amphotericin-b and Leukopenia

In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL). In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS). Median hospitalization duration and costs were not different. RhG-CSF was 6.6 times more expensive per course than CAB. In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective.

Topics: Adult; Amphotericin B; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Ciprofloxacin; Costs and Cost Analysis; Cyclophosphamide; Drug Therapy, Combination; Epirubicin; Female; Fever; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Length of Stay; Leukopenia; Methotrexate; Middle Aged; Neoplasm Metastasis; Netherlands; Prospective Studies; Recombinant Proteins

This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis.. A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020.. The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance.. ChiCTR1900021195. Registered 1 February 2019.

Topics: Amphotericin B; Anemia; Antifungal Agents; HIV Infections; Humans; Induction Chemotherapy; Leukopenia; Prospective Studies; Thrombocytopenia

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.

Topics: Amphotericin B; Animals; Cholesterol; Complement Activation; Complement C3-C5 Convertases; Complement System Proteins; Drug Hypersensitivity Syndrome; Elapid Venoms; Humans; Hypotension; Leukocytosis; Leukopenia; Liposomes; Nanoparticles; Polyethylene Glycols; Rats; Thrombocytopenia; Zymosan

A comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics and in vitro antifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect the in vitro antifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3 or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were tested in vivo to determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely, N-(L-lysyl)-BSG005 (compound 3n) and, especially, L-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable in in vitro and in vivo tests to AMB and that have better toxicological properties.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Cyclophosphamide; Drug Evaluation, Preclinical; Leukopenia; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Nystatin; Polyenes; Sepsis; Small Molecule Libraries; Structure-Activity Relationship

Topics: Aged; Amphotericin B; Antifungal Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Female; Granulocyte Colony-Stimulating Factor; Humans; Invasive Pulmonary Aspergillosis; Itraconazole; Leukopenia; Methyltransferases; Mutation; Tomography, X-Ray Computed; Treatment Outcome

Leishmaniases are parasitic diseases due to a flagellate protozoan of the genus Leishmania. They are transmitted from mammal to mammal by the bite of an arthropod vector: a female sandfly. Among the different clinical presentations, the zoonotic visceral leishmaniasis (ZVL) is due to Leishmania infantum. Dogs are the reservoir and can develop a deadly disease. ZVL is described in China, Pakistan, Latin America and in the Mediterranean region, particularly in the South of France. In recent years, many asymptomatic carriers have been described. Despite the fact that cases in immunocompromised adults are the majority, the classic Mediterranean ZVL in young children is still observed. The classic triad of symptoms is: fever, pallor, splenomegaly and hepatomegaly in half of the cases. The biological orientation is a low blood count (anemia, leuconeutropenia, and thrombocytopenia) and an inflammatory syndrome. Serological tests are useful, but the diagnosis is made by the identification of the parasite in a bone marrow sample. Today, the treatment is done by the liposomal amphotericin B (AmBisome) and the total dose must to be 20 mg/kg.

Topics: Amphotericin B; Anemia; Animals; Anti-Bacterial Agents; Child; Dogs; Female; Fever; Hepatomegaly; Humans; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral; Leukopenia; Neutropenia; Splenomegaly; Thrombocytopenia; Zoonoses

