Therapeutic Advances in Infectious Disease最新文献

Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as Scedosporium spp., Fusarium spp., Trichosporon asahii, and Candida auris. We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.

Background: Severe gram-positive infections are frequent in people who inject drugs, and successful completion of treatment presents unique challenges in this population.

Objectives: We aimed to evaluate the feasibility of a long-acting antibiotic, dalbavancin, as an alternative to standard-of-care antibiotics for severe infections due to vancomycin-susceptible pathogens requiring ⩾2 weeks of therapy.

Design: We designed an investigator-initiated single-arm unblinded prospective cohort study to evaluate the safety and efficacy of an early switch to dalbavancin in two doses administered 1 week apart.

Methods: We screened patients admitted with bloodstream infection, osteomyelitis, septic arthritis, infective endocarditis or deep abscesses, and comorbid substance use disorder (SUD) for eligibility. Consenting patients were switched to dalbavancin within 7 days from their index culture. They were monitored in the hospital for efficacy and safety of the treatment until the second dose of dalbavancin 7 days later and then discharged if stable. Study participants were evaluated with a decision support engine for a hypothetical appropriate level of care regarding their SUD after discharge. Their follow-up was planned for 12 months from the index culture, either in-person or via telehealth/telephone.

Results: The enrollment was terminated early due to significant loss-to-follow-up. In all, 11 patients were enrolled, 4 completed 12 months of follow-up, 2 completed 8 months of follow-up, and 1 was seen once after discharge. The remaining five patients were lost to follow-up immediately after discharge. All 11 patients continued to improve after switching to dalbavancin between the first and second doses. There were two per-protocol failures of treatment. Dalbavancin was well tolerated, though some adverse events were reported.

Conclusion: Dalbavancin may be a safe and effective alternative for an early switch in treating severe gram-positive infections.

Trial registration: The trial was registered as NCT04847921 with clinicaltrials.gov.

Background: Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals.

Methods: This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis.

Results: From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive.

Conclusion: The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.

Background and objective: Fungal empyema is a rare entity which is associated with high mortality. It is mostly seen in immune-compromised hosts. However, there is limited data available on fungal empyema from developing countries regarding risk factors, treatment, and outcome. This study was conducted to determine the risk factors, clinical features, treatment, and outcome of fungal empyema.

Methods: A retrospective observational study was performed on proven fungal empyema cases, admitted at Aga Khan University Hospital, Karachi, Pakistan during January 2018 to May 2021. We excluded all those patients with polymicrobial bacterial and fungal empyema or with negative pleural fluid cultures. A preformed questionnaire was filled out for each case.

Results: A total of 26 patients were diagnosed with fungal empyema with a mean age of 43.6 ± 20.3 years. Of these, 16 (61.5%) patients were male. Diabetes mellitus was the most frequent comorbidity (n = 11, 42.3%), followed by hypertension (n = 9, 34.6%), malignancy (n = 6, 23.1%), and asthma (n = 1, 3.8%). Ten (38.5%) patients had multiple comorbidities. Candida spp. was isolated in 21 (80.8%) patients and Aspergillus spp. in 7 (26.9%) patients. Fusarium spp. was isolated from one (3.9%) patient. Video-assisted thoracoscopy surgery was done in 14 (53.8%) patients and 12 (46.1%) patients were managed with tube thoracostomy. Twenty-one (80.8%) patients received antifungal agents. Overall, in-hospital mortality was 38.5% (n = 10) and all patients developed respiratory failure. Clinical improvement was seen in 16 (61.5%) patients.

Conclusion: Our data suggest that fungal empyema has a poor outcome as almost one-third of our patients died. Early diagnosis and intervention can improve outcome.

Background: Schistosomiasis contributes to 2.5 million disability-adjusted life years globally. Acute and chronic respiratory morbidity of Schistosoma mansoni (S. mansoni) is poorly documented in the literature. We conducted a rapid literature review of the burden of respiratory symptoms and lung function abnormalities among patients with S. mansoni. We also report the immunologic and lung imaging findings from the studies reviewed.

