Therapeutic Advances in Infectious Disease最新文献

Background: Vietnam has one of the highest hepatitis B virus (HBV) infection rates, with approximately 8 million people affected. Although antiviral drug resistance mutations have been reported in treatment-naïve patients with chronic hepatitis B, there is limited data on primary drug resistance mutations in circulating genotypes within this population.

Objectives: This study aimed to investigate primary antiviral drug resistance mutations and common HBV genotypes in treatment-naïve patients with chronic hepatitis B, particularly in cases without well-characterized resistance profiles.

Design: A cross-sectional study.

Methods: We analyzed HBV genotypes and antiviral drug resistance mutations in 113 treatment-naïve patients with chronic hepatitis B in the Yenphong Medical Center, Bacninh Vietnam. The reverse transcriptase (RT) region of the HBV polymerase genes was sequenced to detect mutations.

Results: Genotypes B, C, and G were identified in 85.0% (96/133), 14.1% (16/133), and 0.9% (1/133) of treatment-naïve patients with chronic hepatitis B, respectively. Mutations in the RT region associated with antiviral drug resistance were detected in 32.7% (37/113) of patients. In addition, the most frequent resistance mutations were rtV207M (89.2%, 33/37), followed by A194T, L180M + M204V, V173L + M204I + L80I, and A181T + V207M + A181T, each observed in 2.7% (1/37). Notably, no significant associations were found between resistance mutations and HBV genotype, gender, age, hepatitis B e-antigen status, baseline HBV DNA levels, or level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase.

Conclusion: This study highlights the presence of primary resistance mutations in treatment-naïve patients and underscores the importance of genotypic screening prior to initiating therapy. These findings may inform treatment strategies and help reduce the risk of treatment failure, liver cirrhosis, and hepatocellular carcinoma.

The skin microbiota is crucial in defending against toxic, solar, and pathogenic assaults, yet it can also precipitate dermatosis when its equilibrium is disrupted. The composition and distribution of various microorganisms within the skin maintain a dynamic balance, modulating the barrier function and the immune system, thereby constituting the skin microbiota. This microbiota not only offers new insights into pathological microbe-host interactions and associated dermatoses but also inspires innovative therapeutic strategies that promise high efficacy and reduced symptomatology. In this review, we synthesize recent advancements in the field of skin microbiota, focusing on its relationship with dermatosis and the application of microbiota-based therapies in skin diseases. Our aim is to scrutinize the current understanding of the skin microbiota's role, ranging from a protective barrier to a causative agent of dermatosis.

A 33-year-old man living with advanced HIV with a histologically confirmed diagnosis of Kaposi sarcoma presented during a SARS-CoV-2 outbreak with worsening shortness of breath. He was treated for confirmed SARS CoV-2 infection with minimal symptomatic response, and whilst undergoing KS treatment on the ward developed the rare complication of plastic bronchitis. He had a prolonged hospital admission undergoing treatment for his Kaposi sarcoma and plastic bronchitis whilst being evaluated for concurrent opportunistic infections.

Background: Tuberculosis (TB) affects patients' quality of life due to symptoms and social stigma, especially in low-income settings like Ghana. However, data on factors influencing health-related quality of life (HRQOL) in such environments are limited. Identifying these factors is essential for improving treatment outcomes through holistic care.

Objective: This study determined the impact of sociodemographic and clinical factors on HRQOL at treatment initiation, and monitored changes until the end of treatment.

Design: Prospective observational study.

Methods: A cohort of 378 newly diagnosed patients with drug-susceptible TB (mean age: 45.3 ± 15.1 years) was followed across eight hospitals in the Ashanti and Eastern regions of Ghana. Patients received first-line antitubercular treatment, and HRQOL was assessed at baseline, month 2, and month 6 using an interviewer-administered SF-12v2 questionnaire. Associations between HRQOL and sociodemographic or clinical factors were examined using Chi-square or Fisher's exact tests, while logistic regression was used to estimate crude and adjusted odds ratios (p < 0.05).

Results: At baseline, 78.8% of participants had impaired physical HRQOL, and 25.7% were at risk of depression. At treatment completion, physical HRQOL impairment remained high (59.5%), with 15.0% still at risk of depression. Only 44.7% showed clinically significant improvement in physical HRQOL, while 39.8% improved in mental HRQOL. Employment, HIV-positive status, and alcohol use were associated with poorer mental HRQOL. Extrapulmonary TB patients demonstrated better physical HRQOL at both the beginning and end of treatment but exhibited poorer mental HRQOL at treatment completion. Widowed participants improved mentally despite poorer baseline health, while married individuals had better physical HRQOL. Higher education correlated with better baseline mental health but lower odds of significant HRQOL improvement.

Conclusion: Sociodemographic and clinical factors significantly influenced HRQOL in drug-susceptible TB patients after 6 months of treatment. These findings underscore the importance of targeted mental health support during and after treatment to improve patient well-being.

Background: People with advanced HIV admitted to hospitals are at high risk of mortality. Serious illness can be identified using WHO-defined danger signs ("WHO score") or bedside scores like the quick Sequential Organ Failure Assessment (qSOFA) score.

