critic - treatment of candidemia and invasive candidiasis

Conditions: Candidemia; Invasive Candidiasis

Summary: patients will receive 2mg/kg/day iv daily administration of ambisome® over 30-60 minutes as a reaction to signs/symptoms and positive candida culture

subjects will be enrolled to receive intravenously ambisome® at 2 mg/kg/day for a maximum of 4 weeks. treatment will be discontinued in case of failure, adverse events precluding treatment or success. in case of success ambisome® at 2 mg/kg/day should be administered for at least 5 days after the complete resolution of all clinical findings of an active infection or for at least 8 days after the last positive blood culture or culture from a normally sterile site. it is not recommended to declare failure (and therefore change treatment) before giving at least 5 days of antifungal therapy. failures in patients given less than 5 days of treatment should be well documented (e.g. persistent positive cultures despite catheter removal, clinical deterioration in absence of any explanation other than the fungal infection). follow-up evaluations will be conducted at 2 and 4 weeks after the end of ambisome® therapy. at end of treatment (time point for success or failure) patients may be shifted to oral (not intravenous) antifungals at the discretion of the local investigator, once a complete response has been achieved, if secondary prophylaxis is deemed necessary.

Eligibility criteria:
inclusion criteria: * patients admitted to icu for all medical reasons that meet the inclusion criteria * males or non pregnant females (women of child-bearing potential must have a negative serum or urine pregnancy test at baseline). * subjects who are 14 years old or older. * subjects with at least one positive blood culture isolation of a candida spp. from a specimen or from a normally sterile site (including abdominal catheters), drawn within 96 hours prior to study entry. * subjects who have clinical evidence of infection at some time within 48 hours prior to enrollment, including at least one of the following: 1. temperature\> 38°c on 2 occasions at least 4 hours apart or one determination greater than 38.5°c (internal, at oesophagus, tympani or bladder levels). 2. systolic blood pressure \ 30 mm hg decrease in systolic bp from the subject's normal baseline. 3. signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with candida * subjects or their legal representative (but the subject should sign it in any case when able to) must sign a written informed consent form. written informed consent must be obtained before any study-related procedure is carried out. exclusion criteria: * subjects with a history of allergy or intolerance to ambisome® * subjects who have received systemic antifungal therapy within 15 days prior to inclusion in the study * any severe cardiovascular disease (such as arrhythmias, in particular) which may constitute a contra-indication to ambisome® administration * subjects with an absolute neutrophil count of less than 500/mm3 in the 48 hours before enrolment in the study * subjects with a diagnosis of aids (positive hiv serology in association with either cd4 cell counts \< 200 cells/mm3or history of an opportunistic infection /neoplasm), aplastic anemia, or chronic granulomatous disease. * subjects with moderate or severe liver disease defined as any one or more of the following: \* alkaline phosphatase, alt, ast, or total bilirubin greater than 5 times the uln (upper limit of normal) * subjects with a severe renal impairment defined by a serum creatinine of more than 2.5 mg/dl. * women who are pregnant or breastfeeding. * subjects who are unlikely to survive more than 24 hours. * subjects who previously participated in this study. * subjects who have received within the two weeks before study entry, are receiving or likely to receive any investigational drug (unlicensed new chemical entity).

Keywords: candidemia invasive candidiasis ambisome liposomal amphotericin b