Infectious Disease Reports最新文献

Background/objectives: In an 18- to 24-month Treatment Phase with once-daily efinaconazole 10% solution, subjects with onychomycosis showed an increased rate of cure at Month 24 versus the phase III trials. In order to further improve efficacy, we initiated an extended intermittent efinaconazole Maintenance Phase with use 2-3 times weekly for an additional 24 months from Month 24 to Month 48. These are the first data presented for a 48-month efinaconazole use period.

Methods: For patients completing 18-24 months of once-daily efinaconazole, the target great toenail from the Treatment Phase was graded as 'Clinical Cure' (≤10% affected area) or 'No Clinical Cure' (>10% affected area) at Month 24. Mycological and clinical outcomes were assessed every 4 months from Month 24 to Month 48. There were 35 patients who enrolled in the extension and continued intermittent efinaconazole use to Month 48. Patients with 'Clinical Cure' at M24 were reviewed for sustained cure at M48; patients with 'No Clinical Cure' were reviewed for development of 'Cure' at M48. All patients were reviewed at all visits for adverse events that may be related to efinaconazole use.

Results: 'Clinical Cure' was found in 6 of 35 enrolled patients at Month 24, and clinical cure status was sustained to Month 48 with intermittent efinaconazole maintenance use. For 29 patients with 'No Clinical Cure', 3/29 achieved 'Clinical Cure' status at Month 48 with intermittent efinaconazole. Effective Cure and Complete Cure rates improved over the maintenance period to Month 48 in subjects without clinical cure at Month 24. Younger patients showed higher cure rates over the maintenance period, but age group cure differences did not reach statistical significance in this dataset, and 49% of the ≥70-year population had at least a 20% reduction in nail area with maintenance therapy to Month 48. There was only 1 case of possible efinaconazole application site reaction in the Intermittent Maintenance Period to Month 48; prolonged efinaconazole use to Month 48 does not appear to increase the risk of reaction. Efinaconazole use periods are associated with very low positive culture rates in this dataset, including typical contaminant organisms, suggesting efinaconazole presence in the nail plate is providing prophylactic therapy.

Conclusions: Intermittent efinaconazole may provide suitable prophylaxis of onychomycosis relapse. Prolonged efinaconazole therapy to Month 48 appears to be safe for all ages and can continue to provide prophylaxis of onychomycosis with Intermittent Maintenance use beyond Month 24 to Month 48.

Background: Glucagon-like peptide-1 (GLP-1) agonists are an existing treatment option for patients with insulin-resistant states, which elicit further pleiotropic effects related to immune cell recruitment and vascular inflammation. GLP-1 agonists downregulate the cluster of differentiation 147 (CD147) receptor, one of several receptors for the SARS-CoV-2 spike protein that mediate viral infection of host cells.

Methods: We conducted an open-label prospective safety and tolerability study including biomarker responses of the GLP-1 agonist Liraglutide, administered for 5 days as an add-on therapy to the standard of care within 48 h of presentation in a cohort of 13 patients hospitalized with COVID-19 pneumonia. Biomarker responses were compared in patients admitted to critical care and those not requiring critical care admission (non-critical group).

Results: Liraglutide (0.6 mg, subcutaneously) was well tolerated by all patients and all patients were alive 30 days after diagnosis. Plasma soluble CD147 levels were reduced in the non-critical patient group at day 5 in contrast to critical care-treated patients, who demonstrated an increase in soluble CD147 levels between day 0 and day 5. Patients with milder COVID-19 pneumonia severity also demonstrated improvement in echocardiographic parameters of right and left ventricular function, reduction in plasma Troponin levels, increased CD147 expression on T lymphocytes, and reduction in plasma IL-8.

Conclusions: This first-in-disease use of the GLP-1 agonist Liraglutide demonstrates its safety and tolerability in an unselected cohort of patients hospitalized with COVID-19 pneumonia across a range of clinical severities.

Objectives: Spondylodiscitis can be caused by various microorganisms and has shown a continuous rise in incidence and mortality. The purpose of our study was to analyze the demographic and laboratory data, as well as comorbidities of patients that were surgically treated for spondylodiscitis in our hospital. The causative pathogens involved in the etiology of spinal infections were also assessed. Methods: The study included 92 patients who underwent clinical, radiological, and microbiological analyses including bacterial isolation. According to their culture results, patients were divided into three groups: negative results (n = 29), positive results with Mycobacterium tuberculosis (M. tb.) (n = 26), and positive results with other pathological agents (n = 37). Results: Patients with M. tb. had a significantly lower body mass index (p = 0.022) and were significantly younger (p = 0.024) than the others. The analysis of the complete blood work showed significant differences between the groups regarding fibrinogen levels (p = 0.023), C-reactive protein (p = 0.009), and erythrocyte sedimentation rates (p = 0.042). Results also showed significant differences (p = 0.023) for patients with diabetes mellitus who were more prone to a tuberculosis etiology for their spondylodiscitis compared with patients without the disease. Conclusions: These findings have important implications for adopting individualized treatment strategies underlining the need for identification of patients at high risk for specific causative pathogens.

