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At least 19 recordsLinked to original sources
PubMedDate not supplied

Ketoconazole vs. itraconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results of two nonrandomized studies.

The efficacies of antifungal prophylaxis with ketoconazole and itraconazole, a new triazole, in patients with prolonged granulocytopenia were evaluated in two nonrandomized studies. The conditions other than the drug administered for prophylaxis were equivalent in the two studies. The incidence of fatal fungal infections was significantly higher among patients given ketoconazole than among those given itraconazole (P = .02); this trend was especially evident with fatal infections due to Aspergillus (P = .0045). The level of protection from fatal fungal infection afforded by itraconazole was highly significant among patients who were granulocytopenic for more than 25 days (P less than .0001) and among patients with acute lymphoblastic leukemia (P = .008). Failures of prophylaxis with itraconazole may have been due to inadequate levels of drug in plasma. Although these results must be interpreted with caution because they were obtained in consecutive nonrandomized studies, the use of itraconazole for antifungal prophylaxis in granulocytopenic patients seems to be a major advance and to be especially advantageous in hospitals, where the incidence of fatal aspergillosis in these patients is high.

Adolescent↗
PubMedDate not supplied

Antifungal prophylaxis in bone marrow transplantation.

Deep fungal infection in recipients of bone marrow transplants remains a significant cause of morbidity and mortality. Prolonged neutropenia is the major factor predisposing patients to invasive fungal disease. Candida and Aspergillus species remain the two most common pathogens. Prophylaxis against these organisms with the oral polyenes nystatin and amphotericin B has been disappointing. Systemic amphotericin B is too toxic for prophylactic use, yet it remains the mainstay of therapy for suspected or established deep fungal infection. Ketoconazole is contraindicated in patients receiving cyclosporine prophylaxis against graft-vs.-host disease and appears effective only in high doses associated relatively commonly with adverse reactions. This paper reviews results of antifungal prophylaxis and discusses new measures and agents likely to be of value in the prevention of fungal infection in bone marrow transplantation.

Antifungal Agents↗
PubMed1992

Antifungal prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Ad HOC Working Group.

Neutropenia induced by intensive chemotherapy and allogeneic bone marrow transplantation are increasingly commonly complicated by fungal infections; thus prophylaxis may be justified. The authors surveyed the literature and culled their experience - few randomized trials have been done and definitions have often been poor. In prophylaxis of mucosal candidosis, miconazole and clotrimazole may both be more effective than placebo. Nystatin is ineffective and ketoconazole of medicine efficacy. Fluconazole is effective at 50 mg/day and 400 mg/day. Itraconazole and amphotericin B both need further evaluation. In prevention of systemic candidosis, oral nystatin prophylaxis, up to 4 X 10(6) U/day, is usually unsuccessful, though compliance is variable. Oral amphotericin B in low doses is ineffective, but 50 mg or more 4 times daily may prevent systemic candidosis, though compliance is variable. Oral ketoconazole, 400-600 mg/day, is possibly effective prophylaxis in neutropenia but not after bone marrow transplantation; liver function (often abnormal in these patients) is a problem, as is tolerability. Oral fluconazole is well tolerated, has reliable serum concentrations and is effective following bone marrow transplantation, but the optimum dose is uncertain. In bone marrow transplantation, intravenous amphotericin B, 0.1 mg/kg/day, appears to be effective; there are no data in neutropenia. Oral itraconazole (capsules, 200 mg/day) may be active; data are scanty. In prevention of invasive aspergillosis, itraconazole, 200 mg/day, is probably active, but only if adequate serum concentrations are achieved. New oral and intravenous itraconazole formulations in cyclodextrin may achieve more reliable serum concentrations. No oral drug provides effective prophylaxis against Torulopsis, Fusarium, Trichosporon, or Pseudallescheria.

Antifungal Agents↗
PubMed1989

Antifungal prophylaxis with itraconazole in prolonged neutropenia: correlation with plasma levels.

Seventy-two patients with haematological malignancies were treated prophylactically with itraconazole during remission induction therapy. The incidence of proven fungal infections was 18%, of which 12.5% were fatal. Aspergillus, Torulopsis and Candida proved to be major invasive pathogens. Plasma levels of itraconazole were monitored for all patients. The occurrence of fungal infection is significantly greater in the group where no therapeutic plasma levels were obtained during at least two weeks. There is a clear need to obtain quick information on itraconazole plasma levels in order to adapt dosage during prophylactic treatment in immunocompromised patients. The influence of itraconazole on liver function tests could not be separated from concomitant cytostatic or antibiotic treatment. No jaundice directly related to itraconazole could be found. During itraconazole prophylaxis a shift from classic pathogens such as Aspergillus and Candida, to Fusarium, Torulopsis and Mucor, may be seen.

Adult↗
PubMedDate not supplied

[Antifungal prophylaxis: up-date and prospectives].

