ABSTRACT
OBJECTIVES: Combination of caspofungin and another anti-fungal agent raise expectation of improved efficacy in severe fungal infections including failures to first line therapy. METHODS: We assessed the efficacy and safety of a combination therapy including caspofungin in 17 immunosuppressed or postoperative patients progressive despite standard anti-fungal therapy. RESULTS: The infections included aspergillosis (6), invasive candidiasis (9), mucormycosis (1) and Scedosporium pneumonia (1). Infections had failed one to four prior lines of treatment. The anti-fungal agent combined to caspofungin was either an amphotericin B formulation or an azole. There were 12 favourable responses (71%) and five failures. The survival rate at 3 months was 47%. Eleven patients died within 2-533 days. The causes of death included the initial fungal infection (4), relapse of the infection after switching to oral monotherapy (2), breakthrough aspergillosis (1), and the underlying condition (4). Clinical and renal tolerance were good. Significant hepatic abnormalities were recorded in eight (50%) of the 16 patients evaluable for biological tolerance. CONCLUSION: Caspofungin combined with an azole or with amphotericin B may be of interest in the treatment of serious fungal infections after failure of conventional therapy. Close monitoring of hepatic function is required. These approach should be evaluated in prospective trials.
Subject(s)
Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Fluconazole/administration & dosage , Fluconazole/therapeutic use , Mycoses/drug therapy , Peptides, Cyclic/administration & dosage , Peptides, Cyclic/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Amphotericin B/adverse effects , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Caspofungin , Child, Preschool , Drug Therapy, Combination , Echinocandins , Humans , Lipopeptides , Middle Aged , Peptides, Cyclic/adverse effects , Risk FactorsABSTRACT
A severely neutropenic patient with chronic lymphocytic leukemia developed a diffuse bilateral pulmonary infection while receiving a therapeutic daily dosage of intravenous amphotericin B for Candida glabrata esophagitis. Computed tomography of the chest showed numerous lung nodules, ground glass areas and a pleural effusion. Biopsy of one nodule demonstrated hyaline septate hyphae. Multiple sputum cultures grew Acremonium strictum. Increasing the dose of amphotericin B and the addition of itraconazole did not resolve the infection. Change of treatment to posaconazole given orally at 200 mg four times/d resulted in progressive improvement leading finally to cure after 24 weeks of therapy. Treatment with posaconazole was clinically and biologically well tolerated.
Subject(s)
Acremonium/drug effects , Acremonium/isolation & purification , Amphotericin B/administration & dosage , Immunocompromised Host , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Triazoles/administration & dosage , Administration, Oral , Antifungal Agents/administration & dosage , Biopsy, Needle , Female , Follow-Up Studies , Humans , Microbial Sensitivity Tests , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Risk Assessment , Tomography, X-Ray Computed , Treatment Failure , Treatment OutcomeABSTRACT
An analytical approach based on sheathless on-line coupling of capillary electrophoresis (CE) and electrospray ionization (ESI) quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been developed for providing new insight into the characterization of carbohydrate mixtures. The home-built sheathless CE/
Subject(s)
Carbohydrates/analysis , Electrophoresis, Capillary/methods , Spectrometry, Mass, Electrospray Ionization/methods , Carbohydrate Metabolism, Inborn Errors/enzymology , Carbohydrate Metabolism, Inborn Errors/genetics , Carbohydrate Metabolism, Inborn Errors/urine , Carbohydrate Sequence , Electrophoresis, Capillary/instrumentation , Glycoconjugates/analysis , Glycopeptides/urine , Glycosylation , Hexosaminidases/deficiency , Hexosaminidases/genetics , Humans , Molecular Sequence Data , Polysaccharides/chemistry , Urinalysis/methods , alpha-N-AcetylgalactosaminidaseABSTRACT
Invasive candidiasis is a frequent infection in compromised patient. Several risk factors have been identified and include neutropenia, broad-spectrum antibiotherapy, colonisation with a Candida spp. and presence of central venous catheter. Candidemia is the most common clinical aspect. Diagnosis is based on positive culture of blood, skin biopsy or fine needle aspiration of a deep-seated lesion. Serology is not helpful in severely immunocompromised patients. Prophylaxis is based on strict hygiene and, in neutropenic patients, oral fluconazole. Treatment of an invasive candidiasis depends on the localisation of the infection, of its acute or chronic evolution, on the species involved and on underlying condition. Amphotericin B deoxycholate or in lipid formulation and fluconazole are the antifungal drugs of choice. Removal of a central venous catheter should always be discussed in candidemia.
Subject(s)
Candidiasis , Administration, Oral , Adult , Antifungal Agents/therapeutic use , Candidiasis/diagnosis , Candidiasis/therapy , Catheterization, Central Venous/adverse effects , Female , Fluconazole/administration & dosage , Fungemia/diagnosis , Humans , Immunosuppression Therapy/adverse effects , Infant, Newborn , Leukocyte Transfusion , Male , Neutropenia/complications , Prognosis , Risk Factors , Tomography, X-Ray ComputedABSTRACT
The use of off-line high-performance capillary electrophoresis in connection with nanospray electrospray ionization quadrupole time-of-flight tandem mass spectrometry for identification of complex carbohydrates of biological origin is presented. The method was applied to the identification of O-glycosylated amino acids and -glycopeptides from the urine of patients suffering from a hereditary disease - N-acetylhexosaminidase deficiency. Structural elements typical for O-glycosylation of proteins, like expression of core 1 and 2 type O-glycans with different numbers of N-acetyllactosaminyl repeats and different degrees of sialylation, can be directly detected.
