Therapeutic Advances in Infectious Disease最新文献

Background: Kentucky is one of seven states with high, sustained rural HIV transmission tied to injection drug use. Expanding access to pre-exposure prophylaxis (PrEP) has been endorsed as a key HIV prevention strategy; however, uptake among people who inject drugs (PWID) has been negligible in rural areas. Syringe services programs (SSPs) have been implemented throughout Kentucky's Appalachian region, providing an important opportunity to integrate PrEP services.

Objectives: The primary objective was to examine preliminary efficacy and effect sizes of the study interventions on PrEP initiation among HIV-negative PWID.

Design: Parallel group randomized controlled trial.

Methods: Eighty participants were enrolled from two rural SSP locations in southeastern Kentucky. Following informed consent, participants completed a baseline interview, and were randomized to the intervention comparators. The primary endpoint was PrEP initiation, measured by dispensed PrEP prescription, within the 6-month study period. Analyses employed intent-to-treat (ITT) and per protocol approaches.

Results: In total, 77/80 enrollees (96.2%) completed at least one session of their assigned intervention, regardless of trial arm. Seventy (87.5%) were linked to the embedded PrEP provider for the initial clinical visit; 38 (47.5%) completed a follow-up clinical visit with the provider, 22 (27.5%) were issued a prescription, and 7 (8.8%) initiated PrEP during the study period. We observed a 12.1% difference (14.6% vs 2.5%; ITT) and 12.8% difference (15.4% vs 2.6%; per protocol) in the primary outcome (PrEP initiation), in favor of the experimental intervention.

Conclusion: This pilot trial established proof of concept for integrated PrEP care within SSPs in rural areas, and demonstrated a clinically meaningful difference in PrEP initiation between interventions, which warrants examination in a larger trial. Rates of early care discontinuation indicate a need for ongoing patient engagement strategies and implementation support for community SSPs.

Trial registration: Prospective registration with ClinicalTrials.gov, NCT05037513 (registered August 5, 2021).

Background: Lower respiratory tract infections (LRTIs) pose a significant threat to global health, causing more than 2 million deaths worldwide. This menace is intensified by the alarming increase in drug resistance, which limits the availability of effective antibiotics for bacterial respiratory infections. Consequently, there is an urgent demand for alternative therapeutic options. Phage therapy (PT) has re-emerged as a promising therapeutic approach and as an adjunct to antibiotic treatment.

Objective: This systematic review synthesises the application of PT for LRTIs in humans, providing unified and updated data on the evaluation of the safety and efficacy of PT for LRTIs.

Design: Systematic review.

Data sources and methods: Following the PRISMA guidelines, a comprehensive search strategy was carried out (spanning January 2000 - February 2024) in four databases: PubMed, Scopus, ScienceDirect and Web of Science to retrieve published records of PT for LRTIs in humans only. The reference list of each included study was evaluated for possible inclusion of other relevant articles.

Results: Among the 18 records that fulfilled the inclusion criteria, 70 patients were administered PT. Microbiologically, 71.42% (n = 50/70) of the patients improved; with either the eradication of the pathogen or a decrease in bacterial load, whilst 15.71% (n = 11/70) did not record any improvement. About 5.71% (n = 4/70) recorded a partial/incomplete improvement, whilst 7.14% (n = 5/70) of the patients microbiological outcomes were unspecified. Clinically, up to 74.29% (n = 52/70) of the patients improved, whilst 10.00% (n = 7/70) of the patients showed no improvement. Another 2.86% (n = 2/70) recorded partial/incomplete improvement, whilst 12.86% (n = 9/70) were uncategorized. Phage titres that yielded positive outcomes ranged from 10⁵ to 10¹² PFU/mL. Studies that achieved a substantial phage titre at the site of infection frequently observed notable improvements. Regarding the safety of PT, 77.78% (N = 14/18) of the studies did not record any adverse effects after PT was administered, whilst 16.66% (n = 3/18) of the studies reported adverse effects.

