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Background: Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability ß-lactams (HBBLs). Methods: In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45-78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30-2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95-5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure. Conclusions: FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.
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BACKGROUND: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood. METHODS: We conducted an explanatory, sequential mixed methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse. For each hospital, we conducted surveys, document analysis, and semi-structured interviews with antibiotic stewardship and clinical stakeholders. Data were analyzed separately and mixed during the interpretation phase, where each hospital was examined as a case, with findings organized across cases using a strengths, weaknesses, opportunities, and threats framework to identify factors accounting for differences in antibiotic overuse across hospitals. RESULTS: Surveys included 85 respondents. Interviews included 90 respondents (31 hospitalists, 33 clinical pharmacists, 14 stewardship leaders, 12 hospital leaders). On surveys, clinical pharmacists at hospitals with lower antibiotic overuse were more likely to report feeling: respected by hospitalist colleagues (p=0.001), considered valuable team members (p=0.001), comfortable recommending antibiotic changes (p=0.02). Based on mixed-methods analysis, hospitals with low antibiotic overuse had four distinguishing characteristics: a) robust knowledge of and access to antibiotic stewardship guidance, b) high quality clinical pharmacist-physician relationships, c) tools and infrastructure to support stewardship, and d) highly engaged Infectious Diseases physicians who advocated stewardship principles. CONCLUSION: This mixed-method study demonstrates the importance of organizational context for high performance in stewardship and suggests improving antimicrobial stewardship requires attention to knowledge, interactions, and relationships between clinical teams and infrastructure that supports stewardship and team interactions.
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Purpose: Limited data exist regarding treatment of invasive group A streptococcal (GAS) infections, including safety and efficacy of oral (PO) step-down therapy. We sought to describe current prescribing practices and clinical outcomes for patients with GAS bacteremia across a large health system, including a prespecified subset of patients who stepped down to PO antibiotics. Methods: This retrospective cohort study included adult patients with a positive blood culture for GAS between July 2018 and July 2021. Primary outcomes included frequency of PO step-down, total duration of therapy, duration of intravenous (IV) therapy prior to PO switch, and antimicrobial selection. Secondary outcomes included length of stay (LOS), mortality, adverse events, and clinical failure leading to readmission within 90 days. Results: In total, 280 patients met inclusion criteria. Of these, 46.7% were stepped down to PO antibiotics. Median total duration of therapy was 15 days. Median duration of IV therapy prior to PO switch was 5 days. The predominant definitive antibiotic choice was a beta-lactam. Median LOS was 5 days. Ninety-day mortality was 16.7%. One patient developed an occluded line and one developed Clostridioides difficile-associated diarrhea within 90 days. Ninety-day readmission due to clinical failure was 12.5%. Among cases of uncomplicated skin and soft tissue source, mortality (6.1% vs 2.4%) and readmission (15.2% vs 16.9%) were similar between definitive IV and PO groups. Conclusions: Group A streptococcal bacteremia is a severe infection with a high readmission and mortality rate. Use of PO step-down therapy was common with similar readmission and mortality rates compared with definitive IV therapy.
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Objective: Assess urgent care (UC) clinician prescribing practices and factors associated with first-line antibiotic selection and recommended duration of therapy for sinusitis, acute otitis media (AOM), and pharyngitis. Design: Retrospective cohort study. Participants: All respiratory UC encounters and clinicians in the Intermountain Health (IH) network, July 1st, 2019-June 30th, 2020. Methods: Descriptive statistics were used to characterize first-line antibiotic selection rates and the duration of antibiotic prescriptions during pharyngitis, sinusitis, and AOM UC encounters. Patient and clinician characteristics were evaluated. System-specific guidelines recommended 5-10 days of penicillin, amoxicillin, or amoxicillin-clavulanate as first-line. Alternative therapies were recommended for penicillin allergy. Generalized estimating equation modeling was used to assess predictors of first-line antibiotic selection, prescription duration, and first-line antibiotic prescriptions for an appropriate duration. Results: Among encounters in which an antibiotic was prescribed, the rate of first-line antibiotic selection was 75%, the recommended duration was 70%, and the rate of first-line antibiotic selection for the recommended duration was 53%. AOM was associated with the highest rate of first-line prescriptions (83%); sinusitis the lowest (69%). Pharyngitis was associated with the highest rate of prescriptions for the recommended duration (91%); AOM the lowest (51%). Penicillin allergy was the strongest predictor of non-first-line selection (OR = 0.02, 95% CI [0.02, 0.02]) and was also associated with extended duration prescriptions (OR = 0.87 [0.80, 0.95]). Conclusions: First-line antibiotic selection and duration for respiratory UC encounters varied by diagnosis and patient characteristics. These areas can serve as a focus for ongoing stewardship efforts.