Author reviews the now available strategies for the prophylaxis of primary and opportunistic mycoses. Chemoprophylaxis of opportunistic mycoses that are the most frequently observed fungal infections in Italy, gives satisfactory protection in endogenous fungal infections. On the contrary, fungal exogenous infections are not easily treated. In fact, systematically acting drugs which are also easy to use, are still lacking. Strict reverse isolation seems to achieve good results in these infections.

Administration, Oral↗
PubMed1985

Limits of antifungal prophylaxis by ketoconazole in leukemic patients.

Serum ketoconazole levels in leukemic patients, subjected to ketoconazole prophylaxis, were determined by an agar diffusion assay. High individual variability of drug concentration was noted. In addition, the highest drug concentration observed was less than 1 microgram/ml in 5 out of 6 patients studied. The reliability of prophylaxis of airborne opportunistic fungal infections by ketoconazole seems, therefore, to be hampered, at least in leukemics, by the too low serum concentrations of the drug. The bioassay proved to be highly reproducible and accurate as well as easy and safe to perform.

Adult↗
PubMed1975

The incidence of pathogenic yeasts among open-heart surgery patients-the value of prophylaxis.

The normal levels of commensal yeasts in patients undergoing open-heart surgery are established and the effect of antifungal prophylaxis is assessed. Mouth swabs and feces were taken for culture from patients on admission to hospital and 1,2, and 3 weeks postoperatively. Eighty-seven patients who received normal treatment and 50 patients who were given oral and topical antifungal prophylaxis commencing 12 days before hospitalization were studied. Yeast pathogens, mainly Candida albicans, were isolated from 42 (48.3 per cent) of the normal group on admission. There was a marked increase in the incidence and quantities of yeasts isolated from patients in the immediate postoperative period. The incidence and levels of yeasts in patients receiving antifungal prophylaxis was considerably reduced both on admission and postoperatively. The risk of Candida sepsis in open-heart surgery patients with high levels of commensal yeasts is discussed and the possibility of routine antifungal prophylaxis raised.

Administration, Oral↗
PubMedDate not supplied

Prevention of infection in acute leukemia: a prospective randomized study on the efficacy of two different drug regimens for antimicrobial prophylaxis.

In a prospective study patients with acute leukemia undergoing remission induction therapy were randomized to receive either a regimen of non-absorbable antimicrobial drugs (colistin and neomycin) or of absorbable and non-absorbable drugs (trimethoprim-sulfamethoxazole [TMP-SMZ] and colistin) for antibacterial prophylaxis. For antifungal prophylaxis patients in both groups were given oral amphotericin B. The proportion of patients without acquired infections and the median of study time to the first acquired infection did not differ significantly between the two treatment groups (p greater than 0.05). Septicemias occurred in nine out of 49 recipients of colistin and neomycin and in one out of 56 patients receiving TMP-SMZ and colistin (p = 0.03). Localized infections and fever episodes without proven infections were equally distributed between the two groups. The incidence of febrile days and of days on parenteral antibiotic therapy was significantly lower in the group given TMP-SMZ and colistin (p less than 0.05). The duration of severe granulocytopenia and thrombocytopenia did not differ significantly between the two groups (p greater than 0.05).

Adolescent↗
PubMed1976

Antibodies to Candida after operations on the heart.

The occurrence of yeasts and antibodies to yeasts was studied in patients undergoing open-heart surgery without antifungal prophylaxis, and in a similar group receiving antifungal prophylaxis. An association was demonstrated between the occurrence of commensal yeasts and the appearance of antibodies. None of the patients developed overt systemic or superficial yeast infection. The antigenic stimulus for the post-operative production of antibodies appeared to be the increase in the yeast flora that occurred shortly after operation. When the commensal yeast population was suppressed by antifungal antibiotics, the antibody response was also reduced. The implications of these findings in the interpretation of serological tests for diagnosis of systemic yeast infections are discussed.

Agglutination Tests↗
PubMed1991

Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients.

In a non-randomized study the efficacy of itraconazole in preventing fungal infections in neutropenic patients was investigated. Forty-seven patients with acute leukemia or advanced lymphoblastic lymphoma were enrolled. Ninety-two episodes of severe neutropenia after chemotherapy were observed. Mean duration of neutropenia was 24 days. Norfloxacin was administered as prophylaxis against gram-negative infections and itraconazole 200 mg b.i.d. as antifungal prophylaxis. Surveillance cultures of throat, urine, feces and vagina or prepuce were performed regularly. Four patients died, two patients due to heart failure, two patients due to staphylococcal pneumonia. Only in one case Candida albicans was cultured from bronchoalveolar lavage fluid. No systemic mycosis or Aspergillus fumigatus pneumonia was documented. In a similar group of patients treated in the preceding 18 months nystatin was used as antifungal prophylaxis. In this group of patients six cases of Aspergillus fumigatus pneumonia, two cases of Candida albicans fungemia and one case of Candida glabrata pneumonia occurred of which six patients died. Itraconazole seems to be effective in preventing fungal infections in neutropenic patients and is well tolerated.

