Therapeutic Advances in Infectious Disease最新文献

As a result of the ongoing opioid epidemic, physicians have encountered increasing rates of drug-use-related native tricuspid valve infective endocarditis (DU-TVIE), a complex multi-faceted disease that is best managed by interdisciplinary teams. Despite the large number of patients with DU-TVIE, there is little data to support the optimal treatment strategy with respect to medical and surgical therapy. The recent introduction of percutaneous mechanical aspiration of tricuspid valve vegetations has added another treatment modality that is also of uncertain benefit. Here we review the literature on the management of DU-TVIE and highlight the multi-step treatment approach developed by the multidisciplinary endocarditis team at the University of Kentucky.

Background: With recent increases in syphilis, there is growing interest in expanding screening; however, treatment rates have historically been low.

Objectives: This study examines demographic and clinical factors that may contribute to non-completion of syphilis treatment.

Design: This is a retrospective comparative cohort study of all patients with syphilis from January through November 2018 at an urban, tertiary care hospital.

Methods: Demographics and clinical information were extracted from the electronic medical record. Descriptive statistics and odds ratios (ORs) were calculated.

Results: Of 171 patients with syphilis, 89 (52.0%) completed treatment. Patients ages 40-49 were least likely to complete treatment (OR 0.14; 95% CI 0.03-0.72, p = 0.02) compared to those ages 18-24. Non-heterosexual patients were significantly more likely to complete treatment (OR 3.60; 95% CI 1.13-11.49, p = 0.03) compared to heterosexual patients. Patients diagnosed in the emergency department completed treatment at the lowest rate.

Conclusion: A major gap in syphilis treatment still exists, which must be addressed to achieve optimal impact from syphilis screening programs.

Background: In Iowa, men who have sex with men (MSM) accounted for 54% of persons with HIV in 2022 and Non-Hispanic Black/African Americans were over 10 times more likely to be diagnosed with HIV than Non-Hispanic white Iowans. To address this disparity in HIV incidence and prevalence, the United States (US) government ending the HIV epidemic (EHE) initiative seeks to expand pre-exposure prophylaxis (PrEP) coverage across the United States. Recent data showed that PrEP coverage is suboptimal in Iowa (a rural state), and Black Iowans were less likely to engage with PrEP services.

Objectives: Using capability, opportunity, motivation and behavior (COM-B) model for behavior change, this study sought to identify the key barriers and facilitators to PrEP uptake among Black/African American MSM in small urban areas in Iowa.

Design: This was a phenomenological study aimed to explore subjective views of Black MSM on PrEP use.

Methods: In-depth semistructured interviews were conducted with 12 Black MSM aged 20-42 years in two small urban counties. Broad themes identified from the interview transcripts were analyzed inductively and mapped onto the COM-B constructs deductively.

Results: Results showed that barriers to PrEP uptake were closely associated with five (of six) COM-B subcomponents: physical capability, psychological capability, social opportunity, reflective motivation, and automatic motivation. The thematized barriers were (1) lack of medical insurance; (2) limited PrEP awareness; (3) PrEP stigma; (4) fear of distrust among partners; (5) anticipated side effects; and (6) doubt about PrEP effectiveness. Similarly, facilitators to PrEP uptake were aligned with four subcomponents of COM-B model: physical capability, psychological capability, social opportunity, and physical opportunity. The thematized facilitators were (1) increased PrEP awareness; (2) PrEP access without discrimination; (3) state provision of PrEP to uninsured; and (4) physicians buy-in and recommendation. No motivation-related facilitators were reported.

Conclusion: To reduce the current disparity in HIV incidence and to achieve the EHE goals of expanding PrEP coverage in Iowa, efforts should be directed toward the provision of low-cost or free PrEP services, healthcare providers' training on cultural competence, and the development of culturally appropriate strategies to deliver PrEP to the Black MSM community.

Background: Fungal contamination of hospital water distribution systems has been implicated in outbreaks of healthcare-associated infections.

Objectives: To evaluate the prevalence of fungi in the water distribution system of a tertiary hospital in Nigeria.

Design: This was a descriptive cross-sectional study.

