Evaluation of a risk assessment model to predict infection with healthcare facility-onset Clostridioides difficile.

PURPOSE: We evaluated a previously published risk model (Novant model) to identify patients at risk for healthcare facility-onset Clostridioides difficile infection (HCFO-CDI) at 2 hospitals within a large health system and compared its predictive value to that of a new model developed based on local findings. METHODS: We conducted a retrospective case-control study including adult patients admitted from July 1, 2016, to July 1, 2018. Patients with HCFO-CDI who received systemic antibiotics were included as cases and were matched 1 to 1 with controls (who received systemic antibiotics without developing HCFO-CDI). We extracted chart data on patient risk factors for CDI, including those identified in prior studies and those included in the Novant model. We applied the Novant model to our patient population to assess the model's utility and generated a local model using logistic regression-based prediction scores. A receiver operating characteristic area under the curve (ROC-AUC) score was determined for each model. RESULTS: We included 362 patients, with 161 controls and 161 cases. The Novant model had a ROC-AUC of 0.62 in our population. Our local model using risk factors identifiable at hospital admission included hospitalization within 90 days of admission (adjusted odds ratio [OR], 3.52; 95% confidence interval [CI], 2.06-6.04), hematologic malignancy (adjusted OR, 12.87; 95% CI, 3.70-44.80), and solid tumor malignancy (adjusted OR, 4.76; 95% CI, 1.27-17.80) as HCFO-CDI predictors and had a ROC-AUC score of 0.74. CONCLUSION: The Novant model evaluating risk factors identifiable at admission poorly predicted HCFO-CDI in our population, while our local model was a fair predictor. These findings highlight the need for institutions to review local risk factors to adjust modeling for their patient population.

Optimizing the Treatment of Steroid-Induced Hyperglycemia.

OBJECTIVE: To review therapeutic strategies for the management of patients with steroid-induced hyperglycemia. DATA SOURCES: A literature search of MEDLINE/PubMed (1990 to June 2017) was conducted using the search terms steroid, glucocorticoid, corticosteroid, hyperglycemia, and diabetes as well via review of literature citations. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials and case studies focusing on pharmacological interventions in humans were reviewed for inclusion. Articles discussing islet cell transplant were excluded. DATA SYNTHESIS: Hyperglycemia is a predictable adverse effect of glucocorticoid therapy, which is associated with negative outcomes, including an odds ratio of 1.36 for developing new-onset diabetes. A variety of strategies have been utilized for managing patients who are at risk of complications caused by steroid-induced hyperglycemia. Agents such as sulfonylureas, thiazolidinediones, meglitinides, metformin, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptidase-1 agonists, and insulin have been evaluated in case studies and small clinical trials with varying degrees of success. CONCLUSIONS: Since there are limited clinical data available to guide therapy, strategies that minimize the risk of adverse effects should be selected for the management of steroid-induced hyperglycemia. Therapies that may be safe and effective given current information include DPP-4 inhibitors, metformin, and weight-based neutral protamine Hagedorn insulin.

Evaluation of a Once/Day Tobramycin Regimen to Achieve Target Concentrations in Adult Patients with Cystic Fibrosis.

STUDY OBJECTIVE: To evaluate the success of an initial tobramycin dosing regimen to achieve target peak and trough concentrations in adult patients with pulmonary exacerbations of cystic fibrosis (CF). DESIGN: Retrospective single-center medical record review. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 186 patient encounters where 112 patients with CF were treated for acute pulmonary exacerbations with 10 mg/kg/day of tobramycin between January 1, 2009, and December 5, 2014. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, clinical characteristics, tobramycin data, and pharmacokinetic variables were collected. The primary outcome evaluated the success of the initial tobramycin dosing regimen in attaining the target peak concentration. Secondary end points were achievement of the target trough concentration, achievement of combined peak and trough targets, and incidence of nephrotoxicity. Bivariate and multivariate analyses were performed to evaluate factors associated with achieving target concentrations. Of the 186 patient encounters, 41% achieved the target peak with the first dosing regimen, 62% achieved a target trough, and 23% achieved the target peak and trough. Nephrotoxicity occurred in 10% of patient encounters. A body mass index (BMI) of 18.5-24.9 kg/m(2) was associated with higher odds of meeting the target peak compared with a BMI lower than 18.5 kg/m(2) (odds ratio [OR] 24.5; 95% confidence interval [CI] 5.2-117.2). Conversely, a BMI of 18.5-24.9 kg/m(2) was associated with lower odds of attaining the target trough compared with a BMI lower than 18.5 kg/m(2) (OR 0.16; 95% CI 0.05-0.56). Higher volume of distribution and elimination rate constants (Kel ) were associated with significantly lower odds of achieving the target peak. In addition, higher Kel values were associated with significantly higher odds of achieving the target trough. CONCLUSIONS: The current initial tobramycin regimen did not achieve target serum tobramycin concentrations reliably. Optimization of the initial CF tobramycin dosing regimen is warranted.

