ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01345.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Several factors have contributed to the increasing incidence of fungal infections over the last 2 decades, including the emergence of Acquired Immune Deficiency Syndrome, increased use of myelotoxic chemotherapy and organ transplantations, prolonged use of broad spectrum antibiotics and aggressive intensive care procedures. The two most common opportunistic fungal infections seen today are caused byCandidaspp. andAspergillusspp. Systemic fungal infections in immunocompromised patients have an extremely high mortality and require aggressive therapy. Skill in identifying early clinical features is therefore crucial and the multifaceted role of the nurse is of major importance in the management of at‐risk patients. Nurses are the key resource in the prevention, early detection and treatment of fungal infection. All neutropenic patients should be thoroughly assessed at least twice a day, with special attention given to the most frequent sites of infection – the oral mucosa, lungs, skin, venepuncture sites and perineal area. Although fever is the hallmark of infection, it may be absent in the neutropenic patient who is unable to mount an adequate inflammatory response. It may also be masked by the use of certain drugs, such as steroids or analgesics. When systemic fungal infection is suspected, seriously ill patients require immediate antifungal therapy. Amphotericin B is currently the only agent with a sufficiently broad spectrum of activity to cover all the most common pathogens. Although conventional amphotericin B is effective, however, the required doses often carry significant toxicity, particularly nephrotoxicity. The new, lipid‐based forms of amphotericin B, such as Abelcet®, are indicated for and have been shown to be effective in patients with severe systemic and/or deep mycoses in whom conventional amphotericin B has proven ineffective or is contraindicated because of renal impairment, and in patients who have failed to respond to other antifunga

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01346.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: The incidence of invasive fungal infections is increasing and new fungal species are emerging as important pathogens. In cancer patients, the main risk factor for the development of systemic fungal disease is severe, prolonged neutropenia. Other factors, such as mucosal damage, presence of a central venous line, immunosuppressive therapy and treatment with broad spectrum antibiotics are contributory.Candidaspp. are the fungi most commonly isolated in neutropenic patients. There has been a dramatic increase in non‐C. albicansspecies, such asC. glabrataandC. krusei, largely as a result of extensive prophylactic and therapeutic use of fluconazole, to which these species are largely resistant. In neutropenic patients with candidaemia, amphotericin B is the drug of choice although the conventional formulation may be poorly tolerated. Lipid‐based forms of amphotericin B, such as Abelcet®, are better tolerated and can be given at a much higher dose and should therefore be considered in patients who fail on or are intolerant to the conventional agent. Aspergillosis is the second most frequent fungal infection in neutropenic patients. Primary invasive aspergillosis usually presents on chest X‐ray with lung lesions and the brain is a frequent site of secondary infection. Fluconazole is inactive againstAspergillusspp. and amphotericin B is the standard treatment. Again, lipid‐based forms are better tolerated than the conventional formulation in this setting, and have been shown to achieve response rates of 60% or more in a number of trials. Other potentially life‐threatening fungal infections in which lipid‐based amphotericin B may play an important therapeutic role in the future include cryptococcosis (increasingly problematic in AIDS patients), trichosporonosis, fusariosis and mucormycosis. Further randomized studies should be performed in a range of fungal infections to compare Abelcet®with conventional amphotericin B and other lipid‐based

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01347.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Abelcet®, or Amphotericin B Lipid Complex, is a unique formulation, comprising an equimolar mixture of amphotericin B complexed with two lipids. In preclinical studies, Abelcet® was clearly demonstrated to be less toxic than amphotericin B desoxycholate and to be effective in models where amphotericin B was ineffective at its maximum tolerated dose. Pharmacokinetic studies in animals also showed that the concentration of Abelcet® in blood is similar or reduced compared to levels seen with conventional amphotericin B, with accumulation in the liver, lungs and spleen. Phase I clinical trials determined the optimum tolerated dose of Abelcet® to be 5 mg/kg d‐1. Data are now available for 228 cases (including 51 paediatric cases) of invasive fungal infection treated with Abelcet® in an open‐label emergency‐release protocol. All patients had to have failed on previous amphotericin B or other conventional antifungals, or to have unacceptable toxicity on amphotericin B, or underlying renal disease, or nephrotoxicity due to other drugs. Abelcet® was administered at a dose of 5 mg/kg d‐1for 4 wk. Approximately one‐third of patients had candidiasis, one‐third aspergillosis and one‐third other infections, including fusariosis. Of 183 cases evaluable for response, 126 (69%) had a clinical response (cure or improvement) which was mycologically confirmed in 55% (61/110 tested). Results in paediatric cases were similar to or better than those seen in the group as a whole. When comparisons were made between cases with different types of infection, underlying disease/immunosuppressive disorder, and degree of neutropenia, the response rates were very consistent from group to group. Treatment with Abelcet® was well tolerated and mean serum creatinine levels actually declined during therapy, particularly in patients with pre‐ex

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01348.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY