Therapeutic Advances in Infectious Disease最新文献

Human hookworm infection is caused by the nematodes Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum. Iron deficiency anemia is the hallmark of chronic, moderate-to-heavy-intensity infections, promoting a vicious poverty cycle. Overt severe and acute life-threatening lower gastrointestinal hemorrhage is an extremely rare manifestation of hookworm infection, as well as finding multiple nematodes attached to the colonic mucosae. This rare hookworm presentation with hematochezia from the colon in a patient living with human immunodeficiency virus highlights the importance of physicians' awareness of this neglected tropical disease responsible for high morbidity and burden in healthcare systems of endemic regions.

Background: Whole body 18F-fluorodeoxyglucose positron emission tomography/CT (WBP) may be an important tool for the management of infective endocarditis (IE) by identifying areas of occult primary or metastatic infection. However, the optimal use of this study in patients with IE is unknown.

Objectives: Compare clinical characteristics and outcomes in patients who did and did not have WBP as part of their endocarditis management, and describe the impact that WBP has on the management of IE.

Design: Retrospective cohort study.

Methods: We performed a protocolized chart review of hospitalized patients with suspected IE who were discussed by a multidisciplinary endocarditis team at a tertiary care center between June 2018 and January 2022.

Results: Among 427 patients, there were 114 patients (26.7%) in the WBP group and 313 patients (73.3%) in the non-WBP group. The WBP group was significantly more likely to have end-stage renal disease, intracardiac prostheses, and cardiac devices, while the non-WBP group was more likely to have flail leaflet or paravalvular abscesses. There were no statistically significant differences in mortality, hospital readmission, or length of stay between the two cohorts. The WBP group was more likely to receive longer antibiotic courses and had higher rates of suppressive antibiotics following treatment courses (p < 0.001). The use of WBP directly affected management in 44.6% of those patients, especially when performed to evaluate intravascular prostheses and grafts. Changes in management included further workup, performance of a source control procedure, or a change in the antibiotic regimen.

Conclusion: WBP plays an important role in identifying metastatic foci of infection and directly impacting the management of patients with confirmed or suspected endocarditis. Infected intravascular prostheses were effectively identified via WBP, and as a result, these patients were prescribed longer courses of antibiotics and suppressive antibiotics.

Background: Antimicrobial resistance in uropathogens is increasing globally, particularly in resource-limited settings such as Nepal, limiting treatment options.

Objectives: This study aimed to evaluate the antimicrobial resistance patterns of uropathogens isolated from patients with urinary tract infections (UTIs) in a tertiary care hospital in central Nepal.

Design: This study utilized a retrospective study design.

Methods: We retrospectively observed medical records from August 2023 to February 2024 at Manmohan Memorial Teaching Hospital in Nepal, focusing on patients with significant bacterial growth in urine samples and antibiotic sensitivity analysis for resistance trends.

Results: Escherichia coli (E. coli) (64.7%) and Klebsiella pneumoniae (K. pneumoniae) (15.0%) were the most common uropathogens. Both showed the highest resistance to amoxicillin (>95%), while E. coli demonstrated the lowest resistance to gentamicin (7.4%) and nitrofurantoin (12.2%). Klebsiella pneumoniae also showed low resistance to gentamicin (12.0%) but higher resistance to nitrofurantoin (64.0%).

Conclusion: Empirical therapy, including nitrofurantoin and aminoglycosides, is a viable option for combating antimicrobial resistance in Nepal, necessitating region-specific surveillance and multicentre studies.

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by Bandavirus dabieense. SFTS was first identified in China in 2009 and has been reported since then in neighboring countries and regions. The clinical manifestations of SFTS include fever, thrombocytopenia, and leukocytopenia and are often accompanied by gastrointestinal symptoms and bleeding. In severe cases, patients experience life-threatening immune damage and cytokine storms. Despite nearly 15 years since its discovery, no effective vaccine has been approved. However, significant progress has been achieved in elucidating the mechanisms of host immune responses, accompanied by the clinical implementation of various therapeutic agents. This article provides a comprehensive review of commonly utilized treatments supported by current clinical evidence. Favipiravir has advantages over ribavirin in terms of viral clearance and prognosis. Conventional immunomodulators like interferon, intravenous immunoglobulin, and glucocorticoids have limited effects and may even worsen conditions, whereas novel immunomodulators such as tocilizumab and ruxolitinib have shown potential for improving prognosis. Prophylactic platelet transfusions neither prevent bleeding nor improve clinical outcomes. Additionally, plasma exchange, calcium channel blockers, and arginine can improve laboratory values and expedite viral clearance. In the future, screening Food and Drug Administration-approved drugs and conducting multiomics analyses may lead to the discovery of new effective therapeutic options.

