The Association of Vasopressor Administration through a Midline Catheter with Catheter-related Complications.

Rationale: Little is known about the safety of infusing vasopressors through a midline catheter. Objectives: To evaluate safety outcomes after vasopressor administration through a midline. Methods: We conducted a cohort study of adults admitted to 39 hospitals in Michigan (December 2017-March 2022) who received vasopressors while either a midline or peripherally inserted central catheter (PICC) was in place. Patients receiving vasopressors through a midline were compared with those receiving vasopressors through a PICC and, separately, to those with midlines in place but who received vasopressors through a different catheter. We used descriptive statistics to characterize and compare cohort characteristics. Multivariable mixed effects logistic regression models were fit to determine the association between vasopressor administration through a midline with outcomes, primarily catheter-related complications (bloodstream infection, superficial thrombophlebitis, exit site infection, or catheter occlusion). Results: Our cohort included 287 patients with midlines through which vasopressors were administered, 1,660 with PICCs through which vasopressors were administered, and 884 patients with midlines who received vasopressors through a separate catheter. Age (median [interquartile range]: 68.7 [58.6-75.7], 66.6 [57.1-75.0], and 67.6 [58.7-75.8] yr) and gender (percentage female: 50.5%, 47.3%, and 43.8%) were similar in all groups. The frequency of catheter-related complications was lower in patients with midlines used for vasopressors than PICCs used for vasopressors (5.2% vs. 13.4%; P < 0.001) but similar to midlines with vasopressor administration through a different device (5.2% vs. 6.3%; P = 0.49). After adjustment, administration of vasopressors through a midline was not associated with catheter-related complications compared with PICCs with vasopressors (adjusted odds ratios [aOR], 0.65 [95% confidence interval, 0.31-1.33]; P = 0.23) or midlines with vasopressors elsewhere (aOR, 0.85 [0.46-1.58]; P = 0.59). Midlines used for vasopressors were associated with greater risk of systemic thromboembolism (vs. PICCs with vasopressors: aOR, 2.69 [1.31-5.49]; P = 0.008; vs. midlines with vasopressors elsewhere: aOR, 2.42 [1.29-4.54]; P = 0.008) but not thromboses restricted to the ipsilateral upper extremity (vs. PICCs with vasopressors: aOR, 2.35 [0.83-6.63]; P = 0.10; model did not converge for vs. midlines with vasopressors elsewhere). Conclusions: We found no significant association of vasopressor administration through a midline with catheter-related complications. However, we identified increased odds of systemic (but not ipsilateral upper extremity) venous thromboembolism warranting further evaluation.

A Propensity-Matched Cohort Assessing Impact of a Neutralizing Monoclonal Antibody in Mild-to-Moderate Coronavirus Disease 2019.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoaV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. In randomized clinical trials, patients who were treated with the anti-spike monoclonal antibody bamlanivimab had fewer COVID-19-related hospitalizations or emergency department (ED) visits than the control group. Methods: A retrospective cohort was assembled across a multisite healthcare system between November 20, 2020 and March 31, 2021. Ambulatory COVID-19 patients treated with bamlanivimab (n = 209) were propensity score matched without replacement (1:1) to a pool of 1024 eligible control patients who received similar care without bamlanivimab. The primary endpoint was all-cause mortality or admission at 30 days. Secondary endpoints included hospitalization, critical care admission, oxygenation requirements, and infusion-related reactions. Propensity score matching (PSM) analysis was used to assess the effect of bamlanivimab infusion on the composite endpoint and secondary endpoints. Results: A total of n = 209 matched patients were included in each arm of the study. The absolute standardized difference (stddiff) was calculated and indicated a balance between the groups. Almost all variables had a stddiff of less than 0.10, except for respiratory rate (RR) (stddiff = -0.11). For the primary composite endpoint of the matched cohort, 10.1% (n = 21) of patients in the intervention group were hospitalized or deceased within 30-day postbamlanivimab infusion versus 27.8% (n = 58) in the control group (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.17 to 0.51, P < .001). Conclusion: Patients with ambulatory COVID-19 who received bamlanivimab in the outpatient setting had a statistically significant reduction on the odds of admission postinfusion. Despite bamlanivimab's lack of efficacy on newer SARS-CoV-2 variants, this study demonstrates that neutralizing monoclonal antibodies can be effective against specific variants. If variant identification becomes a more accessible tool in outpatient centers or EDs, more targeted therapeutic options may be considered.

