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The efficacy and safety associated with use of a single oral dose of 150 mg of fluconazole compared to administration of a 100 mg clotrimazole vaginal suppository twice a day for three days in the treatment of vulvovaginal candidiasis were investigated. Involved in the prospective, double-blind, controlled trial conducted at a Bangkok hospital were 103 women with a confirmed diagnosis of vulvovaginal candidiasis who were randomly assigned to a treatment group. Self-assessed clinical improvement was obtained within 1 week in 88.7% of women in the fluconazole group and 90.0% of those in the clotrimazole group. The mycologic cure rate at the 1-week follow-up visit was 79.2% in the fluconazole group and 80.0% in the clotrimazole group; at 4 weeks, these rates were 60.4% and 68.0%, respectively. 3 (5.7%) fluconazole users experienced nausea and 1 (1.9%) reported dizziness, while 11 (22.0%) clotrimazole acceptors had vaginal burning. This study suggests that fluconazole is equally as effective as the traditionally used antifungal agent clotrimazole. Although the former drug has the advantages of oral administration, single dosage, and minimal side effects, it is more expensive.
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PMID:Comparative study of fluconazole and clotrimazole for the treatment of vulvovaginal candidiasis. 748 5

Itraconazole is a new orally active triazole antifungal agent with enhanced activity against Candida species. In the clinical trial described in this paper, we compared the efficacy and safety of itraconazole capsules with those of clotrimazole vaginal tablets and placebo oral capsules for women with acute vulvovaginal candidiasis. Ninety-five patients were randomized in a 2:1:1 fashion to receive itraconazole (200 mg/day), clotrimazole (200 mg/day), or placebo (two capsules per day) for 3 consecutive days. Clinical success rates (cure and improvement) were similar for women who received itraconazole (96%) and clotrimazole (100%) 1 week posttreatment. These response rates were statistically superior to those obtained with placebo treatment (77%, P < 0.05). Negative mycological cultures were found in 95, 73, and 32% of the patients treated with clotrimazole, itraconazole, and placebo, respectively (P < 0.005) [active treatments versus placebo]). By 4 weeks posttreatment, the clinical failure rate for itraconazole was less than that observed for clotrimazole (17 versus 30%), but this difference did not reach statistical significance (P > 0.05; beta = 0.81). Mycological response rates for itraconazole and clotrimazole were also similar. No patients enrolled in this study discontinued treatment because of an adverse event. Minor side effects were reported by 35, 4, and 41% of patients who received itraconazole, clotrimazole, and placebo, respectively. The most common side effects associated with itraconazole therapy were nausea and headache. In summary, itraconazole was found to be as effective and safe as clotrimazole in women with acute candida vaginitis. Moreover, oral therapy was highly favored over intravaginal treatment in our survey of patients.
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PMID:Placebo-controlled trial of itraconazole for treatment of acute vaginal candidiasis. 838 43

In this comparative trial, outpatients with acute sinusitis were randomly assigned to receive levofloxacin (500 mg orally once daily) or amoxicillin-clavulanate (500/125 mg orally 3 times daily) for 10 to 14 days. The success rates (cured and improved) 2 to 5 days after the end of treatment were 88.4% for the 267 clinically evaluable patients who received levofloxacin and 87.3% for the 268 clinically evaluable patients who received amoxicillin-clavulanate. Drug-related adverse events occurred in a smaller percentage of patients in the levofloxacin treatment group (7.4%) than in the amoxicillin-clavulanate treatment group (21.2%). The most common of these were nausea, diarrhea, vaginitis, and abdominal pain for levofloxacin-treated patients and diarrhea, vaginitis, nausea, genital moniliasis, abdominal pain, vomiting, and flatulence for amoxicillin-clavulanate-treated patients. The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult outpatients.
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PMID:Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. 1043 81

