Biomedical subjects

V Letscher-Bru

Publications and source records attributed to V Letscher-Bru.

17 recordsLinked to original sources

PubMed2006

Combination of caspofungin and an azole or an amphotericin B formulation in invasive fungal infections.

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.

Adolescent↗

PubMed2005

Epidemiological study of invasive pulmonary aspergillosis in a haematology unit by molecular typing of environmental and patient isolates of Aspergillus fumigatus.

In order to determine the possible relationship between environmental contamination by Aspergillus fumigatus and occurrence of invasive aspergillosis, a one-year prospective study was carried out in the haematology ward of Hautepierre Hospital, Strasbourg, France. During the study period, 21 environmental isolates and 26 clinical isolates of A. fumigatus were collected. Each was genotyped using a random amplification of polymorphic DNA (RAPD) technique. Thirty-four distinct profiles were identified by RAPD analysis, indicating the great genetic diversity of A. fumigatus isolated from infected patients and from the environment. For two patients, RAPD analysis demonstrated concurrent infection by at least two different strains. In two cases, a genetic similarity was noted between isolates obtained from a patient and from the environment.

Air Microbiology↗

PubMed2005

Invasive aspergillosis in the hematologic and immunologic patient: new findings and key questions in leukemia.

Patients suffering from acute leukemia are at high risk for invasive aspergillosis and a large review and a recent clinical trial have shown that they represent the largest group of patients developing the disease. New host groups such as patients with multiple myeloma or low-grade lymphoproliferative disorders have contributed to an increase in the incidence of invasive aspergillosis over recent years. There are substantial differences in the diagnostic strategy and therapeutic outcome of disease between patients with a hematological malignancy and other host groups such as allogeneic hematopoietic stem cell transplant patients. Galactomannan detection ELISA test is more specific in adult patients with hematological malignancies than in hematopoietic stem cell transplantation recipients. As a result of possible improvement of the underlying immune deficiency upon recovery from neutropenia, survival is higher in leukemic patients with invasive aspergillosis than in other host groups. However, there is currently no evidence of an effective antifungal prophylaxis strategy against aspergillosis in leukemic patients. As these patients account for a majority of the aspergillosis cases, clinical trials on prophylaxis should not only be focused on allogeneic stem transplant recipients but also be designed for the patient with leukemia.

Aspergillosis↗

PubMed2005

Management of systemic fungal infections: alternatives to itraconazole.

For many years, amphotericin B and flucytosine have been the only antifungal agents for invasive fungal infections. Amphotericin B was the standard of care for most of these infections. However, its use was often associated with low efficacy and poor tolerance. Fortunately, the antifungal armamentarium has increased during the past two decades with the addition of several new agents. In addition to itraconazole and fluconazole, lipid formulations of amphotericin B, voriconazole, caspofungin and micafungin have arrived on the market. Other agents are expected to be licensed shortly (anidulafungin, posaconazole). These various antifungal agents differ in their spectrum, pharmacokinetic profile, route of administration, efficacy in clinical trials, safety profile, drug-drug interactions and, importantly, their cost. There is no longer a unique standard agent for all or nearly all invasive fungal infections but a real choice among several agents. The characteristics of these new agents are reviewed to help clinicians in their decision to select an antifungal agent for their patients.

Amphotericin B↗

PubMed2004

[Allergic fungal sinusitis: ten cases].

OBJECTIVES: Diagnosis, nosological individualization, and treatment of allergic fungal sinusitis remain difficult and controversial despite the increasing number of publications. We present ten cases of allergic fungal sinusitis and review the literature to highlight the main clinical, radiological, biological, immunoallergological, mycological, and therapeutics features. MATERIAL AND METHODS: This retrospective study included ten patients (six men and four women, mean age 45 years) with allergic fungal sinusitis diagnosed on the basis of all diagnostic criteria reported in the literature. RESULTS: Six patients had isolated allergic fungal sinusitis which was associated with allergic bronchopulmonary aspergillosis in the four others. Treatment combined endoscopic sinus surgery and corticosteroids, which provided good results in six patients and average results in three. Treatment failure was observed in one patient. CONCLUSION: As in the case of allergic bronchopulmonary aspergillosis, a set of clinical, radiological, histopathological, immunoallergological and mycological criteria is necessary for precise diagnosis and to avoid fungal drift. The most appropriate endoscopic sinus surgery and the best corticosteroid regimen remain to be determined.

