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BACKGROUND: With a unique influenza season occurring in the midst of a pandemic, there is interest in assessing the role of the influenza vaccine in COVID-19 susceptibility and severity. METHODS: In this retrospective cohort study, patients receiving a laboratory test for COVID-19 were identified. The primary outcome was comparison of positive COVID-19 testing in those who received the influenza vaccine versus those who did not. Secondary end points in patients testing positive for COVID-19 included mortality, need for hospitalization, length of stay, need for intensive care, and mechanical ventilation. RESULTS: A total of 27,201 patients received laboratory testing for COVID-19. The odds of testing positive for COVID-19 was reduced in patients who received an influenza vaccine compared to those who did not (odds ratio 0.76, 95% CI 0.68-0.86; P

Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing., In this 48-hospital cohort study of 11 748 patients hospitalized with pneumonia or positive urine cultures, hospital-based antibiotic stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone use during hospitalization, but appeared to partially increase fluoroquinolone prescribing at discharge.

Background The guidelines for peripherally inserted central catheters (PICCs) recommend avoiding insertion if the anticipated duration of use is =5 days. However, short-term PICC use is common in hospitals. We sought to identify patient, provider, and device characteristics and the clinical outcomes associated with short-term PICCs. Methods Between January 2014 and June 2016, trained abstractors at 52 Michigan Hospital Medicine Safety (HMS) Consortium sites collected data from medical records of adults that received PICCs during hospitalization. Patients were prospectively followed until PICC removal, death, or 70 days after insertion. Multivariable logistic regression models were fit to identify factors associated with short-term PICCs, defined as dwell time of =5 days. Complications associated with short-term use, including major (eg, venous thromboembolism [VTE] or central lineassociated bloodstream infection [CLABSI]) or minor (eg, catheter occlusion, tip migration) events were assessed. Results Of the 15,397 PICCs placed, 3902 (25.3%) had a dwell time of =5 days. Most (95.5%) short-term PICCs were removed during hospitalization. Compared to PICCs placed for >5 days, variables associated with short-term PICCs included difficult venous access (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.40-1.69), multilumen devices (OR, 1.53; 95% CI, 1.39-1.69), and teaching hospitals (OR, 1.25; 95% CI, 1.04-1.52). Among those with short-term PICCs, 374 (9.6%) experienced a complication, including 99 (2.5%) experiencing VTE and 17 (0.4%) experiencing CLABSI events. The most common minor complications were catheter occlusion (4%) and tip migration (2.2%). Conclusion Short-term use of PICCs is common and associated with patient, provider, and device factors. As PICC placement, even for brief periods, is associated with complications, efforts targeted at factors underlying such use appear necessary.

Essentials How best to quantify thrombosis risk with peripherally inserted central catheters (PICC) is unknown. Data from a registry were used to develop the Michigan Risk Score (MRS) for PICC thrombosis. Five risk factors were associated with PICC thrombosis and used to develop a risk score. MRS was predictive of the risk of PICC thrombosis and can be useful in clinical practice. SummaryBackground Peripherally inserted central catheters (PICCs) are associated with upper extremity deep vein thrombosis (DVT). We developed a score to predict risk of PICC-related thrombosis. Methods Using data from the Michigan Hospital Medicine Safety Consortium, image-confirmed upper-extremity DVT cases were identified. A logistic, mixed-effects model with hospital-specific random intercepts was used to identify factors associated with PICC-DVT. Points were assigned to each predictor, stratifying patients into four classes of risk. Internal validation was performed by bootstrapping with assessment of calibration and discrimination of the model. Results Of 23 010 patients who received PICCs, 475 (2.1%) developed symptomatic PICC-DVT. Risk factors associated with PICC-DVT included: history of DVT; multi-lumen PICC; active cancer; presence of another CVC when the PICC was placed; and white blood cell count greater than 12 000. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9% for class I, 1.6% for class II, 2.7% for class III and 4.7% for class IV, with marginal predicted probabilities of 0.9% (0.7, 1.2), 1.5% (1.2, 1.9), 2.6% (2.2, 3.0) and 4.5% (3.7, 5.4) for classes I, II, III, and IV, respectively. The risk classification rule was strongly associated with PICC-DVT, with odds ratios of 1.68 (95% CI, 1.19, 2.37), 2.90 (95% CI, 2.09, 4.01) and 5.20 (95% CI, 3.65, 7.42) for risk classes II, III and IV vs. risk class I, respectively. Conclusion The Michigan PICC-DVT Risk Score offers a novel way to estimate risk of DVT associated with PICCs and can help inform appropriateness of PICC insertion.