Objectives: The study aimed at assessing clinical parameters as predictors of in-hospital mortality for people with HIV (PWH) admitted for routine medical care.

Study design: A prospective observational study of all PWH admitted to medical wards at Kamuzu Central Hospital, Lilongwe, Malawi.

Methods: WHO danger signs and qSOFA score were determined at the first encounter, CD4 count tests were performed, and discharge outcomes were recorded. The discriminatory power of different scores for predicting in-hospital mortality was assessed using the area under receiver-operating-characteristic curves (AUROCs).

Results: From November 2022 to May 2023, 401 adults aged ⩾18 years were admitted. Advanced HIV disease (CD4 < 200 cells/mm³) was present in 55.2% (95% CI 50.2-60.2). Overall, in-hospital mortality was 25.7% (95% CI 21.3-30.0). Neither sex, age, CD4 count, nor BMI < 18.5 was significantly associated with mortality. Both the WHO score and qSOFA score were significantly associated with increasing mortality. AUROC for WHO score and qSOFA were 0.68 (95% CI 0.61-0.75) and 0.71 (95% CI 0.64-0.78), respectively. Including BMI or CD4 did not significantly improve AUROC. Using only the individual danger sign "inability-to-walk-unaided" yielded a similar AUROC of 0.68 (95% CI 0.61-0.75).

Conclusion: Increasing WHO danger sign scores were associated with in-hospital mortality; adding BMI or CD4 did not improve predictive accuracy. Notably, the predictive information derived from a single parameter-inability-to-walk-unaided-was as effective as the complete WHO score and was easier to obtain. Given the challenges in comprehensive vital sign recording, this simple measure may prove valuable in triaging PWH admitted to hospitals in resource-limited settings such as Malawi.

Background: Kidney disease, ranging from asymptomatic kidney impairment to end-stage renal disease, remains a public health concern globally. Kidney diseases have been shown to be a significant cause of mortality and morbidity among people living with HIV (PLWH). However, there is limited data on the burden and risk factors for kidney impairment in resource-limited settings.

Objectives: This study aimed to determine the prevalence and factors associated with kidney impairment among PLWH receiving antiretroviral therapy (ART) at a tertiary hospital in Zambia.

Design: This was a retrospective cross-sectional study.

Methods: This study consisted of 374 PLWH aged ⩾18 years and on ART for ⩾ 6 months. We obtained clinical, laboratory, and demographic characteristics from a study that focused on metabolic syndrome among PLWH. Kidney impairment was defined as having an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m². Data was analyzed using STATA version 15. Multivariable logistic regression was used to ascertain factors associated with kidney impairment.

Results: The median age among the study participants was 44 years, and the majority were females, 63.4% (n = 237). The prevalence of kidney impairment was 10.7% (n = 40. After accounting for duration on ART, sex and blood pressure (systolic and diastolic), older age and being on a Dolutegravir (DTG) and tenofovir disoproxil fumarate/lamivudine (TDF/3TC) based regimen was positively associated with kidney impairment (adjusted odds ratio (aOR) 1.09; 95% CI: 1.05, 1.14, p < 0.001) and (aOR 2.44; 95% CI: 1.02, 5.79, p = 0.043), respectively.

Conclusion: The prevalence of kidney impairment was common among adult PLWH and was significantly associated with older age and the use of a DTG and TDF/3TC-based regimen. There is a need to regularly monitor kidney function among people with HIV, especially older people who are on a DTG and TDF/3TC-based regimen.

Background: Understanding how the gut microbiome adapts on exposure to individual antibiotics, with respect to antimicrobial resistance gene (ARG) enrichment, is important.

Objectives: To characterise the changes that occur in the gut microbiome of patients enrolled in an antibiotic clinical trial and to propose methods in which to embed gut microbiome analysis into clinical trials.

Design: This was a prospective cohort study of hospitalised patients who were successfully enrolled and randomised into two clinical trials between January 2021 to December 2021.

Methods: Adult patients admitted to the hospital with a bloodstream infection have been randomised to receive either benzylpenicillin, ampicillin, cefazolin, ceftriaxone, piperacillin-tazobactam or meropenem at a single institution. Faecal specimens were collected at enrolment and every second day until discharge. Each specimen underwent DNA sequencing to determine microbial diversity and ARG abundance.

Results: Ten patients (including six females) were included. DNA concentration and sampling quality were markedly lower for rectal swabs compared to stool samples. Relative abundance of Enterococcus faecium was increased in individual patients where treatment included ampicillin, meropenem and piperacillin-tazobactam. Piperacillin-tazobactam also increased the abundance of key beta-lactamase genes (bla _SHV-100, bla _OXA-392, bla _CMY-18). Ampicillin increased the abundance of bla _TEM-1A. There were no extended-spectrum beta-lactamase (ESBL) or carbapenemase genes detected in our study. The presence of key anaerobes such as Clostridium and Bifidobacterium species appeared to play an important role in colonisation resistance of E. faecium and Clostridioides difficile.