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Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.
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Importance: Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. Objective: To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. Design, Setting, and Participants: This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493â¯724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. Interventions: Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. Main Outcomes and Measures: The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. Results: The baseline period included 207â¯047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183â¯893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. Conclusions and relevance: The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship.
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Programas de Optimización del Uso de los Antimicrobianos , Infecciones del Sistema Respiratorio , Sinusitis , Humanos , Femenino , Adulto , Masculino , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Antibacterianos/uso terapéutico , Atención AmbulatoriaRESUMEN
In late 2019, SARS-CoV-2 caused the greatest global health crisis in a century, impacting all aspects of society. As the COVID-19 pandemic evolved throughout 2020 and 2021, multiple variants emerged, contributing to multiple surges in cases of COVID-19 worldwide. In 2021, highly effective vaccines became available, although the pandemic continues into 2022. There has been tremendous expansion of basic, translational, and clinical knowledge about SARS-CoV-2 and COVID-19 since the pandemic's onset. Treatment options have been rapidly explored, attempting to repurpose preexisting medications in tandem with development and evaluation of novel agents. Care of the seriously ill patient is examined.
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COVID-19 , SARS-CoV-2 , Humanos , Pandemias/prevención & control , Salud GlobalRESUMEN
BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. RESULTS: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). CONCLUSIONS: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.
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Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina , Cloroquina/efectos adversos , Análisis de Datos , Humanos , Hidroxicloroquina/efectos adversosRESUMEN
Twenty of 21 health systems and network-based antimicrobial stewardship programs (ASPs) who were invited participated in a questionnaire, a webinar, and focus groups to understand implementation strategies for system-wide antimicrobial stewardship. Four centralized ASPs structures emerged. Of participating organizations, 3 (15%) confirmed classification as collaborative, 3 (15%) as centrally coordinated, 3 (15%) as in between or in transition between centrally coordinated and centrally led, 8 (40%) as centrally led, 2 (10%) as collaborative, consultative network. One (5%) organization considered themselves to be a hybrid. System-level stewardship responsibilities varied across sites and generally fell into 6 major categories: building and leading a stewardship community, strategic planning and goal setting, development of validated data streams, leveraging tools and technology for stewardship interventions, provision of subject-matter expertise, and communication/education. Centralized ASPs included in this study most commonly took a centrally led approach and engaged in activities tailored to system-wide goals.
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Programas de Optimización del Uso de los Antimicrobianos , Humanos , Antibacterianos/uso terapéutico , Encuestas y CuestionariosRESUMEN
Background: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. Methods: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.
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BACKGROUND: Neutralizing monoclonal antibodies (MAbs) are a promising therapy for early coronavirus disease 2019 (COVID-19), but their effectiveness has not been confirmed in a real-world setting. METHODS: In this quasi-experimental pre-/postimplementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID-19. The primary outcome was a composite of emergency department visits or hospitalizations within 14 days of positive test. Secondary outcomes included adverse events and 14-day mortality. The average treatment effect in the treated for MAb therapy was estimated using inverse probability of treatment weighting and the impact of MAb implementation using propensity-weighted interrupted time series analysis. RESULTS: Pre-implementation (July-November 2020), 7404 qualifying patients were identified. Postimplementation (December 2020-January 2021), 594 patients received MAb treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) historical controls. MAb treatment was associated with decreased likelihood of emergency care or hospitalization (odds ratio, 0.69; 95% CI, 0.60-0.79). After implementation, the weighted probability that a given patient would require an emergency department visit or hospitalization decreased significantly (0.7% per day; 95% CI, 0.03%-0.10%). Mortality was 0.2% (nâ =â 1) in the MAb group compared with 1.0% (nâ =â 71) and 1.0% (nâ =â 57) in pre- and postimplementation controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered serious. CONCLUSIONS: MAb treatment of high-risk ambulatory patients with early COVID-19 was well tolerated and likely effective at preventing the need for subsequent emergency department or hospital care.
