Use Of Fluconazole Research Articles

Efficacy of oral amphotericin B in AIDS patients with thrush clinically resistant to fluconazole

Reports of thrush clinically refractory to azoles in AIDS patients are increasing with the more widespread use of these agents. We studied our own oral preparation of amphotericin B in the treatment of two AIDS patients who developed oral thrush due to Candida glabrata after prolonged fluconazole use. Improvement occurred in both in less than 1 week, with eventual clearing and absence of side effects. Oral amphotericin B may have advantages over alternatives for this increasing problem.

PEM report number 3. Fluconazole

AbstractThree groups of patients who were prescribed the oral anti‐fungal drug fluconazole between September 1988 and January 1989 were studied by Prescription‐Event Monitoring (PEM). The largest group of 13,440 patients, including 560 men, had been treated with a single 150 mg capsule. A smaller group of 798, including 55 men, had received more than one 150 mg capsule and a third small group of 777 patients, including 261 men, had received a course of treatment with 50 mg capsules. The first group was studied between February and June 1989 and the second and third groups in January 1990.In the two groups who had received single or multiple doses of 150 mg, the mean age of women was 34 and 35 years respectively and of men in both groups, 41 years. In the small group receiving 50 mg capsules the patients were considerably older, the males averaging 49 years and the females 46 years. While an overwhelming majority of females were treated for vaginal candidiasis, a significant number of men in the 150 mg groups and almost half the men in the 50 mg group had been treated for oral candidiasis. It was believed that a considerable number of men had been treated prophylactically while their partners were receiving treatment for vaginal candidiasis.General practitioners reported that the single 150 mg capsule had been effective in 85%. As expected, there were many cases of re‐infection or recurrences during the three‐month period of observation.The pattern of events was compared with data obtained from PEM studies of itraconazole and 31 other drugs. Upper respiratory tract and genito‐urinary infections were reported more frequently than with other drugs but the relationship was with the disease being treated rather than with the drug itself.There were four cases of angioneurotic oedema, only two of which were considered to have been possibly related to the use of fluconazole. There were also four reports of liver dysfunction, none of which was considered to be drug related.Although pregnancy is a contra‐indication, a total of 289 were reported. Thirty‐nine had terminated in spontaneous abortion and 38 were terminated therapeutically. Among women who used fluconazole prior to conception there were six abnormal pregnancies including four live births, one stillborn foetus with trisomy‐18 (Edwards' syndrome) and one anencephalic foetus. One mother had used fluconazole a week before conception. The baby had three short fingers on one hand. No abnormalities occurred in babies exposed during their mother's pregnancy.One hundred and twenty‐five deaths were investigated. Eighty of the deaths were due to cancer, 26 to neurological, cardiac or respiratory disease and seven to AIDS. Other or undetermined causes accounted for a further 12 deaths. No death was attributed to treatment.The overall conclusion reached after this study of more than 15,000 patients was that, while many events that had been recorded were attributable to the candidial infection, fluconazole was virtually free from recognizable side‐effects.

Fluconazole-Resistant Candida albicans After Long-term Suppressive Therapy

Candida albicans is generally considered to be susceptible, in vivo, to fluconazole. In the population infected with human immunodeficiency virus, recurrent bouts of oral and esophageal candidiasis have led to increasing use of fluconazole for long-term prophylaxis. With prolonged therapy, the issue of developing resistance emerges. We report a case of fluconazole-resistant C albicans esophagitis that developed after fluconazole was used for more than 600 days.

From Candida to Torulopsis: Funguria in long-term stay patients under the pressure of fluconazole use

The API 20-C clinical yeast identification system (API Laboratory Products Ltd, St. Laurent, Quebec) has given routine clinical laboratories a means of readily discriminating among 15 species of Candida, many species of Cryptococcus, Geotrichum (a mould), Prototheca (an alga), Rhodotorula, Torulopsis, and Trichosporon that had not been previously available. It is to be expected that with the availability of this test, the microbiology laboratory would begin to identify these hitherto unfamiliar species. The unfamiliarity of the new name might well attract the clinicians' attention. We decided to look at the epidemiology of these yeasts in sputum and urine. For the yeast cultures of the first 3 months of 1992, there were 22 individuals with the isolation of Candida albicans from the urine and 10 from the sputum. For non-Candida albicans yeasts, there were 16 from urine (one C. parapsilosis, seven C. tropicalis, six Torulopsis glabrata, and two Trichosporon beigelii) and two from sputum (one C. parapsilosis and one C. tropicalis). Although yeasts other than C. albicans were seldom isolated from the sputum, it was also apparent on review of these cases that only onehalf of patients were admitted with yeasts other than C. albicans or, occasionally, C. tropicalis in the urine. Eight of the 16 patients with non-C. albicans yeasts in the urine on review were shown to have previously had a C. albicans isolated from the urine that had been treated with fluconazole before the appearance of the non-C, albicans isolate. Three-fourths of the patients with funguria had Foley catheters or suprapubic catheters, and the remainder had Texas (condom) catheters (two exceptions). Thus, canTable 1. Isolation of Yeast Species 1991 (as individuals) a

