Therapeutic Advances in Infectious Disease最新文献

Background: Studies comparing the effectiveness of dexamethasone versus methylprednisolone for treating severe-to-critical COVID-19 have produced conflicting results. This study aimed to evaluate the impact of dexamethasone compared with methylprednisolone on in-hospital mortality among patients with severe or critical COVID-19.

Objectives: The objective of this study was to assess the effectiveness of dexamethasone in comparison to methylprednisolone in reducing in-hospital mortality in patients suffering from severe-to-critical COVID-19 pneumonia.

Design: This was a retrospective observational study conducted at a tertiary care academic medical center.

Methods: Clinical data from 706 hospitalized patients with severe or critical COVID-19 in Karachi, Pakistan, were reviewed. Of these patients, 217 received either oral or intravenous dexamethasone, and 393 were treated with methylprednisolone. The primary outcome was in-hospital mortality, while secondary outcomes included the length of hospitalization and the need for mechanical ventilation.

Results: The methylprednisolone group had a male predominance (74% vs 54%; p < 0.001). However, there was no significant difference in median age between the dexamethasone group (55 years) and the methylprednisolone group (57 years) (p = 0.09). Mortality was significantly higher in the methylprednisolone group compared to the dexamethasone group (13.7% vs 3.2%, p < 0.001). Multivariable analysis showed that dexamethasone was associated with lower in-hospital mortality (adjusted odds ratio (aOR): 0.24; 95% CI: 0.09-0.62; p = 0.003). Furthermore, patients in the dexamethasone group had a shorter length of hospital stay (aOR: 0.87 (95% CI: 0.82-0.92)) compared to the methylprednisolone group. A higher proportion of patients required invasive mechanical ventilation in the methylprednisolone group compared to the dexamethasone group (13.7% vs 3.2%; p < 0.001).

Conclusion: Dexamethasone was associated with lower mortality and a reduced length of hospital stay and a lower proportion of patients required mechanical ventilation compared to methylprednisolone in patients with severe-to-critical COVID-19.

Background: Urinary tract infections (UTIs) are common and result in a significant impact on quality of life (QoL). Despite their prevalence, there seems to be a lack of evidence around patient-reported outcomes and measuring tools such as scoring systems and nomograms in UTIs. Patient-reported outcome measures (PROMs) help us measure patient-related symptoms and their QoL.

Objective: Our literature review shows an up-to-date "atlas" of the available PROMs, nomograms and scoring systems that can help clinicians in treatment decisions and track treatment response in patients with UTIs.

Design: Systematic review of the literature.

Data sources and methods: A comprehensive systematic review was carried out on PubMed Medline, Scopus and CINAHL, according to PRISMA guidelines, using search terms related to PROMs, nomograms and scoring systems used in simple and complicated UTIs. A narrative review was done, and tool characteristics, accuracy, validation, and applicability were collected and summarized.

Results: Sixty-two articles (with 16 different PROMs) were included in the final review. These included generic tools such as the 36-Item Short Form Health Survey and specific tools like the Acute Cystitis Symptom Score and Recurrent Urinary Tract Infection Impact Questionnaire, amongst others. While scoring systems seemed to be used for severe infections such as Fournier's gangrene and emphysematous pyelonephritis, nomograms were primarily used for diagnosis and risk prediction. PROMs are useful tools and have utility within the management of patients with UTIs, but further clarity is needed as to which of these tools is most appropriate for each type of UTI as each offer their respective advantages and disadvantages.

Conclusion: This atlas is the first comprehensive review of PROMs, scoring systems and nomograms in the management of UTIs. While PROMs improve patient care, further standardisation, external validation and accuracy are needed. While nomograms and scoring systems can help clinicians, these must be tailored to individual patients based on their specific clinical scenarios.

Trial registration: PROSPERO registration number CRD42025625865.

Background: Mycobacterium avium complex lung disease (MAC-LD) is a chronic, progressive, potentially life-threatening infection. Some cases are refractory to standard guideline-based therapy (GBT), and sputum cultures are persistently positive for acid-fast bacilli. Although an early identification of treatment-refractory MAC-LD is crucial, its risk factors remain unknown.

Objectives: We aimed to identify the risk factors for refractory MAC-LD in response to initial GBT.

Design: A retrospective single-center study was conducted involving consecutive patients with MAC-LD who were diagnosed between 2006 and 2024 and received initial GBT.

Methods: Refractory MAC-LD was defined as sputum culture positivity at least 6 months after the initial GBT. Prognostic factors were identified using Cox proportional hazards analysis, and risk factors for refractory MAC-LD were examined using logistic regression analysis.

Results: Of the 201 patients with definite MAC-LD, 35 (17.4%) had refractory MAC-LD. Patients with refractory MAC-LD had a significantly lower body mass index (BMI), more cavitary lesions on high-resolution computed tomography (HRCT), and higher mortality (log-rank test, p = 0.006) compared to those with non-refractory MAC-LD. A multivariate analysis adjusted for age and sex showed that refractory MAC-LD (adjusted hazard ratio (HR): 2.76; 95% confidence interval (CI): 1.10-6.95; p = 0.030) and cavitary lesions on HRCT (adjusted HR: 2.77; 95% CI: 1.34-5.70; p = 0.005) were significantly associated with all-cause mortality. In addition, a multivariate analysis revealed that lower BMI (odds ratio (OR): 0.68; 95% CI: 0.55-0.85; p < 0.001) and cavitary lesions on HRCT (OR: 2.52; 95% CI: 1.15-5.50; p = 0.020) were independent risk factors of refractory MAC-LD.

Conclusion: Low BMI and cavitary lesions on HRCT are risk factors for refractory MAC-LD.

Background: With the rapid scale-up of dolutegravir-based regimens, there is a declining trend of HIV drug resistance in several resource-limited settings. However, treatment success using second-generation integrase strand-transfer inhibitors (2nd-Gen INSTI) among people living with HIV with long therapeutic experience could be jeopardized by pre-existing drug resistance mutations to first-generation INSTI or even to other drug class.

Objectives: The aim of this systematic review and meta-analysis will be to provide a summary of existing evidence on the HIV susceptibility to 2nd-Gen INSTI among people with multidrug resistance.

Design: This will be a systematic review and meta-analysis.

Methods and analysis: This systematic review will include randomized and non-randomized trials, experimental studies, cohorts, cross-sectional studies, and governmental notices focusing on HIV susceptibility to 2nd-Gen INSTI. The search will consider studies conducted all over the world and published from 2013 to 2024, retrieved from PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Google scholar, African journals online, and Cumulative Index to Nursing and Allied Health Literature. Hand searching of the reference lists of relevant reviews and trials will be conducted, and we will also look for conference abstracts. We will include studies of adults and/or children exposed to dolutegravir, bictegravir, or cabotegravir following treatment failure to more than one drug class. The primary outcomes will be "the level of sensitivity to 2nd-Gen INSTI" and the "rate of viral suppression following exposure to 2nd-Gen INSTI." The secondary outcomes will essentially consist of the determinants of a good virological response (viral load < 1000 copies/mL at 48 weeks) under 2nd-Gen INSTI among participants with a history of multidrug resistance. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permit, random-effects models will be used where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, sex, baseline clinical data, treatment duration, and adherence level).

Discussion: This review will help to strengthen evidence on the effectiveness of 2nd-Gen INSTI by contributing to current knowledge concerning people living with HIV with long therapeutic exposure. The results will, therefore, contribute to set up baseline data for optimal management of people living with HIV harboring multidrug-resistant viruses.

Registration: PROSPERO: CRD42023470922.

Background: Involving pregnant women in HIV prevention trials is key to ensuring that they benefit from efficacious products. MTN-042/DELIVER was a phase IIIb, open-label, multi-site, randomized safety study, the first of its kind to enroll HIV-negative pregnant women into a prevention trial using oral Truvada^® once daily and the Dapivirine Vaginal Ring (DVR) every month. There is limited data on pregnant women's experiences with ring insertion, which we explored.

Objectives: To explore the experiences of pregnant women with DVR insertion during the MTN-042/DELIVER study at MU-JHU Care Limited in Kampala, Uganda.