Simulated Order Verification and Medication Reconciliation during an Introductory Pharmacy Practice Experience.

Objective. To create, implement, and assess a simulated medication reconciliation and an order verification activity using hospital training software. Design. A simulated patient with medication orders and home medications was built into existing hospital training software. Students in an institutional introductory pharmacy practice experience (IPPE) reconciled the patient's medications and determined whether or not to verify the inpatient orders based on his medical history and laboratory data. After reconciliation, students identified medication discrepancies and documented their rationale for rejecting inpatient orders. Assessment. For a 3-year period, the majority of students agreed the simulation enhanced their learning, taught valuable clinical decision-making skills, integrated material from previous courses, and stimulated their interest in institutional pharmacy. Overall feedback from student evaluations about the IPPE also was favorable. Conclusion. Use of existing hospital training software can affordably simulate the pharmacist's role in order verification and medication reconciliation, as well as improve clinical decision-making.

A patient with HIV and tuberculosis with diminished clopidogrel response.

Patients with HIV are at an increased risk for cardiovascular disease, both as a result of treatment with protease inhibitors and from the disease itself. The medication regimens of patients with HIV and cardiovascular comorbidities are complex and require careful assessment for potentially serious drug-drug interactions. We report a case of clopidogrel non-responsiveness in a patient with HIV, latent tuberculosis and cardiovascular disease with a history of myocardial infarction. To our knowledge, this is the first report of significant drug interactions between clopidogrel, isoniazid and ritonavir. This case underscores the importance of a detailed drug interaction screening in infectious disease patients taking complex medication regimens, including clopidogrel.

A review of the advances in chronic obstructive pulmonary disease treatment.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality across the globe and within the United States. Although several medication classes are used for COPD treatment, none of these medications have been shown to significantly improve long-term lung function or mitigate overall disease progression. This review describes the pharmacologic treatment options for COPD and highlights recent studies evaluating the impact of bronchodilators and combination therapy on lung function, mortality, quality of life, and exacerbations. Additionally, indacaterol and roflumilast, 2 new COPD treatment agents approved by the Food and Drug Administration in 2011, are discussed. Pharmacists play an important role in managing and educating patients with COPD and should utilize new evidence to make recommendations.

Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.

BACKGROUND: Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. OBJECTIVE: To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. METHODS: All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the criteria included aged 65 years or older, admitting diagnosis of pneumonia, at least 1 of several chronic diseases, immunocompromising condition, cochlear implant, cerebrospinal fluid leak, current tobacco smoking, pregnancy or having a child in the home less than aged 6 months, or awaiting solid organ transplantation. Patients who had vaccine contraindications/precautions or had been vaccinated in the previous 5 years were ineligible. Data on demographics, presence of vaccine screening, indication, administration, rescheduling, and refusal were collected. The primary endpoint was the rate of pneumococcal vaccine administration in eligible medicine patients. Secondary endpoints included changes in screening rates, vaccine refusal, and order rescheduling. Descriptive statistics and Student's t-test were used to evaluate patient demographic data. Pearson chi-square was used to compare the pre- and post-implementation periods. RESULTS: The rate of pneumococcal vaccine administration in eligible patients significantly improved post-implementation compared with pre-implementation (74.2% vs. 19.1%, respectively, P < 0.001). Rates of vaccine screening were similar pre-implementation (96.0%) and post-implementation (99.3%, P = 0.056). The rates of vaccine refusal in the pre- and post-implementation periods did not significantly differ (10.6% vs. 22.6%, respectively, P = 0.203). CONCLUSIONS: Implementation of vaccine protocol changes was associated with improved pneumococcal vaccination rates in eligible medicine patients. Protocol changes were relatively easy to implement in a large institution, and a similar approach may be implemented at other institutions as an effective way to improve pneumococcal vaccination rates.

Subcutaneous unfractionated heparin for treatment of venous thromboembolism in end-stage renal disease.

