Annals of Pharmacotherapy最新文献

Background: Orthotopic liver transplant (OLT) carries a risk for invasive fungal infections (IFI). A targeted antifungal prophylaxis protocol can identify OLT patients who warrant antifungal prophylaxis. The optimal protocol and appropriate risk factors have yet to be confirmed.

Objective: This study aimed to describe the impact of a targeted antifungal prophylaxis protocol post OLT on rates of IFI and protocol adherence.

Methods: This was a retrospective observational cohort study of patients ≥18 years old with an OLT at Cleveland Clinic. Pre-protocol was defined as June 1, 2019 to May 31, 2020 and post-protocol was June 1, 2021 to May 31, 2022. The primary objective was to determine adherence to the prophylaxis protocol on postoperative day (POD) 0. Secondary objectives included comparing the 90-day incidence of proven or probable IFI post-OLT between groups.

Results: The pre-protocol group included 134 patients, whereas the post-protocol group included 166. Prior to protocol implementation, 73% received clotrimazole, 13% fluconazole, 13% micafungin, and 1% nystatin. After protocol implementation, 63% received clotrimazole, 16% fluconazole, and 21% micafungin. Adherence to the protocol was 66% on POD0 and increased to 84% over the duration of prophylaxis. Rates of IFI development decreased to 3.6% after implementation from 6.7% prior to the protocol (P = 0.22). Median time to IFI was 8 days (interquartile range [IQR] = 2-19) pre-protocol and 15 days (IQR = 6-17) post-protocol.

Conclusions and relevance: The implementation of a post-OLT-targeted antifungal prophylaxis protocol can promote consistency in antifungal prophylaxis. This study showed an 84% adherence rate to the implemented protocol, with numerically lower rates of IFIs post-protocol compared with pre-protocol.

Objective: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP).

Data sources: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023.

Study selection and data extraction: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included.

Data synthesis: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab.

Relevance to patient care and clinical practice in comparison to existing drugs: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents.

Conclusion: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

Background: Poor adherence to lipid-lowering drugs in diabetic patients with dyslipidemia increases has been linked with an increased cardiovascular risk. A better understanding of the determinants of adherence to lipid-lowering drugs and treatment satisfaction among people with diabetes and dyslipidemia is crucial.

Objective: We aimed to assess the prevalence of adherence to lipid-lowering drugs, identify its determinant factors, and evaluate treatment satisfaction among users of lipid-lowering drugs who have diabetes and dyslipidemia.

Methods: We surveyed 398 adult patients with diabetes and dyslipidemia, using a validated medication adherence survey (Adherence to Refills and Medications Scale) and a validated treatment satisfaction survey (Treatment Satisfaction Questionnaire for Medication, TSQM). Sociodemographic and medical history data were collected through questionnaires.

Results: The prevalence of poor medication adherence was 36%. Factors associated with poor adherence included adverse reactions to medications, lack of medication availability, and lack of family support. Adherent patients reported lower low-density lipoprotein-cholesterol (LDL-C) and total cholesterol levels, higher treatment satisfaction, and a higher prevalence of cardiovascular disease and comorbidities. Having a family history of dyslipidemia was negatively associated with adherence, while the number of comorbidities positively influenced it. The scores of TSQM components such as effectiveness, global satisfaction, and convenience were significantly higher in people who were adherent or achieved the LDL-C target.

Conclusion and relevance: Our findings highlight the need for interventions targeting several factors impacting adherence to lipid-lowering drugs in patients with diabetes and dyslipidemia. Managing adverse effects, leveraging family support, and ensuring medication access represent crucial aspects of improving adherence and potentially mitigating cardiovascular risks in this high-risk population.

Objective: To review the literature leading to the Food and Drug Administration (FDA) approval of the first medication, resmetirom, for the treatment of nonalcoholic steatohepatitis (NASH), including the pharmacology, pharmacokinetics, clinical studies, dosing, and adverse effects. Relevant data will be used to discuss how resmetirom impacts clinical practice.

Data sources: A literature search was conducted using MEDLINE from database inception to May 12, 2024. Keywords included non-alcoholic steatohepatitis, nonalcoholic fatty liver disease, and resmetirom. Study selection, data extraction and all English-language studies involving the use of resmetirom for nonalcoholic fatty liver disease (NAFLD)/NASH were included.

Data synthesis: Resmetirom, a thyroid hormone receptor agonist, is administered at daily doses of either 80 mg or 100 mg. The drug was shown to provide NASH resolution as assessed by the NAFLD activity score, 80 mg-24.2%, 100 mg-25.9% compared to 14.2% with the placebo group (P < 0.001). Resmetirom, improved liver fibrosis, 80 mg-25.9%, 100 mg-29.9% compared to 9.7% with the placebo group (P < 0.001). Resmetirom's ability to improve fibrosis in patients with F2-F3 fibrosis offers valuable benefit for patients at risk of progressing to cirrhosis.

Relevance to patient care and clinical practice: Resmetirom expands the medication options available to treat patients with NASH which can be given alongside other medications to optimize metabolic factors such as glucagon-like peptide-1 and hydroxymethylglutaryl-coenzyme A reductase inhibitors. Resmetirom was well tolerated in studies.

