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1.
Pharmacotherapy ; 44(1): 28-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37593883

RESUMO

OBJECTIVES: The immunomodulators tocilizumab and baricitinib improve outcomes in severely ill patients with coronavirus disease 2019 (COVID-19); however, comparative analyses of clinical outcomes related to these agents are lacking. A tocilizumab national shortage shifted treatment to baricitinib in critically ill patients, allowing for an outcome comparison in a similar population. The purpose of this study is to compare clinical outcomes in critically ill COVID-19 patients who received tocilizumab and those who received baricitinib. DESIGN: Retrospective, observational cohort study using generalized estimating equation models, accounting for clustering by hospital and known confounders, to estimate the proportional odds of the ordinal World Health Organization Clinical Progression Scale (WHO-CPS) score at day 14, the primary outcome. Secondary outcomes included WHO-CPS score at day 7. SETTING: Multiple hospitals within the Cleveland Clinic Health System. PATIENTS: Adult patients admitted for COVID-19 between January 2021 and November 2021. INTERVENTIONS: Receipt of tocilizumab, before its shortage, or baricitinib, during shortage. MEASUREMENTS AND MAIN RESULTS: In total, 507 patients were included; 217 received tocilizumab and 290 received baricitinib. Over 96% of patients required ICU admission and 98% received concomitant dexamethasone. Tocilizumab recipients had higher (worse) baseline WHO-CPS scores. After adjustment, tocilizumab use was associated with higher odds of a worse day 14 WHO-CPS score compared with baricitinib (adjusted odds ratio [OR] 1.65 [95% confidence interval (CI) 1.10-2.48]). Similarly, after adjustment, tocilizumab use was associated with higher odds of a worse day 7 WHO-CPS score (adjusted OR 1.65 [95% CI 1.22-2.24]). CONCLUSIONS: Baricitinib use was associated with better WHO-CPS scores at day 14 and day 7 compared with tocilizumab in a cohort of critically ill patients with COVID-19. The odds of having a one unit increase in WHO-CPS score at day 14 was 71% higher with tocilizumab than baricitinib. No difference in mortality or adverse effects was noted.


Assuntos
Anticorpos Monoclonais Humanizados , Azetidinas , COVID-19 , Purinas , Pirazóis , Sulfonamidas , Adulto , Humanos , Tratamento Farmacológico da COVID-19 , Estado Terminal , Estudos Retrospectivos
2.
Open Forum Infect Dis ; 10(12): ofad554, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38088984

RESUMO

A retrospective review of patients unable to take medications by mouth showed short interruptions of therapy for most patients. In a secondary analysis, our data showed maintenance and/or achievement of viral suppression for most patients. A retrospective review of intensive care patients unable to take antiretrovirals by mouth showed 56.6% of patients experiencing a transient interruption in therapy. Additionally, our case series further supports previous literature on crushing dolutegravir and bictegravir regimens to maintain and achieve viral suppression.

3.
Trials ; 24(1): 595, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37716990

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients. METHODS: We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay. DISCUSSION: Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT05568654 . Registered on October 4, 2022.


Assuntos
Anti-Infecciosos , Clostridioides difficile , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Pneumonia , Adulto , Humanos , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pacientes Internados , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Clin Infect Dis ; 77(2): 174-185, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37011018

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable. METHODS: We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality. RESULTS: Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, <15% of very low-risk patients were switched early. CONCLUSIONS: Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates, <15% of very low-risk patients were switched early. Our findings suggest that many more patients could be switched early without compromising outcomes.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Adulto , Humanos , Estudos Retrospectivos , Pneumonia/tratamento farmacológico , Antibacterianos/uso terapêutico , Hospitalização , Tempo de Internação , Infecções Comunitárias Adquiridas/tratamento farmacológico , Administração Oral
5.
Am J Health Syst Pharm ; 80(6): 365-372, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36516457

