amphotericin-b and Neoplasms

Mucormycosis has emerged as an increasingly important fungal disease for immunocompromised children and neonates, with the cutaneous form being one of its most common presentations.. We present a cutaneous mucormycosis case in a 10-year-old girl and analyse reports of single cases and case series of cutaneous mucormycosis in ≤16-year-old patients, recorded in PUBMED from 1953 to 2020, for epidemiology, risk factors, diagnostic and therapeutic procedures and outcome.. 113 cases were enrolled. Median age was 5 years (Interquartile Range [IQR] 10.9), without gender predominance. Underlying conditions were haematologic malignancies/disorders (25.7%), prematurity (23%), solid organ transplantation (3.5%), diabetes mellitus type 1 (4.4%), immunodeficiency and other diseases (14.2%), and no underlying conditions (29.2%). Inoculation occurred through major trauma (12.4%), including surgery and motor vehicle accidents, catheter sites (27.4%), dressings, patches and probes (11.5%), burns and farm-related accidents (8.8%). Rhizopus spp. was most frequently isolated (43.4%), followed by Lichtheimia corymbifera (9.7%), Saksenaea vasiformis (8%), Mucor and Rhizomucor spp. (5.3% each), other species/combinations (7.2%) and unspecified isolates (21.2%). Surgery was combined with antifungals in 62.8%. Each was performed solely in 27.4% and 6.2%, respectively. Amphotericin B was used in 78% (alone in 55.8% and combined with other antifungals in 22.2%) of the cases. Overall mortality was 26.5%. In regression analysis, prematurity and haematologic malignancies/disorders were associated with increased mortality, whereas combination of antifungals and surgery with improved survival.. Cutaneous mucormycosis mainly affects premature infants and children with haematologic malignancies/disorders. Outcome is improved when active antifungal therapy and surgery are combined.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Hematologic Neoplasms; Humans; Infant, Newborn; Mucormycosis; Neoplasms; Rhizopus

Emergent fungal infections are uncommon conditions which frequently lead to death. To our knowledge, only a few cases of invasive infection by Cystobasidium minutum (previously known as Rhodotorula minuta) have been reported. Moreover, several factors are responsible for deep site infections, such as catheter-related fungemia. This report describes the first case report of Cystobasidium minutum causing fungemia in Brazil. The pathogens fungemia was demonstrated by catheter and blood culture-proven, and both yeasts were identified by sequences of D1/D2 rDNA region. After the end of antifungal therapy and catheter removal, a second blood culture was found to be negative and the clinical signs and symptoms of the patient improved.

Topics: Amphotericin B; Antifungal Agents; Basidiomycota; Brazil; Catheter-Related Infections; Deoxycholic Acid; DNA, Fungal; DNA, Ribosomal; Drug Combinations; Female; Fungemia; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Neutropenia

Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Female; Hematologic Neoplasms; Humans; Lymphoma; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections

The oxidative pentose phosphate pathway (PPP) contributes to tumour growth, but the precise contribution of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in this pathway, to tumorigenesis remains unclear. We found that suppression of 6PGD decreased lipogenesis and RNA biosynthesis and elevated ROS levels in cancer cells, attenuating cell proliferation and tumour growth. 6PGD-mediated production of ribulose-5-phosphate (Ru-5-P) inhibits AMPK activation by disrupting the active LKB1 complex, thereby activating acetyl-CoA carboxylase 1 and lipogenesis. Ru-5-P and NADPH are thought to be precursors in RNA biosynthesis and lipogenesis, respectively; thus, our findings provide an additional link between the oxidative PPP and lipogenesis through Ru-5-P-dependent inhibition of LKB1-AMPK signalling. Moreover, we identified and developed 6PGD inhibitors, physcion and its derivative S3, that effectively inhibited 6PGD, cancer cell proliferation and tumour growth in nude mice xenografts without obvious toxicity, suggesting that 6PGD could be an anticancer target.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Humans; Lipogenesis; Neoplasms; Oxidative Stress; Pentose Phosphate Pathway; Phosphogluconate Dehydrogenase; Protein Serine-Threonine Kinases; Ribulosephosphates; Signal Transduction

Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy is used both empirically and therapeutically in these patients.. To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.. Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2014, Issue 1 2014), MEDLINE (to January 2014). Letters, abstracts and unpublished trials were accepted. Contact was made with trial authors and industry.. Randomised clinical trials comparing voriconazole with amphotericin B or fluconazole.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted independently by two review authors.. Three trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infection) in neutropenic cancer patients (849 patients, 58 deaths). The second trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). The third trial compared fluconazole to voriconazole for prophylaxis of fungal infections in patients receiving allogeneic stem cell transplantation (600 patients, number of deaths not stated). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the trial authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from the analysis by the trial authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication to counter side effects and replacement of electrolytes or use of salt water. This choice of comparator resulted in a marked difference in the duration of treatment on the trial drugs (77 days with voriconazole versus 10 days with amphotericin B) and precluded meaningful comparisons of the benefits and harms of the two drugs. The third trial failed to find a difference in fungal free survival or invasive fungal infections at 180 days when voriconazole was compared to fluconazole.. Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of fungal infections in neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions. For prophylactic fungal treatment in patients receiving allogeneic stem cell transplantation, there was no difference between voriconazole and fluconazole regarding fungal free survival or invasive fungal infections.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever.. To compare the benefits and harms of lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.. We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.. Randomised clinical trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.. The two review authors independently assessed trial eligibility and risk of bias and abstracted data.. We found 13 trials (1960 patients). Lipid-based amphotericin B was not more effective than conventional amphotericin B on mortality (relative risk (RR) 0.5; 95% confidence interval (CI) 0.64 to 1.14) but decreased invasive fungal infection (RR 0.65; 95% CI 0.44 to 0.97), nephrotoxicity defined as a 100% increase in serum creatinine (RR 0.45; 95% CI 0.37 to 0.54), and number of dropouts (RR 0.78; 95% CI 0.62 to 0.97).For the drug used in most patients, AmBisome (4 trials, 1214 patients), there was no significant difference in mortality (RR 0.77; 95% CI 0.54 to 1.10) whereas it tended to be more effective than conventional amphotericin B on invasive fungal infection (RR 0.63; 95% CI 0.39 to 1.01, P value 0.053).AmBisome, amphotericin B in Intralipid (6 trials, 379 patients), amphotericin B colloidal dispersion (ABCD) (2 trials, 262 patients), and amphotericin B lipid complex (ABLC) (1 trial, 105 patients) all decreased the occurrence of nephrotoxicity, but conventional amphotericin B was rarely administered under optimal circumstances.. It is not clear whether there are any advantages of lipid-based formulations if conventional amphotericin B is administered under optimal circumstances, and their high cost prohibits routine use in most settings. There is a need for large trials comparing lipid-based formulations of amphotericin B with conventional amphotericin B given in the same dose, with routine premedication for prevention of infusion-related toxicity, and with supplementation with fluid, potassium, and magnesium for prevention of nephrotoxicity.

Topics: Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Humans; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.. To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.. We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.. Randomised clinical trials comparing fluconazole with amphotericin B.. The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.. Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.. Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.

Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

Topics: Amphotericin B; Anti-Bacterial Agents; Dextrans; Drug Delivery Systems; Humans; Liposomes; Macrolides; Neoplasms; Phosphatidylethanolamines; Polyenes; Tuberculosis

Invasive fungal infections (IFI) are the main cause of infectious death in cancer patients, especially in hematological malignancies and hematopoietic transplant recipients. Current epidemiology is characterized by a predominance of IFI caused by molds, mainly aspergillosis, along with a emergence of hard-to-treat fungi such are Zygomicetes, Fusarium and Scedosporium. Voriconazole is a broad spectrum antifungal agent with oral and intravenous formulations, approved by the EMEA for the treatment of invasive aspergillosis, candidemia in non-neutropenic patients, IFI caused by fluconazole-resistant species of Candida as well as Scedosporium and Fusarium infections. However, its use in clinical practice is broader, as empirical antifungal treatment and as secondary prophylaxis. It should be kept in mind the possibility of breakthrough IFI, particularly zygomycosis, in patients treated with voriconazole for long periods.

Topics: Amphotericin B; Antibiotic Prophylaxis; Antifungal Agents; Drug Resistance, Fungal; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Multicenter Studies as Topic; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Salvage Therapy; Spain; Triazoles; Voriconazole; Zygomycosis

Opportunistic fungal infections are a major cause of morbidity and mortality in neutropenic cancer patients and antifungal therapy are used both empirically and therapeutically in these patients.. To compare the benefits and harms of voriconazole with those of amphotericin B and fluconazole when used for prevention or treatment of invasive fungal infections in cancer patients with neutropenia.. MEDLINE and the Cochrane Library (May 2005). Letters, abstracts and unpublished trials were accepted. Contact to authors and industry.. Randomised trials comparing voriconazole with amphotericin B or fluconazole.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by two authors independently.. Two trials were included. One trial compared voriconazole to liposomal amphotericin B as empirical treatment of fever of unknown origin (suspected fungal infections) in neutropenic cancer patients (849 patients, 58 deaths). The other trial compared voriconazole to amphotericin B deoxycholate in the treatment of confirmed and presumed invasive Aspergillus infections (391 patients, 98 deaths). In the first trial, voriconazole was significantly inferior to liposomal amphotericin B according to the authors' prespecified criteria. More patients died in the voriconazole group and a claimed significant reduction in the number of breakthrough fungal infections disappeared when patients arbitrarily excluded from analysis by the authors were included. In the second trial, the deoxycholate preparation of amphotericin B was used without any indication of the use of premedication and substitution with electrolytes and salt water to avoid handicapping this drug. This choice of comparator resulted in a marked difference in the duration of treatment on trial drugs (77 days with voriconazole versus 10 days with amphotericin B), and precludes meaningful comparisons of the benefits and harms of the two drugs.. Liposomal amphotericin B is significantly more effective than voriconazole for empirical therapy of neutropenic cancer patients and should be preferred. For treatment of aspergillosis, there are no trials that have compared voriconazole with amphotericin B given under optimal conditions.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fluconazole; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Randomized Controlled Trials as Topic; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Fungemia; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Premedication; Randomized Controlled Trials as Topic; Risk Factors; Triazoles

To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality.. We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included.. The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P =.01), and a decrease in hospitalization length, with a weighted mean difference of -1.9 days (95% CI, -2.7 to -1.1 days; P <.00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P =.02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P =.02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, -4.3; 95% CI, -10.6 to 2.0 days; P =.2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P =.97).. CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant; Infant, Newborn; Infections; Length of Stay; Male; Neoplasms; Neutropenia; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome

Candidiasis and aspergillosis are the most common fungal infections in hematopoietic stem cell transplant recipients and other hematology/oncology patients. Strategies for reducing the morbidity and mortality associated with these infections include antifungal prophylaxis, empiric therapy in patients with persistent fever and neutropenia, and preemptive therapy. Antifungal therapies include amphotericin B deoxycholate, lipid formulations of amphotericin B, the triazoles (fluconazole, itraconazole, and voriconazole), and the echinocandins (caspofungin and the investigational agents micafungin and anidulafungin). Fluconazole is a reasonable choice for the treatment of invasive candidiasis if the patient has not previously received a triazole and the institution has a low incidence of triazole resistance. If resistance is a concern, an echinocandin, such as caspofungin, is an appropriate option. Voriconazole may be the initial choice in most patients with invasive aspergillosis. If patients are intolerant of or refractory to conventional therapy, effective alternatives include a lipid formulation of amphotericin B or an echinocandin.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Hematopoietic Stem Cell Transplantation; Humans; Liposomes; Mycoses; Neoplasms; Neutropenia; Peptides, Cyclic; Randomized Controlled Trials as Topic; Survival Analysis; Triazoles

Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever.. To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.. MEDLINE and Cochrane Library (November 2001). Letters, abstracts, and unpublished trials. The industry and authors were contacted.. Randomised trials comparing fluconazole with amphotericin B.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by both authors independently.. Sixteen trials (3760 patients, 341 deaths) were included. In 3 large 3-armed trials, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. It was unclear whether there was overlap among the "polyene" trials. We were unable to obtain any information to clarify these issues from the trial authors or from Pfizer, the manufacturer of fluconazole. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded, decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was rarely given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with potassium and magnesium supplements to prevent nephrotoxicity.. Amphotericin B had been disfavoured in several of the trials through their design or analysis. Since intravenous amphotericin B is the only antifungal agent for which there is good evidence suggesting an effect on mortality and is considerably cheaper than fluconazole, it should be preferred.

Topics: Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Mycoses; Neoplasms; Neutropenia; Odds Ratio; Randomized Controlled Trials as Topic

The last decade has been remarkable for the dramatic increase in the prevalence of serious fungal infections in patients with haematological disorders and neutropenic cancer patients. The mortality rate of deep-seated infection has been in excess of 90% and there is no doubt that this is one of the greatest challenges currently facing haematologists and oncologists. The development of the lipid-based drugs - liposomal amphotericin (AmBisome(R)), amphotericin B lipid complex, ABLC (Abelcet(R)), amphotericin B colloidal dispersion, Amphocil (ABCD(R)), has meant that doses of amphotericin B can be safely escalated for the first time whilst the problems of nephrotoxicity, infusion related reactions (including chills, rigors, fevers and hypoxia) can be reduced. These toxicities are variably reduced with AmBisome more than Abelcet and more than Amphocil and there is little information from randomised trials other than for AmBisome. AmBisome used in the setting of persistent fever and neutropenia not responding after 3-4 days of intravenous antibiotics, is associated with less breakthrough systemic fungal infections. There is also much less need for premedication, including steroids, compared with amphotericin B and Abelcet. The use of intermittent doses of Ambisome given prophylactically is now being explored. A new and exciting era of antifungal therapy is opening up with new compounds, such as itraconazole voriconazole, posaconazole and echinocandins, being investigated and for the first time, we also have options for combination therapy and prophylaxis.

Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Costs and Cost Analysis; Hematologic Diseases; Humans; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Opportunistic mycoses have emerged as important causes for morbidity and mortality in pediatric cancer patients, particularly in those with intensively treated hematological malignancies, allogeneic hematopoetic stem cell transplantation, and aplastic anemia. The incidence of invasive fungal infections in these settings may range from 10 to 25 % despite empirical antifungal therapy with an overall case fatality rate of up to 50 and 75 % depending on the organism. Preventive interventions are thus warranted, including but not limited to chemoprophylaxis with antifungal agents. Effective chemoprophylaxis of invasive Candida infections with a long-term benefit for overall survival has been demonstrated in patients with allogeneic bone marrow transplantation. However, its benefit in other high-risk populations is less well established, and a clearly effective approach to chemoprophylaxis for invasive Aspergillus infections has not been documented in appropriately designed clinical trials. This article reviews epidemiology and current approaches to chemoprophylaxis of opportunistic invasive fungal infections in children and adolescents with cancer and/or stem cell transplantation, and provides evidence-based guidelines for indications and modalities of antifungal prophylaxis and antifungal infection control measures in this population.

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Cohort Studies; Double-Blind Method; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Infant, Newborn; Itraconazole; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic; Respiratory Therapy; Risk Factors; Time Factors

Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever.. To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.. MEDLINE and Cochrane Library (March 2000). Letters, abstracts, and unpublished trials. The industry and authors were contacted.. Randomised trials comparing fluconazole with amphotericin B.. Data on mortality, invasive fungal infection, colonisation, use of additional (escape) antifungal therapy and adverse effects leading to discontinuation of therapy were extracted by both authors independently.. Thirteen trials (2977 patients) were included. In 3 large 3-armed trials, which comprised 43% of the patients, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is an ineffective drug in theses circumstances, this approach creates a bias in favour of fluconazole. Furthermore, 79% of the patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. It was unclear whether there was overlap among the "polyene" trials. We were unable to obtain any information to clarify these issues from the trial authors or the manufacturer of fluconazole. There was no significant difference in effect between fluconazole and amphotericin B. Apart from the "polyene" trials, more patients dropped out of the study when they received amphotericin B.. Amphotericin B had been disfavoured in most of the trials through their design or analysis. Since intravenous amphotericin B is the only antifungal agent with a documented effect on mortality and is considerably cheaper than fluconazole, it should be preferred.

Topics: Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Mycoses; Neoplasms; Neutropenia; Odds Ratio; Randomized Controlled Trials as Topic

Patients with cancer who are treated with chemotherapy or receive a bone marrow transplant have an increased risk of acquiring fungal infections. Such infections can be life-threatening. Antifungal drugs are therefore often given prophylactically to such patients, or when they have a fever.. To compare the effect and adverse effects of AmBisome and other lipid soluble formulations of amphotericin B with conventional amphotericin B in cancer patients with neutropenia.. MEDLINE and Cochrane Library. Unpublished trials from conference proceedings and contact to industry.. Randomised trials comparing lipid soluble formulations of amphotericin B with conventional amphotericin B.. Data on mortality, invasive fungal infection, nephrotoxicity, serum creatinine and dropouts were extracted by both authors independently.. AmBisome vs conventional amphotericin B (3 trials, 1149 patients): AmBisome tended to be more effective than conventional amphotericin B for invasive fungal infection (relative risk 0.63, 95% confidence interval 0.39 to 1.01, P=0.053) whereas there was no significant difference in mortality (relative risk 0.74, 95% CI 0.52 to 1.07). AmBisome decreased significantly the incidence of nephrotoxicity, defined as a 100% increase in serum creatinine (relative risk 0.51, 95% CI 0.40 to 0.64). Fewer patients dropped out on AmBisome but the difference was not significant (relative risk 0.78, 95% CI 0.56 to 1. 08). Amphotericin B in Intralipid vs conventional amphotericin B (4 trials, 145 patients): There were no significant differences in clinical effect whereas the patients treated with the lipid soluble formulation experienced significantly less nephrotoxicity (relative risk 0.34, 95% CI 0.15 to 0.75) and smaller increases in serum creatinine (weighted mean difference 32 micromol/l, 95% CI 21 to 43 micromol/l). Amphotericin B colloidal dispersion (ABCD) vs conventional amphotericin B (1 trial, 213 patients): There was lower nephrotoxicity with ABCD (relative risk 0.38, 95% CI 0.25 to 0.59).. AmBisome is a better drug than conventional amphotericin B but its high cost prohibits routine use in most settings. Furthermore, the advantages of AmBisome may be smaller than indicated in our review if conventional amphotericin B is administered under optimal circumstances. It is not clear whether other lipid formulations of amphotericin B could offer a worthwhile advantage compared to conventional amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Humans; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Three cases of Clavispora lusitaniae invasive fungal infections are reported. All three infections appeared in cancer patients presented with fungaemia, one additionally with meningitis. Two of them were breakthrough -- they developed during therapy with conventional amphotericin B with a dose of 0.5 mg kg(-1) day(-1) . All three were cured: two with intravenous fluconazol and one with an increasing dose (1 mg kg(-1) day(-1)) of amphotericin B. In one of two breakthrough cases the sensitivity of the strain to antifungals was tested against antifungal agents and showed in vitro resistance to amphotericin B (MIC 2 eta g ml(-1)).

Topics: Adult; Amphotericin B; Antifungal Agents; Child, Preschool; Fluconazole; Fungemia; Humans; Meningitis, Fungal; Neoplasms; Saccharomycetales

The risk factors, therapy and outcome of ten cases of fungemia due to Candida krusei, appearing during the last 10 years in a single national cancer institution, are analyzed. Univariate analyses did not find any specific risk factors in comparison to 51 Candida albicans fungemias appearing at the same institution and with a similar antibiotic policy. Association with prior fluconazole prophylaxis was not confirmed because only one case appeared in a patient previously treated with fluconazole. However, attributable and crude mortality due to C. krusei fungemias was higher than for C. albicans fungemia. The authors review 172 C. krusei fungemias published within the last 10 years to compare with the incidence, therapy and outcome of C. krusei fungemia from our cancer institute.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Cross Infection; Female; Fluconazole; Fungemia; Humans; Incidence; Male; Middle Aged; Neoplasms; Risk Assessment; Treatment Outcome

New approaches in successful treatment of cancer patients are impaired by increasing incidence of fungal infections with high mortality. Relevant prognostic factors could be identified by numerous trials, such as age, kind and status of disease, intensity of previous chemotherapy, bone marrow transplantation, advanced fungal colonization of gastrointestinal tract. In clinical practice options for prompt and sensitive diagnostics are limited despite of new PCR-techniques. Prophylactic efficiency of polyenes or azoles is proven in high risk patients. Amphotericin B is established for treatment in case of documented or assumed invasive fungal infection. Liposomal preparations are less toxic and at least as effective as conventional amphotericin B in randomized trials.

Topics: Amphotericin B; Antibodies, Fungal; Antifungal Agents; Azoles; Candidiasis; Humans; Neoplasms; Risk Factors

The extensive use of antifungal prophylaxis may have played a role in the increased incidence of invasive fungal infections in immunocompromised patients. Amphotericin B remains the antifungal agent with the broadest spectrum of action available and is thus the standard treatment for immunocompromised patients with proven or suspected fungal infections, especially aspergillosis. However, its potential for nephrotoxicity limits its usefulness. Lipid formulations of amphotericin B may allow therapy to be administered with reduced renal toxicity. Three different lipid formulations of amphotericin B are currently available. These compounds have different pharmacokinetics properties and usually achieve higher serum and/or tissue concentrations than amphotericin B. At present, there are no studies comparing the lipid formulations with each other and only a few randomized trials comparing them with conventional amphotericin B. However, a number of open clinical trials and compassionate-use protocols suggest that lipid-based forms of amphotericin B can achieve good response rates with minimal toxicity in patients with a variety of invasive mycoses, including those who have proved refractory or intolerant to previous therapy with conventional amphotericin B. Unfortunately, the cost of these compounds remains very high and may represent a limiting factor to their use.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Candida; Candidiasis; Drug Resistance, Microbial; Humans; Immunocompromised Host; Lipids; Liposomes; Mycoses; Neoplasms; Risk Factors

To determine whether antifungal agents given prophylactically or empirically decrease morbidity and mortality in patients with cancer complicated by neutropenia.. Meta-analysis of randomised trials of amphotericin B, various lipid soluble formulations of amphotericin B (for example, AmBisome), fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment.. Trials conducted anywhere in the world.. Patients with cancer complicated by neutropenia.. Mortality, invasive fungal infection (defined as positive blood culture, oesophageal candidiasis, or lung or deep tissue infection), and colonisation.. 24 trials with 2758 randomised patients were reviewed; the total number of deaths was 434. Prophylactic or empirical treatment with antifungals as a group bad no effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14). Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the studies were small and the difference in number of deaths was only 15. Antifungal treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to 0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated (95% confidence interval to 48 to 158) one case of fungal invasion was prevented in surviving patients.. There seems to be no survival benefit of antifungal agents given prophylactically or empirically to patients with cancer complicated by neutropenia. These agents should be restricted to patients with proved infection and those in randomised trials. A large, definitive placebo controlled trial of amphotericin B is needed.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Humans; Itraconazole; Ketoconazole; Miconazole; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Invasive fungal infections are one of the leading causes of morbidity and mortality in cancer patients. Amphotericin B deoxycholate is still considered the gold standard of antifungal therapy, although the new triazoles (itraconazole and, especially, fluconazole) have shown to be able to replace amphotericin B for some therapeutic indications. The new lipid formulations of amphotericin B have disclosed new therapeutic perspectives, especially in patients with severe renal failure and documented, infections. At this time, indications, contraindications and limitation of the various drugs in the antifungal armamentarium are still partially unclear. Antifungal prophylaxis with fluconazole may be indicated in high-risk patients, although the duration of such prophylaxis should be limited as much as possible, in order to prevent selection of resistant strains and acquired resistance. Empirical antifungal therapy is used extremely widely (maybe, too widely) in many cancer centres, despite being based on limited clinical data. For this indication, fluconazole may also be effective in patients not receiving fluconazole prophylaxis, in whom Aspergillus infection is unlikely.

