Therapeutic Advances in Infectious Disease最新文献

The resurgence of diphtheria in Nigeria, culminating in an outbreak surpassing previous records, has spotlighted the critical imperative for robust immunization policies amidst a milieu of vaccine hesitancy. This commentary delineates the multifaceted dimensions of the current diphtheria outbreak, which started in May 2022, juxtaposed against historical outbreaks, with a focal examination of the pervasive vaccine hesitancy and its underpinning sociocultural and systemic determinants. The discourse extends to a meticulous evaluation of Nigeria's public health response, underlined by the synergy with international organizations, reflecting a global collaborative ethos in combating the diphtheria menace. A critical appraisal of the prevailing immunization policies unveils a necessity for strategic amendments to invigorate vaccination uptake, essential for curbing the diphtheria outbreak and enhancing public health resilience. The reflections herein advocate for a comprehensive, culturally resonant, and sustainable public health paradigm, encompassing a synergistic approach of policy fortification, community engagement, and international collaboration to navigate the challenges posed by vaccine-preventable diseases epitomized by the ongoing diphtheria outbreak. Through a synthesis of historical lessons, contemporary challenges, and global solidarity, this piece contributes to the broader discourse on enhancing immunization coverage and infectious disease control in Nigeria.

Multiple myeloma is among the most common hematological malignancies and is characterized by a strong susceptibility to infections primarily bacterial and viral and, to a much lesser extent, fungal. There appears to be a slightly increasing frequency of invasive fungal infections. This is attributed to the use of different combinations of newer drugs and patients' exposure to increasing therapeutic lines, and thus to risk factors for invasive fungal infections, especially severe and long-term neutropenia. Novel immunotherapy modalities including bispecific antibodies and chimeric antigen receptor T-cell therapy are being introduced for the treatment of relapsing-refractory forms of the disease. Consequently, in the near future, it can be expected that myeloma patients will exhibit a significantly increased frequency of invasive fungal infections. Therefore, we must carefully monitor all epidemiological trends related to invasive fungal infections in patients with multiple myeloma, both in clinical studies and in real life. This will help us learn to prevent fungal infections, as well as quickly recognize and treat them to reduce their impact on patients' morbidity and mortality. In this review article, we describe in detail the epidemiological characteristics of invasive fungal infections in myeloma patients, the risk factors for these infections, and the treatment and prevention options.

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of IFI, as the diagnosis was made using 28S rDNA/internal transcribed spacer PCR.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made.

Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death.

Design: This is a propensity score-matched cohort study.

Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed.

Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45].

Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

This article aims to provide a practical guide for patient management and an overview of the predictive scorings for Fournier's gangrene (FG) that are available to aid clinicians. A literature was performed reviewing currently used scoring systems for FG and presenting a practical guide for its management based on the available evidence. There are four specific scoring systems available for the assessment of FG although few other non-specific and generic tools also exist. These specific tools include Laboratory Risk Indicator for Necrotizing Fasciitis, Fournier's Gangrene Severity Index, Uludag Fournier's Gangrene Severity Index, and Simplified Fournier's Gangrene Severity Index and help calculate expected mortality. Our proposed algorithm covers primary assessment, resuscitative interventions, initial investigations, urgent care, post-operative care, and long-term follow-up. The management of the FG patient can be divided into initial resuscitation, surgical debridement, ongoing ward management with antibiotic therapy, wound reconstruction, and long-term follow-up. Each facet of care is vital and requires multidisciplinary team expertise for optimal outcomes. Whilst mortality continues to improve, it remains significant, reflecting the severe and life-threatening nature of FG. More research is certainly needed into how this care is individualised, and to ensure that long-term outcomes in FG include quality of life measures after discharge.

Introduction: Uncomplicated Staphylococcus aureus bacteremia remains a leading cause of morbidity and mortality in hospitalized patients. Current guidelines recommend a minimum of 14 days of treatment.

Objective: To evaluate the efficacy and safety of short versus usual antibiotic therapy in adults with uncomplicated S. aureus bacteremia (SAB).

Methods: We developed a search strategy to identify systematic review and meta-analysis of non-randomized studies (NRS), comparing short versus usual or long antibiotic regimens for uncomplicated SAB in MEDLINE, Embase, and the Cochrane Register up to June 2023. The risk of bias was assessed using the ROBINS I tool. The meta-analysis was performed using Review Manager software with a random effect model.

Results: Six NRS with a total of 1700 patients were included. No significant differences were found when comparing short versus prolonged antibiotic therapy as defined by the authors for 90-day mortality [odds ratio (OR): 1.09; 95% confidence interval (CI): 0.82-1.46, p: 0.55; I² = 0%] or 90-day recurrence or relapse of bacteremia [OR: 0.72; 95% CI: 0.31-1.68, p: 0.45; I² = 26%]. Sensitivity analysis showed similar results when comparing a predefined duration of <14 days versus ⩾14 days and when excluding the only study with a high risk of bias.

