Infection最新文献

Avian influenza remains a persistent global health threat, with Asia at its epicentre due to dense poultry production, live bird markets, and cross-species interfaces with ducks and swine. Several pathogenic subtypes continue to cause recurrent zoonotic spillovers with varying human case fatality, reinforcing the region's role as a pandemic hotspot. Surveillance highlights the main key ecological drivers: sustained viral circulation in live bird markets, subclinical infection in domestic ducks, wild birds serving as reservoirs, and multiple species with dual receptors that can act as mixing vessels enabling reassortment. Recent events in the United States, where H5N1 has emerged in dairy cattle with viral RNA detectable in retail milk and human cases arising from both poultry and dairy cattle exposures, further demonstrate the capacity of these viruses to invade new mammalian hosts and the food chain. Advances in poultry vaccination and next-generation antivirals show promise but are constrained by antigenic drift, incomplete protection, logistical barriers, and uneven uptake. Human preparedness remains weakened by diagnostic delays, limited access to therapeutics, and fragmented surveillance. Mitigation requires regionally tailored, One Health-driven strategies, market regulation, duck vaccination, swine surveillance, and rapid therapeutic deployment, together with equitable access to tools and transparent international collaboration to reduce zoonotic risk and strengthen global pandemic readiness. This review synthesizes recent evidence on avian influenza virus infections in Asia, outlining zoonotic risks, key drivers, and mitigation strategies, and concludes that the sustained circulation of these viruses in poultry and wild birds continues to present significant challenges for animal health, public health, and pandemic preparedness, highlighting the importance of strengthened One Health surveillance and control measures.

Background: Infections with Carbapenem-resistant Enterobacterales (CREs) are a serious public health threat. The emergence of distinct New Delhi metallo-beta-lactamase (NDM)-producing K. pneumoniae strains resistant to cefiderocol is a significant concern given the limited armamentarium for these carbapenemases.

Methods: A case series of 12 patients was described from a single institution that had cefiderocol-resistant, NDM-producing K. pneumoniae infections between January 2023 and July 2024. Whole genome sequencing with core SNP analysis was performed to identify resistance mechanisms and clonal relatedness for 9 isolates.

Results: Patients presented with various infections, including skin and soft tissue infections, pneumonia, and bacteremia. Of concern, cefiderocol resistance was seen among patients with and without prior cefiderocol exposure. Genomic analysis for 9 patients revealed NDM-5 in every isolate, along with additional mutations associated with resistance. A cluster of ST147 identified multiple distinct CirA disruptions, suggestive of convergent evolution with or without cefiderocol exposure. Treatment with either ceftazidime-avibactam plus aztreonam or tigecycline was successful in most instances, although microbiologic recurrence occurred in certain cases.

Conclusion: High level cefiderocol resistance among NDM-5 producing K. pneumoniae with siderophore mutations add more challenges to treating CRE infections. Stricter infection control measures along with enhanced surveillance are needed, especially in regions where NDM is endemic to limit additional spread of these variants.

Breakpoints to define the susceptibility of pathogens to antibiotics are becoming increasingly popular as guidance for antimicrobial therapy. Some breakpoints consider divergent concentrations of antibiotics in different compartments, others list one breakpoint for infections at all sites. Compared to the determination of exact minimal inhibitory concentrations (MICs) and relation of these MICs to concentrations achievable in ventricular CSF, the exclusive use of breakpoints for central nervous system (CNS) infections is a setback. The lack of the determination of exact MICs may be a risk, particularly when no clinical breakpoints for CNS infections have been defined. Moreover, the current practice of MIC determination of β-lactam/β-lactamase inhibitor combinations with fixed β-lactamase inhibitor concentrations ignores that often these β-lactamase inhibitor concentrations are not attained in CSF with established antibiotic regimens. In CNS infections, we strongly recommend the exact determination of MICs and their interpretation in relation to the true antibiotic concentrations in the infected compartment.