Topics: Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Fluconazole; Humans; Itraconazole; Mycoses; Neoplasms

The observation of a considerable incidence of fungal infections in oncology patients has promoted a large number of studies both on prophylaxis and treatment in this patient group. Trials using triazoles, especially fluconazole, have shown effect in preventing fungal infections. In neutropenic patients, their role in therapy still remains less clear. Amphotericin B is the drug of choice for most life-threatening infections. With this drug, efforts concentrate upon the amelioration of side effects by sodium loading, administration in lipid emulsions or liposomes. The use of AMB as low-dose systemic prophylaxis or by inhalation needs further study.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Humans; Incidence; Mycoses; Neoplasms; Triazoles

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Clinical Trials as Topic; Disease Susceptibility; Drug Administration Routes; Hematopoietic Cell Growth Factors; Humans; Immunocompromised Host; Leukocyte Transfusion; Mycoses; Neoplasms; Neutropenia; Triazoles

Topics: Amphotericin B; Antifungal Agents; Azoles; Flucytosine; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia

During the last years, the proportion of cancer patients who develop systemic fungal infections has increased steadily. These infections are characterised by high mortality, especially in patients with persistent granulocytopenia and in those receiving allogeneic bone marrow transplants. The most important pathogens in neutropenic patients are Candida and Aspergillus spp. Usually, Candida infections arise from overgrowth in the gastrointestinal tract, while Aspergillus infections are acquired by inhalation of spores. Prophylaxis of systemic fungal infections seems mandatory since optimal strategies for diagnosis and treatment of these infections are lacking. Treatment with the non-absorbable polyenes nystatin and amphotericin B is useful for prophylaxis of superficial fungal infections, provided that compliance of the patients is optimal. The imidazoles ketoconazole and miconazole can reduce the incidence of superficial fungal infections, but there are conflicting data regarding their value for prevention of systemic mycoses. There are several studies indicating that prophylactic use of fluconazole reduces the incidence of mucosal and systemic fungal infections, especially in patients receiving allogeneic bone marrow transplants. Fluconazole shows reduced activity against several Non-albicans spp. and is not active against Aspergillus spp. Itraconazole has in vitro and in vivo activity against several Aspergillus spp. but high serum and tissue levels are necessary. However, bioavailability of itraconazole is reduced in patients with raised gastric pH and no i.v. formulation is available. Although there is some evidence for its prophylactic activity against Aspergillus infections in neutropenic patients, more studies are necessary to confirm these findings. Intravenous amphotericin B cannot be recommended for routine prophylactic use because of its toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Candidiasis; Fluconazole; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections

Deep seated candidosis are the most common invasive fungal infections occurring in various categories of patients including those with cancer, burns as well as patients with AIDS or undergoing organ transplantation. Various clinical entities have to be distinguished with implications for diagnostic procedures as well as for adequate therapy. During the last decade, tremendous progress has been achieved leading to a major reduction of mortality attributable for candidaemia from 80% (in the seventies) to 40% in the nineties, mainly due to early empiric antifungal and better prophylaxis treatment. Other antifungal strategies than conventional amphotericin B are now available and have been shown effective, in particular, new modalities to administer amphotericin B including various lipid formulations, but also new azoles and mainly the triazoles such as fluconazole and itraconazole. Fluconazole has been shown effective as prophylaxis of candidosis including in patients undergoing bone marrow transplantation as well as in treatment of oropharyngeal candidosis and for candidaemia occurring in non-neutropenic patients. More limited data are available on itraconazole so far in particular in patients with documented invasive candidosis, but preliminary reports are encouraging. Oral therapy with systemic efficacy is more easy to recommend and allows ambulatory treatment. Candidosis is not a benign disease and in every single patient with fungemia antifungal treatment is mandatory.

Topics: AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Burns; Candidiasis; Fluconazole; Humans; Incidence; Itraconazole; Neoplasms; Opportunistic Infections; Postoperative Complications; Transplantation

Attachment of antibodies to the surface of liposomes was performed to confer specificity for a certain cell or organ expressing the targeted antigenic determinant. These so-called immunoliposomes are expected to be applied as targeted drug carriers. In this article, the literature concerning in vivo studies of the targeting of immunoliposomes to various sites in the body is reviewed. The anatomical, physiological, and pathological constraints and current progress are described. Moreover, perspectives on the therapeutic feasibility of this drug targeting system are discussed.

Topics: Amphotericin B; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Biological Availability; Candidiasis; Chloroquine; Clinical Trials as Topic; Drug Carriers; Drug Compounding; Drug Evaluation, Preclinical; Humans; Immunoconjugates; Injections, Intravenous; Liposomes; Lung; Lymph Nodes; Malaria; Mice; Neoplasms; Peritoneal Cavity; Plasmodium berghei; Rats; Tissue Distribution

Fever is associated with malignancy and is a common problem in cancer patients. Fever in the cancer patients is closely linked with infection, especially when the patient is granulocytopenic. When fever appears, a series of diagnostic and therapeutic measures must be taken even if precise knowledge of the cause of the infection is lacking. Fever can be caused by infection or by the cancer itself through tumor-related necrosis, hemorrhage or pyrogens. Infection is the more common cause, however. Bacterial and fungal sepsis can coexist and the bacteremia can overshadow the more difficult to determine fungal infection. For this reason it has become accepted practice to administer amphotericin B to granulocytopenic patients who remain febrile after a few days of broad-spectrum antimicrobial therapy and in whom no bacteria can be documented. Viral infection is rarely diagnosed in neutropenic patients without concomitant immunosuppression.

Topics: Amikacin; Amphotericin B; Bacteremia; Bacterial Infections; Ceftazidime; Clinical Trials as Topic; Drug Therapy, Combination; Fever; Fever of Unknown Origin; Humans; Mycoses; Neoplasms; Neutropenia; Vancomycin; Virus Diseases

Fungal infections continue to cause major complications in cancer patients. With the increasing use of aggressive chemotherapy causing prolonged granulocytopenia, and the progress made in the prophylaxis and treatment of bacterial infections, the risk of invasive mycoses has increased, particularly in patients with hematological malignancies. The prognosis of these infections is poor unless they are diagnosed and treated promptly. Early diagnosis, particularly in neutropenic cancer patients, is often difficult and antifungal therapy is frequently unsuccessful because it is not instituted until the infection is in an advanced, fatal phase. In order to reduce the mortality associated with invasive fungal infections, antifungal therapy, usually amphotericin B, has been empirically carried out in neutropenic patients with fever unresponsive to broad-spectrum antibacterial therapy. However, the absence of a marker of the fungal infection, the frequent occurrence in these patients of non-infective fever, which does not require any antimicrobial therapy, and the possible toxicity of amphotericin B represent the major limits of empiric antifungal therapy. In view of the above, the study of improved and less toxic antifungal agents, and the evaluation of new clinical and laboratory methods for an early diagnosis, have been the major goals in research on the opportunistic invasive fungal infections in the last years.

Topics: Amphotericin B; Aspergillosis; Fluconazole; Humans; Itraconazole; Lung Diseases, Fungal; Mycoses; Neoplasms; Serologic Tests; Tomography, X-Ray Computed; Ultrasonography

Candidiasis remains the most frequently encountered fungal infection in patients with profound granulocytopenia and appears to be increasing in frequency. In addition, Candida infections are occurring earlier during remission induction chemotherapy and can be caused by a variety of species such as C. albicans, C. tropicalis, and C. krusei. The most frequent source of disseminated infection is the gastrointestinal tract, as the integrity of the epithelium is disrupted by chemotherapeutic agents. The spectrum of disseminated candidiasis comprises both an acute and a chronic presentation (also known in the literature as hepatosplenic candidiasis). The management of disseminated infection consists of early empiric antifungal therapy with a standard agent, amphotericin B. Unfortunately, responses in the setting of profound granulocytopenia appear to be poor. Other agents that appear to be useful in the management of disseminated candidiasis include 5-flucytosine and fluconazole. Based on animal experimentation, it appears that the combination of these three classes of agents might produce superior results compared with amphotericin B alone. Removal of the central venous catheter does not appear warranted in the setting of profound granulocytopenia, and the role of colony stimulating factors needs to be defined. Given the severity and high mortality associated with disseminated candidiasis in patients with hematologic malignancies, antifungal prophylaxis appears warranted.

Topics: Agranulocytosis; Amphotericin B; Candidiasis; Humans; Neoplasms; Randomized Controlled Trials as Topic

Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Cytokines; Drug Administration Routes; Humans; Imidazoles; Neoplasms; Opportunistic Infections; Polyenes; Triazoles

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Azoles; Aztreonam; Cephalosporins; Fluoroquinolones; Foscarnet; Ganciclovir; Humans; Imipenem; Immunocompromised Host; Infections; Neoplasms; Pneumonia, Pneumocystis; Vancomycin

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Disease Susceptibility; Double-Blind Method; Fluconazole; Humans; Immunocompromised Host; Neoplasms; Neutropenia; Survival Rate

Topics: Adult; Amphotericin B; Animals; Antimetabolites; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buthionine Sulfoximine; Calcium Channel Blockers; Calmodulin; Cardiotonic Agents; Child; Clinical Trials as Topic; Dipyridamole; Drug Evaluation; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Female; Humans; Ketoconazole; Male; Methionine Sulfoximine; Mice; Neoplasms; Nitroimidazoles; Xanthines

Systemic candidiasis is a disease of increasing incidence and proportions, which appears to be associated with the advances in modern medicine. It involves primarily patients with severe debilitating and malignant disease who are receiving immunosuppressive, cytotoxic, antimetabolite, and antibiotic therapy. Side effects of these otherwise major therapeutic agents predispose patients to opportunistic fungal infections, of which candidiasis is the most common. The high morbidity and mortality of disseminated candidiasis in neutropenic patients are difficult obstacles to obtaining the optimal, if not full, potential of modern chemotherapy for cancer. The inability to diagnose early invasive and systemic candidiasis is a major handicap that delays timely initiation of antifungal therapy. The paucity of highly efficacious antifungal agents with low toxicity severely limits the ability to successfully cure systemic fungal infections in cancer patients. Aggressive research into the basic biology of Candida spp. is necessary for directing the development of better diagnostic methods and improved antifungal drugs.

Topics: Amphotericin B; Candidiasis; Flucytosine; Humans; Immune Tolerance; Ketoconazole; Neoplasms; Opportunistic Infections; Risk Factors

Shivering is a common and distressful reaction associated with administration of amphotericin B, a systemic antifungal agent. Shivering occurs as a result of the drug's intrinsic pyrogenicity, and thus resembles febrile shivering. This heat loss phenomenon has metabolic as well as psychologic costs. The intervention approach to amphotericin B-induced shivering includes reporting the phenomenon, restoring lost heat, modifying the rate of heat loss, altering the physiologic determination of heat loss, and giving drugs to suppress shivering. Specific suggestions for interventions are discussed. Supportive care of the patient with cancer who is receiving this drug is briefly mentioned as it relates to thermoregulatory principles. Possible areas of future inquiry into shivering suppression are mentioned.

Topics: Amphotericin B; Body Temperature Regulation; Humans; Neoplasms; Nursing Care; Shivering

As invasive fungal infection remains a common problem in the management of cancer patients, chemoprophylaxis of these opportunistic infections is desperately needed. The most frequently investigated antifungal agents have been nystatin, amphotericin B, and ketoconazole. In placebo-controlled studies, high doses of antifungal agents decreased the positive results from surveillance cultures, and there is some suggestion that such chemoprophylaxis may reduce the incidence of invasive candidiasis in neutropenic cancer patients. However, no oral chemoprophylaxis has effectively prevented aspergillosis or mucormycoses in these patients. There are still many areas of controversy, and the most adequate regimens, if any, remain to be defined.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin

Infection is the major cause of morbidity and mortality in children receiving anticancer therapy. Children who have severe neutropenia (neutrophil count less than 100/mm3) for longer than 2 weeks should receive oral antibiotic prophylaxis. At present, trimethoprim sulfamethoxazole in combination with either nystatin or amphotericin B is the best regimen for reducing the incidence of serious infections. Trimethoprim sulfamethoxazole is very effective in the prevention of Pneumocystis carinii pneumonitis. Clinicans will have to balance the advantages and disadvantages of prophylaxis in patients who are at risk for P. carinii pneumonitis.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Candidiasis; Child; Compliance; Drug Combinations; Humans; Leukemia; Neoplasms; Neutropenia; Nystatin; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Fungal infections of the gastrointestinal tract have risen to higher levels of prevalence in the past decade. Major factors accounting for this increase are social changes, such as the increased ease and frequency of travel, which exposes the individual to environmental conditions that may result in fungal infection; increasing use of antibiotic and hormonal medications by otherwise healthy persons; and improved therapy for other diseases, such as polychemotherapy of cancer with its immunosuppressive effects. Both noninvasive and invasive fungal disease of the intestinal tract in otherwise healthy individuals can be successfully treated. The invasive fungal infections in patients with severe prior underlying disease are often first diagnosed postmortem, but improvement in serologic techniques now offers a possibility of earlier diagnosis and therapeutic intervention.

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Diarrhea; Enteritis; Histoplasmosis; Humans; Imidazoles; Immunosuppression Therapy; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin; Paracoccidioidomycosis; Piperazines; Sulfadiazine

Topics: Amphotericin B; Animals; Candida albicans; Candidiasis; Cell Membrane; Cell Membrane Permeability; Chemical Phenomena; Chemistry; Chromatin; Dogs; Dose-Response Relationship, Drug; Drug Evaluation; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Kinetics; Mice; Microbial Sensitivity Tests; Mycoses; Neoplasms; Neoplasms, Experimental

Topics: Amphotericin B; Diabetes Complications; Diagnosis, Differential; Humans; Mucormycosis; Neoplasms; Paranasal Sinuses; Sinusitis

The aim of this study was to evaluate micafungin efficacy for treatment of invasive candidiasis/candidaemia in patients with cancer. Modified intent-to-treat populations were analysed from two trials: one, in adults and children with confirmed Candida infection, compared micafungin (adults 100 mg day(-1); children 2 mg kg(-1) day(-1)) with liposomal amphotericin B (L-AmB 3 mg kg(-1) day(-1)); and the other, in adults only, compared micafungin (100 or 150 mg day(-1)) with caspofungin (50 mg day(-1); 70 mg loading dose). Primary efficacy endpoint in both trials was treatment success, defined as both clinical and mycological response at end of therapy. In the micafungin/L-AmB trial, 183/489 patients had malignancy (37% neutropenic). In the micafungin/caspofungin trial, 176/572 patients had malignancy (26% neutropenic). Micafungin treatment success rates were generally similar in patients with/without malignancy and to rates observed with L-AmB and caspofungin. Most patients with malignancy and neutropenia were successfully treated by all three drugs. For all drugs, incidence of discontinuations because of treatment-related adverse events was similar for patients with malignancy (≤7.7%) vs. no malignancy (≤8.0%). These results suggest that compared with L-AmB and caspofungin, micafungin was effective and well tolerated in patients with candidiasis/candidaemia with/without malignancy. Further prospective trials are recommended to evaluate comparative outcomes with a primary focus on patients with malignancies and invasive candidiasis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Caspofungin; Child; Child, Preschool; Double-Blind Method; Echinocandins; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Middle Aged; Neoplasms; Treatment Outcome; Young Adult

Assessment of response to invasive aspergillosis (IA) therapy has been challenging in treatment trials.. The causes of death over 12 weeks were categorized prospectively by a blinded data review committee using a priori defined criteria in participants in a randomized comparative trial of voriconazole versus amphotericin B as first-line therapy of proven or probable IA.. Death occurred in 98 of 277 patients during the 12-week course of study. Seventy-three of the 98 deaths (74%) occurred in the first 6 weeks; 25 deaths occurred during the second 6 weeks. Of the 73 deaths during the first 6 weeks, 50 (68%) were judged to be attributable to IA. Of the 25 deaths during the second 6 weeks, only 6 (24%) were judged to be attributable to IA. Fifty of the 56 deaths (89%) attributable to IA occurred during the first 6 weeks.. These data suggest that most deaths due to IA occur during the first 6 weeks after the start of therapy and 6 weeks may be a better interval to judge the effectiveness of antifungal therapy because most deaths after 6 weeks are due to causes related to the underlying disease and its treatment rather than due to IA. Attributable mortality when assessed using a priori definitions and conducted in a blinded manner by a central data review committee can be useful in the assessment of IA therapy.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Cause of Death; Graft vs Host Disease; Humans; Neoplasms; Pyrimidines; Survival Rate; Time Factors; Triazoles; Voriconazole

This study investigates the association of liposomal amphotericin B (L-AmB) with plasma proteins and its impact on the pharmacokinetics of L-AmB in paediatric patients with malignant diseases.. Paediatric oncology patients (n = 39) who received multiple-doses of L-AmB were recruited into this study. The association of the drug with plasma lipoprotein was investigated using single vertical spin density gradient ultracentrifugation and quantitated with a validated HPLC assay. The unbound amphotericin B (AmB) in the plasma was separated by ultrafiltration and determined with a validated LC/MS/MS assay.. The ex vivo lipoprotein distribution of L-AmB found that 68.3 +/- 11.8% of the drug was associated with the high density lipoprotein (HDL) fraction, which demonstrated a significant inverse correlation with posterior Bayesian estimates of L-AmB clearance (r = -0.690, p < 0.01). The average of unbound fraction of AmB in plasma of patients administered with L-AmB was 0.005, but its relationship with L-AmB clearance did not reach a statistical significance.. L-AmB displays different lipoprotein distribution profile from that of the conventional AmB formulation, with L-AmB preferentially associated with HDL in plasma. The inverse correlation of L-AmB clearance to its HDL distribution contributes to the difference in the pharmacokinetic profile of L-AmB.

Topics: Amphotericin B; Antifungal Agents; Bayes Theorem; Child; Child, Preschool; Chromatography, High Pressure Liquid; Chromatography, Liquid; Female; Humans; Infant; Lipoproteins; Lipoproteins, HDL; Liposomes; Male; Neoplasms; Prospective Studies; Protein Binding; Tandem Mass Spectrometry; Ultrafiltration

In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (C(ss,trough)) and plasma creatinine concentrations (C(creat)) were measured in 83 children (age: 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB C(ss,trough) were identified by determining the probability of large (>24%, 75th percentile) increases in C(creat) after 6 days of AmB for a series of C(ss,trough) ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76-1.05 mg/l C(ss,trough) range provided the maximum concentrations that still had a low probability (p < 0.29) of adverse renal effects. 1 mg/kg/day AmB produces C(ss,trough) within this range for children weighing 25-45 kg. Lighter children (10-25 kg) require higher AmB doses (1.25-1.5 mg/kg/day) to achieve target C(ss,trough), while heavier children (45-55 kg) require lower doses (0.75 mg/kg/day). These starting dose guidelines may require individualization and prospective evaluation.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Body Weight; Child; Child, Preschool; Computer Simulation; Creatinine; Cyclosporine; Deoxycholic Acid; Drug Combinations; gamma-Glutamyltransferase; Humans; Immunosuppressive Agents; Infant; Kidney Diseases; Microbial Sensitivity Tests; Models, Biological; Mycoses; Neoplasms; Risk Factors; Urea

Invasive candidiasis is a common and serious complication of cancer and its therapy.. We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication.. 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors.. Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Caspofungin; Echinocandins; Female; Fungemia; Gastrointestinal Neoplasms; Hematologic Neoplasms; Humans; Leukemia; Lipopeptides; Male; Middle Aged; Neoplasms; Neutropenia; Peptides, Cyclic; Retrospective Studies; Species Specificity; United States

Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B.. In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point.. Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events.. Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Caspofungin; Double-Blind Method; Echinocandins; Female; Fever; Humans; Kidney Diseases; Lipopeptides; Liposomes; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Peptides; Peptides, Cyclic; Survival Rate; Treatment Outcome

Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative.. In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy.. A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, -10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal amphotericin B (8 [1.9 percent] vs. 21 [5.0 percent], P=0.02). The voriconazole group had fewer cases of severe infusion-related reactions (P<0.01) and of nephrotoxicity (P<0.001). The incidence of hepatotoxicity was similar in the two groups. Patients receiving voriconazole had more episodes of transient visual changes than those receiving liposomal amphotericin B (22 percent vs. 1 percent, P<0.001) and more hallucinations (4.3 percent vs. 0.5 percent, P<0.001). Parenteral voriconazole was changed to the oral formulation in 22 percent of the voriconazole group, with a reduction in the mean duration of hospitalization by one day in all patients (P=0.17) but by two days in patients at high risk (P=0.03).. Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child; Chronic Disease; Female; Fever; Humans; Infusions, Intravenous; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Prospective Studies; Pyrimidines; Triazoles; Voriconazole

Nephrotoxicity is the major adverse effect of amphotericin B (AmB), often limiting administration of full dosage. Selective distal tubular epithelial toxicity seems to be responsible for the profound potassium wasting that is a major clinical side effect of treatment with AmB. Potassium depletion also potentiates the tubular toxicity of AmB. This study was designed to assess the ability of spironolactone to reduce potassium requirements and to prevent hypokalemia in neutropenic patients on AmB treatment.. In this study 26 patients with various hematological disorders were randomized to receive either intravenous AmB alone or AmB and oral spironolactone 100 mg twice daily when developing a proven or suspected fungal infection.. Patients receiving concomitant AmB and spironolactone had significantly higher plasma potassium levels than those receiving AmB alone (P = 0.0027). Those patients receiving AmB and spironolactone required significantly less potassium supplementation to maintain their plasma potassium within the normal range (P = 0.022). Moreover, urinary potassium losses were significantly less in patients receiving AmB and spironolactone than those receiving AmB alone (P = 0.040).. This study showed that spironolactone can reduce potassium requirements and prevent hypokalemia by reducing urinary potassium loss in neutropenic patients on AmB treatment.

