amphotericin-b and Communicable-Diseases

From the point of view of pharmaceutical design, development of carrier system of antimicrobial agents with functional properties should be required. We introduced here the development-process of liposomal formulations of polyene macrolide antibiotics, amphotericin B (AmB) and nystatin as injectable dosage forms. Both development of the effective encapsulation method of these drugs in liposomes and investigation of the encapsulation mechanism and the molecular states of them are important to determine the optimum lipid composition for therapeutic uses. Enhanced encapsulation of these hydrophobic drugs, long-circulation in blood and high targetability are the required functional properties for the carrier system. Low encapsulation of AmB in liposomes has been overcome by the incorporation of polyethylene glycol-lipid derivatives, DSPE-PEG. Both the hydration with 9% sucrose solution and the complex formation between AmB and DSPE-PEG contribute not only to the enhanced encapsulation of AmB in liposomes but also to the stability and long-circulation properties in blood. Encapsulation mechanism and the molecular states of AmB in liposomes were also investigated by several methods. AmB-encapsulating PEG liposomes (PEG-L-AmB) with optimum lipid composition also showed reduced toxicity and higher therapeutic efficacy on murine model of pulmonary aspergillosis than that of conventionally used AmB formulations. Further enhanced therapeutic effects was observed by using AmB-encapsulating PEG immunoliposomes (34A-PEG-L-AmB) carrying monoclonal antibodies at the distal ends of the PEG chains. On the contrary to AmB, encapsulation characteristics of nystatin were apparently different from that of AmB, though the chemical structure is very similar. Self-association of nystatin with sterol-free lipid membrane dominantly influences on the encapsulation characteristics. Many experiments about the encapsulation of antimicrobial agents in liposomes have been demonstrated by many researchers, but there are not so much drugs developed for commercially used. Optimization of the formulation of functional drug-carrier system should be important for the practical uses.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Communicable Diseases; Drug Carriers; Drug Design; Liposomes; Lung; Nystatin; Phosphatidylethanolamines; Polyethylene Glycols; Solvents

Topics: Amphotericin B; Antifungal Agents; Chemistry, Pharmaceutical; Clinical Trials as Topic; Communicable Diseases; Cost-Benefit Analysis; Drug Carriers; Drug Delivery Systems; Drug Tolerance; Humans; Lipids; Liposomes; Treatment Outcome

Although it has been suggested that selective decontamination of the digestive tract (SDD) decreases postoperative aerobic Gram-negative and fungal infections in orthotopic liver transplantation (OLT), no controlled trials exist in pediatric patients. This prospective, randomized controlled study of 36 pediatric OLT patients examines the effect of short-term SDD on postoperative infection and digestive tract flora. Patients were randomized into two groups. The control group received perioperative parenteral antibiotics only. The SDD group received in addition polymyxin E, tobramycin, and amphotericin B enterally and by oropharyngeal swab postoperatively until oral intake was tolerated (6 +/- 4 days). Indications for operation, preoperative status, age, and intensive care unit and hospital length of stay were no different in SDD (n = 18) and control (n = 18) groups. A total of 14 Gram-negative infections (intraabdominal abscess 7, septicemia 5, pneumonia 1, urinary tract 1) developed in the 36 patients studied. Mortality was not significantly different in the two groups. However, there were significantly fewer patients with Gram-negative infections in the SDD group: 3/18 patients (11%) vs. 11/18 patients (50%) in the control group, P < 0.001. There was also significant reduction in aerobic Gram-negative flora in the stool and pharynx in patients receiving SDD. Gram-positive and anaerobic organisms were unaffected. We conclude that short-term postoperative SDD significantly reduces Gram-negative infections in pediatric OLT patients.

Topics: Adolescent; Amphotericin B; Child; Child, Preschool; Communicable Diseases; Digestive System; Female; Humans; Infant; Liver Transplantation; Male; Mycoses; Polymyxins; Prospective Studies; Tobramycin; Virus Diseases

Topics: Amphotericin B; Communicable Diseases; Critical Illness; Humans; Intraabdominal Infections; Propensity Score; Renal Insufficiency; Retrospective Studies; Sepsis

Use of intra-articular antibiotics for the treatment of arthroplasty infections has gained some interest over the last few years.. Some data exists on its use with bacterial arthroplasty infections.. We used intra-articular amphotericin B in an attempt to cure these joint infections and perform a one stage revision.. Two patients were treated with intra-articular amphotericin B for 6 weeks followed by suppressive fluconazole for 4 months. Intra-articular joint fluid was cultured during this process for re-growth of fungus.. Both patients were treated successfully with the method with follow up showing no evidence of recurrence. IA administration of amphotericin B may be an alternative treatment in these patients.

