Beyond antibiotic prescribing rates: first-line antibiotic selection, prescription duration, and associated factors for respiratory encounters in urgent care.

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.

A Novel Program to Provide Drug Recovery Assistance and Outpatient Parenteral Antibiotic Therapy in People Who Inject Drugs.

BACKGROUND: Safe hospital discharge on parenteral antibiotic therapy is challenging for people who inject drugs (PWID) admitted with serious bacterial infections (SBI). We describe a Comprehensive Care of Drug Addiction and Infection (CCDAI) program involving a partnership between Intermountain Healthcare hospitals and a detoxification facility (DF) to provide simultaneous drug recovery assistance and parenteral antibiotic therapy (DRA-OPAT). METHODS: The CCDAI program was evaluated using a pre-/poststudy design. We compared outcomes in PWID hospitalized with SBI during a 1-year postimplementation period (2018) with similar patients from a historical control period (2017), identified by propensity modeling and manual review. RESULTS: Eighty-seven patients were candidates for the CCDAI program in the implementation period. Thirty-five participants (40.2%) enrolled in DRA-OPAT and discharged to the DF; 16 (45.7%) completed the full outpatient parenteral antibiotic therapy (OPAT) duration. Fifty-one patients with similar characteristics were identified as a preimplementation control group. Median length of stay (LOS) was reduced from 22.9 days (interquartile interval [IQI], 9.8-42.7) to 10.6 days (IQI, 6-17.4) after program implementation (P < .0001). Total median cost decreased from $39 220.90 (IQI, $23 300.71-$82 506.66) preimplementation to $27 592.39 (IQI, $18 509.45-$48 369.11) postimplementation (P < .0001). Ninety-day readmission rates were similar (23.5% vs 24.1%; P = .8). At 1-year follow-up, all-cause mortality was 7.1% in the preimplementation group versus 1.2% postimplementation (P = .06). CONCLUSIONS: Partnerships between hospitals and community resources hold promise for providing resource-efficient OPAT and drug recovery assistance. We observed significant reductions in LOS and cost without increases in readmission rates; 1-year mortality may have been improved. Further study is needed to optimize benefits of the program.

Simple scoring tool to estimate risk of hospitalization and mortality in ambulatory and emergency department patients with COVID-19.

BACKGROUND: Accurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality. METHODS: All consecutive patients testing positive for SARS-CoV-2 from March 25-October 1, 2020 within the Intermountain Healthcare system were included. The cohort was randomly divided into 70% derivation and 30% validation cohorts. A multivariable logistic regression model was fitted for 14-day hospitalization. The optimal model was then adapted to a simple, probabilistic score and applied to the validation cohort and evaluated for prediction of hospitalization and 28-day mortality. RESULTS: 22,816 patients were included; mean age was 40 years, 50.1% were female and 44% identified as non-white race or Hispanic/Latinx ethnicity. 6.2% required hospitalization and 0.4% died. Criteria in the simple model included: age (0.5 points per decade); high-risk comorbidities (2 points each): diabetes mellitus, severe immunocompromised status and obesity (body mass index≥30); non-white race/Hispanic or Latinx ethnicity (2 points), and 1 point each for: male sex, dyspnea, hypertension, coronary artery disease, cardiac arrythmia, congestive heart failure, chronic kidney disease, chronic pulmonary disease, chronic liver disease, cerebrovascular disease, and chronic neurologic disease. In the derivation cohort (n = 16,030) area under the receiver-operator characteristic curve (AUROC) was 0.82 (95% CI 0.81-0.84) for hospitalization and 0.91 (0.83-0.94) for 28-day mortality; in the validation cohort (n = 6,786) AUROC for hospitalization was 0.8 (CI 0.78-0.82) and for mortality 0.8 (CI 0.69-0.9). CONCLUSION: A prediction score based on widely available patient attributes accurately risk stratifies patients with COVID-19 at the time of testing. Applications include patient selection for therapies targeted at preventing disease progression in non-hospitalized patients, including monoclonal antibodies. External validation in independent healthcare environments is needed.

Real-world Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients With Early COVID-19.

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% (n = 1) in the MAb group compared with 1.0% (n = 71) and 1.0% (n = 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.

Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study.

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.