Topics: Amphotericin B; Antifungal Agents; Humans; Hypokalemia; Kidney Function Tests; Mineralocorticoid Receptor Antagonists; Mycoses; Neoplasms; Neutropenia; Potassium; Spironolactone

This study was conducted to characterise the pharmacokinetics of a liposomal pharmaceutical product of amphotericin B (LAB) in three neutropenic cancer patients complicated by suspected fungal infections. LAB was administered at a constant dose of 50 mg/day over 1--6 h by intravenous infusion, and blood samples were obtained between two infusion intervals without complicating the systemic therapy of the patients. Quantitative analysis of amphotericin B (AB) in plasma was established by a validated reversed-phase high-performance liquid chromatographic (HPLC) assay. Model independent pharmacokinetic parameters were estimated using area and moment analysis. Administration of LAB to the first patient (day 1) diagnosed as malignant melanoma resulted in a mean maximum concentration (C(max)) of 679+/-6 ng/ml and a mean minimum concentration (C(min)) of 139+/-9 ng/ml of AB. Pre-dose, C(max) and C(min) values of AB, after multiple LAB dosing to the other two patients both having acute myeloblastic leukemia were found to be 440+/-6, 1140+/-10, 409+/-11 ng/ml (day 19) and 408+/-3, 1180+/-10, and 283+/-1 ng/ml (day 9), respectively. The area under the plasma concentration-time curve (AUC) and the mean residence time (MRT) calculated between the two infusion intervals were 6180 ngh/ml, 7.79 h (day 1) for the first patient; 13,700 ng.h/ml, 10.5 h (day 19) and 14,000 ng.h/ml, 9.93 h (day 9) for the other two patients, respectively. The pharmacokinetic profiles and non-compartmental parameters calculated were comparable for both patients diagnosed with acute myeloblastic leukemia after multiple dosing at steady state, which also demonstrated a twofold increase in their AUC values compared with the AUC of the first patient. Although C(min) values supported the assumption that there was AB accumulation in plasma and this accumulation could be increased at high doses, LAB was administered safely to these patients and well tolerated at the doses given.

Topics: Adult; Amphotericin B; Antifungal Agents; Area Under Curve; Chromatography, High Pressure Liquid; Drug Carriers; Female; Humans; Infusions, Intravenous; Liposomes; Middle Aged; Neoplasms; Neutropenia; Spectrophotometry, Ultraviolet

The efficacy and safety of itraconazole oral solution and a combination of amphotericin B capsules plus nystatin oral suspension were compared in the prophylaxis of fungal infections in neutropenic patients. In an open, randomized, multicentre trial, 144 patients received itraconazole oral solution 100 mg bd, and 133 patients received amphotericin B 500 mg tds plus nystatin 2 MU qds. Overall, 65% of itraconazole-treated patients were considered to have had successful prophylaxis, compared with 53% in the polyene group. Proven deep fungal infections occurred in 5% of patients in each group. Fewer patients receiving itraconazole than amphotericin plus nystatin had superficial infections (3 versus 8%; P = 0.066). This trend in favour of itraconazole was seen in patients with profound neutropenia (neutrophil count <0.1 x 10(9) cells/L at least once) or prolonged neutropenia (neutrophil count <1.0 x 10(9) cells/L for >14 days). The median time to prophylactic failure was longer in the itraconazole group (37 days) than in the polyene group (34 days). The number of patients with fungal colonization (nose, sputum, stool) changed more favourably from baseline to endpoint in the itraconazole group than in the polyene group. Both treatments were safe and well tolerated; however, patients receiving amphotericin plus nystatin had a higher incidence of nausea and rash. In conclusion, itraconazole oral solution at doses of 100 mg bd and oral amphotericin B plus nystatin have similar prophylactic efficacy against fungal infections in neutropenic patients. On the basis of reduced incidence of superficial fungal infections, fungal colonization and specific adverse events, itraconazole may be the preferred treatment.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Itraconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Nystatin

Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting.. To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy.. An open randomized, controlled, multicenter trial, powered for equivalence.. 60 oncology centers in 10 countries.. 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy.. Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution.. Defervescence, breakthrough fungal infection, drug-related adverse events, and death.. For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days.. Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure

To construct a population pharmacokinetic model for the antifungal agent, amphotericin B (AmB), in children with malignant diseases.. A two compartment population pharmacokinetic model for AmB was developed using concentration-time data from 57 children aged between 9 months and 16 years who had received 1 mg kg(-1) day(-1) doses in either dextrose (doseform=1) or lipid emulsion (doseform=2). P-Pharm (version 1.5) was used to estimate the basic population parameters, to identify covariates with significant relationships with the pharmacokinetic parameters and to construct a Covariate model. The predictive performance of the Covariate model was assessed in an independent group of 26 children (the validation group).. The Covariate model had population mean estimates for clearance (CL), volume of distribution into the central compartment (V) and the distributional rate constants (k12 and k21) of 0.88 l h(-1), 9.97 l, 0.27 h(-1) and 0.16 h(-1), respectively, and the intersubject variability of these parameters was 19%, 49%, 55% and 48%, respectively. The following covariate relationships were identified: CL (l h(-1)) = 0.053 + 0.0456 weight (0.75) (kg) + 0.242 doseform and V (l) = 7.11 + 0.107 weight (kg). Our Covariate model provided unbiased and precise predictions of AmB concentrations in the validation group of children: the mean prediction error was 0.0089 mg l(-1) (95% confidence interval: -0.0075, 0.0252 mg l(-1)) and the root mean square prediction error was 0.1245 mg l(-1) (95% confidence interval: 0.1131, 0.1349 mg l(-1)).. A valid population pharmacokinetic model for AmB has been developed and may now be used in conjunction with AmB toxicity and efficacy data to develop dosing guidelines for safe and effective AmB therapy in children with malignancy.

Topics: Adolescent; Age Factors; Amphotericin B; Antifungal Agents; Area Under Curve; Child; Child, Preschool; Computer Simulation; Fat Emulsions, Intravenous; Female; Glucose; Humans; Infant; Male; Models, Statistical; Neoplasms

In a randomized, double-blind, comparative, multicenter trial, liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients, using a composite end point, but was more effective in reducing proven emergent fungal infections, infusion-related toxicities, and nephrotoxicity. The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy.. Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial. Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed.. Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ($48,962 v $43,183; P =.022). However, hospital costs were highly sensitive to the cost of study medication ($39,648 v $43,048 when drug costs were not included; P =.416). Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients.. The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients.

Topics: Adult; Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Carriers; Drug Costs; Economics, Pharmaceutical; Female; Fever; Hospital Costs; Humans; Kidney Diseases; Liposomes; Male; Middle Aged; Neoplasms; Neutropenia

To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer.. A total of 317 neutropenic patients (<500 cells/mm3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criteria, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patient was afebrile, had no clinical or microbiological evidence of fungal infection, and did not require study termination due to lack of efficacy, drug toxicity, or death.. A satisfactory response occurred in 68% of the patients treated with fluconazole (107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of 159 patients). Progressive or new fungal infections during therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse events related to study drug (especially fever, chills, renal insufficiency, electrolyte disturbances, and respiratory distress) occurred more often in patients treated with amphotericin B (128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but only 1 (1%) patient treated with fluconazole were terminated from the study owing to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole versus 34 [21%] patients treated with amphotericin B) and mortality from fungal infection (7 [4%] patients treated with fluconazole versus 5 [3%] patients treated with amphotericin B) were similar in each study group.. Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients. However, because fluconazole may be ineffective in the treatment of Aspergillus, patients at risk for that infection should be evaluated by chest radiograph, computed tomographic scanning, and cultures before the use of empiric fluconazole therapy.

Topics: Amphotericin B; Antifungal Agents; Cause of Death; Female; Fever; Fluconazole; Humans; Infusions, Intravenous; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Treatment Outcome

We performed a prospective, randomized, multicenter trial to evaluate the effectiveness of prophylactic inhalations with aerosolized amphotericin B (aeroAmB) to reduce the incidence of invasive aspergillus (IA) infections in patients after chemotherapy or autologous bone marrow transplantation and an expected duration of neutropenia of at least 10 days. From March 1993 until April 1996, 382 patients with leukemias, relapsed high-grade non-Hodgkin lymphomas, or solid tumors were randomized with a 13:10 ratio to receive either prophylactic aeroAmB inhalations at a dose of 10 mg twice daily or no inhalation prophylaxis in an unblinded fashion. The incidence of proven, probable, or possible IA infections was 10 of 227 (4%) in patients who received prophylactic aeroAmB. This did not differ significantly from the 11 of 155 (7%) incidence in patients who received no inhalation prophylaxis (P =.37). Moreover, no differences in the overall mortality (13% v 10%; P =.37) or in the infection-related mortality (8% v 7%; P =.79) were found. In contrast to other nonrandomized trials, we observed no benefit from prophylactic aeroAmB inhalations, but the overall incidence of IA infections was low.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Aspergillosis; Aspergillus; Bone Marrow Transplantation; Combined Modality Therapy; Female; Humans; Leukemia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Transplantation, Autologous; Treatment Outcome

In a prospective, randomized clinical trial, the toxicity of 1 mg of amphotericin B (AmB) per kg of body weight per day infused in 5% dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease. In an analysis of 82 children who received a full course of 6 days or more of AmB (117 courses), it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion, with there being no difference between the two methods of AmB administration. An intent-to-treat comparison of the numbers of courses affected by acute toxicity (fever, rigors) and chronic toxicity (nephrotoxicity) also indicated that there was no significant difference between AmB infused in dextrose (78 courses) and AmB infused in lipid emulsion (84 courses). The pharmacokinetics of AmB were investigated in 20 children who received AmB in dextrose and 15 children who received AmB in lipid emulsion. Blood samples were collected up to 24 h after administration of the first dose, and the concentration of AmB in plasma was analyzed by a high-performance liquid chromatography assay. The clearance (CL) of AmB in dextrose (0.039 +/- 0.016 liter. h-1. kg-1) was significantly lower (P < 0.005) than the CL of AmB in lipid emulsion (0.062 +/- 0. 024 liter. h-1. kg-1). The steady-state volume of distribution for AmB in dextrose (0.83 +/- 0.33 liter. kg-1) was also significantly lower (P < 0.005) than that for AmB in lipid emulsion (1.47 +/- 0.77 liter. kg-1). Although AmB in lipid emulsion is apparently cleared faster and distributes more widely than AmB in dextrose, this study did not reveal any significant advantage with respect to safety and tolerance in the administration of AmB in lipid emulsion compared to its administration in dextrose in children with malignant disease.

Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Fat Emulsions, Intravenous; Glucose; Humans; Infant; Neoplasms; Prospective Studies

A multicentric randomized trial was undertaken to compare the toxicity of amphotericin B in 5% dextrose with that of amphotericin B in a fat emulsion (Intralipid) in cancer patients. Group 1 (n = 33) received amphotericin B diluted in 5% dextrose with premedication consisting of promethazine plus an antipyretic. Group 2 (n = 28) received amphotericin B diluted in 20% Intralipid without premedication. Amphotericin B was infused daily at a dose of 1 mg/kg of body weight over a 1-h period to members of both groups for empirical antifungal therapy (in neutropenic patients) or for the treatment of documented fungal infections. The majority of patients (80%) received empirical amphotericin B treatment. The two groups were comparable with regard to age, gender, underlying disease, and the following baseline characteristics: use of other nephrotoxic drugs and serum levels of potassium and creatinine. The median cumulative doses of amphotericin B were 240 mg in group 1 and 245 mg in group 2 (P = 0.73). Acute adverse events occurred in 88% of patients in group 1 and in 71% of those in group 2 (P = 0.11). Forty percent of the infusions in group 1 were associated with fever, compared to 23% in group 2 (P < 0.0001). In addition, patients in group 2 required less meperidine for the control of acute adverse events (P = 0.008), and fewer members of this group presented with hypokalemia (P = 0.004) or rigors (P < 0.0001). There was no difference in the proportions of patients with nephrotoxicity (P = 0.44). The success rates of empirical antifungal treatment were similar in the two groups (P = 0.9). Amphotericin B diluted in a lipid emulsion seems to be associated with a smaller number of acute adverse events and fewer cases of hypokalemia than amphotericin B diluted in 5% dextrose.

Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Child, Preschool; Fat Emulsions, Intravenous; Female; Glucose; Humans; Infant; Male; Middle Aged; Neoplasms

Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated.. We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection.. Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia.. These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Female; Fever; Fluconazole; Humans; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Treatment Outcome

Shivering is experienced by up to 70% of patients undergoing amphotericin B therapy. Treatment with meperidine hydrochloride, currently the most widely used medication for controlling amphotericin B-induced shivering, was compared with nefopam hydrochloride, which has been successfully used to treat post-operative shivering.. Forty-five patients with cancer and systemic fungal infections randomly received nefopam hydrochloride, 0.3 mg/kg, meperidine hydrochloride, 0.7 mg/kg, or saline solution intravenously 15 minutes before the cessation of amphotericin B infusion (1 mg/kg for 45 minutes). If shivering persisted, patients in the control (saline solution) group received either nefopam hydrochloride, 0.3 mg/kg, or meperidine hydrochloride, 0.7 mg/kg.. Occurrence of shivering 15 minutes after the cessation of amphotericin B infusion was significantly less frequent in the nefopam (6.6%) and meperidine (40%) groups compared with the control group (66.6%). The incidence of shivering in the nefopam group with respect to the meperidine group was also significantly reduced. Moreover, nefopam administration to 5 persistently shivering patients in the control group definitively stopped the shivering in all of them (100%) in a mean (+/- SD) time of 29.1 +/- 4.8 seconds, while meperidine terminated shivering in 4 (80%) of 5 patients in a mean (+/- SD) time of 200.0 +/- 30.2 seconds. The adverse reactions that can be ascribed to nefopam or meperidine use were nausea and sedation, respectively, and may be considered negligible.. Nefopam seems to be more effective than meperidine in preventing and quickly suppressing amphotericin B-induced shivering.

Topics: Adult; Aged; Amphotericin B; Analgesics, Non-Narcotic; Analgesics, Opioid; Antifungal Agents; Antineoplastic Agents; Female; Humans; Male; Meperidine; Middle Aged; Mycoses; Nefopam; Neoplasms; Shivering; Treatment Outcome

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B. Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15 microg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 microg/mL had peak levels exceeding 40 microg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity. A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of gram-positive bacteremia in cancer patients.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Case-Control Studies; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Humans; Kidney Diseases; Neoplasms; Neutropenia; Risk Factors; Slovakia; Vancomycin

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Fever; Fluconazole; Humans; Immunocompromised Host; Infant; Male; Middle Aged; Mycoses; Neoplasms; Opportunistic Infections; Prospective Studies; Treatment Outcome

A randomized, comparative study was conducted in 502 patients in 23 centres world-wide to assess the efficacy and safety of fluconazole versus nystatin and amphotericin B for prevention of fungal infection in a severely immunocompromised pediatric population. Patients scheduled within 48 hours to undergo chemotherapy or radiotherapy for hematological or oncological malignancies were randomly allocated to receive 3 mg/kg oral fluconazole once daily, 50,000 U/kg oral nystatin four times daily or 25 mg/kg oral amphotericin B four times daily. Prophylaxis began with the initiation of chemotherapy or radiotherapy and continued throughout a patient's hospital stay or period of neutropenia as necessary. The mean duration of fluconazole prophylaxis was 27.8 days and of the oral polyenes 29.2 days. The outcome of prophylaxis with fluconazole was significantly superior to that with the polyenes (p = 0.01). Mycologically verified infections occurred in 5 patients (2.1%) given fluconazole and in 21 (8.4%) given polyenes (p = 0.002). Clinical evaluation at the end of prophylaxis showed that the clinical outcome was definitely or possibly successful in 87% in the fluconazole group and 82% in the polyenes group with no significant differences between the treatment groups. Mycological evaluation demonstrated reduction or control of colonization in 84% in the fluconazole group and 85% in the polyenes group, again with no significant between-group differences. Possibly drug-related side effects, mainly mild to moderate gastrointestinal disturbances, were reported in 38 patients given fluconazole, with eight subsequent withdrawals, and in 21 patients given oral polyenes, with three subsequent withdrawals. Laboratory test abnormalities occurred in 28 patients given fluconazole and 24 given polyenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Amphotericin B; Candida; Child; Child, Preschool; Female; Fluconazole; Hematologic Diseases; Humans; Immunocompromised Host; Infant; Infant, Newborn; Male; Mycoses; Neoplasms; Nystatin

The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7%; P = 0.43); death was caused by primary gram-positive infections in three patients (1%) in each treatment group. When used for initial empirical antibiotic therapy in febrile, neutropenic patients, teicoplanin was at least as efficacious as vancomycin, but it was associated with fewer side effects.

Topics: Adolescent; Adult; Aged; Amikacin; Amphotericin B; Bacteremia; Ceftazidime; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacterial Infections; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Prospective Studies; Teicoplanin; Vancomycin

Topics: Adult; Amphotericin B; Anemia, Aplastic; Bone Marrow Transplantation; Candidiasis; Female; Humans; Incidence; Leukemia; Liposomes; Male; Metabolic Diseases; Neoplasms; Transplantation, Autologous; Transplantation, Homologous

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.

Topics: Amphotericin B; Bone Marrow Transplantation; Candidiasis; Disease Susceptibility; Double-Blind Method; Fluconazole; Humans; Immunocompromised Host; Neoplasms; Neutropenia; Survival Rate

We compared high-dose ketoconazole (800 mg/kg per day, orally) with amphotericin B (0.5 mg/kg per day, intravenously) for empirical antifungal therapy in a prospective, randomized study of persistently or recurrently febrile granulocytopenic cancer patients. Among 97 patients eligible for empirical antifungal therapy, 20 (21%) of these patients were ineligible for randomization to ketoconazole treatment because of their inability to tolerate oral medications. Among 72 patients eligible for randomization, 64 were assessable (32 in each arm of the study). Five of six patients with proved fungal infections who were randomized to receive ketoconazole treatment required crossover to amphotericin B treatment because of progressive infection. The conditions of three of these five patients improved after receiving amphotericin B. The frequency of transaminase elevation was higher in those receiving ketoconazole, while the frequency of azotemia was higher in those receiving amphotericin B. Bioavailability of ketoconazole was unpredictable. Amphotericin B remains the drug of choice for empirical antifungal therapy in granulocytopenic patients; whereas, lack of a parenteral formulation, ineffectiveness against proved mycoses, and unreliable bioavailability preclude high-dose ketoconazole from being an appropriate compound for this purpose.

Topics: Adult; Agranulocytosis; Amphotericin B; Fever; Humans; Immune Tolerance; Ketoconazole; Mycoses; Neoplasms; Prospective Studies

We report a prospective, randomized, controlled study of antifungal chemoprophylaxis in forty immunocompromised children with hematologic malignancies, receiving respectively itraconazole, ketoconazole, amphotericin-B and no prophylaxis. Fungal isolates from patients' saliva or stools were obtained from 19/40 patients (Candida albicans from 15 patients). Disseminated infection was never observed. Fungal isolates were significantly less frequent in the ketoconazole group of patients vs any other group. Systemic antifungal chemoprophylaxis with ketoconazole appears more effective even than the recently introduced itraconazole.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Feces; Female; Humans; Infant; Itraconazole; Ketoconazole; Male; Mycoses; Neoplasms; Pharynx; Prospective Studies

The optimal management of fever in granulocytopenic patients remains controversial. Invasive fungal infections are common and life-threatening but are difficult to diagnose early. In this randomized study, we investigated the potential value of empiric administration of amphotericin B (versus no empiric antifungal therapy) in 132 patients remaining febrile and granulocytopenic despite broad-spectrum antibiotic therapy for four days.. The patients were divided into two groups: 68 who were randomly assigned to receive empiric amphotericin B, and 64 who were randomly assigned to continue only the protocol antibiotics that they were already receiving. Amphotericin B was administered intravenously as follows: every other day at a dose of 1.2 mg/kg body weight or daily at a dose of 0.6 mg/kg body weight. Clinical response was evaluated as success or failure, depending upon the febrile course after randomization.. Based on the evolution of fever, the response rate was 69% in the group of patients receiving empiric amphotericin B and 53% for the other group (p = 0.09). There were six documented (four severe) fungal infections in 64 patients randomized not to receive the antifungal therapy as compared to only one fungemia among 68 patients treated empirically with amphotericin B (p = 0.1). No deaths due to fungal infection occurred among the patients receiving empiric amphotericin B compared to four in the other group (p = 0.05). However, this study did not demonstrate a difference in survival between the two groups of patients (with or without empiric amphotericin B). The benefit of empiric administration of amphotericin B was primarily observed in specific subgroups of patients, such as those who did not receive any antifungal prophylaxis (78% versus 45%, p = 0.04), those who were severely granulocytopenic (69% versus 46%, p = 0.06), febrile patients with a clinically documented infection (75% versus 41%, p = 0.03), and patients older than 15 years of age (67% versus 47%, p = 0.06).. These data suggest a benefit for early amphotericin B treatment in granulocytopenic patients with continued fever despite antibiotic therapy.

Topics: Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Clinical Trials as Topic; Fever; Humans; Infusions, Intravenous; Multicenter Studies as Topic; Mycoses; Neoplasms; Random Allocation; Regression Analysis; Time Factors

Topics: Adult; Amphotericin B; Animals; Antimetabolites; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buthionine Sulfoximine; Calcium Channel Blockers; Calmodulin; Cardiotonic Agents; Child; Clinical Trials as Topic; Dipyridamole; Drug Evaluation; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Female; Humans; Ketoconazole; Male; Methionine Sulfoximine; Mice; Neoplasms; Nitroimidazoles; Xanthines

Fungal infections in neutropenic cancer patients have increased in frequency and constitute an important cause of morbidity and mortality. Empiric antifungal therapy is often administered to those patients who have failed to respond to antibacterial antibiotics. We conducted a prospective, randomized trial of amphotericin B and ketoconazole for 172 neutropenic cancer patients with presumed or proven fungal infections. Overall, amphotericin B and ketoconazole were equally effective. Amphotericin B may have been more effective than ketoconazole for the treatment of pneumonia. Also, five of eight Candida tropicalis infections treated with amphotericin B responded, whereas all eight infections treated with ketoconazole failed to respond (P = 0.03). Response rates for localized fungal infections were similar with both drugs. Ketoconazole should not be used as empiric antifungal therapy at institutions where there is a high frequency of infections caused by Aspergillus spp. or C. tropicalis because this agent lacks activity in vitro against these species.

Topics: Adolescent; Adult; Aged; Amphotericin B; Female; Humans; Ketoconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Prospective Studies; Random Allocation

As invasive fungal infection remains a common problem in the management of cancer patients, chemoprophylaxis of these opportunistic infections is desperately needed. The most frequently investigated antifungal agents have been nystatin, amphotericin B, and ketoconazole. In placebo-controlled studies, high doses of antifungal agents decreased the positive results from surveillance cultures, and there is some suggestion that such chemoprophylaxis may reduce the incidence of invasive candidiasis in neutropenic cancer patients. However, no oral chemoprophylaxis has effectively prevented aspergillosis or mucormycoses in these patients. There are still many areas of controversy, and the most adequate regimens, if any, remain to be defined.

