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.
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.
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.
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.