Therapeutic Advances in Infectious Disease最新文献

Emerging evidence from the REPRIEVE study cohort has further clarified the association between abacavir use and cardiovascular risk. This analysis, along with previous findings, demonstrates a significant elevation in time to first major adverse cardiovascular events (MACE) among adults living with HIV with current or past abacavir exposure. Given the availability of safer, equally effective alternative ART regimens with fewer cardiovascular risks, the continued clinical relevance of abacavir in adults living with HIV should be critically reassessed. Considering these findings, abacavir should be considered an obsolete option for most, if not all, adults living with HIV. This perspective shift emphasizes the importance of selecting ART regimens that optimize long-term cardiovascular health while achieving durable virologic suppression in the modern era of HIV treatment.

Background: While isavuconazole (ISA) has demonstrated non-inferiority to voriconazole (VCZ) for invasive aspergillosis (IA) in clinical trials, real-world comparisons are limited.

Objectives: To compare treatment completion, adverse events, hospitalizations, and healthcare costs in patients treated with VCZ versus ISA for IA.

Design: Retrospective cohort study using Merative MarketScan claims data (2017-2020).

Methods: Adults (⩾18 years) diagnosed with IA (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes) who received VCZ or ISA monotherapy were included. Treatment completion was defined as ⩾42 days of therapy. Descriptive statistics and logistic regression were used to assess outcomes and predictors of antifungal selection, adverse events, hospitalizations, and treatment completion.

Results: Among 335 patients, 84% (n = 282) received VCZ and 16% (n = 53) received ISA. Baseline characteristics were comparable, although the VCZ group had higher Medicaid enrollment, and the ISA group had more patients with malignancy. Treatment completion rates were comparable (92% each, p = 1), as were median treatment durations (VCZ: 120 days, ISA: 112 days, p = 0.95). Adverse event rates were not significantly different (VCZ: 49%, ISA: 60%, p = 0.18), but CNS-related events occurred more frequently with ISA (16% vs 9%, p = 0.32). VCZ was associated with lower outpatient pharmacy costs (median $1,596.68 vs $11,000.66, p < 0.001) and total hospitalization costs (median $40,681.89 vs $121,545.89, p = 0.01). Malignancy was associated with lower odds of receiving VCZ (OR 0.30, p = 0.001), and younger age predicted higher odds of treatment incompletion (OR 0.97, p = 0.035). Female sex was associated with increased adverse event risk. Notably, VCZ use was not associated with increased adverse events or treatment incompletion.

Conclusion: VCZ was prescribed five times more frequently than ISA for IA, despite similar treatment durations and completion rates. VCZ was associated with lower costs and did not increase the risk of adverse events or treatment discontinuation. These findings suggest that VCZ remains commonly used and potentially more cost-effective treatment option for IA.

Introduction: Skin abscesses are one of the most common infections among people who inject drugs (PWID).

Objective: To examine factors associated with the frequency of abscesses in the previous 3 months among PWID.

Design: We conducted a cross-sectional analysis of baseline data from a prospective longitudinal cohort of PWID.

Methods: Between April 2021 and November 2022, PWID were recruited from community settings in Los Angeles, CA, and Denver, CO. Participants completed an interview covering sociodemographic, drug use, and related risk behaviors. Participants were asked if they had abscesses in the last 3 months. Those reporting "yes" quantified the number of abscesses. Responses were classified as None, 1, or 2 or more. We used bivariate analysis and multi-nominal regression to examine factors associated with the frequency of abscesses.

Results: Among participants (n = 472), 62% reported no abscesses, 16% reported 1 abscess, and 22% reported 2+ abscesses in the last 3 months. Compared to participants with no abscess, 1 abscess was associated with receiving buprenorphine treatment (adjusted odds ratio (AOR) = 3.27; 95% CI = 1.58, 6.78), being injected by another person (AOR = 3.06; 95% CI = 1.72, 5.45), injecting 3+ times a day (as compared to less than daily, AOR = 2.92; 95% CI = 1.28, 6.65), licking syringe prior to injection (AOR = 1.96; 95% CI = 1.03, 3.74), and being Latino (AOR = 0.25; 95% CI = 0.12, 0.54). Having 2+ abscess was associated with daily heroin use (AOR = 2.35; 95% CI = 1.26, 4.39), being injected by another person (AOR = 1.92; 95% CI = 1.16, 3.18), daily methamphetamines use (0.50; 95% CI = 0.30, 0.83) and those reporting 10+ rushed injection (as compared to none, AOR = 1.85, 95% CI = 1.04, 3.29) in the last 3 months.

