Cabotegravir + rilpivirine (CAB + RPV-LA) is a long-acting antiretroviral therapy (ART) that can be utilized for people with human immunodeficiency virus (HIV) who face barriers to daily ART. Here, we describe the implementation of a program that provides low-barrier access to CAB + RPV-LA for people with HIV and opioid use disorder at a syringe exchange.
Background: Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE).
Methods: This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout.
Results: We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers).
Conclusions: Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.
Background: Probiotics have been used to prevent antibiotic-associated diarrhea (AAD), but practical guidelines are sparse. This trial evaluated the efficacy and safety of a high-dose, multistrain probiotic mix (Sinquanon), specially designed for prevention of AAD in adults.
Methods: A phase IV, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over 5 months. Participants receiving broad-spectrum antibiotics were administered the specialized probiotic mix or placebo from the first dose of antibiotics until 14 days after the last antibiotic dose. The primary outcome measure was the incidence of AAD.
Results: In total, 564 participants were randomized (probiotic mix: 285; placebo: 279), of which 9 participants discontinued the trial early (probiotic mix: 3; placebo: 6), had no efficacy data, and were excluded from the efficacy analysis. The 555 remaining participants completed the trial and were included in the efficacy analysis (probiotic mix: 282; placebo: 273). AAD occurred less frequently in the studied probiotic mix versus placebo group (9.2% vs 25.3%, P < .001), resulting in an absolute risk reduction of 16% and a number needed to treat of 6 (95% confidence interval, 4.55-10.49). A significant improvement in the average gastrointestinal quality of life in the studied probiotic mix versus placebo group was also observed. There were no clinically relevant differences in the incidence of adverse events between the studied probiotic mix and the placebo group.
Conclusions: The specially designed high-dose, multistrain probiotic mix (Sinquanon) demonstrated to be beneficial compared with placebo in the prevention of AAD in adults who received broad-spectrum antibiotics.
Clinicaltrialsgov identifier and url: NCT05607056; https://classic.clinicaltrials.gov/ct2/show/NCT05607056.
Antibiotic-associated diarrhea (AAD) frequently complicates treatment of infections. A recent randomized, double-blind, placebo-controlled trial tested a proprietary probiotic mixture and found that it reduced the incidence of AAD by 16%. This is encouraging for patients, but future progress on probiotics for AAD and other conditions depends on transparency around strain selection, probiotic design guided by preclinical mechanistic studies, and rigorously conducted human studies.
Background: Cefiderocol is the first antibiotic with effluent flow rate-based dosing recommendations outlined in the product label for patients receiving continuous renal replacement therapy (CRRT). We aimed to investigate the population pharmacokinetics of cefiderocol among patients receiving CRRT and validate these dosing recommendations.
Methods: A multicenter, prospective cefiderocol pharmacokinetic study among intensive care unit patients receiving CRRT was conducted (2022-2023). Blood sampling was performed at steady-state and cefiderocol concentrations were assayed by validated liquid chromatography-tandem mass spectrometry. Population pharmacokinetic analyses were conducted in Pmetrics using R software. The free time above the minimum inhibitory concentration (f T > MIC) and total daily area under the concentration time curve (AUCdaily) were calculated.
Results: Fourteen patients with effluent flow rates ranging from 2.1 to 5.1 L/h were enrolled. Cefiderocol concentrations best fitted a 2-compartment model. Mean ± standard deviation (SD) parameter estimates for clearance, central compartment volume, and intercompartment transfer constants (k12 and k21) were 3.5 ± 1.5 L/hour, 10.7 ± 8.4 L, 3.9 ± 1.8 hours-1, and 2.2 ± 2.2 hours-1, respectively. With simulations based on product label dosing recommendations, all patients achieved 100% fT > MIC up to MIC 8 mg/L with an AUCdaily (mean ± SD) of 1444 ± 423 mg × hour/L. Cefiderocol was well tolerated among the 14 patients.
Conclusions: The current package insert dosing recommendations resulted in pharmacodynamically optimized cefiderocol exposures. Cefiderocol concentrations exceeded relevant MIC breakpoints in all patients at each effluent flow rate, and AUCdaily was within the range observed in patients in the phase 3 clinical trials, suggestive of a safe and therapeutic drug profile.
Background: The 2023 "International Working Group on the Diabetic Foot/Infectious Disease Society of America Guidelines on the Diagnosis and Treatment of Diabetes-Related Foot Infections" (DFIs) provides recommendations for Pseudomonas coverage based on the climate region.
Methods: This was a retrospective national study of veterans between 1/1/2010 and 3/23/2024 with diabetes mellitus and a culture below the malleolus wound. Prevalence of Pseudomonas was categorized based on climate zones according to the International Energy Conservation Code. Multivariable logistic regression was used to determine odds ratios and 97.5% CIs.
Results: The prevalence of Pseudomonas significantly varied between US climates. Pseudomonas was most prevalent within the Hot Humid climate, where it was isolated in 11.6% of DFI cultures. Pseudomonas was least prevalent within the Very Cold climate, where it was isolated in 6.2% of cultures. In the multivariable logistic regression model, hot and humid climates were associated with an odds of P. aeruginosa of 1.92 (97.5% CI, 1.69-2.20), a hot, dry climate was associated with an odds of 1.65 (97.5% CI, 1.44-1.90), and a humid climate was associated with an odds of 1.65 (97.5% CI, 1.45-1.89). A lower Charlson Comorbidity Index, inpatient admission, recent antipseudomonal antibiotic use, and swabs were less likely to have Pseudomonas. Recent admission increased the odds of P. aeruginosa (odds ratio [OR], 1.34; 97.5% CI, 1.27-1.41). History of P. aeruginosa was associated with an increase in P. aeruginosa (OR, 8.90; 97.5% CI, 8.29-9.56).