The most frequent cause of upper urinary tract infection remains E. coli. Other organisms are found in complicated infections associated with diabetes mellitus, instrumentation, stone, and immunosuppression. The pathogenesis of acute pyelonephritis is reviewed herein, with an emphasis on the virulence factors responsible for its initiation, including urothelial adhesion by P-fimbriae of E. coli and other common factors including hemolysin and aerobactin. Renal damage does not always ensue following such infection. It is seen when toxic oxygen radicals are released during the ischemic episode and the respiratory burst of phagocytosis is marked and prolonged. These events occur when effective antibacterial treatment is delayed when the diagnosis is not made early or when socioeconomic factors prevent treatment. The scarring of chronic pyelonephritis leads to the loss of renal tissue and function and may progress to end-stage renal disease. With effective antibacterial therapy, the immune response by both T and B lymphocytes leads to antibodies that assist in bacterial eradication. Therapy must be both rapid and effective. In many instances, antibacterial agents may be used as outpatient therapy. If the Gram stain shows only gram-negative organisms and if the infection is community acquired, oral outpatient therapy with trimethoprim/sulfamethoxazole or a fluoroquinolone may suffice if the patient has no nausea. When the patient is septic, hospitalization and treatment with parenteral antibiotics are needed. Both ceftriaxone and gentamycin are cost-effective parenteral therapy because only once-daily dosing is needed. If gram-positive organisms are found, an enterococcus should be suspected, and a beta-lactam penicillin such as piperacillin or a third-generation cephalosporin such as ceftriaxone is indicated. If penicillin allergy exists, vancomycin should be used. If the patient does not improve rapidly, diagnostic studies including ultrasound and CT will assist in the diagnosis of obstruction, abscess, or emphysematous pyelonephritis. Most of these complications are now rapidly treated percutaneously, with surgical therapy following as needed. Complicated infections, such as those occurring in patients with anatomic abnormalities, stone, or immunosuppression, are often caused by organisms other than E. coli, and long-term antibacterial therapy often leads to fungal infections such as candidiasis. A recrudescence of tuberculosis is occurring, often with resistance to antituberculous drugs. The increased incidence has been associated with the immunosuppression of AIDS but is also occurring in intravenous drug users, perhaps because of poor nutrition but also owing to noncompliance with treatment. The symptoms of renal tuberculosis are usually limited to fever, frequency, urgency, and dysuria. Hematuria with sterile pyuria is the usual laboratory finding. The young urologist should remember this renal disease in the differential diagnosis of hematuria, because medical therapy can provide a cure.
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PMID:Management of pyelonephritis and upper urinary tract infections. 1058 16

Caspofungin is the first in a new class of antifungal agents, the glucan synthesis inhibitors, that interfere with fungal cell wall synthesis. Caspofungin exhibited in vitro and in vivo efficacy against a wide range of fungi and yeasts including Aspergillus and Candida species. A complete or partial response to caspofungin therapy was seen in 40.7% of immunocompromised adults with invasive aspergillosis who did not respond to, or did not tolerate, other antifungal agents in a noncomparative multicentre study. Caspofungin was effective in patients with oropharyngeal or oesophageal candidiasis, according to the preliminary results of 2 randomised double-blind trials. Caspofungin was generally well tolerated in a multicentre noncomparative trial involving patients with invasive aspergillosis. One or more drug-related clinical adverse effects were experienced by 13.8% of caspofungin recipients (the most common were fever, nausea, vomiting and complications associated with the vein into which caspofungin was infused). The tolerability of caspofungin appeared to be better than that of amphotericin B and similar to that of fluconazole in double-blind, randomised trials involving patients with mucosal candidiasis.
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PMID:Caspofungin. 1146 73

Sheehan's syndrome and lymphocytic hypophysitis often occur in relation to pregnancy, making their differentiation difficult. We describe a 52-yr-old woman with hypopituitarism, Hashimoto's thyroiditis and candidiasis. She was admitted to our hospital because of nausea, vomiting and constipation. Her menstruation stopped in her early thirties. She thereafter developed kyphosis and loss of axillary and pubic hair. Levels of serum Na, Cl and glucose were all low, and hormonal studies were consistent with anterior pituitary hypofunction. Although she had blood transfusion because of hemorrhage at her first delivery, the delivery of her second child was normal followed by resumption of regular menstruation. In addition to hypopituitarism, she had Hashimoto's thyroiditis and candidiasis. Laboratory tests showed an increased Thl ratio, which is related to induction of cellular immunity, and the presence of HLA DR4, which is often associated with polyglandular autoimmune syndrome. These results suggested that the pituitary lesion might be due to lymphocytic hypophysitis rather than Sheehan's syndrome.
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PMID:A case of hypopituitarism associated with Hashimoto's thyroiditis and candidiasis: lymphocytic hypophysitis or Sheehan's syndrome? 1178 64

