Bridging the gap: An approach to reporting antimicrobial stewardship metrics specific to solid organ transplant recipients.

BACKGROUND: This study seeks to describe inpatient antimicrobial use (AU) utilizing the National Healthcare Safety Network-AU (NHSN-AU) framework among solid organ transplant recipients (SOTr) within 12 months after transplant. METHODS: This cross-sectional study included SOTr ≥ 18 years of age who underwent transplantation from January 2015 to December 2016 at a Midwestern US transplant center. Inpatient AU was followed for 12 months post-transplant. Hospital days present up to 12 months post-transplant, AU variables, and Clostridioides difficile infection (CDI) occurrences were analyzed. RESULTS: The cohort of 530 SOTr included 225 kidney (42.5%), 171 liver (32.3%), 45 lung (8.5%), 40 heart (7.5%), 39 multivisceral (7.4%), seven small bowel (1.3%), and three pancreas (0.6%) transplants. Total days of therapy (DOT) were 22 782 among the cohort, with a median of 5 days [interquartile range [IQR], 1-12]. Lung and liver transplants had the most total DOT (6571 vs. 5569 days), while lungs and small bowels had the highest median DOT (13 [IQR, 2-56] vs. 12 [IQR, 2-31]). The facility-wide DOT/1000 days were lowest in pancreas and highest in lung transplants (5.3 vs. 428.1). Small bowel transplants received the most resistant-Gram-positive infection and hospital-onset infection agents for facility-wide DOT/1000 days present. Pancreas and kidney transplants accounted for the most high-risk CDI agents. CDI occurred in 34 patients, with kidney and liver transplants experiencing 13 each. CONCLUSION: This study represents one of the first reports of AU in SOTr utilizing the NHSN-AU framework. More studies are needed for further peer-to-peer comparison of AU in this complex patient population.

Safety and Efficacy of a Percutaneously Inserted Ventricular Support Device Purge Solution Heparin 25 U/mL.

BACKGROUND: The Impella is a percutaneous ventricular assist device (pVAD) that provides temporary hemodynamic support to patients with cardiogenic shock or for protected percutaneous coronary intervention. The manufacturer recommends a 50-U/mL concentration of heparin purge solution (or 25 U/mL as an alternative), with systemic heparin to maintain therapeutic anticoagulation during device support. Concomitant use of systemic heparin with the purge solution may increase the risk of bleeding. OBJECTIVES: The primary objective of this study was to describe the prevalence of thrombosis and bleeding using a less-concentrated heparin purge solution (25 U/mL) in combination with systemic heparin therapy. METHODS: This was a retrospective observational cohort study of patients who required at least 12 hours of pVAD support and received 25-U/mL concentration of heparin purge solution between January 1, 2014, and May 31, 2017. The primary end points were the rate of thrombotic and bleeding events. Secondary end points included the percentage of time within the therapeutic activated partial thromboplastin time (aPTT) range. Descriptive statistics were utilized for data analysis. RESULTS: Of the 161 patients screened, 100 met inclusion criteria; 63% of patients experienced a bleeding event, with Bleeding Academic Research Consortium (BARC) type 3a being the most common. Median percentages of subtherapeutic and supratherapeutic aPTT values were similar between the bleeding and nonbleeding groups. Two patients experienced thrombotic events. CONCLUSION AND RELEVANCE: Based on our findings, the device thrombosis rate was 2% and the rate of major bleeding (BARC 3a and higher) was 35%. This study provides descriptive outcomes data of a lower-concentration heparin purge solution.

High-Dose Daptomycin Is Well Tolerated via 2-Minute IV Push Administration.

BACKGROUND: The purpose of this study was to evaluate the safety of administering high-dose daptomycin (HDD; > 6 mg/kg actual body weight) as a 2-minute intravenous (IV) push (IVP) compared to traditional 30-minute IV piggyback (IVPB) infusion. METHODS: Retrospective cohort study comparing patients receiving HDD as an IVP or IVPB infusion. The primary outcome was the proportion of patients with a documented infusion-related reaction (IRR) to daptomycin. RESULTS: Three hundred patients were included in the final analysis, 200 patients received IVP, and 100 patients received IVPB representing a total of 1697 administrations. Median (IQR) daptomycin dose was IVP 700 mg (550-900) and IVPB 700 mg (600-900), with mg/kg doses of 8.2 (7.9-10) and 8.3 (8-10), respectively. After adjudication, IRR occurred in 1% of subjects in each treatment group. CONCLUSIONS: This study provides data in more than 1100 administrations of HDD administered via IVP. Infusion-related reactions were documented in 1% of patients regardless of infusion method, suggesting comparable safety to traditional infusion methods. This practice may be useful during fluid shortage and in the outpatient setting.