The growing population of transplant survivors receiving a solid organ transplantation (SOT) or a hematopoietic cell transplantation (HCT) and the emergence of cellular therapies are contributing to an increase in high-risk travelers to different regions of the world. Timely pretravel evaluations are essential for risk stratification and a segway to planning proper immunization, personalized antimicrobial prophylaxis, and preventative counseling based on individual medical conditions, immune status, and potential drug-drug interactions. In addition, clinicians can provide emergency and specialized medical center contacts as available. We herein review the available strategies for the prevention and management of travel-related infections in adult recipients of HCT and SOT.

Background: Nontuberculous mycobacteria disease is an emerging opportunistic infection that is often refractory to therapy. Interleukin 7 (IL-7) is a pleiotropic cytokine with broad-ranging effects that enhance immunity and augment monocyte/macrophage anti-Mycobacterium avium killing in vitro.

Objectives: This study evaluated IL-7 in patients with refractory Mycobacterium avium complex lung disease (MAC-LD).

Design: Prospective, single-center, randomized, study of IL-7 in patients with refractory MAC-LD.

Methods: Randomization (two sets of 4 weekly IL-7 injections) was stratified based on the presence of pulmonary cavities. The primary outcome was sputum culture conversion to negative within 6 months. Exploratory outcomes included investigation of potential molecular mechanisms of immunosuppression via single-cell RNA sequencing (scRNA-seq).

Results: Of the eight participants enrolled, six completed the IL-7 regimen, one completed one 4-week therapy, and one received a single dose of IL-7. All six participants who completed the regimen showed an increased absolute lymphocyte count (ALC), yet none converted their sputum culture to negative at 6 months. Similarly, there were no differences in secondary outcomes compared to baseline. IL-7 was well tolerated, and two participants showed an increase in time-positivity for MAC in their sputum culture. scRNA-seq revealed increased expression of genes involved in immunosuppressive pathways.

Conclusion: In adults with refractory MAC-LD, IL-7 did not result in sputum culture conversion. IL-7 reversed the underlying lymphopenia associated with MAC-LD and led to a sustained increase in ALC. The study was limited by a small sample size, and although a longer course of IL-7 combined with newer antimicrobials for may warrant further investigation, structural lung disease may be a stronger predictor of cure than immune dysfunction in MAC-LD.

Trial registration: The trial was registered in clinicaltrials.gov (NCT04154826).

Background: Pneumonia remains a significant global health concern, particularly for children in low- and middle-income countries. Despite advancements in medical care and the availability of effective medication, treatment failure still occurs.

Objective: This study evaluated the incidence, associated factors, and outcomes of treatment failure among children under 5 years with pneumonia.

Design: A prospective observational study.

Method: We conducted this study among children under 5 years hospitalized with pneumonia at the pediatric ward of Mbarara Regional Referral Hospital over a period of 3 months. We enrolled the participants in the study consecutively. Data was analyzed using SPSS software Version 27. Logistic regression was used to determine factors associated with treatment failure.

Results: A total of 216 children aged between 0 and 59 months were included in the study. The incidence of treatment failure after 48 h was 53 (24.5%). A total of 32 (60.4%) cases of treatment failure occurred early (between 48 and 72 h), while 21 (39.6%) occurred late (after 72 h). Distance of >5 km from the nearest health facility (adjusted odds ratio (AOR) = 2.2, 95% CI: 1.1-4.4, p-value = 0.029), severe acute malnutrition (AOR = 6.2, 95% CI: 2.4-16.1, p-value < 0.001), and adverse drug reaction (AOR = 6.9, 95% CI: 2.6-18.4, p-value < 0.001) were independent predictors of treatment failure. The outcomes of treatment failure included prolonged hospitalization, death, referral to a higher-level facility, and complications of pneumonia.

Conclusion: Our study identified a high incidence of treatment failure among children under 5 years in this setting. There is a need for early and accurate diagnosis, which includes culture and sensitivity tests, timely initiation of effective antibiotic therapy, active pharmacovigilance, and close monitoring of patients with acute malnutrition to reduce the likelihood of treatment failure.

Background: Extrapulmonary tuberculosis (EPTB) poses a public health challenge, particularly among individuals with human immunodeficiency virus (HIV). However, many EPTB cases arise in those without HIV, leaving the underlying factors unclear.

Objectives: This study aims to characterize patients with pulmonary tuberculosis (PTB) and EPTB, exploring the differences in associated factors for each type in patients with and without HIV.

Design: An analytical observational study was conducted on a cohort of tuberculosis (TB) patients diagnosed between 2014 and 2021 in a referral hospital in Bogotá, Colombia.

Methods: Patients were categorized into PTB or EPTB based on the site of infection. Data on demographic and clinical variables were collected, comparing the two groups. A multivariate logistic regression model was created to identify factors associated with EPTB compared to PTB.

