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1.
Infect Control Hosp Epidemiol ; : 1-7, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39387193

RESUMO

BACKGROUND: Reducing rehospitalization has been a primary focus of hospitals and payors. Recurrence of Clostridioides difficile infection (CDI) is common and often results in rehospitalization. Factors that influence rehospitalization for CDI are not well understood. OBJECTIVE: To determine the risk factors that influence rehospitalization caused by CDI. DESIGN: A retrospective cohort study from January 1, 2018, to December 31, 2018, of patients aged ≥18 who tested positive for C. difficile while hospitalized. SETTING: Academic hospital. METHODS: The risk of rehospitalization was assessed across exposures during and after the index hospitalization using a Cox proportional hazards model. The primary outcome of this study was 60-day CDI-related rehospitalization. RESULTS: There were 559 hospitalized patients with a positive CD test during the study period, and 408 patients were included for analysis. All-cause rehospitalization was 46.1% within 60 days of the index hospital discharge. Within 60 days of discharge, 68 patients developed CDI, of which 72.5% (49 of 68) were rehospitalized specifically for the management of CDI. The risk of rehospitalization in patients with CDI was higher among patients who were exposed to systemic antibiotics ([adjusted hazard ratio] aHR: 2.78; 95% CI, 1.36-5.64) and lower among patients who had post-discharge follow-up addressing C. difficile (aHR: 0.53; 95% CI, 0.28-0.98). CONCLUSIONS: Exposure to systemic antibiotics increased the risk of rehospitalization due to CDI, while post-discharge follow-up decreased the risk of rehospitalization due to CDI. Comprehensive transitions of care for hospitalized patients with C. difficile may reduce the risk of CDI-related rehospitalization.

2.
Drugs Context ; 132024.
Artigo em Inglês | MEDLINE | ID: mdl-38770371

RESUMO

Background: Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as first-line treatment in 2017. Reported national surveillance data in the USA estimated INSTI-R to be 6.3% as of 2018. This article aims to describe estimated prevalence of INSTI-R within a single clinic network in Chicago, IL, USA, and identify risk factors for resistance and virological failure (VF). Methods: This was a retrospective, single-centre study of adults with HIV starting an INSTI-containing regimen between September 2017 and 2020. The primary endpoint was the difference in INSTI-R of the sample population compared with the national prevalence. Other outcomes included VF and documented INSTI-R mutations. Results: Of 948 participants screened, 321 were included. Eight people had baseline INSTI-R testing results available, of which five had INSTI-R at baseline for an estimated prevalence of 1.6%. This estimation was significantly less than the national estimated prevalence of 6.3% (p<0.001). VF occurred in 26 (7.8%) individuals. Because no participants acquired INSTI-R during the study period, investigators were unable to identify risk factors associated with the development of INSTI-R. People with high pre-treatment viral loads had 1.21 (95% CI 1.05-1.39) higher odds of VF. Conclusions: Amongst participants on INSTI-containing regimens, INSTI-R rates were estimated to be lower than the estimated national prevalence. Detectable pre-switch viral loads were more associated with VF than undetectable viral loads.

3.
Antibiotics (Basel) ; 13(5)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38786164

RESUMO

Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.