Conclusions: The prevalence of DFI organisms varies within different US climates. Utilization of local climate information may allow for more accurate and targeted empiric antibiotic selection when treating DFIs.
Background: Current vancomycin monitoring guidelines recommend monitoring 24-hour area under the concentration-time curve (AUC) to minimum inhibitory concentration ratios for patients with serious methicillin-resistant Staphylococcus aureus infections. However, there are sparse data on the safety, feasibility, and efficacy of vancomycin AUC monitoring for outpatients. Traditional AUC pharmacokinetic calculations require 2 concentrations, while bayesian software allows for single-concentration AUC estimations.
Methods: We conducted a single-center, quasi-experimental, interrupted time series study of patients enrolled in the outpatient parenteral antimicrobial therapy program at our institution for vancomycin management. Our institution implemented a pharmacist-driven vancomycin AUC monitoring program from September 2019 to February 2020, and again from September 2022 to March 2023. Patients enrolled underwent vancomycin monitoring using an AUC goal of 400-600 mg⋅h/L, estimated through bayesian modeling. Patients enrolled in the outpatient parenteral antimicrobial therapy program from July 2021 through August 2022 for trough-based monitoring were used for comparison. The primary outcome was nephrotoxicity incidence, defined as a serum creatinine increase by ≥0.5 mg/dL or ≥50% during outpatient vancomycin therapy.
Results: We enrolled 63 patients in the AUC group and 60 patients in the trough-based group. Nephrotoxicity was significantly lower in the AUC cohort (6.3% vs 23.3%; P = .01). The number of unusable vancomycin concentrations was also significantly lower in the AUC cohort (0% vs 6%; P < .01). There was no difference in composite 90-day all-cause mortality or readmission (33.3% vs 38.3%; P = .56).
Conclusions: Following implementation of a pharmacist-driven AUC monitoring program, patients were less likely to develop nephrotoxicity during outpatient vancomycin therapy.
Background: The efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) have been demonstrated in treatment-naive clinical trials. However, real-world evidence for this regimen in late-presenting patients with HIV-1 (PWH) is lacking. We investigated the virologic and safety outcomes of BIC/FTC/TAF in late-presenting PWH.
Methods: This retrospective cohort analysis consisted of late-presenting PWH who initiated an antiretroviral regimen of BIC/FTC/TAF between June 2021 and June 2023. Treatment effectiveness, defined as HIV-1 RNA <50 copies/mL, was analyzed. Changes in immunologic, metabolic, liver, and renal parameters were evaluated. Late-presenting PWH were defined as surviving PWH with CD4 <200 cells/μL or surviving patients who met the criteria for AIDS-defining conditions with a CD4 ranging from 200 to 499 cells/μL.
Results: A total of 130 participants were included in the study. At week 48, 93.8% (122/130) of the patients achieved HIV-1 RNA levels <50 copies/mL. CD4 increased by 150.0 cells/μL, and CD4/CD8 increased by 0.16 (P < .001). Sixteen (12.3%) participants experienced adverse events, and 6 (4.6%) experienced drug-related adverse events. None of the participants discontinued treatment due to either a lack of effectiveness or adverse events.
Conclusions: BIC/FTC/TAF demonstrated robust virologic suppression and tolerability in patients presenting late in the course of HIV infection.
Background: Artemether-lumefantrine is the most widely used treatment for uncomplicated malaria and it is dosed based on weight bands according to World Health Organization (WHO) guidelines. However, children are vulnerable to underdosing. Inadequate dosing can lead to treatment failure and drug resistance.
Methods: Nutritional parameters for 372 363 children <5 years old in 25 high-malaria-burden countries were acquired from the Demographic and Health Surveys program. Prevalence of attaining day 7 lumefantrine concentrations ≥200 ng/mL and remaining reinfection free for 42 days were evaluated using a simulation-based approach with a population pharmacokinetic-pharmacodynamic model. Besides the WHO-recommended lumefantrine dosing regimen (twice daily for 3 days), we explored 3 adjusted regimens: extended (2 extra days of dosing), increased (1 extra 120-mg tablet per dose), and intensified (thrice daily for 3 days). We also explored an alternative method dosing malnourished children based on expected weight for age.
Results: We estimated that 75% of children reached the 200 ng/mL lumefantrine threshold and 77% were malaria free for 42 days when using WHO treatment guidelines. By switching to the alternative dosing method, 5% more children achieved target lumefantrine levels; 22% more achieved the target using the alternative dosing and the extended regimen. With combined alternative plus extended dosing, 97% of children reached 200 ng/mL lumefantrine and 88% were malaria free for 42 days.
Conclusions: This study highlights the inadequacies of weight-based lumefantrine dosing for young and underweight children and supports the need of clinical trials using extended dosing based on expected weight in malnourished children.
The SIMPL'HIV study investigated whether switching to dolutegravir (DTG) + emtricitabine (FTC) was noninferior to continuing combined antiretroviral therapy for maintaining HIV-1 suppression at 144 weeks. The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between groups, confirming DTG + FTC's safety and efficacy for long-term management of HIV-1 infection.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：