Conclusion: Based on recently published data originating mainly from observational studies, PT has shown considerable efficacy and safety in the treatment of LRTIs. However, there is a lack of uniform methodologies and protocols across different PT cases in the management of LRTIs. Consequently, there is a need for additional clinical studies to establish standardised pharmacokinetic elements and an overall protocol for PT. By doing so, we can fully unlock the potential of PT in effectively managing clinical bacterial infections, including LRTIs.

This narrative review explores the risks related to infection in immunocompromised travelers due to conditions other than transplantation, and evaluates the evidence behind current prophylactic strategies, including immunizations, antimicrobials, and non-pharmacological interventions, to prevent various infection and how the current evidence applies to this special patient population, from the perspective of a US-based traveler.

Background: Human herpesvirus-8 (HHV8) can present with cutaneous or extracutaneous manifestations. While violaceous skin lesions characterize cutaneous Kaposi sarcoma, extracutaneous HHV8 is challenging to diagnose due to nonspecific symptoms.

Objectives: We evaluated the role of microbial cell-free DNA next-generation sequencing (mcfDNA NGS) in diagnosing HHV8-related illness.

Design: Retrospective analysis.

Methods: Between 2017 and 2024, we reviewed the medical charts of 10 immunosuppressed patients at a quaternary care center who had positive HHV8 mcfDNA NGS results.

Results: The clinical and laboratory turnaround times of mcfDNA NGS were 3 and 1 days, respectively (8.5 and 7 days for immunohistochemistry vs 5.5 and 2 days for serum HHV8 polymerase chain reaction). Eight patients received HHV8-related diagnoses, while two had unrelated conditions. Management changed in six patients post-testing due to outpatient specialist referral or adjusting antimicrobials.

Conclusion: mcfDNA NGS can aid clinicians in identifying HHV8-related diseases before tissue sampling and adjusting treatment plans in patients with nonspecific disease manifestations.

Background: Daptomycin pharmacokinetics and pharmacodynamics data relative to higher doses in patients are necessary for clinical practice.

Objectives: A monocentric, prospective study that enrolled patients with a diagnosis of Staphylococcus spp. infective endocarditis treated with daptomycin according to clinical practice, to evaluate the pharmacokinetics/pharmacodynamics of different daptomycin daily doses (group A: 8-10 and group B: 11-12 mg/kg).

Design and methods: A monocentric, prospective, cohort study that enrolled patients with a diagnosis of Staphylococcus spp. infective endocarditis treated with daptomycin. Daptomycin was administered by intravenous infusion over a 30-min period for at least five consecutive days before PK study.

Results: Twenty-two patients were included. Native valve infectious endocarditis (IE) was diagnosed in 9 patients, prosthetic valve IE was diagnosed in 10 patients and 3 patients had concomitant intracardiac device infections. All patients showed a microbiologic response with negative blood cultures by day 5 (1-3 interquartile rate (IQR) 3-8). The median calculated AUC_0-24 was 1298 (1-3 IQR 1069-1484) and 1459 (1-3 IQR 1218-1711) µg*h/mL, with the corresponding clearance of 0.49 (1-3 IQR 0.37-0.57) and 0.57 (1-3 IQR 0.40-0.71) L/h, respectively. A value of area under the curve/minimum inhibitory concentration (AUC/MIC) > 666 was reached by all patients; however, 4 out of 15 patients in group A and 1 out of 14 patients in group B did not reach the pharmacokinetic/pharmacodynamic (PK/PD) target of 1061; therefore, AUC/MIC equal to or above 1061 was reached by 73.3% in group A and 92.9% in group B.

Conclusion: From a PK/PD point of view, all patients reached the value of AUC/MIC > 666, while roughly 70% of patients in group A and 90% in group B reached the target value of AUC/MIC>1061. Even if this cut-off value is arbitrary, 11-12 mg/kg daily dose could be taken into consideration in case of serious infections characterised by a high inoculum or in cases of prosthetic valve infections.

Background: Vulvovaginal candidiasis and urinary tract infections caused by Candida are common diseases. While the most common causative agent is C. albicans, other species, such as non-C. albicans, can also be responsible. Susceptibility to antifungal drugs varies among Candida species, but there is very limited information available from Vietnam.