A liposomal formulation of Amphotericin B (AmBisome), with small unilamellar vesicles containing amphotericin B, shows characteristic pharmacokinetics as liposomes, and in consequence, has different pharmacological activity and toxicity from amphotericin B deoxycholate (Fungizone). In this study, we evaluated the antifungal pharmacodynamic characteristics of AmBisome against Candida albicans using the in vitro time-kill method and murine systemic infection model. A time-kill study indicated that the in vitro fungicidal activities of AmBisome and Fungizone against C. albicans ATCC 90029 increased with increasing drug concentration. For in vivo experiments, leucopenic mice were infected intravenously with the isolate 4 hr prior to the start of therapy. The infected mice were treated for 24 hr with twelve dosing regimens of AmBisome administered at 8-, 12-, 24-hr dosing intervals. Correlation analysis between the fungal burden in the kidney after 24 hr of therapy and each pharmacokinetic/pharmacodynamic parameter showed that the peak level/MIC ratio was the best predictive parameter of the in vivo outcome of AmBisome. These results suggest that AmBisome, as well as Fungizone, has concentration-dependent antifungal activity. Furthermore, since AmBisome can safely achieve higher concentrations in serum than Fungizone, AmBisome is thought to have superior potency to Fungizone against fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Kidney; Leukopenia; Male; Mice; Microbial Sensitivity Tests

The role of the immunomodulator tuftsin in enhancing the antifungal activity of liposomal amphotericin B against Cryptococcus neoformans in leucopenic mice was assessed.. In the present study, we investigated the antifungal activity of amphotericin B liposomes with tuftsin grafted on the surface. Mice were treated with free amphotericin B as well as liposomal formulations after C. neoformans infection. For prophylactic studies, mice were pre-treated with liposomal tuftsin (50 microg/mL) for three consecutive days prior to C. neoformans infection (7 x 10(5) cfu/mouse). Chemotherapy, with tuftsin-free and tuftsin-bearing amphotericin B liposomes, was started 24 h post C. neoformans infection. The role of tuftsin in immunoaugmentative therapy was assessed by survival and cfu of treated mice.. Amphotericin B entrapped in tuftsin-bearing liposomes showed increased anticryptococcal activity in the murine model. Moreover, tuftsin pre-treatment further augmented the antifungal activity of liposomal amphotericin B in leucopenic mice. Incorporation of tuftsin in liposomes resulted in increased anticryptococcal activity of liposomal amphotericin B compared with amphotericin B deoxycholate and conventional liposomal amphotericin B formulations.. The enhanced anticryptococcal activity of amphotericin B in tuftsin-liposomes can be attributed to the immune-stimulating property of tuftsin. Tuftsin activates the key immune cells, due to the presence of its receptors on macrophages and neutrophils, for a better fight against pathogens. Simultaneous liposome-mediated delivery of amphotericin B to the site of infection kills the pathogens more effectively.

Topics: Amphotericin B; Animals; Antifungal Agents; Brain; Cryptococcosis; Dose-Response Relationship, Drug; Drug Synergism; Immunologic Factors; Leukocytes; Leukopenia; Liposomes; Lung; Mice; Mice, Inbred BALB C; Tuftsin

The efficacy of intravenous injections of a liposomal formulation of amphotericin B (AmBisome) and amphotericin B deoxycholate (Fungizone) was evaluated in immunocompetent and temporarily leucopenic mouse models of disseminated aspergillosis using seven isolates of Aspergillus.. Mice were infected with the organisms via tail veins. At 4 h after infection, antifungals were administered intravenously. For 30 days the number of mice surviving was recorded.. AmBisome at 1 mg/kg or higher significantly prolonged the survival time of mice infected with five out of seven isolates of Aspergillus compared with the control group. There was no difference in in vivo activity between AmBisome and Fungizone at 1 mg/kg in six isolates of Aspergillus. At the maximum tolerated dose of antifungals, however, AmBisome (10 mg/kg) showed greater efficacy than Fungizone (1 mg/kg).. These results suggest that the overall protective activity of AmBisome against disseminated aspergillosis is superior to that of Fungizone.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus; Immunocompetence; Immunosuppression Therapy; Leukopenia; Male; Maximum Tolerated Dose; Mice; Microbial Sensitivity Tests; Survival Analysis

Topics: Adult; Amphotericin B; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Autoimmune Diseases; Azathioprine; Fatal Outcome; Female; Humans; Hydrocephalus; Immunocompromised Host; Immunosuppressive Agents; Leukopenia; Lung Diseases, Fungal; Neuroaspergillosis; Prednisone; Thrombocytopenia

We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 x 10(3) to 3 x 10(3) conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Atmosphere Exposure Chambers; Cortisone; Costs and Cost Analysis; Cyclophosphamide; Disease Models, Animal; Disease Progression; Female; Immunosuppressive Agents; Inhalation Exposure; Leukopenia; Lung; Mice; Mice, Inbred BALB C; Pulmonary Alveoli; Reproducibility of Results; Survival Analysis

In this report, a case of Fusarium fungaemia developed in an acute lymphoblastic leukemia (ALL) patient was presented. A seven year old girl who had weakness, loss of appetite, paleness and ecchymosis on legs applied to Pediatric Hematology Service and cytotoxic chemotherapy was started after she had been diagnosed as ALL-L1. Her chemotherapy was stopped because of increase in fever, leukopenia and neutropenia. Central venous catheter and peripheral blood cultures were obtained. Fusarium thapsinum was recovered from blood cultures, obtained in two consecutive days. Thereupon central venous catheter of the patient was removed and intravenous amphotericin B was added to the therapy. On the fifth day of febrile neutropenia attack, her fever was decreased after the onset of antifungal therapy. Radiological examinations were normal and no fungal growth was observed in the later blood cultures. On the 21st day of amphotericin B therapy, chemotherapy was started again and amphotericin B was changed to peroral itraconazole (200 mg/day) at the fifth week. The patient whose itraconazole therapy was stopped after three months, was still in remission and continued receiving her prolonged therapy. In conclusion, Fusarium infections which manifest with fungaemia and fever as the only symptoms, should be taken into consideration in neutropenic patients receiving immunosuppressive therapy.

Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Catheterization, Central Venous; Catheters, Indwelling; Child; Female; Fever; Fungemia; Fusarium; Humans; Immunosuppressive Agents; Itraconazole; Leukopenia; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma

In the present study, we have evaluated prophylactic role of various immunomodulators viz. lipopolysachharide, protein A and tuftsin to impart protection against experimental candidiasis in leukopenic mice. Both free as well as liposomised form of nystatin was not effective enough in offering complete cure against less susceptible isolate of Candida albicans (JNMCR) infection in immunodebilitant mice. Interestingly, the pretreatment of leukopenic mice with immunomodulators before challenging them with C. albicans increased therapeutic efficacy of the nystatin against systemic candidiasis. Efficacy of the treatment was evaluated on the basis of survival of the animals as well as fungal load in systemic circulation and various organs viz. liver, kidney, spleen and lungs of the treated animals.

Topics: Amphotericin B; Animals; Antifungal Agents; Candida albicans; Candidiasis; Drug Compounding; Drug Resistance, Fungal; Female; Immunologic Factors; Intercalating Agents; Kidney; Leukopenia; Lipopolysaccharides; Liposomes; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nystatin; Staphylococcal Protein A; Tuftsin

The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after Aspergillus fumigatus inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with A. fumigatus and in reducing the dissemination of A. fumigatus to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Carriers; Female; Humans; Immunosuppression Therapy; Leukocyte Count; Leukopenia; Liposomes; Lung Diseases, Fungal; Polyethylene Glycols; Rats; Treatment Outcome