Successful treatment of Candida albicans osteomyelitis with fluconazole

The case of a 63-year-old man who developed Candida albicans osteomyelitis is reported. Because of renal impairment, fluconazole was chosen as treatment rather than amphotericin B. The patient made a full recovery. This is the first report of the successful use of fluconazole in the treatment of candidal osteomyelitis.

Successful Use of Fluconazole for Treatment of Urinary Tract Fungal Infections

Two cases are reported that demonstrate significant activity of the new antifungal agent, fluconazole, in treating urinary tract fungal infections. One patient was severely immunocompromised with the underlying complication of renal failure and the other presented with a much simpler case of candidal cystitis that responded quickly despite unfavorable in vitro susceptibility testing.

Is There a Role for Fluconazole in the Treatment of Vulvovaginal Candidiasis?

To review the data describing the use of fluconazole in the treatment of vulvovaginal candidiasis (VVC). A MEDLINE search of the English-language literature and a bibliographic review of pertinent articles examining the use of fluconazole in the treatment of VVC. Relevant open and controlled studies reporting on the efficacy, associated adverse effects, or both of fluconazole for the treatment of VVC are reviewed. Appropriate conclusions and/or data are extracted from each article and described. Studies comparing fluconazole with ketoconazole and topical antifungal agents such as clotrimazole and miconazole have shown fluconazole to be equally efficacious with minimal adverse effects. Most of these trials used single-dose fluconazole, which would theoretically lead to a high degree of medication compliance. Fluconazole also has shown promise at diminishing VVC relapse or recurrence, possibly because of more complete vaginal and rectal eradication of Candida species. Pharmacoeconomically, single-dose fluconazole therapy is cost-effective; however, the recent approval of miconazole and clotrimazole by the Food and Drug Administration for over-the-counter use may limit this potential advantage. Until additional data are available, fluconazole may be considered a treatment alternative for women with VVC who experience frequent relapses or recurrences, or for those who are noncompliant with standard therapy.

Blastomycosis.

Blastomycosis is a rare but important fungal infection that occurs primarily in the south central and midwestern United States. Epidemics of blastomycosis related to a point-source exposure include patients of all ages and both sexes; however, cases of endemic blastomycosis are usually in young to middle-aged adults and are reported more for men than for women. Pneumonia is the most common manifestation of blastomycosis, and the lungs are almost always the organ initially infected. Skin, bone, prostate, and central nervous system are the next most frequently infected organs in descending order. Amphotericin B is curative, but because of its toxic effects, oral agents have been investigated as therapy for blastomycosis. ketoconazole should replace amphotericin B as therapy for blastomycosis that is not life threatening. Itraconazole is an experimental agent that is perhaps even more effective than ketoconazole. The therapeutic usefulness of fluconazole for blastomycosis remains unproven. For patients with life-threatening or central nervous system blastomycosis, amphotericin B remains the treatment of choice.

Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS.

Eight patients with AIDS were treated orally with 800 mg of fluconazole daily for cryptococcal meningitis for a mean duration of 4.5 months. Previous antifungal treatment had failed for all of the patients. No major toxicity was observed. Three patients died from cryptococcal infection. High-dose fluconazole may be effective salvage therapy for cryptococcal meningitis.

Fluconazole Failure in the Treatment of Invasive Mycoses

Fluconazole is a recently licensed antifungal agent that has gained widespread use in the medical community. Despite a lack of controlled trials in invasive fungal infections, this agent is often prescribed because of ease of administration and concern over amphotericin B toxicity. Three cases of systemic fungal infections in which fluconazole use resulted in unambiguous microbiologic and clinical failure are reported.

Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole.

In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants. To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990. The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro. In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.

