TREATMENT Candida Infections MUCOCUTANEOUS CANDIDA INFECTION
The treatment of mucocutaneous candidiasis is summarized in Table 115-2. CANDIDEMIA AND SUSPECTED HEMATOGENOUSLY DISSEMINATED CANDIDIASIS
All patients with candidemia are treated with a systemic antifungal agent. A certain percentage of patients, including many of those who have candidemia associated with an indwelling intravascular catheter, probably have “benign” candidemia rather than deep-organ seeding. However, because there is no reliable way to distinguish benign candidemia from deep-organ infection, and because antifungal drugs less toxic than amphotericin B are available, antifungal treatment for candidemia—with or without clinical evidence of deep-organ involvement—has become the standard of practice. In addition, if an indwelling intravascular catheter is present, it is best to remove or replace the device whenever feasible.
The drugs used for the treatment of candidemia and suspected disseminated candidiasis are listed in Table 115-3. Various lipid formulations of amphotericin B, three echinocandins, and the azoles fluconazole and voriconazole are used; no agent within a given class has been clearly identified as superior to the others. Most institutions choose an agent from each class on the basis of their own specific microbial epidemiology, strategies to minimize toxicities, and cost considerations. Unless azole resistance is considered likely, fluconazole is the agent of choice for the treatment of candidemia and suspected disseminated candidiasis in nonneutropenic, hemodynamically stable patients. Initial treatment in the context of likely azole resistance depends, as mentioned above, on the epidemiology of the individual hospital. For example, certain hospitals have a high rate of recovery of C. glabrata, while others do not. At institutions where non-albicans Candida species are frequently recovered, therapy with an echinocandin is typically started while the results of sensitivity testing are awaited. For hemodynamically unstable or neutropenic patients, initial treatment with broader-spectrum agents is desirable; these drugs include polyenes, echinocandins, or later-generation azoles such as voriconazole. Once the clinical response has been assessed and the pathogen specifically identified, the regimen can be altered accordingly. At present, the vast majority of C. albicans isolates are sensitive to fluconazole. Isolates of C. glabrata and C. krusei are less sensitive to fluconazole and more sensitive to polyenes and echinocandins. C. parapsilosis is less sensitive to echinocandins in vitro; however, this lesser sensitivity is considered nonsignificant.
Some generalizations exist regarding the management of specific Candida infections. Recovery of Candida from sputum is almost never indicative of underlying pulmonary candidiasis and does not by itself warrant antifungal treatment. Similarly, Candida in the urine of a patient with an indwelling bladder catheter may represent colonization only rather than bladder or kidney infection; however, the threshold for systemic treatment is lower in severely ill patients in this category since it is impossible to distinguish colonization from lower or upper urinary tract infection. If the isolate is C. albicans, most clinicians use oral fluconazole rather than a bladder washout with amphotericin B, which was more commonly used in the past. Caspofungin has been used with success; although echinocandins are poorly excreted into the urine, they may be an option, especially for non-albicans isolates. The doses and duration are the same as for disseminated candidiasis. The significance of the recovery of Candida from abdominal drains in postoperative patients is unclear, but again the threshold for treatment is generally low because most of the affected patients have been subjected to factors predisposing to disseminated candidiasis.
Removal of the infected valve and long-term antifungal therapy constitute appropriate treatment for Candida endocarditis. Although definitive studies are not available, patients usually are treated for weeks with a systemic antifungal agent (Table 115-2) and then given chronic suppressive therapy for months or years (sometimes indefinitely) with an oral azole (usually fluconazole at 400–800 mg/d).
Hematogenous Candida endophthalmitis is a special problem requiring ophthalmologic consultation. When lesions are expanding or are threatening the macula, an IV polyene combined with flucytosine (25 mg/kg four times daily) has been the regimen of choice, although comparative studies with other regimens have not yet been reported. As more data on the azoles and echinocandins become available, new strategies involving these agents are developing. Of paramount importance is the decision to perform a partial vitrectomy. This procedure debulks the infection and can preserve sight, which may otherwise be lost as a result of vitreal scarring. All patients with candidemia should undergo ophthalmologic examination because of the relatively high frequency of this ocular complication. Not only can this examination detect a developing eye lesion early in its course; in addition, identification of a lesion signifies a probability of ~90% of deep-organ abscesses and may prompt prolongation of therapy for candidemia beyond the recommended 2 weeks after the last positive blood culture. Although the basis for the consensus is a very small data set, the recommended treatment for Candida meningitis is a polyene (Table 115-3) plus flucytosine (25 mg/kg four times daily). Successful treatment of Candida-infected prosthetic material (e.g., an artificial joint) nearly always requires removal of the infected material followed by long-term administration of an antifungal agent selected on the basis of the isolate’s sensitivity and the logistics of administration.