Topics: Administration, Oral; Administration, Topical; Amphotericin B; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Miconazole; Mycoses; Neoplasms; Nystatin

The prevention of fungal infections in granulocytopenic patients seems necessary to improve the final outcome of neoplastic patients. In particular, aspergillosis and candidiasis represent common life-threatening infections among the patients with acute hematological malignancies. Despite extensive investigations during this last decade, the optimal approaches to prevent these complications are still controversial. This situation probably reflects and stresses the numerous factors which predispose to these opportunistic fungal infections. Therefore, the effective prophylaxis of candidiasis and aspergillosis should result from the use of basic and specific approaches. General and simple measures including well trained personnel (physicians, nurses but also individuals in charge of the housekeeping, etc.), careful patient teaching of personal hygiene and control of the food intake (limited to cooked food diet), will reduce the acquisition of potential fungal pathogens. Moreover, the isolation in a laminar air flow room seems to be the optimal specific technique to prevent the colonization as well as the development of pulmonary aspergillosis. The meticulous evaluation of the respiratory sinus status as well as surveillance cultures obtained from the nose have been shown to be helpful to predict patients at high risks. Until now, there is no systemic chemoprophylaxis available to decrease the incidence of invasive aspergillosis. However, the topical application of antifungal agent using nasal spray or aerosols should be further investigated. Exogenous candidiasis such as catheter or TPN products related yeast infections can be avoided by aseptic manipulations. Endogenous candidiasis, resulting from the dissemination of the yeasts from the gastro-intestinal tract (which represents the major reservoir), are still much more difficult to prevent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Agranulocytosis; Amphotericin B; Aspergillosis; Candidiasis; Clinical Trials as Topic; Humans; Ketoconazole; Neoplasms; Neutropenia; Nystatin; Patient Isolation

Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non-Candida albicans species in mixed oral infections with Candida albicans. Non-C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity.. An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014-2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied.. Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2-3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non-C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin.. C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer.. The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candida albicans; Candidiasis, Oral; Drug Resistance, Fungal; Fluconazole; Humans; Microbial Sensitivity Tests; Neoplasms

Opportunistic fungal infections by. Over a period of three years, 325 cancer patients suspected to. Seventy-four cancer patients had. The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.

Topics: Amphotericin B; Anidulafungin; Antifungal Agents; Candida; Candidemia; Candidiasis; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Microbial Sensitivity Tests; Neoplasms

Amphotericin B is a broad-spectrum antifungal agent and is the backbone of the treatment for medically important opportunistic fungal pathogens in children. This study aimed to compare the nephrotoxicity associated with L-AmB in children with acute lymphoblastic leukemia and acute myeloid leukemia.. A total of 112 pediatric acute lymphoblastic leukemia or acute myeloid leukemia patients who received treatment with L-AmB (Ambisome®) at the University of Health Sciences Dr Behcet Uz Children's Hospital over 7 years were included. The incidence of hypokalemia, decreased estimated glomerular filtration rate and presence of acute kidney injury was recorded.. The average L-AmB treatment duration was 17.1±15.0 days. Five patients (4.4%) of the patients had grade I acute renal injury according to KDIGO criteria and 16 patients (14.2%) had increased risk for kidney injury according to RIFLE criteria. There were no patients with eGFR decrease above 50% and no renal injury and failure were observed during L-AmB treatment. The rate of patients with hypokalemia in the pre-treatment was 17.9% and the post-L-AmB group was 50.0%. The rate of hypokalemia was higher in the post-treatment group (P=0.0015). Among the 112 patients, only two patients (1.7%) required cessation of L-AmB treatment due to resistant hypokalemia despite supplementation.. Hypokalemia was more common compared to glomerulotoxicity and acute renal injury (according to KDIGO and RIFLE criteria) in pediatric leukemia patients treated with L-AmB. Hypokalemia developed in nearly half of the patients and the study shows the need for randomized controlled trials and strategies for hypokalemia associated with L-AmB treatment.

Topics: Acute Kidney Injury; Amphotericin B; Child; Humans; Kidney; Neoplasms; Retrospective Studies

There is a worldwide concern regarding the antimicrobial resistance and the inappropriate use of antifungal agents, which had led to an ever-increasing antifungal resistance. This study aimed to identify the antifungal susceptibility of colonized Candida species isolated from pediatric patients with cancer and evaluate the clinical impact of antifungal stewardship (AFS) interventions on the antifungal susceptibility of colonized Candida species. Candida species colonization was evaluated among hospitalized children with cancer in a tertiary teaching hospital, Shiraz 2017-2018. Samples were collected from the mouth, nose, urine, and stool of the patients admitted to our center and cultured on sabouraud dextrose agar. The isolated yeasts identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). DNA Extracted and PCR amplification was performed using the ITS1 and ITS4 primer pairs and Msp I enzyme. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) for amphotericin B, caspofungin, and azoles. The prevalence of Candida albicans in the present study was significantly higher than other Candida species. Candida albicans species were completely susceptible to the azoles. The susceptibility rate of C. albicans to amphotericin B and caspofungin was 93.1% and 97.1%, respectively. The fluconazole MIC values of Candida albicans decreased significantly during the post-AFS period (P < 0.001; mean difference: 72.3; 95% CI of the difference: 47.36-98.62). We found that ‏52.5% (53/117) of the isolated C. albicans were azole-resistant before AFS implementation, while only 1.5% (2/102) of the isolates were resistant after implementation of the AFS program (P < 0.001). C. albicans fluconazole and caspofungin resistant rate also decreased significantly (P < 0.001) after implementation of the AFS program [26 (32.9%) versus 0 (0.0%) and 11 (10.9%) versus 1 (0.9%), respectively]. Besides, fluconazole use (p < 0.05) and fluconazole expenditure reduced significantly (about one thousand US$ per year) after the AFS program. Our results confirm the positive effect of optimized antifungal usage and bedside intervention on the susceptibility of Candida species after the implementation of the AFS program. C. albicans and C. glabrata exhibited a significant increase in susceptibility after the execution of the AFS program.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Antimicrobial Stewardship; Candida; Caspofungin; Child; Child, Preschool; Colony Count, Microbial; Disease Susceptibility; Drug Resistance, Fungal; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Neoplasms; Triazoles

This study determined the prevalence of Candida spp. in the saliva of cancer patients. Furthermore, we assessed the antimicrobial activity of mouthwashes against the isolated strains and its susceptibility to amphotericin B and fluconazole.. Thirty-four cancer patients undergoing radiotherapy, chemotherapy alone or combined treatment were investigated for oral Candida spp. colonization and compared in regard to mucositis presence. The maximum inhibitory dilution was used to assess the antimicrobial activity of Periogard®, Cepacol® Cool Ice and 0.12 % Chlorhexidine Digluconate mouthwashes against the isolates. In parallel, susceptibility to amphotericin B and fluconazole was determined by agar-based E-test. Data did not adhere to normal distribution as inferred by the Shapiro-Wilk test and statistical analysis was conducted by non-parametric McNemar test (α0.05).. Twenty-seven participants (79.4 %) were male, 19 (55.9 %) had mucositis and 9 (26.5 %) were colonized by Candida spp. 12 different strains of Candida spp. were isolated, being Candida albicans the most prevalent strain. Risk of Candida spp. colonization was increased by almost twofold among the participants with mucositis (odds ratio: 1.84; 95 % confidence interval: 0.37-9.07). Mouthwash Cepacol® Cool Ice presented better antimicrobial activity against Candida spp. while 0.12 % Chlorhexidine exhibited the worst activity. All strains were sensitive to amphotericin B, and 2 non-albicans strains were dose-dependent sensitive to fluconazole.. Considering the increased risk of colonization byCandida spp. in patients with mucositis, and the emergence of antifungal drug resistance, the antiseptics use could benefit the maintenance of cancer patient's oral health.

Topics: Amphotericin B; Antifungal Agents; Candida; Drug Resistance, Fungal; Female; Fluconazole; Humans; Male; Microbial Sensitivity Tests; Mouthwashes; Neoplasms; Prevalence; Saliva

Taiwanofungus camphoratus is a parasitic mushroom found in the heartwood of Cinnamomum kanehirai and is used as a nutritional supplement. It has an anticancer action, both alone and synergistically with amphotericin B (AmB).. The study intended to assess the efficacy of a T camphoratus ethanol extract (TCEE) combined with AmB for patients with metastatic cancer whose cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy.. The research team performed a retrospective analysis as a pilot study.. The study took place at a single hospital (Taipei Medical University Hospital, Taipei, Taiwan).. Participants were 9 patients at the hospital who were terminally ill with metastatic cancer.. The participants had received daily doses of 2-3 g of the TCEE in combination with a weekly dose of 20-25 mg of AmB in 500 cc of 5% glucose water, given intravenously in 4-6 h.. Outcome measures included (1) a primary evaluation index measuring the efficacy of the treatment; (2) a measure of tumor burden that was estimated using the response evaluation criteria in solid tumors (RECIST 1.1), (3) a secondary evaluation index measuring survival duration, and (4) safety.. The mean treatment time was 54.4 ± 18.3 wk. At the end of the study, 2 patients showed a continued complete response, 1 patient had a continued partial response, and 1 patient showed a stable disease. The other 5 participants had times to progression ranging from 24 to 48 wk, with a mean of 35.6 wk. The mean survival time was 57.8 ± 18.5 wk, and 5 patients were still alive at the end of the study.. For patients whose metastatic cancer did not respond to multiline chemotherapy or who were unwilling to receive chemotherapy, the use of TCEE as an adjuvant therapy to AmB resulted in tumor suppression and a delay in time to disease progression. The preliminary results reported here can be used to guide a future, more extensive clinical study of the combination.

Topics: Amphotericin B; Antifungal Agents; Antrodia; Biological Products; Ethanol; Humans; Neoplasm Metastasis; Neoplasms; Pilot Projects; Retrospective Studies; Taiwan; Treatment Outcome

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Cancer Care Facilities; Child; Child, Preschool; Egypt; Female; Hematologic Neoplasms; Hospitals, Pediatric; Humans; Immunocompromised Host; Male; Mucormycosis; Neoplasms; Opportunistic Infections; Retrospective Studies; Risk Factors; Treatment Outcome; Triazoles

Conidiobolomycosis is a rare fungal infection that affects adults in tropical regions. We report a 42-year-old male patient who was referred to the Sulaiman Al Habib Hospital, Dubai, United Arab Emirates (UAE), in 2013 with excessive nasal bleeding and a suspected nasal tumour. He reported having briefly visited central India nine months previously. Computed tomography and magnetic resonance imaging showed a highly vascularised mass in the nasal cavity. However, after surgical excision, initial treatment with amphotericin B deoxycholate was unsuccessful and the disease progressed, leading to external and internal nasal deformation and necessitating further excision and facial reconstruction. Histopathological analysis of the second biopsy revealed Splendore-Hoeppli changes consistent with a fungal infection. Microbiological findings subsequently confirmed

Topics: Adult; Amphotericin B; Antifungal Agents; Conidiobolus; Humans; Male; Mycoses; Nasal Cavity; Neoplasms; Tomography, X-Ray Computed; United Arab Emirates; Zygomycosis

The 28-day crude mortality rate in 68 cancer patients with fluconazole-susceptible dose-dependent

Topics: Amphotericin B; Antifungal Agents; Azoles; Candida glabrata; Candidemia; Drug Resistance, Fungal; Echinocandins; Female; Fluconazole; Humans; Male; Middle Aged; Neoplasms; Polyenes; Retrospective Studies

Immunomodulatory drugs (IMiDs) present one example of immunomodulatory agents that improve cancer immunotherapy. Based on the cytotoxic activity of natural killer (NK) cells against cancer cells, a high throughput screening method for the identification of novel immunomodulatory molecules with the potential to stimulate NK cell cytotoxicity against cancer cells was designed and tested using an approved drug library. Among the primary hit compounds, the anti-fungal drug amphotericin B (AMP-B) increased the cytotoxicity of NK cell line and human primary NK cells in a direct manner. The increase in NK cell activity was related to increased formation of NK-target cell conjugates and the subsequent granule polarization toward target cells. The results of the present study indicate that AMP-B could serve a dual function as an anti-fungal and immunomodulatory drug.

Topics: Amphotericin B; Antifungal Agents; Cell Line; Cells, Cultured; Cytoplasmic Granules; Humans; Immunologic Factors; Immunotherapy; Killer Cells, Natural; Neoplasms

A set of crown ethyl acyl derivatives based on 18-crown-6 moiety was synthesized and evaluated for biological activity. In vitro antiproliferative profiling demonstrated significant activities against HBL-100, HeLa, SW1573 and WiDr human cell lines. The most active compound exhibited GI

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antineoplastic Agents; Candida albicans; Candidiasis; Cell Line, Tumor; Cell Proliferation; Crown Ethers; Drug Screening Assays, Antitumor; Humans; Neoplasms; Staphylococcal Infections; Staphylococcus aureus; Structure-Activity Relationship

A 2.5-year-old girl was admitted due to splenomegaly and pancytopenia. Laboratory analysis revealed pancytopenia and hypergammaglobulinemia, and due to the absence of fever and the relevant clinical and hematological presentation the child was initially suspected for acute lymphoblastic leukemia. Bone marrow aspiration displayed macrophages and extracellular space containing Leishmania amastigotes. Visceral leishmaniasis diagnosis due to Leishmania infantum was confirmed by the presence of high titers of Leishmania antibodies and by PCR. The patient was successfully treated with liposomal amphotericin B but during the third post-treatment day significant increases in the levels of serum uric acid, blood urea nitrogen, and phosphate were registered. The child was successfully treated with hydration and urine alkalization and resulted in full recovery of the metabolic abnormalities.

Topics: Amphotericin B; Child, Preschool; Female; Humans; Leishmania infantum; Leishmaniasis, Visceral; Neoplasms; Pancytopenia; Splenomegaly; Syndrome

The clinical, microbiological, and histopathological findings of six patients with mucosal leishmaniasis are reported. Five of these patients were Spanish with no history of travel abroad, while the other was from Bolivia but had lived in Spain for more than 5 years. Two patients had no underlying disease, while the other four had several other medical conditions. Lesions were located in the nose in three patients and in the larynx in the other three. Symptoms included difficulty in swallowing, nasal obstruction, dysphonia, and polypoid lesions mimicking cancer. The diagnosis was based on the identification of parasites, or on PCR assay or culture. Five patients were treated with liposomal amphotericin B and the other with antimonial compounds.

Topics: Adult; Aged; Amphotericin B; Animals; Female; Humans; Larynx; Leishmania infantum; Leishmaniasis, Mucocutaneous; Male; Middle Aged; Neoplasms; Nose; Polymerase Chain Reaction; Spain

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient's risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.

Topics: Amphotericin B; Antifungal Agents; Candidiasis, Invasive; Catheter-Related Infections; Chemotherapy-Induced Febrile Neutropenia; Clinical Trials as Topic; Combined Modality Therapy; Drug Monitoring; Drug Therapy, Combination; Echinocandins; Fungemia; Humans; Immunocompromised Host; Immunotherapy; Invasive Pulmonary Aspergillosis; Mycoses; Neoplasms; Salvage Therapy; Triazoles

Topics: Amphotericin B; Antifungal Agents; Humans; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Pyrimidines; Triazoles

Many scientists have reported Candida species to be of great concern because of the high frequency that they colonize and infect human hosts, particularly cancer patients. Moreover, in the last decades Candida species have developed resistance to many antifungal agents. Based on this, we aimed to identify and determine the prevalence of Candida spp from blood culture bottles among cancer patients and their antifungal resistance pattern.. From the blood culture bottles isolation and identification of the Candida spp were performed by conventional microbiological techniques. The in vitro antibiotic resistance pattern of the isolates was determined by CLSI guidelines. Genomic DNA was isolated and amplified. Each gene was separated by agar gel electrophoresis.. Identification of Candida spp was based on the presence of yeast cells in direct examination, culture and DNA extraction. Of the 68 blood samples collected during the study period (April 2013 to October 2013), five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were identified as Candida albicans and 3 (60%) were Candida non-albicans.. High resistance to amphotricin B was observed among all the Candida non-albicans isolates. Regular investigations into antifungal resistance will help us to get an updated knowledge about their antibiotic resistance pattern which may help the physician in selecting the antibiotics for empirical therapy.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidiasis; DNA, Fungal; Drug Resistance, Bacterial; Humans; Incidence; Neoplasms; Polymerase Chain Reaction; Prognosis

Aerosolized amphotericin B lipid complex (aeABLC) has been successfully used to prevent fungal disease. Experience with aeABLC as treatment of fungal lung disease is limited.. We evaluated the safety and efficacy of aeABLC adjunct therapy for fungal lung disease in a retrospective study of 32 immunosuppressed adults. All values are given as ± standard deviation.. National Cancer Institute-designated Comprehensive Cancer Center.. Acute leukemia (69%) and severe neutropenia (63%) were common. Fifty-six percent of patients had undergone allogeneic hematopoietic stem cell transplantation 185 ± 424 days prior to aeABLC was commenced.. High-dose corticosteroids were administered during aeABLC in 28% of patients. Fungal lung disease was proven or probable in 41% of patients. Most patients (78%) received concurrent systemic antifungal therapy for a median of 14 ± 18 days before aeABLC. The median cumulative aeABLC dose was 1050 ± 2368 mg, and the median duration of aeABLC therapy was 28 ± 130 days. Most patients (78%) received 50 mg aeABLC twice daily. Partial or complete resolution of fungal lung disease was noted in 50% of patients. In three patients (9%) modest cough, mild bronchospasm, and transient chest pain with accompanying nausea and vomiting resolved completely after discontinuation of aeABLC. No patient required hospitalization for drug toxicity or had a serious (grade III or IV) drug-related adverse event.. Treatment with aeABLC was tolerated without serious toxicity and may be considered in the setting of severe immunosuppression, cancer, and/or hematopoietic stem cell transplantation in patients with difficult-to-treat fungal lung disease.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lung Diseases, Fungal; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies; Severity of Illness Index; Young Adult

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Brazil; Candida; Candidemia; Child; Child, Preschool; Cross Infection; Female; Hematologic Neoplasms; Hospital Mortality; Humans; Infant; Intensive Care Units; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tertiary Care Centers; Young Adult

The tolerability of amphotericin B lipid complex in patients with previous severe infusion reactions to liposomal amphotericin B is unclear. We reviewed the charts of 40 such patients at a tertiary care cancer center and found that amphotericin B lipid complex administration was uneventful in 34 patients (85% [95% confidence interval, 69%-93%]).

Topics: Adult; Amphotericin B; Antifungal Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusion Pumps; Male; Middle Aged; Neoplasms; Retrospective Studies; Tertiary Care Centers

Literature provides much evidence regarding liposomal amphotericin B treatment for fungal infections in neonates and infants. Relevant data regarding critically ill paediatric patients of older age are scarce. We aimed to present our experience regarding liposomal amphotericin B use in critically ill paediatric patients from a tertiary-care paediatric hospital in Athens, Greece.. We prospectively identified all paediatric patients who received treatment with liposomal amphotericin B in the intensive care unit of a tertiary-care paediatric hospital during a 3-year period (2005-2008). Data were retrieved from the evaluation of the available medical records.. Twenty-three (nine females, mean age: 26·4 months, range: 5-39 months) critically ill paediatric patients were included; 12 had malignancy. In 16 of the 23 included children, liposomal amphotericin B was administered for the treatment of confirmed fungal infections (all but one were invasive), whereas in seven patients, it was used as pre-emptive treatment. One patient received voriconazole concomitantly. Eleven of the 16 children with documented infections were cured; five improved. Six of the seven children who received pre-emptive treatment also showed clinical improvement. Nine deaths were noted, all attributed to underlying diseases. Two cases of hepatotoxicity and one case of nephrotoxicity (all leading to drug-discontinuation) occurred. Seven and five cases of mild reversible hypokalaemia and hyponatraemia, respectively, were also noted.. According to the findings of our small case series, liposomal amphotericin B may provide a useful treatment option for fungal infections of vulnerable critically ill paediatric patients with considerable comorbidity.

Topics: Amphotericin B; Antifungal Agents; Chemical and Drug Induced Liver Injury; Child, Preschool; Comorbidity; Drug Monitoring; Female; Greece; Hospitals, Pediatric; Humans; Hypokalemia; Hyponatremia; Infant; Intensive Care Units, Pediatric; Liposomes; Male; Mycoses; Neoplasms; Prospective Studies; Renal Insufficiency

The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy.. Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment.. Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%-11.0%] in this population. It was most frequent in patients treated with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%).. OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidiasis; Candidiasis, Oral; Female; France; Humans; Male; Middle Aged; Neoplasms; Oropharynx; Pharyngeal Diseases; Young Adult

Intensified chemotherapy and hematopoietic stem cell transplantation result in severe and prolonged granulocytopenia with an increased risk of invasive fungal infections. The major fungal species that cause serious infections in cancer patients are Candida species and Aspergillus species. The main features of Candida infection in this context are oropharyngeal candidiasis and Candida esophagitis, chronic disseminated candidiasis, also known as hepatosplenic candidiasis, and candidemia. Aspergillus can cause severe lung infection but also sinusal or CNS infection. Because invasive fungal infections are severe and often life-threatening, preventive and empirical managements have become standard practice. An increasing number of antifungal drugs is now available, notably lipid formulations of amphotericin B (liposomal amphotericin B), new azoles with broad spectrum of activity and echinocandin.

Topics: Agranulocytosis; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Azoles; Candidiasis; Child; Cryptococcosis; Echinocandins; Humans; Mycoses; Neoplasms; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Treatment Outcome

Fungal biofilms produce a small number of persister cells which can tolerate high concentrations of fungicidal agents. Persisters form upon attachment to a surface, an important step in the pathogenesis of Candida strains. The periodic application of antimicrobial agents may select for strains with increased levels of persister cells. In order to test this possibility, 150 isolates of Candida albicans and C. glabrata were obtained from cancer patients who were at high risk for the development of oral candidiasis and who had been treated with topical chlorhexidine once a day. Persister levels were measured by exposing biofilms growing in the wells of microtiter plates to high concentrations of amphotericin B and plating for survivors. The persister levels of the isolates varied from 0.2 to 9%, and strains isolated from patients with long-term carriage had high levels of persisters. High-persister strains were isolated from every patient with Candida carriage of more than 8 consecutive weeks but from no patients with transient carriage. All of the high-persister isolates had an amphotericin B MIC that was the same as that for the wild type, indicating that these strains were drug-tolerant rather than drug-resistant mutants. Biofilms of the majority of high-persister strains also showed an increased tolerance to chlorhexidine and had the same MIC for this antimicrobial as the wild type. This study suggests that persister cells are clinically relevant, and antimicrobial therapy selects for high-persister strains in vivo. The drug tolerance of persisters may be a critical but overlooked component responsible for antimicrobial drug failure and relapsing infections.