4.
Am J Health Syst Pharm ; 81(15): e402-e411, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38470061

RESUMO

PURPOSE: To review the composition, preparation, proposed mechanism of action, safety, efficacy, and current place in therapy of Rebyota (fecal microbiota, live-jslm). SUMMARY: As the first agent in a new class of drugs, live biotherapeutic products (LBPs), fecal microbiota, live-jslm offers another therapeutic approach for the prevention of recurrent Clostridioides difficile infection (rCDI). LBPs are given following antibiotic therapy for C. difficile to reintroduce certain bacteria present in the normal microbiome, as a means to reconstitute the microbiome of infected individuals. This review provides a summary of phase 2 and 3 clinical trials, product information, discussion of data limitations, and recommendations for place in therapy. High efficacy rates compared to placebo with sustained response up to 24 months after administration have been reported. The majority of adverse events identified were mild to moderate without significant safety signals. CONCLUSION: Fecal microbiota, live-jslm has consistently been shown in randomized trials to be safe and effective in reducing rCDI. Its approval marks the culmination of decades of work to identify, characterize, and refine the intestinal microbiome to create pharmaceutical products.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Transplante de Microbiota Fecal , Humanos , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/microbiologia , Transplante de Microbiota Fecal/métodos , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/efeitos dos fármacos , Fezes/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Recidiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária/métodos
5.
HIV AIDS (Auckl) ; 15: 705-711, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38050483

RESUMO

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet antiretroviral therapy regimen. B/F/TAF has become a popular treatment choice because of its small tablet size, high barrier to resistance, favorable tolerability, and limited drug-drug interaction profile. Continued research on B/F/TAF has revealed additional potential for this regimen. This review presents recent literature supporting the use of B/F/TAF as an option for consolidating therapy and maintaining virologic suppression in individuals despite M184V/I mutations. Additionally, children are a unique patient population with limited antiviral options. Standard dose B/F/TAF has demonstrated similar drug exposure in children and adolescents as adults, and low-dose B/F/TAF is approved for children living with HIV greater than two years of age and weighing at least 14 kg. Data supporting this recommendation is described in this review. Finally, despite a lack of prospective data, B/F/TAF may have a role in the future of pre- and post-exposure prophylaxis. This review discusses these discoveries and the continued exploration of the hidden potential of B/F/TAF.

6.
Anaerobe ; 84: 102788, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37931679

RESUMO

Among 23 patients with multiply recurrent Clostridioides difficile infection (mrCDI) who received bezlotoxumab at the end of antibiotic treatment a sustained clinical response of 91 % at 30 days and 78 % at 90 days was achieved. Bezlotoxumab administered at the end of antibiotic treatment was effective in patients with mrCDI.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Recidiva , Antibacterianos/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/prevenção & controle
7.
J Pharm Pract ; : 8971900231167929, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37018738

RESUMO

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed.

8.
Pharmacotherapy ; 43(4): 305-320, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36938645

RESUMO

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Feminino , Humanos , Estados Unidos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Emtricitabina/uso terapêutico
9.
Drugs Context ; 122023.
Artigo em Inglês | MEDLINE | ID: mdl-36843620

RESUMO

Antimicrobial stewardship programmes in the outpatient setting have recently become an area of focus in an effort to improve antimicrobial prescribing. The Centers for Disease Control and Prevention and The Joint Commission have recently addressed this concern and provided a framework for the implementation of an outpatient stewardship programme. This manuscript offers detailed guidance on how to design and implement an outpatient antimicrobial stewardship programme and reviews the literature on current strategies. Challenges related to initiating and maintaining outpatient stewardship efforts are also discussed. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

10.
J Clin Pharm Ther ; 47(10): 1720-1724, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36059105

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Antiretrovirals have a high drug interaction potential, which can lead to increased toxicity and/or decreased efficacy. Multiple databases are available to assess drug-drug interactions. The aim of our study was to compare interaction identification for commonly used ARVs and concomitant medications between six different online drug-drug interaction databases. COMMENT: This was a cross-sectional review using each of the following six databases: LexiComp®, Clinical Pharmacology®, Micromedex®, Epocrates®, University of Liverpool, and University of Toronto. Sixteen antiretroviral drugs and 100 of the DrugStats Database "Top 200 of 2019" list of medications were included. Each of the six databases identified a different number of actual or potential interactions. The number of interactions ranged from 211 to 283. WHAT IS NEW AND CONCLUSIONS: A variety of databases exist with inconsistent identification of actual or potential drug-drug interactions amongst them. It may be beneficial to cross-reference multiple databases prior to making decisions regarding patient care.


