Systemic antifungal prophylaxis reduces invasive fungal in acute myelogenous leukemia: a retrospective review of 833 episodes of neutropenia in 322 adults.
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Adolescent↗
Biomedical subjects
E J Anaissie
Publications and source records attributed to E J Anaissie.
Fusariosis associated with pathogenic fusarium species colonization of a hospital water system: a new paradigm for the epidemiology of opportunistic mold infections.
We sought the reservoir of Fusarium species in a hospital with cases of known fusarial infections. Cultures of samples from patients and the environment were performed and evaluated for relatedness by use of molecular methods. Fusarium species was recovered from 162 (57%) of 283 water system samples. Of 92 sink drains tested, 72 (88%) yielded Fusarium solani; 12 (16%) of 71 sink faucet aerators and 2 (8%) of 26 shower heads yielded Fusarium oxysporum. Fusarium solani was isolated from the hospital water tank. Aerosolization of Fusarium species was documented after running the showers. Molecular biotyping revealed multiple distinct genotypes among the isolates from the environment and patients. Eight of 20 patients with F. solani infections had isolates with a molecular match with either an environmental isolate (n=2) or another patient isolate (n=6). The time interval between the 2 matched patient-environment isolates pairs was 5 and 11 months, and 2, 4, and 5.5 years for the 3 patient-patient isolate pairs. The water distribution system of a hospital was identified as a reservoir of Fusarium species.
Air Microbiology↗
Nosocomial aspergillosis is waterborne.
Nosocomial invasive aspergillosis can cause life-threatening infections among immunosuppressed patients and is thought to be primarily airborne. Despite the use of appropriate hospital air filtration systems, however, the incidence of this infection continues to increase. In this article, we present our hypothesis, which is that nosocomial aspergillosis can be airborne from a water source in the hospital. If confirmed by ongoing studies, this hypothesis would imply a change in the current infection control practices aimed at preventing nosocomial aspergillosis.
Aspergillosis↗
Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.
Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.
Antifungal Agents↗
Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia.
Hematogenous candidiasis adds substantially to the morbidity and mortality rates of patients with cancer. Little is known about the risk factors and outcome in patients with breakthrough (BT) candidemia while on systemic antifungal therapy. All 479 episodes of candidemia in 474 consecutive patients with candidemia that was diagnosed at M. D. Anderson Cancer Center from 1988 through 1992 were studied retrospectively. A total of 49 patients had BT candidemia, defined as candidemia that developed after at least 5 days of systemic antifungal therapy. Risk factors for BT candidemia and predictors of mortality were investigated. Multivariate analysis revealed that intensive care unit stay, neutropenia, use of corticosteroids, and duration of neutropenia as significant risk factors for BT candidemia. Seventy-six percent of patients with BT candidemia died, compared with 50% of patients with non-BT infection. In multivariate analysis, intensive care unit stay, being and remaining neutropenic, APACHE III score, and disseminated disease were independent prognostic factors. In conclusion, identification of risk factors and predictors of a poor outcome in patients with cancer with BT candidemia may have important implications in early diagnosis and appropriate therapy of these patients.
Candidiasis↗
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↗
Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study.
We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C(max)) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 microg/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC(24)) changed to 692, 1,062, 860, and 554 microg x h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of >or=7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections.
Adult↗
Predictors of outcome in cancer patients with candidemia.
BACKGROUND: Hematogenous candidiasis is associated with a substantial mortality and morbidity in critically ill patients. Candidemia is the best marker for hematogenous infection; therefore, most studies have examined the outcome of candidemia. However, few have focused on the predictors of outcome in cancer patients with candidemia. MATERIALS AND METHODS: We conducted a MEDLINE search for all study reports published from 1974 to 1999 on candidemia and prognostic factors including predictors of mortality. Ten articles that provided sufficient data were evaluated in detail. RESULTS: The overall mortality rate was reported to be 33%-75%. Univariate analyses identified severity of underlying disease, performance status, neutropenia, Candida species, source of candidemia and the extent of visceral involvement as important prognostic variables. In multivariate analyses, however, only host factors and extent of infection (rather than infecting Candida species) were predictive of mortality. CONCLUSIONS: Older age, poor performance status, presence and persistence of neutropenia, and extensive organ involvement with candidiasis are the most important prognostic factors for candidemia in cancer patients.
