completion of standard-of-care antibiotic treatment for rCDI. These exploratory analyses evaluated the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs), treatment success at 8 weeks, sustained clinical response at 6 months, and incidence of rehospitalization for rCDI during study participation.

Results: The hospitalization subgroup included 74 of 697 (10.6%) participants. Within 6 months following RBL administration, 47 (63.5%) and 350 (56.7%) participants in the hospitalization and nonhospitalization subgroups experienced TEAEs, respectively; most TEAEs were of mild to moderate severity. Serious TEAEs in the hospitalization subgroup were frequently related to preexisting conditions; none were related to RBL or its administration. Most participants (87.8% [65/74]) in the hospitalization subgroup were not rehospitalized within 6 months. Treatment success at 8 weeks was 62.5% (45/72) and 75.1% (449/598) among participants in the hospitalization and nonhospitalization subgroups, respectively. Of those achieving treatment success, 86.7% (39/45) and 91.3% (410/449) had sustained clinical response through 6 months in the hospitalization and nonhospitalization subgroups, respectively.

Conclusion: RBL was safe and effective in a subgroup of hospitalized participants in the PUNCH CD3-OLS study. Efficacy in this subgroup was slightly lower than in nonhospitalized participants, but rCDI-related rehospitalization remained rare.

Trial registration: NCT03931941.

Introduction: Candidemia is a notable cause of morbidity and mortality in critically ill children. The Pediatric (Paed)-EQUAL scale, which includes 11 clinical and microbiological assessment parameters, was recently developed to improve guideline compliance in pediatric patients with candidemia. The aim of our study was to evaluate compliance with the Paed-EQUAL scale in pediatric patients with candidemia and to demonstrate its relationship with survival.

Methods: We retrospectively analyzed the clinical and microbiological characteristics and compliance with the Paed-EQUAL scale parameters of patients aged 1 month to 18 years who were diagnosed with candidemia and admitted to our pediatric intensive care unit over a 10-year period. Among the 117 candidemia cases identified, 103 were included in the study. We evaluated the associations between survival and various parameters, including the Paed-EQUAL score and candidemia-related clinical and microbiological characteristics.

Results: The 30-day mortality rate in our cohort was 17.5%. The Paed-EQUAL score had a significant discriminatory ability for identifying mortality outcomes. In the entire cohort, patients with a score of ≥ 16.5 had a greater likelihood of survival (AUC 0.742; p = 0.001). Separate analyses for patients with and without central venous catheters (CVCs) revealed that the discriminatory performance increased to an excellent level (AUC 0.913) among those without CVCs, which was based on a lower optimal cutoff (≥ 12.5). Multivariable regression revealed that the presence of breakthrough candidemia was associated with 10.5-fold greater odds of mortality (OR 10.52, 95% CI 1.66-66.7; p = 0.013), whereas each 1-point increase in the Paed-EQUAL score was associated with 1.4-fold greater odds of survival (OR 0.703, 95% CI 0.53-0.89; p = 0.004). Individual Paed-EQUAL components had no significant predictive role in assessing mortality risk.

Conclusion: The present study revealed that the Paed-EQUAL score can predict mortality in pediatric patients with candidemia. Patients with a Paed-EQUAL score of ≥ 16.5 had significantly higher rates of survival.

Introduction: This study aims to deliver contemporary, population-based estimates of herpes zoster (HZ) incidence, temporal trends, complications, healthcare utilisation and direct costs among general adults and adults with increased-risk conditions.

Methods: A retrospective cohort study using the Yinzhou Integrated Health Platform (2015-2021; China) was performed. Incident HZ was ascertained after a 1-year washout; increased-risk conditions were pre-specified (immunocompromising/autoimmune). We calculated age-/sex-standardised incidence, assessed trends with joinpoint regression and summarised HZ-related outpatient visits, hospitalisations and direct medical costs [Chinese yuan (¥) and US dollars ($)].