Results: The study encompassed 533 patients: 310 with PTB and 223 with EPTB, of which only 65 (14.7%) were HIV positive. PTB patients exhibited higher rates of active smoking, smoking cessation, diabetes mellitus (DM), and other pulmonary diseases. The logistic regression identified HIV infection as the only factor associated with EPTB (OR 2.36 (1.54-3.61), p < 0.001). Conversely, quitting smoking (OR 0.58 (0.35-0.96) p = 0.038), DM (OR 0.41 (0.21-0.82) p = 0.011), chronic obstructive pulmonary disease (COPD) (OR 0.18 (0.08-0.4) p < 0.001), other pulmonary diseases (OR 0.21 (0.61-0.77) p = 0.019), or those using immunosuppressants (OR 0.44 (0.20-0.96) p = 0.04) exhibited a negative association with EPTB compared to PTB. Specific models for pleural and lymph node TB revealed distinct associations, with HIV strongly linked to lymph node TB (OR 3.38, 95% CI 1.57-7.26, p = 0.002).

Conclusion: EPTB is primarily associated with HIV infection, while smoking, DM, COPD, other pulmonary diseases, and immunosuppressant use are associated with PTB. Variability in associated factors for specific EPTB forms underlines the need for tailored research into the predisposing factors for EPTB, particularly in HIV-negative patients.

Background: Understanding factors that predict progression to severe COVID-19 is critical. Antibodies targeting SARS-CoV-2 spike protein confer protection, while the N protein of SARS-CoV-2 plays roles in viral replication and immune dysfunction. This study explores the significance of N protein and anti-spike antibodies on disease severity, progression, and mortality.

Objectives: To evaluate the relationship between SARS-CoV-2 N protein and anti-spike antibody levels with disease severity, clinical outcomes, and mortality in hospitalized patients with COVID-19.

Design: A secondary analysis of serologic data from participants in the ACTIV-1 randomized clinical trial, which evaluated immunomodulators for the treatment of hospitalized patients with COVID-19.

Methods: A subanalysis of the ACTIV-1 immune modulator trial was conducted. Samples collected at randomization were tested for N protein levels and anti-spike antibodies. Logistic regression and linear models were employed to examine the association between serological measures and clinical outcomes, including 28-day mortality as well as progression to high-flow nasal cannula (HFNC) and invasive mechanical ventilation (MV).

Results: Among the 496 participants with detectable serum N protein, the median was 1143 ng/dL, and levels decreased from 2559 ng/dL in participants randomized at 6 days of symptom onset to 477.6 ng/dL at 11 days. Higher anti-spike antibody levels were seen as the days from symptom onset progressed or disease severity increased. Greater disease severity at randomization was associated with 28-day mortality, prolonged days of oxygenation, ventilation, hospitalization, and risk of new non-invasive ventilation, HFNC, MV, or extracorporeal membrane oxygenation use. N protein levels were associated with a higher risk of new non-invasive ventilation or HFNC use, longer oxygenation duration, and extended hospitalization. Anti-spike antibody serologies were not associated with clinical outcomes.

Conclusion: N protein levels could provide insights into COVID-19 disease progression and prognosis. Further research is needed to explore the clinical implications of these findings to optimize patient care and enhance outcomes.

Background: In many low- and middle-income countries, including Ethiopia, dolutegravir (DTG)-based regimens are the preferred first-line regimens for people living with HIV (PLWH). However, there are concerns about hyperglycemia and, in certain circumstances, diabetes mellitus in individuals who have switched to DTG.

Objective: To assess the prevalence and factors associated with hyperglycemia among PLWH on DTG-based antiretroviral therapy (ART).

Design: An institutional-based cross-sectional study.

Methods: The study was carried out from December 1, 2021 to February 30, 2022, and included 423 participants who were recruited via a simple random sampling technique. We enrolled PLWH aged 18 years or older who had been on DTG-based ART for more than 6 months. Data were collected by using an interviewer-administered structured questionnaire, medical card review, physical measurement, and biochemical measurements. Hyperglycemia was defined as a fasting blood glucose level ⩾110 mg/dl. Multivariable logistic regression was used to identify factors associated with hyperglycemia, using SPSS version 26.0 software. Variables with a p-value of <0.05 were considered statistically significant.

Results: The prevalence of hyperglycemia among PLWH receiving DTG-based ART was 12.1% (95% CI: 9.2-15.1). Age (AOR = 1.04, 95% confidence interval (CI): 1-1.08, p = 0.036), BMI (AOR = 1.09, 95% CI: 1.01-1.17, p = 0.022), and triglyceride level (AOR = 2.44, 95% CI: 1.28-4.64, p = 0.006) were significant predictors of hyperglycemia among PLWH on DTG-based ART.

Conclusion: Overall, our study revealed a high prevalence of hyperglycemia (12.1%) among PLWH receiving DTG-based ART. Age, BMI, and triglyceride levels were significant predictors of hyperglycemia. These findings underscore the importance of monitoring blood glucose levels in PLWH receiving DTG-based ART, with a special emphasis on patients with advanced age, increased BMI, and increased triglyceride levels.