Age Factors↗
Incidence of imipenem hypersensitivity reactions in febrile neutropenic bone marrow transplant patients with a history of penicillin allergy.
The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies. Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed. The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.
Adult↗
Investigation of an outbreak of gram-negative bacteremia among hematology-oncology outpatients.
OBJECTIVE: To identify risk factors associated with an outbreak of gram-negative bacteremia (GNB). SETTING: A university hospital. PATIENTS: Hematology-oncology outpatients. DESIGN: Retrospective case-control study. RESULTS: Thirty-eight patients developed GNB; 13 patients experienced more than one episode, and eight blood cultures grew more than one gram-negative organism. The most frequently isolated organisms were Stenotrophomonas maltophilia, Klebsiella pneumoniae, Acinetobacter baumannii, and Acinetobacter johnsonii. When the GNB patients (cases) were compared with randomly selected hematology-oncology patients (controls), central venous catheter (CVC) self-care (71% vs 39%; P=.02), and duration of recent hospital stay (median, 15 vs 4 days; P=.01) were identified as risk factors. In a logistic regression model, duration of recent hospital stay was the only risk factor significantly associated with GNB (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; P<.02). CONCLUSIONS: Hematology-oncology patients providing their own CVC care who have recently been hospitalized for more than 2 weeks may be at increased risk of GNB. CVCs should be protected from possible environmental contamination in hematologyoncology patients. Patients providing their own CVC care should undergo continued rigorous education regarding proper CVC care.
Adult↗
Outpatient therapy for febrile neutropenia: who, when, and how?
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Ambulatory Care↗
Treatment of murine fusariosis with SCH 56592.
Doses of 10 to 100 mg of the azole antifungal agent SCH 5692/kg of body weight/day were studied in immunocompetent mice as therapy for systemic infection by Fusarium solani. Treatment was begun 1 h after intravenous infection and continued daily for 4 or 13 doses. Prolongation of survival and organ clearance were dependent on both the dose and the duration of SCH 56592 therapy, with the best results seen at 50 and 100 mg/kg/day. The results at the highest doses of SCH 56592 used (50 or 100 mg/kg/day) were comparable to those obtained with amphotericin B at 1 mg/kg/day. SCH 56592 has potential for therapy of systemic infections caused by F. solani.
Animals↗
Optimizing voriconazole susceptibility testing of Candida: effects of incubation time, endpoint rule, species of Candida, and level of fluconazole susceptibility.
Voriconazole is a new triazole antifungal agent that has potent activity against many isolates of Candida, including Candida krusei and Candida glabrata. In this work, we studied the impact of glucose supplementation, incubation time, agitation of the plates prior to reading, endpoint determination rule, visual versus spectrophotometric reading, Candida species, and fluconazole MIC on the MIC of voriconazole for Candida isolates tested by using the microdilution format assay of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A antifungal susceptibility testing methodology. For both voriconazole and fluconazole, a spectrophotometric endpoint of 50% reduction in turbidity relative to the growth control correlated most closely with the NCCLS-defined visual endpoint of "prominent decrease in turbidity." Correlation was generally better after 24 h of incubation than after 48 h. Supplementation of the medium to contain 20 g of glucose/liter did not alter the MIC significantly but did enhance growth and simplify visual readings. All Candida species appeared potentially susceptible to voriconazole, including isolates of C. krusei. For some isolates for which fluconazole MICs were markedly elevated voriconazole MICs were also elevated, but the clinical significance of these observations remains to be determined.
Amphotericin B↗
Infections in patients with chronic lymphocytic leukemia treated with fludarabine.
