IGNITE: Confronting the Challenge of Multidrug-Resistant Gram-Negative Pathogens in the Hospital

Faculty

Needs Statement

According to data from the National Nosocomial Infections Surveillance (NNIS) System in 2003, the Gram-negative pathogen Pseudomonas aeruginosa was the second most common pathogen causing nosocomial pneumonia in the intensive care unit (ICU), responsible for 18.1% of these infections. Acinetobacter spp also caused hospital-acquired pneumonia (HAP) and accounted for 6.9% of ICU pneumonia infections. Multidrug-resistant strains of P aeruginosa and A baumannii are increasingly recognized as serious threats in the hospital. According to NNIS data from 1992 through 2003, the resistance of P aeruginosa to imipenem was 21.1%, 29.5% to quinolones, and 31.9% to third-generation cephalosporins. The resistance to all 3 antibiotic classes is increasing. P aeruginosa possesses many mechanisms of resistance to antimicrobial agents, including slow porin channels, multidrug efflux pumps, inactivating enzymes, and mutational resistance.

While the arsenal of antimicrobial agents for treatment of nosocomial Gram-negative infections has grown, in clinical practice appropriate therapy is not always implemented in a timely manner. In one study, 34.3% of patients with nosocomial infections initially received inadequate antimicrobial therapy. In this study, the mortality rate among patients receiving inadequate initial antimicrobial treatment was 52.1%, compared with an overall mortality rate of 12.2% (relative risk 4.26; P<0.001). In their recent, jointly issued guidelines for management of HAP, ventilator-associated pneumonia, and healthcare-associated pneumonia, the American Thoracic Society and the Infectious Diseases Society of America focus on the importance of pneumonia as a cause of morbidity and mortality in hospitalized patients, despite advances in antimicrobial therapy. The major goals of these evidence-based guidelines emphasize early, appropriate antibiotics in adequate doses, with avoidance of excessive antibiotics by deescalation of initial antibiotic therapy (based on microbiologic cultures and the clinical response of the patient), and shortening the duration of therapy to the minimum effective period.

Because many infections encountered in the ICU are polymicrobial or must be treated empirically before the pathogen is identified, a broad spectrum of antimicrobial activity is of great importance in initial therapy. β-lactam antibiotics have traditionally been an important class of agents for treatment of Gram-negative infections. However, as quickly as new β-lactam antibiotics have been introduced over the past 20 years, new β-lactamases, which confer resistance to β-lactam antibiotics, have also emerged. Carbapenems, which possess wide antibacterial spectra and impressive β-lactamase stability, therefore offer a realistic option for treatment in the critical care setting. In clinical practice dosing and administration of carbapenems is an important issue because imipenem has been associated with seizures in an apparent dose-dependent manner. Duration of infusion with carbapenem agents is also a focus of extensive research. A new carbapenem agent, doripenem, offers in vitro activity against some resistant Gram-negative strains and also clinical success in the treatment of pneumonia and intraabdominal infections.

The incidence of P aeruginosa and A baumannii in nosocomial pneumonia, along with high rates of multidrug resistance and inadequate antimicrobial therapy in the clinical setting, underscore the need for education on new strategies to improve clinical outcomes in infections due to resistant organisms in the ICU.

Target Audience

The activity is intended for critical care physicians, surgeons, hospitalists, infectious diseases physicians, and pharmacists.

Objectives

1. Discuss patterns and mechanisms of antimicrobial resistance in Gram-negative pathogens, notably P aeruginosa and A baumannii;
2. Identify patterns in mortality rates related to inadequate initial antimicrobial treatment;
3. Implement treatment strategies for at-risk patients incorporating appropriate initial treatment and deescalation of therapy where warranted;
4. Evaluate the utility of broad-spectrum agents, including carbapenems, for treatment of pneumonia and intraabdominal infections in patients at risk for resistant pathogens;
5. Identify issues in optimizing treatment with carbapenem agents.

Accreditation

Medicine
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the University of Kentucky College of Medicine and Rxperience. The University of Kentucky College of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The University of Kentucky College of Medicine designates this educational activity for a maximum of 1.00 AMA PRA Category 1 Credits™. Each physician should claim only those hours of credit actually spent in the educational activity.

The University of Kentucky College of Medicine presents this activity for educational purposes only. Participants are expected to utilize their own expertise and judgment while engaged in the practice of medicine. The content of the presentations is provided solely by presenters who have been selected for presentations because of recognized expertise in their field.

Pharmacy
The University of Kentucky College of Pharmacy is approved by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity has been assigned ACPE # 022-999-08-020-H01-P and will award 1.00 contact hours (0.1 CEUs) of continuing pharmacy education credit in states that recognize ACPE providers. Statements of credit will indicate hours and CEUs based on successful completion of a posttest (score 70% or higher) and will be issued upon completion of the activity. The college complies with the Criteria for Quality for continuing education programming.

Activity Sponsorship

This activity is jointly sponsored by the University of Kentucky and Rxperience. Supported by an unrestricted educational grant from Ortho-McNeil Janssen Scientifc Affairs, LLC.