Lindsay M. Daniels

Impact of a rapid peptide nucleic acid fluorescence in situ hybridization assay on treatment of Candida infections.

PURPOSE The impact of a rapid peptide nucleic acid fluorescence in situ hybridization (PNA FISH) assay with an antimicrobial stewardship intervention on the treatment of Candida infections was studied. METHODS The utility of implementing the PNA FISH assay with an antimicrobial stewardship intervention in hospitalized patients with candidemia was evaluated by measuring the median time to Candida species identification, time to targeted therapy, and clinical outcomes, including time to culture clearance, hospital length of stay, and hospital mortality. Secondary objectives included determining the cost-effectiveness of the PNA FISH assay by assessing estimated antifungal drug costs (as average wholesale price) before (June 26, 2009-September 19, 2010) and after (September 20, 2010-June 13, 2011) test implementation and confirming test accuracy. For both groups, laboratory personnel notified the physician of the results of Grams stain from blood culture. RESULTS Time to targeted therapy significantly decreased after the implementation of the PNA FISH assay (p = 0.0016). The postimplementation group had a higher rate of culture clearance (p = 0.01). Median time to species identification was 0.2 day with the PNA FISH test versus 4 days with routine methods (p < 0.001). Accounting for the cost of the test itself and the cases in which patients were switched to more-expensive therapy on the basis of the test, we estimated that the PNA FISH test resulted in savings of approximately

Development of a Treatment Algorithm for Streptococci and Enterococci from Positive Blood Cultures Identified with the Verigene Gram-Positive Blood Culture Assay

415 per patient. CONCLUSION Implementing a PNA FISH test to identify Candida species from yeast-positive blood cultures in conjunction with a pharmacy-driven antimicrobial stewardship protocol decreased the time to targeted antifungal therapy and the time to culture clearance.

Impact of a Rapid Microarray-Based Assay for Identification of Positive Blood Cultures for Treatment Optimization for Patients with Streptococcal and Enterococcal Bacteremia

ABSTRACT Seventy-eight blood cultures with a Gram stain result of Gram-positive cocci in pairs and/or chains were evaluated with the Nanosphere Verigene Gram-positive blood culture (BC-GP) assay. The overall concordance of the assay with culture was 89.7% (70/78 cultures), allowing for the development of a targeted treatment algorithm.

Implementation of targeted interventions to decrease antiretroviral-related errors in hospitalized patients

ABSTRACT Implementation of the Verigene Gram-positive blood culture test led to reductions in time to acceptable antibiotic overall (1.9 versus 13.2 h, respectively; P = 0.04) and time to appropriate antibiotic for patients with vancomycin-resistant Enterococcus (4.2 versus 43.7 h; P = 0.006) and viridans group Streptococcus (0.2 versus 7.1 h; P = 0.02).

Severe Sepsis Caused by Arcanobacterium haemolyticum: A Case Report and Review of the Literature

PURPOSE The implementation and effectiveness of targeted interventions aimed at decreasing the frequency of antiretroviral-related errors in hospitalized patients with human immunodeficiency virus (HIV) are described. SUMMARY A prospective investigation conducted at the University of North Carolina Hospitals revealed a high rate of antiretroviral-related errors occurring on admission to the hospital and throughout a patients hospital stay. The high frequency of errors emphasized the need for targeted interventions aimed at preventing these errors and quickly identifying and resolving errors that do occur. Several interventions aimed at decreasing this error rate were instituted, including the addition of computer alerts for incorrect doses and drug interactions to the pharmacy order-entry system, distribution of an educational pocket-sized card among the staff, addition of commercially available combination antiretroviral products to the hospital formulary, updates of the computerized prescriber-order-entry (CPOE) system to include common dosage defaults, involvement of the infectious diseases consultation service to evaluate prescribed regimens of newly admitted patients with HIV, and daily review of newly initiated anti-retroviral regimens by a clinical pharmacist trained in HIV care. A follow-up analysis was conducted after these interventions were implemented to evaluate their effectiveness. Of the 78 patients identified during the postintervention analysis, 12 (15%) had at least one error in their initial drug regimen versus 49 patients (72%) in the preintervention study (p < 0.001). CONCLUSION Antiretroviral medication error rates decreased after the implementation of targeted interventions that included distributing an educational pocket-sized card, adding alerts to the pharmacy order- entry system, incorporating default dosages into the CPOE system, and adding combination antiretrovirals to the formulary.

Clinical Outcomes with Rapid Detection of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Isolates from Routine Blood Cultures

Objective: To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum. Case Summary: An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and suríace and surgical swabs from the patients left lower extremity grew A haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg onca daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up. Discussion: A. haemolyticum Is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, Including penicillins, cephalosporins, carba-penems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole. Conclusions: To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend (he use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.

