Resolution of multidrug-refractory oesophageal candidiasis in an AIDS patient after treatment with caspofungin.

Abstract

Azole-resistant or refractory candidiasis in patients with advanced HIV disease was a commonly encountered therapeutic challenge in the era before the advent of highly active antiretroviral therapy (HAART) [1]. Since the introduction of HAART, the rates of symptomatic oropharyngeal candidiasis and of Candida albicans colonization have significantly decreased among HIV-infected patients [2–4]. Furthermore, the complete resolution of refractory candidiasis has been documented in AIDS patients experiencing immune reconstitution after treatment with HAART regimens [5–7]. However, the increasing failure of second- and third-line HAART regimens will probably lead to the reappearance of patients with multidrug-resistant candidiasis of problematical management. We describe here an AIDS patient with oropharyngeal and oesophageal candidiasis of 2 years’ duration, unresponsive to all available therapies, that was successfully treated with caspofungin. A 48-year-old man had been followed at our Institute since 1993, when he was diagnosed with HIV infection. Over the years, he had suffered from recurrent episodes of oral candidiasis, which responded to topical antifungal agents or short-term therapy with fluconazole. He had also developed a number of AIDS-defining diseases, such as cytomegalovirus retinitis and disseminated Mycobacterium avium-complex disease. Moreover, the patient had failed several HAART regimens and developed resistance to all current antiretroviral drug classes, as shown by genotypic and phenotypic assays. Although he had been on multidrug rescue therapy including stavudine, lamivudine, didanosine, abacavir, amprenavir, and lopinavir/ritonavir for one year, his CD4 cell count was 46 cells/μl and plasma HIV-RNA level was 424 717 copies/ml. He was also receiving trimethoprim–sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia, ganciclovir and azithromycin as secondary prophylaxis for, respectively, cytomegalovirus and M. avium- complex infections. Since September 1999 the patient had had thrush and complained of recurrent dysphagia and vomiting. Cultures from oral swabs had yielded C. albicans, and endoscopic examination documented grade 2–3 oesophageal candidiasis, but treatment with different antifungal drugs (fluconazole at high doses, ketoconazole, itraconazole oral solution, amphotericin B both orally and intravenously, liposomal amphotericin B, and voriconazole) had only led to partial responses. In November 2001 caspofungin became available in Italy within a compassionate use study. After giving written informed consent, the patient was enrolled in the study and received caspofungin at a dose of 50 mg a day intravenously in our outpatient clinic. After 2 weeks, oral Candida lesions completely disappeared, whereas endoscopy showed only rare scattered oesophageal lesions. For the first time in 2 years, the patient did not complain of dysphagia or vomiting. After 4 weeks’ treatment, endoscopy revealed complete resolution of Candida oesophagitis, and the drug was therefore discontinued. No general laboratory test abnormality or clinical adverse event occurred throughout the treatment period. Caspofungin (formerly MK-0991) is a member of a novel class of antifungal agents, the echinocandins, which act as non-competitive inhibitors of 1,3-β-d-glucan synthase activity [8,9]. This drug has recently been approved in the United States for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies. Caspofungin has potent fungicidal activity against pathogenic yeasts, including most species of Candida, against Aspergillus species and other filamentous and dimorphic fungi [9]. According to the preliminary results of the trials conducted so far, caspofungin has demonstrated good efficacy and tolerability in patients with oropharyngeal or oesophageal candidiasis [10]. The novel mechanism of action of the echinocandins makes this class of drug particularly attractive for the treatment of patients with azole-resistant candidiasis. The patient described here was in an advanced stage of HIV disease and had a history of mucosal candidiasis, which had required prolonged exposure to azoles and amphotericin B. He had developed a multidrug-refractory Candida infection that, although non-life-threatening, greatly impaired his quality of life. HAART regimens had also had little impact on the disorder, because of the lack of a sustained immunological response. Exceeding all expectations, the treatment with caspofungin led to a quick complete resolution of the patient's symptoms and the disappearance of his oral and oesophageal lesions. In conclusion, our case supports the results of the clinical trials with caspofungin. Although the long-term efficacy of therapy with caspofungin is not yet known, and recurrences of candidiasis are expected unless immune reconstitution occurs, we believe that this drug may be of great benefit for HIV-infected individuals with multidrug-refractory candidiasis or other serious fungal infections. Salvatore Sollimaa Mario Corbellinoa Paola Cicconia Manuela Piazzaa Ottavia Viganòa Spinello Antinorib