Case report and cohort analysis of drug-induced liver injury associated with daptomycin.

A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia without concurrent multiorgan dysfunction or elevation of his creatinine kinase level. After ruling out other etiologies, the liver injury was attributed to daptomycin and was subsequently resolved. A single-center retrospective cohort analysis of baseline and follow-up liver function panels (n = 614) from all admissions from 2008 to 2013 during which daptomycin was administered did not reveal any other cases of probable or definite drug-induced liver injury associated with daptomycin.

Risk evaluation and mitigation strategy compliance for pulmonary hypertension medications after policy implementation with computerized provider order entry support.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Treatment for pulmonary hypertension includes medications with risk evaluation and mitigation strategy (REMS) programs. Health-system inpatient pharmacies dispensing these agents must comply with inpatient REMS dispensing criteria. Implementing a health-system policy with computerized provider order entry (CPOE) decision support may improve REMS compliance. METHODS: This was a retrospective, quasi-experimental study comparing REMS compliance before and after development of a policy with CPOE decision support that was implemented in August 2019. Patients 18 years of age or older with a diagnosis of pulmonary hypertension were included if they received at least one dose of an endothelin receptor antagonist or riociguat while hospitalized. Patients were included in the preintervention group if they were hospitalized between August 1, 2017, and August 31, 2019, and in the postintervention group if they were hospitalized between September 1, 2019, and August 31, 2021. The primary outcome was the REMS compliance rate. Secondary endpoints included the time to REMS compliance and independent factors associated with failed or delayed REMS compliance. RESULTS: A total of 150 patients were included, with 75 patients in both the pre- and postintervention groups. Compliance increased significantly from the preintervention (50%) to postintervention (92%) group (P < 0.001). Time to compliance was also significantly reduced from 770 minutes in the preintervention group to 140 minutes in the postintervention group (P = 0.031). Factors independently associated with REMS compliance were being in the postintervention group (odds ratio, 16.9; 95% confidence interval, 5.8-49.2) and being admitted to a pulmonary hypertension center for comprehensive care. (odds ratio, 7.8; 95% confidence interval, 2.9-21.2). CONCLUSION: A health-system policy with CPOE decision support improved both the rate of and time to compliance with inpatient REMS dispensing procedures.

The impact of pharmacist-directed patient education and anticoagulant care coordination on patient satisfaction.

BACKGROUND: Patient satisfaction data played a role in determining Medicare reimbursement as of October 2012. Clinical pharmacy services could improve satisfaction of hospital inpatients but it is unclear whether this relates to performance on standardized hospital surveys. OBJECTIVE: To describe the impact on patient satisfaction of patient education and follow-up care coordination provided by an inpatient pharmacist-directed anticoagulation service (PDAS). METHODS: This study was conducted at an urban, tertiary care hospital. PDAS is a clinical pharmacy service that has improved transition-of-care, safety, and efficacy involving anticoagulation at our institution. Patients receiving inpatient anticoagulation during February 2001-April 2007 (pre-PDAS) and December 2008-December 2010 (post-PDAS), who responded to a mail-in survey, were included. Survey items included satisfaction ("How satisfied were you with the medical care?"), amount of information ("Was the amount of information you received about your medicine...?"), clarity of information ("Was the clarity of the information about your medicine...?"), answer quality ("Were the answers to your questions about your medicine...?"), and spoke to a pharmacist ("Did a pharmacist speak with you during your stay?"). Response options for amount of information, clarity of information, answer quality, and satisfaction used a symmetric 5-point Likert-type scale, with options 1-5 indicating most to least positive, respectively. Options 1-2 were considered positive and options 3-5 were considered negative. Primary analysis compared patient satisfaction (defined as rate of positive responses) between pre-PDAS and post-PDAS respondents. χ² test was used for all comparisons. RESULTS: Surveys were distributed to 1694 patients after discharge, with 687 (40.6%) responding. Post-PDAS respondents had improved patient satisfaction for all positive response items, compared to pre-PDAS scores. Amount of information increased by 37.2%, clarity of information increased by 35.2%, answer quality increased by 29.5%, and satisfaction increased by 10.6% (p < 0.001 for all comparisons). CONCLUSIONS: Hospitals deploying focused programs with systematic approaches to patient-pharmacist communication may positively impact patient satisfaction.

A failure in the medication delivery system-how disclosure and systems investigation improve patient safety.