Methods: We carried out a comprehensive literature search in Embase and MEDLINE from the inception of the databases to 13th March 2023.

Results: A total of 2243 patients with S. mansoni were reported from 24 case reports, 11 cross-sectional studies, 7 case series, 2 cohort studies and 2 randomized controlled trials. The prevalence of any respiratory symptom was 13.3-63.3% (total number of patients studied, n = 149). The prevalence of the individual symptoms among patients with S. mansoni in whom respiratory symptoms were sought for was as follows: cough (8.3-80.6%, n = 338), dyspnea (1.7-100.0%, n = 200), chest pain (9.0-57.1%, n = 86), sputum production (20.0-23.3%, n = 30) and wheezing (0.0 - 20.0%, n = 1396). The frequency of the symptoms tended to be higher in acute schistosomiasis. Restrictive lung disease was prevalent in 29.0% (9/31). The commonest chest imaging findings reported were nodules (20-90%, n = 103) and interstitial infiltrates (12.5-23.0%, n = 89). Peripheral blood eosinophilia was prevalent in 72.0-100.0% of patients (n = 130) with acute schistosomiasis and correlated with symptoms and imaging abnormalities. Three case reports in chronic S. mansoni reported elevated C-reactive protein, leucocyte, neutrophil and absolute eosinophil counts, eosinophil percentage, IgE and IgG4.

Conclusion: There is a high prevalence of respiratory morbidity among patients with S. mansoni, particularly in the acute stage of the infection, although the studies are relatively small. Larger studies are needed to characterize respiratory morbidity in chronic schistosomiasis and determine the underlying clinical and immunological mechanisms.

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB.

Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG.

Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively.

Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Background: The prevalence of sexually transmitted infections (STIs) remains high worldwide. Despite the worldwide increase in the incidence of STIs every year, there are few reports on the frequency of STIs with different pathogens according to age and gender. Accordingly, a study was conducted to determine trends in co-infection with STIs by age and gender in Cheonan, South Korea from 2017 to 2021.

Objectives: To identify trends by age or sex in co-infection of STIs in this region.

Design: A retrospective study was conducted on clinical samples examined at Dankook University Hospital from January 2017 to November 2021. A total of 3297 specimens were collected from patients visiting Dankook University Hospital (Cheonan, Korea), and statistical analysis was performed on patients ranging in age from 1 day to 93 years.

Methods: Multiplex polymerase chain reaction, the most efficient method to diagnose a bacterial infection, was performed using an MJ Research PTC-200 Thermal Cycler (Marshall Scientific, Richmond, VA, USA) and a Seeplex STD Detection Kit (Seegene, Seoul, Republic of Korea). The co-infection rate with STI pathogens was analyzed according to age and sex.

Results: Of the 3297 clinical samples, 1017 (30.9%) tested positive for sexually transmitted pathogens, ranging from one to six co-infections. Analysis of the co-infection rate by age revealed that the average age gradually decreased as the total number of co-infection pathogens increased. The co-infection percentage and age distribution of STIs differed according to sex. Co-infection was more prevalent in female patients. Furthermore, co-infection in male patients occurred frequently in the 30-39-year-old group, while those in female patients occurred in the 20-29- and 30-39-year-old groups.

Conclusion: Our statistical analysis showed that STI co-infections were more common among younger than older people. Therefore, it helps in recognizing STIs at a young age and provides possible indicator data to prevent STIs at a young age. In addition, further research is needed on co-infection in other regions.

Background: Antifungal diagnostic capacity has been documented in various countries, there is a lack of comprehensive research on clinical mycology diagnostics and treatment in Hungary.

Methods: We conducted an online survey encompassing questions that explored various aspects of the mycology diagnostic and antifungal therapy-related information. The survey aimed to gather details about institutional profiles, perceptions of invasive fungal infections (IFIs), and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring.