Overdiagnosis of urinary tract infection linked to overdiagnosis of pneumonia: a multihospital cohort study.

Urinary tract infection (UTI) and community-acquired pneumonia (CAP) are the most common infections treated in hospitals. UTI and CAP are also commonly overdiagnosed, resulting in unnecessary antibiotic use and diagnostic delays. While much is known individually about overdiagnosis of UTI and CAP, it is not known whether hospitals with higher overdiagnosis of one also have higher overdiagnosis of the other. Correlation of overdiagnosis of these two conditions may indicate underlying hospital-level contributors, which in turn may represent targets for intervention. To evaluate the association of overdiagnosis of UTI and CAP, we first determined the proportion of hospitalised patients treated for CAP or UTI at 46 hospitals in Michigan who were overdiagnosed according to national guideline definitions. Then, we used Pearson's correlation coefficient to compare hospital proportions of overdiagnosis of CAP and UTI. Finally, we assessed for 'diagnostic momentum' (ie, accepting a previous diagnosis without sufficient scepticism) by determining how often overdiagnosed patients remained on antibiotics on day 3 of hospitalisation. We included 14 085 patients treated for CAP (11.4% were overdiagnosed) and 10 398 patients treated for UTI (27.8% were overdiagnosed) across 46 hospitals. Within hospitals, the proportion of patients overdiagnosed with UTI was moderately correlated with the proportion of patients overdiagnosed with CAP (r=0.53, p<0.001). Over 80% (81.8% (n=952/1164) of UTI; 89.9% (n=796/885) of CAP) of overdiagnosed patients started on antibiotics by an emergency medicine clinician remained on antibiotics on day 3 of hospitalisation. In conclusion, we found overdiagnosis of UTI and CAP to be correlated at the hospital level. Reducing overdiagnosis of these two common infections may benefit from systematic interventions.

Antibiotic Overuse After Hospital Discharge: A Multi-hospital Cohort Study.

BACKGROUND: Antibiotics are commonly prescribed to patients as they leave the hospital. We aimed to create a comprehensive metric to characterize antibiotic overuse after discharge among hospitalized patients treated for pneumonia or urinary tract infection (UTI), and to determine whether overuse varied across hospitals and conditions. METHODS: In a retrospective cohort study of hospitalized patients treated for pneumonia or UTI in 46 hospitals between 1 July 2017-30 July 2019, we quantified the proportion of patients discharged with antibiotic overuse, defined as unnecessary antibiotic use, excess antibiotic duration, or suboptimal fluoroquinolone use. Using linear regression, we assessed hospital-level associations between antibiotic overuse after discharge in patients treated for pneumonia versus a UTI. RESULTS: Of 21 825 patients treated for infection (12 445 with pneumonia; 9380 with a UTI), nearly half (49.1%) had antibiotic overuse after discharge (56.9% with pneumonia; 38.7% with a UTI). For pneumonia, 63.1% of overuse days after discharge were due to excess duration; for UTIs, 43.9% were due to treatment of asymptomatic bacteriuria. The percentage of patients discharged with antibiotic overuse varied 5-fold among hospitals (from 15.9% [95% confidence interval, 8.7%-24.6%] to 80.6% [95% confidence interval, 69.4%-88.1%]) and was strongly correlated between conditions (regression coefficient = 0.85; P < .001). CONCLUSIONS: Antibiotic overuse after discharge was common and varied widely between hospitals. Antibiotic overuse after discharge was associated between conditions, suggesting that the prescribing culture, physician behavior, or organizational processes contribute to overprescribing at discharge. Multifaceted efforts focusing on all 3 types of overuse and multiple conditions should be considered to improve antibiotic prescribing at discharge.

Assessment of Testing and Treatment of Asymptomatic Bacteriuria Initiated in the Emergency Department.

