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E J Anaissie

Publications and source records attributed to E J Anaissie.

At least 19 recordsLinked to original sources
PubMed2006

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients.

The duration of neutropenia (absolute neutrophil count (ANC) < or = 100/microl) identifies cancer patients at risk for infection. A test that precedes ANC > or = 100/microl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC > or = 100/microl in 99% of patients after the first Mel-ASCT by (mean+/-s.d.) 4.23+/-1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11+/-1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count > or = 100/microl to the time to ANC > or = 100/microl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC> or = 100/microl.

Cohort Studies↗
PubMed2006

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients.

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.

Analysis of Variance↗
PubMed2006

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Adult↗
PubMed2005

International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia.

Candida spp. are the fourth leading cause of bloodstream infections, and non-albicans species are increasing in importance. Micafungin is a new echinocandin antifungal agent with excellent in vitro activity against Candida spp. Pediatric, neonatal, and adult patients with new or refractory candidemia were enrolled into this open-label, noncomparative, international study. The initial dose of micafungin was 50 mg/d (1 mg/kg for patients <40 kg) for infections due to C. albicans and 100 mg/d (2 mg/kg for patients <40 kg) for infections due to other species. Dose escalation was allowed. Maximum length of therapy was 42 days. A total of 126 patients were evaluable (received at least five doses of micafungin). Success (complete or partial response) was seen in 83.3% patients overall. Success rates for treatment of infections caused by the most common Candida spp. were as follows: C. albicans 85.1%, C. glabrata 93.8%, C. parapsilosis 86.4%, and C. tropicalis 83.3%. Serious adverse events related to micafungin were uncommon. Micafungin shows promise as a safe and effective agent for the treatment of newly diagnosed and refractory cases of candidemia. Large-scale, randomized, controlled trials are warranted.

Adolescent↗
PubMed2004

Lipid formulations of amphotericin B preserve and stabilize renal function in HSCT recipients.

The current study assessed renal function based on medical records in adult hematopoietic stem cell transplant (HSCT) recipients with proven or probable invasive fungal infection (IFI) transplanted between 1995 and 2000. We confirm that amphotericin B deoxycholate (AmB-d) is nephrotoxic in a large percentage of HSCT recipients. Due to nephrotoxicity, defined as serum creatinine (SCr) >2.5 mg/dl or a 100% increase in SCr from baseline, 88% of patients treated with AmB-d were switched to a lipid formulation of amphotericin B (LFAB). In total, 53% of patients initiated on AmB-d were switched within the first week of therapy. Significantly more patients (70.6%) treated with AmB-d experienced a 100% increase in SCr from baseline compared to patients treated with either AmBisome (44.4%) or Abelcet (41.2%). A Cox Proportional Hazards Model revealed that, compared to patients initiated on AmBisome or Abelcet, the risk of nephrotoxicity (RR=1.5 vs AmBisome; RR=1.7 vs Abelcet), dialysis (RR=2.4 vs AmBisome; RR=1.4 vs Abelcet), and death (RR=2.0 vs AmBisome; RR=1.1 vs Abelcet) were all increased for patients initiated on AmB-d. Study results suggest that renal function improves and mortality declines when an LFAB is given to HSCT patients as initial therapy rather than as second-line therapy, the current practice.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

The clinical spectrum of stenotrophomonas (xanthomonas) maltophilia respiratory infection.

During a 15-month retrospective clinical study in an academic referral-based cancer center, 26 patients with S. maltophilia respiratory tract infections were identified (which were associated with bacteremia in 13 patients). Five of these 26 patients had previously undescribed sinopulmonary involvement. The infections were typically nosocomial. Nine patients with solid tumors had malignant involvement of the respiratory tract (five with obstruction). In two patients, the infection co-existed with pulmonary aspergillosis. Fifteen patients (58%) died of the infection. The factors that correlated with a poor outcome included bacteremic pneumonia, persistent neutropenia, presence of obstruction, development of septic shock or multiple organ dysfunction, and delay in institution of appropriate antibiotic therapy. In multivariate analysis, only septic shock and delayed therapy remained significant. Trimethoprim-sulfamethoxazole and/or ticarcillin-clavulanate were most commonly associated with a favorable outcome.

Journal Article↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