Topics: Adult; Aged; Biofilms; Candida albicans; Candidiasis; Carrier State; Chlorhexidine; Dose-Response Relationship, Drug; Female; Genes, Fungal; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mouth; Mouthwashes; Mutation; Neoplasms; Young Adult

Invasive zygomycosis accounts for a significant proportion of all invasive fungal diseases (IFD), but clinical data on the clinical course and treatment response are limited.. Fungiscope-A Global Rare Fungal Infection Registry is an international university-based case registry that collects data of patients with rare IFD, using a web-based electronic case form at www.fungiscope.net.. Forty-one patients with invasive zygomycosis from central Europe and Asia were registered. The most common underlying conditions were malignancies (n = 26; 63.4%), diabetes mellitus (n = 7; 17.1%) and solid organ transplantation (n = 4; 9.8%). Diagnosis was made by culture in 28 patients (68.3%) and by histology in 26 patients (63.4%). The main sites of infection were the lungs (n = 24; 58.5%), soft tissues (n = 8; 19.5%), rhino-sinu-orbital region (n = 8; 19.5%) and brain (n = 6; 14.6%). Disseminated infection of more than one non-contiguous site was seen in six patients (14.6%). Mycocladus corymbifer was the most frequently identified species (n = 10, 24.4%). A favourable response was observed in 23 patients (56.1%). Overall survival was 51.2% (n = 21). At diagnosis, four patients (9.8%) were on continuous antifungal prophylaxis with itraconazole (n = 1; 2.4%) or posaconazole (n = 3; 7.3%). Initial targeted treatment with activity against zygomycetes was administered to 34 patients (82.9%). Liposomal amphotericin B was associated with improved response (P = 0.012) and survival rates (P = 0.004).. Pathogen distribution and, consequently, drug susceptibility seem to vary across different geographic regions. Furthermore, protection from invasive zygomycosis for patients on posaconazole prophylaxis is not absolute. Our findings indicate that the use of liposomal amphotericin B as first-line treatment for patients diagnosed with zygomycoses merits further investigation, preferably in the form of a clinical trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Asia; Child; Child, Preschool; Databases, Factual; Diabetes Complications; Europe; Female; Humans; Immunocompromised Host; Male; Middle Aged; Mucorales; Neoplasms; Organ Transplantation; Survival Analysis; Treatment Outcome; Young Adult; Zygomycosis

Topics: Adrenal Cortex Hormones; Amphotericin B; Animals; Communicable Diseases; Cyclosporine; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Immunosuppressive Agents; Leishmania infantum; Leishmaniasis, Visceral; Liposomes; Lymphohistiocytosis, Hemophagocytic; Macrophages; Middle Aged; Neoplasms; Opportunistic Infections; Pancytopenia; Polymerase Chain Reaction; Splenomegaly

The purpose of this work was to identify differences in incidence, risk factors, microbiology, treatment, and clinical outcome of candidemia in neonates, children, and adults that might impact on management.. Cases of candidemia in Australia were identified prospectively by blood culture surveillance over 3 years. Episodes of candidemia in neonatal, pediatric, and adult age groups were analyzed and compared.. Of 1005 incident cases, 33 occurred in neonates, 110 in children, and 862 in adults. The respective annual age-specific incidences were 4.4, 0.9, and 1.8 per 100,000 population. Prematurity and ICU admission were major risk factors in neonates. Hematologic malignancy and neutropenia were significantly more frequent in children than in neonates and adults. Diabetes, renal disease, hemodialysis, and recent surgery were more common in adults. Candidemia was attributed to a vascular access device in 58% of neonates, 70% of children, and 44% of adults. Candida albicans caused approximately 48% of cases in all of the age groups. Candida parapsilosis was significantly more common in neonates and children (42% and 38% vs 15%). Candida glabrata was infrequent in neonates and children (9% and 3% vs 17%). Significantly more isolates from children were susceptible to fluconazole compared with those from adults (95% vs 75%). Fluconazole-resistant candidal isolates were infrequent in all of the age groups. Neonates and children were more likely to receive amphotericin B compared with adults. Adults were more likely to receive fluconazole. Survival rates at 30 days were 78% in neonates, 90% in children, and 70% in adults.. This study identifies significant differences in candidemia in neonates, children, and adults. Neonatologists and pediatricians must consider age-specific differences when interpreting adult studies and developing treatment and prevention guidelines.

Topics: Adult; Amphotericin B; Antifungal Agents; Australia; Candida albicans; Candidiasis; Child; Child, Preschool; Comorbidity; DNA Fingerprinting; Female; Fluconazole; Humans; Incidence; Infant, Newborn; Infant, Premature; Male; Neoplasms; Risk Factors; Seroepidemiologic Studies; Systemic Inflammatory Response Syndrome

To assess safety, tolerance and efficacy of liposomal amphotericin B (LAMB) in a large unselected series of paediatric cancer/haematopoietic stem cell transplantation (HSCT) patients requiring LAMB therapy.. The study included 84 children and adolescents (median age: 11 years) who received 141 consecutive courses of LAMB for prophylaxis (32), empirical therapy (83), possible (19) or probable/proven (7) invasive infections. LAMB was administered until intolerance or maximum efficacy at dosages individually determined by the responsible physician.. Fifty-nine courses were post-HSCT (42%, 49 allogeneic), and 92 courses were started during granulocytopenia (65%). The median duration of LAMB therapy was 13 days (range 1-79), and the median maximum dosage was 2.8 mg/kg (range 0.93-5.10). Mild-to-moderate adverse events were noted during 109 courses (77%; hepatic, 58.8%; electrolyte wasting, 52.5%; renal, 31.9%; infusion-related reactions, 8.5%); adverse events necessitating discontinuation of LAMB occurred in 6 courses (4.3%; renal, 3; anaphylaxis, 2; hepatic, 1). While median hepatic transaminase, alkaline phosphatase and blood urea nitrogen values were slightly (P < 0.01) higher at end of treatment (EOT), bilirubin and creatinine values were not different from baseline. Complete or partial responses were observed in 16/19 and 2/7 courses for possible and probable/proven invasive infections. Thirty-two of 33 courses of prophylaxis and 74 of 83 courses of empirical therapy were completed with success. Overall survival was 90.8% at 3 months post-EOT.. LAMB had acceptable safety and tolerance and was useful in prevention and treatment in unselected, mostly granulocytopenic paediatric patients undergoing treatment for cancer or HSCT.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Infant; Male; Mycoses; Neoplasms; Stem Cell Transplantation; Treatment Outcome; Young Adult

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second-line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future.

Topics: Administration, Oral; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Cephalosporins; Data Collection; Deoxycholic Acid; Drug Combinations; Drug Therapy, Combination; Fever; Fluoroquinolones; Hematopoietic Stem Cell Transplantation; Humans; Korea; Neoplasms; Neutropenia; Prospective Studies; Surveys and Questionnaires; Time Factors; Treatment Failure

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains. Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae fungemia was more frequently associated with stem cell transplant and neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less amenable to AMB therapy.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Fungal; Female; Fungemia; Humans; Male; Middle Aged; Mutation; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Female; Home Care Services, Hospital-Based; Humans; Infant; Infusions, Intravenous; Liposomes; Male; Neoplasms; Outpatients

Topics: Adult; Amphotericin B; Antifungal Agents; England; Humans; Male; Medication Errors; Mycoses; Neoplasms

We describe drug-drug interactions (DDIs) encountered with antifungals in clinical practice.. Retrospective observational study of hospitalized adults receiving systemic antifungal treatment in the intensive care unit (ICU) and in the infectious diseases unit (IDU) of the University Hospital of Bordeaux, France between 1996 and 2001. All treatment episodes with antifungal agent were examined and all prescribed concomitant medication identified for potential drug-drug interactions (PDDI)-serious events occurring during treatment were adjudicated for clinical DDI.. There were 150 treatment episodes with antifungal agent in 105 patients. Fluconazole was used in 48% of the treatment episodes, amphotericin B in 46%, itraconazole in 4.7% and flucytosine in 1.3%. One hundred and sixteen PDDIs were identified related to the use of amphotericin B (81.0%), fluconazole (17.2%) or itraconazole (1.7%). Of these, 22 were associated with a clinical evidence of adverse interaction (hypokalemia, increased creatininemia or nephrotoxicity). All these clinical drug-drug interactions (CDDIs) were with amphotericin B. They were due to furosemide (36.4%), cyclosporine (31.8%) and hydrocortisone (18.2%). PDDIs were mostly associated with leukaemia (40.4%), HIV infection (24.6%) and cancer (10.5%).. In ICU and IDU, systemic antifungal treatments lead to many PDDIs, mainly related to the type of antifungal used and to the pathology treated. Clinical DDI seem more common with amphotericin.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Creatinine; Cyclosporine; Drug Interactions; Female; Fluconazole; France; Furosemide; HIV Infections; Hospitals, University; Humans; Hydrocortisone; Hypokalemia; Intensive Care Units; Itraconazole; Kidney Diseases; Leukemia; Male; Middle Aged; Neoplasms; Retrospective Studies

Activity and efficacy of liposomal amphotericin B have been established for the treatment of severe fungal infections. Nephrotoxic side effects, especially during prolonged administration, are regarded as a major disadvantage. In this study we examined the response rates and side effects, particularly nephrotoxicity, of treatment with liposomal amphotericin B in a large cohort of patients.. 406 patients treated with liposomal amphotericin B between January 1999 and August 2003 in participating German hospitals were included. Documentation included demographic and clinical data, reason for the treatment with liposomal amphotericin B, length of treatment, response to antifungal treatment and side effects.. 42.4% of the 406 patients were females. Their ages ranged from 1 day to 77 years. 83 % of the patients had malignancies and 65.5 % had fever of unknown origin (FUO). Mean duration of treatment with liposomal amphotericin B was 20 +/- 20 days, at an average dose of 2.3 mg/kg/d. 209 patients (51.5 %) showed complete response (CR),105 patients (25.9 %) partial response (PR) and 51 (12.6 %) patients died during the observation. 80.0 % of patients with FUO showed complete or partial response of symptoms. Mean serum creatinine increased from 0.9 mg/kg before start of therapy with liposomal amphotericin B to 1.1 mg/kg during treatment. Side effects (common toxicity criteria > grade 1) occurred in 94 patients (23/2 %). Among these hypokalemia (6.2 %) and liver damage (5,2 %) were the most common. Nephrotoxicity was documented in 17 patients (4.2 %).. Liposomal amphotericin B is a safe and efficacious antifungal drug in the treatment of severe invasive fungal infections and fever of unknown origin. Nephrotoxicity is usually not a limiting factor when using liposomal amphotericin B, if it is administered in approved dosage.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Cohort Studies; Female; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Kidney; Liposomes; Male; Middle Aged; Mycoses; Neoplasms; Prospective Studies; Treatment Outcome

The objective of this study was to determine if total plasma and lipoprotein cholesterol (C) and triglyceride (TG) concentrations could predict the degree of nephrotoxicity caused by the antifungal agent amphotericin B (AmpB); and to use the average amount of potassium supplementation received daily as a indicator of nephrotoxicity in pediatric oncology patients.. Plasma samples from 18 patients (ages < 17 years) who were receiving AmpB due to suspected or confirmed fungal infection at British Columbia Children's Hospital were analyzed for lipid concentrations. The high density lipoprotein (HDL) fractions were separated by precipitation; total (TOT) plasma and fraction C and TG concentrations were measured by enzymatic colorimetric assays; and low density lipoprotein (LDL) C levels were determined by Friedewald's formula. Changes in serum creatinine levels from baseline and amounts of potassium supplementation were used as indicators of nephrotoxicity; both were obtained from patients' medical charts. Pearson correlation coefficients (r) were determined and considered significant if P < 0.05.. The total cumulative AmpB dose, adjusted for weight, does not seem to predict AmpB-induced nephrotoxicity. Positive but relatively weak correlations were found between total potassium supplementation and LDL C (r = 0.489, P < 0.02); and TOT C (r = 0.551, P < 0.01). In addition, a positive but relatively weak correlation between the average amount of potassium supplementation per day above baseline and HDL C (r = 0.407; P < 0.02) was observed.. Differences in total plasma and LDL cholesterol concentrations may be used as predictors of AmpB-induced nephrotoxicity in pediatric oncology patients.

Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Cholesterol; Creatinine; Female; Humans; Infant; Kidney Diseases; Kidney Function Tests; Male; Mycoses; Neoplasms; Prognosis; Triglycerides

To describe the clinical characteristics, treatment, and outcomes of cryptococcosis in HIV-negative patients.. HIV-negative adult patients with positive culture for Cryptococcus neoformans who attended Ramathibodi Hospital between 1987 and 2003 were retrospectively reviewed.. During the 17 year review period, 40 HIV-negative patients with cryptococcosis were identified. Of these, 37 patients had medical records available for study. The mean age was 49+/-18 (range 16-83) years and 73% were female. Twenty-four patients (65%) had associated underlying conditions. The most common associated conditions included immunosuppressive drug treatment (41%), presence of systemic lupus erythematosus (16%), malignancies (16%), and diabetes mellitus (14%). C. neoformans was mainly recovered from cerebrospinal fluid (32%), blood (28%), and sputum/bronchoalveolar lavage/lung tissue (28%). Twenty-three patients (62%) had disseminated cryptococcosis. Six of 14 patients with cryptococcal meningitis were asymptomatic. About half of the patients were treated with amphotericin B and subsequent fluconazole. Five patients (14%) were initially misdiagnosed and treated for tuberculosis or bacterial infection. The overall mortality rate was 27%.. Cryptococcosis is not rare in HIV-negative patients. The mortality rate is high. Early recognition of cryptococcosis and use of appropriate antifungal therapy in these patients may improve clinical outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Cryptococcosis; Cryptococcus neoformans; Diabetes Complications; Female; Fluconazole; Health Surveys; HIV Infections; HIV Seronegativity; Hospitals, University; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Male; Middle Aged; Neoplasms; Retrospective Studies; Thailand; Treatment Outcome

A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 pediatric oncology patients who received multiple doses of L-AmB with a dose range from 0.8 to 5.9 mg/kg of body weight/day. The patient cohort had an average age of 7 years (range, 0.2 to 17 years) and weighed an average of 28.8 +/- 19.8 kg. Population pharmacokinetic analyses were performed with NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion variability (BOV), and intraindividual variability were estimated. The influence of patient characteristics on the pharmacokinetics of L-AmB was explored. The final population pharmacokinetic model was evaluated by using a bootstrap sampling technique. The L-AmB plasma concentration-time data was described by a two-compartment pharmacokinetic model with zero-order input and first-order elimination. The population mean estimates of clearance (CL) and volume of distribution in the central compartment (V1) were 0.44 liters/h and 3.12 liters, respectively, and exhibited IIV (CL, 10%) and significant BOV (CL, 46% and V1, 56%). The covariate models were CL (liters/h) = 0.44 . e(0.0152.(WT-21)) and V1 (liters) = 3.12.e(0.0241.(WT-21)), where WT is the patient's body weight (kg) centered on the study population cohort median of 21 kg. Model evaluation by the bootstrap procedure indicated that the full pharmacokinetic model was robust and parameter estimates were accurate. In conclusion, the pharmacokinetics of L-AmB in pediatric oncology patients were adequately described by the developed population model. The model has been evaluated and can be used in the design of rational dosing strategies for L-AmB antifungal therapy in this special population.

Topics: Adolescent; Amphotericin B; Antifungal Agents; Body Surface Area; Body Weight; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Liposomes; Male; Models, Biological; Models, Statistical; Neoplasms; Software

Bloodstream infections due to Candida spp. are associated with significant mortality and morbidity. This study analysed the epidemiology and outcome of candidemia cases in a teaching hospital in central Taiwan.. We retrospectively studied the clinical characteristics and antifungal susceptibility of isolates and risk factors for mortality in 91 cases of candidemia treated from January 1, 2001 to June 30, 2003.. The mean age of the patients was 67 years (range, 30-90 years). Three episodes (3%) were community acquired. Adequate antifungal therapy was given to 78 patients (78%). Cancer (38.5%) and diabetes mellitus (36.3%) were the 2 most common underlying diseases. The most frequent risk factors identified for candidemia were prior broad-spectrum antibiotic use (84.6%), central venous catheterization (83.5%) and Candida colonization (79.5%). The most frequent isolates were Candida albicans (64.8%) and Candida tropicalis (19.8%). All of the C. albicans and C. tropicalis isolates were sensitive to fluconazole (minimal inhibitory concentration

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; APACHE; Candida; Candidiasis; Catheterization, Central Venous; Community-Acquired Infections; Cross Infection; Diabetes Complications; Female; Fluconazole; Fungemia; Hospitals; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Neoplasms; Prognosis; Retrospective Studies; Risk Factors; Shock; Statistics as Topic; Taiwan

The incidence and severity of fungal infections in children with malignant diseases treated with intensive chemotherapy or allogeneic hematopoietic cell transplantation on the hematology-oncology department Children's Hospital Salata Medical School University of Zagreb is analyzed. The efficacy of antifungal therapy is presented.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Child; Child, Preschool; Croatia; Deoxycholic Acid; Drug Combinations; Fungemia; Hematopoietic Stem Cell Transplantation; Hospitals, Pediatric; Hospitals, Teaching; Humans; Immunocompromised Host; Infant; Liposomes; Lung Diseases, Fungal; Mycoses; Neoplasms; Postoperative Complications; Retrospective Studies; Treatment Outcome

Invasive aspergillosis (IA) can occur despite prior prophylactic or empiric use of triazoles or amphotericin B (AMB). Although profound immunosuppression may account for breakthrough IA, resistance of Aspergillus to antifungals may also play a role. To examine this question, we measured the minimal inhibitory concentration of 105 Aspergillus isolates recovered from 105 cancer patients (64 with IA, 41 with Aspergillus colonization) to AMB, itraconazole (ITC), and voriconazole (VRC) using the National Committee for Clinical Laboratory Standards (NCCLS) M38-A microdilution and E-test methods. We also determined the minimal fungicidal concentration (MFC) of these agents and the minimal effective concentration (MEC) of caspofungin (CAS) using standardized methods. We then collected information regarding pre-exposure to AMB or triazoles (fluconazole, ITC, VRC) within 3 months before Aspergillus isolation. Pre-exposure of cancer patients to AMB or triazoles was associated with increased frequency of non-fumigatus Aspergillus species. Aspergillus isolates recovered from patients who previously received AMB exhibited higher E-test AMB MICs compared with isolates from patients without prior AMB exposure (P = 0.01). In addition, the AMB MICs by E-test were higher in triazole-pre-exposed patients compared with those not exposed to triazoles (P = 0.001). The ITC and VRC MICs by E-test were not affected by prior AMB or triazole exposure. Finally, neither the AMB, ITC, and VRC MICs and MFCs by NCCLS method nor CAS MECs showed such changes. In conclusion, cancer patients with positive Aspergillus cultures who are pre-exposed to AMB or triazoles have high frequency of non-fumigatus Aspergillus species. These Aspergillus isolates were found to be AMB-resistant by the more sensitive E-test method.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Chemoprevention; Culture Media; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Neoplasms; Triazoles

Systemic fungal infections remain a major clinical problem in immunocompromised patients. Presumed systemic fungal infections (PSFI) are treated empirically with an intravenous antifungal agent to reduce the occurrence of documented infections and associated mortality. The objective of this study was to compare the cost-effectiveness of intravenous itraconazole (IVitra) treatment with the current first-line empirical treatment of PSFI with conventional amphotericin B (CAB) in cases of neutropenic cancer and bone marrow transplantation (BMT). Cost-effectiveness was expressed as cost per additional "responder" (defined as a patient without fever or major toxicity). We developed a medical decision analytical tree that included probabilities of toxicity, response and pathogen documentation, and second-line treatments. Clinical data were obtained from randomized clinical trials, and resource use data were obtained from a panel of clinical experts. The total cost of treating PSFI per neutropenic cancer patient was lower for IVitra than for CAB, and this lower cost resulted from a reduced need for second-line antifungals. In a cost-effectiveness analysis, IVitra treatment was superior to CAB treatment. Compared with current treatment with CAB, IVitra therapy was shown to be a cost-effective and cost-saving empirical treatment for PSFI in neutropenic cancer patients and BMT patients.

Topics: Amphotericin B; Antifungal Agents; Costs and Cost Analysis; Humans; Itraconazole; Korea; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Advances in medical therapy have greatly improved the survival of children suffering from cancer. Although progress has been made in the eradication of malignant disease there is growing concern for the development of fungal infections in patients treated with chemotherapy.. We reviewed all episodes of pediatric candidemia that occurred between January 1988 and December 2000. We analyzed the general characteristics of this population, risk factors, microbiology features, treatment, complications, and outcome.. Seventeen cases of candidemia were observed during the 12 years of the study at an estimated incidence of 0.4%. Neutropenia occurred at the onset of infection in 13/17 (76.5%) children. A central venous device was present in all cases. Seventy-seven percent of the infections were caused by Candida albicans and in 85% of patients, yeasts had colonized the gastrointestinal tract. In 9/17 patients visceral dissemination was documented. Overall, in 77% of the episodes the outcome was favorable.. Candidemia is a rare but severe complication in pediatric oncology. Even if the prognosis is better in children than in adults, Candida septicemia remains of great concern since a high percentage of these infections result in visceral dissemination and mortality is still elevated.

Topics: Adolescent; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Candidiasis; Child; Child, Preschool; Female; Humans; Incidence; Infant; Male; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Child; Child, Preschool; Drug Resistance, Bacterial; Fever; Humans; Infant; Meropenem; Neoplasms; Neutropenia; Prospective Studies; Thienamycins; Vancomycin

This study was undertaken to study the resistance of Candida species isolated from oropharyngeal swabs of cancer patients to ketoconazole (KET), fluconazole (FLU), amphotericin B (AmpB), and flucytosine (FCU). The most common species identified was C. albicans, followed by C. tropicalis, C. glabrata, C. famata, C. krusei, C. kefyr, and C. gulliermondii. The minimum inhibitory concentration (MIC) of the antifungal agents was evaluated by RPMI 1640 medium with microdilution method. There were no C. albicans strains resistant to KET, FLU and AmpB. All Candida isolates were found highly susceptible to AmpB (MIC AmpB < 1 microg/ml), followed by KET (MIC KET < or =8 microg/ml), FLU (MIC FLU < or =8 microg/ml) and FCU (MIC FCU < or =4 microg/ml). The main conclusion of this study is that prophylactic therapy planned according to typing and antifungal susceptibility will contribute to the prevention of invasive fungal infections in immunosuppressied oncology patients.