OBJECTIVE: To report 3 cases of venous thromboembolism (VTE) in patients with end-stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH) bridged with warfarin. CASE SUMMARIES: Three patients with ESRD were successfully treated for VTE with unmonitored, fixed-dose subcutaneous UFH every 12 hours and dose-adjusted warfarin. The first patient was initiated on continuous infusion UFH for deep-vein thrombosis, but due to poor vascular access, nurses were unable to consistently measure anti-Xa levels. Therefore, subcutaneous UFH 17,500 units (∼245 units/kg/dose) every 12 hours was initiated. Oral warfarin 5 mg/day was started the following day. The patient received 4 days of inpatient subcutaneous UFH and then was discharged to complete the bridge as an outpatient. The second patient received subcutaneous UFH 10,000 units (∼244 units/kg/dose) every 12 hours and oral warfarin 2.5 mg/day to treat a nonocclusive thrombus along her right femoral vein hemodialysis catheter. The patient received 1 day of inpatient subcutaneous UFH treatment prior to discharge and continued bridge therapy with warfarin as an outpatient. The third patient was initiated on subcutaneous UFH 20,000 units (∼223 units/kg/dose) every 12 hours and oral warfarin 7.5 mg/day due to a subtherapeutic INR (1.50) 5 days after receiving fresh frozen plasma to reduce her therapeutic INR for a procedure. The patient received 2 doses of subcutaneous UFH as an inpatient before treatment was discontinued because her INR was therapeutic at 2.3. DISCUSSION: Subcutaneous UFH has been used to treat VTE since the early 1980s; however, with the advent of low-molecular-weight heparin (LMWH), subcutaneous UFH use diminished. Several studies comparing the use of subcutaneous UFH to both continuous infusion UFH and LMWH concluded that subcutaneous UFH is a safe and efficacious alternative. The 2008 Chest Guidelines for Antithrombotic Therapy for Venous Thromboembolic Disease support the use of subcutaneous UFH for the treatment of VTE with a Grade 1A recommendation and provide a Grade 2C recommendation for use of UFH over LMWH for patients with VTE and severe renal failure. CONCLUSIONS: Safe and convenient treatment options for VTE in patients with ESRD are limited. Fixed-dose, unmonitored subcutaneous UFH as a bridge to warfarin therapy is an effective option in patients with ESRD and those with financial restrictions. The pharmacist plays a key role in identifying patients for whom subcutaneous UFH treatment may be a viable alternative, recommending an appropriate dosing regimen, and educating health-care professionals and patients about safe use.

Nephrogenic diabetes insipidus induced by two amphotericin B liposomal formulations.

Immunocompromised patients are at risk for invasive molds and resistant fungal infections for which amphotericin B may be the only feasible treatment. Nephrogenic diabetes insipidus (DI) and renal tubular acidosis are known adverse effects of conventional amphotericin B; however, nephrogenic DI has been uncommonly associated with liposomal amphotericin B formulations. We describe an 18-year-old woman with aplastic anemia who developed invasive aspergillosis. She began treatment with high-dose (10 mg/kg/day) liposomal amphotericin B at home; however, her condition worsened, and she was hospitalized. Therapy with liposomal amphotericin B was continued until the patient began having symptoms consistent with nephrogenic DI. These symptoms resolved after discontinuation of liposomal amphotericin B; however, after rechallenge with lipid complex amphotericin B (5 mg/kg/day), the symptoms returned. The patient's nephrogenic DI was successfully treated with diuretics. Use of the Naranjo adverse drug reaction probability scale score indicated a probable relationship between liposomal amphotericin B and the development of nephrogenic DI. To our knowledge, this is the third report of nephrogenic DI induced by liposomal amphotericin B. This adverse effect is one of many severe adverse effects caused by all formulations of amphotericin B. A clear understanding of these adverse effects is vital for the clinician to successfully weigh the risks and benefits of antifungal therapy.

Confirmed beta16 Arg/Arg polymorphism in a patient with uncontrolled asthma.

OBJECTIVE: To report a case of confirmed beta(16) Arg/Arg polymorphism (Arg/Arg) in a patient with uncontrolled asthma. CASE SUMMARY: A 49-year-old black female presented to the emergency department with acute shortness of breath with subsequent intubation. After extubation, she reported multiple hospitalizations for asthma with one prior intubation, adherence to asthma medications, and very frequent use of her short-acting beta(2)-agonist (SABA). Because of her asthma history, self-reported adherence, and race, she was tested for beta(2)-adrenoreceptor genotype, which revealed Arg/Arg. Based on these findings, beta(2)-agonists were discontinued and tiotropium (maintenance) and ipratropium (primary rescue) were initiated as part of her asthma regimen. Application of the Naranjo probability scale revealed probable causality between uncontrolled asthma in our patient and SABA use. The patient is followed in our outpatient pulmonary clinic and, at time of writing, had not been admitted to our hospital for asthma-related events. DISCUSSION: Approximately 15% of Americans with asthma are Arg/Arg, with an increased prevalence in black and Asian populations. It is hypothesized that changes in the degree of sensitivity or desensitization to the bronchodilator effect of beta(2)-agonists may occur in these individuals. Data exist, although they are conflicting, suggesting that inhaled beta(2)-agonists may worsen clinical outcomes. Trials have reported declines in peak expiratory flow rates plus increases in asthma symptoms and exacerbations when SABAs have been used regularly in patients with Arg/Arg. Studies evaluating long-acting beta(2)-agonists (LABAs) have inconsistent results. Preliminary data suggest that anticholinergics may serve as a beneficial primary rescue medication instead of beta(2)-agonists in patients with Arg/Arg. CONCLUSIONS: Clinicians should be aware of factors (eg, race and polymorphisms) that may predict unfavorable outcomes with regular SABA and possibly LABA use. Patients with poor asthma control despite adherence to asthma therapy may benefit from beta(2)-adrenoreceptor genotyping and, possibly, from anticholinergics.