Two paradigms for the evaluation of surrogate markers in randomized clinical trials have been proposed: the causal effects paradigm and the causal association paradigm. Each of these paradigms rely on assumptions that must be made to proceed with estimation and to validate a candidate surrogate marker (S) for the true outcome of interest (T). We consider the setting in which S and T are Gaussian and are generated from structural models that include an unobserved confounder. Under the assumed structural models, we relate the quantities used to evaluate surrogacy within both the causal effects and causal association frameworks. We review some of the common assumptions made to aid in estimating these quantities and show that assumptions made within one framework can imply strong assumptions within the alternative framework. We demonstrate that there is a similarity, but not exact correspondence between the quantities used to evaluate surrogacy within each framework, and show that the conditions for identifiability of the surrogacy parameters are different from the conditions, which lead to a correspondence of these quantities.

Triggering events for acute aortic dissections are incompletely understood. We sought to investigate whether there is an association between admission for acute type A aortic dissection (ATAAD) to the University of Michigan Medical Center and the reported annual influenza activity by the Michigan Department of Health and Human Services. From 1996–2019 we had 758 patients admitted for ATAAD with 3.1 admissions per month during November-March and 2.5 admissions per month during April-October (p = 0.01). Influenza reporting data by the Michigan Department of Health and Human Services became available in 2009. ATAAD admissions for the period 2009–2019 (n = 455) were 4.8 cases/month during peak influenza months compared to 3.5 cases/month during non-peak influenza months (p = 0.001). ATAAD patients admitted during influenza season had increased in-hospital mortality (11.0% vs. 5.8%, p = 0.024) and increased 30-day mortality (9.7 vs. 5.4%, p = 0.048). The results point to higher admission rates for ATAAD during months with above average influenza rates. Future studies need to investigate whether influenza virus infection affects susceptibility for aortic dissection, and whether this risk can be attenuated with the annual influenza vaccine in this patient population.

Catheter exchange over a guidewire is frequently performed for malfunctioning peripherally inserted central catheters (PICCs). Whether such exchanges are associated with venous thromboembolism is not known.We performed a retrospective cohort study to assess the association between PICC exchange and risk of thromboembolism. Adult hospitalized patients that received a PICC during clinical care at one of 51 hospitals participating in the Michigan Hospital Medicine Safety consortium were included. The primary outcome was hazard of symptomatic venous thromboembolism (radiographically confirmed upper-extremity deep vein thrombosis and pulmonary embolism) in those that underwent PICC exchange vs those that did not.Of 23,010 patients that underwent PICC insertion in the study, 589 patients (2.6%) experienced a PICC exchange. Almost half of all exchanges were performed for catheter dislodgement or occlusion. A total of 480 patients (2.1%) experienced PICC-associated deep vein thrombosis. The incidence of deep vein thrombosis was greater in those that underwent PICC exchange vs those that did not (3.6% vs 2.0%, P .001). Median time to thrombosis was shorter among those that underwent exchange vs those that did not (5 vs 11 days, P = .02). Following adjustment, PICC exchange was independently associated with twofold greater risk of thrombosis (hazard ratio [HR] 1.98; 95% confidence interval [CI], 1.37-2.85) vs no exchange. The effect size of PICC exchange on thrombosis was second in magnitude to device lumens (HR 2.06; 95% CI, 1.59-2.66 and HR 2.31; 95% CI, 1.6-3.33 for double- and triple-lumen devices, respectively).Guidewire exchange of PICCs may be associated with increased risk of thrombosis. As some exchanges may be preventable, consideration of risks and benefits of exchanges in clinical practice is needed.

