Diagnosis and therapy of invasive candida infections [Review Article]

ABSTRACT

To review the current status of diagnosis and treatment of invasive Candida infections. In recent years, Candida species have emerged as the fourth most frequent cause of nosocomial bloodstream infections, thus acquiring similar clinical significance as other familiar bacterial pathogens commonly associated with hospital-acquired sepsis. Despite growing clinical importance of Candida, a large number of patients die due to undiagnosed invasive candidiasis. With the current limitations of laboratory diagnostic tests, an understanding of the clinical setting or the risk factors in which a Candida species assumes the role of a destructive pathogen is extremely crucial for suspecting an early diagnosis. The information provided in this article has been obtained through Medline search and is largely based on the recommendations made by various expert groups on the subject. The diagnosis of invasive candidiasis is problematic due to the following reasons [i] blood cultures may remain negative in about 50% of the patients with proven candidiasis, [ii] candidemia, a marker of dissemination, does not necessarily establish a disseminated disease, [iii] ophthalmologic examination is a valuable tool in diagnosing disseminated candidiasis but retinal lesions are found in less than 30% of candidemia patients and [iv] serologic tests lack sensitivity and specificity To improve isolation of Candida species from blood, use of Isolator lysis centrifugation method is recommended. Likewise, specificity and sensitivity of antigen detection in serum specimens can be enhanced by frequent sampling. All patients, even with a single positive blood culture, need to be treated with systemic antifungal therapy Amphotericin B is the standard drug for the treatment of invasive and disseminated candidiasis, particularly in neutropenic patients. 5-flucytosine in combination with amphotericin B is recommended for the treatment of severe Candida infections specially those associated with endophthalmitis, endocarditis, suppurative thrombophlebitis and meningitis, and also if the infection is caused by C. lusitaniae or C. glabrata. Liposomal formulations of amphotericin B, despite their decreased nephrotoxicity, have not been found to enhance therapeutic efficacy in clinical conditions. They should be used restrictively only for patients who are intolerant of or refractory to conventional amphotericin B therapy Fluconazole [400mg/d] is an effective and safe alternative to amphotericin B [0.5 -0.6mg/kg] for treatment of invasive candidiasis. Since the drug has excellent cerebrospinal penetration and is excreted unchanged through the kidneys, it is especially useful for the treatment of meningeal and genitourinary Candida infections. Considering its high safety profile, fluconazole can be selectively administered in much higher doses [>/= 600mg/day]. Until more sensitive and specific laboratory tests become available, an integrated approach based on blood cultures, serodiagnostic tests, and careful repeated clinical evaluation of the patients for evidence of hematogenous dissemination, should form the basis for the diagnosis of invasive and disseminated candidiasis. Early recognition of the risk factors with a high index of suspicion remains an integral component of the diagnostic approach: