Emily L. Heil

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

Rapid Testing Using the Verigene Gram-Negative Blood Culture Nucleic Acid Test in Combination with Antimicrobial Stewardship Intervention against Gram-Negative Bacteremia

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.

Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria

ABSTRACT Rapid identification of microorganisms and antimicrobial resistance is paramount for targeted treatment in serious bloodstream infections (BSI). The Verigene Gram-negative blood culture nucleic acid test (BC-GN) is a multiplex, automated molecular diagnostic test for identification of eight Gram-negative (GN) organisms and resistance markers from blood culture with a turnaround time of approximately 2 h. Clinical isolates from adult patients at the University Maryland Medical Center with GN bacteremia from 1 January 2012 to 30 June 2012 were included in this study. Blood culture bottles were spiked with clinical isolates, allowed to incubate, and processed by BC-GN. A diagnostic evaluation was performed. In addition, a theoretical evaluation of time to effective and optimal antibiotic was performed, comparing actual antibiotic administration times from chart review (“control”) to theoretical administration times based on BC-GN reporting and antimicrobial stewardship team (AST) review (“intervention”). For organisms detected by the assay, BC-GN correctly identified 95.6% (131/137), with a sensitivity of 97.1% (95% confidence interval [CI], 90.7 to 98.4%) and a specificity of 99.5% (95% CI, 98.8 to 99.8%). CTX-M and OXA resistance determinants were both detected. Allowing 12 h from Gram stain for antibiotic implementation, the intervention group had a significantly shorter duration to both effective (3.3 versus 7.0 h; P < 0.01) and optimal (23.5 versus 41.8 h; P < 0.01) antibiotic therapy. BC-GN with AST intervention can potentially decrease time to both effective and optimal antibiotic therapy in GN BSI.

Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections

ABSTRACT Introduction: Extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed. Areas covered: This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly β-lactam-β-lactamase inhibitor combinations and cefepime (FEP). Expert opinion: Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC β-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.

Implementation of an Infectious Disease Fellow-Managed Penicillin Allergy Skin Testing Service

ABSTRACT Ceftazidime-avibactam is a novel cephalosporin–beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

Anemia Management in Patients with Chronic Viral Hepatitis C

An inpatient penicillin allergy skin testing program can be successfully managed by infectious diseases fellows under attending supervision offering a novel practice area for infectious diseases practitioners.

Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration

OBJECTIVE: To review the literature regarding current strategies for the management of anemia associated with treatment for chronic viral hepatitis C (HCV) in adults. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched (January 1980-October 2012) for articles in English using the search terms anemia, ribavirin, dose reduction, erythropoietin stimulating agents, hepatitis C, HIV, liver transplant, telaprevir, and boceprevir. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search. DATA SYNTHESIS: Standard of care for patients infected with HCV genotype 1 now requires a triple therapy regimen including an HCV NS3 protease inhibitor. These regimens lead to significantly higher rates of anemia compared to prior dual therapy regimens. Development of an optimal management strategy should begin with risk stratification. Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80% of the initial ribavirin dose to achieve optimal sustained virologic response (SVR) with dual therapy. The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates. Limited data have been published regarding the management of anemia with triple therapy; however, efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia. CONCLUSIONS: Anemia is a common adverse event associated with the use of ribavirin, and, more recently, the new HCV protease inhibitors. Ribavirin dose reduction should continue to be used as an initial anemia management strategy, with the use of erythropoietin alfa 40,000 units once weekly reserved for patients whose hemoglobin does not adequately respond to initial management strategies.

Ceftaroline Fosamil: A Brief Clinical Review

ABSTRACT Extended-infusion ceftolozane-tazobactam treatment at 1.5 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa in a critically ill patient on continuous venovenous hemofiltration. Serum drug concentrations were measured at 1, 4, 5, 6, and 8 h after the start of infusion. Prefilter levels of ceftolozane produced a maximum concentration of drug (Cmax) of 38.57 μg/ml, concentration at the end of the dosing interval (Cmin) of 31.63 μg/ml, time to Cmax (Tmax) of 4 h, area under the concentration-time curve from 0 to 8 h (AUC0–8) of 284.38 μg · h/ml, and a half-life (t1/2) of 30.7 h. The concentrations were eight times the susceptibility breakpoint for the entire dosing interval.

