Annals of Pharmacotherapy最新文献

Background: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.

Objective: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.

Methods: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.

Results: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.

Conclusion and relevance: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

Background: Fixed-rate infusions of weight-based neuromuscular blocking agents (NMBAs) were adopted during the COVID pandemic to limit caregiver exposure during titrations. Although fixed-rate infusions are supported in studies of acute respiratory distress syndrome (ARDS), the optimal scalar for weight-based NMBAs in patients with obesity remains controversial.

Objective: This study sought to compare change in oxygenation using two weight-based dosing strategies for atracurium in obese patients with ARDS. Secondary outcomes included total atracurium dose, mortality, and intensive care unit (ICU) and ventilator-free days.

Methods: Following an institutional practice update to use ideal body weight (IBW) for patients with obesity, we retrospectively compared adults (≥18 years) with ARDS and a body mass index (BMI) ≥ 30 kg/m² who received atracurium (15 µg/kg/min) based on actual body weight (ABW) with those using IBW. The primary outcome was change in PaO₂/FiO₂ ratio (P/F) 48 hours after atracurium initiation. Analysis-of-covariance compared change in P/F between groups after adjustment for confounders.

Results: The IBW group (n = 123), compared with the ABW group (n = 133), had lower baseline P/F (85.0 [71.0, 118.3] vs 93.3 [76.0, 128.3], P = 0.025) and sequential organ failure assessment (SOFA) score (9.7 ± 2.6 vs 10.5 ± 2.6, P = 0.015), with greater use of steroids (96% vs 89%, P = 0.032) and prone positioning (72% vs 58%, P = 0.015). No difference was detected in change in P/F at 48 hours (adjusted least squares mean [95% confidence interval, CI]: 55.8 [37.0, 74.5] vs 56.9 [39.6, 74.1], P = 0.90). Atracurium doses were higher in the ABW group (97.4 mg/h [84.4, 110.3] vs 55.4 [47.2, 65.7], P < 0.001). There was no difference in hospital mortality, ICU mortality, and ICU-free days or ventilator-free days.

Conclusion and relevance: In patients with obesity with ARDS receiving fixed-rate atracurium infusions, the change in P/F at 48 hours did not differ based on weight. Atracurium dosed on IBW may use less total drug without compromising ability to improve oxygenation. This is the first study comparing the dosing weight used for continuous infusion atracurium in hospitalized, critically ill ARDS patients with obesity. Additional studies are warranted to optimize dosing in obese patients.

Objective: This article reviews the published data encompassing the development, pharmacology, efficacy, and safety of travoprost, intracameral implant, a treatment for reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension.

Data sources: A literature search was conducted from drug discovery until September 2024 through PubMed, MEDLINE, and National Institutes of Health Clinical Trials Registry utilizing the following search terms: iDose, travoprost, intracameral implant, OTX-TIC, open-angle glaucoma, and ocular hypertension.

Study selection and data extraction: All relevant English-language studies, or studies that could be appropriately translated into English, containing the pharmacology, pharmacokinetics, safety, and efficacy of travoprost intracameral implant were selected for review.

Data synthesis: Travoprost implants showed significant reductions in IOP compared with other treatment options with fewer limitations often associated with topical medications resulting in travoprost implant patients favoring reduced concomitant use of topical IOP-lowering medications (with 81% of patients being medication free).

Relevance to patient care and clinical practice in comparison with existing drugs: Due to limited compliance with topical treatment modalities, the travoprost implant presents a promising alternative pathway for drug delivery. With a duration of 3 years and removal of the need for patient dexterity and application compliance, the travoprost implant serves an unmet need for patients and prescribers.

Conclusion: Travoprost intracameral implant is a safe and effective delivery system for intracameral travoprost administration for patients with OAG or ocular hypertension.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic agent for Pneumocystis jiroveci pneumonia (PJP) and toxoplasmosis after solid organ transplant (SOT). Compared with other agents, it has additional activity against Nocardia species.

Objective: The purpose of this study was to evaluate the incidence of Nocardia infection in SOT patients receiving TMP-SMX or an alternative agent for opportunistic infection (OI) prophylaxis.

Methods: This retrospective analysis included transplant recipients at a large urban medical center over a period of 4 years. All patients received either TMP-SMX or an alternative agent for PJP prophylaxis. The primary outcome was the incidence of Nocardia infection within 24 months posttransplant. Secondary outcomes included resistance rates of Nocardia isolates, usage rates of alternative prophylactic agents, reasons for using alternative agents, and rate of conversion from an alternative agent back to TMP-SMX.

Results: A total of 791 adult SOT recipients who received PJP or toxoplasmosis prophylaxis were included. Mean age at transplantation was 60.9 years with the majority of patients being male (67.3%) lung transplant recipients (63.6%). TMP-SMX was the most commonly used initial prophylactic agent (84.6%), followed by atovaquone (15.4%). Of the 791 SOT recipients, 16 (2.0%) were diagnosed with nocardiosis within 24 months posttransplant. Patients receiving alternative agents had a higher incidence of infection compared with those receiving TMP-SMX prophylaxis (P < 0.001).

Conclusion and relevance: Our findings suggest that OI prophylaxis with TMP-SMX may be protective against nocardiosis in SOT recipients. If possible, patients who are switched to an alternative agent due to TMP-SMX intolerance should be re-challenged when the adverse effect resolves. Most patients in our study were able to tolerate re-initiation, suggesting that the adverse effects associated with TMP-SMX may be temporary and may not warrant discontinuation.

Objective: The objective was to review the pharmacology, efficacy, and safety of intravenous ceftobiprole in the treatment of bloodstream infections, acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP).

Data sources: PubMed and ClinicalTrials.gov were searched using the following terms: ceftobiprole, ceftobiprole medocaril, ceftobiprole medocaril sodium, Zevtera, and BAL5788.

Study selection and data extraction: Articles published in English between January 1985 and August 15, 2024, related to pharmacology, safety, efficacy, and clinical trials were reviewed.

Data synthesis: Ceftobiprole has shown similar efficacy to comparator antibiotics in CAP, ABSSSIs, and bloodstream infections. Overall treatment success in patients with bacteremia was 69.8% and 68.7%; 91.3% and 88.1% with ABSSSIs and 86.6% and 87.4% with CAP in ceftobiprole and comparator groups, respectively. Finally, in the management of HAP and VAP, ceftobiprole was inferior in the VAP population. Ceftobiprole had a favorable safety profile with gastrointestinal adverse effects occurring more frequently than comparators.

Relevance to patient care and clinical practice in comparison to existing drugs: Clinicians have limited options to treat multidrug-resistant infections. Ceftobiprole has demonstrated efficacy against causative pathogens in specific infections including methicillin-resistant Staphylococcus aureus bacteremia (SAB), ABSSSI, and CAP and may be considered a viable alternative. However, ceftobiprole's impact on HAP, VAP, and febrile neutropenia needs to be further delineated.

Conclusion: Ceftobiprole's broad-spectrum activity makes it a viable option for treating patients hospitalized with CAP, ABSSSI, and SAB. Further studies are needed in severely ill HAP or VAP, febrile neutropenia, and pediatric patients.

Objective: To review the evidence and discuss use of pivmecillinam in uncomplicated acute cystitis.

Data sources: A literature search was conducted utilizing PubMed (from 2000 through August 2024) and ClinicalTrials.gov. Medical Subject Headings (MeSH) terms, such as mecillinam or pivmecillinam and urinary tract infections, were utilized. Additional references were identified by reviewing literature citations.

Study selection and data extraction: Articles were limited to English language publications evaluating the efficacy or safety of pivmecillinam for urinary tract infections (UTIs) in adult populations.

Data synthesis: Data from 6 randomized controlled trials support pivmecillinam for acute uncomplicated cystitis at doses of 200 to 400 mg 3 times daily for 3 to 7 days, with more consistent clinical and bacteriologic cure observed with 400 mg doses and longer therapy durations. Clinical evaluation of 400 mg 2 to 3 times daily is available with use more common in non-US Food and Drug Administration (FDA)-approved populations, such as men, pregnancy, and multidrug resistant infections. There are limited data supporting pivmecillinam for pyelonephritis; routine use is cautioned until further clinical data are available.

Relevance to patient care and clinical practice in comparison with existing drugs: As resistance to first-line antimicrobials rises, the need for safe and effective treatment options remains high. Pivmecillinam represents a new therapeutic option available in the United States for outpatient management of uncomplicated acute cystitis.

Conclusion: Pivmecillinam could be a key agent for uncomplicated acute cystitis. Utilization will likely be cost driven, but the promise of low resistance encourages the place in therapy when other agents are not susceptible to infecting uropathogens.