Methods: Swabs and water samples were collected from taps and faucets in the hospital categorized into low (Accidents and Emergency Unit, Children Emergency Unit, Acute Stroke Unit and the 24 in-patient hospital wards) and high-risk (Renal Dialysis Unit, Central Sterile Services Department, Theatres and Intensive Care Units (ICUs)) units based on the vulnerability of patients being managed there. The membrane filtration method for water analysis was used. Where possible, isolates cultured were identified to species level. In total, 105 water and 49 swab samples were collected for analysis.

Results: All analysed water samples grew fungi. A total of 289 (high-risk; n = 178; low-risk; n = 111) and 76 fungi isolates were recorded from water and swab samples, respectively, with 31 different species identified. Aspergillus was the most predominant genus with five different species: Aspergillus niger (9.9%), terreus (4.4%), flavus (3.3%), fumigatus (8.8%) and versicolor (2.20%) isolated. Twenty-five and 18 species of fungi were identified in the low and high-risk units, respectively. The labour ward (n = 46; 25.8%) and modular theatre (n = 47; 42.3%) were the most contaminated units. Cladosporium spp. and Paecilomyces spp. were the most frequently isolated fungi in the low and high-risk units, respectively. The dialysis centre (n = 9; 8.1%) and renal transplant theatre (n = 7; 6.31%) had the lowest contamination rates in the high-risk units. Aspergillus niger, Cephalosporium curtipes, Penicillium chrysogenum and Penicillium glabrum were each identified in 4/6 units from which swabs were taken. The facility had no documented protocol for its water safety and quality.

Conclusion: Our data reveal a high rate of contamination of hospital water sources by fungi, some of which are known to cause life-threatening infections. For better water treatment and water tank cleaning and disinfection, a standard protocol is advised. Ensuring that the water distribution systems in hospital settings are free of fungal contaminants is important to prevent the possibility of waterborne mycosis outbreaks.

Invasive fungal infections (IFIs) are associated with high mortality rates and mostly affect patients with compromised immunity. The incidence of IFIs is increasing worldwide with the expanding population of susceptible patients. Candida and other yeast infections represent a major component of IFIs. Rare Candida/yeast infections have also increased in recent years and pose considerable diagnostic and management challenges as they are not easily recognized by routine phenotypic characteristic-based diagnostic methods and/or by the automated yeast identification systems. Rare Candida/yeasts also exhibit reduced susceptibility to antifungal drugs making proper management of invasive infections challenging. Here, we review the diagnosis and management of 60 cases of rare Candida/yeast IFIs described so far in Kuwait, an Arabian Gulf country in the Middle East. Interestingly, majority (34 of 60, 56.7%) of these rare Candida/yeast invasive infections occurred among neonates or premature, very-low-birth-weight neonates, usually following prior bacteremia episodes. The clinical details, treatment given, and outcome were available for 28 of 34 neonates. The crude mortality rate among these neonates was 32.2% as 19 of 28 (67.8%) survived the infection and were discharged in healthy condition, likely due to accurate diagnosis and frequent use of combination therapy. Physicians treating patients with extended stay under intensive care, on mechanical ventilation, receiving broad spectrum antibiotics and with gastrointestinal surgery/complications should proactively investigate IFIs. Timely diagnosis and early antifungal treatment are essential to decrease mortality. Understanding the epidemiology and spectrum of rare Candida/yeast invasive infections in different geographical regions, their susceptibility profiles and management will help to devise novel diagnostic and treatment approaches and formulate guidelines for improved patient outcome.

Common variable immunodeficiency (CVID) is the most common humoral immune deficiency in adults, characterized by recurrent sinopulmonary bacterial infections. Invasive fungal infections are rarely associated with CVID. Late-onset combined immunodeficiency (LOCID) is a recently recognized variant of CVID with low CD4 counts and immunoglobulins deficiency. The current study reveals the first documented case of invasive pulmonary aspergillosis (Aspergillus terreus) in a patient with LOCID. A 52-year-old female with a recurrent history of sinopulmonary infections presented with acute onset fever and shortness of breath. Blood culture and bronchoalveolar lavage culture grew A. terreus. Further evaluation revealed low immunoglobulins (IgG, IgM and IgA). Moreover, she also had low CD4 counts (<200 cells/µL). The patient was successfully treated with voriconazole and immunoglobulin therapy. Finally, the study discusses LOCID as a potential risk factor for invasive fungal infections, which can be easily overlooked and cause poor outcomes.