Cost implications of alternative treatments for aids patients with cryptococcal meningitis. Comparison of fluconazole and amphotericin b-based therapies

The extra demands placed upon health care resources by management of AIDS patients have increased the focus on cost implications of therapeutic alternatives. Cryptococcal meningitis is a common life-threatening infection in AIDS patients, usually treated with amphotericin B, often in combination with flucytosine. Administered intravenously, this therapy is associated with frequent and often severe side effects. Fluconazole is a new alternative which can be given orally once daily and has fewer such side effects. The purpose of this study was to examine the cost implications of these different therapies for both primary and maintenance treatment of cryptococcal meningitis. Comparison of these two therapies in recent clinical trials has indicated that fluconazole is at least as effective as amphotericin B, and therefore cost-minimisation analysis is an appropriate method to study the economic consequences of the alternative treatments. Patient management and resource-use information for both treatments was obtained using a modified Delphi technique with a panel of European physicians experienced in the treatment of this disease, and three models were developed to reflect the variability of practice evident among the panel members. U.K. health care costs were used to value these resources. The results indicated that, despite the higher cost of the drug itself, the costs associated with fluconazole were likely to be markedly less than those for amphotericin B for primary treatment, and similar or slightly cheaper for maintenance treatment. Over 1 year of treatment, the saving from the use of fluconazole would be in the range of 4000-14,000 pounds.

Retinitis following disseminated cryptococcosis in a renal allograft recipient

A case of retinitis following disseminated cryptococcus neoformans infection in a renal allograft recipient is reported. Therapy with oral fluconazole showed a remarkable improvement at the end of 8 weeks. This is the first report of the use of fluconazole in the treatment of cryptococcal retinitis.

Comparative Study of Fluconazole and Clotrimazole in the Treatment of Vulvovaginal Candidiasis

Fluconazole is a new oral triazole antifungal with good activity against Candida spp. In this study, we investigated the effectiveness and tolerability of a three-day course of treatment with fluconazole compared with clotrimazole vaginal tablets in nonpregnant women with acute Candida vaginitis. Of the 90 evaluable patients who received fluconazole, 76 (84 percent) were asymptomatic seven to ten days after treatment compared with 84 of 95 (88 percent) treated with clotrimazole. An additional ten patients in the fluconazole group (11 percent) and seven in the clotrimazole group (7 percent) had improvement in their signs and symptoms. Only four patients in each group (4 percent) were considered treatment failures. Mycological cures were obtained in 89 and 93 percent of patients treated with fluconazole and clotrimazole, respectively, seven to ten days posttreatment. Clinical cure rates remained high one month posttreatment: 79 percent in the fluconazole group and 83 percent in the clotrimazole group. Both therapies were well tolerated. One patient discontinued treatment after she developed diarrhea while receiving fluconazole. The most common adverse effects associated with fluconazole use were nausea (six percent) and diarrhea (three percent). No clinically significant laboratory abnormalities were observed. In this investigation, oral fluconazole therapy was found to be as safe and effective as clotrimazole vaginal tablets in women with acute vulvovaginal candidiasis.

<I>Aspergillus</I>肺炎を合併した慢性肉芽腫症に対するFluconazoleの効果

Aspergillus infection is the most frequent fungal infection associated with chronic granulomatous disease (CGD), and often results in a life-threatening situation. This report describes the use of high-dose fluconazole, a new antifungal agent, for invasive Aspergillus infection in a patient with CGD. A 27-month-old boy was sent to our hospital because of unknown fever in October, 1988. He was then admitted for pneumonia and pleural effusion of the right lung in February, 1989. Treatment with antibiotics was ineffective, and cultures of throat and pleural fluid were negative. In May, 1989, Aspergillus fumigatus was cultured from a subcutaneous abscess at the point of pleural puncture. Therefore we speculated that Aspergillus might have been the cause of pneumonia. The patient was diagnosed as having CGD by NBT test. Treatment with miconazole, flucitocin and amphotericin-B syrup was ineffective. From July, 1989, he was given 100 mg/day fluconazole d.i.v., but the drug did not reach an effective serum concentration to combat Aspergillus. However, an effective concentration of fluconazole was reached at a dose of 250 mg/day, and the chest X-ray findings subsequently improved, despite occasional high fever and continued high CRP. In July, 1990, the route of fluconazole administration was changed from d.i.v. to p.o. at the same dose, resulting in a serum concentration of fluconazole higher than that achieved with d.i.v. treatment. Both the clinical and laboratory findings showed improvement thereafter. Therapy for Aspergillus infection associated with CGD was found to necessitate high doses of anti-fungal drugs over a long period, although treatment with previously employed anti-fungal drugs could not be continued due to their adverse side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of Gram‐positive and Candida albicans infections using teicoplanin and fluconazole: a randomized study in neutropenic children

