Comparison of therapeutic activity of fluconazole and itraconazole in the treatment of oesophageal candidiasis in AIDS patients: a double-blind, randomized, controlled clinical study

The aim of this study was to assess the role and therapeutic efficacy of two azole antifungal drugs, fluconazole and itraconazole, in the treatment of endoscopically-diagnosed Candida oesophagitis in patients with Acquired Immunodeficiency Syndrome (AIDS). The study considered 120 Human Immunodeficiency Virus (HIV)-positive patients (67 males and 53 females, mean age 27 +/- 5) at their first episode of oesophageal candidiasis diagnosed by endoscopy (Kodsi's grade II endoscopic classification). The patients were double-blindly randomized into 2 groups of 60 patients each according to the pharmacological therapy administered: a) the patients in the first group received fluconazole (100 mg b.i.d. per os); b) the patients in the second group received itraconazole (100 mg b.i.d. per os). In order to evaluate the efficacy of the pharmacological therapy, a clinical examination was performed every week up to the end of the follow-up period (2 months); endoscopic examination was performed at the end of pharmacological treatment (3 weeks). All patients selected for the study gave their informed consent. Complete remission of endoscopic lesions was observed in 45 patients (75%) in the fluconazole group and in 23 patients (38%) in the itraconazole group (p < 0.001); partial remission of endoscopic lesions was observed in 15 patients (25%) in the fluconazole group and in 28 patients (47%) in the itraconazole group (p < 0.05). No response was observed in 9 patients (15%) in the itraconazole group. Complete clinical remission was observed in 47 patients (78%) in the fluconazole group and in 44 patients (73%) in the itraconazole group (p = n.s.); partial clinical remission was observed in 13 patients (22%) in the fluconazole group and in 12 patients (20%) in the itraconazole group (p =- m.s.). No clinical response was observed in 4 patients (7%) in the itraconazole group. No side-effects worthy of note were observed in the patients of either treatment group. The results of this study demonstrated that fluconazole is associated with higher rates of endoscopic and clinical cure than itraconazole, with a statistically significant difference as regards endoscopic cure. Both drugs appear to be safe and well tolerated. Nevertheless, further controlled clinical investigations are needed to improve our knowledge of the therapeutic action of antifungal drugs in the treatment of Candida oesophagitis in HIV disease.     

Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, < 500/microL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.     

Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS

BACKGROUND: Candidiasis is a frequent complication of infection with the human immunodeficiency virus (HIV); however, few data exist about the natural history, prevention, and treatment of mucosal candidiasis in women. OBJECTIVE: To evaluate the safety and effectiveness of weekly fluconazole prophylaxis for mucosal candidiasis in women infected with HIV. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 14 sites participating in the Community Programs for Clinical Research on AIDS (CPCRA). PATIENTS: 323 women with HIV infection and CD4+ cell counts of 300 cells/mm3 or less. INTERVENTION: 200 mg of fluconazole per week or placebo. Open-label fluconazole for candidiasis prophylaxis was permitted after two oropharyngeal or vaginal episodes or one esophageal episode. MEASUREMENTS: Development of mucosal candidiasis, clinical and in vitro resistance of Candida species to fluconazole, survival, and adverse events. RESULTS: After a median follow-up of 29 months, 72 of 162 patients receiving fluconazole and 93 of 161 patients receiving placebo had at least one episode of candidiasis (relative risk [RR], 0.56 [95% Cl, 0.41 to 0.77); P < 0.001). Weekly fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [Cl, 0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [Cl, 0.40 to 1.00]; P = 0.05) but not esophageal candidiasis (RR, 0.91 [Cl, 0.48 to 1.72]; P > 0.2). Relative risks were similar for women who had a history of mucosal candidiasis (RR, 0.5 [Cl, 0.35 to 0.75]) and those who did not (RR, 0.69 [Cl, 0.35 to 1.34]). Absolute risk reduction for patients with a history of infection was 25.6 per 100 person-years, which is more than twice the reduction of 11.2 per 100 person-years seen in patients with no history of infection. This difference reflects the higher risk of patients who previously had an infection. Candida albicans was not usually resistant to fluconazole in vaginal specimens in clinical or in vitro settings; such resistance occurred in less than 5% of patients in each group. CONCLUSIONS: Weekly fluconazole (200 mg) seems to be safe and effective in preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role in the management of HIV-infected women who are at risk for recurrent mucosal candidiasis.     