Adolescent↗
PubMed1987

Incidence of endogenous and exogenous opportunistic fungal infections in relation to different prophylactic measures: clinical and microbiological study of 431 immunocompromised patients.

Two groups of immunocompromised patients were studied with the aim of pointing out the possibilities of antifungal prophylaxis in this type of patient. All patients received oral treatment with nystatin, but only the patients of one group were also in strict reverse isolation. It has been confirmed that chemoprophylactic treatments may control opportunistic endogenous mycoses effectually. On the contrary, only reverse isolation seems to be effective against airborne exogenous fungal infections. Because of the difficulty and high cost of this practice, different modalities for a really generalizable antifungal prophylaxis are required. At present only the detection of new systemic antifungal drugs, which are not toxic and are easy to use, seems hopeful.

Fungi↗
PubMed1990

Heart transplantation: intraoperative management, postoperative therapy and complications.

Currently, heart transplantation (HTX) is performed as an orthotopic cardiac replacement according to the technique of Lower and Shumway in over 95% of the cases with good results. Survival after heterotopic HTX, by contrast, remain poor (one year survival: 50%). Postoperative therapy compiles primarily prophylactic measures to prevent complications, especially organ rejection and infections. Immunosuppressive prophylaxis generally includes a triple drug therapy consisting of cyclosporin, prednisolone, and azathioprine for maintenance therapy. Initially there is often an additional application of poly- or monoclonal antibodies. The prime measure to prevent infection during the initial hospital stay will be reversed isolation of the recipient. Initial antibiotic prophylaxis resembles that of conservative cardiac surgery, but in addition antiviral and antifungal prophylaxis is applied. The most common postoperative complication following HTX is cardiac rejection, which is detected by routine endomyocardial biopsies. At our institution the incidence of rejection decreases from 3.07 episodes per patient in the first 3 months to 1.97 episodes during the last 6 months of the first year after HTX. In general, acute rejection is treated by methylprednisolone (3 x 500 mg/day) or anti-T-cell-antibodies. Infections often occur following intervals of increased immunosuppression, usually early postoperatively and following therapy of acute rejections. Often, invasive diagnostic measures have to be taken rapidly in order to allow for specific therapy (antibiotics, antimycotic treatment, virostatic agents). Close follow-up of the heart transplant recipient and rapid therapy of possible postoperative complications enable the current one-year survival rates of 80% or more.

Anesthesia↗
PubMed1986

Prophylaxis of mycotic infections in immunocompromised patients: a review of 27 reports and publications.

During the last three years, several studies have investigated the potential of ketoconazole for antifungal prophylaxis in immunocompromised patients. Ketoconazole 200 mg o.d. seems to have some effect, but this daily dose is considered too low. Studies using higher doses suggest an increased prophylactic effect with 400 mg and adequate prophylaxis with 600 mg ketoconazole daily. When compared with other antifungals, ketoconazole seems to be superior to nystatin and as effective as amphotericin B (500 mg t.i.d.).

Amphotericin B↗
PubMed1990

Prophylaxis of candidiasis in cancer patients.

Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated.

Adolescent↗
PubMed1985

Prophylaxis of oropharyngeal candidiasis with clotrimazole.

A total of 202 evaluable cancer patients were randomly assigned to receive or not receive oral clotrimazole as antifungal prophylaxis during hospitalization. Oropharyngeal candidiasis occurred in 1% of the former patients and 27% of the latter patients (P less than .00001). Candida sp were cultured from the initial throat specimens of 53 control patients and 55 patients who received prophylaxis. Oropharyngeal candidiasis subsequently developed in 2% of the former patients and 38% of the latter patients (P = less than .00001). Oral clotrimazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients.

Adolescent↗
PubMedDate not supplied

Prophylaxis of oropharyngeal candidiasis with fluconazole.

A total of 112 cancer patients who could ultimately be evaluated were randomly assigned in a double-blind study to receive either fluconazole or placebo as antifungal prophylaxis during hospitalization. Thrush, defined by appropriate lesions in the oropharynx and confirmed by scrapings and cultures positive for Candida species, occurred in 2% of the 58 patients given fluconazole and in 28% of the 54 patients given placebo (P = .0003). Candida species were cultured from initial throat specimens from 29 patients given fluconazole and from 26 patients given placebo. Oropharyngeal candidiasis was detected subsequently in 3% of the former patients and 54% of the latter patients (P = .0001). Adverse reactions that were probably due to or aggravated by fluconazole occurred in only four patients and consisted of transient liver function abnormalities in three instances and nausea and vomiting in one. Oral fluconazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients.

Adult↗
PubMedDate not supplied

Empiric therapy with amphotericin B in febrile granulocytopenic patients.

The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis. Current studies continue to indicate that prompt empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients ensures earlier treatment of deep mycoses. The roles of newer antifungal triazole compounds and of liposomal and lipid complexes of amphotericin B in empiric antifungal therapy must be investigated further in thoughtfully designed, randomized clinical trials.

Agranulocytosis↗