Heated (20 min at 70 degrees C) amphotericin B-desoxycholate (hAMB-DOC) was further characterized, as was another formulation obtained after centrifugation (60 min, 3000 x g), hcAMB-DOC. Conventional AMB-DOC consisted of individual micelles (approximately 4 nm in diameter) and threadlike aggregated micelles, as revealed by cryo-transmission electron microscopy. For both hAMB-DOC and hcAMB-DOC, pleiomorphic cobweb structures were observed with a mean particle size of approximately 300 nm as determined by laser diffraction. The potent antifungal activity of AMB-DOC against Candida albicans is not reduced by heating. Effective killing of C. albicans (>99.9% within 6 h) was obtained at 0.1 mg/liter with each of the AMB formulations. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release ((86)Rb(+)) from C. albicans of > or =50% was observed at 0.8, 0.4, and 0.4 mg/liter, respectively. After heating of AMB-DOC, toxicity was reduced 16-fold as determined by red blood cell (RBC) lysis. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, hemolysis of > or =50% was observed at 6.4, 102.4, and 102.4 mg/liter, respectively. In contrast, AMB-DOC and its derivates showed similar toxicities in terms of cation release from RBC. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release ((86)Rb(+)) of > or =50% was observed at 1.6, 0.8, and 0.8 mg/liter, respectively. In persistently leukopenic mice with severe invasive candidiasis, higher dosages of both hAMB-DOC and hcAMB-DOC were tolerated than those of conventional AMB-DOC (3 versus 0.8 mg/kg of body weight, respectively), resulting in significantly improved therapeutic efficacy. In conclusion, this new approach of heating AMB-DOC may be of great value for further optimizing the treatment of severe fungal infections.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Chemistry, Pharmaceutical; Leukopenia; Mice; Temperature

In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable Candida albicans in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg . day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Drug Carriers; Leukopenia; Liposomes; Mice

The biodistribution of liposomal amphotericin B (L-AmB; AmBisome) and amphotericin B-desoxycholate were compared after a single injection of drug in uninfected immunocompetent mice and in leucopenic mice 6 h after inoculation with Candida albicans. Amphotericin B-desoxycholate was administered at the maximum tolerated dose (MTD) of 0.3 mg/kg whereas L-AmB was given at either 0.3 mg/kg or the MTD of 7 mg/kg. Amphotericin B (AmB) concentrations in the blood, liver, spleen, lungs and kidneys were determined by HPLC analysis at various intervals during the 48 h after administration. The biodistribution of both preparations of AmB followed similar patterns in both uninfected immunocompetent mice as well as those that were leucopenic and infected with C. albicans. Administration of L-AmB resulted in increased concentrations of drug in the blood, liver, and spleen but decreased concentrations in the kidney and lung. Hepatosplenic uptake of L-AmB was highly dose dependent with 7 mg/kg resulting in a relatively prolonged blood circulation. Blood and tissues retained high AmB concentrations after administration of L-AmB at the MTD. By using radiolabelled L-AmB, it was found that the high AmB concentrations in blood represented liposome-associated AmB and that during circulation in blood slow release of AmB occurred.

Topics: Amphotericin B; Animals; Candidiasis; Chromatography, High Pressure Liquid; Cyclophosphamide; Drug Carriers; Female; Gallium Radioisotopes; Isotope Labeling; Leukopenia; Liposomes; Mice; Mice, Inbred BALB C; Tissue Distribution

Pegylated amphotericin B (AmB) liposomes (PEG-AmB-LIP) were compared with laboratory-prepared nonpegylated AmB liposomes (AmB-LIP), a formulation with a lipid composition the same as that in AmBisome, as well as with industrially prepared AmBisome regarding their in vitro antifungal activities, toxicities, blood residence times, and therapeutic efficacies. Killing of Candida albicans (> 99.9%) during short-term (6-h) incubation was observed at 0.2 mg of AmB per liter for AmB desoxycholate, 0.4 mg of AmB per liter for PEG-AmB-LIP, 0.8 mg of AmB per liter for AmB-LIP, and 12.8 mg of AmB per liter for AmBisome. The maximum tolerated doses of PEG-AmB-LIP, AmB-LIP, and AmBisome were 15, 19, and > 31 mg of AmB per kg of body weight, respectively. In contrast to AmB-LIP, the blood residence time of PEG-AmB-LIP was prolonged and dose independent. In a model of systemic candidiasis in leukopenic mice at a dose of 5 mg of AmB per kg, PEG-AmB-LIP was completely effective and AmB-LIP was partially effective, whereas AmBisome was not effective. AmB-LIP at 11 mg of AmB per kg was partially effective. AmBisome at 29 mg of AmB per kg was completely effective. In conclusion, the therapeutic efficacies of AmB liposomes can be improved by preparing AmB liposomes in which a substantial reduction in toxicity is achieved while antifungal activity is retained. In addition, therapeutic efficacy is favored by a prolonged residence time of AmB liposomes in blood.