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.     

Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen. The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance. Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidal infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation .     

Comparison of itraconazole and ketoconazole in HIV-positive patients with oropharyngeal or esophageal candidiasis. Human Immunodeficiency Virus Itraconazole Ketoconazole Project Group

The efficacy of oral itraconazole and ketoconazole in the treatment of oropharyngeal and/or esophageal candidiasis, and the rate of post-treatment relapse, were compared in a multicenter, prospective, double-blind, double-dummy, randomized, parallel-group trial. A total of 143 adult HIV-positive patients with oropharyngeal and/or esophageal candidiasis were assigned to receive either itraconazole or ketoconazole (200 mg/day). Patients with oropharyngeal and esophageal candidiasis were treated for 2 and 4 weeks, respectively. Patients were evaluated clinically and mycologically after 1, 2 and 4 (for esophageal patients) weeks of therapy, and relapses were compared in a 6-week post-treatment follow-up period. Of 129 evaluable patients, 98 had oropharyngeal candidiasis and 31 esophageal infection. CDC classification, CD4+ cell counts, and number of previous episodes of oropharyngeal or esophageal candidiasis were comparable in both groups. Oropharyngeal infection was cleared clinically at 21 days in 71% of patients receiving itraconazole and 60% receiving ketoconazole, and esophageal candidiasis was cleared at 41 days in 100% of patients receiving itraconazole and 91% receiving ketoconazole. Marginally significant differences were found between itraconazole and ketoconazole in rates of clearing of infection clinically in patients with oropharyngeal and esophageal candidiasis (p = 0.0614 and 0.0781, respectively). Mean rates of infection relapse were not statistically different in the two treatment groups. Adverse events were generally mild and not considered drug related. Itraconazole is marginally more efficacious than ketoconazole in the treatment of oropharyngeal and esophageal candidiasis in HIV-positive patients and both drugs appear safe and well tolerated.     

Relationship between feed withdrawal and viscera condition of broilers

An AIDS patient with disseminated histoplasmosis who improved during treatment with fluconazole but remained fungemic and subsequently relapsed is described. Isolates obtained from blood during therapy showed a progressive increase in fluconazole MIC from 0.625 to 20 micrograms/ml. The pretreatment, or parent, isolate and the posttreatment, or relapse, isolate demonstrated identical genetic patterns by PCR fingerprinting with three different primers. Fluconazole was less potent inhibitor of the growth of the relapse isolate than of the pretreatment isolate (50% inhibitory concentration [IC50] = 11.7 microM), while itraconazole was more potent (relapse isolate IC50 = 0.0011 microM versus pretreatment isolate IC50 = 0.0064 microM). Neither the increased sensitivity to itraconazole nor the decreased activity of fluconazole on the growth of the relapse isolate results from changes in the intracellular content of these agents. To reach 50% inhibition of ergosterol synthesis in both the parent and relapse isolates, about 2 nM itraconazole was needed; with fluconazole, 50% inhibition was achieved at 20.9 microM and 55.5 microM, respectively. Resistance to fluconazole may develop during treatment and results from decreased sensitivity of ergosterol synthesis.     

Response to fluconazole and itraconazole of Candida spp. in denture stomatitis

The significance of Candida albicans in the development of denture stomatitis (DS), as well as the clinical and microbiological efficacy of treatment with fluconazole and itraconazole was studied in 115 patients affected with DS and 200 controls (100 healthy patients with dental prosthesis and 100 healthy patients without prosthesis). Specimens were taken from all patients; subsequently all patients with positive culture of the DS group were treated with fluconazole. A second specimen was taken after 15 days of treatment with fluconazole, and if the results were positive again, treatment with itraconazole was instituted and the patients were given appointments for taking a third specimen. The incidence of C. albicans was 92% in the group of patients with DS. After treatment with fluconazole, a clinical cure of 97% and a microbiological cure of 78% was obtained in the patients with DS. In 3.2% of the cases strains resistant to fluconazole were found. The cases of microbiological resistance to fluconazole were treated with itraconazole resulting in a clinical cure of 100% and a microbiological cure of 77%. The results show the poor correlation of the clinico-microbiological response after treatment with these antifungal agents in denture stomatitis.     

