Harvesting the low-hanging fruit? Comparative assessment of intravenous to oral route antimicrobial conversion policy implementation.

Policies that promote conversion of antibiotics from intravenous to oral route administration are considered "low hanging fruit" for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.

Conventional Antifungals for Invasive Infections Delivered by Unconventional Methods; Aerosols, Irrigants, Directed Injections and Impregnated Cement.

The administration of approved antifungals via unapproved formulations or administration routes (such as aerosol, direct injection, irrigation, topical formulation and antifungal-impregnated orthopedic beads or cement) may be resorted to in an attempt to optimize drug exposure while minimizing toxicities and/or drug interactions associated with conventional (systemic) administrations. Existing data regarding such administrations are mostly restricted to uncontrolled case reports of patients with diseases refractory to conventional therapies. Attribution of efficacy and tolerability is most often problematic.

Impact of select risk factors on treatment outcome in adults with candidemia.

Background: Studies examining relationships between patient-related factors and treatment outcome in patients with candidemia are limited and often based on all-cause mortality.

Objective: Our purpose was to examine the impact of concurrent renal replacement therapy (RRT) and other pre-specified factors on treatment outcome among adults with candidemia.

Methods: This Institutional Review Board (IRB)-approved, single-center, case-cohort study included patients over 18 years of age admitted to Duke University Hospital between Jun 1, 2013 and Jun 1, 2017 with a blood culture positive for Candida spp.

Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms.

Background: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin.

Objective: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events.

Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia.

Background: Penicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia.

Methods: In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy.

Impact of automatic infectious diseases consultation on the management of fungemia at a large academic medical center.

Purpose: The impact of automatic infectious diseases (ID) consultation for inpatients with fungemia at a large academic medical center was studied.

Methods: In this single-center, retrospective study, the time to appropriate antifungal therapy before and after implementing a policy requiring automatic ID consultation for the management of fungemia for all patients with an inpatient positive blood culture for fungus was examined. The rates of ID consultation; the likelihood of receiving appropriate antifungal therapy; central venous catheter (CVC) removal rates; performance of ophthalmologic examinations; infection-related length of stay (LOS); rates of all-cause inhospital mortality, death, or transfer to an intensive care unit within 7 days of first culture; and inpatient cost of antifungals were also evaluated.

Role of isavuconazole in the treatment of invasive fungal infections.

Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles.

Challenges in Preparation of Cumulative Antibiogram Reports for Community Hospitals.

Knowledge of local antimicrobial resistance is critical for management of infectious diseases. Community hospitals' compliance with Clinical and Laboratory Standards Institute (CLSI) guidance for creation of cumulative antibiograms is uncertain. This descriptive cohort study of antibiogram reporting practices included community hospitals enrolled in the Duke Infection Control Outreach Network.

Sulfonylurea Prescribing Patterns After the Introduction of DPP-4 Inhibitors and GLP-1 Receptor Agonists.

Purpose: Although newer agents (dipeptidyl peptidase [DPP]-4 inhibitors and glucagon-like peptide [GLP]-1 receptor agonists) are available for the treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), the impact of the availability of these agents on the use of second-generation sulfonylureas (SUs) is unknown. This article presents percentages of patients prescribed SUs, using data from the National Ambulatory Medical Care Survey (NAMCS). The associations between SU prescribing and prespecified variables of interest were also explored.

Risk factors associated with unfavorable short-term treatment outcome in patients with documented Pseudomonas aeruginosa infection.

Background: Invasive infections with Pseudomonas aeruginosa (PA) are associated with significant morbidity and mortality. While risk factors for mortality have been identified, their influence on short-term outcomes impacting treatment selection has not been reported.

Objectives: The objective of this study was to evaluate the relationship between select patient- and treatment-related factors and short-term outcomes in patients with PA pneumonia and/or bacteremia.

Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam.

Study Objectives: To determine whether the addition of piperacillin-tazobactam leads to an increased incidence of nephrotoxicity in patients receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity.

Design: Single-center, retrospective cohort study.

Setting: Large, academic, tertiary-care hospital.

Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology-oncology patients: a retrospective cohort study.

In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS.

Recent advances in the treatment of life-threatening, invasive fungal infections.

Introduction: Invasive fungal infections (IFIs) pose significant morbidity and are often life-threatening to many high-risk patients. Timely diagnosis and treatment of these infections with optimal therapy is imperative.

Areas Covered: Advances have been made in diagnostic biomarkers such as peptide nucleic acid fluorescent in situ hybridization, β-D-glucan and galactomannan, although more research is needed in this area to assist with both diagnosis and monitoring for improvement of IFI management.

Utility of a clinical risk factor scoring model in predicting infection with extended-spectrum β-lactamase-producing enterobacteriaceae on hospital admission.

