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INTRODUCTION: There are known disparities in the treatment of infectious diseases. However, disparities in treatment of complicated urinary tract infections (UTIs) are largely uninvestigated. OBJECTIVES: We characterized UTI treatment among males in Veterans Affairs (VA) outpatient settings by age, race, and ethnicity and identified demographic characteristics predictive of recommended first-choice antibiotic therapy. METHODS: We conducted a national, retrospective cohort study of male VA patients diagnosed with a UTI and dispensed an outpatient antibiotic from January 2010 through December 2020. Recommended first-choice therapy for complicated UTI was defined as use of a recommended first-line antibiotic drug choice regardless of area of involvement (ciprofloxacin, levofloxacin, or sulfamethoxazole/trimethoprim) and a recommended duration of 7 to 10 days of therapy. Multivariable models were used to identify demographic predictors of recommended first-choice therapy (adjusted odds ratio [aOR] > 1). RESULTS: We identified a total of 157,898 males diagnosed and treated for a UTI in the outpatient setting. The average antibiotic duration was 9.4 days (±standard deviation [SD] 4.6), and 47.6% of patients were treated with ciprofloxacin, 25.1% with sulfamethoxazole/trimethoprim, 7.6% with nitrofurantoin, and 6.6% with levofloxacin. Only half of the male patients (50.6%, n = 79,928) were treated with recommended first-choice therapy (first-line drug choice and appropriate duration); 77.6% (n = 122,590) were treated with a recommended antibiotic choice and 65.9% (n = 104,070) with a recommended duration. Age 18-49 years (aOR 1.07, 95% confidence interval [CI] 1.03-1.11) versus age ≥65 years was the only demographic factor predictive of recommended first-choice therapy. CONCLUSIONS: Nearly half of the patients included in this study did not receive recommended first-choice therapies; however, racial and ethnic disparities were not identified. Underutilization of recommended first-choice antibiotic therapy in complicated UTIs continues to be an area of focus for antimicrobial stewardship programs.
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Antibacterianos , Infecções Urinárias , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fatores Etários , Assistência Ambulatorial , Antibacterianos/uso terapêutico , Estudos de Coortes , Etnicidade , Disparidades em Assistência à Saúde/etnologia , Grupos Raciais , Estudos Retrospectivos , Estados Unidos , United States Department of Veterans Affairs , Infecções Urinárias/tratamento farmacológico , AdolescenteRESUMO
PURPOSE: Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. METHODS: This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. RESULTS: Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. CONCLUSION: Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture sites.
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Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Combinação de Medicamentos , United States Department of Veterans Affairs , Humanos , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , Masculino , Estudos Retrospectivos , Feminino , Compostos Azabicíclicos/uso terapêutico , Idoso , Pessoa de Meia-Idade , Estados Unidos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pacientes Internados , Idoso de 80 Anos ou mais , Estudos de Coortes , VeteranosRESUMO
INTRODUCTION: Limited data exist regarding real-world utilization of nirmatrelvir/ritonavir. We identified predictors of nirmatrelvir/ritonavir use among Veterans Affairs (VA) outpatients nationally. METHODS: We conducted a retrospective cohort study among outpatients with coronavirus disease 2019 (COVID-19) who were eligible to receive nirmatrelvir/ritonavir between January and December of 2022, to identify factors associated with nirmatrelvir/ritonavir use (i.e., demographics, medical history, prior medication and healthcare exposures, frailty, and other clinical characteristics) using multivariable logistic regression. RESULTS: We included 309,755 outpatients with COVID-19 who were eligible for nirmatrelvir/ritonavir, of whom 12.2% received nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir uptake increased from 1.1% to 23.2% over the study period. Factors associated with nirmatrelvir/ritonavir receipt included receiving a COVID-19 booster vs. none (adjusted odds ratio [aOR] 2.19 [95% confidence interval [CI] 2.12-2.26]), age ≥ 50 vs. 18-49 years (aORs > 1.5 for all age groups ≥ 50 years), having HIV (aOR 1.36 [1.22-1.51]), being non-frail vs. severely frail (aOR 1.22 [1.13-1.33]), and having rheumatoid arthritis (aOR 1.12 [1.04-1.21). Those with concomitant use of potentially interacting antiarrhythmics (aOR 0.35 [0.28-0.45]), anticoagulants/antiplatelets (aOR 0.42 [0.40-0.45]), and/or psychiatric/sedatives (aOR 0.84 [0.81-0.87]) were less likely to receive nirmatrelvir/ritonavir. CONCLUSIONS: Despite increases over time, overall utilization of nirmatrelvir/ritonavir was low. Predictors of nirmatrelvir/ritonavir utilization were consistent with known risk factors for progression to severe COVID-19, including older age and underlying medical conditions. Unvaccinated and undervaccinated patients and those receiving potentially interacting medications for cardiovascular or mental health conditions (antiarrhythmic, alpha-1 antagonist, anticoagulant/antiplatelet, sedative/hypnotic/psychiatric) were less likely to receive nirmatrelvir/ritonavir. Further education of prescribers and patients about nirmatrelvir/ritonavir treatment guidelines is needed to improve overall uptake and utilization in certain high-risk subpopulations.
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INTRODUCTION: Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. METHODS: The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. RESULTS: Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. CONCLUSION: We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.
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INTRODUCTION: Lyme disease is the most common vectorborne disease in the Northern hemisphere with more than 400 000 new cases in the USA annually. Lyme meningitis is an uncommon but potentially serious clinical manifestation of Lyme disease. Intravenous ceftriaxone had been the first-line treatment for Lyme meningitis, but is associated with a high rate of complications. Although efficacy and effectiveness (or real-world evidence) data for oral doxycycline are limited, practice guidelines were recently expanded to recommend either oral doxycycline or ceftriaxone as first-line treatments for Lyme meningitis. Our goal is to compare oral doxycycline with intravenous ceftriaxone for the treatment of Lyme meningitis on short-term recovery and long-term quality of life. METHODS AND ANALYSIS: We are performing a prospective cohort study at 20 US paediatric centres located in diverse geographical range where Lyme disease is endemic. The clinical care team will make all antibiotic treatment decisions for children with Lyme meningitis, as per usual practice. We will follow enrolled children for 6 months to determine time of acute symptom recovery and impact on quality of life. ETHICS AND DISSEMINATION: Boston Children's Hospital, the single Institutional Review Board (sIRB), has approved the study protocol with the other 19 enrolling sites as well as the Utah data coordinating centre relying on the Boston Children's Hospital sIRB. Once the study is completed, we will publish our findings in a peer-reviewed medical journal.
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Doença de Lyme , Meningite , Criança , Humanos , Ceftriaxona/uso terapêutico , Doxiciclina/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Doença de Lyme/complicações , Doença de Lyme/tratamento farmacológicoRESUMO
Background: Pediatricians' offices are primary locations for pediatric influenza vaccination; however, pharmacists are also well-positioned as immunizers. Considering the current COVID-19 pandemic and Public Readiness and Emergency Preparedness (PREP) Act, pharmacists' authority to vaccinate children has been recently expanded. Methods: We used the de-identified Optum ClinformaticsTM Data Mart database to identify demographic and clinical predictors of pharmacist-administered pediatric influenza vaccination compared with influenza vaccination in pediatricians' offices. Procedures codes for influenza vaccinations among children were captured for the 2016-2017 influenza season. Logistic regression was used to identify significant predictors. Results: We included 336 841 children receiving influenza vaccines by a pharmacist (5.2%) or in pediatricians' offices (94.8%). The following significant predictors were identified: older pediatric age groups (13-17 years odds ratio [OR] 91.51, 5-12 years OR 35.41), states allowing pharmacist-administered influenza vaccination at younger ages (no age restrictions OR, 26.68, minimum age 2-4 years old OR, 33.76), influenza vaccination outside of pediatricians' offices in the previous year (pharmacist-administered OR, 22.18, convenience care OR 4.15, emergency care OR 1.69), geographic region (South OR, 2.02, Midwest OR 1.60, and West OR 1.38), and routine health exam or follow-up in the prior 6-months (OR, 1.59). Conclusions: The strongest drivers of pharmacist-administered pediatric influenza vaccination were older pediatric age, more lenient minimum age restrictions, and previous influenza vaccination in a pharmacy. Due to the COVID-19 pandemic, the PREP Act, and forthcoming pediatric COVID-19 vaccines for children, pharmacists may play a greater role in pediatric vaccination resulting in sustained changes in pediatric vaccination practices.