Curative treatment with fluconazole in 5 cases of invasive candidiasis

BACKGROUND: Amphotericin B is the treatment of choice for invasive and disseminated Candida sp. infections. Fluconazole is an antifungal drug with less toxicity. Because of its pharmacokinetic properties, fluconazole can be specially useful in the treatment of invasive candidiasis. Although it is useful in several forms of candidiasis, its efficacy in deep-seated candidal infections is not totally proved due to the lack of comparative studies with amphotericin. In order to contribute new data about the usefulness of fluconazole in the treatment of invasive candidiasis, we report 5 patients which cured with this antifungal drug. METHODS: The clinical records of those patients with invasive candidiasis that cured with fluconazole were retrospectively reviewed. RESULTS: Fluconazole was used in 2 patients after detecting toxicity to amphotericin. Fluconazole was used from the beginning in the other 3 patients. None of the patients were neutropenic. All the patients cured without recurrence. CONCLUSIONS: In this series, the employment of fluconazole was a non-toxic and effective alternative to amphotericin B in nonneutropenic patients with invasive candidiasis.     

Clinical and laboratory profile of sixty patients with AIDS: a South Indian study

Sixty patients who fulfilled the WHO case definition of acquired immunodeficiency syndrome (AIDS) were admitted and treated between January 1993 and June 1995 in JIPMER Hospital, Pondicherry, South India. Their mean age was 30.3 +/- 6.4 years. Male: female ratio was 5 : 1. The heterosexual route was the major mode of transmission (96.7%). Fever was the commonest presentation (98.3%), followed by weight loss (85%) and cough (36.7%). The commonest opportunistic infection seen was tuberculosis (pulmonary, extrapulmonary - single or in combination) followed by esophageal candidiasis. Cryptococcal meningitis, intestinal crytosporidiosis, CNS toxoplasmosis, Pneumocystis pneumonia and group B Salmonella septicemia were the other infections encountered. Ten out of the 38 patients with tuberculosis were followed up on antituberculous treatment for 6 months. Seven out of 18 patients with esophageal candidiasis were treated with ketoconazole.     

A comparison of fluconazole and itraconazole in the management of denture stomatitis: a pilot study

OBJECTIVES: To compare fluconazole capsules (50 mg daily for 14 days) and itraconazole capsules (100 mg daily for 15 days) in the treatment of denture stomatitis, using objective clinical and mycological outcome measures. METHODS: Twenty complete denture wearers with denture stomatitis were enrolled. At baseline, palatal erythema was measured with an electro-optical instrument, a denture disc specimen was collected from the fitting surface of the denture for culture and an oral rinse and imprint cultures were collected for mycological culture. Ten patients received fluconazole capsules (50 mg daily for 14 days) and 10 received itraconazole capsules (100 mg daily for 15 days). Palatal erythema was reassessed and the microbiological specimens re-collected on day 14. RESULTS: The most common form of denture stomatitis seen in this group of patients was Newton's Type II. All patients responded to advice to leave their dentures out at night but there was a poor overall improvement in denture hygiene. There was an objective reduction in palatal erythema following treatment with both fluconazole and itraconazole. A wide range of yeasts were isolated from the mouths of all the denture stomatitis patients before treatment. C. albicans was the most common isolate. A mycological cure was achieved in only five of the 20 patients, one in the fluconazole group and four in the itraconazole group. A further eight patients in the fluconazole group and three in the itraconazole group had reduced yeast counts by the second visit. CONCLUSION: Fluconazole and itraconazole were of comparable efficacy in the treatment of denture stomatitis, on the basis of reduction in palatal erythema and mycological culture.     