Conclusion: Our findings underscore a multi-level approach to reducing abscesses in this population. Increased education around safe injection practices, institutional interventions-that is, addressing healthcare stigmatization and expanding clinical harm reduction-as well as structural interventions (safe supply, overdose prevention programs, housing) should be considered.

Background: Influenza is a significant public health challenge, characterized by severe disease progression and considerable societal burden. Patients at high risk of influenza-related complications require special attention in routine clinical practice.

Objectives: This study aimed to compare the effects of antiviral treatments for influenza on the incidence of bacterial complications, adverse events, and disease duration in high-risk outpatients.

Design: Multicenter, non-interventional, observational cohort study.

Methods: The study was conducted during the 2023-2024 influenza epidemic season and included 1867 high-risk outpatients treated with oseltamivir, umifenovir, kagocel, or imidazolyl ethanamide pentanedioic acid.

Results: Bacterial complications occurred in 18.87% (n = 335) of high-risk patients, with 17.41% (n = 309) requiring antibacterial therapy. The hospitalization rate was 1.24% (n = 22), and the average disease duration was 8 days. The incidence of bacterial complications varied among treatment groups: oseltamivir (18.96%, n = 102), umifenovir (12.17%%, n = 51), kagocel (22.00%%, n = 110), and imidazolyl ethanamide pentanedioic acid (22.64%%, n = 72). Adverse events were reported in 4.76% (n = 84) of patients, most commonly gastrointestinal disorders (91.67%, n = 77), followed by allergic reactions (8.33%, n = 7). The incidence of adverse events was significantly higher in the oseltamivir group compared to other treatments.

Conclusion: The etiotropic agents oseltamivir and umifenovir demonstrated comparable efficacy in managing influenza in high-risk patients, as reflected by their impact on bacterial complication rates and disease duration. Both drugs may be recommended for the treatment of high-risk influenza patients.

Background: Hyperuricemia is associated with an elevated risk of cardiovascular diseases (CVD) among people with HIV (PLWH). However, there is a paucity of studies examining the factors associated with hyperuricemia among PLWH in sub-Saharan Africa.

Objective: This study aimed to determine the prevalence and factors associated with hyperuricemia among PLWH at a tertiary hospital in Uganda.

Design: We conducted a cross-sectional study among PLWH receiving antiretroviral therapy (ART) at the HIV clinic at Kiruddu National Referral Hospital in Kampala, Uganda.

Methods: Data were collected using a structured questionnaire, anthropometric and blood pressure measurements, and analysis of fasting blood glucose, blood lipids, glycated hemoglobin, and serum uric acid of blood samples from participants. Modified Poisson regression with robust standard errors was used to assess factors associated with hyperuricemia. Statistical significance was set at p < 0.05 for all analyses.

Results: Among 390 PLWH, the mean (SD) age was 41.4 (12.3) years, and 209 (53.6%) were female. A total of 360 (92.3%) were on dolutegravir-based ART regimens, and 94.7% (306/323) were virally suppressed (viral load < 1000 copies/mL). The prevalence of hyperuricemia was 21.3% (83/390). Current alcohol use (adjusted prevalence ratio (aPR) = 2.07, 95% CI: 1.26, 3.41, p = 0.004) and increased respiratory rate (aPR = 1.09, 95% CI: 1.02, 1.16, p = 0.015) were independently associated with hyperuricemia. Lower oxygen saturation, duration on ART, and increased diastolic blood pressure, triglycerides, weight, BMI, and circumferences (waist, hip, neck, and mid-upper arm) were associated with hyperuricemia at bivariable analysis but lost significance after adjusting for confounders.

Conclusion: One in five PLWH had hyperuricemia in this study. Alcohol use was identified as a potential modifiable risk factor for hyperuricemia. While alcohol cessation programs are needed to mitigate the risk of hyperuricemia, studies should explore the effect of hyperuricemia on lung function among PLWH.

Background: Moderate-risk ampC beta-lactamase-producing Enterobacterales (HECK-Yes organisms) render many beta-lactams ineffective.

Objective: This study evaluates selective reporting (SR) of antimicrobial susceptibility testing (AST) results to improve antibiotic prescribing for these infections.

Design: A retrospective quasi-experimental study evaluating patients before and after the implementation of SR.

Methods: SR of AST results for HECK-Yes organisms was implemented at a 1500-bed medical center. A retrospective study compared antibiotic prescribing before and after implementation in patients with positive blood or respiratory cultures.

Results: Fifty patients were included in both pre- and post-implementation groups with similar baseline characteristics. Post-implementation, appropriate antibiotics within 24 h of AST report increased by 24% (62% pre vs 86% post, p = 0.01). A total of 30-day mortality, clinical success, and microbiological failure rates were similar between groups.