BACKGROUND: Fludarabine, a purine analogue with activity in chronic lymphocytic leukemia, is usually well tolerated. Although serious infections after fludarabine therapy have been described, a systematic analysis of the risk factors for such infections in chronic lymphocytic leukemia is lacking. OBJECTIVE: To determine the risk factors for major infection in patients with chronic lymphocytic leukemia treated with fludarabine. DESIGN: Retrospective review of medical records. SETTING: Cancer center. PATIENTS: 402 patients with chronic lymphocytic leukemia not previously treated or treated with chlorambucil (with or without prednisone) who received fludarabine (30 mg/m2 of body surface area per day for 5 days) with or without prednisone at 4-week intervals. RESULTS: Infections occurred more often in previously treated (144 of 248 [58%]) than in previously untreated (53 of 154 [34%]) patients (P < 0.001). Listeriosis or pneumocystosis occurred in 12 of 170 (7%) previously treated patients receiving fludarabine plus prednisone, 0 of 78 previously treated patients receiving fludarabine alone, and 2 of 154 (1%) previously untreated patients receiving fludarabine plus prednisone (P = 0.003). Univariate analysis identified previous chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum beta2-microglobulin level (P < 0.001), low serum albumin level (P = 0.024), elevated serum creatinine concentration (P = 0.008), and low granulocyte count (P = 0.003) as risk factors for infection. Multivariate analysis identified Rai stage III or IV (odds ratio, 1.98 [95% CI, 1.17 to 3.94]), previous treatment (odds ratio, 2.24 [CI, 1.43 to 3.51]), and elevated serum creatinine concentration (odds ratio, 1.98 [CI, 1.09 to 3.67]) as statistically significant independent risk factors for major infection. A baseline granulocyte count of more than 1000 cells/microL was protective (odds ratio, 0.54 [CI, 0.29 to 0.99]). Five (26%) of 19 patients with a CD4 count less than 50 cells/mL developed cutaneous zoster compared with 9 (6%) of 139 patients with a CD4 count greater than 50 cells/mL (P = 0.01). CONCLUSIONS: Fludarabine used in previously treated patients with chronic lymphocytic leukemia may be associated with infections involving T-cell dysfunction, such as listeriosis, pneumocystosis, mycobacterial infections, and opportunistic fungal and viral infections. Prophylaxis or presumptive therapy should be initiated in the appropriate setting.
Analysis of Variance↗
Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients.
We studied the potential of multidimensional flow cytometry to evaluate the frequency and maturation/activation status of dendritic cells in minimally manipulated peripheral blood mononuclear cell preparations (i.e., only separated on Ficoll-Hypaque) of normal donors and cancer patients. A rare subset of HLA-DR+ leukocytes (less than 1% mononuclear cells) was detected in blood of normal donors that displayed all the features of dendritic cells: these cells had high forward-light-scatter characteristics and coexpressed CD4, CD86 and CD54 surface antigens, but lacked the lineage-associated surface markers of T cells, B cells, monocytes, granulocytes or NK i.e. they were CD3-, CD19-, CD20-, CD14-, CD11b-, CD16-, CD56-). These physical and phenotypic properties were virtually identical to those of immunomagnetically sorted leukocytes characterized as dendritic-cells on the basis of morphology, phenotype and high stimulatory activity in allogeneic mixed-lymphocyte cultures. Using this flow-cytometric approach we observed that the frequency of dendritic cell-like cells in peripheral blood mononuclear cell specimens of cancer patients receiving chemotherapy alone or those recovering from stem cell transplantation was significantly lower than that of normal individuals (mean +/- SE: 0.36 +/- 0.05%, 0.14 +/- 0.06%, and 0.75 +/- 0.04% respectively). Multidimensional flow-cytometric analysis of dendritic cells might represent an important new tool for assessing immunocompetence, and for monitoring the effects of therapeutic regimens on the immune system.
Dendritic Cells↗
Predictors of adverse outcome in cancer patients with candidemia.
BACKGROUND: Many factors, including severity of illness, neutropenia, intravenous catheter management, and drug therapy may affect the outcome of candidemia in cancer patients. METHODS: The records of all patients at M. D. Anderson Cancer Center who developed one or more positive blood cultures for Candida spp between January 1, 1988, and December 31, 1992, were retrospectively reviewed. Four hundred ninety-one episodes of candidemia were identified, for which 476 had complete medical records, which were reviewed in detail. RESULTS: By 3-month follow-up, 52% of the patients had died. Neutropenia, higher APACHE III score, and visceral dissemination were associated with poor prognosis. Cure rates, adjusted for severity of illness, were similar for fluconazole and amphotericin B treatment. Exchange of central venous catheters was associated with a modest improvement in prognosis. CONCLUSION: Several factors that influence the outcome of candidemia in cancer patients have been identified. These factors may be relevant for the clinical management of cancer patients with candidemia, and for the design of therapeutic trials.
Adult↗
Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases.
The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.
Adult↗
Immunomodulation for the treatment of invasive fungal infections.
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Humans↗