NHLBI-NIAID working group on antimicrobial strategies and cardiothoracic surgery
Report of the national heart, lung and blood institute-national institute of allergy and infectious diseases working group on antimicrobial strategies and cardiothoracic surgery

https://doi.org/10.1016/j.ahj.2003.08.016Get rights and content

Abstract

Infections related to cardiac surgery increase morbidity and mortality, and increase cost and use of health resources. With the widespread use of synthetic materials, whether in prosthetic valves or vascular conduits, bacterial infection and, more rarely, fungal complications can be devastating, requiring prolonged antimicrobial therapy and, at times, re-operations with high morbidity and mortality rates. With the US population aging and living longer, cardiac surgery is applied to an older population with significant comorbidities, making the threat from infectious complications significant. The dwindling armamentarium of existing antimicrobial agents, a limited pharmaceutical pipeline of future therapies, and the emergence of antimicrobial-resistant bacteria have increased the challenge of treating cardiothoracic infections. Thus, there is critical need for addressing the existing and emerging issues in this area to develop new safe and effective strategies to address the clinical challenges facing cardiothoracic surgeons.

As a result of this need, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases convened a Working Group on April 4 and 5, 2002, in Bethesda, Md, which explored both basic science and clinical research opportunities in the prevention and treatment of major infections after cardiac surgery. Because of its importance as the most common pathogen in this setting, the focus of discussions was on the prevention and treatment of Staphylococcus aureus infections. This report summarizes the 5 main areas that the Working Group targeted (epidemiology of infections, molecular mechanisms of infections and complications, current pharmacotherapy, new frontiers, and clinical trial design) and highlights the recommendations that were set forth by the Working Group.

Section snippets

Epidemiology of infections

Cardiovascular infections caused by S aureus are an urgent national medical problem. The continued expanding use of invasive cardiovascular procedures and devices in medical practice has exacerbated the growing clinical problems posed by S aureus. Since 1980, the National Nosocomial Infectious Surveillance Systems (NNIS) of the Centers for Disease Control reports increases in the rate of S aureus bacteremia ranging from 122% to 283% in individual hospitals.1 Of even more concern is the changing

Molecular mechanisms of infections and complications

Distinct molecular mechanisms are used by S aureus in the pathogenesis of cardiovascular infections. These include: (1) regulatory elements and pathways controlling staphylococcal virulence; (2) major surface adhesins that are critical for the staphylococci to adhere to cardiovascular surgical sites and implanted devices; and (3) host factors that may significantly influence the development of cardiovascular surgical site infections, both on a molecular level and a biochemical level.

There are 2

Current pharmacotherapy

Cardiovascular infections are primarily caused by coagulase-positive and -negative staphylococci and other antimicrobial-drug resistant pathogens. The increasing frequency of methicillin-resistant staphylococci as pathogens in the clinical setting has led to the extensive use of vancomycin, currently the most commonly used antibiotic for empiric therapy of these infections. The potential for development of glycopeptide intermediate or resistant staphylococcal infections14, 15 and concerns about

New frontiers

Agents for active and passive immunizations for prevention and therapy of S aureus infections are being developed by several companies.

Inhibitex (Atlanta, Ga) uses immunization-based therapies, such as vaccines, monoclonal antibodies, and plasma-derived immunoglobulins, to target bacterial microbial surface components recognizing adhesive matrix molecules (MSCRAMM) common to staphylococcal species. The efficacy of MSCRAMM protein antibodies was demonstrated in a rabbit model of

Clinical study designs

All new agents and treatment strategies need to be tested in clinical settings. In planning clinical trials, it is critical to decide whether mechanistic trials are preferable to elucidate pathways by which infections occur and can be treated, versus pragmatic trials defining the most effective approach to diagnosis and treatment and directly improving the quality of care.30 The optimal study design includes selection of appropriate populations and end points. Small, detailed trials are needed

Recommendations

Databases such as the VAH, STS, Duke, and CCF should be used and expanded to study prospectively the incidence and type of infection in a large group of patients undergoing heart surgery.

Basic science research projects into virulence mechanisms and infectivity of S aureus and other pathogens in cardiovascular surgical situations and device use should be supported.

Liaisons with industry should be fostered, and incentives for novel product development and clinical evaluation in cardiovascular

Acknowledgements

We thank the members of the Working Group, who contributed to the discussion and recommendations presented in this paper: Franklin D. Lowy, MD, Columbia University, New York, NY (co-chair); John A. Waldhausen, MD, the Pennsylvania State University College of Medicine, Hershey, Pa (co-chair); Arnold Bayer, MD, Harbor UCLA Medical Institute, Torrence, Calif; Robert Califf, MD, Duke University Medical Center, Durham, NC; George Eliopoulos, MD, Beth Israel Deaconess Medical Center, Boston, Mass;

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