Conclusion: SR improved appropriate antibiotic prescribing for moderate-risk ampC-producing Enterobacterales (e.g., HECK-Yes) infections.

Background: Pseudomonas aeruginosa is known to cause hospital-acquired infections. This bacterium produces β-lactamase enzymes that enzymatically degrade β-lactam drugs, reducing their efficacy.

Objective: The objective of this investigation was to examine the occurrence, susceptibility, and production of various β-lactamases by multidrug-resistant P. aeruginosa (MDR-PA) and to determine the risk factors associated with extensively drug-resistant P. aeruginosa (XDR-PA) and their β-lactamases.

Design: A descriptive cross-sectional study was conducted to investigate the occurrence, susceptibility, and β-lactamase production of MDR-PA and the risk factors associated with XDR-PA. The study involved collecting and analyzing 390 specimens from different 390 participants over a period from August 2021 to April 2023.

Methods: The study utilized standard methodologies to screen and characterize P. aeruginosa. The antimicrobial-resistant patterns and presence of MDR-PA and XDR-PA were determined following standard guidelines supported by the Clinical Laboratory Standards Institute (CLSI) using various methods such as the disk diffusion method and colistin disk elution tests. Combined disk and inhibitor-based tests were used to determine extended-spectrum β-lactamases (ESBL), Metallo-β-lactamases (MBL), and AmpC-β-lactamases (AmpC) using two different methods. Clinical data were extracted from the medical records and patient requisition forms provided by clinicians. Clinical data were extracted for XDR-PA and β-lactamases applying binary logistic regression by adjusting for the confounding factors.

Results: In our study, the antimicrobial-resistant pattern showed significant differences (p < 0.05) in the antibiotic-resistant pattern among β-lactamase and non-β-lactamase. The prevalence of MBL-P. aeruginosa was determined to be 13.5%, while ESBL accounted for 23.8%, and AmpC accounted for 20.5%. Coexistence of MBL + ESBL, ESBL + AmpC, MBL + AmpC, and MBL + ESBL + AmpC was determined to be 5.3%, 2.8%, 2.3%, and 4.1%, respectively. Among the nine assessed risk factors in a multivariate regression model, prolonged hospital stays (odd ratio = 11.2, 95% CI 3.7-33.8) provided substantial risk compared to other risk factors for the colonization of XDR-PA. Similarly, in a multivariate model, previous therapy with immunosuppressant drugs (OR = 6.7, 95% CI 1.5-29.3) was found to be the leading risk factor for the colonization of β-lactamase producers P. aeruginosa.

Conclusion: Identification of XDR-PA and β-lactamases among MDR-PA isolates is crucial to prevent the use of unnecessary antibiotics. Early and prompt diagnosis of drug-resistant pathogens prevents treatment failure and encourages proper antibiotic therapy. Therefore, it is necessary to implement strict po

Staphylococcus aureus bacteremia (SAB) remains a major clinical challenge, with persistently high mortality despite advancements in antimicrobial therapy. The evolving epidemiology of SAB, characterized by a rise in community-acquired infections, increased use of indwelling medical devices, and a growing burden of metastatic complications, adds to its complexity. Given these challenges, adjunctive β-lactam therapy has been proposed as a strategy to enhance bactericidal activity and improve patient outcomes. β-lactams may exert synergistic effects when combined with other antistaphylococcal agents by saturating multiple penicillin-binding proteins and modifying bacterial cell wall structure, thereby increasing susceptibility to host immune responses. Early evidence for adjunctive β-lactam therapy emerged from retrospective studies and incidental observations of "unplanned synergy," which suggested improved bacterial clearance. Subsequent randomized controlled trials have explored this approach, with some demonstrating reductions in bacteremia duration. However, survival benefits have been inconsistent, and concerns regarding acute kidney injury (AKI) have tempered enthusiasm. Recent investigations, however, suggest that judicious β-lactam selection and targeted patient selection can mitigate AKI risk. A limitation of many randomized controlled trials evaluating combination therapy for SAB is the adoption of uniform treatment protocols that fail to account for patient heterogeneity. This approach may limit the generalizability of findings and obscure potential benefits in specific patient subgroups. Conversely, retrospective analyses suggest that high-risk patients, including those with rapid blood culture positivity, inadequate source control, significant comorbidities, and metastatic disease, may derive the greatest benefit from early combination therapy. Optimizing SAB management necessitates a multifaceted strategy that incorporates patient-specific clinical factors, refined risk stratification, and innovative assessment frameworks. Approaches such as the Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) enable holistic evaluations of treatment efficacy and safety, accounting for the overall patient experience. Future research should prioritize individualized treatment strategies, leveraging biomarkers and refined risk stratification to identify patients most likely to benefit from adjunct β-lactam therapy while minimizing adverse events.