Conclusion: Resmetirom serves as an attractive option in patients diagnosed with NASH with evidence of advanced fibrosis (F2-F3) in combination with exercise, diet, and other multimodal therapies targeting metabolic risk factors.

Background: Intravenous (IV) antibiotics have historically been considered standard of care for treatment of bloodstream infections (BSIs). Recent literature has shown sequential oral (PO) therapy to be noninferior to IV antibiotics for certain pathogens and disease states. However, a gap exists in the literature for BSI caused by Enterococcus faecalis.

Objective: To compare outcomes of definitive sequential PO therapy to definitive IV therapy in patients with E faecalis BSI.

Methods: Multicenter, retrospective, matched cohort study of adult patients with at least one blood culture positive for E faecalis from January 2017 to November 2022. Patients with polymicrobial BSI, concomitant infections requiring prolonged IV antibiotic therapy, those who did not receive antibiotic therapy, and those who died within 72 hours of index culture were excluded. Subjects were matched based on source of infection in a 2:1 (IV:PO) ratio. The primary outcome was a composite of all-cause mortality and treatment failure. Secondary outcomes included hospital length of stay (LOS), antibiotic duration, and 30-day readmission rate.

Results: Of the 186 patients who met criteria for inclusion, there was no statistically significant difference in the primary composite outcome for PO compared to IV therapy (14.5% vs 21.8%; OR 0.53 [0.23-1.25]) or 30-day readmission (17.5% vs 29%; OR 0.53 [0.25-1.13]). Hospital LOS was significantly longer in patients receiving IV-only therapy (6 days vs 14 days; P < 0.001).

Conclusion and relevance: Sequential oral therapy for E faecalis BSI had similar outcomes compared to IV-only treatment and may be considered in eligible patients.

Background: Owing to increasing local Escherichia coli resistance and current guidelines for the treatment of acute pyelonephritis (APN) over 14 years old, an evaluation of local prescribing patterns is warranted.

Objective: The purpose of this study was to evaluate local prescribing patterns and appropriateness of antibiotics in acute uncomplicated APN.

Methods: This is a retrospective cohort study of female patients aged 18 to 89 years diagnosed with APN and positive urine culture growing E. coli. Exclusion criteria included pregnancy, immunocompromised status, and complicated urinary tract infections. Outcomes included antibiotic appropriateness and its effects on hospital admission, hospital length of stay, and 30-day readmission.

Results: Between 2017 and 2022, 308 female patients were diagnosed with APN and had positive urine cultures, with 104 seen only in the emergency department (ED) and 109 admitted to the hospital. Patients seen in the ED had a significant increase in E. coli resistance to discharge antibiotics (12.5% vs 2.8%, P = 0.0070). In those patients discharged on antibiotics resistant to E. coli, significantly more patients returned to the ED in 30 days (31.3% vs 10.7%, P = 0.0155).

Conclusion and relevance: Patients seen only in the ED were more likely to have resistant organisms to discharge antibiotics compared with those admitted to the hospital. Patients discharged on antibiotics resistant to E. coli had a 3-fold increase in returning to the ED within 30 days regardless of admitted location. Follow-up of all cultures should be performed, and patients resistant to discharge antibiotics should be contacted and antibiotic regimens changed.

Background: Piperacillin/tazobactam (PIPC/TAZ), which is a combination of a beta-lactam/beta-lactamase inhibitor, often causes liver enzyme abnormalities. The albumin-bilirubin (ALBI) score is a simple index that uses the serum albumin and total bilirubin levels for estimating hepatic functional reserve. Although patients with low hepatic reserve may be at high risk for drug-induced liver enzyme abnormalities, the relationship between PIPC/TAZ-induced abnormal liver enzymes levels and the ALBI score remains unknown.

Objective: This study aimed to elucidate the relationship between PIPC/TAZ-induced abnormal liver enzyme levels and the ALBI score.

Methods: This single-center retrospective case-control study included 335 patients. The primary outcome was PIPC/TAZ-induced abnormal liver enzyme levels. We performed COX regression analysis with male gender, age (≥75 years), alanine aminotransferase level (≥20 IU/L), and ALBI score (≥-2.00) as explanatory factors. To investigate the influence of the ALBI score on the development of abnormal liver enzyme levels, 1:1 propensity score matching between the ≤-2.00 and ≥-2.00 ALBI score groups was performed using the risk factors for drug-induced abnormal liver enzyme levels.

Results: The incidence of abnormal liver enzyme levels was 14.0% (47/335). COX regression analysis revealed that an ALBI score ≥-2.00 was an independent risk factor for PIPC/TAZ-induced abnormal liver enzyme levels (adjusted hazard ratio: 3.08, 95% coefficient interval: 1.207-7.835, P = 0.019). After 1:1 propensity score matching, the Kaplan-Meier curve revealed that the cumulative risk for PIPC/TAZ-induced abnormal liver enzyme levels was significantly higher in the ALBI score ≥-2.00 group (n = 76) than in the <-2.00 group (n = 76) (P = 0.033).

Conclusion and relevance: An ALBI score ≥-2.00 may predict the development of PIPC/TAZ-induced abnormal liver enzyme levels. Therefore, frequent monitoring of liver enzymes should be conducted to minimize the risk of severe PIPC/TAZ-induced abnormal liver enzyme levels in patients with low hepatic functional reserve.