Adult↗

PubMed2002

Acremonium strictum pulmonary infection in a leukemic patient successfully treated with posaconazole after failure of amphotericin B.

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.

Acremonium↗

PubMed2002

Chronic disseminated Trichosporon asahii infection in a leukemic child.

We report a case of chronic disseminated Trichosporon asahii infection in a leukemic child. Administration of amphotericin B lipid complex resulted in rapid control and improvement of the initial infection but failed to prevent the development of chronic disseminated disease. Cure was achieved after treatment was changed to a 20-month course of itraconazole. This case report demonstrates that Trichosporon species can cause chronic disseminated disease with a pattern similar to that of disease caused by Candida species.

Acute Disease↗

PubMed2001

[Visceral candidiasis].

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.

Administration, Oral↗

PubMed2001

Efficacy of amphotericin B lipid complex in the treatment of invasive fungal infections in immunosuppressed paediatric patients.

The safety and efficacy of amphotericin B lipid complex (ABLC) were evaluated in a retrospective study of 46 paediatric patients with invasive infections. The study included a large proportion of patients who were refractory to or intolerant of conventional antifungal therapy. The mean age of the children was 9.7 +/- 4.8 years. Primary underlying conditions included mainly haematopoietic stem cell transplantation, leukaemia and lung transplantation. The mean daily dose given was 4.11 mg/kg for a mean duration of 38.7 days. At the end of therapy, 38 of 46 (83%) patients responded successfully to treatment with ABLC, including 18 of 23 (78%) with aspergillosis and 17 of 19 (89%) with candidiasis. ABLC was well tolerated, with a low incidence of adverse events. The mean creatinine value was 74.5 microl/mol/l at baseline and 78.2 micromol/l at the end of therapy. These results support the use of ABLC in the treatment of invasive fungal infections in children, including patients who have previously failed, or are intolerant of, traditional antifungal regimens.

Adolescent↗

PubMed2001

Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion.

The aim of this study was to review the characteristics and outcome of 21 patients with invasive mucormycosis treated with amphotericin B colloidal dispersion (ABCD) in five phase I and phase II studies. Mucormycosis is an increasing concern in immunocompromised patients, in whom mortality exceeds 60%. The standard treatment has been amphotericin B combined with surgical debridement. Twenty-one patients with invasive mucormycosis treated with ABCD, a lipid complex of amphotericin B and cholesteryl sulfate, were identified. Patients were given ABCD on the basis of pre-existing renal insufficiency, development of nephrotoxicity during amphotericin B therapy, or fungal infection that failed to respond to amphotericin B. Response could be evaluated in 20 patients, all of whom had bone marrow or organ transplantation, haematologic malignancies, or diabetes. Infection was disseminated in six patients and localised to the sinuses, lower respiratory tract, or skin in the other patients. ABCD was given at a mean dose of 4.8 mg/kg per infusion for a mean duration of 37 days. Twelve of 20 patients responded to ABCD therapy. Response rates were similar when patients were treated with ABCD alone (4/7) and ABCD combined with surgery (8/13), with more complete response obtained in the latter group. No difference in response rate was observed in leukaemic patients (3/5) or transplant recipients (6/10) compared to diabetics (3/5). No renal or hepatic toxicity was observed. These results compare favourably with the results of standard treatment and suggest that ABCD combined with surgery may be a useful therapy in patients with mucormycosis.

Adolescent↗

PubMed2001

[New lipid formulations of amphotericin B. Review of the literature].