BACKGROUNDPeripherally inserted central catheters (PICCs) are associated with central-line–associated bloodstream infections (CLABSIs). However, no tools to predict risk of PICC-CLABSI have been developed.OBJECTIVETo operationalize or prioritize CLABSI risk factors when making decisions regarding the use of PICCs using a risk model to estimate an individual’s risk of PICC-CLABSI prior to device placement.METHODSUsing data from the Michigan Hospital Medicine Safety consortium, patients that experienced PICC-CLABSI between January 2013 and October 2016 were identified. A Cox proportional hazards model with robust sandwich standard error estimates was then used to identify factors associated with PICC-CLABSI. Based on regression coefficients, points were assigned to each predictor and summed for each patient to create the Michigan PICC-CLABSI (MPC) score. The predictive performance of the score was assessed using time-dependent area-under-the-curve (AUC) values.RESULTSOf 23,088 patients that received PICCs during the study period, 249 patients (1.1%) developed a CLABSI. Significant risk factors associated with PICC-CLABSI included hematological cancer (3 points), CLABSI within 3 months of PICC insertion (2 points), multilumen PICC (2 points), solid cancers with ongoing chemotherapy (2 points), receipt of total parenteral nutrition (TPN) through the PICC (1 point), and presence of another central venous catheter (CVC) at the time of PICC placement (1 point). The MPC score was significantly associated with risk of CLABSI (PCONCLUSIONThe MPC score offers a novel way to inform decisions regarding PICC use, surveillance of high-risk cohorts, and utility of blood cultures when PICC-CLABSI is suspected. Future studies validating the score are necessary.Infect Control Hosp Epidemiol2017;38:1155–1166

Background Broad-spectrum (BS) antibiotics directed against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are commonly used for health-care associated pneumonia (HCAP) treatment. Many patients with HCAP do not have a microbiologically confirmed diagnosis. The goal of this study was to evaluate the impact of antibiotic de-escalation on clinical outcomes in patients with HCAP without a microbiological diagnosis. Methods This is a retrospective cohort study of adult, non-ICU, medical patients hospitalized with HCAP between January 2016 and February 2018 at 46 Michigan hospitals. Exclusions included extrapulmonary infection, severe immune suppression, or clinical instability on day 4. Included patients: (1) lacked any positive culture (blood/sputum); (2) started on empiric anti-P. aeruginosa and anti-MRSA therapy by hospital day 2; (3) switched to a narrow-spectrum (NS) regimen (no anti-P. aeruginosa or anti-MRSA coverage) or maintained on BS antibiotics (anti-P. aeruginosa ± anti-MRSA) by therapy day 4 (Figure 1). Mortality, readmission, Clostridium difficile infection, and adverse events from antibiotics were compared between the BS and NS groups. Data were analyzed using logistic generalized estimating equation models and inverse probability of treatment weighting. Results Of 363 patients with HCAP included, 73 (20%) were switched to an NS regimen. Of 290 patients maintained on anti-PSA BS regimens, 47.6% also continued anti-MRSA therapy. The median age was 72 (IQR, 61–81) and Charlson comorbidity index was 4 (IQR, 2–6) of the entire cohort. Baseline characteristics were similar between BS and NS groups, except more patients had chronic kidney disease in the BS group. On multivariable analysis, no other baseline factors were found to be associated with use of BS antibiotics on day 4. Both total and IV antibiotic duration were longer in the BS group (10 vs. 8 days, P = 0.002, and 4 vs. 3 days, P < 0.001, respectively). On adjusted analysis, there were no differences in patient outcomes (Figure 2). Conclusion Among patients with HCAP started on empiric MRSA and PSA coverage without microbiological diagnosis, clinical outcomes were similar in patients switched to an NS antibiotic and those maintained on BS antibiotics. Our findings suggest a potential role for antimicrobial stewardship in promoting antibiotic de-escalation in this population. Disclosures All authors: No reported disclosures.