Topics: Amphotericin B; Antifungal Agents; Candida; Disease Susceptibility; Fluconazole; Flucytosine; Humans; Ketoconazole; Microbial Sensitivity Tests; Mycoses; Neoplasms; Oropharynx

We evaluated the value of Aspergillus PCR as a tool for diagnosing invasive aspergillosis from whole-blood samples during antifungal therapy. In a 3-year study, 36 patients receiving antifungal therapy due to chest radiographic findings highly suggestive of fungal pneumonia were evaluated. The PCR results from whole-blood samples were compared to those obtained from bronchoalveolar lavage fluids and/or tissue specimens. A total of 205 whole-blood samples, 15 fine-needle aspirations or tissue biopsy specimens, and 21 bronchoalveolar lavage fluids and tracheal secretions were analyzed using PCR. Of the 36 patients, 15 had proven, 9 had probable, and 12 had possible invasive Aspergillus infection according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. For patients with proven infection the sensitivity values of PCR in lung and blood samples were 100 and 40%, respectively. The negative predictive value of blood monitoring under conditions of antifungal treatment was 44%. Clearance of fungal DNA from blood was associated with resolution of clinical symptoms in six of nine patients with proven infection. Repeated positive PCR results for Aspergillus were associated with fatal outcome, as three of six patients died. For patients with probable infection the sensitivity values of PCR in lung fluid and blood were 66 and 44%, respectively. The benefit of PCR diagnosis using whole-blood samples is limited when sampling takes place after treatment has been started. Performance of Aspergillus PCR using tissue samples is recommended in addition to microscopic examination and culture technique for sensitive detection of fungal infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus; Base Sequence; Bronchoalveolar Lavage Fluid; DNA Primers; DNA, Fungal; Humans; Leukemia; Middle Aged; Neoplasms; Polymerase Chain Reaction; Pyrimidines; Transplantation; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Fever; Humans; Lipopeptides; Liposomes; Mycoses; Neoplasms; Neutropenia; Peptides; Peptides, Cyclic; Pyrimidines; Triazoles; Voriconazole

Topics: Amphotericin B; Antifungal Agents; Caspofungin; Echinocandins; Fever; Humans; Infusions, Intravenous; Lipopeptides; Mycoses; Neoplasms; Neutropenia; Peptides, Cyclic

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candida; Candidiasis; Drug Resistance, Microbial; Female; Fluconazole; Humans; Itraconazole; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Treatment Outcome

To review our recent experience with protothecosis in patients with cancer at The University of Texas MD Anderson Cancer Center, and compare these cases with others reported in the literature.. We report on three patients with protothecosis and cancer who were seen at The University of Texas MD Anderson Cancer Center from January 1979 to May 2002, and reviewed all cases of protothecosis in patients with cancer reported in the literature since 1966.. Overall, 13 cases of protothecosis complicating cancer were evaluated. The median age of the patients was 41 years (range, 7-73 years). Seven patients (54%) had an underlying hematologic malignancy, and one infection occurred after bone marrow transplantation. Neutropenia was uncommon in these patients (14%). Prototheca wickerhamii was the most common Prototheca species identified as the causative agent of infection. Skin infection was the most common presentation of protothecosis, occurring in five patients (38%), followed by disseminated disease in three patients (23%), algaemia in three patients (23%), pulmonary infection in one patient (8%), and olecranon bursitis in one patient (8%). Information on the use of antifungal therapy was available for ten patients. Seven of the ten patients received amphotericin B, while three received triazoles (fluconazole in two, itraconazole in one). Breakthrough protothecosis occurred during the administration of systemic antifungal therapy with itraconazole in one patient. All seven patients who received amphotericin B showed a response, as did one of the three patients given triazoles. Seven (58%) of the patients died during the study period, only one (17%) of protothecosis.. Protothecosis is an uncommon infection in cancer patients, implying that Prototheca spp. have a low pathogenic potential in this population. Pulmonary involvement in particular is uncommon in these patients. Amphotericin B appears to be the most effective antifungal agent; the role of triazoles in treating protothecosis is uncertain, but they may be less effective.

Topics: Adult; Aged; Amphotericin B; Female; Humans; Infections; Male; Neoplasms; Prototheca

Topics: Amphotericin B; Aspergillosis; Cause of Death; Humans; Lung Diseases, Fungal; Mycoses; Neoplasms; Opportunistic Infections

A common complication of the intensive therapy that children with cancer receive is infection. The Oncology Unit of The Children's Hospital at Westmead maintains a comprehensive database of all admissions for suspected sepsis. From July 1994 to June 1999 broad-spectrum antibiotics were commenced in 2331 episodes. With early and aggressive use of empirical amphotericin B, 545 courses were given. Bacteraemia was documented in 701 episodes and invasive fungal disease in 73. Trends seen during the study included: (i) the proportion of febrile neutropenic patients receiving granulocyte colony stimulating factor increased from 40% to 60%; (ii) the mean neutrophil count at cessation of antibiotics fell from 0.97 to 0.63 x 10(9) cells/L for patients not receiving growth factors; (iii) the proportion of non-albicans Candida species infections increased. In addition, an outbreak of infection caused by Scedosporium sp. was documented; (iv) first-line empirical antibiotic combinations containing vancomycin fell from 20% to 7%; and (v) the ability to maintain or escalate anti-fungal therapy with reduced nephrotoxicity through use of lipid formulations of amphotericin was increasingly apparent in high-risk patients. During the study, infection was the primary cause of death in 11 non-bone marrow transplant (BMT) patients (five fungal, four viral, one bacterial infection and one sepsis syndrome) and five BMT patients (two bacterial and three viral). A prospective randomized study of toxicity due to amphotericin B given in either lipid emulsion or dextrose showed no significant difference, but both groups showed a lower incidence of amphotericin B intolerance in comparison with the adult series. The inability to reduce toxicity of amphotericin B by simple mixing with lipid emulsion has led to increasing use of commercially available lipid formulations of amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Bacteremia; Child; Drug-Related Side Effects and Adverse Reactions; Humans; Mycoses; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic

Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans. We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center.. We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records.. When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008).. C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.

Topics: Amphotericin B; Antifungal Agents; APACHE; Bone Marrow Transplantation; Candida albicans; Candidiasis; Case-Control Studies; Female; Fluconazole; Fungemia; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Postoperative Complications; Regression Analysis; Treatment Outcome

In order to assess the risk factors for breakthrough candidemia (candidemia occurring in patients receiving at least 3 days of systemic fluconazole or amphotericin B), 270 cases of candidemia occurring in two tertiary hospitals were analyzed. Using multivariate analysis, profound neutropenia (<100/mm(3)) (odds ratio [OR], 9.14), use of corticosteroids (OR, 3.17), and heavy antibiotic exposure (previous use of 2 or more antibiotics for at least 14 days) (OR, 2.93) were identified as risk factors. Neither the susceptibility of the isolates nor the presence of a catheter was found to be a risk factor. These data suggest that gastrointestinal colonization plays a major role in the development of breakthrough candidemia.

Topics: Amphotericin B; Anti-Bacterial Agents; Candidiasis; Fluconazole; Fungemia; Humans; Multivariate Analysis; Neoplasms; Neutropenia; Odds Ratio; Retrospective Studies; Risk Factors

In cancer patients with persistent fever and neutropenia, amphotericin B is administered for the early treatment and prevention of the clinically occult invasive fungal infections. The major drawback of the conventional amphotericin B is its nephrotoxicity. We have previously showed that massive potassium, sodium, and magnesium supplementation, which corresponds to the amount lost in kidney during amphotericin B administration, as well as vigorous hydration, can markedly reduce nephrotoxicity of conventional amphotericin B. Clinical courses of four oncological patients treated with conventional amphotericin B suspected or proven fungal infection for a period of 24 days (two patients), 39 days, and 47 days are described. During the long-term amphotericin B administration with nephroprotective measures, no severe renal function decrease was observed in any of our patients. Massive ion supplementation corresponding to the amounts lost in kidney, as well as the vigorous hydration are effective in the prevention of the renal function decrease induced by the long-term conventional amphotericin B therapy.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Immunocompromised Host; Kidney; Male; Middle Aged; Mycoses; Neoplasms

Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well-documented in children. As far as gastrointestinal side-effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1-3 mg kg-1. Additionally, patients with high-dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg(-1) three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side-effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed.

Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Female; Humans; Infant; Lipase; Liposomes; Male; Mycoses; Neoplasms; Neutropenia; Pancreatitis; Pancrelipase; Retrospective Studies

Candida lusitaniae is an infrequent cause of fungemia. We identified 12 cases of C. lusitaniae fungemia that occurred at the University of Texas M. D. Anderson Cancer Center from 1988 to 1999. The mean age of patients was 48 years (range 20--70 years). Eight patients had hematologic malignancy or had received a bone marrow transplant, and 4 had a solid tumor. Most patients (75%) were neutropenic (<10(3)/mm(3)). Treatment with amphotericin B alone failed for 3 of 6 patients, irrespective of neutropenic status. Fluconazole was effective as a single agent in 3 patients with solid tumors. The combination of amphotericin B plus fluconazole was effective treatment for two-thirds of patients with hematologic malignancy, despite persistence of neutropenia. The mortality rate associated with C. lusitaniae infection was 25%. C. lusitaniae presents as breakthrough fungemia in immunocompromised patients and is associated with failure of amphotericin B therapy. Fluconazole may be a useful agent in the treatment of this infection.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Bone Marrow Transplantation; Candida; Candidiasis; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Humans; Immunocompromised Host; Male; Middle Aged; Neoplasms; Neutropenia; Treatment Failure

Topics: Adolescent; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Child; Female; Fluconazole; Humans; Liposomes; Lung Diseases, Fungal; Male; Middle Aged; Neoplasms; Nystatin; Treatment Failure; Treatment Outcome

Amphotericin B (AmB) is still the most common anti-fungal agent used to treat systemic fungal infections. It is known that this antibiotic acts by forming pores with the ergosterol contained in the membranes of fungi, but it also interacts with the cholesterol contained in the membranes of eukaryotic cells, hence its toxicity. AmB may also interact with the most common oxidation products of cholesterol found in vivo, together with interacting with biosynthetic precursors of cholesterol, namely, lanosterol and 7-dehydrocholesterol (7-DHC). The purpose of the present work was to study the interactions in solution between AmB and these various sterols, the techniques used being UV-Vis spectroscopy and differential scanning calorimetry. The results are globally interpreted in terms of the structural differences between the sterols. We show that AmB selectively interacts with 7-DHC which, according to a recent hypothesis proposed in the literature, has been identified in connexion with a therapeutic strategy against hepatocellular carcinomas. We find that the affinity of AmB towards 7-DHC is even greater than the affinity of the antibiotic towards ergosterol. We also find that AmB selectively interacts with the principal oxidation product of cholesterol, 7-ketocholesterol, a situation that has to be taken into account when AmB is administered.

Topics: Amphotericin B; Antifungal Agents; Calorimetry, Differential Scanning; Humans; Neoplasms; Spectrophotometry, Ultraviolet; Sterols

Topics: Administration, Oral; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Deoxycholic Acid; Drug Combinations; Fever; Humans; Infusions, Intravenous; Itraconazole; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Treatment Failure

Twelve cases of Trichosporon spp. fungemias occurring in a national cancer institution within 10 years are described. The trend of hematogenous trichosporonosis within the last 10 years is increasing. While no cases occurred in 1988-1991, after 1991, Trichosporon spp. was the most common species among non-Candida spp. fungemias in 1993-1997. The 12 cases of fungemia included 5 that started while the patients were receiving prophylaxis with oral itraconazole, and 2 appeared despite empiric therapy with amphotericin B. Five of the 12 fungemias were catheter associated. Risk factors for fungemia were: central venous catheter, broad-spectrum antibiotics (third-generation cephalosporins plus aminoglycoside); all but 1 had neutropenia and were receiving antineoplastic chemotherapy. All but 2 of the patients died of systemic fungal infection (83.3% mortality). Amphotericin B was administered to all but 1 patient, who was not treated because he died the day after his culture was found to be positive for T. beigelii, before antifungals were administered. All cases infected with T. pullulans were catheter related, and all these patients died. One of the remaining 9 fungemias was caused by T. capitatum (Blastoschizomyces capitatus), and 8 by T. beigelii. Only 2 patients were cured, 1 with a combination therapy with amphotericin B plus fluconazole, and 1 with amphotericin B monotherapy. Several risk factors (neutropenia, acute leukemia, prior therapy or prophylaxis with antifungals and catheter as source of fungemia, breakthrough fungemia) were significantly associated with Trichosporon spp. fungemia, in comparison to 63 C. albicans candidemia occurring in the same period at the same institution. Attributable mortality of hematogenous trichosporonosis was also significantly higher (83.3% vs. 15.8%, P<0.001) than that of hematogenous candidiasis.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Catheterization, Peripheral; Cause of Death; Cephalosporins; Chemoprevention; Female; Fungemia; Humans; Itraconazole; Male; Middle Aged; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Risk Factors; Trichosporon

Fungal infections are an important cause of morbidity and mortality in patients with malignancies. Therefore, the use of amphotericin B (AmB) is essential for these patients. Results from the literature to date show that renal toxicity is the most serious adverse effect of AmB. Renal impairment manifests as a decrease in glomerular filtration and damage to tubular function. Currently, there is no reliable method of preventing nephrotoxicity. We have observed that sodium supplementation alone may not prevent nephrotoxicity. We noted that a large decrease in serum potassium and magnesium was followed by a significant reduction in creatinine clearance and an increase in both serum urea and creatinine. Therefore, we surmised that potassium and magnesium supplements corresponding to the amounts lost by the kidneys, as well as sufficient hydration, are necessary to prevent renal function damage. We decided to test our hypothesis in 32 cancer patients. During AmB therapy, serum electrolyte concentrations and biochemical parameters of renal function and fluid balance were monitored frequently. The daily ion supplementation corresponded to the amount lost through the kidneys. The total duration of administration ranged from 4 to 39 days, with a mean of 13.7 days (median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88 mg/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The daily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesium was 9.0 mmol. The frequency of infusion-related side-effects was only 10.0%. These reactions were treated with hydrocortisone. We observed a significant increase in potassium and magnesium lost through the kidneys, and a significant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinine and ion imbalances. Interestingly, the average creatinine clearance did not decrease, but actually increased slightly, though to a statistically insignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use. Sufficient hydration of patients and ion supplementation corresponding to the amount lost by the kidneys is an effective prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use of AmB. The frequency of

Topics: Adult; Amphotericin B; Anti-Inflammatory Agents; Antifungal Agents; Creatinine; Diuresis; Female; Fluid Therapy; Glomerular Filtration Rate; Humans; Hydrocortisone; Infusions, Intravenous; Kidney; Kidney Diseases; Kidney Tubules; Magnesium; Male; Middle Aged; Mycoses; Neoplasms; Potassium; Sodium; Urea; Water-Electrolyte Balance

Topics: Amphotericin B; Antifungal Agents; Candidiasis; Drug Carriers; Fatal Outcome; Fungemia; Humans; Lipids; Neoplasms; Treatment Failure

Forty-five cases of fungaemia due non-albicans Candida spp. (NAC) in a single National Cancer Institution within 10 years were analysed for aetiology, risk factors and outcome. There had been 12 cases of fungaemia that were due to C. krusei, 14 due to C. parapsilosis, 7 due to C. (T.) glabrata, 6 to C. tropicalis, 2 to C. guillermondii, 2 to C. lusitaniae, 1 to C. stellatoidea, and 1 to C. rugosa. Comparison of 45 NAC fungaemia with 75 episodes of C. albicans fungaemia revealed differences only in two risk factors: previous empiric therapy with amphotericin B (16.0 vs 2.2%, P<0.01) appeared more frequently in cases of C. albicans fungaemia, and prior prophylaxis with fluconazole (8.9 vs 0%, P<0.02) was conversely more frequently observed with NAC. The incidence of other risk factors, such as underlying disease, chemotherapy, antibiotic prophylaxis or therapy, treatment with corticosteroids, catheter insertion, mucositis, cytotoxic chemotherapy, and neutropenia, was similar in both groups. There was no difference either in attributable or in overall mortality between NAC and C. albicans fungaemia in our cancer patients.

Topics: Adrenal Cortex Hormones; Amphotericin B; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Candida; Candida albicans; Candidiasis; Catheterization; Chi-Square Distribution; Cross Infection; Fluconazole; Fungemia; Humans; Incidence; Neoplasms; Neutropenia; Outcome Assessment, Health Care; Prospective Studies; Risk Factors; Slovakia

Meta-analyses may become biased if the reported data in the individual trials are biased and if overlap among trials cannot be identified. We describe the unanticipated problems we encountered in collecting data for a meta-analysis comparing a new antifungal agent, fluconazole, with amphotericin B in patients with cancer complicated by neutropenia. In 3 large trials that comprised 43% of the patients identified for the meta-analysis, results for amphotericin B were combined with results for nystatin in a "polyene" group. Because nystatin is recognized as an ineffective drug in these circumstances, this approach creates a bias in favor of fluconazole. Furthermore, 79% of the patients were randomized to receive oral amphotericin B, which is poorly absorbed and not an established treatment, in contrast to intravenous amphotericin B, which was administered in 4 of 5 placebo-controlled trials, or 86% of patients. It was unclear whether there was overlap among the "polyene" trials, and it is possible that results from single-center trials were included in multicenter trial reports. We were unable to obtain information to clarify these issues from the trial authors or the manufacturer of fluconazole. Two of 11 responding authors replied that the data were with the drug manufacturer and two indicated that they did not have access to their data because of change of affiliation. In the meta-analyses, fluconazole and amphotericin B (mostly given orally) had similar effects (13 trials), whereas nystatin was no better than placebo (3 trials). Since individual trials are rarely conclusive, investigators, institutions, and pharmaceutical companies should provide essential details about their work to ensure that meta-analyses can accurately reflect the studies conducted and that patients will realize maximum benefits from treatments. We recommend that investigators keep copies of their trial data to help facilitate accurate and unbiased meta-analyses.

Topics: Amphotericin B; Antifungal Agents; Fluconazole; Humans; Meta-Analysis as Topic; Mycoses; Neoplasms; Neutropenia; Nystatin; Opportunistic Infections; Publication Bias; Randomized Controlled Trials as Topic; Research Design

Platelet transfusion support is required during bone marrow aplasia following ablative chemotherapy and bone marrow progenitor cell transplantation (BMT). Amphotericin-B is frequently given to these patients, both therapeutically and prophylactically, and has been described to have a negative impact on the results of platelet transfusions. We conducted a prospective study of the effect of amphotericin-B on transfused platelet recovery and survival in 81 BMT or acute leukaemia patients. One hundred and ninety-five platelet transfusions administered to 81 consecutive patients were analysed. The platelets were transfused 2 h after the completion of amphotericin-B. Using this schedule resulted in no effect of amphotericin-B on platelet recovery or survival, although platelet increments were modestly depressed in patients receiving high- vs. low-dose amphotericin-B. We conclude that the timing of amphotericin-B infusion be evaluated in patients demonstrating poor platelet recovery and survival. Transfusing platelets at least 2 h after the completion of amphotericin-B decreases the detrimental effect of this antifungal agent on transfused platelet recovery and survival.

Topics: Amphotericin B; Antifungal Agents; Blood Platelets; Bone Marrow Transplantation; Cell Survival; Drug Administration Schedule; Graft Survival; Humans; Immunocompromised Host; Mycoses; Neoplasms; Platelet Count; Platelet Transfusion; Retrospective Studies; Thrombocytopenia; Time Factors

Forty-one episodes of breakthrough fungaemia occurring over a 7.5 year period in the National and St Elizabeth's Cancer Institutes in Bratislava, Slovakia, were analysed. Five of them occurred during prophylaxis with fluconazole (one Torulopsis glabrata, one Hansenula anomala, two Candida krusei and one Candida parapsilosis), ten with itraconazole (three Trichosporon pullulans, one Trichosporon beigelii, one Cryptococcus laurentii, three Candida albicans and two T. glabrata), 11 during prophylaxis with ketoconazole (one Candida norvegenesis, one C. parapsilosis, one C. krusei, one Candida tropicalis, five C. albicans, one Candida stellatoidea and one C. laurentii and 15 during empirical therapy with amphotericin B (ten C. albicans, two T. beigelii and three Candida lusitaniae). The most frequent risk factors for breakthrough fungaemia were neutropenia, previous therapy with multiple antibiotics and recent catheter insertion. Comparing these episodes with 38 non-breakthrough fungaemias (appearing at the same institute in the same period) differences in certain risk factors were noted: breakthrough fungaemias were more frequently observed in patients with acute leukaemia (39.0% vs 5.2%, P < 0.001), mucositis (34.2% vs 13.1%, P < 0.05), prophylaxis with quinolones (58.5% vs 15.8%, P < 0.0001) and catheter-associated infections (29.3% vs 2.6%, P < 0.003). In this subgroup overall mortality (36.6% vs 28.8%) or early attributable mortality (22.0% vs 23.6%) were not significantly different.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Fluconazole; Fungemia; Humans; Incidence; Itraconazole; Ketoconazole; Male; Mitosporic Fungi; Neoplasms; Pichia; Retrospective Studies; Risk Factors; Slovakia; Treatment Outcome

A retrospective analysis of 48 patients with documented or probable invasive aspergillosis (IA) prior to bone marrow transplantation (BMT) was conducted in 16 centers. Treatment of primary IA was medical in all 48 patients and surgical in 20; clinicoradiological resolution of IA occurred in 30 of 48 patients. Pretransplantation risk factors for relapse IA, total mortality, and IA-related mortality were analyzed by multivariate logistic regression with the following dichotomous risk factors: surgery as part of the initial treatment, resolution of IA by the time of BMT, donor type, conditioning regiment, total-body irradiation, T cell depletion, immunosuppressive therapy, type of antifungal prophylaxis, and growth factor prophylaxis. Conditioning with busulfan/cyclophosphamide was associated with a beneficial outcome for total survival and reduced IA-related mortality. Posttransplantation risk factors such as the development of graft-vs.-host disease (GVHD), therapy for GVHD, and the duration of neutropenia did not have a significant effect on relapse IA, IA-related mortality, or total mortality. The overall incidence of relapse IA was lower than expected (33% [16 of 48 patients]), but the mortality rate among relapsed patients was 88% (14 of 16). Patients receiving prophylaxis with absorbable or intravenous antifungals had less relapses of IA than did those not receiving prophylaxis (12 of 41 vs. four of seven, respectively). This finding reflects the need for better prophylaxis and new antifungal treatments for patients undergoing BMT who have a history of IA.

Topics: Amphotericin B; Anemia, Aplastic; Antifungal Agents; Aspergillosis; Bone Marrow Transplantation; Flucytosine; Humans; Logistic Models; Multivariate Analysis; Neoplasms; Recurrence; Regression Analysis; Retrospective Studies; Risk Factors; Transplantation Conditioning

Amphotericin B treatment in oncological patients is irrepaceable due to the high frequency of mycotic infections. From data in the literature ensues that the most serious undesirable effect of amphotericin B is nephrotoxicity, manifested by a reduced glomerular filtration and impaired tubular function (in particular the development of hypokalemia, and hypomagnesaemia). Prophylaxis of nephrotoxicity is despite major efforts unsatisfactory. In the submitted work the authors tested in a major group of patients their working hypothesis based on previous observations, that prophylactic replacement of the increasing ion losses in urine during amphotericin B treatment without waiting for a decline of serum concentrations of these ions, along with adequate hydration delays or eliminates the decline of glomerular functions.. During amphotericin B therapy of 25 oncological patients renal functions, Na, K and Mg urinary excretion and the serum concentrations of these ions were followed up in detail. The urinary losses were replaced. No overall prophylaxis to prevent acute toxic reactions associated with administration of the drug was used. The mean dose of amphotericin B was 0.82 mg/kg, the mean diuresis 3662 ml/24 hours. Acute toxic reactions calling for hydrocortisone administration were observed only in 6% of the patients. During treatment the urinary K and Mg losses increased significantly and had to one replaced. There was also a significant increase of the excretory fractions of K and Na. However there were no significant changes of serum ions nor a rise of creatinine. The creatinine clearance even increased slightly though insignificantly (1.384 ml/s as compared with 1.392 ml/s).. Consequential hydration of patients and prophylactic replacement of urinary ion losses during amphotericin B therapy are effective in preventing ion disbalances and a decline of glomerular functions. Acute toxic reactions associated with administration of amphotericin B are infrequent.