INTRODUCTION: Amphotericin B (amB) remains the gold standard for treatment of invasive fungal infections. Lipid formulations of amB have been developed in an attempt to improve both efficacy and tolerability (especially renal toxicity): amB lipid complex (ABLC), liposomal amB (AmBisome), amB colloidal dispersion (ABCD) and amB in lipid emulsion (Intralipid). This review analyzes the data available in the literature. CURRENT KNOWLEDGE AND KEY POINTS: ABLC, AmBisome and ABCD are effective in various fungal infections, including invasive aspergillosis, systemic candidiasis, cryptococcal meningitis, mucormycosis and fusariosis. These formulations are also effective in persistent febrile neutropenia and in leishmaniosis. The three formulations show little renal toxicity and are safer than conventional amB in this respect. Preliminary data are available on amB in Intralipid: infusion-related adverse effects are reduced, but few data are available on efficacy in documented mycoses. FUTURE PROSPECTS AND PROJECTS: Large-scale comparative clinical trials may clarify issues of relative efficacy in various forms of fungal infections.

Amphotericin B↗

PubMed2000

Fungal infections in patients with neutropenia: challenges in prophylaxis and treatment.

Fungal infections are a leading cause of mortality in patients with neutropenia. Candidiasis and aspergillosis account for most invasive fungal infections. General prophylactic measures include strict hygiene and environmental measures. Haemopoietic growth factors shorten the duration of neutropenia and thus may reduce the incidence of fungal infections. Fluconazole is appropriate for antifungal prophylaxis and should be offered to patients with prolonged neutropenia, such as high-risk patients with leukaemia undergoing remission induction or consolidation therapy and high-risk stem cell transplant recipients. Empirical antifungal therapy is mandatory in patients with persistent febrile neutropenia who fail to respond to broad-spectrum antibacterials. Intravenous amphotericin B at a daily dose of 0.6 to 1 mg/kg is preferred whenever aspergillosis cannot be ruled out. Lipid formulations of amphotericin B have demonstrated similar efficacy and are much better tolerated. Fluconazole is the best choice for acute candidiasis in stable patients; amphotericin B should be used in patients with unstable disease. Use of fluconazole is restricted by the existence of resistant strains (Candida krusei and, to a lesser extent, C. glabrata). Amphotericin B still remains the gold standard for invasive aspergillosis. Lipid formulations of amphotericin B are effective in aspergillosis and because they are less nephrotoxic are indicated in patients with poor renal function. Itraconazole is an alternative in patients who have good intestinal function and are able to eat. Mucormycosis, trichosporonosis, fusariosis and cryptococcosis are less common but require specific management. New antifungal agents, especially new azoles, are under development. Their broad in vitro spectrum and preliminary clinical results are promising.

Antifungal Agents↗

PubMed1999

Isolated renal Aspergillus abscess in an AIDS patient with a normal CD4+ cell count on highly active antiretroviral therapy.

Isolated renal Aspergillus abscess is a very rare complication of HIV infection. It usually occurs in patients with severe immune deficiency. The case of a 29-year-old HIV-infected homosexual male, a nonintravenous drug abuser, who developed a right renal Aspergillus abscess despite normalization of the CD4+ cell count after highly active antiretroviral treatment is described. When antimicrobial treatment failed (amphotericin B followed by itraconazole), he was cured by right nephrectomy and remains in good health 3 months later with no recurrence. In cases of Aspergillus renal abscess in HIV-infected patients, surgery is the treatment of choice, especially in the current era of highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed1999

Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability.

Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%. Moreover, amB is toxic, especially for the kidneys. New formulations have been developed in an attempt to improve both efficacy and tolerability. In an attempt to reduce toxicity, a number of investigators have reconstituted amB in a lipid emulsion, but few data are available on efficacy in documented infections. An improvement in immediate and renal tolerance was obtained with equivalent daily dose regimens, but the therapeutic index does not appear to be improved. This approach cannot be recommended at present. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (AmBisome). The efficacy of ABCD on various fungal infections has been assessed in open trials, with a response rate of 49% in aspergillosis, 70% in candidiasis, and 67% in mucormycosis. In two randomized trials comparing ABCD with amB in invasive aspergillosis and in persistent febrile neutropenia, the response rates were equivalent. ABCD was less nephrotoxic. In contrast, immediate reactions to ABCD were as frequent and severe as with amB. These immediate effects are more frequent during the first infusions and lessen as treatment continues. The recommended dose is 3-4 mg/kg/day. ABLC appeared to be effective as rescue therapy in various types of invasive mycoses, with a response rate of 42% in aspergillosis, 67% in candidiasis, and 82% in fusariosis. Efficacy identical to that of amB was demonstrated in a comparative randomized trial involving patients with invasive candidiasis. General and renal tolerability is improved compared with amB. The recommended dose regimen is 5 mg/kg/day. Liposomal amB (AmBisome) is the only truly liposomal formulation. The response rates in preliminary trials were 66% in aspergillosis and 81% in candidiasis. Several comparative studies have confirmed that this formulation has similar or superior efficacy relative to amB in various fungal infections and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. The optimal dosing remains unclear but is generally between 3 and 5 mg/kg/day. A double-blind trial comparing the tolerance of liposomal amB and ABLC demonstrated that both infusion-related events and nephrotoxicity were significantly lower for liposomal amB. In sum, the new lipid formulations of amB are effective in various invasive fungal infections. The three formulations exhibit reduced nephrotoxicity compared with conventional amB. Large-scale comparative clinical trials may clarify issues of relative efficacy in various forms of mycotic infections.

Amphotericin B↗

PubMed1999

Candida catenulata fungemia in a cancer patient.

We report the first case of fungemia due to Candida catenulata, a contaminant of dairy products. C. catenulata was isolated from three blood cultures of a patient with gastric cancer. The patient failed to respond to fluconazole but recovered after treatment was switched to amphotericin B. In vitro, C. catenulata was susceptible to amphotericin B and itraconazole and was also susceptible to fluconazole in dose-dependent manner. The likely portal of entry was the digestive tract, as the patient often ate cheese and had multiple gastric ulcerations.

Adult↗

PubMed1998

Protective effect of vaccination with a combination of recombinant surface antigen 1 and interleukin-12 against toxoplasmosis in mice.

We studied the immune response induced in mice by recombinant Toxoplasma gondii surface antigen 1 (rSAG1) protein, alone or combined with interleukin-12 (IL-12) as an adjuvant, and the protective effect against toxoplasmosis. Immunization with rSAG1 alone induced a specific humoral type 2 immunity and did not protect the animals from infection. In contrast, immunization with rSAG1 plus IL-12 redirected humoral and cellular immunity toward a type 1 pattern and reduced the brain parasite load by 40%.

Adjuvants, Immunologic↗

PubMedDate not supplied

Role of gamma interferon and T cells in congenital Toxoplasma transmission.

In the BALB/c mouse model, primary infection with Toxoplasma gondii during the second third of gestation leads to a high percentage of infected foetuses. However, immunity induced by infection contracted before pregnancy prevents parasites from crossing the placenta and completely protects the foetuses, as well as the pregnant women. In order to clarify the roles of CD4+, CD8+ T lymphocytes and IFN-gamma in this protection, pregnant BALB/c mice were treated with depleting monoclonal antibodies against CD4, CD8, IFN-gamma, or control antibody. Only the foetuses of the groups treated with anti-CD8 and anti-IFN-gamma antibodies developed congenital toxoplasmosis. The maternal production of IFN-gamma was depressed in the mice depleted of CD4 and CD8 cells (P < 0.001). Determination of the blood parasite load demonstrated that materno-foetal transmission of T. gondii correlates with maternal parasitaemia. Together, these results show that CD8+ T lymphocytes and IFN-gamma play an important role in protection against congenital toxoplasmosis during reinfection.

Animals↗