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PURPOSE: This report describes our process of 4 health systems coming together to agree on standard use criteria for remdesivir as a coronavirus disease 2019 (COVID-19) treatment for patients in Utah. We hope our process provides a framework for remdesivir use in other states and insights on future use of other therapeutic agents that may also be in short supply, such as vaccines and monoclonal antibodies. SUMMARY: Emergency use authorization (EUA) criteria for COVID-19 treatments often allow for broad use of a treatment relative to limited supplies. Without national criteria, each health system must develop further rationing criteria. Health systems in Utah worked together as part of the state's crisis standards of care workgroup to develop a framework for how to limit the EUA criteria for remdesivir to match available supplies. The 4 largest health systems were represented by infectious diseases specialists, chief medical officers, and pharmacists. The group met several times online and communicated via email over a 9-day period to develop the criteria. The clinicians agreed to use this framework to develop criteria for future therapeutics such as monoclonal antibodies. CONCLUSION: The unique collaboration of the 4 health systems in Utah led to statewide criteria for use of remdesivir for patients with COVID-19, ensuring similar access to this limited resource for all patients in Utah.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Servicio de Farmacia en Hospital/normas , Guías de Práctica Clínica como Asunto , SARS-CoV-2 , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/uso terapéutico , Alanina/administración & dosificación , Alanina/uso terapéutico , Antivirales/administración & dosificación , Humanos , UtahRESUMEN
Developing and improving an antimicrobial stewardship program successfully requires evaluation of numerous factors. As technology progresses and our understanding of antimicrobial resistance grows, careful consideration should be taken to ensure that a program meets the needs of the institution and is achievable given the available resources. In this review, we explore fundamental initiatives and strategies for both new and established antimicrobial stewardship programs, including the specific areas to target and key elements required for sustainable implementation.
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RATIONALE: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates. OBJECTIVE: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19. METHODS: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective. RESULTS: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury. CONCLUSIONS: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation. CLINICAL TRIAL REGISTRATION: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.
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BACKGROUND: A subset of patients with COVID-19 develops a hyperinflammatory syndrome that has similarities with other hyperinflammatory disorders. However, clinical criteria specifically to define COVID-19-associated hyperinflammatory syndrome (cHIS) have not been established. We aimed to develop and validate diagnostic criteria for cHIS in a cohort of inpatients with COVID-19. METHODS: We searched for clinical research articles published between Jan 1, 1990, and Aug 20, 2020, on features and diagnostic criteria for secondary haemophagocytic lymphohistiocytosis, macrophage activation syndrome, macrophage activation-like syndrome of sepsis, cytokine release syndrome, and COVID-19. We compared published clinical data for COVID-19 with clinical features of other hyperinflammatory or cytokine storm syndromes. Based on a framework of conserved clinical characteristics, we developed a six-criterion additive scale for cHIS: fever, macrophage activation (hyperferritinaemia), haematological dysfunction (neutrophil to lymphocyte ratio), hepatic injury (lactate dehydrogenase or asparate aminotransferase), coagulopathy (D-dimer), and cytokinaemia (C-reactive protein, interleukin-6, or triglycerides). We then validated the association of the cHIS scale with in-hospital mortality and need for mechanical ventilation in consecutive patients in the Intermountain Prospective Observational COVID-19 (IPOC) registry who were admitted to hospital with PCR-confirmed COVID-19. We used a multistate model to estimate the temporal implications of cHIS. FINDINGS: We included 299 patients admitted to hospital with COVID-19 between March 13 and May 5, 2020, in analyses. Unadjusted discrimination of the maximum daily cHIS score was 0·81 (95% CI 0·74-0·88) for in-hospital mortality and 0·92 (0·88-0·96) for mechanical ventilation; these results remained significant in multivariable analysis (odds ratio 1·6 [95% CI 1·2-2·1], p=0·0020, for mortality and 4·3 [3·0-6·0], p<0·0001, for mechanical ventilation). 161 (54%) of 299 patients met two or more cHIS criteria during their hospital admission; these patients had higher risk of mortality than patients with a score of less than 2 (24 [15%] of 138 vs one [1%] of 161) and for mechanical ventilation (73 [45%] vs three [2%]). In the multistate model, using daily cHIS score as a time-dependent variable, the cHIS hazard ratio for worsening from low to moderate oxygen requirement was 1·4 (95% CI 1·2-1·6), from moderate oxygen to high-flow oxygen 2·2 (1·1-4·4), and to mechanical ventilation 4·0 (1·9-8·2). INTERPRETATION: We proposed and validated criteria for hyperinflammation in COVID-19. This hyperinflammatory state, cHIS, is commonly associated with progression to mechanical ventilation and death. External validation is needed. The cHIS scale might be helpful in defining target populations for trials and immunomodulatory therapies. FUNDING: Intermountain Research and Medical Foundation.
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Coronavirus disease (COVID-19) is a potentially fatal illness with no proven therapy beyond excellent supportive care. Treatments are urgently sought. Adaptations to traditional trial logistics and design to allow rapid implementation, evaluation of trials within a global trials context, flexible interim monitoring, and access outside traditional research hospitals (even in settings where formal placebos are unavailable) may be helpful. Thoughtful adaptations to traditional trial designs, especially within the global context of related studies, may also foster collaborative relationships among government, community, and the research enterprise. Here, we describe the protocol for a pragmatic, active comparator trial in as many as 300 patients comparing two current "off-label" treatments for COVID-19-hydroxychloroquine and azithromycin-in academic and nonacademic hospitals in Utah. We developed the trial in response to local pressures for widespread, indiscriminate off-label use of these medications. We used a hybrid Bayesian-frequentist design for interim monitoring to allow rapid, contextual assessment of the available evidence. We also developed an inference grid for interpreting the range of possible results from this trial within the context of parallel trials and prepared for a network meta-analysis of the resulting data. This trial was prospectively registered (ClinicalTrials.gov Identifier: NCT04329832) before enrollment of the first patient.Clinical trial registered with www.clinicaltrials.gov (NCT04329832).
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Azitromicina , Infecciones por Coronavirus , Hidroxicloroquina , Pandemias , Neumonía Viral , Adulto , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Monitoreo de Drogas/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Masculino , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , Resultado del Tratamiento , Utah , Tratamiento Farmacológico de COVID-19RESUMEN
Improving antibiotic prescribing in outpatient settings is a public health priority. In the United States, urgent care (UC) encounters are increasing and have high rates of inappropriate antibiotic prescribing. Our objective was to characterize antibiotic prescribing practices during UC encounters, with a focus on respiratory tract conditions. This was a retrospective cohort study of UC encounters in the Intermountain Healthcare network. Among 1.16 million UC encounters, antibiotics were prescribed during 34% of UC encounters and respiratory conditions accounted for 61% of all antibiotics prescribed. Of respiratory encounters, 50% resulted in antibiotic prescriptions, yet the variability at the level of the provider ranged from 3% to 94%. Similar variability between providers was observed for respiratory conditions where antibiotics were not indicated and in first-line antibiotic selection for sinusitis, otitis media, and pharyngitis. These findings support the importance of developing antibiotic stewardship interventions specifically targeting UC settings.
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Antibacterianos , Infecciones del Sistema Respiratorio , Atención Ambulatoria , Antibacterianos/uso terapéutico , Humanos , Prescripción Inadecuada , Pacientes Ambulatorios , Pautas de la Práctica en Medicina , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Estudios Retrospectivos , Estados UnidosRESUMEN
Successful antimicrobial stewardship programs rely on engagement with hospital administrators. Antimicrobial stewards should understand the unique pressures and demands of hospital and health system administration and be familiar with key terminology and regulatory requirements. This article provides guidance on strategies for engaging hospital and health system administration to support antimicrobial stewardship, including recommendations for designing a successful antimicrobial stewardship program structure, pitching resource requests, setting meaningful and measurable goals, achieving and communicating results, and fostering ongoing relationships with hospital and health system administration.
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Programas de Optimización del Uso de los Antimicrobianos/métodos , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Administración de los Servicios de Salud , Hospitales , Colaboración Intersectorial , Antibacterianos/uso terapéutico , Comunicación en Salud , HumanosRESUMEN
BACKGROUND: To guide rational antibiotic selection in community-onset pneumonia, we previously derived and validated a novel prediction tool, the Drug-Resistance in Pneumonia (DRIP) score. In 2015, the DRIP score was integrated into an existing electronic pneumonia clinical decision support tool (ePNa). METHODS: We conducted a quasi-experimental, pre-post implementation study of ePNa with DRIP score (2015) vs ePNa with health-care-associated pneumonia (HCAP) logic (2012) in ED patients admitted with community-onset pneumonia to four US hospitals. Using generalized linear models, we used the difference-in-differences method to estimate the average treatment effect on the treated with respect to ePNa with DRIP score on broad-spectrum antibiotic use, mortality, hospital stay, and cost, adjusting for available patient-level confounders. RESULTS: We analyzed 2,169 adult admissions: 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015; inadequate initial empirical antibiotics were prescribed in 1.1% and 0.5%, respectively (P = .12). A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 and 33.0% in 2015 (P < .001). Vancomycin days of therapy per 1,000 patient days in 2012 were 287.3 compared with 238.8 in 2015 (P < .001). In the primary analysis, the average treatment effect among patients using the DRIP score was a reduction in broad-spectrum antibiotic use (OR, 0.62; 95% CI, 0.39-0.98; P = .039). However, the average effects for ePNa with DRIP on mortality, length of stay, and cost were not statistically significant. CONCLUSIONS: Electronic calculation of the DRIP score was more effective than HCAP criteria for guiding appropriate broad-spectrum antibiotic use in community-onset pneumonia.