Bezlotoxumab: A Novel Agent for the Prevention of Recurrent Clostridium difficile Infection

ABSTRACT Staphylococcus aureus is a common cause of bacteremia, with a substantial impact on morbidity and mortality. Because of increasing rates of methicillin-resistant Staphylococcus aureus, vancomycin has become the standard empirical therapy. However, beta-lactam antibiotics remain the best treatment choice for methicillin-susceptible strains. Placing patients quickly on the optimal therapy is one goal of antimicrobial stewardship. This retrospective, observational, single-center study compared 33 control patients utilizing only traditional full-susceptibility methodology to 22 case patients utilizing rapid methodology with CHROMagar medium to detect and differentiate methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains hours before full susceptibilities were reported. The time to targeted therapy was statistically significantly different between control patients (mean, 56.5 ± 13.6 h) and case patients (44.3 ± 17.9 h) (P = 0.006). Intensive care unit status, time of day results emerged, and patient age did not make a difference in time to targeted therapy, either singly or in combination. Neither length of stay (P = 0.61) nor survival (P = 1.0) was statistically significantly different. Rapid testing yielded a significant result, with a difference of 12.2 h to targeted therapy. However, there is still room for improvement, as the difference in time to susceptibility test result between the full traditional methodology and CHROMagar was even larger (26.5 h). This study supports the hypothesis that rapid testing plays a role in antimicrobial stewardship by getting patients on targeted therapy faster.

Levetiracetam‐Induced Acute Generalized Exanthematous Pustulosis

During the past decade, the incidence and severity of Clostridium difficile infection (CDI) have significantly increased, leading to a rise in CDI‐associated hospitalizations, health care costs, and mortality. Although treatment options exist for CDI, recurrence is frequent following treatment. Furthermore, patients with at least one CDI recurrence are at an increased risk of developing additional recurrences. A novel approach to the prevention of recurrent CDI is the use of monoclonal antibodies directed against the toxins responsible for CDI as an adjunct to antibiotic treatment. Bezlotoxumab, a human monoclonal antibody that binds and neutralizes C. difficile toxin B, is the first therapeutic agent to receive United States Food and Drug Administration approval for the prevention of CDI recurrence. Clinical studies have demonstrated superior efficacy of bezlotoxumab in adults receiving antibiotic therapy for CDI compared with antibiotic therapy alone for the prevention of CDI recurrence. Bezlotoxumab was well tolerated in clinical trials, with the most common adverse effects being nausea, vomiting, fatigue, pyrexia, headache, and diarrhea. The demonstrated efficacy, safety, and characteristics of bezlotoxumab present an advance in prevention of CDI recurrence.

Drug–Drug Interaction Between Isavuconazole and Tacrolimus: Is Empiric Dose Adjustment Necessary?

Antiepileptic drugs have been associated with many adverse effects, including different types of rashes; however, the frequency of rash varies among the drugs. The most common adverse effects associated with levetiracetam include somnolence, asthenia, headache, dizziness, and behavioral abnormalities. Until recently, rash had not been reported as an adverse effect of levetiracetam in adults. We describe a 45‐year‐old, African‐American woman who developed a desquamating rash after starting levetiracetam for a witnessed seizure. The rash improved after the drug was discontinued, but on rechallenge, the desquamating rash reappeared. The patient was hospitalized, levetiracetam was discontinued, and supportive care and treatment with triamcinolone 0.1% cream and oral prednisone were started. Her rash was biopsied, and she was diagnosed with drug‐induced acute generalized exanthematous pustulosis (AGEP). With topical and oral steroid treatment the patients rash improved, and she was discharged on hospital day 4. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patients development of AGEP and levetiracetam exposure. To our knowledge, this is the first case report of levetiracetam‐induced AGEP. Although levetiracetam is usually well tolerated, clinicians should be aware of this potential adverse drug reaction in patients who develop severe skin reactions while receiving this drug.

Clinical review of Clostridium difficile infection: an update on treatment and prevention

A paucity of data currently exists regarding drug–drug interaction (DDI) with tacrolimus and isavuconazole coadministration. Current literature provides conflicting recommendations on whether an empiric tacrolimus dose reduction is necessary when coadministered with isavuconazole. A 47-year-old African American female with acute lymphoblastic leukemia underwent an allogenic stem cell transplant (alloSCT) and was subsequently placed on routine posttransplant therapy including tacrolimus for immunosuppression and posaconazole for antifungal prophylaxis. Tacrolimus was empirically dose reduced due to the expected DDI with posaconazole based on current recommendations. Due to a persistently prolonged QTc interval and need for mold coverage, antifungal prophylaxis was ultimately changed to isavuconazole at standard recommended dosing. Tacrolimus was empirically dose reduced by 40% based on limited available literature at the time; however, tacrolimus trough concentrations subsequently declined, requiring an increase in tacrolimus dose to maintain therapeutic trough concentrations. Adequate isavuconazole absorption was documented through pharmacokinetic and pharmacodynamic data by measuring an isavuconazole trough concentration and directly observing isavuconazole’s shortening effect on the QTc interval, respectively. Our experience in an alloSCT patient suggests that an empiric tacrolimus dose reduction is not required when isavuconazole is initiated, but close tacrolimus therapeutic drug monitoring should rather be performed to guide tacrolimus dosing.