[This corrects the article DOI: 10.1177/20499361241256290.].

Chronic pulmonary aspergillosis (CPA) is a challenging respiratory infection caused by the environmental fungus Aspergillus. CPA has a poor prognosis, with reported 1-year mortality rates ranging from 7% to 32% and 5-year mortality rates ranging from 38% to 52%. A comprehensive understanding of the pathogen, pathophysiology, risk factors, diagnosis, surgery, hemoptysis treatment, pharmacological therapy, and prognosis is essential to manage CPA effectively. In particular, Aspergillus drug resistance and cryptic species pose significant challenges. CPA lacks tissue invasion and has specific features such as aspergilloma. The most critical risk factor for the development of CPA is pulmonary cavitation. Diagnostic approaches vary by CPA subtype, with computed tomography (CT) imaging and Aspergillus IgG antibodies being key. Treatment strategies include surgery, hemoptysis management, and antifungal therapy. Surgery is the curative option. However, reported postoperative mortality rates range from 0% to 5% and complications range from 11% to 63%. Simple aspergilloma generally has a low postoperative mortality rate, making surgery the first choice. Hemoptysis, observed in 50% of CPA patients, is a significant symptom and can be life-threatening. Bronchial artery embolization achieves hemostasis in 64% to 100% of cases, but 50% experience recurrent hemoptysis. The efficacy of antifungal therapy for CPA varies, with itraconazole reported to be 43-76%, voriconazole 32-80%, posaconazole 44-61%, isavuconazole 82.7%, echinocandins 42-77%, and liposomal amphotericin B 52-73%. Combinatorial treatments such as bronchoscopic triazole administration, inhalation, or direct injection of amphotericin B at the site of infection also show efficacy. A treatment duration of more than 6 months is recommended, with better efficacy reported for periods of more than 1 year. In anticipation of improvements in CPA management, ongoing advances in basic and clinical research are expected to contribute to the future of CPA management.

Background: Identifying secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) presents challenges due to the ECMO circuit's influence on traditional signs of infection.

Objectives: This study evaluates procalcitonin as a diagnostic marker for secondary infections in patients receiving ECMO with influenza or COVID-19 infection.

Design: Single-center retrospective cohort study.

Methods: All adult patients receiving veno-venous ECMO with underlying influenza or COVID-19 from November 2017 to October 2021 were included. Patient demographics, time receiving ECMO, culture data, and procalcitonin levels were examined. The first procalcitonin within 3 days of infection was compared to negative workups that were collected at least 10 days from the last positive culture. Furthermore, we compared procalcitonin levels by the type of pathogen and site of infection.

Results: In this study, 84 patients with influenza or COVID-19 who received ECMO were included. A total of 276 procalcitonin labs were ordered in this cohort, with 33/92 (36%) of the secondary infections having an associated procalcitonin value. When comparing procalcitonin levels, there was no significant difference between the infection and negative workup groups [1 ng/mL (interquartile ranges, IQR: 0.4-1.2) versus 1.3 (0.5-4.3), p = 0.19]. Using 0.5 ng/mL as the cut-off, the sensitivity of procalcitonin was 67% and the specificity was 30%. In our cohort, the positive predictive value of procalcitonin was 14.5% and the negative predictive value was 84%. There was no difference in procalcitonin by type of organism or site of infection. Procalcitonin levels did not routinely decline even after an infection was identified.

Conclusion: While procalcitonin is a proposed potential diagnostic marker for secondary infections in patients receiving ECMO, this single-center study demonstrated low sensitivity and specificity of procalcitonin in identifying secondary infections. Furthermore, there was no association of procalcitonin levels with etiology of infection when one was present. Procalcitonin should be used cautiously in identifying infections in veno-venous ECMO.