Topics: Aged; Amphotericin B; Antifungal Agents; Arthroplasty, Replacement, Knee; Candida; Candidiasis; Communicable Diseases; Female; Fluconazole; Humans; Injections, Intra-Articular; Knee Prosthesis; Male; Prosthesis-Related Infections; Synovial Fluid; Treatment Failure

We report a cluster of three extremely-low birth weight (ELBW), preterm neonates who developed late-onset sepsis (LOS) by Trichosporon asahii within a span of 1 week period. Two of these cases had the initial diagnosis of respiratory distress syndrome and the third one was admitted for low birth weight and prematurity. Initial sepsis screen was negative and blood culture was sterile in all. Late-onset sepsis was developed after the first week of life and the presenting features were lethargy, feeding intolerance, bleeding manifestations, positive sepsis screen and severe thrombocytopaenia. The isolates were sensitive to voriconazole but resistant to both amphotericin-B and fluconazole on all occasions. All the infants were treated with liposomal amphotericin-B before the availability of culture reports but the clinical deterioration was rapid and all three neonates succumbed to death before we could procure voriconazole. The source of the outbreak could not be identified from multiple surface cultures from the unit and screening of the health care staffs. We emphasise the need for high index of suspicion for unusual fungal pathogens, resistant to conventional antifungal drugs while treating preterm neonates with LOS.

Topics: Amphotericin B; Antifungal Agents; Communicable Diseases; Drug Administration Schedule; Drug Resistance, Fungal; Fatal Outcome; Guideline Adherence; Humans; Infant; Infant, Newborn; Infant, Premature; Sepsis; Trichosporon; Trichosporonosis; Voriconazole

Visceral leishmaniasis (VL, kala-azar) is caused by Leishmania spp, a parasite that is commonly encountered in Mediterranean countries. Leishmaniasis usually presents with fever, hepatosplenomegaly, lymphadenopathy, and pancytopenia.. The aim of the study was to prospectively examine the characteristics of cytopenia associated with VL and compare it with other post-infectious cytopenias observed in children with febrile illnesses.. We studied 112 children, aged (mean) 4.0 (SD, 3.8) years (range, 0-14 years), who were admitted to the pediatric ward because of febrile cytopenia associated with infections, during a 2-year period (March 2005 to June 2007). Study participants were investigated with measurement of acute-phase reactants, bacterial cultures, and serologic tests.. Pancytopenia was detected in 9 (8%) of 112 patients (5 boys), with a mean age of 4.5 (SD, 3.0) years.The mean value of white blood cell was 3827 (SD, 1455)/mL; absolute neutrophil count, 1229 (SD, 655)/mL; hemoglobin, 8.3 (SD, 1.1) g/dL; and platelet count, 88,200 (SD, 20,186)/mL. All patients with pancytopenia had fever (mean duration, 8.9 [SD, 8.7] days) (maximum temperature, 39.5°C [SD, 0.6°C]) and hepatosplenomegaly (9/9), whereas 2 of 9 had lymphadenopathy. In these patients, a bone marrow aspiration was performed, and VL was detected in all 9 samples. They were treated with liposomal amphotericin B and had an excellent response rate. Pancytopenia resolved within a mean period of 17.6 (SD, 17.3) days (range, 8-60 days), and there was no relapse during a 2 years' follow-up.. In endemic countries, leishmaniasis is the main cause of febrile pancytopenia among children in whom hematologic malignancy has been ruled out.

Topics: Adolescent; Amphotericin B; Antiprotozoal Agents; Child; Child, Preschool; Communicable Diseases; Endemic Diseases; Female; Greece; Humans; Infant; Infant, Newborn; Leishmaniasis, Visceral; Male; Pancytopenia; Prospective Studies

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

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Clindamycin; Communicable Diseases; Fluconazole; HIV Infections; Humans; Opportunistic Infections; Pentamidine; Pyrimethamine; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Amphotericin B; Child; Communicable Diseases; Encephalitis; Female; Humans; Immunoglobulins; Injections, Spinal; Male; Prognosis

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; Candida albicans; Candidiasis; Chloramphenicol; Communicable Diseases; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Nystatin; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Tetracycline