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Suboptimal antibiotic prescribing may be more common in patients living in rural versus urban areas due to various factors such as decreased access to care and diagnostic testing equipment. Prior work demonstrated a rural health disparity of overprescribing antibiotics and longer durations of antibiotic therapy in the United States; however, large-scale evaluations are limited. We evaluated the association of rural residence with suboptimal outpatient antibiotic use in the national Veterans Affairs (VA) system. Outpatient antibiotic dispensing was assessed for the veterans diagnosed with an upper respiratory tract infection (URI), pneumonia (PNA), urinary tract infection (UTI), or skin and soft tissue infection (SSTI) in 2010-2020. Rural-urban status was determined using rural-urban commuting area codes. Suboptimal antibiotic use was defined as (1) outpatient fluoroquinolone dispensing and (2) longer antibiotic courses (>ten days). Geographic variation in suboptimal antibiotic use was mapped. Time trends in suboptimal antibiotic use were assessed with Joinpoint regression. While controlling for confounding, the association of rurality and suboptimal antibiotic use was assessed with generalized linear mixed models with a binary distribution and logit link, accounting for clustering by region and year. Of the 1,405,642 veterans diagnosed with a URI, PNA, UTI, or SSTI and dispensed an outpatient antibiotic, 22.8% were rural-residing. In 2010-2020, in the rural- and urban-residing veterans, the proportion of dispensed fluoroquinolones declined by 9.9% and 10.6% per year, respectively. The rural-residing veterans were more likely to be prescribed fluoroquinolones (19.0% vs. 17.5%; adjusted odds ratio (aOR), 1.03; 95% confidence interval (CI), 1.02-1.04) and longer antibiotic courses (53.8% vs. 48.5%; aOR, 1.19, 95% CI, 1.18-1.20) than the urban-residing veterans. Among a large national cohort of veterans diagnosed with URIs, PNA, UTIs, and SSTIs, fluoroquinolone use and longer antibiotic courses were disproportionally more common among rural- as compared to urban-residing veterans. Outpatient antibiotic prescribing must be improved, particularly for rural-residing patients. There are many possible solutions, of which antibiotic stewardship interventions are but one.
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Introduction. Stenotrophomonas maltophilia is an important multidrug-resistant Gram-negative pathogen. While largely a hospital-acquired pathogen, there have been increasing reports of the pathogen in the community.Gap Statement. Trends in S. maltophilia prevalence and resistance rates that include outpatient isolates are unknown.Aim. We described recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system.Methodology. The study identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018 across all VA hospitals, long-term care facilities/units, and outpatient settings. Annual S. maltophilia resistance rates were evaluated. Multidrug resistant (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95â% confidence intervals using Joinpoint software.Results. Over the 9 year study period, 18 285 S. maltophilia cultures were identified (57â% hospital, 3â% long-term care, 40â% outpatient). The most common source of S. maltophilia cultures were respiratory cultures (34.6â%) followed by urine cultures (30.4â%). In VA hospitals and long-term care facilities, the number of S. maltophilia cultures decreased significantly (by 5.4% and 8.4â% per year respectively). Overall, 3.1â% of isolates were MDR which remained stable over the study period. Resistance to other antibiotics assessed mostly remained stable, except SMX/TMP resistance decreased significantly by 8.5â% (2010, 15â%; 2018, 6â%) per year in VA hospitals.Conclusion. While previous work has recognized S. maltophilia as primarily a nosocomial pathogen, the present study found that 40â% of cultures collected were among outpatients. Between 2010 and 2018, the number of positive S. maltophilia cultures decreased significantly in the national VA Healthcare System. Resistance to SMX/TMP decreased over the study period in VA hospitals and now more closely reflects previously reported resistance rates worldwide (0-10â%). MDR S. maltophilia remained stable and low in the national VA Healthcare System.