Design: A description of secondary data from the MTN-042/DELIVER study.

Methods: Participant randomization was to either DVR or Truvada in varying ratios into three successive cohorts (based on gestational age). Ring self-insertion was required at enrolment and every 4 weeks until delivery. Pre-insertion counselling and supervised ring placement assessment were done. Enrollment data were collected to include counselling sessions, insertion tactics, ring self-insertion scores (Very difficult: 3+ attempts and/or pain, severe discomfort, Difficult: 2 attempts and/or moderate discomfort, Easy: 1 attempt with some ring repositioning and/or mild discomfort, Very easy: Smooth insertion and positioning in one attempt with no discomfort), assistance during insertion, encountered challenges and ring expulsion during use.

Results: Out of 154 participants, 73% were randomized to the ring. At enrolment, all participants attempted self-insertion. Only one participant required additional counselling. The squatting position was uniformly favoured. Across all cohorts, 95% of participants had easy/very easy ring self-insertion. Five percent had difficult ring self-insertion, with some variations across cohorts. Challenges included difficulty in folding, gripping, inserting the ring far enough, requiring multiple attempts and reluctance to insert it. No expulsions during ring use were reported.

Conclusion: Most pregnant women managed to insert the Ring themselves. However, participants above 36 weeks required more help with ring insertion compared to others. This suggests that it may be beneficial to encourage pregnant women to start using this HIV prevention method early in pregnancy, to minimize potential initial insertion challenges in late pregnancy.

Trial registration: The primary study, MTN-042/DELIVER is registered as ID NCT03965923 at https://www.ClinicalTrials.gov.

To address the coronavirus disease 2019 (COVID-19) pandemic, several antiviral agents targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for clinical use. However, antivirals that can be administered irrespective of risk factors were lacking until the approval of ensitrelvir fumaric acid (hereafter, ensitrelvir) in Japan, which took effect in November 2022. Ensitrelvir is an oral SARS-CoV-2 3C-like protease inhibitor currently approved in Japan and Singapore. This narrative review summarizes preclinical, clinical trial, and real-world data on ensitrelvir. The efficacy and safety of ensitrelvir were assessed in a seamless, randomized, double-blind, placebo-controlled, phase II/III study conducted in Japan, South Korea, and Vietnam (Japan Registry of Clinical Trials identifier, jRCT2031210350). This study enrolled patients with mild-to-moderate COVID-19 symptoms or asymptomatic individuals irrespective of the presence of risk factors for severe illness. Overall, ensitrelvir demonstrated favorable antiviral efficacy and symptom improvement, with an acceptable safety profile. In the phase III part, the time to resolution of the composite of five typical COVID-19 symptoms showed a difference between the ensitrelvir 125 mg and placebo groups, and the difference in median was approximately 1 day when the patients were randomized in less than 72 h of disease onset. This study is one of the clinical trials that used patient symptoms as a clinical efficacy endpoint. Additional clinical trials are currently underway to investigate the efficacy and safety of ensitrelvir in various patient populations. Moreover, published evidence generally supports the effectiveness of ensitrelvir in routine clinical practice and its antiviral activity against various SARS-CoV-2 variants of concern. Further research is granted to establish ensitrelvir as a novel antiviral treatment. Royalty-free licensing agreements concluded between drug manufacturers and the Medicines Patent Pool will facilitate access to COVID-19 therapeutics, including ensitrelvir, in low- and middle-income countries.

Background: Sepsis is one of the leading causes of morbidity and mortality worldwide. Early detection and reliable prediction of sepsis-related mortality are crucial. The prognostic value of National Early Warning Score 2 (NEWS-2) in sepsis patients with cardiovascular and neurovascular diseases is not well elucidated.

Objectives: This study aims to evaluate and compare the qSOFA, SOFA, qPitt, and NEWS-2 scores for predicting mortality in sepsis and septic shock patients.

Design: An observational retrospective study was conducted involving patients with sepsis or septic shock.

