Pharmacokinetics-pharmacodynamics, computer decision support technologies, and antimicrobial stewardship: the compass and rudder.

The first guidelines for conducting antimicrobial stewardship in the hospitalized setting were published in 2007. These guidelines recommend that stewardship programs employ the science of pharmacokinetics-pharmacodynamics (PK-PD) as well as adopting computerized decision support technologies when possible. The United States Food and Drug Administration have adopted PK-PD as a cornerstone in the evaluation of antimicrobial agents during clinical development.

Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects.

Background And Objectives: Dalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects.

Methods: Ten subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo.

Need and potential of antimicrobial stewardship in community hospitals.

Preventing, reducing, and controlling the emergence of antimicrobial-resistant organisms is a major public health challenge requiring the participation of the entire medical community and public health agencies. Antimicrobial stewardship programs (ASPs) have the potential to integrate the many and sometimes disparate individuals and organizations that rely on antimicrobial agents in an effort to better control antimicrobial prescribing, possibly minimizing the emergence of resistant organisms. Developing and implementing ASPs can be a major challenge for community-based hospitals.

Community transmission in the United States of a CTX-M-15-producing sequence type ST131 Escherichia coli strain resulting in death.

A middle-aged woman developed fatal urosepsis due to a multidrug-resistant Escherichia coli strain representing sequence type ST131, a recently emerged, disseminated, multidrug-resistant extraintestinal pathogen, after presumably having acquired it from her extensively antibiotic-exposed sister with chronic recurrent cystitis. Susceptibility results (reported on day 4) showed resistance to the initially selected regimen.

Antimicrobial stewardship: application in the intensive care unit.

Critical-care units can be barometers for appropriate antimicrobial use. There, life and death hang on empirical antimicrobial therapy for treatment of infectious diseases. With increasing therapeutic empiricism, triple-drug, broad-spectrum regimens are often necessary, but cannot be continued without fear of the double-edged sword: a life-saving intervention or loss of life following Clostridium difficile infection, infection from a resistant organism, nephrotoxicity, cardiac toxicity, and so on.

Quality pneumonia care: distinguishing community-acquired from health care-associated pneumonia.

Purpose: Differences in the definition, demographics, risk factors, etiology, and treatment for health care-associated pneumonia (HCAP) versus community-acquired pneumonia (CAP) are discussed.

Summary: Health care-associated infections (HCAI) represent a population of outpatients with exposure to health care institutions and procedures who develop nosocomial-like infections. HCAI are etiologically similar to nosocomial infections with gram-negative organisms, methicillin-resistant Staphylococcus aureus (MRSA), and multidrug-resistant (MDR) pathogens predominating.

Rational dosing of antimicrobial agents: pharmacokinetic and pharmacodynamic strategies.

Purpose: Using the principles of pharmacokinetic (PK) and pharmacodynamic (PD) dosing, the optimal dosing strategies of beta-lactams, macrolides, fluoroquinolones, and aminoglycosides for the treatment of community-acquired pneumonia (CAP) are reviewed.

Summary: The optimal dosing of antimicrobials according to PK and PD principles is one method to reduce the misuse and overuse of the agents and antimicrobial resistance. Based on PK/PD profiles, antimicrobial agents are divided into three groups: agents with concentration-dependent killing (e.

Guidelines and quality for community-acquired pneumonia: measures from the Joint Commission and the Centers for Medicare and Medicaid Services.

Purpose: The rationales for and recent updates on quality measures for the treatment of community-acquired pneumonia (CAP) are reviewed.

Summary: CAP continues to be among the most common causes of emergency department visits, hospitalization, and death in the United States. The Joint Commission of Accredited Health Care Organizations in conjunction with the Centers for Medicare and Medicaid Services (CMS) and the Infectious Diseases Society of America have published seven quality measures designed to improve the overall treatment of CAP.

Antimicrobial stewardship: shepherding precious resources.

Purpose: Differences in antimicrobial stewardship program (ASP) strategies, evidences supporting the benefits of ASPs, barriers to implementing ASPs, and suggestions for overcoming the barriers are discussed.

Summary: Developing and implementing an ASP can facilitate more judicious use of antimicrobials. Prior authorization and prospective audit with feedback are two distinct methods of ASPs.

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).

An overview of harms associated with beta-lactam antimicrobials: where do the carbapenems fit in?

The US Institute of Medicine's focus on patient safety has motivated hospital administrators to facilitate a culture of safety. As a result, subcommittees of the pharmacy and therapeutics committee have emerged in many hospitals to focus on adverse events and patient safety. Antimicrobial harms have gained the attention of practicing clinicians and hospital formulary committees, because they top the list of drugs that are associated with adverse events and because of certain serious harms that have ultimately led to the withdrawal of some antimicrobial agents.

Clostridium difficile infection: a critical overview.

Clostridium difficile is a gram-positive, spore-forming, toxin-producing anaerobic bacillus identified as the causal agent of a variety of manifestations typically isolated to the colon, but in its severe form, it can lead to sepsis and death. C. difficile infection due to a toxin gene variant strain (BI/NAP1) has been identified at the center of outbreaks and has resulted in increased mortality.

Antimicrobial stewardship: concepts and strategies in the 21st century.