Conclusion: Differential changes in anaerobic bacterial genera on exposure to antibiotics may be a key determinant of colonisation resistance. The pre-analytical phase of microbiome analysis is a critical factor in data quality and interpretation.

Background: The prevalence of tuberculosis (TB) multi-drug resistance is increasing worldwide, including in Tanzania. This trend hinders the attainment of sustainable development goal number three as it increases the number of cases of the disease and treatment costs. Fewer cases of drug resistance have been reported over time, making it necessary to demand models that can handle an excessive number of zero counts. This study employed the zero-inflated Poisson (ZIP) models suitable for such data to assess drug resistance patterns.

Objective: To examine the TB drug resistance spatiotemporal risk patterns and associated risk factors using health facility case notification data.

Design: A retrospective cohort study utilizing TB drug resistance case notification data from the District Health Information System 2 for Tanzania Mainland between 2018 and 2020.

Methods: The study was conducted in Tanzania Mainland and utilized TB drug resistance case data from 184 councils. Six hundred fifty-two (652) TB drug resistance cases were analyzed using the Bayesian ZIP spatiotemporal model to identify high-risk areas and risk factors for TB drug resistance. The deviance information criterion guided model selection.

Results: The findings revealed a higher prevalence of drug resistance among males (65.2%), individuals aged 35-49 years (33.7%), persons living without HIV (66.4%) and new TB cases (70.7%). Spatiotemporal modelling indicated significant relationships between drug resistance and sex, age, TB treatment history and HIV status. Males were 1.4 times more likely to develop drug resistance than females. Children aged 0-4 and 5-14 years were 25 and 8.3 times less likely to develop drug resistance than adults aged 35-49. Persons living with HIV and those with unknown HIV status were 1.2 and 3.4 times less likely to develop drug resistance, respectively, than persons living without HIV. Individuals with a previous TB treatment history were three times more likely to develop drug resistance compared to new cases.

Conclusion: The Bayesian ZIP spatiotemporal models provide critical insights by identifying high-risk populations and areas, enabling targeted interventions to control multi-drug resistant TB. The study further concludes that resistance to anti-TB drugs is highly associated with sex, age and previous treatment history. To mitigate its spread and impact, the study recommends strengthening awareness campaigns on adherence to treatment guidelines and understanding the risk factors associated with TB drug resistance.

Background: Reduced or delayed access to medical resources on weekends could lead to worsening outcomes, in critically ill infected patients requiring intensive care unit (ICU) admission.

Objective: To investigate the "weekend effect," on critically ill infected patients in Japanese ICUs for the first time.

Design: Multicenter retrospective cohort study.

Methods: We examined data from Japanese ICU patients participating in the DIANA study, a multicenter international observational cohort study. This prospective investigation enrolled critically ill patients with infections admitted to the ICU. The primary endpoint was successful discharge from the ICU within 28 days of admission. Outcome measures were evaluated through both univariate and covariate Cox regression analyses, providing hazard ratios (HRs) along with estimated 95% confidence intervals (CIs).

Results: Out of the 276 patients enrolled in the DIANA study across 31 facilities, 208 patients (75.4%) meeting the inclusion criteria were included in the analysis. The weekday ICU admission group comprised 156 patients (75.0%), while the weekend ICU admission group comprised 52 patients (25.0%). In the multivariate Cox regression analysis, there were no statistically significant differences observed in the rates of ICU discharge alive within 28 days and 14 days (28 days, HR: 0.94, 95% CI: 0.63-1.40; 14 days, HR: 0.97, 95% CI: 0.64-1.48). Furthermore, the overall ICU mortality rates at 28 days and 14 days after ICU admission did not show statistical significance between patients admitted on weekends and those admitted on weekdays (ICU mortality, 28 days: 13.5% vs 11.5%, p = 0.806; 14 days: 7.7% vs 10.9%, p = 0.604).

Conclusion: The rates of ICU discharge alive within 28 days after ICU admission did not differ significantly between weekday and weekend admissions, both in the unadjusted and adjusted analyses. Moreover, further well-designed studies are warranted to thoroughly assess this effect.

Antimicrobial resistance (AMR) poses a significant global health threat by diminishing the effectiveness of once-powerful antimicrobial agents, leading to higher rates of illness and death, along with escalating healthcare costs. While bacterial resistance is a primary concern, resistance is also increasing against antifungal, antiparasitic, and antiviral drugs. Many of the last-resort drugs are becoming less effective due to AMR. Projections indicate that by 2050, AMR could cause up to 10 million deaths annually, making it the leading cause of death worldwide, a situation that could result in a post-antibiotic era with substantially increased morbidity and mortality. This review aims to raise awareness about the dangers of AMR and its potential to become a silent global pandemic. It begins by examining antimicrobial drugs, followed by a discussion on AMR, focusing on resistance to antibacterial, antifungal, antimalarial, and antiviral drugs, along with its effects on health, and the economy, and prioritized global pathogens. Finally, it explores preventive measures and innovative strategies to combat AMR.