BACKGROUND: Reducing antibiotic use in patients with asymptomatic bacteriuria (ASB) has been inpatient focused. However, testing and treatment is often started in the emergency department (ED). Thus, for hospitalized patients with ASB, we sought to identify patterns of testing and treatment initiated by emergency medicine (EM) clinicians and the association of treatment with outcomes. METHODS: We conducted a 43-hospital, cohort study of adults admitted through the ED with ASB (February 2018-February 2020). Using generalized estimating equation models, we assessed for (1) factors associated with antibiotic treatment by EM clinicians and, after inverse probability of treatment weighting, (2) the effect of treatment on outcomes. RESULTS: Of 2461 patients with ASB, 74.4% (N = 1830) received antibiotics. The EM clinicians ordered urine cultures in 80.0% (N = 1970) of patients and initiated treatment in 68.5% (1253 of 1830). Predictors of EM clinician treatment of ASB versus no treatment included dementia, spinal cord injury, incontinence, urinary catheter, altered mental status, leukocytosis, and abnormal urinalysis. Once initiated by EM clinicians, 79% (993 of 1253) of patients remained on antibiotics for at least 3 days. Antibiotic treatment was associated with a longer length of hospitalization (mean 5.1 vs 4.2 days; relative risk = 1.16; 95% confidence interval, 1.08-1.23) and Clostridioides difficile infection (CDI) (0.9% [N = 11] vs 0% [N = 0]; P = .02). CONCLUSIONS: Among hospitalized patients ultimately diagnosed with ASB, EM clinicians commonly initiated testing and treatment; most antibiotics were continued by inpatient clinicians. Antibiotic treatment was not associated with improved outcomes, whereas it was associated with prolonged hospitalization and CDI. For best impact, stewardship interventions must expand to the ED.

Surviving the surge: Evaluation of early impact of COVID-19 on inpatient pharmacy services at a community teaching hospital.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has presented novel challenges to healthcare systems; however, an analysis of the impact of the pandemic on inpatient pharmacy services has not yet been conducted. METHODS: Results of an observational assessment of operational and clinical pharmacy services at a community teaching hospital during the first weeks of the COVID-19 pandemic are presented. Service outcomes of the inpatient pharmacy were evaluated from February 1 to April 8, 2020. Outcomes during the weeks preceding the first COVID-19 admission (February 1 to March 11, 2020) and during the pandemic period (March 12 to April 8, 2020) were compared. Evaluated outcomes included daily order verifications, clinical interventions, and usage of relevant medications. An exploratory statistical analysis was conducted using Student's t test. RESULTS: During the pandemic period, the number of new order verifications decreased from approximately 5,000 orders per day to 3,300 orders per day (P < 0.01), a reduction of 30% during the first 4 weeks of the pandemic compared to the weeks prior. Average daily pharmacokinetic dosing consults were reduced in the pandemic period (from 82 to 67; P < 0.01) compared to the prepandemic period; however, total daily pharmacist interventions did not differ significantly (473 vs 456; P = 0.68). Dispensing of hydroxychloroquine, azithromycin, enoxaparin, and sedative medications increased substantially during the pandemic period (P < 0.01 for all comparisons). CONCLUSION: The operational and clinical requirements of an inpatient pharmacy department shifted considerably during the first weeks of the COVID-19 pandemic. Pharmacy departments must be adaptable in order to continue to provide effective pharmaceutical care during the pandemic.

A Deeper Dive Into Antibiotic Stewardship Needs: A Multihospital Survey.

In a 2016 survey of 46 Michigan hospitals, we identified four key needs for antibiotic stewardship: clinically-relevant antibiotic data, monitoring compliance, syndrome-specific interventions, and discharge stewardship. A stewardship initiative now addresses these needs within the Michigan Hospital Medicine Safety Consortium.

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.

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.

Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients.

BACKGROUND: Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. METHODS: This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. RESULTS: Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h-∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. CONCLUSIONS: Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.

Standard versus prolonged doripenem infusion for treatment of gram-negative infections.