Importance Treatment of asymptomatic bacteriuria (ASB) with antibiotics is a common factor in inappropriate antibiotic use, but risk factors and outcomes associated with treatment of ASB in hospitalized patients are not well defined. Objective To evaluate factors associated with treatment of ASB among hospitalized patients and the possible association between treatment and clinical outcomes. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 2016, through February 1, 2018, at 46 hospitals participating in the Michigan Hospital Medicine Safety Consortium. A total of 2733 hospitalized medical patients with ASB, defined as a positive urine culture without any documented signs or symptoms attributable to urinary tract infection, were included in the analysis. Exposures One or more antibiotic dose for treatment of ASB. Main Outcomes and Measures Estimators of antibiotic treatment of ASB. Secondary outcomes included 30-day mortality, 30-day hospital readmission, 30-day emergency department visit, discharge to post–acute care settings,Clostridioides difficileinfection (formerly known asClostridium difficile) at 30 days, and duration of hospitalization after urine testing. Results Of 2733 patients with ASB, 2138 were women (78.2%); median age was 77 years (interquartile range [IQR], 66-86 years). A total of 2259 patients (82.7%) were treated with antibiotics for a median of 7 days (IQR, 4-9 days). Factors associated with ASB treatment included older age (odds ratio [OR], 1.10 per 10-year increase; 95% CI, 1.02-1.18), dementia (OR, 1.57; 95% CI, 1.15-2.13), acutely altered mental status (OR, 1.93; 95% CI, 1.23-3.04), urinary incontinence (OR, 1.81; 95% CI, 1.36-2.41), leukocytosis (white blood cell count >10 000/μL) (OR, 1.55; 95% CI, 1.21-2.00), positive urinalysis (presence of leukocyte esterase or nitrite, or >5 white blood cells per high-power field) (OR, 2.83; 95% CI, 2.05-3.93), and urine culture with a bacterial colony count greater than 100 000 colony-forming units per high-power field (OR, 2.30; 95% CI, 1.83-2.91). Treatment of ASB was associated with longer duration of hospitalization after urine testing (4 vs 3 days; relative risk, 1.37; 95% CI, 1.28-1.47). No other differences in secondary outcomes were identified after propensity weighting. Conclusions and Relevance Hospitalized patients with ASB commonly receive inappropriate antibiotic therapy. Antibiotic treatment did not appear to be associated with improved outcomes; rather, treatment may be associated with longer duration of hospitalization after urine testing. To possibly reduce inappropriate antibiotic use, stewardship efforts should focus on improving urine testing practices and management strategies for elderly patients with altered mental status.

Background Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design Retrospective cohort study. Setting 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients 6481 general care medical patients with pneumonia. Measurements The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary funding source Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.

Background Existing guidelines, including Choosing Wisely recommendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patients with chronic kidney disease (CKD). Objective To describe the frequency of and characteristics associated with PICC use in hospitalized patients with stage 3b or greater CKD (glomerular filtration rate [GFR]

Background Community-acquired pneumonia (CAP) guidelines recommend transition to an oral (PO) β-lactam (BL) regimen or fluoroquinolone (FQ) when patients are clinically stable. Due to collateral damage associated with FQs, stewardship efforts often focus on reducing initial FQ use for CAP therapy. We hypothesized that FQ use remains prevalent in CAP treatment despite initial intravenous (IV) BL therapy, and examined factors associated with switching to a PO BL vs. an FQ and the impact on outcomes. Methods In this retrospective cohort study, data were collected from January 2016 through February 2018 on non-ICU medical patients admitted with CAP at 46 Michigan hospitals. Patients were included if they received IV BL (ceftriaxone or ampicillin-sulbactam) plus macrolide/doxycycline by hospital day 2 and switched to a PO respiratory FQ or BL by therapy day 4. Exclusions included positive culture, concomitant infection, HCAP, unstable on day 4, or severe immune deficiency. Data were analyzed using logistic generalized estimating equation models, accounting for hospital-level clustering; outcomes were adjusted using the inverse probability of treatment weighting by propensity scores. Results. Of 555 included patients, 54.4% were switched to a PO BL vs. 45.6% to an FQ by day 4 of therapy. The groups had similar durations of therapy (8 days), time to clinical stability, prior antibiotics, and COPD, but the BL group was older, with a higher Pneumonia Severity Index, CURB-65, and more cardiovascular (CV) disease (Figure 1). In multivariable analysis, CV disease and higher CURB-65 were more common and diabetes (DM) less common in the PO BL group (Figure 2). Sharing antibiotic use data with providers were associated with less FQ use (83.1% vs. 70.8%, OR 0.51, 95% CI 0.27, 0.97, P = 0.04). On adjusted analysis there were no differences in patient outcomes (Figure 3). Conclusion. Among CAP patients started on an IV BL regimen, nearly half were switched to a PO FQ by therapy day 4, including more patients with DM. Although there were sicker patients in the BL group, there were no differences in outcomes between cohorts. To reduce FQ use, stewardship programs should share antibiotic use data and provide guidance for step-down therapy in clinically stable CAP patients. Disclosures All authors: No reported disclosures.

National guidelines1 recommend objective risk stratification for venous thromboembolism (VTE) in hospitalized medical patients. The Padua Prediction Score risk assessment model2 is recommended to categorize patients as high or low risk. The Michigan Hospital Medicine Safety Consortium (HMS), a statewide quality collaborative aimed at preventing adverse events in hospitalized medical patients, collects detailed data on VTE risk factors, prophylactic treatment, and outcomes. Using data from the HMS,3 we sought to determine whether patients in this cohort were receiving appropriate VTE prophylaxis.