Topics: Amphotericin B; Antifungal Agents; Humans; Kidney; Mycoses; Neoplasms; Opportunistic Infections

Sixty four episodes of bacteraemia that appeared during antimicrobial prophylaxis with an oral quinolone plus an azole in neutropenic cancer patients were compared with 128 cases of bacteraemia in a cohort of controls matched for age, sex, underlying disease, neutropenia and vascular catheter in situ to assess differences in aetiology, cost of therapy and outcome. Patients who received prophylaxis had breakthrough bacteraemias of a different aetiology compared with the control group: they had significantly fewer multiply-resistant strains (21.9 vs. 51.5, P < 0.04) and a longer afebrile neutropenic period (9.55 days vs. 4.1, P < 0.001). Patients who received prophylaxis also had bacteraemias that were significantly more frequently caused by viridans streptococci (9.4%, vs. 1.7%, P < 0.01), enterococci (15.6% vs. 7.2%, P < 0.05) and Stenotrophomonas maltophilia (17.2% vs. 3.4%, P < 0.01). The cost of antimicrobial therapy per case (37401 SKK (1091 USD) vs. 31808 SKK (899 USD), P < 0.05) was also significantly higher in cases than controls; however, the number of administered antibiotics (4.18 vs. 3.21 per case, P = NS) was similar in both groups. There were no differences in outcome between both groups. However patients who received prophylaxis had significantly longer periods of afebrile neutropenia (9.55 days vs. 4.1, P < 0.001) and bacteraemia developed later than in controls. Also, the incidence of polymicrobial bacteraemia caused by multiresistant strains was lower among cases (21.9 vs. 51.5, P < 0.04).

Topics: Amikacin; Amphotericin B; Antibiotic Prophylaxis; Bacteremia; Bacterial Infections; Case-Control Studies; Catheters, Indwelling; Ceftazidime; Drug Therapy, Combination; Enterococcus; Female; Fluconazole; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Neoplasms; Neutropenia; Ofloxacin; Retrospective Studies; Streptococcal Infections; Treatment Outcome; Vancomycin; Xanthomonas

The paper presents an analysis of fungemia cases which were caused by C. parapsilosis in a cancer center within 10 years, with the aim to compare risk factors and the outcome with fungemias caused by C. albicans and other non-albicans Candida spp. fungemias. Before 1990 (1988-1989) in our institutes C. parapsilosis fungemias were not observed at all. During 1990-1997, the proportion of C. parapsilosis among fungemias increased, in 1990-1993 from 0% to 7.1% in 1996-1997 to 14.2-15%. It represents 25% out of non-albicans Candida spp. fungemias and 7.9% out of all fungemias and is the third commonest pathogen after C. albicans (50.5%) and C. krusei (9.9%). Two from eight (25%) C. parapsilosis fungemias were breakthroughs, one appeared during prophylaxis with ketoconazol and one with fluconazol. Considering the proportion of C. parapsilosis among blood cultures, 13 of 170 blood cultures contained C. parapsilosis (6.6% among all yeasts from blood cultures). C. parapsilosis was the second commonest fungal organism isolated from blood cultures (after C. albicans) in our cancer center. Infected vascular catheters were surprisingly not the major risk factor: central venous catheters were documented as a source in two cases only. The commonest risk factors were similar to those occurring with other fungemias--such as preceding antimicrobial therapy (62.5%), neutropenia (50%) and prior prophylaxis with azoles.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida; Candida albicans; Candidiasis; Child; Female; Fluconazole; Fungemia; Humans; Incidence; Male; Microbial Sensitivity Tests; Neoplasms; Risk Factors

Topics: Amphotericin B; Antifungal Agents; Humans; Neoplasms; Neutropenia

Fusarium infection is increasingly reported in immunocompromised patients. The role of central venous catheters as potential portals of entry for Fusarium is possibly underestimated. Four cases of catheter-related fusarial infection in children with acute leukemia or a solid tumor are described. These patients had an excellent response to removal of the central venous catheter and treatment with amphotericin B.

Topics: Amphotericin B; Antifungal Agents; Catheterization, Central Venous; Child; Child, Preschool; Female; Fungemia; Fusarium; Humans; Immunocompromised Host; Male; Neoplasms

A total of 59 febrile neutropenic episodes were retrospectively recorded at Hôtel-Dieu de France Hospital between August 1st 1991 and December 31st 1992. These episodes were recorded in 51 cancer patients. Median neutropenia was less than one week in 50% of the cases. The etiology of these fever was documented in 27 episodes (46%) and in 70% of the cases gram (-) rods were documented. B-Lactam and Aminoglycoside antibiotics were used in 34 episodes at the initial treatment of these patients. Success rate at this initial treatment or with a modification of the antibiotic therapy was recorded in 85% of the patients. Only 15% of the patients failed to this antibiotherapy, 2/3 of them had their disease in progression. The systemic use of Amphotericine E in those patients with prolonged febrile neutropenia and the concommitent use of growth factors in a sub-group of patients at high risk could lead to a higher success rate in these patients.

Topics: Adult; Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Female; Fever; Hospitalization; Humans; Male; Neoplasms; Retrospective Studies; Risk Factors

To identify factors that may aid in the diagnosis and treatment of patients with malignant neoplasms in whom hepatic abscesses develop.. Retrospective review of medical records.. Thirty-seven oncology patients in whom hepatic abscesses developed at the National Cancer Institute, Bethesda, Md, between June 1954 and October 1989.. Among 37 cancer patients, bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%) had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant neoplasm (P2 = .014). Two patients with fungal abscesses (10%) had a prior invasive procedure (P2 = .004) and 19 (95%) had prior chemotherapy (P2 < .0001). As compared with fungal abscesses, bacterial abscesses were larger (P2 < .00001) and fewer (P2 = .004). Antibiotics and percutaneous or surgical drainage effectively treated bacterial abscesses. Amphotericin B usually eradicated hepatic fungal infections.. The results of this study reveal the importance of the clinical setting in the diagnosis of hepatic abscesses in cancer patients. Aggressive treatment of these abscesses is indicated and is frequently effective.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drainage; Female; Humans; Liver Abscess; Male; Medical Audit; Middle Aged; Mycoses; Neoplasms; Retrospective Studies; Risk Factors; Survival Rate

A pilot study was conducted to evaluate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for fungal infections in patients with cancer. GM-CSF was added to amphotericin B in the treatment of cancer patients with proven major-organ or disseminated fungal infection. The dose of GM-CSF ranged from 100 to 750 micrograms/(m2.d). Of eight evaluable patients, six had a neutrophil response to GM-CSF. Four of these patients were completely cured of the fungal infection, and two had a partial response. However, a capillary-leak syndrome developed in three patients, an adverse effect suggesting that the dose of GM-CSF was excessive.

Topics: Adult; Aged; Amphotericin B; Capillary Permeability; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunocompromised Host; Leukocyte Count; Male; Middle Aged; Mycoses; Neoplasms; Neutrophils; Pilot Projects; Recombinant Proteins; Syndrome

Of the 393 children who underwent BM autotransplantation in the pediatric oncology unit of the Institut Gustave Roussy between February 1979 and September 1991, 14 (3.56%) developed disseminated Candida infection within 3 months. This incidence was far lower than in other published series. Eleven of the 14 patients recovered from the infection, giving a far higher survival rate (78%) than among adult BM transplant recipients (usually < 30%). All 14 patients had four or more risk factors and persistent BM aplasia (median, 25 days); six had Candida tropicalis infection. Four cases of deep visceral involvement were documented, two of which were lethal. Clinical signs were relatively uniform and included secondary high-grade fever (> 40 degrees C) for 8 days; half the patients developed cardiovascular impairment, respiratory distress, neurological disturbances (altered consciousness or delirium) and severe diarrhoea, within as little as 10 days after transplantation. Blood cultures rapidly became positive after the onset of clinical signs and this permitted prompt treatment with a combination of amphotericin B and 5-fluorocytosine; in addition, central catheters were removed. Blood cultures became sterile within 4 days of treatment in 10 of the 14 cases. The generally favourable outcome in this series could be related to the young age of the patients, the absence of GVHD, the absence of total body irradiation in the conditioning regimen, and early antifungal treatment.

Topics: Adolescent; Amphotericin B; Bone Marrow Transplantation; Candidiasis; Child; Child, Preschool; Diarrhea; Female; Fever; Humans; Male; Neoplasms; Retrospective Studies; Treatment Outcome

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Drug Therapy, Combination; Female; Flucytosine; Follow-Up Studies; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Neoplasms; Opportunistic Infections; Prognosis; Retrospective Studies; Treatment Outcome

We reviewed all 155 episodes of central venous catheter-associated fungemia among inpatients at the National Cancer Institute during a 10-year period. Candida species accounted for 98% of episodes. Fungemia was documented by culture of blood drawn through catheters in 50% of cases and by culture of both catheter-drawn and peripheral blood in 39%; mortality and the rate of dissemination were similar for these two groups. Four management strategies were used: catheter removal, antifungal therapy (with amphotericin B), both, or neither; indications for the use of both modes of treatment included fever, neutropenia, long-term indwelling catheterization, positive cultures of both catheter-drawn and peripheral blood, isolation of Candida tropicalis, and fungal isolation from two or more blood cultures. Disseminated fungal infection was documented in 82% of cases with these features but also in 35% of the less severe cases treated only with catheter removal. In addition, nine (82%) of 11 cases managed only with antifungal therapy had a negative outcome (either death from disseminated infection or the recurrence of fevers and/or fungemia), a finding suggesting that intravascular catheters should be removed in fungemia. Virtually all cases of catheter-associated fungemia in patients with cancer are clinically significant and require prompt therapy with amphotericin B.

Topics: Adolescent; Adult; Aged; Amphotericin B; Candidiasis; Catheterization, Central Venous; Catheters, Indwelling; Chemotherapy, Adjuvant; Child; Child, Preschool; Cross Infection; Female; Fungemia; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Retrospective Studies

The nephrotoxicity of various combinations of antibiotics--aminoglycosides, cephalosporins, vancomycin, amphotericin B--in 171 oncologic patients is described. The most nephrotoxic combination seems to be cefotaxime plus gentamicin, ceftriaxone plus amikacin and amphotericin B with cephalosporin, vancomycin or aminoglycoside. Less toxic was netilmicin with penicillin or cephalosporin, and vancomycin.

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Cephalosporins; Drug Therapy, Combination; Humans; Kidney; Neoplasms; Retrospective Studies; Vancomycin

Amphotericin B concentration was measured by high-pressure liquid chromatography (HPLC) and by bioassay in tissues of 11 cancer patients who died from infection and/or their underlying disease after having received amphotericin B entrapped into sonicated liposomes (ampholiposomes). These concentrations were compared to those measured in 28 patients who had only received the commercially available preparation of amphotericin B-Na deoxycholate complex (Fungizone). The fungistatic and fungicidal titres of the tissue homogenates were also evaluated using two strains of Candida spp. and one strain of Cryptococcus neoformans to determine the bioactivity of amphotericin B incorporated in our liposomes. Tissue concentrations varied with the tested tissues and were correlated with the total dose of amphotericin B administered whether given as amphotericin B-Na deoxycholate or ampholiposomes. Amphotericin B concentrations measured by bioassay in tissue methanolic extracts reached 58-81% of concentrations measured by HPLC, whereas only 15-41% was recovered from the unextracted homogenates. Fungicidal titres were seldom measured in tissues, but fungistatic titres were observed and were linearly correlated with amphotericin B concentration measured by HPLC. These results were similar for the patients who received only amphotericin B-Na deoxycholate and for those who received both preparations (amphotericin B-Na deoxycholate and ampholiposomes). Our results suggest that the tissue distribution of amphotericin B is not significantly modified by the type of preparation (deoxycholate complex or liposomes) and that most of the tissue-bound amphotericin B is not bioactive. However, higher daily doses of amphotericin B can be administered safely when incorporated in liposomes and therefore high tissue concentrations may be obtained more rapidly with ampholiposomes than with amphotericin B-Na deoxycholate.

Topics: Adult; Aged; Amphotericin B; Biological Assay; Biological Availability; Candida; Chromatography, High Pressure Liquid; Cryptococcus neoformans; Deoxycholic Acid; Female; Fungi; Humans; Liposomes; Male; Middle Aged; Neoplasms; Tissue Distribution

Topics: Amphotericin B; Antineoplastic Agents; Candidiasis; Disease Susceptibility; Hepatitis; Humans; Neoplasms; Splenic Diseases

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Topics: Adult; Amphotericin B; Blood Transfusion; Bone Marrow Transplantation; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasms

Fungal surveillance cultures have been studied as potential predictors of invasive or disseminated mycoses. Several studies have demonstrated that the presence of Candida tropicalis in mucosal surveillance cultures has a high predictive value for invasive fungal infection due to this pathogen in granulocytopenic patients. By comparison, surveillance cultures for Candida albicans have a poor positive predictive value for invasive fungal infection. The value of routine surveillance cultures of the nares for Aspergillus spp. has not been consistently confirmed. The use of surveillance cultures for less common fungal pathogens, such as Trichosporon beigelii, also remains unclear. Fungal surveillance cultures of the inanimate hospital environment have proven useful in identifying the source of conidia in well-defined clusters or outbreaks of nosocomial aspergillosis and other mycoses. As investigational tools, fungal surveillance cultures also may be useful for studying the effects of new antifungal agents on mucosal flora. Fungal surveillance cultures, especially for C. tropicalis and possibly Aspergillus spp. in high-risk populations, may be useful when a pathogen-directed approach to antifungal therapy is used. However, the time required, diagnostic limitations, and expense of routine mucosal fungal surveillance cultures must be balanced against the effect of this information on therapeutic decisions. Empirical antifungal therapy and early diagnostic approaches for high-risk patients may obviate the need for routine fungal surveillance cultures while decreasing the frequency of invasive mycoses.

Topics: Amphotericin B; Bacteria; Fungi; Humans; Mouth Diseases; Mycoses; Neoplasms

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Cryptococcosis; Disease; Heart Transplantation; Humans; Immunosuppression Therapy; Itraconazole; Ketoconazole; Male; Neoplasms; Opportunistic Infections

An open, prospective study was performed to evaluate the clinical usefulness of sodium chloride loading for prevention of amphotericin-B-induced nephrotoxicity in 37 patients requiring 44 courses of amphotericin B treatment. The median duration of the treatment course was 22 days (range, 9-136 days), and mean cumulative dose per patient was 1117 mg (range, 231-7831 mg). During amphotericin B treatment, all patients received 50 to 100 ml of 10% sodium chloride (85 to 171 mmol NaCl) via an intravenous line for prevention of amphotericin-B-induced nephrotoxicity evaluated by serum creatinine levels. Using this regimen, none of the patients developed significant nephrotoxicity (increase in serum creatinine of more than twice baseline level, or serum creatinine level greater than or equal to 2.0 mg/dl, respectively) despite the co-administration of other potentially nephrotoxic drugs. It was not necessary to discontinue treatment with amphotericin B in any of the patients. There were no side effects due to sodium chloride loading. Our results demonstrate that sodium chloride loading is useful for the prevention of amphotericin-B-induced nephrotoxicity.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Glomerular Filtration Rate; Humans; Kidney; Leukemia; Middle Aged; Neoplasms; Opportunistic Infections; Saline Solution, Hypertonic

We have studied amphotericin B concentrations in tissues of 13 cancer patients who died after having received 75 to 1,110 mg (total dose) of amphotericin B-deoxycholate for suspected or proven disseminated fungal infection. Amphotericin B concentrations were measured by high-pressure liquid chromatography (HPLC) and by bioassay, the latter being done on tissue homogenates as well as on tissue methanolic extracts. The fungistatic and fungicidal titers of the tissue homogenates were also tested against three strains of Candida albicans and one strain of Aspergillus fumigatus. Tissue concentrations of amphotericin B measured by HPLC varied with the tested tissues as well as with the total dose of amphotericin B-deoxycholate administered and ranged from 0.4 to 147.1 micrograms/g. A mean of 38.3% (range, 23.0 to 51.3%) of the total dose was recovered by HPLC from all of the tested organs. Bioassay of tissue methanolic extracts reached 58 to 81% of the concentration measured by HPLC, whereas only 15 to 41% was recovered from the homogenates. Overall, 27.5% of the total dose was recovered from the liver, 5.2% was recovered from the spleen, 3.2% was recovered from the lungs, and 1.5% was recovered from the kidneys. The median concentration in bile was 7.3 micrograms/ml, suggesting that biliary excretion could contribute to amphotericin B elimination to an estimated range of 0.8 to 14.6% of the daily dose. Fungicidal titers were seldom measured in tissues, but fungistatic titers were observed and were linearly correlated with amphotericin B concentration measured by HPLC. In conclusion, only a small proportion of the amphotericin B administered as amphotericin B-deoxycholate to patients seems diffusible and bioactive.

Topics: Adult; Aged; Amphotericin B; Antifungal Agents; Aspergillus fumigatus; Candida albicans; Chromatography, High Pressure Liquid; Deoxycholic Acid; Drug Combinations; Female; Humans; Male; Middle Aged; Mycoses; Neoplasms; Tissue Distribution

To evaluate the role of amphotericin B (AmB) in the biochemical modulation of antineoplastic agents, AmB was administered as a continuous infusion over a period of 52 to 120 h to 14 patients (26 courses) with advanced carcinomas. Continuous infusion amphotericin B (CI-AmB) was delivered at a rate of 0.5 to 0.8 mg/kg/d (19-31 mg/m2/d). The AmB plateau levels assayed by HPLC ranged from 0.7 to 1.9 micrograms/mL and were directly related to the infusion rate. The AmB plasma disposition was biphasic, with mean half-lives of 17 h for the first phase and 11 d for the terminal phase, and a mean residence time of 12 d. Biochemical modulation of antineoplastic agents (lomustine, doxorubicin, cyclophosphamide) by CI-AmB was not demonstrated clinically. Acute toxicities of fever and chills were noted in only 3 of the 26 courses. Reversible renal toxicity was observed in 23 courses. Therapeutic antifungal plasma levels were rapidly reached and maintained for the duration of infusion, with a reduction of acute toxicities associated with shorter infusions. These observations provide impetus for further clinical investigation of CI-AmB.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Infusions, Intravenous; Kidney Diseases; Male; Middle Aged; Neoplasms

We reviewed 60 consecutive flexible bronchoscopies done during a 36-month period in 48 pediatric cancer patients with undiagnosed pulmonary infiltrates. Diagnostic procedures during bronchoscopy included 40 brushings, 50 bronchoalveolar lavages, and 6 transbronchial and mucosal biopsies. A total of 16 specific diagnoses were made by bronchoscopy (27% diagnostic yield), including infection (12), pulmonary leukemia (3), and lymphoma (1). The largest proportion of specific diagnoses came from lavage (14/50) and the smallest from brushings (1/40). Biopsies were also useful for selected patients. The low overall yield for bronchoscopy was probably due to the routine use of empiric broad-spectrum antibiotics and antifungal therapy, as well as trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonitis. Subsequent specific diagnoses were obtained by other procedures (open biopsy, needle aspiration, or autopsy) for 10 patients with negative bronchoscopy results and 3 patients with diagnostic bronchoscopies. These additional diagnoses included 7 infections (Pneumocystis carinii (1), Candida tropicalis (1), cytomegalovirus (1), and Aspergillus (4), and 6 other diagnoses with nonspecific histologic findings. A positive bronchoscopy result may be useful, but negative bronchoscopy findings do not justify delaying other diagnostic procedures or discontinuing antibiotic and antifungal therapy in children with cancer and pulmonary infiltrates.

Topics: Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Biopsy; Bronchoscopy; Child; Child, Preschool; Humans; Lung Diseases; Neoplasms; Pneumonia, Pneumocystis; Therapeutic Irrigation

Among 3,501 individuals receiving endoscopic examination for the upper digestive tract, 41 were found to have esophageal candidiasis including 17 malignancies, 14 immunological disorders, 4 diabetes mellitus, 7 other underlying diseases and 7 apparently healthy subjects. The diagnosis was made either by brushing of the esophagus or by histological examination of the biopsied specimen. Systemic invasion of fungi was observed mainly in patients with malignancy involving the hematopoietic system, and most of them had been treated by corticosteroids, antibiotics or anticancer agents. Although complications associated with esophageal candidiasis are rare, it is emphasized that those patients with malignancy as well as impared immunity should be carefully examined for esophageal candidiasis, in order to prevent the fungi from developing invasive candidiasis. It should be noted that a few cases of gastric ulcer treated by H2 blocker revealed esophageal candidiasis, suggesting that decrease of gastric acidity might be one of the factors involved in this pathological condition.

Topics: Amphotericin B; Autoimmune Diseases; Candidiasis; Esophageal Diseases; Esophagoscopy; Female; Humans; Immune Tolerance; Ketoconazole; Male; Middle Aged; Neoplasms; Prospective Studies

Topics: Amphotericin B; Drug Carriers; Humans; Liposomes; Mycoses; Neoplasms

A pilot study with amphotericin B incorporated in sonicated liposomes (ampholiposomes) made of egg phosphatidylcholine, cholesterol and stearylamine in a molar ratio 4:3:1 was performed in cancer patients with fungal infections. Fifteen patients received a total of 117 intravenous infusions of ampholiposomes. The total dose of amphotericin B administered per patient ranged from 20 to 1004 mg (mean 472 mg). The number of infusions per patient varied from 1 to 20 (mean 8) and the duration of treatment from 1 to 29 days (mean 10 days). Infusion of doses up to 1.8 mg/kg was well tolerated. None of the common side-effects of Fungizone, the colloidal suspension of amphotericin B, occurred; it was noteworthy that patients had no renal function impairment. Serum amphotericin B concentrations given as ampholiposomes were much higher than those obtained with Fungizone. With a daily treatment schedule, peak and trough serum amphotericin B concentrations, as measured by HPLC, were 10 to 20 micrograms/ml and 5 to 10 micrograms/ml respectively; while they did not exceed 2 micrograms/ml and 1 microgram/ml with Fungizone. Amphotericin B given as ampholiposomes had a prolonged serum beta half-life (25.3 +/- 16.0 h). Higher serum antifungal activity was observed with ampholiposomes as compared to Fungizone. We concluded that ampholiposomes have a better therapeutic index than Fungizone.