DEFPARAM: a program package for aligning elliptical sections of biological objects containing an n-fold symmetry

BACKGROUND: Oesophageal candidiasis is the most common cause of oesophageal symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be better tolerated than capsules or tablets in children or patients with oesophageal symptoms. We performed a prospective study of the safety and efficacy of fluconazole suspension. METHODS: Patients with HIV infection; odynophagia, dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate in the oesophagus; and microscopic confirmation of fungal infection on biopsy or brushing specimens were eligible. Patients received fluconazole oral suspension (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2 weeks after symptom resolution. Repeat endoscopy was performed after completion of therapy. RESULTS: Forty-two patients enrolled in the study: 40 were male, mean (+/- s.e.) age was 37 +/- 2 years and mean CD4 cell count was 67 +/- 14/mm3. One patient was not evaluable because he received amphotericin during the first week of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy. Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2) led to early termination of therapy in 5 patients, all of whom had clinical and endoscopic cure. CONCLUSIONS: Symptoms resolved in 100% of patients with AIDS and oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of patients had symptom resolution within 2 weeks. Determining whether the more rapid clinical cure in this study, compared with a previous trial which employed capsules, is related to an additional topical antifungal effect of the suspension, will require further study.     

Comparative evaluation of fluconazole 50 mg and 100 mg versus itraconazole 100 mg in the treatment of dermatomycoses

In the above double-blind multicenter study the efficacy and tolerability of 50 and 100 mg doses of fluconazole were compared with 100 mg itraconazole in 178 patients with T. corporis, T. cruris, and T. pedis infections. All patients were submitted to clinical and mycological examination before starting, at weekly intervals during treatment, and 4 and 8 weeks after its conclusion. Duration of the three therapeutic regimes was 15 days for T. corporis and T. cruris, and 30 days for T. pedis infection. The percentage of symptomatic cure was 85% and 86.5%, respectively for 50 and 100 mg fluconazole, and 83% for itraconazole. Mycologic cure was achieved in 81.4% of patients treated with 50 mg fluconazole, 83.3% in those treated with 100 mg fluconazole, and 67.9% in those treated with 100 mg itraconazole. None of the groups showed changes in laboratory parameters. It is concluded that all three treatment schemes had high antimycotic activity, but fluconazole both 50 and 100 mg daily was superior. Both drugs were well tolerated and compliance was good.     

Fluconazole. An update of its antimicrobial activity, pharmacokinetic properties, and therapeutic use in vaginal candidiasis

Fluconazole is a bis-triazole antifungal drug which has a pharmacokinetic profile characterised by its high water solubility, low affinity for plasma proteins, and metabolic stability. After a single 150 mg oral dose, therapeutic concentrations in vaginal secretions are rapidly achieved and are sustained for a duration sufficient to produce high clinical and mycological responses in nonimmunocompromised patients with vaginal candidiasis (candidosis). At this dosage, clinical and mycological responses have compared favourably with responses achieved after multiple dose regimens of other oral and intravaginal antifungal agents. Clinical efficacy rates have ranged between 92 and 99% at short term evaluation (5 days post-treatment). At 80 to 100 days post-treatment clinical efficacy rates of 91% have been reported. In addition, limited data indicate that fluconazole is more effective than placebo as prophylactic treatment of frequently recurring vaginal candidiasis. Single oral doses of fluconazole 150 mg are well tolerated. Most frequently observed adverse events are gastrointestinal symptoms, which are generally mild and transient in nature. Thus, fluconazole is a valuable alternative to established systemic and intravaginal azole antifungal drugs which are used to treat vaginal candidiasis. Moreover, in view of its favourable patient acceptability and compliance profile compared with alternative treatments, single-dose oral fluconazole should be considered as a first-line therapeutic choice for the treatment of women with vaginal candidiasis.     