RESUMO

PURPOSE: To evaluate the impact of a standardized order set and medication-use process on antiretroviral medication errors in sexual assault (SA) patients presenting to the emergency department (ED) for nonoccupational postexposure prophylaxis (nPEP). METHODS: In November 2019, a multidisciplinary group collaborated on an initiative to improve the nPEP medication-use process for SA patients presenting to the EDs within a large integrated health system. Electronic medical records of patients 13 years of age or older who presented for SA examination and were prescribed nPEP during the pre- (February 2018-August 2019) and poststandardization (February 2020-August 2021) periods were included. The primary objective was to compare the proportion of patients experiencing a medication error before and after SA/nPEP process standardization. Data regarding the following medication errors were evaluated: incomplete regimen; inappropriate/duplicative regimen; dosing, frequency, or quantity prescribed error; and initiation of nPEP without an HIV test. RESULTS: Two hundred six patients met criteria for inclusion. A higher proportion of patients experienced medication errors in the prestandardization group relative to the poststandardization group (46.5% vs 11.9%, P < 0.001). Fifty-five errors were observed in the prestandardization group, compared to 16 errors in the poststandardization group. The majority of errors in the prestandardization group were directly related to antiretroviral regimens, while the majority of errors in the poststandardization group involved initiation of nPEP without an HIV test. CONCLUSION: The standardization of the SA/nPEP process was associated with significantly lower medication error rates. Optimization of medication-use technology is an effective strategy in reducing medication errors.


Assuntos
Infecções por HIV , Erros de Medicação , Humanos , Erros de Medicação/prevenção & controle , Serviço Hospitalar de Emergência , Registros Eletrônicos de Saúde , Antirretrovirais , Profilaxia Pós-Exposição , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle
6.
Open Forum Infect Dis ; 9(12): ofac601, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36540389

RESUMO

Background: Best practice guidelines recommend that patients at risk for sexually transmitted infections (STIs), such as gonorrhea (GC) and chlamydia, should also be tested for human immunodeficiency virus (HIV) and syphilis. This prospective quality assurance study aimed to increase HIV and syphilis testing rates in emergency departments (EDs) across the Cleveland Clinic Health System from January 1, 2020 through January 1, 2022. Methods: A multidisciplinary team of emergency medicine, infectious diseases, pharmacy, and microbiology personnel convened to identify barriers to HIV and syphilis testing during ED encounters at which GC/chlamydia were tested. The following interventions were implemented in response: rapid HIV testing with new a workflow for results follow-up, a standardized STI-screening order panel, and feedback to clinicians about ordering patterns. Results: There were 57 797 ED visits with GC/chlamydia testing completed during the study period. Human immunodeficiency virus testing was ordered at 5% of these encounters before the interventions were implemented and increased to 8%, 23%, and 36% after each successive intervention. Syphilis testing increased from 9% before the interventions to 12%, 28%, and 39% after each successive intervention. In multivariable analyses adjusted for age, gender, and location, the odds ratio for HIV and syphilis testing after all interventions was 11.72 (95% confidence interval [CI], 10.82-12.71; P ≤.001) and 6.79 (95% CI, 6.34-7.27; P ≤.001), respectively. Conclusions: The multidisciplinary intervention resulted in improved testing rates for HIV and syphilis.

7.
Chest ; 162(3): 543-555, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35134384

RESUMO

BACKGROUND: Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes. RESEARCH QUESTION: In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes? STUDY DESIGN AND METHODS: This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied. RESULTS: Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5% tested positive. Testing increased from 15.4% to 35.6% from 2010 to 2015 and was 28.9% during flu season (October-May) vs 8.2% in June to September. Patients testing positive for influenza received antiviral agents more often and antibacterial agents less often and for shorter courses than patients testing negative (5.3 vs 6.4 days; P < .001). Influenza-positive patients receiving oseltamivir on hospital day 1 (n = 2,585) experienced lower 14-day in-hospital mortality (adjusted OR, 0.75; 95% CI, 0.59-0.96), lower costs (adjusted ratio of means, 0.88; 95% CI, 0.81-0.95), and shorter length of stay (adjusted ratio of means, 0.88; 95% CI, 0.84-0.93) vs patients receiving oseltamivir later or not at all (n = 1,742). INTERPRETATION: Even during flu season, most patients with CAP in this study went untested for influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes.