Results: Among 5.42 million person-years, including 790,410 subjects, 25,855 incident HZ events were identified. Overall incidence was 4.77/1000 person-years (PY) [95% confidence interval (CI) 4.71-4.83] and 16.13/1000 PY (95% CI 15.25-17.06) in increased-risk adults [incidence rate ratio (IRR) 3.44 versus in adults without immunocompromising conditions or autoimmune diseases (AIDs)]. Incidence rose with age (peak 70-79 years overall; 60-69 years increased-risk) and was higher in women. Postherpetic neuralgia (PHN) was the most frequent complication (8.96% overall; 10.88% increased-risk). Standardised incidence increased from 4.67 to 7.51/1000 PY during 2015-2021 [annual percentage change (APC) 7.94%], with a steep rise to 2019 and plateau thereafter. Hospitalisation among incident HZ was 1.35%. Mean direct cost per episode was Chinese yuan (¥)625.52 [US dollars ($)94.35] for outpatients and ¥8854.03 ($1335.45) for inpatients; increased-risk outpatients incurred higher mean costs (¥1205.47, $181.82). Across strata, complications - especially PHN - were associated with more visits and higher expenditure.

Conclusions: HZ imposes a rising, age- and risk-concentrated burden in Chinese adults, with PHN being the principal driver of resource use and costs. These real-world estimates support prioritising zoster vaccination for adults ≥ 50 years and clinically vulnerable groups, and integrating HZ surveillance and management within chronic-disease programmes.

Introduction: Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste.

Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux).

Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events.

Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges.

Invasive meningococcal disease (IMD) in older adults frequently presents with atypical clinical manifestations, including bacteremic pneumonia, often without classical meningeal signs or sepsis, which presents clinicians with diagnostic challenges, and may delay treatment, which contributes to the high mortality observed in older adults. Within the broader resurgence of IMD observed since relaxation of quarantine measures introduced to mitigate the impact of the COVID-19 pandemic, there has been a notable increase in reporting of such atypical cases. The aim of this review is to summarize epidemiological, diagnostic, and treatment aspects of non-meningeal forms of IMD in older patients, with a focus on meningococcal pneumonia. By convention, laboratory confirmation requires N. meningitidis detection by culture, polymerase chain reaction (PCR), or antigen detection. In most cases, presentation of meningococcal pneumonia is similar to that of other forms of community-acquired pneumonia, and cerebrospinal fluid sampling may be non-informative. This places a premium on early blood culture for N. meningitidis, allied with testing of respiratory samples (e.g., broncho-alveolar washes). Many cases are linked to isolates of serogroups Y and W. When confirmed, treatment with third-generation cephalosporins is generally preferred. Chemoprophylaxis and vaccination of close contacts is essential for controlling onward meningococcal disease transmission and prevention of further cases.

Antibiotic discovery and antibiotic prescribing represent two domains that both stand to benefit from artificial intelligence (AI)-driven progress in the near future. In this article, we discuss these parallel advances and the potential future synergy between AI-enabled antibiotic discovery and AI-assisted antibiotic prescribing. Although multiple challenges remain before these two domains meaningfully converge, their integration could amplify the strengths of each: discovery pipelines generating broader, more diverse classes of antibacterial agents, and prescribing tools capable of matching these agents to individual patients with unprecedented precision. Such a scenario could transform antibiotic therapy by enabling AI-supported, patient-specific treatment decisions while reinforcing the principles of precision medicine and antimicrobial stewardship.

Introduction: Respiratory syncytial virus (RSV) is an important cause of hospitalizations among adults. Following bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine licensure and implementation, two studies have documented population-level reductions in RSV hospitalizations in the United Kingdom (UK), ranging from 30% to 62% in England and Scotland, respectively. Separately, vaccine effectiveness (VE) studies have been conducted in a number of settings. The question arises: Is there a relationship between these population-level reductions in RSV hospitalizations and real-world VE estimates from the first season post-implementation of bivalent RSVpreF, and do the impact findings reflect what would be expected from the VE estimates?

Methods: Publicly available estimates for end-of-season-1 (EOS1) bivalent RSVpreF VE against RSV-related hospitalization were identified. Using these VE estimates, the expected vaccine impact across all potential vaccine coverage values was calculated using the formula impact = VE * uptake. We additionally estimated expected VE based on the impact findings from the RDD analyses.