Background & objectives: Multidrug-resistant (MDR) Klebsiella pneumoniae poses a critical treatment challenge. Colistin remains a last-resort antibiotic but is limited by nephrotoxicity and resistance. Though clinical data are limited, Doxycycline has demonstrated in vitro synergy with colistin. Colistin-meropenem is frequently used as a comparator regimen, despite mixed evidence on its synergistic activity. This study evaluates the efficacy, microbiological response, and safety of colistin-doxycycline versus colistin-meropenem in MDR Gram-negative infections.

Methods: A double-blind, randomized controlled trial was conducted at a teaching hospital. Adult patients with culture-confirmed MDR Klebsiella pneumoniae infections were randomized to receive colistin-doxycycline or colistin-meropenem. The primary outcome was clinical cure, defined as resolution of infection signs without therapy escalation and in-hospital mortality. Secondary outcomes included microbiological eradication, acute kidney injury (AKI), and treatment-related adverse events. Patients were followed throughout hospitalization and for 14 days post-treatment.

Results: A total of 46 patients were enrolled, with 23 patients in each group. Clinical cure rates were significantly higher in the colistin-doxycycline group (87.0% vs. 46.7%, p = 0.012), and mortality was lower (69.6% vs. 86.7%, p = 0.017). Microbiological eradication was also superior (p = 0.016), and nephrotoxicity incidence was numerically lower (19.1% vs. 33.3%, p = 0.092). Faster resolution of inflammation (p < 0.05) and reduced need for mechanical ventilation (60.9% vs. 33.3%, p = 0.028) were observed in the colistin-doxycycline group.

Conclusions: Colistin-doxycycline showed superior efficacy to colistin-meropenem in MDR Klebsiella pneumoniae infections, with higher cure rates, better bacterial eradication, and a favorable safety trend. These results support its potential as a possible alternative option in managing MDR Gram-negative infections, though confirmation in larger multicenter trials is needed.

Background: Candida auris is a significant cause of severe infections in immunocompromised patients, contributing to its frequent occurrence in healthcare settings. Although Candida species are typically linked to candidemia, deep-seated infections like osteomyelitis have also been observed, though they are rarely documented in literature. A 72-year-old man with Guillain-Barré syndrome (GBS) and quadriplegia, status-post tracheostomy and gastrostomy tube placement, presented with new right facial droop and aphasia. A brain CT was unremarkable. Labs were significant for leukocytosis, anemia, and elevated lactic acid consistent with septic shock. A CT scan of the abdomen and pelvis revealed fluid in both hip joints, concerning for source of infection. Fluid cultures from his left hip grew Candida auris. He was subsequently also diagnosed with Candida auris osteomyelitis and discitis of the thoracic spine, confirmed by PET scan and follow-up fine-needle aspiration. The patient had persistent infection despite treatment with Amphotericin B and micafungin for nine months but has shown clinical and radiographic signs of improvement. A full 12-month course of antifungal therapy is to be completed.

Conclusion: This case underscores the importance of thorough tissue, joint, and vertebral sampling for accurate diagnosis, and highlights the urgent need for standardized treatment protocols for Candida auris osteomyelitis to improve patient outcomes.

Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors' quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.

Highly pathogenic avian influenza A(H5N1) continues to pose a significant threat to global health due to its increasing geographic spread, high mortality in human cases, and expanding host range, including recent mammalian infections. Antiviral therapy remains a key strategy alongside vaccination, especially for controlling outbreaks and limiting disease severity. This article provides a comprehensive, up-to-date overview of antiviral agents with established or investigational activity against H5N1, including both globally approved drugs and regionally licensed compounds, such as arbidol and triazavirin in Russia and laninamivir and favipiravir in Japan. We detail the mechanisms of action, approval status, resistance patterns, and efficacy data in H5N1-specific models. The recent regulatory approvals of onradivir, suraxavir marboxil, and ZX-7101A in China are highlighted, along with emerging antivirals in advanced development. We summarize findings from relevant clinical trials and discuss key resistance-associated mutations identified in recent H5N1 isolates. Although several agents show promise in preclinical studies, clinical data specifically for H5N1 remain nonexistent. Challenges persist around resistance monitoring, access to novel therapies, and regulatory harmonization. Expanding the antiviral armamentarium through accelerated evaluation and integration of both traditional and innovative compounds will be essential to pandemic preparedness and effective H5N1 outbreak response.