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Infecções por Bactérias Gram-Negativas , Stenotrophomonas maltophilia , Veteranos , Adulto , Humanos , Estados Unidos/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Testes de Sensibilidade MicrobianaRESUMO
In our retrospective cohort study, we evaluated trends in pharmacist-administered pediatric influenza vaccination rates in the United States and corresponding state-level pharmacist pediatric vaccination authorization models, including minimum age requirements, vaccination protocols, and/or prescription requirements. An administrative health claims database was used to capture influenza vaccinations in children less than 18 years old with 1 year of continuous enrollment and joinpoint regression was used to assess trends. Of the 3,937,376 pediatric influenza vaccinations identified over the study period, only 3.2% were pharmacist-administered (87.7% pediatrician offices, 2.3% convenience care clinics, 0.8% emergency care, and 6.0% other locations). Pharmacist-administered pediatric influenza vaccination was more commonly observed in older children (mean age 12.65 ± 3.26 years) and increased significantly by 19.2% annually over the study period (95% confidence interval 9.2%-30.2%, p < 0.05). The Northeast, with more restrictive authorization models, represented only 2.2% (n = 2816) of all pharmacist-administered pediatric influenza vaccinations. Utilization of pharmacist-administered pediatric influenza vaccination remains low. Providing children with greater access to vaccination with less restrictions may increase overall vaccination rates. Due to the COVID-19 pandemic and the Public Readiness and Emergency Preparedness Act, pharmacists will play a major role in vaccinating children.
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BACKGROUND: Annually, pediatric influenza vaccination coverage estimates are ascertained from health surveys, such as the National Immunization Survey (NIS-Flu). From 2010 to 2017, vaccination coverage among children ranged from 51 to 59 %. Recognizing the limitations of national health survey data, we sought to describe temporal trends in pediatric influenza vaccination coverage, and demographic differences among a commercially insured large national cohort from 07/01/2010 to 06/30/2017. METHODS: Influenza vaccination coverage was assessed among children (<18 years) with continuous enrollment in the de-identified Optum Clinformatics® Data Mart database, and from NIS-Flu. Time trends in vaccination coverage were assessed using Joinpoint regression, overall and stratified by age group, sex, and geographic region. RESULTS: The average annual pediatric influenza vaccination coverage was 33.4 % in our study population versus 56.5 % reported from NIS-Flu during the same period (p-value < 0.0001). Vaccination coverage was highest in children 6 months-4-years old at 52.6 % (versus 68.8 % NIS-Flu, p-value < 0.0001), and lowest in the 13-17-year-old age group at 20.1 % (versus 42.8 % NIS-Flu, p-value < 0.0001). Vaccination coverage over time remained stable in our study population (average annual percent change 1.8 %, 95 % confidence interval [CI] -2.3 % to 6.0 %) versus significantly increasing by 2.8 % in NIS-Flu (95 % CI 0.3 % to 5.3 %). CONCLUSIONS: Vaccination coverage in our commercially insured pediatric population was 51.4% lower than estimates from NIS-Flu during the same period, suggesting the need for more accurate vaccination coverage surveillance, which will also be critical in future COVID-19 vaccination efforts. Effective interventions are needed to increase pediatric influenza vaccination rates to the Healthy People 2020 target of 70%.
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COVID-19 , Vacinas contra Influenza , Influenza Humana , Criança , Estados Unidos , Humanos , Adolescente , Influenza Humana/prevenção & controle , Vacinas contra COVID-19 , Vacinação , Inquéritos EpidemiológicosRESUMO
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, n = 6/97; 12.5%, n = 10/80, respectively) and ceftazidime-avibactam (5.2%, n = 5/97; 12.5%, n = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. IMPORTANCE We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , Adulto , Humanos , Estudos Retrospectivos , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Tazobactam/farmacologia , Tazobactam/uso terapêutico , Antibacterianos/efeitos adversos , Carbapenêmicos/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/farmacologia , Fluoroquinolonas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana MúltiplaRESUMO
We have previously identified substantial antibiotic treatment heterogeneity, even among organism-specific and site-specific infections with treatment guidelines. Therefore, we sought to quantify the extent of treatment heterogeneity among patients hospitalized with P. aeruginosa pneumonia in the national Veterans Affairs Healthcare System from Jan-2015 to Apr-2018. Daily antibiotic exposures were mapped from three days prior to culture collection until discharge. Heterogeneity was defined as unique patterns of antibiotic treatment (drug and duration) not shared by any other patient. Our study included 5300 patients, of whom 87.5% had unique patterns of antibiotic drug and duration. Among patients receiving any initial antibiotic/s with a change to at least one anti-pseudomonal antibiotic (n = 3530, 66.6%) heterogeneity was 97.2%, while heterogeneity was 91.5% in those changing from any initial antibiotic/s to only anti-pseudomonal antibiotics (n = 576, 10.9%). When assessing heterogeneity of anti-pseudomonal antibiotic classes, irrespective of other antibiotic/s received (n = 4542, 85.7%), 50.5% had unique patterns of antibiotic class and duration, with median time to first change of three days, and a median of two changes. Real-world evidence is needed to inform the development of treatment pathways and antibiotic stewardship initiatives based on clinical outcome data, which is currently lacking in the presence of such treatment heterogeneity.
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BACKGROUND: Medication treatment strategies for Crohn disease (CD) include step-up (SU) therapy, beginning with oral anti-inflammatory agents, and top-down (TD) therapy, beginning with biologics or immunomodulators. The real-world utilization and short-term medical costs associated with these treatment strategies are not well described. OBJECTIVE: To examine the prevalence of TD therapy use over time and compare the first-year direct medical expenditures among patients initiating CD medication treatment with SU and TD therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of Optum Clinformatics Data Mart examining adult patients with CD newly initiated on medication therapy from 2010 to 2018. Included patients had a CD-indicated medication dispensed within 60 days after their initial CD diagnosis, were continuously enrolled in the health plan throughout the study period, and did not have comorbidities treated with a biologic also indicated for CD. A generalized linear model was used to quantify the differences in adjusted mean first-year CD-specific, direct nonpharmacy medical costs between users of TD and SU therapy. RESULTS: We identified 3,157 patients newly initiating medication therapy for CD (2,392 [75.8%] patients treated with SU therapy and 765 [24.2%] treated with TD therapy). The use of TD therapy over the study period increased from 17% in 2011 to 31% in 2017. TD therapy was also associated with a 149.8% ($1,230) higher adjusted average per-patient first-year CD-direct nonpharmacy medical cost compared with SU therapy (adjusted ratio of cost for TD compared with SU [2.498, 95% CI = 2.12-2.95]). CONCLUSIONS: In patients newly initiating medication therapy for CD, TD therapy use increased between 2010 and 2017 and was associated with higher first-year nonpharmacy medical expenditure. These findings align with the strategy of initiating TD therapy in patients with a higher disease burden. Further research is needed to determine long-term overall health care costs and clinical outcomes associated with SU and TD strategies in a real-world setting. DISCLOSURES: Dr Caffrey received research funding from Gilead, Merck, Pfizer, and Shionogi and is a speaker for Merck. The views expressed are those of the author and do not necessarily reflect the position or policy of the US Department of Veterans Affairs. Material is based on work supported, in part, by the Office of Research and Development.