Large worldwide surveillance studies report that resistance to nearly all classes of antimicrobial is increasing, as is the emergence of what have been termed pan-drug-resistant and extremely drug-resistant pathogens. Concomitantly, bacterial binding sites have been exploited by available antimicrobials, and there has been a decline in the development of antimicrobials using novel mechanisms of action. These trends have prompted healthcare facilities to adopt antimicrobial stewardship programs (ASPs) and infection control programs (ICPs) to monitor antimicrobial use while simultaneously optimizing treatment, outcome, and cost.

Measures to control and prevent Clostridium difficile infection.

Control of Clostridium difficile infection (CDI) outbreaks in health care facilities presents significant challenges to infection control specialists and other health care workers. C. difficile spores survive routine environmental cleaning with detergents and hand hygiene with alcohol-based gels.

Treatment of Clostridium difficile infection.

Recent outbreaks of Clostridium difficile infection (CDI) in North America have been due to a more virulent, possibly more resistant strain that causes more-severe disease, making prompt recognition of cases and optimal management of infection essential for a successful therapeutic outcome. Treatment algorithms are presented to help guide the management of patients with CDI. Metronidazole has been recommended as initial therapy since the late 1990s and continues to be the first choice for all but seriously ill patients and those with complicated or fulminant infections or multiple recurrences of CDI, for whom vancomycin is recommended.

Antimicrobial-associated risk factors for Clostridium difficile infection.

Antimicrobial therapy plays a central role in the pathogenesis of Clostridium difficile infection (CDI), presumably through disruption of indigenous intestinal microflora, thereby allowing C. difficile to grow and produce toxin. Investigations involving animal models and studies performed in vitro suggest that inhibitory activity against C.

Postmarketing clinical experience in patients with skin and skin-structure infections treated with daptomycin.

A registry describing daptomycin's clinical use was analyzed to describe treatment of skin and skin-structure infections (SSSIs). The Cubicin Outcomes Registry and Experience (CORE) 2004 retrospectively collected demographic, microbiologic, and clinical outcome information of patients treated with daptomycin (Cubicin; Cubist Pharmaceuticals, Inc., Lexington, MA).

Efficacy of hospital cleaning agents and germicides against epidemic Clostridium difficile strains.

Objective: To compare the effects of hospital cleaning agents and germicides on the survival of epidemic Clostridium difficile strains.

Methods: We compared the activity of and effects of exposure to 5 cleaning agents and/or germicides (3 containing chlorine, 1 containing only detergent, and 1 containing hydrogen peroxide) on vegetative and spore forms of epidemic and non-epidemic C. difficile strains (3 of each).

Clostridium difficile-associated disease: changing epidemiology and implications for management.

Clostridium difficile-associated disease (CDAD) is increasingly being reported in many regions throughout the world. The reasons for this are unknown, are likely to be multifactorial, and are the subject of several current investigations. In addition to the upsurge in frequency of CDAD, an increased rate of relapse/recurrence, disease severity and refractoriness to traditional treatment have also been noted.

Antimicrobial stewardship and the role of pharmacokinetics-pharmacodynamics in the modern antibiotic era.

Antimicrobial stewardship, a term coined by Dale Gerding, is defined as the optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance development. Methods to promote and ensure good antimicrobial stewardship have been implemented and studied, and have typically provided tangible benefits in terms of a reduction in overall or targeted antimicrobial usage and resistance emergence. Although most of the programmatic antimicrobial stewardship efforts have been conducted in acute care inpatient settings, some strategies usually involving education have been evaluated in the outpatient venue.

Antimicrobial-associated QT interval prolongation: pointes of interest.

Until recently, cardiac toxicity manifesting in the form of arrhythmias related to QT interval prolongation was uncommonly appreciated within the antimicrobial class of drugs, but it was well described among antiarrhythmic agents. Antimicrobials that are associated with QT prolongation include the macrolides/ketolides, certain fluoroquinolones and antimalarials, pentamidine, and the azole antifungals. Although, in most cases, mild delays in ventricular repolarization caused by these drugs are clinically unnoticeable, they may serve to amplify the risk for torsades de pointes (TdP) when prescribed in the setting of other risk factors.

Stability of cefepime and metronidazole prepared for simplified administration as a single product.

The stabilities of cefepime and metronidazole were determined after preparation of a single admixture product in view of its potential use as a simple and cost-effective therapeutic alternative for infections caused by many aerobic and anaerobic pathogens. The stability of cefepime 1000 or 2000 mg mixed with metronidazole 500 or 1500 mg was evaluated via high-performance liquid chromatography after storage for up to 336 h at 4 or 23 degrees C. Cefepime was stable in all 4 degrees C samples for up to 336 h, retaining > or =95% of initial concentrations.

Hospital-based strategies for combating resistance.

Selective pressures generated by the indiscriminate use of beta-lactam antibiotics have resulted in increased bacterial resistance across all beta-lactams classes. In particular, the use of third-generation cephalosporins has been associated with the emergence of extended-spectrum beta-lactamase-producing and AmpC beta-lactamase-producing Enterobacteriaceae and vancomycin-resistant enterococci. Conversely, beta-lactams (e.