We have shown that the combination of teicoplanin (T) and ceftriaxone (C) given once daily as first-line empirical antimicrobial therapy is very effective (85%) and safe in febrile neutropenic children (ICAAC, 1988). Like others (ICAAC, 1989) we have stressed the new life-threatening problems with Streptococcus mitis and Strep. sanguis. Considering the regular sensitivity of Gram-positive organisms to T, it is possible that the introduction of the glycopeptide at the onset of aplasia may be helpful. The high incidence of fungal infection or superinfection supports the routine use of an effective antifungal agent when fever is still present or relapse occurs. Our study was designed to assess the prevention of (1) staphylococcal and streptococcal infections using T when the central catheter is being placed, and (2) candida infection by the simultaneous use of a new anti-mycotic agent fluconazole (F) administered once-daily. Patients were randomized into two arms of the study. Arm A received T 6 mg/kg/d and F 3 mg/kg/d starting when the catheter was put in place. If fever occurred, C 50 mg/kg/d and amikacin (A) 15 mg/kg/d were added and T increased to 10 mg/kg/d. If a febrile relapse occurred, amphotericin B was added. In arm B the combination of the three agents T 10 mg/kg/d, C 50 mg/kg/d and A 15 mg/kg/d was started only if there was fever. Amphotericin B was used in febrile relapses. Forty-six patients were eligible (23 in each arm; no statistically significant differences between the two groups). The mean age of the patients was 8 years and mean duration of aplasia 23 and 24 d. Results were as follows: arm A the duration of T + F alone was 10 d, 22 patients had a febrile episode with 1 Gram-positive, 11 Gram-negative and one candida strain isolated in eight patients. C + A were effective in 72% of these patients. There were no deaths. In arm B, fever occurred in all patients during the first 6 d, with eight Gram-positive and six Gram-negative organisms isolated in nine patients. C + T + A were successful in 83% of patients. A bacterial superinfection was documented in four patients, candida superinfection in seven patients and one patient died from Candida parakrusei septicaemia. When the total amount of C and A used in both arms was compared, there was a reduction in 20% of the two agents in arm A, but T was equivalent in both arms. Treatment was well tolerated in both arms.(ABSTRACT TRUNCATED AT 400 WORDS)

Fluconazole: A New Triazole Antifungal Agent

Fluconazole is a fluorine-substituted, bis-triazole antifungal agent. Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes. Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models. Fluconazole can be administered both orally and intravenously. Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively. Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89. Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug. Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts. Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis. Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available. Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole. Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin. Rifampin appears to decrease metabolic clearance of fluconazole. Fluconazole is available as oral and parenteral formulations. Once-daily doses of 100-400 mg are recommended. Dosage reduction is advised for patients with impaired renal function.

Effects of Preventive, Early, and Late Antifungal Chemotherapy with Fluconazole in Different Granulocytopenic Models of Experimental Disseminated Candidiasis

To investigate the potential use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, its in vivo antifungal activity was studied in three models of disseminated candidiasis in persistently granulocytopenic rabbits: acute, subacute, and chronic disseminated candidiasis. Fluconazole was compared with the combination of amphotericin B and flucytosine for preventive, early, and late treatment of disseminated candidiasis, depending on the model. Fluconazole was most effective when used for preventive or early treatment of acute and subacute disseminated candidiasis. When compared with the combination of amphotericin B plus flucytosine, fluconazole was similarly effective in early treatment of acute and subacute disseminated candidiasis. When treatment was delayed 6 days after established infection, fluconazole was less active in clearing tissues in comparison with its activity in preventive and early treatment. The combination of amphotericin B plus flucytosine, however, was significantly more active than fluconazole in treatment of chronic disseminated candidiasis in all tissues. In summary, fluconazole was most effective against disseminated candidiasis in persistently granulocytopenic rabbits when used for prevention or early treatment.

Experimental Basis for Use of Fluconazole for Preventive or Early Treatment of Disseminated Candidiasis in Granulocytopenic Hosts

To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits. Fluconazole was more effective when used for systemic prophylaxis or early treatment of disseminated candidiasis than for delayed treatment. Fluconazole was as effective as amphotericin B plus flucytosine in preventive and early treatment of disseminated candidiasis but was significantly less effective than amphotericin plus flucytosine in the treatment of chronic candidiasis. Dose-response studies demonstrated that the antifungal effect of fluconazole was dose- and time-dependent. Studies of the pharmacokinetics of fluconazole in rabbits demonstrated a long half-life in plasma and a large volume of distribution, properties that correspond to the attainment of high levels of penetration into tissues at multiple organ sites. We conclude that fluconazole is effective for prevention and early treatment of disseminated candidiasis in persistently granulocytopenic rabbits and that the evaluation of its use in preventive or early treatment of disseminated candidiasis in carefully designed clinical trials is warranted.

Cutaneous cryptococcosis: treatment with oral fluconazole

A case of cutaneous cryptococcosis is described in an immunocompromised patient. The initial lesion developed on the dorsum of the hand following trauma and was initially thought to be neoplastic. Satellite subcutaneous lesions developed in a 'sporotrichoid' pattern along the forearm. Treatment with oral fluconazole resulted in the complete resolution of the lesions. This is the first published report of the use of fluconazole in the treatment of cutaneous cryptococcosis.