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Doença de Crohn , Adulto , Efeitos Psicossociais da Doença , Doença de Crohn/tratamento farmacológico , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Estudos Retrospectivos , Estados UnidosRESUMO
SATB2-associated syndrome (SAS) is an autosomal dominant multisystemic disorder caused by alterations in the SATB2 gene. In addition to a predominant neurodevelopmental phenotype, individuals with SAS often present with feeding difficulties and growth retardation that persist past infancy. In this study, we present growth and measurement data from 211 individuals (53.6% male, 46.4% female) with SAS due to different molecular mechanisms. To delineate growth in this population, we constructed SAS-specific growth charts by sex from birth to 10 years of age. Smoothed SAS percentiles were superimposed with normative percentiles from WHO (birth to <24 months) and CDC (24 months to 10 years) growth charts. Individuals with SAS tend to display slower postnatal growth with 22.2% (32/144), 19.0% (26/137), and 21.6% having at least one weight, height, or weight-for-length /body mass index (BMI) measurement below -2 standard deviations, respectively. The SAS 50th centile BMI was consistently below the normative data 50th centile and negative mean Z-scores were seen across almost all age groups analyzed for both genders. Individuals with chromosomal abnormalities displayed significantly lower weight for age Z-score, height for age Z-scores, occipitofrontal head circumference for age Z-scores, and BMI for age Z-scores compared to either missense or null variants.
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Gráficos de Crescimento , Proteínas de Ligação à Região de Interação com a Matriz , Índice de Massa Corporal , Peso Corporal , Feminino , Humanos , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Síndrome , Fatores de Transcrição/genéticaRESUMO
Pseudomonas aeruginosa infections are challenging to treat due to multi-drug resistance (MDR) and the complexity of the patients affected by these serious infections. As new antibiotic therapies come on the market, limited data exist about the effectiveness of such treatments in clinical practice. In this comparative effectiveness study of ceftolozane/tazobactam versus aminoglycoside- or polymyxin-based therapies among hospitalized patients with positive MDR P. aeruginosa cultures, we identified 57 patients treated with ceftolozane/tazobactam compared with 155 patients treated with aminoglycoside- or polymyxin-based regimens. Patients treated with ceftolozane/tazobactam were younger (mean age 67.5 vs. 71.1, p = 0.03) and had a higher comorbidity burden prior to hospitalization (median Charlson 5 vs. 3, p = 0.01) as well as higher rates of spinal cord injury (38.6% vs. 21.9%, p = 0.02) and P. aeruginosa-positive bone/joint cultures (12.3% vs. 0.7%, p < 0.0001). Inpatient mortality was significantly lower in the ceftolozane/tazobactam group compared with aminoglycosides or polymyxins (15.8% vs. 27.7%, adjusted odds ratio 0.39, 95% confidence interval 0.16−0.93). There were no significant differences observed for the other outcomes assessed. In hospitalized patients with MDR P. aeruginosa, inpatient mortality was 61% lower among patients treated with ceftolozane/tazobactam compared to those treated with aminoglycoside- or polymyxin-based regimens.
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Activated platelets have known antimicrobial activity against Staphylococcus aureus. Accelerated clearance of platelets induced by S. aureus can result in thrombocytopenia and increased mortality in patients. Recent studies suggest that P2Y12 inhibition protects platelets from accelerated clearance. We therefore evaluated the effect of P2Y12 inhibition on clinical outcomes in patients with S. aureus bacteremia across a large national cohort. Our retrospective cohort (2010 to 2018) included patients admitted to Veterans Affairs (VA) hospitals with blood cultures positive for S. aureus and treated with standard-of-care antibiotics. Employing propensity score-matched Cox proportional hazards regression models, we compared clinical outcomes in patients treated with clopidogrel for at least the 30 days prior to admission and continuing for at least 5 days after admission to patients without any P2Y12 inhibitor use in the year preceding admission. Mortality was significantly lower among clopidogrel users than P2Y12 inhibitor nonusers (n = 147 propensity score-matched pairs): the inpatient mortality hazard ratio (HR) was 0.11 (95% confidence interval [CI], 0.01 to 0.86), and 30-day mortality HR was 0.43 (95% CI, 0.19 to 0.98). There were no differences in 30-day readmission, 30-day S. aureus reinfection, microbiological clearance, or thrombocytopenia. Clopidogrel use at the time of infection reduced in-hospital mortality by 89% and 30-day mortality by 57% among a cohort of patients with S. aureus bacteremia. These results support the need to further study the use of P2Y12 inhibitors as adjunctive therapy in S. aureus bloodstream infections.
