Infection最新文献

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.

Purpose: Isavuconazole is effective against invasive aspergillosis (IA) and mucormycosis (IM) and may improve clinical outcomes compared to alternative antifungal treatments. However, real-world evidence regarding its clinical use and the health economic burden of inpatient treatment for IA and IM of patients with haematological malignancies remains limited.

Methods: A retrospective, matched, multicentre cohort study was conducted in six German tertiary care centres. The study included adults with haematological or oncological diseases who were diagnosed with proven, probable, or possible IA or IM. We compared clinical and health economic outcomes under first-line treatment initiated with isavuconazole (case group) vs. liposomal amphotericin B (L-AmB) and/or voriconazole (control group) between 2016 and 2021. A micro-costing approach was used to assess direct treatment costs.

Results: We included 198 patients (99 per group), most with a probable or possible classification. Median length of hospital stay was 44 days (interquartile range [IQR] 27-74) in the isavuconazole group and 39 days (IQR 26-56) in the control group (p = 0.285). All-cause mortality rates were 29% and 31% (p = 0.530), with fungal-related deaths occurring in 21% (n = 6) and 23% (n = 7, p = 0.862), respectively. Mean antifungal drug acquisition and overall treatment costs were significantly higher in the isavuconazole group (€22,389 vs. €12,801, p = 0.003; €49,042 vs. €39,369, p = 0.030, respectively), while mean hospitalisation costs were comparable (€28,570 vs. €31,160, p = 0.406).

Conclusion: Our real-world analysis confirmed that first-line treatment initiated with isavuconazole resulted in clinical outcomes equivalent to those of L-AmB and/or voriconazole in patients with IA or IM. However, treatment costs during the in-patient stay were higher with isavuconazole.

Purpose: Fluconazole is the recommended step-down therapy from echinocandins for fluconazole-susceptible Candida spp in critically ill patients with invasive candidiasis. However, standard fluconazole dosing does not achieve adequate exposure in these patients. We aimed to identify factors impacting fluconazole pharmacokinetic-pharmacodynamic (PKPD) target attainment and provide a dosing regimen ensuring adequate target attainment in critically ill patients.

Methods: A population pharmacokinetics study (popPK) was conducted, combining fluconazole concentration data from eight studies. We used multiple imputation to handle missing covariate data, and Monte Carlo simulations to identify a dosing regimen with at least 90% probability of PKPD target attainment (PTA) in every patient. The PKPD target is the 24-hour area under the unbound concentration-time curve over the minimum inhibitory concentration of 100.

Results: Data from 177 critically ill patients were included. A two-compartment popPK model with linear elimination described the data best. Continuous renal replacement therapy (CRRT) status, estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and total body weight were statistically significant covariates. However, with standard dosing, only CRRT status and total body weight were clinically relevant, as PTA dropped below 90% for all patients on CRRT, and for patients off-CRRT above 60 kg. A weight-based loading dose and flat maintenance doses of 400 mg (off-CRRT) and 800 mg (CRRT) predicted ≥ 90% PTA across the weight range.

Conclusion: We have developed a fluconazole dosing regimen, stratified by weight and CRRT status, that may achieve adequate PTA in critically ill patients. External validation is awaited.

Introduction: Tuberculosis (TB) remains a significant global health issue, with extrapulmonary manifestations accounting for a notable proportion of cases. Perianal tuberculosis, however, is a rare presentation of TB, often leading to delayed diagnosis due to its nonspecific symptoms and similarity to other perianal diseases.

Methods: We present a case of perianal TB as primary manifestation leading to the diagnosis of simultaneous pulmonary TB, and a review of the literature based on a search in Medline.

Results: A 47-year-old male presented with perianal pain and purulent discharge. Histopathological examination and PCR analysis following surgical intervention confirmed the diagnosis of perianal TB. Chest imaging revealed nodular and cavitary lung lesions, indicating active pulmonary TB. The patient was initiated on a 9-month anti-tuberculosis treatment. Contact tracing identified latent TB infections among two close family members. Our literature search identified 59 relevant publications comprising 195 cases. The majority of the patients were male (88%), with a median age of 42 years, and originated from high prevalence regions. In many instances, diagnosis was delayed, with a mean duration of approximately two years from symptom onset to confirmation (median 6 month). Pulmonary tuberculosis was concurrently present in one third of the cases.

Conclusion: Diagnosis of perianal TB is often delayed due to its rarity and nonspecific clinical presentation. TB must be considered in the differential diagnosis of ulcerative, fistulous and abscess-forming lesions of the perianal area, especially if recurrent, and in patients originating from high prevalence countries of TB. In many cases, further diagnostic evaluations reveal simultaneous pulmonary tuberculosis, underscoring the importance of a comprehensive diagnostic approach. From a clinical and public health perspective, early diagnosis and prompt initiation of treatment are essential to prevent disease progression and transmission.