Assuntos
Infecções Comunitárias Adquiridas , Influenza Humana , Pneumonia , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Hospitalização , Humanos , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Estudos Retrospectivos
8.
Curr Med Res Opin ; 38(3): 443-450, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34714213

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common among hospitalized patients with community-acquired pneumonia (CAP). We aimed to estimate and compare the risk of AKI for various antibiotic combinations in adults hospitalized for CAP. METHODS: We conducted a retrospective cohort study of the Premier Healthcare Database containing all admissions for 660 US hospitals from 2010 to 2015. We included adults aged ≥18 years hospitalized with CAP and considered 6 different antibiotic combinations based on continuous use in the first 3 hospital days. The primary outcome was incident AKI, defined by ICD-9 codes 584.5-584-9. We evaluated associations of AKI with in-hospital mortality and length-of-stay. We excluded patients who were admitted directly to the intensive care unit, had AKI codes present on admission or had dialysis in the first 2 days. We used generalized linear mixed models with the hospital as a random effect and covariate adjustment for patient demographics, comorbidities, other treatments on day 0/1, and hospital characteristics. RESULTS: The total sample included 449,535 patients, 3.15% of whom developed AKI. All other regimens but fluoroquinolones exhibited higher AKI odds than 3rd generation cephalosporin with or without macrolide. The combination of piperacillin/tazobactam and vancomycin with or without other antibiotics was associated with the highest AKI odds (OR = 1.89; 95% CI: 1.73-2.06). Patients with incident AKI had an increased odds of hospital mortality (OR = 6.37; 95% CI: 6.07-6.69) and longer length-of-stay (mean multiplier = 1.84; 95% CI: 1.82, 1.86). CONCLUSION: Compared to 3rd generation cephalosporin with or without macrolide, piperacillin/tazobactam, vancomycin, and their combination were associated with higher odds of developing AKI, which in turn were associated with worse clinical outcomes.


Assuntos
Injúria Renal Aguda , Infecções Comunitárias Adquiridas , Pneumonia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adolescente , Adulto , Antibacterianos/efeitos adversos , Cefalosporinas , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Humanos , Macrolídeos , Masculino , Combinação Piperacilina e Tazobactam/efeitos adversos , Estudos Retrospectivos , Vancomicina/efeitos adversos
9.
Clin Transplant ; 35(11): e14464, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34405461

RESUMO

BACKGROUND: Vaccine preventable diseases can affect solid organ transplant recipients post-transplant. Therefore, the administration of vaccines and assessment of serologic response should be prioritized in the pre-transplant period. METHODS: This single-center, retrospective study included 349 adult heart or lung transplant candidates between December 1, 2017 and November 30, 2019. We describe vaccination or serologic status for hepatitis A, hepatitis B, tetanus, pneumococcal, influenza, and other recommended vaccinations among heart or lung transplant candidates. RESULTS: Eighty-two heart transplant candidates (91%) and 77 lung transplant candidates (30%) received an ID consult prior to transplant. More patients completed the pneumococcal series (66.7% vs. 28.6%, P = .045) in the heart transplant group that received an ID consult. In the lung transplant group, patients with an ID consult demonstrated higher rates of immunity to hepatitis A (84.4% vs. 72.9%, P = .047), hepatitis B (75.3% vs. 56.9%, P = .005), and measles (71.4% vs. 52.5%, P = .005) compared to those without. CONCLUSIONS: Our results demonstrate the value of consulting ID and administering vaccinations in the early evaluation phase, prior to transplant listing. Opportunities remain to better optimize vaccination rates prior to transplant in heart and lung transplant candidates.


Assuntos
Vacinas contra Influenza , Transplantados , Adulto , Humanos , Pulmão , Estudos Retrospectivos , Vacinação
11.
Am J Health Syst Pharm ; 78(7): 568-577, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33537767

RESUMO

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.


Assuntos
Tratamento Farmacológico da COVID-19 , Quimioterapia Combinada/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pandemias , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
12.
Cleve Clin J Med ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597176

RESUMO

Bamlanivimab and casirivimab-imdevimab are novel virus-neutralizing monoclonal antibodies authorized to treat mild to moderate COVID-19 in outpatients at risk for progression to severe disease. Treatment early in the disease may show efficacy in reducing progression to severe disease, although safety and efficacy data are limited. They are not authorized for hospitalized patients with more advanced disease.

