UMLS:C0027947 - FACTA Search

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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently succeeded in eradicating a Fusarium infection by treatment with liposomal amphotericin B (L-AmB). The patient, a 22-year-old man with acute lymphoblastic leukaemia (ALL), developed fever and diffuse cutaneous maculopapular necrotising nodules during post-chemotherapy neutropenia. Fusarium verticilloides was isolated from the skin, and hyphae were observed on direct microscopy. Despite increased WBC and amphotericin B (AmB) treatment (0.7 mg/kg/day for 11 days), he remained febrile and a chest X-ray revealed pulmonary lesions. Fusarium infection was confirmed by bronchial aspirate. AmB was increased to 1 mg/kg/day, and continued for 16 days (total dose 1630 mg). A slight improvement was observed at tomography, but nephrotoxicity developed. Treatment was changed to L-AmB (3 mg/kg/day). The patient received this drug for 20 days (total dose of 3850 mg) with complete regression of the pulmonary lesions. No adverse event occurred, and nephrotoxicity resolved. The patient was discharged from hospital cured of the Fusarium infection and in clinical and haematological remission. No relapse of fusariosis occurred, despite additional courses of intensive chemotherapy. Ambisome could represent an important advance in antifungal treatment since it allows aggressive treatment and eradication of mycoses refractory to conventional therapy while avoiding renal toxicity.
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PMID:Efficacy of liposomal amphotericin B (AmBisome) in the eradication of Fusarium infection in a leukaemic patient. 142 36

The last decade has been remarkable for the dramatic increase in the prevalence of serious fungal infections in patients with haematological disorders and neutropenic cancer patients. The mortality rate of deep-seated infection has been in excess of 90% and there is no doubt that this is one of the greatest challenges currently facing haematologists and oncologists. The development of the lipid-based drugs - liposomal amphotericin (AmBisome(R)), amphotericin B lipid complex, ABLC (Abelcet(R)), amphotericin B colloidal dispersion, Amphocil (ABCD(R)), has meant that doses of amphotericin B can be safely escalated for the first time whilst the problems of nephrotoxicity, infusion related reactions (including chills, rigors, fevers and hypoxia) can be reduced. These toxicities are variably reduced with AmBisome more than Abelcet and more than Amphocil and there is little information from randomised trials other than for AmBisome. AmBisome used in the setting of persistent fever and neutropenia not responding after 3-4 days of intravenous antibiotics, is associated with less breakthrough systemic fungal infections. There is also much less need for premedication, including steroids, compared with amphotericin B and Abelcet. The use of intermittent doses of Ambisome given prophylactically is now being explored. A new and exciting era of antifungal therapy is opening up with new compounds, such as itraconazole voriconazole, posaconazole and echinocandins, being investigated and for the first time, we also have options for combination therapy and prophylaxis.
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PMID:Lipid-based amphotericin B: a review of the last 10 years of use. 1128 60

The hazards associated with invasive candidiasis and aspergillosis in oncology patients are well recognised. These conditions typically present late in treatment, often after prolonged or recurrent episodes of neutropenia. We report the occurrence of Absidia corymbifera infection causing rhinocerebral zygomycosis in two children with acute lymphoblastic leukaemia, early in the induction phase of treatment and within a 3-month interval, in the same oncology unit. The initial presentation of facial pain was rapidly followed by the development of cranial nerve palsies, cavernous sinus thrombosis, diabetes insipidus, seizures and death within 9 days of symptom onset, despite aggressive management with high-dose liposomal amphotericin (Ambisome), surgical debridement and local instillation of amphotericin solution. These cases highlight the need for awareness of zygomycosis as a potentially lethal fungal infection that can present even with short duration exposure to the usual risk factors. Their occurrence within a limited time period raises questions as to the relative importance of environmental exposure. The failure of medical and surgical intervention to impact on the course illustrates the need to develop appropriate preventative strategies which may have to incorporate measures to reduce the environmental exposure of susceptible patients.
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PMID:Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia. 1131 46

Invasive fungal infections are rare but life-threatening infections, most often occurring in immunocompromised patients. For a long time, Amphotericin B has been the best choice for treatment, because it is fungicidal with a broad antifungal spectrum and minimal risk of resistance development. The therapeutic use of amphotericin B has, however, been limited by its toxicity-both acute as well as chronic. To counter this, amphotericin B has been encapsulated in liposomes, which reduces its toxicity and allows higher doses to be given. Ambisome is a true, spherical, small unilamellar liposome with a median size of 80 nm. The pharmacokinetic profile was changed, and the maximum concentration and AUC of amphotericin B after AmBisome treatment were greater than those found with the conventional drug. The highest tissue concentrations of AmBisome were found in the liver and spleen, and less than 1% of the administered dose was recovered in other organs. At Huddinge University Hospital, we were the first to use and report on the experience of AmBisome. We now have more than 12 years' experience in transplant recipients, with a good safety profile, improved rate of curing mycological proven infections and reduced mortality in fungal infections. In two placebo-controlled prophylactic trials, we found that AmBisome was effective for preventing fungal colonization and invasive fungal infections, respectively, in allogeneic stem cell and liver transplantation. In uncontrolled and, more recently, in randomized controlled studies at other centers, AmBisome has revealed less toxicity and an efficacy equal or superior to that of the conventional drug in treating neutropenia-associated fever and proven invasive fungal infections in both adults as well as in children. Although investigators tend to increase the dose used, the optimal dose for probable or proven infection is still under debate. Based on our own experience in using AmBisome and the experience at other centers, we can conclude that AmBisome represents a major breakthrough in the treatment of invasive fungal infections, especially in immunocompromised patients.
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PMID:Liposomal amphotericin B (AmBisome) for fungal infections in immunocompromised adults and children. 1152 21

Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Antimicrob Agents Chemother 57:1866-1871, 2013, https://doi.org/10.1128/AAC.02226-12). We here investigated the role of immune suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus harboring a TR₃₄/L98H mutation in the cyp-51A gene. Survival of treated animals at day 14 in both immunosuppressed models was significantly better than that of nontreated controls. A dose-response relationship was observed that was independent of the azole-resistant mechanism and the immunosuppression method used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16 mg/kg of body weight for the WT strain and the TR₃₄/L98H isolate. In the steroid-treated group, 90.9% survival and 100% survival were achieved for the WT isolate and the TR₃₄/L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50% effective dose (ED₅₀) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00 mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the TR₃₄/L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to 2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for the TR₃₄/L98H isolate in the steroid-treated group. Overall, there were no significant differences between the two different immunosuppressed conditions in the efficacy of L-AmB against the wild-type and azole-resistant isolates (P > 0.9). However, the required L-AmB exposure was significantly higher than that seen in the immunocompetent model.
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PMID:In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression Models of Invasive Aspergillosis. 2841 40