Hair clipping: another hazard for granulocytopenic patients?
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Aged↗
Biomedical subjects
R Hopfer
Publications and source records attributed to R Hopfer.
The emerging role of Fusarium infections in patients with cancer.
Infection due to Fusarium species is an increasing cause of serious potentially fatal disease in patients with cancer. We described 9 patients with infection caused by Fusarium species during a 4-year period at the M. D. Anderson Hospital. The spectrum of infections included disseminated disease in 4 patients, skin or soft-tissue infections in 3, pneumonia in 1, and fungemia in 1. All 4 patients with disseminated infection had culture- and biopsy-proven skin lesions caused by Fusarium species and the blood cultures yielded the organism in 3 of these 4 patients. Maxillary sinusitis was the presenting manifestation of Fusarium infection in 2 of these 4 patients, suggesting that paranasal sinuses are potential portals of entry for the infection. Eight patients had a hematological malignancy and 7 were neutropenic at the onset of their infection. Patients with deep-seated infections remained neutropenic and died from infection despite treatment with amphotericin B. All 5 isolates tested in vitro showed resistance to ketoconazole and miconazole, whereas 3 were susceptible to amphotericin B. Fusarium species could play a role in producing myelosuppression and fungal cultures are required to differentiate it from the more commonly encountered Aspergillus species. Fusarium species are emerging as a serious, potentially fatal, pathogen in patients with cancer.
Adolescent↗
Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study.
Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.
Adolescent↗
Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections.
Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency. Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier. Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice. The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals. The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes. AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi. By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells. Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals.
Amphotericin B↗
Systemic candidiasis in cancer patients.
Two hundred thirty-five fungal infections occurred in patients with malignant diseases over a four-year period. One hundred eighty-eight were due to Candida species and Torulopsis glabrata and are reviewed herein. The frequency was highest in patients with acute leukemia (11.9 per 100 registrations) with a frequency of 0.8 per 100 registrations in all cancer patients at this institution. Three or more predisposing factors were present in more than 50 percent of the cases; antecedent myelosuppression, chemotherapy, and antibiotic therapy were most common. Blood cultures were positive in only 35 percent of patients with disseminated candidiasis. Twenty-nine of 55 patients (53 percent) had candidemia without identifiable organ infection recovered. Eleven were given no systemic antifungal therapy and recurrence of infection was documented in two patients. Only six (4.5 percent) of 133 patients with proved deep organ infections recovered. Respiratory failure was the clinical cause of death in 62 percent of patients. Clinical features, cultures, and serologic tests were usually of no assistance in establishing the diagnosis early in the course of the infection.
Acute Disease↗
Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells.
Amphotericin B is an efficacious but extremely toxic anti fungal drug. Recently it has been shown that the incorporation of Amphotericin B in multilamellar liposomes results in a marked reduction in drug toxicity in mice with no loss of anti fungal potency. Until now, the mechanistic basis of the enhanced therapeutic index of liposomal Amphotericin B has been unclear. In this report, however, we show that the in vivo effects can be mimicked in vitro where free but not liposomal Amphotericin B causes lysis of erythrocytes while both free and liposomal drug kill fungal cells. These results suggest that the markedly improved therapeutic index of liposomal Amphotericin B is largely due to a fundamental alteration in the ability of the drug to interact with mammalian cell membranes rather than to alterations in pharmacokinetics or drug distribution.
Amphotericin B↗
Aspergillus epiglottitis.
A 21-year-old woman with acute lymphocytic leukemia developed clinical and radiographic signs of epiglottitis. Premortem and postmortem histologic studies showed invasive aspergillosis; Aspergillus flavus was grown in culture. The necrotizing nature of this infection is explained by the predilection of Aspergillus sp. for invasion of blood vessels. The usual causative agents of epiglottitis are bacteria; the association with fungal infection has not been previously described.
Adult↗
Effects of sterols on the therapeutic efficacy of liposomal amphotericin B in murine candidiasis.
Incorporation of amphotericin B (AMP-B) into phospholipid vesicles (liposomes) has been shown previously to decrease AMP-B toxicity while retaining the antifungal efficacy of the drug. In this report, the role of sterols in the formulation of liposomes as well as in their effectiveness in the treatment of murine candidiasis have been investigated. The presence of ergosterol or cholesterol at different lipid ratios did not augment the encapsulation efficiency of AMP-B as compared with vesicles containing phospholipids alone. There was no significant difference in the survival time of mice infected with Candida albicans treated with sterol-containing vesicles compared with those treated with sterol-free vesicles. These findings suggest that the sterol-free liposomes might be of advantage for delivering AMP-B because of its simple formulation, lack of toxicity, and ease of preparation.
Amphotericin B↗
New spectrum of fungal infections in patients with cancer.
We report on 44 cancer patients who had serious infections with unusual fungal pathogens and who were cared for at our cancer center between 1974 and 1986. Twelve different fungal species accounted for these infections, including Trichosporon beigelii, Fusarium species, Geotrichum candidum, Curvularia species, Drechslera species, Penicillium species (but not Penicillium marneffei), Rhodotorula rubra, Pseudallescheria boydii, Pichia farinosa, Torulopsis pintolopesii, Saccharomyces cerevisiae, and Cunninghamella bertholletiae. Skin lesions were noted in seven patients, and sinusitis occurred in four. Twenty-four patients had disseminated infection, 12 had involvement of a single organ, and eight had fungemia alone. Features that correlated with a poor prognosis were persistent neutropenia and disseminated visceral infection but not fungemia alone. We suggest that unusual fungi have now emerged as significant pathogens in this patient population. Fungal sinusitis, previously caused by Aspergillus species and the phycomycetes, also occurs as a result of some of these newly recognized fungi. A high level of suspicion should be maintained when any of these unusual fungi are cultured from clinical specimens from immunocompromised patients.
Adolescent↗