Objective: To validate the utility of a previously published scoring model (Italian) to identify patients infected with community-onset extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EKP) and develop a new model (Duke) based on local epidemiology.

Methods: This case-control study included patients 18 years of age or more admitted to Duke University Hospital between January 1, 2008, and December 31, 2010, with culture-confirmed infection due to an ESBL-EKP (cases). Uninfected controls were matched to cases (3:1).

Constructing unit-specific empiric treatment guidelines for catheter-related and primary bacteremia by determining the likelihood of inadequate therapy.

This study aimed to determine the feasibility of using likelihood of inadequate therapy (LIT), a parameter calculated by using pathogen frequency and in vitro susceptibility for determination of appropriate empiric antibiotic therapy for primary bloodstream infections. Our study demonstrates that LIT may reveal differences in traditional antibiograms.

Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations.

Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions.

Ceftaroline fosamil for treatment of community-acquired pneumonia: findings from FOCUS 1 and 2 and potential role in therapy.

Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP.

Potential role of tigecycline in the treatment of community-acquired bacterial pneumonia.

Tigecycline is a member of the glycylcycline class of antimicrobials, which is structurally similar to the tetracycline class. It demonstrates potent in vitro activity against causative pathogens that are most frequently isolated in patients with community-acquired bacterial pneumonia (CABP), including (but not limited to) Streptococcus pneumoniae (both penicillin-sensitive and -resistant strains), Haemophilus influenzae and Moraxella catarrhalis (including β-lactamase-producing strains), Klebsiella pneumoniae, and 'atypical organisms' (namely Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila). Comparative randomized clinical trials to date performed in hospitalized patients receiving tigecycline 100 mg intravenous (IV) × 1 and then 50 mg IV twice daily thereafter have demonstrated efficacy and safety comparable to the comparator agent.

Echinocandins: addressing outstanding questions surrounding treatment of invasive fungal infections.

Purpose: Recent in vitro and clinical data addressing outstanding issues regarding the selection, dosing, and monitoring of echinocandins for the treatment of invasive fungal infections (IFIs) are reviewed.

Summary: The echinocandins (caspofungin, micafungin, and anidulafungin) are attractive treatment options for the treatment of select IFIs, most notably invasive candidiasis and treatment-refractory invasive aspergillosis. A literature review of English-language articles published between January 2007 and May 2010 was performed using the terms caspofungin, micafungin, anidulafungin, and echinocandin.

Overview of treatment options for invasive fungal infections.

The introduction of several new antifungals has significantly expanded both prophylaxis and treatment options for invasive fungal infections (IFIs). Relative to amphotericin B deoxycholate, lipid-based formulations of amphotericin B have significantly reduced the incidence of nephrotoxicity, but at a significant increase in drug acquisition cost. Newer, broad-spectrum triazoles (notably voriconazole and posaconazole) have added significantly to both the prevention and treatment of IFIs, most notably Aspergillus spp.

Echinocandin pharmacodynamics: review and clinical implications.

Echinocandins have made a significant impact in the treatment of select invasive fungal infections, most notably invasive candidiasis and aspergillosis. However, treatment outcomes for such infections are still less than optimal, prompting an examination of dosing and administration techniques in an attempt to exploit known pharmacodynamic properties and improve outcomes. Echinocandins generally exhibit concentration-dependent, fungicidal activity against Candida spp.

Telavancin: a new lipoglycopeptide for gram-positive infections.

Telavancin is a lipoglycopeptide derivative of vancomycin. Similar to vancomycin, it demonstrates activity in vitro against a variety of Gram-positive pathogens, including but not limited to methicillin-resistant Staphylococccus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Modifications to vancomycin's structure expanded telavancin's spectrum of activity in vitro to include organisms such as glycopeptide-intermediate S.

Insights from the Society of Infectious Diseases Pharmacists on antimicrobial stewardship guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.

In 2007, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America published a document that addressed the major considerations for the justification, description, and conduct of antimicrobial stewardship programs. Our document is intended to continue the dialogue of these formalized programmatic strategies. We briefly review the guidelines, including the two primary strategies (prospective auditing with feedback, and preauthorization), and the supplemental strategies (education, information technology, transitional therapy, de-escalation or streamlining, and dose optimization).

Antimicrobial stewardship programs: how to start and steer a successful program.

Background: Antimicrobial stewardship programs (ASPs) promote the appropriate use of antimicrobials by selecting the appropriate dose, duration, and route of administration. The appropriate use of antimicrobials has the potential to improve efficacy, reduce treatment-related costs, minimize drug-related adverse events, and limit the potential for emergence of antimicrobial resistance.

Objective: To summarize ASP tactics that can improve the appropriate use of antimicrobials in the hospital setting.