Echinocandins are a new class of antifungal agents with a novel mechanism of action (interference with fungal cell wall synthesis). Caspofungin (Cancidas), Caspofungin MSD) is the first echinocandin to be approved and is administered intravenously. Caspofungin 50 mg/day had similar efficacy to intravenous fluconazole 200 mg/day and was at least as effective as intravenous amphotericin B 0.5 mg/kg/day in patients with oesophageal candidiasis in two randomised, double-blind studies. A favourable combined clinical and endoscopic response occurred in 81% of caspofungin recipients versus 85% of fluconazole recipients and in 74% of caspofungin recipients versus 63% of amphotericin B recipients. A favourable combined response rate of approximate, equals 90% and approximate, equals 60% occurred in the stratum of patients with oesophageal candidiasis who received caspofungin or amphotericin B in a third randomised, double-blind study. Caspofungin (70 mg loading dose followed by 50 mg/day) had similar efficacy to intravenous amphotericin B (0.7-1.0 mg/kg/day in patients with neutropenia and 0.6-0.7 mg/kg/day in patients without neutropenia) in patients with invasive candidiasis in a double-blind, randomised trial. A favourable overall response occurred in 73.4% of caspofungin recipients and in 61.7% of amphotericin B recipients. In a noncomparative study, salvage therapy with caspofungin (70 mg loading dose followed by 50 mg/day) was effective in patients with invasive aspergillosis who were refractory to or did not tolerate standard antifungal therapy. A favourable response (complete plus partial response) occurred in 37 of 83 patients (45%). Caspofungin was generally well tolerated in clinical trials; it had similar tolerability to intravenous fluconazole and was better tolerated than intravenous amphotericin B. Significantly fewer caspofungin than amphotericin B recipients reported chills, fever, nausea or infusion-related adverse events. In conclusion, caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative trials, caspofungin had similar efficacy to fluconazole and was at least as effective as amphotericin B in oesophageal candidiasis and had similar efficacy to amphotericin B in invasive candidiasis. In addition, caspofungin had similar tolerability to fluconazole and was better tolerated than amphotericin B in these indications. Caspofungin was also effective in patients with invasive aspergillosis who were refractory to or intolerant of standard antifungal agents. Thus, caspofungin provides an alternative to triazoles or amphotericin B in oesophageal candidiasis and an alternative to amphotericin B in invasive candidiasis, as well as being an effective salvage therapy in invasive aspergillosis.
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PMID:Caspofungin: a review of its use in oesophageal candidiasis, invasive candidiasis and invasive aspergillosis. 1449 60

Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1-314 days). The overall rate of response was 56% (95%CI, 41-70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20-70); Candida glabrata, 38% (14-68); Candida krusei, 70% (35-93); Candida tropicalis, 67% (30-93); and other Candida spp., 100% (40-100). The response rate in patients who had failed previous azole therapy was 58% (42-73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei.
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PMID:Voriconazole salvage treatment of invasive candidiasis. 1456 39

Cryptococcus neoformans affections during HIV-infection are frequent and serious. The aim of this study was to analyse the epidemiological, clinical, biological and therapeutic characteristics of cryptococcal meningitis in HIV-positive patients, admitted into the Center for Tropical Diseases Ho Chi Minh City (Vietnam), during a 5-month period (May-September 2001). Twenty-one patients (20 men and one woman) were included (identification of C. neoformans from the cerebrospinal fluid). The mean age was 28 years. The majority of patients had been living in Ho Chi Minh City (48%). The use of drugs and unprotected sexual relations were the principal risk factors of HIV-infection. The paucity and the confusion of clinical signs and symptoms, along with a high frequency of meningitis have been analysed. Clinical presentation features included: headache (95%), emaciation (90%), oro-pharyngeal candidiasis (90%), stiff neck (80%), nausea/vomiting (70%), fever (67%), coughing (38%), diarrhoea (33%), skin lesions (5%), convulsion (5%), photophobia (5%), and hemiparesis (5%). The severity of the prognosis was mainly linked to the delay before hospitalization, to the possible association with other opportunistic infections, and to the availability of appropriate treatment.
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PMID:[Cryptococosis and HIV/AIDS: a review of 21 cases reported in the Tropical Diseases Centre, Ho Chi Minh City (Vietnam)]. 1504 39

Anidulafungin is a novel antifungal agent which, like other echinocandins, inhibits beta-(1,3)-D-glucan synthase and disrupts fungal cell-wall synthesis. It has marked antifungal activity against a broad spectrum of Candida spp. and Aspergillus spp., including amphotericin B- and triazole-resistant strains. In clinical trials, anidulafungin has primarily been evaluated in patients with oesophageal and invasive candidiasis. Preliminary data are emerging for other indications such as invasive aspergillosis. In a large, multicentre, double-blind, double-dummy, randomised trial in patients with oesophageal candidiasis, intravenous anidulafungin 50 mg/day was as effective as oral fluconazole 100 mg/day regarding end-of-treatment rates of endoscopic cure and clinical and microbiological success. Duration of treatment was approximately 2-3 weeks, and patients in both groups received a loading dose of study drug (twice the daily maintenance dose) on day 1. Anidulafungin is generally well tolerated. Across the dosage range 50-100 mg/day, adverse events appear not to be dose- or infusion-related. In the largest clinical trial to date, the most common treatment-related adverse events were phlebitis/thrombophlebitis, headache, nausea, vomiting and pyrexia.
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PMID:Anidulafungin. 1545 42


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