Methods: Data were collected between 2023 and 2024. Baseline measures included sociodemographic and clinical characteristics. All subjects were identified from a database of a highly complex healthcare institution focused on the diagnosis and treatment of cardiovascular and neurovascular diseases. The scores qSOFA, SOFA, NEWS-2, and qPitt were collected from medical records and analyzed. A sample size was estimated. The area under the receiver operating characteristic curve (AUROC) analysis was established for each score. A multivariate analysis adjusted for confounding factors through logistic regression was performed.

Results: A total of 126 participants were included, with a median age of 72 years (IQR: 59-81), and 76 (60.32%) being men. The overall mortality rate in the population was 19.8%, with 84% of deaths occurring in males. Statistically significant differences in variables such as heart failure, mild liver disease, and atrial fibrillation were observed between the groups (p < 0.05). The NEWS-2 score with a cut-off point of ⩾8 showed a significant association with mortality (p = 0.0001). The AUROC for NEWS-2 was 0.80, compared to a ROC of 0.6960 for qPitt, 0.6776 for SOFA, and 0.5868 for qSOFA (χ² = 16.60, Prob > χ² = 0.0009).

Conclusion: NEWS 2 exhibits better performance in predicting mortality among elderly adults with cardiovascular and neurovascular diseases suffering from sepsis or septic shock, compared to the qPitt, SOFA, and qSOFA scores.

Fostemsavir, a prodrug of the first-in-class gp120-directed attachment inhibitor temsavir, is indicated in combination with other antiretrovirals for the treatment of multidrug-resistant HIV-1 in adults who are heavily treatment-experienced (HTE). Temsavir binds to HIV-1 gp120, close to the CD4 binding site, preventing the initial interaction of HIV-1 with CD4 on the host cell. Amino acid substitutions at four positions in gp120 have been identified as important determinants of viral susceptibility to temsavir (S375H/I/M/N/T/Y, M426L/P, M434I/K, M475I), with a fifth position (T202E) recently described. For most currently circulating group M HIV-1 subtypes, the prevalence of these resistance-associated polymorphisms (RAPs) is low. As with many other antiretrovirals, the impact of RAPs is modified by other changes in the target molecule. Different regions of gp120 interact to modify the temsavir binding pocket, with multiple amino acids playing a role in determining susceptibility. Extensive variability of HIV-1 gp120 means the susceptibility of clinical isolates to temsavir is also highly variable. Importantly, in vitro measurement of the susceptibility of clinical isolates to temsavir does not necessarily capture the range of susceptibilities of the heterogeneous mix of viruses generally present in each isolate. Due to these factors and limited phenotypic clinical data, thus far, no relevant phenotypic cutoff or genotypic algorithms have been derived that reliably predict response to fostemsavir-based therapy in individuals who are HTE; therefore, pre-treatment temsavir resistance testing may be of limited benefit. In the phase III BRIGHTE study, re-suppression after virologic failure was observed in some participants despite treatment-emergent genotypic and/or phenotypic evidence of reduced temsavir susceptibility, and substantial CD4+ T-cell count increases occurred even among participants with HIV-1 RNA ⩾40 copies/mL at Week 240. Clinical management of people who are HTE and experience virologic failure during treatment with fostemsavir-based regimens requires an individualized approach with consideration of potential benefits beyond virologic suppression.

[This corrects the article DOI: 10.1177/20499361211032048.].

Background: Mpox was declared a Public Health Emergency of International Concern by the World Health Organization in August 2024, following an outbreak in Africa. Public engagement on YouTube provides insights into public perceptions during such crises.

Objectives: We analyzed public discourse and sentiments related to Mpox, focusing on thematic trends in YouTube comments.

Design: A qualitative synthesis employing thematic content analysis of YouTube comments.

Methods: The YouTube API retrieved 50 videos each for "Mpox" and "Monkeypox." After exclusions, 50 relevant videos remained, and the top 10 by views were analyzed. From 10,567 comments extracted, 2826 were analyzed using Latent Dirichlet Allocation modeling to identify themes.

Results: Key themes included geopolitical concerns, disease spread, conspiracy theories, public health measures, and religious interpretations. Comments revealed mixed views on vaccines, lockdowns, and mistrust in authorities.

Conclusion: Effective health communication must address scientific, cultural, and geopolitical dimensions while countering misinformation and fostering trust.