Topics: Adult; Aged; Amphotericin B; Aspergillosis; Female; Humans; Liposomes; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Neoplasms; Sonication; Time Factors

Topics: Agranulocytosis; Amphotericin B; Aspergillosis; Candidiasis; Humans; Liposomes; Neoplasms

Topics: Acyclovir; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Herpes Labialis; Humans; Mouth Diseases; Mycoses; Neoplasms

In order to determine if it was possible to reverse clinically evident chemotherapeutic drug-resistance, 51 evaluable patients received chemotherapy (in doses and schedules on which they had previously demonstrated tumor progression) together with amphotericin B (AMB). AMB was given in 1-, 2-, or 4-day courses. There was 1 complete response (2%), and 5 partial responses (10%). Response rates tended to be higher in the 4-day treatment program (23%) than in the 1- or 2-day AMB treatment schedules (8%). Toxicity was that expected with chemotherapy (myelosuppression), or AMB alone (fever, chills, and reversible mild azotemia). We conclude that AMB is only infrequently able to reverse clinical drug-resistance, but that this might have palliative effects in a small number of patients in whom other standard chemotherapeutic drugs lack clinical effectiveness.

Topics: Adult; Aged; Amphotericin B; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Drug Resistance; Female; Humans; Male; Middle Aged; Neoplasms; Pilot Projects

Paranasal sinusitis occurred in 52 immunosuppressed cancer patients treated over 5 years at the University of Maryland Cancer Center. Twenty-one patients had aspergillus sinusitis; Aspergillus sp, including flavus and niger were directly recovered from sinus in 19 of the 21 infections. Two other patients with sinus involvement and positive nose cultures for Aspergillus flavus or fumigatus and microbiologically documented pulmonary aspergillosis were considered clinically, although not microbiologically, documented. Predisposing factors for aspergillus sinusitis during the 60 days prior to infection diagnosis were granulocyte count less than 500 microliter (mean duration, 42 days versus 14 days for sinusitis of other etiology; P less than 0.001), prolonged hospitalization (mean duration, 22 days versus 14 days for patients with nonfungal sinusitis; P less than 0.001), and prolonged antibiotic therapy (mean duration, 22 days versus 9 days; P less than 0.001). Treatment with amphotericin B was initially successful for 18 of 21 patients; however, 11 of 18 patients had infection recurrence that always developed at time of tumor exacerbation and reinstitution or intensification of chemotherapy. These findings suggest that aspergillus sinusitis in cancer patients is seen in association with prolonged neutropenia and antibiotic therapy, is amenable to therapy, but tends to recur with relapse of malignancy.

Topics: Adult; Agranulocytosis; Amphotericin B; Aspergillosis; Humans; Immunosuppression Therapy; Length of Stay; Middle Aged; Neoplasms; Recurrence; Sinusitis

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Topics: Adolescent; Adult; Amphotericin B; Aspergillosis; Candidiasis; Female; Histoplasmosis; Humans; Leukemia; Liposomes; Lymphoma; Male; Middle Aged; Mucormycosis; Mycoses; Neoplasms; Sarcoma, Kaposi

Disseminated candidiasis is likely to become an increasing problem in cancer patients. It has occurred in patients undergoing intensive chemotherapy, thermotherapy, and bone marrow transplant. The availability of broad-spectrum cephalosporins with biliary excretion is likely to increase the problem. Although localized candidiasis responds to both topical and parenteral therapy, systemic candidiasis is often fatal, especially in neutropenic patients. A major obstacle to control of this infection is inadequate diagnostic techniques. It is to be hoped that continuing research will yield more effective diagnostic and therapeutic measures.

Topics: Amphotericin B; Antibodies, Fungal; Candidiasis; Cephalosporins; Humans; Ketoconazole; Leukemia; Miconazole; Neoplasms; Pneumonia

Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period. One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein. The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution. Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common. Blood cultures were positive in only 35 percent of patients with disseminated candidiasis. Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered. Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients. Only six (4.5 percent) of 133 patients with proved deep organ infections recovered. Respiratory failure was the clinical cause of death in 62 percent of patients. Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.

Topics: Acute Disease; Amphotericin B; Bacterial Infections; Bacteriological Techniques; Candida; Candidiasis; Cytomegalovirus Infections; Humans; Ketoconazole; Leukemia; Lymphoma; Miconazole; Mycoses; Neoplasms; Neutropenia

Topics: Administration, Intranasal; Agranulocytosis; Amphotericin B; Aspergillosis; Humans; Lung Diseases, Fungal; Neoplasms; Neutropenia

It has been suggested that empiric broad-spectrum antibiotics, instituted for fever in the presence of granulocytopenia, should continue to be administered, even when infection is not demonstrable, to those patients who remain persistently febrile and granulocytopenic. Therefore, the consequences of discontinuing antibiotics when the presence of infection is doubted in this setting were evaluated. In 16 (3.7 percent) of 429 episodes of fever and granulocytopenia for which empiric antibiotic therapy was instituted, after approximately four days, persistence of both fever and granulocytopenia was found, and yet infection was prospectively classified at that time as "doubtful." The initial empiric antibiotic regimen was therefore discontinued after a mean of 4.8 (median 5.0) days. Discontinuation of antibiotics proved appropriate for half of the patients; eight patients received no systemic therapeutic antibiotics with no evidence of infection during a period of at least two weeks. The other eight patients had antibacterial antibiotics reinstituted within a mean of 2.4 days; six infections were subsequently demonstrable. Six of these eight patients also required or were believed to require antifungal therapy with intravenous amphotericin B for presumed fungal infections. Patients with relapsed leukemia or lymphoma and those with a likelihood of continued profound granulocytopenia (counts below 100/microliters) or both were the ones who tended to require reinstitution of antibiotics. Discontinuation of antibiotics when infection was considered doubtful despite persistence of both fever and granulocytopenia was, therefore, successful in eight of 16 patients. Reinstitution of antibiotics was required in the eight remaining patients. No definite rule appears to be applicable to all patients.

Topics: Agranulocytosis; Amikacin; Amphotericin B; Anti-Bacterial Agents; Fever; Humans; Lactams; Neoplasms

Invasive fungal infections are becoming increasingly frequent among immunocompromised patients and especially among cancer patients. The most common pathogens identified are Candida species, Aspergillus species, Cryptococcus neoformans, and Mucor species. Amphotericin B remains the mainstay of antifungal therapy. However, the toxicity of this drug may limit its use and, in addition, both failures and relapses have been reported. 5-Fluorocytosine and imidazoles, such as miconazole and ketoconazole, have been shown to be active, mainly on yeast organisms. The emergence of 5-fluorocytosine-resistant strains warrants caution for its administration as a single agent. The specific role of ketoconazole has not yet been established in large studies. In our experience, ketoconazole seems to be effective in the treatment of severe oral candidiasis in non-neutropenic cancer patients. Moreover, ketoconazole administered prophylactically to neutropenic patients decreases the number of positive surveillance cultures in these patients. The rare incidence of major toxicity and the ability to administer ketoconazole orally represent also major arguments for further investigation of ketoconazole activity by prospective controlled studies.

Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Candidiasis; Candidiasis, Oral; Drug Therapy, Combination; Humans; Imidazoles; Ketoconazole; Lung Diseases, Fungal; Miconazole; Microbial Sensitivity Tests; Mycoses; Neoplasms; Neutropenia; Piperazines

Topics: Amphotericin B; Antineoplastic Agents; Asparaginase; Endotoxins; Escherichia coli; Humans; Hypersensitivity; Interferons; Lipopolysaccharides; Neoplasms; Pyrogens

The natural history of candidiasis in general surgical patients has been poorly documented, and the toxicity of amphotericin B is widely heralded. For these reasons therapy for candidiasis is frequently withheld in situations where antimicrobial treatment seems indicated on clinical grounds. The clinical courses of 47 general surgical patients who received amphotericin therapy for presumed Candida infection were reviewed. Nineteen patients had had solid tumors, but 12 were either localized or resected tumors. Only nine patients had received prior cancer themotherapy. Twenty-one patients were treated for fungemic disease, 10 for Candida in peritonitis fluid, and 16 for apparent colonization associated with fever and organ failure syndromes. Pre-existing renal or other organ failure was the primary determinant of survival with 4/22 survivors (18%) in patients with renal failure compared with 17/25 (78%) survivors in patients without such organ failure. In patients with serum creatinine values less than 2.5 mg/dl, amphotericin therapy was associated with a transient 30% fall in creatinine clearance and a proportionate rise in serum creatinine. Dose response curves were determined and revealed substantial sterilization of cultures in both fungemic and nonfungemic patients receiving greater than or equal to 6 mg/kg. This was confirmed by autopsy material. We suggest that in this acutely ill patient popoulation uncontrolled infection is the primary determinant of organ failure. Short-term limited dosing with amphotericin B (6-8 mg/kg total dose) in conjunction with appraisal of clinical response is adequate therapy for most presumed Candida infections. Long-term high dose therapy, such as that recommended in immuodepressed patients, is not a routine necessity.

Topics: Acute Kidney Injury; Amphotericin B; Candidiasis; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Neoplasms; Peritonitis; Postoperative Complications; Sepsis; Surgical Procedures, Operative

Topics: Adolescent; Adult; Agranulocytosis; Amphotericin B; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Carbenicillin; Cephalothin; Child; Child, Preschool; Drug Therapy, Combination; Fever of Unknown Origin; Gentamicins; Humans; Mycoses; Neoplasms; Prospective Studies; Random Allocation

At temperatures above 37 degrees C, the abilities of many, but not of all, anticancer drugs to kill cells increases substantially. The increased cytotoxic rate can vary smoothly with temperature (e.g., nitrosoureas or cis-platinum(II) diamminedichloride) or show a marked threshold near 43 degrees C (e.g., adriamycin or bleomycin). Clinically, the increased cell killing rate can be used in the combination of localized hyperthermia and systemic chemotherapy. Drugs can also be useful in the study of cell killing by heat. Aliphatic alcohols which mimic and interact with heat, tend to be localized in lipid-rich regions of the cell, i.e., membranes. Heat modifies the rate at which plant lectins agglutinate cells and also modifies capping rates; most likely, these changes reflected membrane alterations. Because other data strongly imply that proteins are involved in cell death, we think that the first step in hyperthermic killing of cells involves damage to specific membrane-associated proteins.

Topics: Alcohols; Amphotericin B; Animals; Antineoplastic Agents; Cell Survival; Concanavalin A; Glucose; Hot Temperature; Humans; Neoplasms; Structure-Activity Relationship

Topics: Amphotericin B; Bacterial Infections; Child; Flucytosine; Humans; Infections; Mycoses; Neoplasms; Protozoan Infections; Virus Diseases

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Amphotericin B; Antigens, Fungal; Child; Collagen Diseases; Cryptococcosis; Female; Flucytosine; Hodgkin Disease; Humans; Ireland; Latex Fixation Tests; Male; Middle Aged; Neoplasms; Sarcoidosis; United Kingdom

The interaction of hyperthermia (41--45 degrees C) and chemotherapeutic agents frequently results in increased cytotoxicity over that predicted for an additive effect, although to date only a very limited number of drugs have been examined for such a possible interaction. At 42 degrees C, the upper limit of temperature useful for whole-body hyperthermia, the most promising agents of those examined to date appear to be the nitrosoureas and cis-platinum. Insufficient data exist for cyclophosphamide, whose long plasma half-life makes it an attractive candidate. Localized heating seems optimum at higher temperatures (43--45 degrees C). At these temperatures, not only those drugs effective at 42 degrees C but particularly bleomycin and possibly amphotericin B become candidates. No data exist in the literature on possible "thermic sensitizers," i.e., drugs which are noncytotoxic at 37 degrees C but which become effective at elevated temperatures. Two special cases are Adriamycin and actinomycin D. These drugs may be contraindicated for clinical use, since not only synergism but also protection by hyperthermia have been demonstrated, depending upon the time-sequence relationships of the heat and drug treatments.

Topics: Alkylating Agents; Amphotericin B; Animals; Antineoplastic Agents; Bleomycin; Cell Survival; Cells, Cultured; Cisplatin; Cricetinae; Drug Evaluation, Preclinical; Drug Tolerance; Hot Temperature; Humans; Hyperthermia, Induced; Neoplasms

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.

Topics: Adolescent; Amphotericin B; Anemia; Child; Child, Preschool; Female; Heart; Humans; Hypokalemia; Infant; Kidney; Liver; Male; Mycoses; Neoplasms; Neutropenia; Thrombocytopenia

Infections of children with malignant disease, especially of the lympho-reticular system, are characterized by their severity, with a high mortality, as a consequence of defective immunocompetence. According to the immunosurveillance theory, temporary immune defects could have even facilitated the malignant growth. The neoplastic disease itself contributes to the immunodeficiency by multiple mechanisms. The powerful cytostatic-cytocidal drugs reduce the immune response also, especially in the phases of bone marrow depression. Granulocytopenia shows the most significant correlation with the incidence of serious infections. The different forms of hospital infections have been reviewed and classified as 1. bacterial, fungal and, rarely, (but most dangerous) protozoal infections, 2. endogenous infections with the patient's own anaerobic intestinal flora and 3. viral infections. The perspectives of up-to-date chemotherapy and management of the immunodeficiency e.g. with leucocyte transfusions, and attempts to prevent infection are discussed.

Topics: Amphotericin B; Antineoplastic Agents; Bacterial Infections; Blood Transfusion; Child; Communicable Diseases; Cross Infection; Humans; Immunologic Surveillance; Immunosuppression Therapy; Leukocytes; Leukopenia; Miconazole; Mycoplasma Infections; Mycoses; Neoplasms; Nutrition Disorders; Nystatin; Patient Isolation; Protozoan Infections; Tetracyclines; Virus Diseases

Topics: Amphotericin B; Animals; Antineoplastic Agents; Cell Division; Cell Membrane; Cell Survival; Ergosterol; Humans; Leukemia L1210; Mice; Neoplasms

Seven patients with metastatic tumors resistant to therapy with adriamycin, BCNU, plus cyclophosphamide received the same chemotherapy combined with amphotericin B. One complete response (acute myelomonocytic leukemia), two partial responses (carcinoma of the breast and multiple myeloma), and one case with objective improvement (carcinoma of the breast) were observed in seven evaluable trials. Myelosuppression was not consistently changed by addition of amphotericin B. Fever and chills were common after amphotericin B. Bronchospasm and hypotension occurred twice. Amphotericin B reverses resistance to adriamycin-containing chemotherapy regimens in some patients.

Topics: Adult; Aged; Amphotericin B; Breast Neoplasms; Carmustine; Cyclophosphamide; Doxorubicin; Drug Resistance; Drug Therapy, Combination; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Multiple Myeloma; Neoplasms

The clinical and pathological findings in 46 patients with cryptococcosis at Memorial Sloan-Kettering Cancer Center from 1956 to 1972 are reported. The striking predilection for cryptococcal infection in patients with leukemias and lymphomas is again confirmed. Of 41 patients with neoplastic disease, those with chronic lymphatic leukemia (CLL), Hodgkin's Disease, chronic myelogenous leukemia (CML), myeloma and lymphosarcoma had the highest incidence of cryptococcosis. In all cases, neoplastic disease was widespread when infection occurred. All of these patients had leukopenia and absolute lymphopenia at the time of infection. Thirty-nine were on steroids. Thirty-one patients with neoplastic disease had disseminated infection. Review of pathology revealed a spectrum of inflammatory lesions. Histiocytic-lymphocytic infiltrates occurred in the central nervous system in 10 patients. In six cases, reaction was granulomatous. There were single instances of suppurative and fibrotic reactions. Mortality from infection was high in patients with neoplastic disease. Twenty-four of 28 deaths occurred within 60 days as a result of infection. Within one year, 10 more patients died, nine of cryptococcosis. Only three survived more than one year, and all patients died within 600 days. Twenty-nine patients with neoplastic disease received amphotericin B. Only nine survived more than 60 days.

Topics: Amphotericin B; Antigens, Bacterial; Central Nervous System; Cryptococcosis; Cryptococcus neoformans; Female; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lung; Lymphoma, Large B-Cell, Diffuse; Male; Multiple Myeloma; Neoplasms

Fungal infections are increasing in frequency, especially among patients with haematological malignancies. The fungi which cause most of the infections in cancer patients are Candida spp. and Aspergillus spp. These fungi seldom infect individuals with normal host defence mechanisms. Many factors predispose patients to fungal infection, including neutropenia, lymphopenia, gastro-intestinal ulceration, intravenous catheters and adrenal corticosteroid therapy. Candida spp. cause 5 major types of infection: dermatitis, thrush, gastro-intestinal, primary organ and disseminated infection. Aspergillus spp. and Phycomycetes cause pulmonary, disseminated or rhino-cerebral infection. Cryptococcus neoformans usually causes meningitis but may cause pneumonia or disseminated infection. The diagnosis of fungal infection is often made only at postmortem examination, because it is difficult to isolate the aetiological agent from sites of infection. Amphotericin B remains the mainstay of antifungal therapy, but is seldom effective in the patient with compromised host defences. Successful management of these infections in the future will depend upon improvement in diagnostic capabilities as well as the introduction of more effective and less toxic antifungal agents.

Topics: Amphotericin B; Aspergillosis; Candidiasis; Humans; Leukemia; Lymphoma; Mycoses; Neoplasms; Nocardia Infections

Aspergillus infections in patients with cancer are difficult to diagnose, and such diagnoses are frequently made at necropsy. Earlier therapy has been proposed to provide better response. We reviewed 17 consecutive patients with documented aspergillosis to determine the impact of earlier diagnosis and prompt treatment with amphotericin B. Sixteen had hematologic malignancies, and all had marked granulocytopenia. Six were diagnosed and treated within 96 h of the appearance of infiltrates. Three of these six had complete resolution of all signs and symptoms of aspergillus infection. The other three had a partial response to therapy despite continued granulocytopenia. All 11 patients in whom antifungal therapy was either delayed (six) or not given (five) for at least 2 weeks after the infiltrate was present diet with progressive aspergillosis aggressive diagnostic methods to establish the diagnosis of aspergillosis are warranted so that antifungal therapy can be started early, which may then be successful in resolving these potentially fatal infections.

Topics: Agranulocytosis; Amphotericin B; Aspergillosis; Humans; Lymphoma; Neoplasms; Time Factors

Topics: Amphotericin B; Antineoplastic Agents; Cell Membrane; Deoxycholic Acid; Drug Therapy, Combination; Humans; Neoplasms

Twenty-one patients with advanced metastatic cancer received amphotericin B (AmB) plus BNUC in a Phase I chemotherapy trial. Of 11 patients with measurable metastases from bronchogenic carcinoma, five had partial antitumor responses lasting 1.5 to 12+ months, and one had objective improvement. Only two of six patients with other types of tumors had objective improvement of short duration. No consistent evidence of immunologic stimulation was observed in eight patients studied. These results suggest that amphotericin B may increase the therapeutic ratio of BCNU, and further trials of this new concept in chemotherapy of advanced tumors are in progress. The dose-limiting toxicity was myelosuppression, usually thrombocytopenia. No enhancement of BCNU toxicity by the addition of AmB was observed. The recommended dose for future studies is: AmB, 7.5 mg/m2 on day 1, 15 mg/m2 on day 1, 30 mg/m2 on days 3 and 4; plus BCNU, 250 mg/m3 on day 4. The regimen is repeated every 6 to 8 weeks.

Topics: Amphotericin B; Blood Platelets; Bone Marrow; Carmustine; Drug Therapy, Combination; Granulocytes; Humans; Neoplasm Metastasis; Neoplasms

Topics: Amphotericin B; Ampicillin; Brain Abscess; Candidiasis; Cryptococcosis; Enterobacteriaceae Infections; Esophagitis; Herpes Simplex; Humans; Infections; Meningitis; Meningitis, Listeria; Mucormycosis; Neoplasms; Pharyngitis; Stomatitis; Toxoplasmosis

One hundred consecutive subclavian catheter insertions were performed by the surgical house staff of Martland Hospital, Newark, New Jersey, over a ten month period. The only complications were three punctures of the subclavian artery and one systemic infection. The following conclusions were drawn from these data. Maintaining a closed intravenous system with minimal manipulation of the catheter is the most important factor in avoiding infectious complication. Neither the routine use of irrigation of the catheter with amphotericin B nor insertion of the catheter under strict aseptic conditions is necessary to minimize infectious complications. The morbidity related to insertion of the catheter can be kept to a minimum if the catheters are inserted by experienced personnel.

Topics: Amphotericin B; Asepsis; Catheterization; Emergencies; Escherichia coli Infections; Humans; Neoplasms; Parenteral Nutrition; Punctures; Sepsis; Subclavian Vein; Surgical Procedures, Operative; Surgical Wound Infection; Therapeutic Irrigation; Time Factors

Transfer factor is a dialyzable extract of sensitized leukocytes, which transfers reactivity from skin test-positive donors to skin test-negative recipients. Transfer factor supplied by our laboratory has been used therapeutically to induce cellular immunity in 78 patients around the world. Many patients received multiple doses of transfer factor ranging from 1 unit given every 6 months for 3 years to 1 unit every week for 6 months to as much as 8 units per week for a brief period. A total of 299 units of transfer factor have been given. Diseases in which transfer factor appeared to cause improvement include the Wiskott-Aldrich syndrome, severe combined immunodeficiency disease, mucocutaneous candidiasis, chronic active hepatitis, coccidioidmycosis, dysgammaglobulinemia, Behcet disease, aphthous stomatitis, linear morphea, familial keratoacanthoma and malignancy.

Topics: Amphotericin B; Behcet Syndrome; Binding Sites, Antibody; Candidiasis, Cutaneous; Coccidioidomycosis; Dysgammaglobulinemia; Hepatitis; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunotherapy; Keratoacanthoma; Macrophage Migration-Inhibitory Factors; Monocytes; Neoplasms; Scleroderma, Localized; Stomatitis, Aphthous; Transfer Factor; Wiskott-Aldrich Syndrome

Topics: Adult; Amphotericin B; Anemia, Aplastic; Blood; Candida; Candidiasis; Catheterization; Cryptococcus; Female; Fungi; Humans; Immunity; Immunosuppressive Agents; Leukopenia; Male; Middle Aged; Mycoses; Neoplasms; Prognosis

Topics: Amphotericin B; Cholesterol; Humans; Neoplasms

Topics: Amphotericin B; Candida; Candidiasis; Diabetes Complications; Humans; Iatrogenic Disease; Neoplasms; Prognosis; Rheumatic Heart Disease

Topics: Adrenocorticotropic Hormone; Amphotericin B; Blood Transfusion; Bone Marrow Examination; Drug Therapy; England; Geriatrics; Histoplasmosis; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Pathology; Prednisolone; Sarcoma; Toxicology

Topics: Alkaline Phosphatase; Amphotericin B; Biopsy; Black People; Cryptococcosis; Hepatomegaly; Humans; Liver Diseases; Lymph Nodes; Mesenchymoma; Muscular Diseases; Neoplasms; Serologic Tests; Surgical Procedures, Operative; Thigh

Topics: Amphotericin B; Anti-Bacterial Agents; Antineoplastic Agents; Candidiasis; Drug Therapy; Esophagoscopy; Esophagus; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Sarcoma