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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Antifungal prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Ad HOC Working Group. 161 30

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.
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PMID:Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients. 166 Jan 8

We report a case of Aspergillus arthritis of the shoulder in a renal transplant recipient. Cultures of three joint fluid specimens grew Aspergillus fumigatus. Itraconazole as sole treatment resulted in initial clinical and roentgenographic improvements but failed to prevent deterioration in joint function. A relapse with fatal neurologic involvement occurred. Immune deficiency-inducing risk factors for aspergillosis include neutropenia and corticosteroid therapy. Previously published cases of Aspergillus arthritis of limb joints are reviewed. The advantages and limitations of itraconazole as single drug therapy are outlined.
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PMID:Aspergillus arthritis of the shoulder in a renal transplant recipient. Failure of itraconazole therapy. 778 40

The increase of organ transplantations during the last decades conjointly with the prescription of heavy immunosuppressive drugs, has led to an increased incidence of new invasive aspergillosis (IA). This study is a report of the Broussais Hospital experience from 1968 to 1993 on kidney, heart and heart and lungs transplantations. It concerns 21 IA cases. Incidence was 0.5% for kidney, 4.5% for heart and 18% for heart and lungs transplantations. The most important risk factors were the increase of immunosuppressive therapy (66% of the cases), neutropenia (19%), and renovation of the hospital wards (36%). Lung was the most frequent site of infection (95% of the cases), clinical symptoms were no significant. Diagnosis procedures were realised on biopsy (23%) and on bronchoalveolar lavage (66%). Usual amphotericin B treatment was disappointing: mortality rate of 77%, the liposomal preparation of the drug seemed to be more efficient: mortality rate of 50%. Itraconazole appeared to be used in succession with a careful adaptation of posology. Prophylactic amphotericin B in a local way (sprays and aerosols) led to a good efficiency jointly with the patient isolation during constructions in the hospital area.
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PMID:[Aspergillosis and renal, heart and lung transplantation]. 787 59

A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin ITRA and OH-ITRA, respectively, were 287 +/- 109 ng/ml and 629 +/- 227 ng/ml at day -1 and 378 +/- 147 ng/ml and 725 +/- 242 ng/ml at day +1. The maximum Cmin values were observed at day +3. Six patients at day -1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.
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PMID:Pharmacokinetics of itraconazole oral solution in allogeneic bone marrow transplant patients receiving total body irradiation. 967 58

Fungal infection is a serious complication in immunocompromised patients, especially those with neutropenia. Itraconazole (ITZ) is expected to be an effective prophylactic agent for fungal infection because it has more activity against Aspergillus species than fluconazole and it is less toxic than amphotericin-B. However, ITZ is available only as an oral capsule, the absorption of which is thought to depend on the presence of acid in the stomach. In this study, the effect of famotidine, an H2-blocker, on the absorption of ITZ was investigated. Patients undergoing chemotherapy for hematological malignancies were enrolled. To minimize the effect of famotidine, the time of ITZ intake was different from that of famotidine intake. The plasma concentrations of ITZ with or without taking famotidine were determined just before and 4 h after ITZ intake. Mean trough and peak concentrations of ITZ without famotidine were 332 ng/ml and 476 ng/ml, respectively. When famotidine was co-administered, the concentrations decreased to 204 ng/ml and 315 ng/ml, respectively. Statistical analyses revealed significant differences between trough concentrations in the presence and absence of famotidine (p = 0.008). There was also a clear tendency toward higher peak concentrations in the plasma concentrations with famotidine (p = 0.06). These findings suggest that famotidine decreases the plasma concentration of ITZ in patients undergoing chemotherapy. Close monitoring of the plasma concentration of ITZ and dose adjustment are required for efficient prophylaxis.
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PMID:Plasma concentration of itraconazole in patients receiving chemotherapy for hematological malignancies: the effect of famotidine on the absorption of itraconazole. 982 10

Fungal colonization has been associated with an increased rate of invasive fungal infections in neutropenic patients. This study evaluates weekly fungal surveillance cultures from the oropharyngeal and perianal space as well as other suspected sites in 219 courses of myelosuppressive chemotherapy with itraconazole antifungal prophylaxis in 116 neutropenic patients with acute leukaemia. Itraconazole was given from the start of chemotherapy in one of six different dosing regimens. Fungal colonization occurred in 68 (31%) of courses, which was lower than in a historical control group without prophylaxis (53%, P = 0.004). Twenty-six per cent of these 116 isolates had a growth rate of more than 50 colony forming units (CFU) per culture. Candida glabrata (51%), Candida albicans (18%) and Candida krusei (4%) were the most frequently isolated species. Higher median itraconazole trough concentrations were associated with a lower growth rate in the cultures (< or = 50 CFU/culture versus > 50 CFU/culture): 710 (430-1180) ng ml-1 versus 900 (560-1650) ng ml-1 (P = 0.015). The use of itraconazole solution--compared with capsules--led to a reduced growth rate (P = 0.035). In conclusion, compared with historical controls itraconazole antifungal prophylaxis reduces the incidence and the extent of fungal colonization during neutropenia in patients with acute leukaemia.
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PMID:Fungal surveillance cultures during antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia. 1053 31

Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis. Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation. More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra. Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.
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PMID:A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. 1071 3

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.
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PMID:Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B. 1085 49

A 73-y-old female with a history of adenocarcinoma of colon and refractory anemia developed febrile neutropenia following chemotherapy. Therapy with iv infusion of amphotericin B deoxycholate (AmBd) was initiated on day 8 of hospital admission. Premedications included acetaminophen, diphenhydramine and meperidine. Patient developed rigor, chill and elevated temperature approximately 100 min into the infusion. The infusion was temporarily discontinued and rigors subsided following administration of 25 mg meperidine im. Infusion was continued after cessation of the rigors with no further sequelae. During each infusion of AmBd over the next 3 d, the patient developed rigor, chill and elevated temperature which was managed with meperidine. However, on day 4 she developed respiratory distress, bronchospasm and visible cyanosis with oxygen saturation of 88% while on 2 L oxygen. The infusion was stopped and the symptoms subsided with administration of albuterol via nebulizer. Amphotericin lipid formulation infusion was reinstituted after 3 d because of the patient's worsening clinical status. However, the patient developed severe respiratory distress approximately 130 min into the infusion. The infusion was discontinued and she was treated with albuterol via nebulizer. Itraconazole therapy was instituted without any adverse sequelae. Clinicians should be aware of this potential adverse event since it can occur with all formulation of amphotericin.
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PMID:Respiratory distress secondary to both amphotericin B deoxycholate and lipid complex formulation. 1092 87


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