A recent medication error at Vanderbilt University Medical Center contributed to the death of a patient. The ensuing criminal indictment of the administering nurse has shaken the medical community. This has led to clinical staff questioning whether they can disclose patient safety incidents without fear of criminal prosecution. However, because of the publicity of this case, hospitals can benefit from the lessons learned and mitigate the risk of this and similar events at their facilities. To uncover the most impactful and relevant safety recommendations, the Vanderbilt case is examined from a systems investigation perspective using the available public information gathered from media reports, the Tennessee Bureau of Investigation report, and Vanderbilt's corrective action plan submitted to CMS. We present an example of how hospitals can benefit from disclosure: Henry Ford Health used the Vanderbilt case study as part of its medication safety continuous improvement initiatives, which are underpinned by available medication safety recommendations from the Institute for Safe Medication Practices. Using this experience and the lessons learned from the Vanderbilt case, a proactive action plan is presented for hospitals nationwide to prevent the recurrence of this medication error. Without disclosure, these analyses and safety recommendations would not have been possible.

Evaluating the Impact of Substance Use Disorder Resources on Outcomes of Persons Who Inject Drugs with Infections.

OBJECTIVE: The aim of the study is to evaluate the impact of inpatient substance use disorder (SUD) resources on outcomes of persons who inject stimulants and/or opioids (PWIDs) with infections. METHODS: This retrospective cohort evaluated PWIDs hospitalized from July 1, 2020, to May 31, 2021, and prescribed an antimicrobial course. The patients were compared based on inpatient implementation of SUD resources, including consultation of addiction medicine/behavioral health, implementation of an opioid withdrawal treatment protocol, or continuation/initiation of medications for opioid use disorder. The primary outcome was a composite of antibiotic completion, no unplanned discharge, and no 30-day readmission. Notable secondary outcomes included length of stay and presence of stigmatizing language in the electronic medical record. RESULTS: A total of 119 patients were analyzed-74 (62.2%) received SUD resources. The primary outcome was met by 43 patients with SUD resources implemented (58.1%) and 19 patients without resources (42.2%, P = 0.093). After adjustment for infection type, implementation of SUD resources (adjusted odds ratio, 2.593; 95% confidence interval, 1.162-5.789) was independently associated with primary outcome success. The patients who received SUD resources had a median length of stay of 7 days (4-13.3) compared with 4 days (2-6.5) in those without resources ( P < 0.001). Stigmatizing language was present in 98% of patient electronic medical records. CONCLUSIONS: Patient care provided to PWIDs with infections is optimized when SUD resources are implemented. This study further supports the necessity of improving SUD management when PWIDs are admitted to healthcare facilities.

Evaluation of the selection of cerebrospinal fluid testing in suspected meningitis and encephalitis.

Diagnostic stewardship interventions can decrease unnecessary antimicrobial therapy and microbiology laboratory resources and costs. This retrospective cross-sectional study evaluated factors associated with inappropriate initial cerebrospinal fluid (CSF) testing in patients with suspected community-acquired meningitis or encephalitis. In 250 patients, 202 (80.8%) and 48 (19.2%) were suspected meningitis and encephalitis, respectively. 207 (82.8%) patients had inappropriate and 43 (17.2%) appropriate testing. Any inappropriate CSF test was greatest in the immunocompromised (IC) group (n = 54, 91.5%), followed by non-IC (n = 109, 80.1%) and HIV (n = 44, 80%). Ordering performed on the general ward was associated with inappropriate CSF test orders (adjOR 2.81, 95% CI [1.08-7.34]). Laboratory fee costs associated with excessive testing was close to $300,000 per year. A stepwise algorithm defining empiric and add on tests according to CSF parameters and patient characteristics could improve CSF test ordering in patients with suspected meningitis or encephalitis.

Outcomes associated with apixaban vs warfarin in patients with renal dysfunction.

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Treatment of patients with chronic thrombo embolic pulmonary hypertension: focus on riociguat.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation-perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy. However, up to one-third of patients are not candidates for the surgery, either due to distal and inaccessible nature of the lesions or comorbid conditions. Due to remodeling that occurs in nonobstructed pulmonary vessels, a portion of patients who have undergone PEA have residual CTEPH after the procedure, attributable to high shear stress prior to PEA. This phenomenon has led to the understanding of a so-called "two-compartment model" of CTEPH, opening the door to pharmacologic treatment strategies. In 2013, riociguat, a soluble guanylate cyclase stimulator, was approved in the US and Europe for the treatment of inoperable or persistent/recurrent CTEPH. This article reviews the current management of CTEPH with a focus on riociguat.

Riociguat: a novel new drug for treatment of pulmonary hypertension.

