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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Overcoming Life-Threatening Bacterial And Fungal Infections: Case-Based Discussions And Evidence-Based Strategies


GOAL
To provide infectious disease physicians and other healthcare professionals interested in infectious disease with up-to-date information on the treatment of patients with life-threatening bacterial and fungal infections.

TARGET AUDIENCE
This activity is designed for infectious disease physicians and other healthcare professionals interested in infectious disease. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine and University of Tennessee College of Pharmacy take responsibility for the content, quality, and scientific integrity of this CE activity. At the conclusion of this activity, the participant should be able to:

  • Describe the epidemiology of zygomycosis infections and outline an approach to their prevention and treatment.
  • Integrate evidence-based practices into the management of patients with fungal infections.
  • Develop clinical strategies for the management of patients with hospital-acquired pneumonia and diabetic foot infection, incorporating principles from published treatment guidelines.
  • Contain the resistance epidemic by implementing policies for the judicious use of antibiotic therapy.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2.5 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

This program is approved for 2.5 hours (0.25 CEUs) and is cosponsored by the University of Tennessee College of Pharmacy, which is approved by the American Council on Pharmacy Education as a provider of continuing pharmaceutical education. A statement of CE credit will be mailed within 4 weeks of successful completion and evaluation of the program. ACPE program #064-000-05-212-H01.

The estimated time to complete this educational activity: 2.5 hours.
Release date: June 15, 2006. Expiration date: June 15, 2008.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Merck and Company.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:

PROGRAM DIRECTORS

John G. Bartlett, MD
Professor, Department of Medicine
Chief, Division of Infectious Diseases
Johns Hopkins University School of  Medicine
Baltimore, Maryland
Dr Bartlett reports serving as a consultant for Abbott Laboratories, Bristol-Myers Squibb Company, GlaxoSmithKline, and the HIV Advisory Board.

John R. Graybill, MD
Professor, Department of Medicine
Chief, Division of Infectious Diseases
University of Texas Health Science Center
San Antonio, Texas
Dr Graybill reports receiving grants/research support from Astellas, Merck and Company, Pfizer Inc, Schering-Plough, and Vicuron; serving as a consultant for Merck and Company, Pfizer Inc, and Schering-Plough; and receiving honoraria from Merck and Company and Schering-Plough.

PARTICIPATING FACULTY

Donald E. Craven, MD
Professor of Medicine
Tufts University School of Medicine
Chair, Infectious Diseases
Lahey Clinic Medical Center
Burlington, Massachusetts
Dr Craven reports receiving grants/research support from Bard; serving as a consultant for Johnson & Johnson; and receiving honoraria from Cubist Pharmaceuticals, Elan, Merck and Company, Pfizer Inc, and Wyeth.

George H. Karam, MD
Paula Garvey Manship Professor of Medicine
Louisiana State University School of Medicine
New Orleans, Louisiana
Dr Karam reports receiving honoraria from Merck and Company and Pfizer Inc.

John Perfect, MD
Professor of Medicine
Division of Infectious Diseases
Duke University
Durham, North Carolina
Dr Perfect reports receiving grants/research support from Astellas, Enzon, Merck and Company, Pfizer Inc, and Schering-Plough; serving as a consultant for Astellas, Enzon, Merck and Company, Pfizer Inc, and Schering-Plough; and receiving honoraria from Astellas, Enzon, Merck and Company, Pfizer Inc, and Schering-Plough.

Jack D. Sobel, MD
Professor and Division Chief
Infectious Diseases
Wayne State University School of Medicine
Detroit, Michigan
Dr Sobel reports receiving grants/research support from Astellas and Merck and Company; serving as a consultant for 3M Pharmaceuticals, Merck and Company, and Pfizer Inc; and receiving honoraria from 3M Pharmaceuticals, Merck and Company, Pfizer Inc, and Schering-Plough.

James S. Tan, MD, MACP, FCCP
Professor and Vice Chairman of Internal Medicine
Head, Infectious Disease Section
Northeastern Ohio Universities College of Medicine
Chairman, Department of Medicine
Summa Health System
Akron, Ohio
Dr Tan reports receiving honoraria from Aventis, Pfizer Inc, and Wyeth.

John Wingard, MD
Professor of Medicine
Department of Medicine
Director, Blood and Bone Marrow Transplant Program
University of Florida
Shands Cancer Center
Division of Hematology/Oncology
Gainesville, Florida
Dr Wingard reports receiving grants/research support from Merck and Company and Pfizer Inc; serving as a consultant for Merck and Company, Pfizer Inc, Schering-Plough, and Vical; receiving honoraria from Merck and Company and Pfizer Inc; serving as an investigator for Fujisawa and Ortho-McNeil; and serving on the speakerÕs bureau for Merck and Company and Pfizer Inc.

Notice: The audience is advised that articles in this CE activity contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Graybill—aminocandin, anidulafungin, caspofungin, posaconazole, and micafungin.
Dr Perfect—antifungal drugs without specific indications.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Overcoming Life-Threatening Bacterial And Fungal Infections: Case-Based Discussions And Evidence-Based Strategies
John G. Bartlett, MD, and John R. Graybill, MD 

Life-Threatening Fungal Infections
For many years, mycoses were considered to be "rare" and, as a result, the treatment options were limited, often to only amphotericin B. Although amphotericin B was effective for treating most infections, the "toxicity cost" was nearly prohibitive. Today, we have numerous antifungal agents from which to choose (eg, amphotericin B and its lipid formulations, fluconazole, voriconazole, itraconazole, caspofungin, and micafungin) and several more that will most likely become widely available in the near future (eg, posaconazole and anidulafungin). The question for mycologists, then, is whether we need more drugs or should we be using our current drugs more effectively?

