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.

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.

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.

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.

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.

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.

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.