Riociguat is the first approved medication from the novel class of soluble guanylate cyclase (sGC) stimulators and the only agent approved for treating both chronic thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH). The novel mechanism of riociguat lies in its ability to restore the homeostatic and therapeutic effects of nitric oxide that are diminished as a result of phenotypic alterations associated with pulmonary hypertension (PH). Improvements in 6-minute walk distance (6MWD) in patients with PAH during the phase 3 PATENT-1 trial were comparable to other oral agents approved for the treatment of PAH. Improvements in 6MWD in patients with CTEPH during the phase 3 CHEST-1 trial were greater than those previously observed with other oral PAH-directed therapies. Hypotension is the dose-limiting adverse effect of riociguat and dose titration is performed gradually according to systolic blood pressure. Riociguat was tolerated at maximal doses by most patients during PATENT-1 and CHEST-1 and was well tolerated during long-term extension studies. Key factors to consider with riociguat are a patient's systolic blood pressure, drug interactions mediated by CYP1A1, CYP3A4, and P-glycoprotein, cost, and teratogenicity requiring enrollment in a Risk Evaluation and Mitigation Strategy program. Recently published guidelines recommend riociguat monotherapy as an option for treatment-naïve patients with World Health Organization Functional Class (WHO FC) II or III symptoms or as add-on therapy for patients with persistent WHO FC III or IV symptoms being treated with an ERA or inhaled prostanoid. Postmarketing experience and ongoing clinical investigations will further define the safety and role of riociguat in patients with PAH and other types of PH.

Dosing of vancomycin in patients with continuous-flow left ventricular assist devices: a clinical pharmacokinetic analysis.

PURPOSE: To describe the pharmacokinetics of vancomycin in patients with continuous-flow left ventricular assist devices (CF-LVADs). METHODS: Eligible patients were ≥18 years old, implanted with a Heart Mate II CF-LVAD during January 2008-April 2012, and treated with vancomycin ≥48 hours for infection. Key exclusion criteria were unstable renal function, acute heart failure exacerbation, hemodynamic instability, and recent surgery. First-order elimination rate constant (Ke) and volume of distribution (Vd) were estimated using ideal (IBW), adjusted (AdjBW), actual (ABW), and fixed body weights. Estimated parameters were compared with measured pharmacokinetic parameters, which were calculated from steady state peak and trough vancomycin levels using one-compartment model equations. RESULTS: Twelve patients were included (age 44.9 ± 15 years, 91.7% male, 58.3% obese, CLcr 79.2 ± 27 mL ∙ min⁻¹). Common treatment indications were health-care associated pneumonia (41.7%), driveline infection (25%), and sepsis (16.7%). All methods of predicting Ke provided overestimates (p<0.05), ranging from 47 to 79%, depending on body habitus. METHODS: of predicting Vd using ABW in obese patients yielded overestimates of 74.5% (p<0.05), where IBW predictive Vd equations provided accurate assessments regardless of body habitus. CONCLUSIONS: General population methods may not accurately estimate the pharmacokinetic parameters of vancomycin for compensated heart failure patients implanted with CF-LVADs.

Naltrexone/bupropion: an investigational combination for weight loss and maintenance.

Naltrexone/bupropion is an investigational combination for weight loss and maintenance in patients who are obese or have a BMI ≥ 27 kg/m(2) with comorbid diabetes, hypertension or hyperlipidemia. Pooled results from four phase 3 trials reveal placebo-subtracted mean weight loss of 4.7% (range 3.2-5.2%) with naltrexone/bupropion after 1 year (p < 0.001 vs. placebo in each trial). The placebo-subtracted proportion of patients achieving ≥5% weight loss with naltrexone/bupropion ranged from 26 to 33% (p < 0.001 vs. placebo in each trial). In the majority of phase 3 trials, naltrexone/bupropion significantly improved proportion of patients achieving ≥10% weight loss, waist circumference, triglycerides, high-density lipoprotein, fasting insulin, insulin resistance, and obesity-specific quality of life compared to placebo. In patients with diabetes, naltrexone/bupropion therapy decreased hemoglobin A1c (HbA1c) approximately 0.5% more than placebo (p < 0.001). Common side effects associated with naltrexone/bupropion include nausea, constipation, vomiting, dizziness, and dry mouth. Greater improvement in systolic blood pressure and pulse were seen with placebo compared to naltrexone/bupropion (p < 0.001). Further studies are necessary to determine the effect of naltrexone/bupropion on cardiovascular outcomes. The safety and efficacy of naltrexone/bupropion in weight management is reviewed in this article.