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Bacteriemia , Infecções Estafilocócicas , Trombocitopenia , Antibacterianos/farmacologia , Bacteriemia/microbiologia , Clopidogrel/farmacologia , Clopidogrel/uso terapêutico , Estudos de Coortes , Humanos , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Trombocitopenia/tratamento farmacológicoRESUMO
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin reactions. Colistin is a last resort antibiotic with a historically poor safety profile. The association between colistin and SJS/TEN has not been previously quantified. RESEARCH DESIGN AND METHODS: We identified colistin and SJS/TEN adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and calculated effect estimates using OpenEpi. RESULTS: From January 2013 through March 2021, 964 adverse events were reported for colistin. Colistin was listed as a secondary suspect drug in 13 SJS/TEN adverse event reports (1.3%), with a reporting odds ratio of 29.6 (95% confidence interval [CI] 17.1-51.1), and proportional reporting ratio of 29.2 (95% CI 17.0-50.2). Limitations of any FAERS study include the voluntary nature of reporting, unclear causal relationship between drug and adverse reaction, underreporting, and wide confidence intervals for rare adverse events like SJS/TEN. CONCLUSIONS: Colistin was not the primary suspect drug in any SJS/TEN adverse event reports. We did identify a statistically significant safety signal for SJS/TEN with colistin as a secondary suspect drug. SJS/TEN is not currently included in the colistin product label. This association should be further explored in other pharmacoepidemiologic drug safety studies.
Assuntos
Síndrome de Stevens-Johnson , Sistemas de Notificação de Reações Adversas a Medicamentos , Colistina/efeitos adversos , Humanos , Farmacovigilância , Estudos Retrospectivos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologiaRESUMO
The objectives were to analyze treatment, clinical outcomes, and predictors of mortality in hospitalized patients with Acinetobacter baumannii infection. This was a retrospective cohort study of inpatients with A. baumannii cultures and treatment from 2010 to 2019. Patients who died during admission were compared to those who survived, to identify predictors of inpatient mortality, using multivariable unconditional logistic regression models. We identified 4,599 inpatients with A. baumannii infection; 13.6% died during admission. Fluoroquinolones (26.8%), piperacillin-tazobactam (24%), and carbapenems (15.6%) were used for treatment. Tigecycline (3%) and polymyxins (3.7%) were not used often. Predictors of inpatient mortality included current acute respiratory failure (adjusted odds ratio [aOR] 3.94), shock (aOR 3.05), and acute renal failure (aOR 2.01); blood (aOR 1.94) and respiratory (aOR 1.64) infectious source; multidrug-resistant A. baumannii (MDRAB) infection (aOR 1.66); liver disease (aOR 2.15); and inadequate initial treatment (aOR 1.30). Inpatient mortality was higher in those with MDRAB versus non-MDRAB (aOR 1.61) and in those with CRAB versus non-CRAB infection (aOR 1.68). Length of stay >10 days was higher among those with MDRAB versus non-MDRAB (aOR 1.25) and in those with CRAB versus non-CRAB infection (aOR 1.31). In our national cohort of inpatients with A. baumannii infection, clinical outcomes were worse among those with MDRAB and/or CRAB infection. Predictors of inpatient mortality included several current conditions associated with severity, infectious source, underlying illness, and inappropriate treatment. Our study may assist health care providers in the early identification of admitted patients with A. baumannii infection who are at higher risk of death.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Estudos RetrospectivosRESUMO