Objectives: To determine the species distribution and antifungal susceptibility patterns of Candida isolated from urine and vaginal samples of patients tested at the Medlatec healthcare system in 2023.

Design: Cross-sectional study.

Methods: The study describes a cross-sectional analysis of over 102 Candida isolates obtained from urine and vaginal samples of patients using the testing services at Vietnam Medlatec healthcare system from January to December 2023. Species identification of Candida isolates was performed using germ tube test and Vitek^® 2 systems. Antifungal susceptibility testing was carried out using the VITEK^® 2 card for yeast fungi. Minimum inhibitory concentrations for these isolates were classified according to the Clinical and Laboratory Standards Institute guidelines (M27-A3 and M27M44S-ED3).

Results: In this investigation, five different Candida species were identified. Among these isolates, C. albicans (78.43%) was the most frequent, followed by C. tropicalis (11.76%), C. glabrata (4.91%), C. parapsilosis (1.96%), and C. krusei (0.98%). The resistance rates to fluconazole, voriconazole, caspofungin, micafungin, and amphotericin B were 7.7%, 4.2%, 4.0%, 1.0% and 1.0%, respectively.

Conclusion: The most common species found in this population was C. albicans. Our findings also showed a high frequency of non-albicans Candida species causing fungal urinary tract infections. The resistance rates of isolated Candida strains to echinocandins and amphotericin B were low, while some strains were found to be resistant to fluconazole and voriconazole.

Background: Outpatient parenteral antibiotic therapy (OPAT) enhances patient safety, improves outcomes, and reduces healthcare costs by decreasing 30-day readmissions and adverse events. However, the optimal structure and follow-up protocols for OPAT programs remain undefined. Identifying high-risk patients for readmission and managing adverse drug events (ADEs) are critical components of OPAT care.

Objectives: This study aimed to evaluate the impact of a dedicated OPAT clinic on hospital readmissions, and quantified the administrative workload required to manage patients on OPAT post-discharge.

Design: A retrospective, pre-post cohort study compared patient outcomes before and after the implementation of a dedicated OPAT clinic across a single clinic and multiple hospitals.

Methods: Patients discharged on OPAT from October 2018 to March 2019 (control group) and from September 2021 to February 2022 (intervention group) were included. The primary outcome was 30-day hospital readmission. Secondary outcomes included administrative workload measured by telephone calls and nursing tasks. Data were analyzed using univariate and multivariate logistic regression models to identify independent risk factors for readmission.

Results: A total of 361 patients were included (median age 63 years, 62.1% men). Of these, 239 patients (66.2%) received OPAT post-clinic implementation. Common diagnoses included bacteremia (17.7%) and osteomyelitis (17.5%), with MRSA (17.2%) and Streptococci (14.4%) as predominant pathogens. The median OPAT duration was 14 days, and the median hospital stay was 7 days. Readmissions within 30 days occurred in 24.9% of patients, while 27.7% visited the emergency department. ADEs were reported in 18.9% of patients. Readmission rates decreased from 30.5% in the pre-clinic cohort to 20.1% in the post-clinic cohort (p ⩽ 0.05). The OPAT clinic managed 690 calls, illustrating the substantial administrative burden associated with coordinating care. Most calls addressed lab results (22.6%) and peripherally inserted central catheter-related issues (11.3%).

Conclusion: The implementation of a dedicated OPAT clinic was associated with reduced readmissions and improved patient management, suggesting that structured follow-up care may improve outcomes. This study highlights the administrative challenges of OPAT, emphasizing the need for dedicated personnel and efficient coordination. Future research should focus on optimizing OPAT care models and establishing sustainable funding strategies.

Background: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking.

Objectives: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR.Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke's Medical Center from March 2017 to February 2023.

Methods: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA results with clinical diagnosis. A descriptive analysis of the patient and clinical characteristics was performed.

Results: A total of 113 mcfDNA tests in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were performed in the study period. The most common clinical syndromes were pneumonia (36%), fever of unknown origin (16%), and intra-abdominal infections (15%). Most (80, 71%) of the mcfDNA test results were positive for microorganisms. Twenty-seven (24%) cases were classified as positive clinical impact, 82 (73%) were neutral and 4 (3%) were negative, respectively.