13.
Open Forum Infect Dis ; 7(11): ofaa513, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33269298

RESUMO

BACKGROUND: The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies. METHODS: This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness. RESULTS: One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001). CONCLUSIONS: Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.

14.
medRxiv ; 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32577687

RESUMO

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

15.
Ann Pharmacother ; 54(5): 457-463, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31729245

RESUMO

Background: Centers for Disease Control and Prevention recommends 3 months of once-weekly rifapentine/isoniazid (3HP) for latent tuberculosis infection (LTBI) treatment given by directly observed therapy (DOT) or self-administered therapy (SAT) in patients ≥2 years old. 3HP has been associated with increased incidence of hepatic, gastrointestinal, flu-like, and cutaneous adverse drug reactions (ADRs) compared with isoniazid monotherapy. Objective: This study evaluated 3HP completion rates and tolerability for LTBI treatment in a real-world setting. Methods: A single-center retrospective cohort with a nested case-control study, comparing patients experiencing ADRs with those who did not, evaluated patients ≥18 years old receiving 3HP by DOT or SAT for LTBI at Cleveland Clinic from October 2011 through July 2018. Information on baseline characteristics, 3HP administrations, and ADRs were collected. Results: Of 199 patients screened, 144 were included (111 DOT, 33 SAT). 3HP completion rates were high at 82.6% and similar between DOT and SAT groups. During treatment, 92/144 (63.9%) patients experienced any ADR. The most common ADR included flu-like symptoms (38.2%) and gastrointestinal (31.9%) and hepatic (2.1%) reactions. Despite high rate of overall ADRs, rates of significant ADRs (grade 2 or higher) were 4.2%. Overall, 9% of patients discontinued 3HP because of ADRs. After adjusting for other factors associated with ADRs at baseline, SAT was not associated with increased incidence of ADRs, but female sex was a significant predictor (odds ratio = 2.61 [95% CI, 1.23 to 5.56]). Conclusion and Relevance: This study observed high 3HP treatment completion rates, low incidence of significant ADRs, and low discontinuation rates resulting from ADRs.


Assuntos
Antituberculosos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Estudos de Casos e Controles , Terapia Diretamente Observada/métodos , Esquema de Medicação , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Tuberculose Latente/epidemiologia , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Autoadministração
16.
J Int Assoc Provid AIDS Care ; 18: 2325958219867325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516088

RESUMO

Simplifying or switching antiretroviral therapy (ART) in treatment-experienced people living with HIV (PLWH) may improve adherence, tolerability, toxicities, and/or drug-drug interactions. The purpose of this review is to critically evaluate the literature for efficacy and safety associated with switching or simplifying ART in treatment-experienced PLWH. A systematic literature search using MEDLINE was performed from January 1, 2010 to April 30, 2018. References within articles of interest, the Department of Health and Human Services guidelines, and conference abstracts were also reviewed. Switch/simplification strategies were categorized as those supported by high-level clinical evidence and those with emerging data. Rates of virologic suppression were noninferior for several switch/simplification strategies when compared to baseline ART. Potential for reducing adverse events was also seen. Additional evidence for some strategies, including most 2-drug regimens, is needed before they can be recommended.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Terapia Antirretroviral de Alta Atividade/normas , Substituição de Medicamentos/normas , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos como Assunto , Substituição de Medicamentos/estatística & dados numéricos , Humanos , Guias de Prática Clínica como Assunto , Resposta Viral Sustentada , Estados Unidos
17.
Curr Infect Dis Rep ; 21(10): 38, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31494771