Endoscopic-pathologic correlates of Candida esophagitis in acquired immunodeficiency syndrome

Although Candida esophagitis is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), there has been no systematic study of the endoscopic and pathologic manifestations of this disease. During a 53-month period, 141 patients with AIDS and Candida esophagitis were studied. All patients had the severity of esophagitis graded prospectively and esophageal mucosal biopsies performed. Tissue biopsies were evaluated for histologic evidence of ulceration, extent of candidiasis, and presence of viral cytopathic effect. Follow-up was obtained. There appeared to be a uniform endoscopic appearance; with increasing severity, the scattered mucosal plaques coalesced, resulting in circumferential disease and luminal impingement. The pathologic pattern of Candida esophagitis was homogenous. Plaque material was composed primarily of desquamated superficial hyperplastic hyperkeratotic squamous epithelium and inflammatory cells, with infiltration by fungal elements and bacteria consistent with superinfection. Although endoscopic and histopathologic ulcer was commonly seen in these patients (32%), only four patients had ulcer believed secondary to Candida esophagitis alone. In conclusion, in patients with AIDS, Candida esophagitis is a superficial mucosal infection resulting in characteristic endoscopic and histopathologic patterns.     

Surgeon''s experience as a factor for emetic sequelae after middle ear surgery

OBJECTIVE: To evaluate the efficacy of melaleuca oral solution in AIDS patients with fluconazole-resistant oropharyngeal candida infections. DESIGN: A prospective, single center, open-labeled study. SETTING: A university-based inner-city HIV/AIDS clinic. PATIENTS: Thirteen patients with AIDS and oral candidiasis documented to be clinically refractory to fluconazole, as defined by failure to respond to a minimum of 14 days of > or = 400 mg fluconazole per day. Additionally, patients had in vitro resistance to fluconazole, defined by minimal inhibitory concentrations of > or = 20 microg/ml. INTERVENTIONS: Patients were given 15 ml melaleuca oral solution four times daily to swish and expel for 2-4 weeks. MAIN OUTCOME MEASURES: Resolution of clinical lesions of oral pseudomembranous candidiasis lesions. Evaluations were performed weekly for 4 weeks and at the end of therapy for clinical signs of oral candidiasis. Quantitative yeast cultures were performed at each evaluation. RESULTS: A total of 13 patients were entered into the study, 12 were evaluable. At the 2-week evaluation, seven out of 12 patients had improved, none were cured, and six were unchanged. At the 4-week evaluation, eight out of 12 patients showed a response (two cured, six improved), four were non-responders, and one had deteriorated. A mycological response was seen in seven out of 12 patients. A follow-up evaluation 2-4 weeks after therapy was discontinued revealed that there were no clinical relapses in the two patients who were cured. CONCLUSIONS: Melaleuca oral solution appears to be effective as an alternative regimen for AIDS patients with oropharyngeal candidiasis refractory to fluconazole.     

A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute

BACKGROUND: Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. METHODS: To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. RESULTS: Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B. CONCLUSIONS: In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.     

Refractory mucosal candidiasis in patients with human immunodeficiency virus infection

Difficult-to-manage mucosal candidal infection has been a hallmark of individuals with advanced infection due to human immunodeficiency virus type 1. In this AIDS Commentary, Drs. Fichtenbaum and Powderly comprehensively review the literature and their experience with refractory candidiasis in such patients. Of interest is their delineation of resistance, a lack of susceptibility to an antifungal agent in vitro among patients with refractory or clinically unresponsive disease. These authors believe that the establishment of resistance should be based upon standards established by the National Committee on Clinical Laboratory Standards, which they propose to define as a failure to respond to systematic therapy with specific doses of itraconazole, fluconazole, or parenterally or orally administered amphotericin B within 14 days. There have been many definitions of "refractory candidiasis," and the one proposed by these authors will be debated; however, this definition has the advantage of establishing a standard by which to judge the efficacy of their proposed algorithm for the treatment of persistent or refractory oropharyngeal candidal infections. Drs. Fichtenbaum and Powderly have performed a useful service in their attempt to bring coherence to the management of this common and often vexing problem.     

Evaluation of the fungitest kit by using strains from human immunodeficiency virus-infected patients: study of azole drug susceptibility

One hundred eighteen Candida clinical isolates from human immunodeficiency virus-infected patients were tested for their susceptibilities to fluconazole and itraconazole by Fungitest and the National Committee for Clinical Laboratory Standards MIC method. Fungitest results depended on both yeast species and antifungal agents. This test is able to detect sensitive strains (97% agreement with results of the MIC method in tests with fluconazole and 84% agreement in tests with itraconazole) but has a poor capacity to detect resistant strains (26% agreement in tests with fluconazole and 5% agreement in tests with itraconazole).