Conclusion: Shorter-duration regimens could be considered as an alternative option for uncomplicated SAB in low-risk cases. However, based on a small number of studies with significant methodological limitations and risk of bias, the benefits and harms of shorter regimens should be analyzed with caution. Randomized clinical trials are needed to determine the best approach regarding the optimal duration of therapy.

Infective endocarditis (IE) is a condition with low prevalence but high mortality rates within intensive care units. Microbiologically, most cases are attributed to Gram-positive cocci, while Gram-negative bacilli are less commonly involved. This case report describes a patient with IE caused by Citrobacter koseri (C. koseri) with secondary bacteremia due to blunt testicular trauma and epididymitis. We conducted a review of the literature to assess the clinical and associated risk factors of this underreported condition. Elderly and urinary tract infections could be associated with this entity. Cefazolin was used as the final targeted treatment. The use of precision medicine in IE is required for specific interventions.

[This corrects the article DOI: 10.1177/20499361241228342.].

Background: Sepsis is a leading cause of morbidity and mortality especially in low- and middle-income countries such as Nigeria. Training of health workers using digital platforms may improve knowledge and lead to better patient outcomes.

Objectives: To assess the effectiveness of a digital health educational module on sepsis in improving the knowledge of medical doctors in Cross River State Nigeria on the diagnosis and management of patients presenting with sepsis.

Design: Quasi-experimental analytical study.

Methods: We developed and deployed a sepsis module through an innovative application (Sepsis tutorial app) to doctors in Calabar, Nigeria. We assessed quantitative pre- and post-intervention knowledge scores for those completing the tutorial on sepsis between both assessments. A user satisfaction survey evaluated the content of the tutorial and the usability of the app.

Results: One hundred and two doctors completed the course. There were more males than females (58.8% versus 41.2%). Over half (52%) were junior doctors, a minority were general practitioners and house officers (3% and 5%, respectively), and 72.6% had practiced for periods ranging from 1 to 15 years post-qualification. Gender and age appeared to have no significant association with pre- and post-test scores. The oldest age group (61-70) had the lowest mean pre- and post-test scores, while general practitioners had higher mean pre- and post-test scores than other cadres. The majority (95%) of participants recorded higher post-test than pre-test scores with a significant overall increase in mean scores (25.5 ± 14.7%, p < 0.0001). Participants were satisfied with the content and multimodal delivery of the material and found the app usable.

Conclusion: Digital training using context-responsive platforms is feasible and may be used to close the critical knowledge gap required to respond effectively to medical emergencies such as sepsis in low- to middle-income settings.

Background: Metagenomic next-generation sequencing (mNGS) testing identifies thousands of potential pathogens in a single blood test, though data on its real-world diagnostic utility are lacking.

Objectives: Determine the diagnostic utility of mNGS testing in practice and factors associated with high clinical utility.

Design: Retrospective cohort study of mNGS tests ordered from June 2018 through May 2020 at a community teaching hospital.

Methods: Tests were included if ordered for diagnostic purposes in patients with probable or high clinical suspicion of infection. Exclusions included patient expiration, hospice care, or transfer outside of the institution. Utility criteria were established a priori by the research team. Two investigators independently reviewed each test and categorized it to either high or low diagnostic utility. Reviewer discordance was referred to a third investigator. The stepwise multiple regression method was used to identify clinical factors associated with high diagnostic utility.

Results: Among 96 individual tests from 82 unique patients, 80 tests met the inclusion criteria for analysis. At least one potential pathogen was identified in 58% of tests. Among 112 pathogens identified, there were 74 bacteria, 25 viruses, 12 fungi, and 1 protozoon. In all, 46 tests (57.5%) were determined to be of high diagnostic utility. Positive mNGS tests were identified in 36 (78.3%) and 11 (32.4%) of high and low diagnostic utility tests, respectively (p < 0.001). Antimicrobials were changed after receiving test results in 31 (67.4%) of high utility tests and 4 (11.8%) of low utility tests (p < 0.0001). In the multiple regression model, a positive test [odds ratio (OR) = 10.9; 95% confidence interval (CI), 3.2-44.4] and consultation with the company medical director (OR = 3.6; 95% CI, 1.1-13.7) remained significantly associated with high diagnostic utility.

Conclusion: mNGS testing resulted in high clinical utility in most cases. Positive mNGS tests were associated with high diagnostic utility. Consultation with the Karius^® medical director is recommended to maximize utility.