RESUMO

PURPOSE OF REVIEW: HIV treatment simplification is typically indicated for virologically suppressed patients with no baseline resistance-associated mutations (RAMs) or prior virologic failure (VF) to the simplification regimen. Simplification can occur to minimize pill burden, toxicities, drug-drug interactions, or costs. As most studies for treatment simplification excluded patients with baseline RAMs or prior VF, this review is aimed to critically analyze data regarding treatment simplification in treatment-experienced patients. RECENT FINDINGS: Antiretroviral (ARV) regimens containing three-, two-, and one-drug(s) have been scarcely studied to assess virologic efficacy in treatment-experienced patients. Three-drug regimens with the most data and highest efficacy are with integrase strand transfer inhibitors (INSTIs). Regimens including dolutegravir (DTG) and bictegravir have been shown to maintain efficacy in patients with certain baseline RAMs. Dual therapy regimens include the use of DTG plus either lamivudine (3TC), rilpivirine (RPV), or other ARVs. None of these studies evaluated patients with baseline DTG resistance. Baseline RAMs to 3TC were not a predictor of VF in patients on DTG/3TC. Efficacy was seen with DTG/RPV; however, studies showed high rates of discontinuation. DTG plus boosted-protease inhibitors were studied in smaller but promising studies. Two small studies assessed the use of monotherapy with boosted darunavir or DTG, both showing virologic efficacy. Currently, three- and two-drug ARV regimens may be considered in this population with most studies evaluating the use of DTG and bictegravir without baseline INSTI RAMs. Future studies should include heavily treatment-experienced patients with a variety of baseline RAMs and a larger sample size.

18.
Transpl Infect Dis ; 21(5): e13160, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419347

RESUMO

Immunization rates in pre-liver transplant patients have been historically below rates for immunocompetent patients. At Cleveland Clinic, an infectious diseases (ID) consult is required for all patients during the liver transplant evaluation and may beneficially impact vaccination rates. The goal of this study was to evaluate pre-transplant vaccination rates in pre-liver transplant candidates. This single-center, retrospective chart review included adults transplanted between January 1, 2013, and December 31, 2016. Prior to transplant, rates of vaccination and/or documented seropositivity were 35% for hepatitis B vaccine, 92% for hepatitis A vaccine, 57% for pneumococcal conjugate vaccine, 62% for pneumococcal polysaccharide vaccine, and 77% for influenza vaccine. Vaccination rates were higher than to previously reported. Rates were also higher for several vaccines compared to transplant candidates for other organs without ID consult. With ongoing ID consult requirements for liver transplant candidates, combined with standardization of vaccine recommendations via technology, and increased multi-disciplinary collaboration, vaccination rates should improve further.


Assuntos
Transplante de Fígado , Transplantados , Vacinação/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Vacinas/administração & dosagem
20.
Pharmacotherapy ; 39(6): 709-717, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31049983

RESUMO

OBJECTIVE: Respiratory viral polymerase chain reaction (RV PCR) tests assist in rapidly identifying viral pathogens and differentiating viral versus bacterial causes of pneumonia. Studies evaluating the use of RV PCR tests on antibiotic use in adults have demonstrated mixed results. We implemented an antimicrobial stewardship (ASP) intervention for patients with a positive RV PCR test result who were receiving broad-spectrum antibiotics and aimed to assess the impact on antibiotic usage. METHODS: Retrospective quasi-experimental study of adult hospitalized patients comparing time to antibiotic deescalation, duration of antibiotic therapy, and antiviral use preintervention (January-March 2016) and postintervention (January-March 2017). RESULTS: Of 172 ASP alerts reviewed, 55 (32%) were considered actionable. Of these, 47% of interventions were accepted. No significant difference was observed in median time to antibiotic deescalation (pre: 2.7 days vs post: 2.3 days, p=0.88). Time to discontinuation of antimicrobial therapy pre- and postintervention was reduced from 4 to 1.9 days (p=0.057) for piperacillin-tazobactam, from 2.7 to 1.8 days (p=0.75) for ceftriaxone, and from 3.6 to 2 days (p=0.4) for levofloxacin, respectively. Time to initiation of oseltamivir for influenza was significantly shorter in the postintervention group (pre: 11.3 hrs vs post: 3.6 hrs, p=0.02). CONCLUSION: A third of patients receiving broad-spectrum antibiotics with a positive RV PCR had an opportunity for antimicrobial optimization, although this did not translate into a significant impact on the time to antibiotic deescalation or overall antibiotic use. Combination of RV PCR results with biomarkers to rule out bacterial coinfections and chest radiographic findings may help enhance the likelihood of accepted antibiotic deescalation recommendations and represents an area of future research.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/estatística & dados numéricos , Antivirais/uso terapêutico , Pneumonia/diagnóstico , Pneumonia/virologia , Reação em Cadeia da Polimerase , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde/tendências , Estudos Retrospectivos , Fatores de Tempo
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