Assuntos
Antirretrovirais , Infecções por HIV , Antirretrovirais/efeitos adversos , Estudos Transversais , Bases de Dados Factuais , Interações Medicamentosas , Infecções por HIV/tratamento farmacológico , Humanos
11.
Expert Opin Drug Metab Toxicol ; 18(4): 245-259, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35594628

RESUMO

INTRODUCTION: Cefiderocol is a siderophore cephalosporin antibiotic and first of its kind approved by the Food and Drug Administration for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years or older caused by susceptible organisms. Cefiderocol's unique mechanism of iron chelation improves Gram-negative membrane penetration as the bacteria's iron uptake mechanism recognizes the chelated iron antibiotic and iron for entry. This also allows for the evasion of cefiderocol from cell entry-related resistance mechanisms. AREAS COVERED: This review covers the mechanism of action, resistance mechanisms, pharmacokinetics in various patient populations, and pharmacodynamics. Relevant literature evaluating efficacy and safety are discussed. EXPERT OPINION: Limited treatment options are available for the treatment of carbapenem-resistantorganisms. Clinical trials have demonstrated that cefiderocol is no worse than alternative treatment options for cUTIs and HABP/VABP, but more data are currently available to support the use of beta-lactam beta-lactamase inhibitor agents, where susceptible. Mortality differences demonstrated in patients with pneumonia and bloodstream infections must further be explored and logistical and practical considerations regarding susceptibility testing and use as monotherapy vs. combination therapy must be considered prior to confidently recommending cefiderocol for regular use in systemic infections.


Assuntos
Cefalosporinas , Infecções por Bactérias Gram-Negativas , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Ferro/farmacologia , Ferro/uso terapêutico , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases/farmacologia , Cefiderocol
13.
Clin Pharmacokinet ; 61(1): 17-46, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34651282

RESUMO

A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies comparing plasma and ELF concentrations of antibacterial agents have been published and are summarized in this review. The majority of the studies included in this review determined ELF concentrations of antibacterial agents using bronchoscopy and bronchoalveolar lavage, and this review focuses on intrapulmonary penetration ratios determined with area under the concentration-time curve from healthy human adult studies or pharmacokinetic modeling of various antibacterial agents. If available, pharmacokinetic/pharmacodynamic parameters determined from preclinical murine infection models that evaluated ELF concentrations are also provided. There are also a limited number of recently published investigations of intrapulmonary penetration in critically ill patients with lower respiratory tract infections, where greater variability in ELF concentrations may exist. The significance of these changes may impact the intrapulmonary penetration in the setting of infection, and further studies relating ELF concentrations to clinical response are needed. Phase I drug development programs now include assessment of initial pharmacodynamic target values for pertinent organisms in animal models, followed by evaluation of antibacterial penetration into the human lung to assist in dosage selection for clinical trials in infected patients. The recent focus has been on ß-lactam agents, including those in combination with ß-lactamase inhibitors, particularly due to the rise of multidrug-resistant infections. This manifests as a large portion of the review focusing on cephalosporins and carbapenems, with or without ß-lactamase inhibitors, in both healthy adult subjects and critically ill patients with lower respiratory tract infections. Further studies are warranted in critically ill patients with lower respiratory tract infections to evaluate the relationship between intrapulmonary penetration and clinical and microbiological outcomes. Our clinical research experience with these studies, along with this literature review, has allowed us to outline key steps in developing and evaluating dosage regimens to treat extracellular bacteria in lower respiratory tract infections.


Assuntos
Antibacterianos , Pulmão , Animais , Líquido da Lavagem Broncoalveolar , Broncoscopia , Cefalosporinas , Humanos , Camundongos
14.
Drugs Context ; 102021.
Artigo em Inglês | MEDLINE | ID: mdl-33643421

RESUMO

The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10-15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone - it will require a continued, robust and multi-faceted approach to disease treatment and prevention.

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