Results: Six real-world studies evaluating bivalent RSVpreF VE were identified from the United States, UK, and Denmark; they documented 67-91% bivalent RSVpreF VE against RSV-related hospitalizations. Calculated impact using these six VE estimates closely aligned with the measured results estimated from the UK analyses. VEs calculated in turn from impact estimates ranged from 91% [Scotland] to 76% [England], closely aligning with expected results.

Conclusions: These early results indicate that the extent of expected population-level impact achieved can be reliably predicted from VE studies and national coverage data. Bivalent RSVpreF use can have a substantial public health and economic impact by reducing RSV-related hospitalizations, as seen in this initial UK vaccination program. Protection of older adults from severe RSV disease is off to a promising start and implementation efforts to boost vaccine uptake should be a priority for health care workers, public health practitioners, and policymakers.

Introduction: The molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) impact transmission, clinical presentation, and treatment. Contemporary data on the molecular epidemiology of MRSA causing healthcare-associated (HA) infections in Latin America are scarce. In this study, we aimed to assess the molecular epidemiology, virulence genes, and antimicrobial susceptibility of MRSA bloodstream infections (BSI) isolates from Brazil.

Methods: A multicenter, prospective study in 14 Brazilian hospitals was conducted from August/2022 to August/2023. MRSA isolates recovered from HA-BSIs were sent to a central laboratory for whole-genome sequencing (WGS) and antimicrobial susceptibility testing.

Results: Of 255 S. aureus, 66 (25.9%) were MRSA, and 47 were submitted to WGS. The most frequent clonal complex (CC) was CC5 (n = 34, 72.3%), mostly of sequence types (ST) 105 (19/34; 55.9%) and ST5 (6/34; 17.6%). ST105(CC5)-SCCmecII-t002 was the commonest strain (10/47, 56.2%), detected in three of four studied regions, followed by the ST8(CC8)-SCCmecIV strains with distinct spa types (9/47; 19.2%). Three new MLST alleles were discovered, resulting in new ST designations 10,174, 10,175, and 10,176. Furthermore, the resulting phylogeny revealed three well-defined clades. Twenty-eight virulence genes were detected. All isolates were susceptible to vancomycin, linezolid, and ceftaroline, while susceptibility to daptomycin and delafloxacin was 88.9% and 51.2%, respectively.

Conclusions: The recently reported ST105(CC5)-SCCmecII-t002 clone has disseminated in hospitals from different Brazilian regions, together with other lineages that have been previously associated with community-associated infections, composed a new molecular landscape of MRSA causing HA BSIs in Brazil.

People with HIV (PWH) are disproportionately affected by viral hepatitis as a result of overlapping transmission routes, reduced vaccine immunogenicity, altered disease progression, and unique therapeutic considerations under HIV-related immunosuppression. Although the scale-up of antiretroviral therapy (ART) and direct-acting antivirals (DAAs) has significantly improved outcomes, viral hepatitis remains a major cause of liver-related morbidity and mortality in this population. This virus-specific review summarizes current knowledge and recent advances in the epidemiology, vaccination, and treatment strategies for hepatitis A through E (i.e., hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV); HAV-HEV) among PWH. HAV has re-emerged in community outbreaks among men who have sex with men (MSM), with prolonged or atypical presentations in people who are immunocompromised, underscoring the need for improved vaccination coverage and durable immunity. HBV coinfection remains the most clinically significant challenge, requiring lifelong dual-active ART and raising persistent concerns about poor vaccine response and long-term protection. HCV has become curable with DAAs, yet reinfection-particularly among MSM and people who inject drugs-remains a major barrier to microelimination. HDV, though less prevalent, causes severe liver disease and now has promising targeted therapies under clinical use or investigation. HEV is increasingly recognized as an underdiagnosed pathogen and potentially chronic infection in people who are immunocompromised, with limited diagnostic availability and global accessibility to effective vaccine. Effective hepatitis prevention and treatment in PWH must address the immunologic, clinical, and virologic nuances of each virus. Integrated models of care that combine HIV and hepatitis services are essential to improving long-term liver health, reducing disparities, and advancing toward global goals of viral hepatitis elimination.