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Biomedical subjects

E Anaissie

Publications and source records attributed to E Anaissie.

At least 55 records · Page 3Linked to original sources

Invasive Aspergillus sinusitis during bone marrow transplantation.

Aspergillus sinusitis is usually a lethal condition in bone marrow transplanted patients. We report the case of a patient known to have a sinus infection with Aspergillus flavus before treatment with allogenic bone marrow transplantation for a refractory acute myelogenous leukemia. Exacerbation of the sinusitis during the neutropenic period required a multidisciplinary approach. Cure was achieved after treatment with a combination of surgery (Caldwell-Luc procedure), long term ABCD (amphotericin B colloidal dispersion) therapy (7 months) and granulocyte transfusions during the period preceding engraftment. The use of granulocyte transfusion in this salvage setting is discussed. Aggressive multimodality management of aspergillus sinusitis in immunosuppressed patients may lead to a cure and might not preclude allogenic transplantation.

Adult↗

Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients.

Invasive fungal infections, including disseminated candidiasis and invasive pulmonary aspergillosis, are important causes of morbidity and mortality in neutropenic patients. The recent development of fluconazole, itraconazole, lipid formulations of amphotericin B, and recombinant cytokines have expanded our therapeutic armamentarium. Clinical trials have elucidated new strategies for utilizing these compounds in the prevention and treatment of opportunistic mycoses. The population of more severely immunocompromised patients, however, continues to expand and the spectrum of drug-resistant fungi, including but not limited to Candida spp, Fusarium spp, Zygomycetes, and dematiaceous moulds, continues to evolve, thus presenting new challenges to recent therapeutic advances. Development of new antifungal chemotherapeutic agents and novel approaches for augmentation of host response will be required to meet these new mycologic challenges.

Antifungal Agents↗

Role of catheter colonization and infrequent hematogenous seeding in catheter-related infections.

Adult cancer patients were prospectively studied to determine the relationship between ultrastructural and microbiologic catheter colonization and clinical catheter-related infections. Participants included 38 patients whose central venous catheters were removed because of suspected catheter infection (16 patients) or other noninfectious causes (22 controls). The presence of clinical infection was determined. Catheters were examined by microbiologic methods (sonication and roll-plate culture) and by scanning and transmission electron microscopy. Ultrastructural microbial colonization and biofilm formation were universal and occurred as early as one day after catheter insertion. The extent of biofilm formation was unrelated to the clinical status of patient or the catheter microbiological findings. Secondary seeding of catheters was rarely seen. Catheter microbial biofilm formation occurs early, is universal and does not necessarily represent an infectious condition.

Adult↗

Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi.

The purpose of the study was to evaluate the interlaboratory agreement of broth dilution susceptibility methods for five species of conidium-forming (size range, 2 to 7 microns) filamentous fungi. The methods used included both macro- and microdilution methods that were adaptations of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (m27-P). The MICs of amphotericin B, fluconazole, itraconazole, miconazole, and ketoconazole were determined in six centers by both macro- and microdilution tests for 25 isolates of Aspergillus flavus, Aspergillus fumigatus, Pseudallescheria boydii, Rhizopus arrhizus, and Sporothrix schenckii. All isolates produced clearly detectable growth within 1 to 4 days at 35 degrees C in the RPMI 1640 medium. Colony counts of 0.4 x 10(6) to 3.3 x 10(6) CFU/ml (mean, 1.4 x 10(6) CFU/ml) were demonstrated in 90% of the 148 inoculum preparations. Overall, good intralaboratory agreement was demonstrated with amphotericin B, fluconazole, and ketoconazole MICs (90 to 97%). The agreement was lower with itraconazole MICs (59 to 79% median). Interlaboratory reproducibility demonstrated similar results: 90 to 100% agreement with amphotericin B, fluconazole, miconazole, and ketoconazole MICs and 59 to 91% with itraconazole MICs. Among the species tested, the MICs for S. schenckii showed the highest variability. The results of the study imply that it may be possible to develop a reference method for antifungal susceptibility testing of filamentous fungi.

Aspergillus↗

Role of granulocyte-macrophage colony-stimulating factor as adjuvant treatment in neutropenic patients with bacterial and fungal infection.

The results are presented of two preliminary studies conducted to assess the role of GM-CSF as adjuvant treatment in neutropenic patients with bacterial or fungal infections. In the first study the effect of GM-CSF on the rate of response to antibiotics was assessed. Febrile neutropenic patients (n = 91) were randomized to receive ticarcillin-clavulanate plus netilmicin with or without GM-CSF (60 micrograms/m2). Response rates were significantly higher in patients who received antibiotics plus GM-CSF (p = 0.05). An increase in neutrophil count was seen in 89% of GM-CSF patients with initial low neutrophil counts (< 100/microliters) compared with 67% of control patients (p = 0.04). In the second study the activity of GM-CSF in patients with fungal infections was assessed. Neutropenic patients with documented fungal infections received amphotericin B plus GM-CSF. Of the eight evaluable patients, six responded and four had a complete response to treatment. The neutrophil counts of the two non-responding patients did not increase substantially during GM-CSF treatment and both died of their fungal infection. The prognosis of neutropenic patients with fungal infections is usually poor and the results of this pilot study are therefore very encouraging. The two studies show that GM-CSF is able to stimulate neutrophil recovery in neutropenic patients and may improve the response to antibiotic and antifungal treatment.