Pittet et al showed nearly a decade ago that the fungal pathogen responsible for most of the in-hospital mortalities (even more so than all bacterial pathogens) was Candida, especially Candida albicans (Table 1).1 More recently, in 2000, we saw that Candida infections were associated with significant increases in attributable mortality and mean lengths of stay for adults and children (Table 2).2 These outcomes result in higher attributable costs approaching $100 000 per child and $40 000 per adult.2

The trends in attributable mortality from candidemia are confirmed in 2 other studies, which compare the crude mortality rates in cases and controls from 2 different eras: 1983 to 1986 and 1997 to 2001. As shown in the Figure, mortality rates (crude and attributable) with candidemia have not improved dramatically in the era of azoles compared with the era of amphotericin B.3,4

In addition, although candidemia remains an important problem for infectious disease specialists, filamentous pathogens (eg, Aspergillus spp, Zygomycetes, and Fusarium) are increasing in prevalence and worsening patient outcomes, even if they have not yet attained the notoriety and pervasiveness of candidiasis. Furthermore, the clinical challenges are not restricted to fungal pathogens, as the antifungal agents themselves can complicate treatment decisions. We must now consider each drug's toxicity, pharmacodynamic/pharmacokinetic parameters, and potential role in combination therapy, as well as epidemiologic factors such as endemic mycoses, susceptibility testing, other emerging yeast, and changing definitions (eg, new treatment success criteria for febrile neutropenia, and the cost-benefit analyses of prophylaxis).

The articles presented in this monograph (which are based on a satellite symposium that was held in conjunction with the 45th Annual Meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy [ICAAC] on December 17, 2005, in Washington, DC) address at least some of these burgeoning issues. John Wingard, MD, discusses the emergence of zygomycoses, offering some possible explanations as to why these infections are increasing in severity and presenting an approach to their management. John Perfect, MD, and Jack D. Sobel, MD, discuss some of the challenges associated with more common mycoses. Dr Perfect presents a case in which the clinician must consider the possibility of infection with multiple organisms that may change over time, and which addresses the role of biopsy and underscores the importance of determining the cause of the disease (which may not always be the fungus itself). Dr Sobel discusses candidiasis and the importance of localizing the infection site, which will help determine the need for and selection of therapy, and a case of candidal endocarditis, in which surgical interventions must be considered as first-line therapy and the choice of fungicidal agent may depend on more than just the minimum inhibitory concentration for the organism.

Life-Threatening Bacterial Infections
The American Thoracic Society first published guidelines on hospital-acquired pneumonia in 1997; these have recently been updated to include not only new therapies but also new classifications of pneumonia: specifically, hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP).5

Hospital-acquired pneumonia, which is most often caused by bacteria, accounts for up to 25% of all intensive care unit infections and is associated with mortality rates of up to 70%.5,6 HAP is defined as pneumonia that occurs 48 hours or more after admission, and which was not incubating at the time of admission. VAP refers to pneumonia that arises more than 48 to 72 hours after endotracheal intubation. HCAP includes any patient who was hospitalized in an acute care hospital for 2 or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic.5 As demonstrated by Donald E. Craven, MD, HCAP is included in the spectrum of HAP and VAP, and patients with HCAP need therapy for multidrug-resistant pathogens. Dr Craven reviews the latest guidelines on HCAP with a focus on resistance prevention via modifiable risk factors and identification of management principles—early, appropriate, and adequate therapy, with shortened treatment times and de-escalation strategies. He also presents a case study to illustrate these principles.

Foot infections in patients with diabetes are exceedingly common and can become limb and life threatening. James S. Tan, MD, MACP, FCCP, reviews the 2004 update of guidelines for managing diabetic foot infections, noting that optimal management requires both appropriate culture and appropriate antibiotic.7

George H. Karam, MD, relates his experience with Hurricane Katrina in Baton Rouge, Louisiana, to our response to bacterial resistance. As he notes, the lessons we have learned from this national disaster apply to the principle of antibiotic stewardship, and he uses 3 organisms as examples: Pseudomonas aeruginosa, community-associated methicillin-resistant Staphylococcus aureus, and Clostridium difficile with profound degrees of toxin production.

Also included in this monograph are summaries of 6 poster presentations from ICAAC, which are related to the topics presented by our main authors.

Conclusions
Although guidelines provide clinicians with a strategic approach to disease prevention, diagnosis, and treatment, many therapeutic decisions remain controversial and each case must be considered individually in the setting of local patterns of microbial epidemiology and resistance. The prompt and accurate diagnosis of fungal and bacterial infections, along with aggressive yet tailored therapy, is imperative for optimizing patient outcomes and minimizing the spread of antimicrobial resistance.

REFERENCES

1. Pittet D, Li N, Woolson RF, Wenzel RP. Microbiological factors influencing the outcome of nosocomial bloodstream infections: a 6-year, validated, population-based model. Clin Infect Dis. 1997;24:1068-1078.
2. Zaoutis TE, Argon J, Chu J, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis.
Clin Infect Dis. 2005;41:1232-1239.
3. Wey SB, More M, Pfaller M, et al. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med. 1988;148:2642-2645.
4. Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis. 2003;37:1172-1177.
5. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.
6. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in medical ICUs in the United States: National Nosocomial Infections Surveillance System. Crit Care Med. 1999;27:887-892.
7. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004;39:885-910.

*Professor, Department of Medicine, Chief, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
 Professor, Department of Medicine, Chief, Division of Infectious Diseases, University of Texas Health Science Center, San Antonio, Texas.
Address correspondence to: John G. Bartlett, MD, Professor, Department of Medicine, Chief, Division of Infectious Diseases, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 437, Baltimore, MD 21287.
E-mail: jb@jhmi.edu.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his/her article and all its contents.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.