Background: This systematic review reports on treatments for onychomycosis in patients with diabetes and the drug interactions with other drugs in regard to the complicated diabetic patient profile. Methods: The recommendations in the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist were applied and the included studies were evaluated using the Consolidated Standards of Reporting Trials (CONSORT) statement and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Searches were conducted in November 2023, using the PubMed (Medline), Scopus, Cochrane Library, and Web of Science databases; studies on antifungal treatments for onychomycosis in patients with diabetes were included. Two authors performed the study selection and data extraction, and any discrepancies between the two reviewers were resolved through discussions with a third reviewer. This review was registered in PROSPERO (CRD42023442107). Results: The systematic review included 10 studies that met the selection criteria. Mycological cures for mild to moderate onychomycosis were: Ageratina pichinchensis (8.6%), 8% ciclopirox (8.6% 24 weeks and 54.3% 48 weeks), 10% efinaconazole (56.5-58.33%), terbinafine (73-76.6%), itraconazole (88.2%), and laser therapy (43.8%). No serious adverse effects or drug interactions were observed because patients with major complications, such as peripheral vascular disease, diabetic neuropathy, liver and renal dysfunction, poorly controlled diabetes, and severe onychomycosis, were excluded. Conclusions: The antifungal treatments described in the included studies are safe for patients with well-controlled diabetes, but there are currently no studies involving patients with diabetes and multiple complications, such as diabetic foot syndrome or severe onychomycosis. Thus, further research is needed in terms of this patient profile.

Background/Objectives: Vaccine hesitancy, recognized by the WHO as a significant global health threat, undermines vaccination efforts. This study aimed to adapt and validate the Parent Attitudes about Childhood Vaccines (PACV) Survey for Croatian parents to understand vaccine hesitancy better. Methods: A cross-sectional study with 1814 Croatian parents was conducted using the PACV survey, translated using a double-back translation method. The psychometrics of the questionnaire were examined, including content validity, dimensionality, construct validity, discriminant validity, and reliability. Confirmatory factor analysis (CFA) assessed the original model's validity, but the original model fit poorly, prompting exploratory factor analysis (EFA) to identify latent factors. Reliability was measured using Cronbach's alpha and McDonald's omega. Results: EFA identified a five-factor model with factors labeled "Safety", "Schedule", "Attitudes", "Behavior", and "Trust". Subsequent CFA confirmed this model with acceptable to good fit indices. Discriminant validity was also confirmed. Reliability analyses indicated high internal consistency, with total Cronbach's alpha at 0.926 and McDonald's omega at 0.931. Conclusions: The adapted PACV is a valid and reliable tool for identifying vaccine hesitancy among Croatian parents. This study revealed high vaccine hesitancy among Croatian parents, emphasizing the need for targeted interventions.

Background/Objectives: Zika disease is caused by the Zika virus (ZIKV) and represents a major public health problem because of the complications in newborn babies from mothers who were infected during pregnancy. It is estimated that 80% of infected pregnant women are asymptomatic, which complicates the identification of infected individuals. In this study, we aimed to detect ZIKV in asymptomatic pregnant women and the effects in the newborns were analyzed. Methods: The presence of ZIKV was evaluated through endpoint reverse transcription-polymerase chain reaction (RT-PCR) in 114 blood samples from pregnant women treated at two hospitals in the state of Veracruz, Mexico. There was a follow-up of the participants until the birth of their newborns. Results: ZIKV RNA was detected in 4.4% (n = 5) of cases. In two positive cases, two consecutive samples were obtained, and one case of persistence of ZIKV in serum after 90 days after delivery was identified. A total of 80% of the positive cases were identified after the third trimester of pregnancy and 20% after the second trimester. Although ZIKV was shown to be a risk factor for low weight and low size at birth and prematurity, after adjustment for other variables, it did not show a significant association. In contrast, preeclampsia/eclampsia was identified as a significant risk factor for low birth weight. Conclusions: The prevalence of ZIKV found in this study suggests a latent circulation of this virus and highlights the importance of epidemiological surveillance in endemic zones. The prolonged viremia that was found suggests the need for more research because of the high impact which can mean the possible dissemination of the virus to the vector.