The Essential Role of Pharmacists in Antimicrobial Stewardship

Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.

Impact of Changes in Urine Culture Ordering Practice on Antimicrobial Utilization in Intensive Care Units at an Academic Medical Center.

The rapid increase in antibiotic resistance in conjunction with a decline in discovery and development of new antibiotics and widespread misuse of antibiotics is considered a global crisis. In response to this escalating problem, President Obama implemented the National Strategy on Combating AntibioticResistant Bacteria through Executive Order 13676. Within 3 years, the plan mandates that the Centers for Medicare and Medicaid Services (CMS) will issue new Conditions of Participation (CoP) to advance compliance with the Centers for Disease Control and Prevention (CDC)’s Core Elements of Hospital Antibiotic Stewardship Programs. Because the preservation of antibiotics is a significant public health imperative, the Society of Infectious Diseases Pharmacists (SIDP) and the American Society of Health-System Pharmacists (ASHP), support the inclusion of antimicrobial stewardship as a condition of participation for CMS. This position paper highlights the critical importance of pharmacists with training in antimicrobial stewardship in an effective antimicrobial stewardship program. As outlined in the CDC’s Core Elements document, successful stewardship programs must have not only physician leadership and accountability but also drug expertise from a pharmacist leader. This stance is further supported by the ASHP’s Statement on the Pharmacist’s Role in Antimicrobial Stewardship and Infection Prevention, which advocates that pharmacists take prominent roles in antimicrobial stewardship programs due to their unique expertise, understanding of, and influence over antimicrobial use within an organization. Accrediting bodies, regulatory agencies, and qualityassurance organizations have recognized the threat of antimicrobial resistance and the need for healthcare organizations to take proactive measures. Most medium-to-large hospitals have antimicrobial stewardship programs, but special efforts are needed in smaller hospitals and non-acute settings such as ambulatory and long-term care. Stewardship efforts are just as important in these settings and require new models to include the expertise of infectious disease (ID) physicians and pharmacists. While antimicrobial stewardship is the responsibility of every pharmacist regardless of practice setting, the importance of pharmacists with specialized training in infectious diseases and stewardship to provide leadership to an antimicrobial stewardship program cannot be overstated. The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) guidelines for the development of institutional antimicrobial stewardship programs highlight that a pharmacist with ID training should be a core member of the antimicrobial stewardship team. Ideally, every stewardship program would employ an ID pharmacist with formal ID training gained through completion of an accredited post-graduate year 2 (PGY2) residency or fellowship in ID, combined with board certification and relevant practice experience. Furthermore, pharmacists should maintain their ID skills through continuing education and continuing professional development. ASHP and SIDP provide structured goals, objectives, and targeted educational outcomes for PGY2 residencies in ID to ensure that all graduates of these programs have a solid foundation in the principles of antimicrobial stewardship. In the United States, there are more than 5,000 registered hospitals but only ~400 pharmacists with formal postgraduate ID training. Currently, only 70 ASHP-accredited PGY2 ID programs exist, making the reality of having an ID-trained pharmacist at every hospital a significant challenge. To meet the growing demand for ID-trained pharmacists to build stewardship programs across the country, more PGY2 ID programs need to be developed. To accomplish this, however, significant federal funding and incentives are needed. In the short term and for small/rural hospitals where it may not be feasible or fiscally responsible to have ID-trained pharmacy specialists on staff, options for training in antimicrobial stewardship outside of formal post-graduate training programs do exist. Certificate programs or traineeships in ID concepts and antimicrobial stewardship are highly encouraged if completion of more robust structured training programs is not possible. These resources allow pharmacists access to more