Topics: Amphotericin B; Animals; Antifungal Agents; Candidiasis; Cyclophosphamide; Drug Carriers; Female; Kidney; Leukopenia; Liposomes; Mice; Mice, Inbred BALB C

The in-vitro activities of amphotericin B-desoxycholate (AmB-DOC), liposomal amphotericin B (L-AmB) and fluconazole were determined against a single strain of Candida albicans. In addition, the efficacies of these agents in the treatment of systematic candidosis in both immunocompetent and leucopenic mice were compared. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of AmB-DOC and L-AmB were similar, but on the basis of time-kill studies, the fungicidal activity of L-AmB was significantly less than that of AmB-DOC. In immunocompetent mice, the dosage of AmB-DOC was limited by toxicity, resulting in a maximum tolerated dosage (MTD) of 0.4 mg/kg/day during treatment for 5 days; L-AMB was less toxic, the MTD being 7 mg/kg/day following a treatment period of the same duration. Both AmB-DOC and L-AmB led to significant reductions in the numbers of C. albicans in the kidneys of these mice and prevented relapse of infection after completion of treatment. Fluconazole in dosages of 0.4 and 64 mg/kg/day resulted in initial reductions in the numbers of cfu but failed to prevent relapse. In leucopenic mice, treatment for 5 days with AmB-DOC in a dosage of 0.3 mg/kg/day resulted in survival of the animals and a significant reduction in the numbers of cfu in the liver, spleen and lungs. However, there was no reduction in the number of cfu in the kidneys and this led to relapse of infection once therapy was terminated. Fluconazole in a dosage of 64 mg/kg/day produced effects which were similar to those of AmB-DOC; prolonged treatment with fluconazole for 18 days did not improve the efficacy of this agent. Only treatment with high-dosage (7 mg/kg/day) L-AmB was effective in significantly reducing the numbers of cfu of C. albicans in the kidneys and other organs of leucopenic mice, as well as preventing relapse, even in severely infected animals.

Topics: Amphotericin B; Animals; Candidiasis; Deoxycholic Acid; Drug Carriers; Drug Combinations; Female; Fluconazole; Immunocompetence; Leukopenia; Liposomes; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests

The efficacy of SCH 39304 (SCH) against Aspergillus fumigatus was assessed with an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Therapy with SCH at 10 or 15 mg/kg of body weight per day was begun 24 h after lethal challenge and compared with therapy with amphotericin B at 1.5 mg/kg/day. Compared with untreated controls, SCH reduced mortality and also reduced the tissue burden of A. fumigatus 100- to 1,000-fold in liver, kidney, and lung tissues. SCH at 15 mg/kg/day and amphotericin B eliminated A. fumigatus in liver, kidney, and lung tissues. In addition, both dosages of SCH significantly eliminated the organism from brain tissues, compared with controls. Both SCH and amphotericin B decreased or eliminated circulating aspergillus antigen. These results show that new azoles can be as effective as amphotericin B in eradicating the organism from tissues and offer promise in improving the treatment of invasive aspergillosis.