Results: As of May 2023, a total of 17 institutions responded to the questionnaire. Seven participants categorized the institutional incidence of IFI as 'very low', four as 'low', and six as 'mild'. The majority of centers identified Candida spp. (94%) and Aspergillus spp. (82%) as the most prevalent fungal pathogens. Nearly half of the laboratories (47%) reported using matrix-assisted laser desorption/ionization-time of flight mass spectrometry for identification. All institutions had access to microscopy and culture-based diagnostic approaches. A significant number of centers had access to antigen detection (71%) and various molecular assays (59%). Regarding antifungal agents, all reporting sites used at least one triazole, with voriconazole (77%) being the most common mold-active azole. Furthermore, 71% of the centers applied at least one formulation of amphotericin B, and 65% to one echinocandin. However, only 18% of the centers used 5-flucytosine.

Conclusion: Resource availability for diagnosing and treating IFI in Hungary varies across hospitals based on location. Surveys help identify gaps and limitations in this area. To address these challenges, interregional cooperation within Hungary could be a facilitating strategy.

Background: The first case of COVID-19 virus was reported in Africa on 14 February 2020. The pandemic became more aggressive in the continent during the second wave than the first wave. Promoting vaccination behavior is an unparalleled measure to curb the spread of the pandemic. Regarding this, the health belief model (HBM) is the major model for understanding health behaviors. This study aimed to examine predictors of intended COVID-19 vaccine acceptance in the second wave of the pandemic among university students in Ethiopia using HBM.

Methods: A cross-sectional study was conducted among 423 randomly selected medical and health science students at the University of Gondar from 21 August to 15 September 2020. Analysis of data was performed using STATA 14.0. Linear regression analysis was applied and a p value of less than 0.05 was used to declare statistical significance.

Results: Among the total participants, 293 [72.2% (95.0%: CI: 67.2-76.8)] of them scored above the mean of COVID-19 vaccine acceptance. HBM explained nearly 46.3% (adjusted R² = 0.463) variance in intention to receive the COVID-19 vaccine. Year of study (β = 0.288; 95% CI: 0.144-0.056), using social media (β = 0.58; 95% CI: 1.546-2.804), existing chronic disease (β = 0.12; 95% CI: 0.042-0.433), perceived overall health condition (β = 0.117; 95% CI: 0.307-0.091), perceived susceptibility (β = 0.58; 95% CI: 1.546-2.804), perceived benefit (β = 0.338; 95% CI: 1.578-2.863), and cues to action (β = 0.49; 95% CI: 0.388-0.99) were significantly associated with intended COVID-19 vaccine acceptance at p value < 0.5.

Conclusion: Approximately, three-quarters of the participants were above the mean score of COVID-19 vaccine acceptance, which is higher compared to previous reports in resource-limited settings. Interventions in this study setting chould include placing emphasis on the risks of acquiring COVID-19, enhancing perceived benefits of COVID-19 vaccination and improving cues to action by advocating COVID-19 vaccination. Our findings also implied that social media health campaigns are significant factor in COVID-19 vaccination behavioral change in this study setting.

Cabotegravir (CAB) and rilpivirine (RPV) is the first complete long-acting (LA) injectable regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression in people with HIV-1 who are virologically suppressed on a stable antiretroviral regimen that is administered monthly (Q1M) or every 2 months (Q2M). As an alternative regimen to lifelong daily oral antiretroviral therapy, Q1M or Q2M dosing schedules are associated with increased patient satisfaction and treatment preference. In addition, it may address challenges associated with daily oral dosing, including fear of treatment disclosure or stigma, anxiety related to oral dosing adherence, and the daily reminder of HIV disease status. Cabotegravir + RPV LA is administered by clinical staff as two intramuscular injections dosed Q1M or Q2M. In this review, we share practical dosing guidance for CAB+RPV LA injectable therapy, including how to initiate therapy, schedule injection visits, manage dosing interruptions due to missed or delayed injection visits, manage errors in dosing, and transition to alternative antiretroviral therapy after discontinuation. Practical guidance on the clinical management of CAB+RPV LA dosing, including a detailed discussion using case-based scenarios that may be encountered in clinical practice, is provided. The clinician-administered CAB+RPV LA regimen has dosing management considerations that are flexible and considerate of the patient and has the potential to provide a highly desirable and efficacious alternative to daily oral antiretroviral therapy for many people with HIV-1.