Therapeutic Advances in Infectious Disease最新文献

Background: Persistent low-level viraemia (PLLV) is a risk factor for virologic failure among people receiving antiretroviral therapy (ART).

Objectives: We assessed the prevalence and predictors of PLLV among individuals receiving Dolutegravir-based ART in southern Nigeria.

Design: This retrospective cohort study used routine program data from electronic medical records of persons receiving Dolutegravir-based first-line ART in 154 PEPFAR/USAID-supported health facilities in Akwa Ibom and Cross Rivers states, Nigeria.

Methods: Clients on first-line Dolutegravir-based ART ⩾6 months, who had a viral load result in the 12 months preceding October 2021 (baseline), and a second viral load result by September 2022 were included. Persons with low-level viraemia (LLV) (viral load 51-999 copies/ml) received additional adherence support. The outcome analysed was PLLV (two consecutive LLV results). Indices were summarized using descriptive statistics, and predictors of PLLV were determined using multivariate logistic regression.

Results: In total, 141,208 persons on ART were included, of which 63.3% (n = 89,944) were females. The median age was 36 [29-44] years, median ART duration was 19 [11-42] months. At the end of the study, 10.5% (14,759/141,208) had initial LLV, 90.1% (13,304/14,759) of which attained undetectable viral load (⩽50 copies/ml), and 1.1% (163/14,759) transitioned to virologic failure (⩾1000 copies/ml) by the end of the study. PLLV prevalence was 0.9% (1292/141,208). Increasing ART duration [adjusted odds ratio (aOR) = 1.0; 95% confidence interval (CI): 1.005-1.008; p < 0.001] and viral suppression (<1000 copies/ml) before initial LLV (aOR = 1.7; 95% CI: 1.50-2.00; p < 0.001) were positively associated with PLLV, while receipt of tuberculosis preventive therapy reduced the likelihood of PLLV (aOR = 0.3; 95% CI: 0.10-0.94; p = 0.039).

Conclusion: PLLV was uncommon among individuals receiving dolutegravir-based ART and was associated with longer ART duration, prior viral suppression, and non-receipt of tuberculosis preventive therapy. This strengthens recommendations for continuous adherence support and comprehensive health services with ART, to prevent treatment failure.

Background: Anti-annexin A2 (AA2) antibodies have been described in Lyme arthritis and erythema migrans, although they have not been described in post-treatment Lyme disease (PTLD).

Objectives: Determine whether anti-AA2 antibodies are present among patients with PTLD and determine the clinical relevance of these antibodies.

Design and methods: Anti-AA2 levels were tested serially in a longitudinal cohort of 44 patients with acute Lyme disease, 22 with a return to health (EM RTH), and 22 with PTLD. Anti-AA2 antibodies were also assessed in a cross-sectional group of 281 patients with PTLD.

Results: Anti-AA2 antibodies were highest after antimicrobial therapy in both the EM RTH and PTLD cohorts. By 6 months, there was no difference between EM RTH and healthy controls. Anti-AA2 antibodies were higher in the cross-sectional PTLD group (79.69 versus 48.22 units, p < 0.0001), though with no difference in total symptom burden.

Conclusion: Anti-AA2 persists in PTLD, though did not identify a clinical phenotype.

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.].