Topics: Amphotericin B; Animals; Antifungal Agents; Antigens, Fungal; Aspergillosis; Enzyme-Linked Immunosorbent Assay; Immunosuppression Therapy; Leukopenia; Rabbits; Triazoles

Topics: Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Drug Therapy, Combination; gamma-Globulins; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematologic Diseases; Humans; Leukopenia; Mycoses; Sepsis

The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the efficacies of the triazoles appeared to be due to differences in their pharmacokinetics and the dosage schedule that was used. For amphotericin B there was a good correlation between in vitro and in vivo efficacy, but this was not true of the triazole derivatives. These results further demonstrate that, with the methods used in this study, in vitro susceptibility testing of triazoles may not be predictive of in vivo activity against isolates of H. capsulatum.

Topics: Amphotericin B; Animals; Antifungal Agents; Female; Fluconazole; Histoplasma; Histoplasmosis; Leukopenia; Mice; Microbial Sensitivity Tests; Triazoles

The recovery of an adequate granulocyte count after chemotherapy is the most important prognostic factor in neutropenic patients. In granulocytopenic patients, the risk of infection is very high and its course usually severe. Empiric antibiotic treatment must be started as soon as fever rises and blood cultures have been taken. The combination of an anti-pseudomonas penicillin with an aminoglycoside is presently the standard empiric therapy for febrile granulocytopenic patients. If the clinical response is inadequate, antimicrobial therapy should be adjusted to a bactericidal activity of greater than 1:16 in the serum. If antibiotic therapy fails, a fungal infection should be considered and amphotericin B added empirically. Patients must be closely supervised for superinfections. Therapeutic transfusions of granulocytes have proven useful in severe granulocytopenia and when antibiotic therapy has failed.

Topics: Amphotericin B; Anti-Bacterial Agents; Drug Antagonism; Drug Therapy, Combination; Humans; Klebsiella Infections; Leukemia; Leukocyte Count; Leukopenia; Mycoses; Pseudomonas Infections

Topics: Adolescent; Amphotericin B; Female; Humans; Leukocyte Count; Leukopenia; Mandibular Neoplasms; Sarcoma, Ewing; Time Factors

Topics: Amphotericin B; Candidiasis; Humans; Leukopenia; Male; Middle Aged; Sepsis; Shock, Septic

A 6-year-old boy with acute monocytic leukemia and therapy-induced leukopenia developed multiple necrotizing skin lesions where an intravenous administration unit had been secured to his arm and hand. Biopsy and cultures demonstrated Aspergillus flavus as the etiologic agent without evidence of systemic dissemination. Resolution of the infection occurred following systemic amphotericin B therapy and a granulocyte transfusion.

Topics: Amphotericin B; Aspergillosis; Aspergillus flavus; Blood Transfusion; Child; Dermatomycoses; Granulocytes; Humans; Leukemia, Myeloid; Leukopenia; Male

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: Agranulocytosis; Amphotericin B; Anemia, Aplastic; Anemia, Hemolytic; Anti-Bacterial Agents; Ataxia; Bacitracin; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Chloramphenicol; Deafness; Gastrointestinal Diseases; Gentamicins; Humans; Kanamycin; Kidney Diseases; Leukopenia; Lung Diseases; Neomycin; Neuromuscular Diseases; Nitrofurantoin; Optic Neuritis; Peripheral Nervous System Diseases; Skin Diseases; Streptomycin; Sulfonamides; Tetracycline; Thrombocytopenia; Vertigo

Topics: Adolescent; Age Factors; Agranulocytosis; Amphotericin B; Bone Marrow; Child; Child, Preschool; Female; Hepatomegaly; Histoplasmosis; Humans; Leukemia, Lymphoid; Leukopenia; Male; Radiography; Remission, Spontaneous; Splenomegaly

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: Amidines; Amphotericin B; Anemia; Animals; Antimony; Blood Protein Electrophoresis; Child, Preschool; Chloroquine; Complement Fixation Tests; Diagnosis, Differential; Dogs; Haplorhini; Hepatomegaly; Humans; Leishmaniasis, Mucocutaneous; Leishmaniasis, Visceral; Leukopenia; Liver Function Tests; Metronidazole; Rodentia; Skin Tests; Splenomegaly