BACKGROUND: Doripenem is the most recently introduced carbapenem, with a broad spectrum of antimicrobial activity. Preliminary data indicated that activity is optimized by maximizing the time that serum concentration remains above the minimum inhibitory concentration; however, limited clinical data are available to support this approach. OBJECTIVE: To compare clinical outcomes before and after implementation of a hospital-wide initiative extending the duration of infusion for doripenem from 1 hour (standard) to 4 hours (prolonged). METHODS: This retrospective, quasi-experimental study compared clinical outcomes associated with doripenem administered as a 1-hour infusion versus a 4-hour infusion for treatment of suspected or documented infections caused by gram-negative organisms. Outcomes were assessed for the entire cohort, as well as for the subpopulation of patients admitted to the intensive care unit. RESULTS: Two hundred patients were included; 106 patients received doripenem via standard infusion and 94 patients via prolonged infusion. No significant differences were noted between the treatment groups in clinical success, length of stay, or duration of treatment when the entire cohort was evaluated. In the critically ill subgroup, pneumonia, standard-infusion doripenem, and concomitant bacteremia were independent predictors of clinical failure (adjusted odds ratio [95% CI] 7.8 [2.4-25.6], 5.5 [1.6-18.7], and 7.0 [1.6-31.3], respectively). Additionally, critically ill patients who received doripenem via standard infusion were significantly more likely to experience recurrence of infection or death within 90 days. No significant differences were noted in length of stay or duration of bacteremia. CONCLUSIONS: The duration of infusion did not significantly impact outcomes when the entire cohort was compared; however, prolonged infusion of doripenem was associated with significantly improved clinical outcomes among critically ill patients. These findings support the use of prolonged infusion of doripenem for critically ill patients.

Preserving renal function in liver transplant recipients with rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitors.

Early renal dysfunction following liver transplantation is associated with increased morbidity and mortality. To evaluate the impact of delayed initiation of calcineurin inhibitor on renal function, we conducted a retrospective study comparing 118 liver transplant recipients who received rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitor with 80 liver transplant recipients who received no antibody and early initiation of calcineurin inhibitor (control group). All patients received mycophenolate mofetil and steroids. Delayed calcineurin inhibitor initiation with anti-thymocyte globulin was associated with significant improvement in renal function throughout the first year post-transplant. At 12 months post-transplant, patients treated with this regimen experienced lower serum creatinine (1.4 +/- 0.5 versus 1.7 +/- 0.5 mg/dL, P < 0.001), a higher estimated glomerular filtration rate (57.4 +/- 20.5 versus 43.7 +/- 14.4 mL/min/1.73 m(2), P < 0.001), and less dependence on dialysis (0.8% versus 13%, P < 0.001) in comparison with no antibody and early calcineurin inhibitor initiation. Patient survival and graft survival were similar between groups; however, there was a trend of a lower incidence of early biopsy-proven acute rejection with anti-thymocyte globulin. Overall infection and cytomegalovirus infection were significantly lower in anti-thymocyte globulin-treated patients, and there was no increased incidence of hepatitis C recurrence in comparison with controls. In conclusion, delayed initiation of calcineurin inhibitor with anti-thymocyte globulin in liver transplant recipients is safe and is associated with improvements in renal function and a lower incidence of early acute rejection in comparison with no antibody and early initiation of calcineurin inhibitor.

Proposed relationship between intravenous immunoglobulin and thrombosis in renal transplant recipients.

OBJECTIVE: To report 2 cases of intravenous human immunoglobulin (IVIG)-associated thrombosis in kidney transplant patients. CASE SUMMARY: Both cases involved female patients presenting to Henry Ford Hospital in Detroit for renal transplantation. Patient 1 presented with systemic lupus erythematosus, positive for both anticardiolipin and anti-DNA antibody. Patient 2, postnephrectomy, was found to have moderate hyperhomocysteinemia, with a total plasma homocysteine level of 3.9 mg/L. Both patients were considered highly sensitized and at high risk for rejection due to the presence of either high panel reactive antibody or a positive B cell flow cytometry crossmatch, in addition to other risk factors. Therefore, IVIG was considered a viable treatment option to be included in induction therapy. IVIG was administered both peri- and postoperatively, and both patients experienced immediate graft function with good urine output. Within 24 hours following transplantation, elevations in serum creatinine and decreases in urine output were seen. Subsequently, kidney exploration was performed and palpable thrombi in renal arteries and veins were detected. Immediate nephrectomy was performed in both cases. DISCUSSION: Currently, evidence derived from case reports highlights numerous risk factors for IVIG-associated thrombosis, one of which appears to be a hypercoagulable state. It has also been reported that some IVIG products contain amounts of anticardiolipin antibodies; these antibodies may potentiate thrombosis in the presence of hypercoagulable states, such as hyperhomocysteinemia or antiphospholipid syndrome. In these 2 patients, the Naranjo probability scale indicated that there was a possible association between the thrombotic events and the use of IVIG. CONCLUSIONS: Prospective trials evaluating the safety of IVIG in highly sensitized transplant patients are scarce. Therefore, it is imperative that the benefits and risks be weighed when considering the use of IVIG in highly sensitized transplant patients.