Conclusion: In SOTR, mcfDNA sequencing can add a positive clinical impact in a quarter of the cases and identify microorganisms beyond conventional microbiological testing across clinical syndromes. The negative clinical impact was rare. However, larger prospective studies are needed to define the optimal timing and utilization of mcfDNA in the sequence of diagnostic evaluation for syndrome-specific workup in SOTR.

Summary: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool that can identify difficult-to-detect microorganisms in SOTR. Our study demonstrates that the mNGS test resulted in a positive clinical impact in 1 out of 4 patients.

Tuberculosis can present myriad manifestations, affecting multiple organ systems. Common central nervous system (CNS) manifestations include vomiting, headache, blurred vision, neck stiffness, altered sensorium, seizures, and focal neurological deficits. Epilepsia partialis continua (EPC) is a rare manifestation of CNS tuberculosis. An 11-year-old female patient presented with abnormal twitching movements on the left side, specifically involving the upper limbs, while maintaining full awareness, which is suggestive of EPC. This was preceded by symptoms such as headache, poor appetite, and abdominal pain for 3 months, along with a transient episode of weakness in the left upper limb. An electroencephalogram revealed abundant spike-wave discharges from F8 T4 and C4 P4 in the right hemisphere. The EPC was refractory to anti-seizure medications. Brain MRI revealed multiple contrast-enhancing lesions and magnetic resonance spectroscopy showed a lipid peak that suggested tuberculomas. Further investigations confirmed multisystem involvement, including the gastrointestinal and genitourinary tracts. The treatment of EPC involves addressing the underlying etiology alongside the use of anti-seizure medications. In our patient, the EPC responded well to antitubercular therapy combined with corticosteroids. Given the prevalence of tuberculosis in developing countries, it should be considered early in the differential diagnosis, as it is a treatable cause of EPC.

Background: Dolutegravir (DTG), a novel antiretroviral therapy (ART) for HIV, is increasingly adopted across sub-Saharan Africa. However, its impact on blood pressure in Ethiopia remains unclear, highlighting a need for further studies.

Objective: This study aimed to investigate the association between DTG-based first-line regimens and other covariates of high blood pressure (HBP) among adults living with HIV receiving care at health facilities in Hawassa City, southern Ethiopia.

Design: A cross-sectional study.

Methods: Data were collected between January 2023 and May 2024 among 444 systematically selected adults, complemented with a review of their medical records. HBP was defined according to the seventh report of the Joint National Committee (JNC7) guidelines, with a threshold of systolic or diastolic blood pressure of ⩾120/80 mmHg. Multivariable logistic regression analysis was performed to identify predictors of HBP. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were computed to determine statistically significant associations.

Results: Of the study participants, 58.3% were women and 41.7% were men, resulting in a response rate of 95.5%. The mean (standard deviation (SD]) age of the participants was 38.4(±8.9) years. The prevalence of HBP was 57.9% (95% CI: 52.5-62.4), with 40.5% classified as prehypertension and 17.3% as hypertension. Among participants with hypertension, 84.4% were newly diagnosed. Initiating ART with DTG-based regimens was associated with higher odds of HBP (AOR 5.9; 95% CI: 1.5-22.7) and switching to DTG-based regimens also increased the odds of HBP (AOR 3.8; 95% CI: 1.1-13.9). Other significant covariates associated with HBP included being male (AOR 2.6; 95% CI: 1.4-4.9), age >45 years (AOR 2.0; 95% CI: 1.2-3.4), high waist-to-height ratio (AOR 2.4; 95% CI: 1.1-4.9), inadequate vegetable intake (AOR 1.7; 95% CI: 1.0-2.7), low physical activity (AOR 2.4; 95% CI: 1.1-5.4), and LDL-cholesterol (AOR 1.1; 95% CI: 1.0-1.2).

Conclusion: Proactive blood pressure screening and management are important for individuals on DTG-based regimens. In addition, early identification and intervention of modifiable risk factors through comprehensive strategies and regular screenings are pivotal for improving cardiovascular health among individuals on ART.