A Standard of Care for Invasive Fungal Infections for the United Kingdom

Abstract & Commentary

Synopsis: A standard of care for dealing with invasive fungal infections based on the best available evidence was proposed by organizations in the United Kingdom.

Source: Denning DW, et al. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect Dis. 2003;3:230-240.

The incidence of invasive fungal infections in all developed nations continues to increase despite the success of combination antiretroviral therapy in reducing the incidence of AIDS. This trend is likely to continue reflecting an increase in the susceptible population, which includes patients treated for malignancies, recipients of transplants, those given intensive care, and neonates. Denning and colleagues were struck by 3 observations. Far from being inevitable, the mortality associated with invasive fungal diseases could be lowered dramatically with improved management as had been achieved in France; the outcome from cancer in the United Kingdom was lower than in other developed countries; and the practice of mycology in the United Kingdom was far from ideal. They, therefore, set out to define those standards of care that should help lower mortality due to invasive fungal infections to a minimum. The intention was to define absolute standards that could be audited. To help them in their task, they consulted widely and adopted the scales proposed by the Infectious Diseases Society of America to assess the quality of the evidence.

Table

Standard of Care for Management— United Kingdom

1. Identify clearly requests for microbiology, histology, and radiology coming from immunocompromised patients

2. Patients with candidaemia

· Remove or replace central venous catheters except when long-term access is needed when careful individual assessment should be made

· Treat with a systemic antifungal agent at an appropriate dose

3. Treatment within 6 h of transplant recipients or profoundly neutropenic patients with a systemic antifungal agent at an appropriate dose active against molds when there is

· A new positive culture of Aspergillus or mold

· A new pulmonary infiltrate or cerebral abnormalities consistent with a fungal infection

4. Treat patients with cryptococcal meningitis initially with amphotericin B deoxycholate > 0.7 mg/kg/d or > 4 mg/kg/d lipid-based amphotericin B with flucytosine 75-100 mg/kg/d (adjusted for renal function)

Beginning with microbiology, they nailed their colors firmly to the mast. The laboratory should use the tests detailed in the Figure, which should provoke little comment from microbiologists. However, and here is the rub, this also presupposes that clinicians will obtain specimens from their patients, something that is frequently not done for a variety of reasons. Similarly, no

one would quibble about the standards expected of histopathology except that, once again, tissue is seldom available from patients in life and also postmortem, as there are fewer autopsies being undertaken. Ironically, radiology has come to play an increasingly important role since CT scans are now generally available and increasingly being requested for those patients most at risk of developing invasive fungal infection, particularly neutropenic patients and recipients of transplants. There may well be some geographical variation in the indications for ordering a CT scan (eg, some would include a positive PCR for Aspergillus or a positive galactomannan test), but the principle is clear—a CT scan or other appropriate imaging technique should be ordered when any of the criteria detailed in the Figure are met. (To see chart, click here.)

Comment by J. Peter Donnelly, PhD

The standard of care for management proposed in the Table reflects opinions and practices in the United Kingdom. However, few would disagree with the notion that requests for radiology, microbiology, or histopathology from immunocompromised patients should always indicate this fact. Moreover, the management of candiaemia and the transplant recipient or profoundly neutropenic patient would not cause a stir, as it is in line with what experts now agree. However, the agents used to treat these entities, as well as cryptococcosis, may seem peculiar to the United Kingdom. Be that as it may, this document could easily serve as a basis for setting standards in other countries, including those belonging to the European Union and even further beyond. While intellectually appealing, it will take more than just a consensus to persuade the different hospitals and institutes to accept the standards as their practice and then to implement them. A body will also have to be established to oversee auditing to help maintain the standard, which will require funding and commitment by the participants, their professional associations, and their health care providers, not an easy task these days. Nevertheless, these standards fit well in the context of dealing with invasive fungal diseases since there is a consensus about defining them, more options for diagnosing them, more agents available to treat them, and a willingness to move away from more passive management involving empirical therapy to a more pro-active stance of early recognition and preemptive treatment.

Dr. Donnelly is Clinical Microbiologist University Hospital Nijmegen, The Netherlands Section Editor, Microbiology