Purpose: Candida spp. has emerged as major fungal pathogens, especially in immunocompromised individuals, posing significant challenges in clinical settings. Their growing prevalence and increasing resistance to antifungal agents underscore the urgent need for systematic investigation into resistance mechanisms. Constant monitoring of resistance-associated mutations is essential to mitigate drug resistance and develop effective therapeutic strategies.

Method: We developed CanDRes, a manually curated, open-access resource cataloging mutations linked to antifungal resistance in Candida spp. Mutations were systematically compiled from published literature, focusing on those identified in drug-resistant clinical isolates. Each entry was annotated with gene-level information, drug associations, organism specificity, resistance mechanisms, and evidence-based validation scores. 3D structures of mutant proteins were developed and are available for download from the CanDRes database.

Results: CanDRes encompasses 1053 unique mutations across 56 genes from drug-resistant strains of 13 Candida spp., assessed against 19 antifungal drugs. The database also includes resistance mechanisms, protein sequences, predicted 3D structural models, and mutation plots. These data provide a valuable foundation for understanding molecular resistance patterns and for guiding therapeutic decision-making.

Conclusion: Our study emphasizes the critical need to investigate antifungal resistance in Candida spp., which are among the most clinically challenging fungal pathogens. Understanding the mechanisms driving resistance to frontline antifungals can improve treatment strategies. CanDRes serves as a free and accessible resource for clinicians and researchers aiming to address antifungal resistance. Users can access CanDRes via https://candres.bicnirrh.res.in/ .

Background: Sepsis survivors are affected by a broad spectrum of long-term impairments, which overlap with Long-Covid and sequelae after influenza in their clinical presentation. However, we lack comparative assessments on the burden of long-term outcomes, particularly with patients being recruited from the same, contemporary patient population. Therefore we compared long-term outcomes after respiratory sepsis (RS), SARS-CoV-2-associated sepsis (SS) and influenza-associated sepsis (IS).

Methods: Retrospective, population-based cohort study. We included patients > 15 years hospitalized with RS, SS and IS between 01/2020 and 12/2020 in Germany, who received intensive care unit treatment. We compared mortality, readmissions, prevalence of diagnoses in the cognitive, psychological or medical domain, and the number of impaired domains in the 12 months post-discharge between the three survivor cohorts, adjusting for between-group differences in relevant covariates by inverse propensity score weighting based on generalized propensity scores.

Results: Our study included 12,854 patients, of which 8,201 were RS, 3,964 SS and 689 IS survivors. RS survivors had a considerably higher risk for 12-month mortality compared to SS and IS survivors (relative risk, 1.77 [95% CI, 1.54-2.03]; P < 0.001 and relative risk, 1.37 [95% CI, 1.14-1.65]; P = 0.001, respectively). They were more often rehospitalized, affected by multiple domain impairments, cognitive decline and impairments related to the severity of acute disease, e.g. complications of the tracheostoma, compared to survivors after SS and IS. RS survivors had a lower risk for being affected by medical diagnoses compared to SS. Risks for psychological diagnoses did not differ between RS and the other survivor groups.

Conclusions: Although respiratory sepsis survivors seem to be affected by more severe long-term impairments, the overall burden of post-acute sequelae among all survivor groups is high. This warrants efforts to provide targeted aftercare for all survivor populations after life-threatening infections.