Sulfonamides without trimethoprim in the treatment of Nocardia infections: A case report and literature review.

Sulfonamides are recommended as part of first-line therapy for most Nocardia infections, with trimethoprim-sulfamethoxazole (TMP-SMX) considered the drug of choice for susceptible isolates. However, in the case of central nervous system, disseminated disease, and other serious Nocardia infections, TMP-SMX should not be used as monotherapy. The preferred treatment for a patient unable to take TMP-SMX because of allergy or intolerance remains uncertain. Prior to the availability of TMP-SMX in 1973, other sulfonamides were mainstays of treatment. We describe a Nocardia infection successfully treated with sulfadiazine in a lung transplant recipient who could not tolerate TMP-SMX. A review of similar cases reported in the literature provides insight into the successful treatment of Nocardia infections with sulfonamide regimens not containing trimethoprim in transplant recipients and other immunocompromised hosts.

Interventions to improve antibiotic prescribing at hospital discharge: A systematic review.

A large proportion of antibiotic use associated with hospitalization occurs immediately after discharge, representing an important focus for antimicrobial stewardship programs. This review identified few studies evaluating the effect of interventions aimed at improving discharge antibiotic prescribing. Antimicrobial stewardship to improve postdischarge antibiotic prescribing is an unmet need warranting further study.

Which Nursing Home Residents With Pneumonia Are Managed On-Site and Which Are Hospitalized? Results from 2 Years' Surveillance in 14 US Homes.

OBJECTIVES: Pneumonia is a frequent cause of hospitalization among nursing home (NH) residents, but little information is available as to how clinical presentation and other characteristics relate to hospitalization, and the differential use of antimicrobials based on hospitalization status. This study examined how hospitalized and nonhospitalized NH residents with pneumonia differ. DESIGN: Data from a 2-year prospective study of residents who participated in a randomized controlled trial. SETTING AND PARTICIPANTS: All residents from 14 NHs in North Carolina followed for pneumonia over a 2-year period. METHODS: Clinical features, antimicrobial treatment, hospitalization, and demographic data on residents with a pneumonia diagnosis were abstracted from charts; NH information was obtained from NH administrators. RESULTS: A total of 509 pneumonia episodes were reported for 395 unique residents; the incidence was not higher in the winter months, and 28% were hospitalized. The likelihood of hospitalization did not differ by clinical characteristics except that residents with a respiratory rate >25 breaths per minute were more likely to be hospitalized. Being on hospice [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.5-7.4] and not having dementia (OR 1.9, 95% CI 1.1-3.2) also related to increased likelihood of hospitalization. Fluoroquinolone (usually levofloxacin) monotherapy was the most common treatment (54%) in both settings, and ceftriaxone monotherapy varied by hospitalization status (7% of hospitalized vs 16% treated on-site). Approximately 36% of nonhospitalized residents received antimicrobials for more than 7 days. CONCLUSIONS/IMPLICATIONS: Respiratory rate is associated with hospitalization but was not documented for more than a quarter of residents, suggesting the clinical benefit of more consistently conducting this assessment. Differential hospitalization rates for persons with dementia and on hospice suggest that care is being tailored to individuals' wishes, but this assumption merits study, as does use of fluoroquinolones (due to side effects) and treatment duration (due to potential contribution to antibiotic resistance).

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

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.

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

INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention. AREAS COVERED: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed. EXPERT OPINION: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first-line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.

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

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.

Impact of a rapid microarray-based assay for identification of positive blood cultures for treatment optimization for patients with streptococcal and enterococcal bacteremia.

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).

Clinical outcomes with rapid detection of methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates from routine blood cultures.

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.

Development of a treatment algorithm for streptococci and enterococci from positive blood cultures identified with the Verigene Gram-positive blood culture assay.

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.

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 Gram's 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 $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.

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

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 patient's 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.

Severe sepsis caused by Arcanobacterium haemolyticum: a case report and review of the literature.

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 surface and surgical swabs from the patient's 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 once 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, carbapenems, 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 the use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.