Introduction: We sought to evaluate the effects of a 12-week pulmonary rehabilitation (PR) program on lung function, mechanics, as well as pulmonary and systemic inflammation in a cohort of 33 individuals with moderate to severe post-COVID-19. Material and Methods: The pulmonary rehabilitation (PR) program employed a combination of aerobic and resistance exercises. Thirty minutes of treadmill training at 75% of the maximum heart rate, combined with 30 min resistance training consisting of 75% of one maximum repetition, three times a week throughout 12 weeks. Results: PR improved the lung function, FVC (p < 0.02), FEV1 (p < 0.02), FEV1/FVC (p < 0.01), MEF25% (p < 0.006), MEF50% (p < 0.03), and MEF75% (p < 0.02). PR also positively influenced lung mechanics, reducing respiratory impedance (Z5Hz, p < 0.03), respiratory reactance (X5Hz, p < 0.01), resistance of the entire respiratory system (R5Hz, p < 0.03), central airway resistance (RCentral, p < 0.03), and peripheral airway resistance (RPeripheral, p < 0.02). Moreover, muscle strength gains were evident, with significant improvements observed in hand grip strength for both the right (p < 0.02) and left (p < 0.01) hands, as well as maximal inspiratory (p < 0.02) and expiratory (p < 0.03) pressures. Additionally, PR exhibited anti-inflammatory effects by reducing the pro-inflammatory cytokines IL-1β (p < 0.0001) and IL-6 (p < 0.0001) and increasing the anti-inflammatory IL-1RA (p < 0.0004) and IL-10 (p < 0.003) and anti-viral IFN-γ (p < 0.0002) and IFN-β (p < 0.008) cytokines in breath condensate and serum samples. Conclusions: Collectively, these findings highlight the effectiveness of PR in ameliorating COVID-19 sequel across respiratory system, skeletal muscle, and immune responses. This highlights its promising potential as a therapeutic intervention for individuals recovering from COVID-19.

Background: Invasive aspergillosis is an extremely rare condition in healthy and immunocompetent individuals, and very few cases have been reported in previously healthy, pregnant, or postpartum women. Method: We describe a case of invasive aspergillosis in a puerperal patient and present literature review results. Case: We present a case of fulminant invasive pulmonary aspergillosis with cerebral, cardiac, and gastric involvement in a young woman, occurring a few days after an elective cesarean section. The patient succumbed after intensive care unit admission, and the diagnosis was made postmortem through autopsy. Conclusion: A total of 20 cases of invasive aspergillosis have been previously reported in pregnant or postpartum women, with high mortality. The risk of opportunistic fungal infections during pregnancy and postpartum should not be underestimated.

Background: The 2023 European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE) highlighted the essential role of multimodal imaging in the diagnostic algorithm of IE and its complications.

Methods: We hereby report a case series of IE in which the diagnosis was confirmed or excluded by the use of multimodal imaging during the period between January 2024 and July 2024 at the Infectious Diseases Clinic, Perugia Hospital, Italy.

Results: Six patients were retrospectively included. Prosthetic valve endocarditis (PVE) was suspected in four patients and native valve endocarditis (NVE) in two cases. In patients with prosthetic valves, 18F FDG-PET/CT was performed, except in one case (P1) where cardiac CTA was performed for suspicion of perigraft aneurysm. Patients underwent transesophageal echocardiography (TOE), which was diagnostic in two cases and inconclusive in the remaining cases. In case of inconclusive TOE, the use of multimodal imaging added a major criterion and allowed us to consider (from 'rejected' to 'possible') or confirm (from 'possible' to 'definite') the diagnosis of EI based on the 2023 Duke-ESC Criteria. In one case (P6), it was possible to exclude the diagnosis. For patients with diagnostic TOE, 18F FDG-PET/CT allowed for the enhancement of diagnostic accuracy, identifying the site of valve involvement and the extension of the infection to the device (cases P3 and P5, respectively).

Conclusions: In clinical practice, the use of cardiac CTA and/or 18F FDG-PET/CT based on the latest ESC guidelines demonstrated a significant impact on the diagnosis and therapeutic management of IE.

Background/objectives: Common Variable Immunodeficiency Disease (CVID) and other immunodeficiencies can present in subtle and variable ways. Whether or not a genetic lesion can be identified, there are not well understood biomarkers that quantitatively describe how severe a deficiency is. Here we discuss two possible ranking systems, CD4/CD8 T cell ratios and Immune Health Grades, and how such data maybe applicable to some immunodeficiencies.

Methods: This is not a systematic review, but we identify papers relating to immunodeficiencies with enough data to comment on the CD4/CD8 and Immune Health Grade. We also summarized relevant data publicly available from USIDNET, a website that compiles data on immunodeficiencies, and provide two new cases that illustrate ways that this information can alter clinical assessment.

Results: We review the HIV literature on CD4/CD8 T cell data and how this correlates with both immunologic function and comorbidity better than CD4 count alone. The ratio aslso relates to a new system called Immune Health Grades (IHG) derived from young adult to elderly subjects from many NIH cohorts without HIV. CVID is often thought of as an antibody problem, but in fact most patients also have low CD4/CD8 ratio and other cellular abnormalities. We review IDNET to categorize nine molecular immunodeficiencies including two subcategories of CVID into low, normal, or high ratios. Finally, we present two new cases in the literature of patients with recurrent infection and discuss how viewing the cases through the "lens" of CD4/CD8 ratio and IHG can facilitate clinical decisions.

Conclusions: Emerging data suggests at least some immunodeficiencies can be grouped by how abnormal their CD4/CD8 ratio or IHG. This represents a clinically available biomarker that can be tracked to see if the condition is worsening or not.