Introduction. Acinetobacter baumannii is a top-priority pathogen of the World Health Organization (WHO) and the Centers for Disease Control (CDC) due to antibiotic resistance.Gap Statement. Trends in A. baumannii resistance rates that include community isolates are unknown.Aim. Identify trends in A. baumannii resistance rates across the Veterans Affairs (VA) Healthcare System, including isolates from patients treated in hospitals, long-term care facilities and outpatient clinics nationally.Methodology. We included A. baumannii clinical cultures collected from VA patients from 2010 to 2018. Cultures were categorized by location: VA medical centers (VAMCs), long-term care (LTC) units [community living centers (CLCs)], or outpatient. We assessed carbapenem resistance, multidrug resistance (MDR) and extensive drug resistance (XDR). Time trends were assessed with Joinpoint regression.Results. We identified 19â376 A. baumannii cultures (53% VAMCs, 4% CLCs, 43% outpatient). Respiratory cultures were the most common source of carbapenem-resistant (43â%), multidrug-resistant (49â%) and extensively drug-resistant (21â%) isolates. Over the study period, the number of A. baumannii cultures decreased significantly in VAMCs (11.9% per year). In 2018, carbapenem resistance was seen in 28% of VAMC isolates and 36% of CLC isolates, but only 6% of outpatient isolates, while MDR was found in 31% of VAMC isolates and 36% of CLC isolates, but only 8 % of outpatient isolates. Carbapenem-resistant, multidrug-resistant and extensively drug-resistant A. baumannii isolates decreased significantly in VAMCs and outpatient clinics over time (VAMCs: by 4.9, 7.2 and 6.9%; outpatient: by 11.3, 10.5 and 10.2% per year). Resistant phenotypes remained stable in CLCs.Conclusion. In the VA nationally, the prevalence of A. baumannii is decreasing, as is resistance. Carbapenem-resistant and multidrug-resistant A. baumannii remain common in VAMCs and CLCs. The focus of infection control and antimicrobial stewardship efforts to prevent transmission of resistant A. baumannii should be in hospital and LTC settings.
Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii , Farmacorresistência Bacteriana , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Carbapenêmicos , Hospitais , Humanos , Assistência de Longa Duração , Pacientes Ambulatoriais , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Antibiotic use is associated with several antibiotic-related harms in vulnerable, older long-term care (LTC) residents. Suboptimal antibiotic use may also be associated with harms but has not yet been investigated. The aim of this work was to compare rates of poor clinical outcomes among LTC residents with UTI receiving suboptimal versus optimal antibiotic treatment. METHODS: We conducted a retrospective cohort study among residents with an incident urinary tract infection (UTI) treated in Veterans Affairs LTC units (2013-2018). Potentially suboptimal antibiotic treatment was defined as use of a suboptimal initial antibiotic drug choice, dose frequency, and/or excessive treatment duration. The primary outcome was time to a composite measure of poor clinical outcome, defined as UTI recurrence, acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation. Shared frailty Cox proportional hazard regression models were used to compare the time-to-event between suboptimal and optimal treatment. RESULTS: Among 19,701 LTC residents with an incident UTI, 64.6% received potentially suboptimal antibiotic treatment and 35.4% experienced a poor clinical outcome. In adjusted analyses, potentially suboptimal antibiotic treatment was associated with a small increased hazard of poor clinical outcome (aHR 1.06, 95% CI 1.01-1.11) as compared with optimal treatment, driven by an increased hazard of CDI (aHR 1.94, 95% CI 1.54-2.44). CONCLUSION: In this national cohort study, suboptimal antibiotic treatment was associated with a 6% increased risk of the composite measure of poor clinical outcomes, in particular, a 94% increased risk of CDI. Beyond the decision to use antibiotics, clinicians should also consider the potential harms of suboptimal treatment choices with regards to drug type, dose frequency, and duration used.