Adolescent↗

A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy.

The in vitro susceptibilities of 130 Xanthomonas maltophilia isolates to 12 antibiotics--trimethoprim-sulfamethoxazole, minocycline, ticarcillin-clavulanate, ceftazidime, cefoperazone, cefoperazone-sulbactam, imipenem, ciprofloxacin, and the investigational quinolones PD 117558, PD 117596, PD 127391, and sparfloxacin--were determined by a microtiter broth dilution technique. Other than the investigational quinolones, the most active antibiotics were minocycline, trimethoprim-sulfamethoxazole, and ticarcillin-clavulanate, in order. However, the first two were not bactericidal, while about half of the isolates exhibited intermediate susceptibility to ticarcillin-clavulanate. Patterns of susceptibility to trimethoprim-sulfamethoxazole and ciprofloxacin relative to the years of isolation of these strains reflected the development of resistance to the antibiotic prophylaxis practices in the hospital. We recommend that a combination of antibiotics, such as trimethoprim-sulfamethoxazole, minocycline, and ticarcillin-clavulanate, at or close to the maximum tolerated doses be in the treatment of serious X. maltophilia infections.

Anti-Bacterial Agents↗

Granulocyte colony-stimulating factor supportive treatment following intensive chemotherapy in acute lymphocytic leukemia in first remission.

BACKGROUND: The efficacy of granulocyte colony-stimulating factor (G-CSF) in reducing neutropenia and its associated complications in adults with acute lymphocytic leukemia (ALL) undergoing intensive chemotherapy in first remission was evaluated. METHODS: Fourteen adult patients with ALL in first remission received intensive chemotherapy consisting of mitoxantrone 5 mg/m2 intravenously (IV) over 1 hour daily for 3 days, cytosine arabinoside (ara-C) 3 g/m2 IV over 2 hours every 12 hours x 4 on days 1 and 2, vincristine 2 mg IV on day 1, solumedrol 50 mg IV twice daily for 5 days, and G-CSF 5 micrograms/kg subcutaneously daily starting on day 4 until granulocyte recovery. Their outcome was compared with that of 14 consecutive patients who received the same intensification chemotherapy, but without G-CSF. The latter patients had been entered on the same ALL protocol from April 1990 through June 1991. RESULTS: G-CSF administration was associated with a significant shortening in the duration of neutropenia. The number of days to granulocyte recovery above 0.5 x 10(3)/microliters was 14 in the G-CSF group versus 18 days in the historical group (P < 0.001). Two episodes of documented infections were observed in the G-CSF group compared with four episodes in the historical group. Death during intensification therapy occurred in 2 of 14 patients in the historical group, but in none of the 14 patients receiving G-CSF. CONCLUSIONS: G-CSF as an adjunct to intensive chemotherapy in adults with ALL in first remission yielded positive results. Future studies incorporating growth factors supportive care during remission, induction, and consolidation may reduce treatment-related morbidity and mortality, increase the dose-intensity delivery of therapy, and potentially improve patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗

Invasive candidiasis during granulocytopenia.

Candidiasis remains the most frequently encountered fungal infection in patients with profound granulocytopenia and appears to be increasing in frequency. In addition, Candida infections are occurring earlier during remission induction chemotherapy and can be caused by a variety of species such as C. albicans, C. tropicalis, and C. krusei. The most frequent source of disseminated infection is the gastrointestinal tract, as the integrity of the epithelium is disrupted by chemotherapeutic agents. The spectrum of disseminated candidiasis comprises both an acute and a chronic presentation (also known in the literature as hepatosplenic candidiasis). The management of disseminated infection consists of early empiric antifungal therapy with a standard agent, amphotericin B. Unfortunately, responses in the setting of profound granulocytopenia appear to be poor. Other agents that appear to be useful in the management of disseminated candidiasis include 5-flucytosine and fluconazole. Based on animal experimentation, it appears that the combination of these three classes of agents might produce superior results compared with amphotericin B alone. Removal of the central venous catheter does not appear warranted in the setting of profound granulocytopenia, and the role of colony stimulating factors needs to be defined. Given the severity and high mortality associated with disseminated candidiasis in patients with hematologic malignancies, antifungal prophylaxis appears warranted.

Agranulocytosis↗

Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for fungal infection in patients with cancer.

A pilot study was conducted to evaluate the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for fungal infections in patients with cancer. GM-CSF was added to amphotericin B in the treatment of cancer patients with proven major-organ or disseminated fungal infection. The dose of GM-CSF ranged from 100 to 750 micrograms/(m2.d). Of eight evaluable patients, six had a neutrophil response to GM-CSF. Four of these patients were completely cured of the fungal infection, and two had a partial response. However, a capillary-leak syndrome developed in three patients, an adverse effect suggesting that the dose of GM-CSF was excessive.

Adult↗

Ultrastructural analysis of indwelling vascular catheters: a quantitative relationship between luminal colonization and duration of placement.

To assess the degree of luminal and extraluminal colonization of long-term central venous catheters (CVC), 359 indwelling silicone CVC from 340 consecutive cancer patients were examined. All CVC were cultured by the roll-plate and sonication quantitative culture techniques. Semiquantitative electron microscopy was done on 39 CVC associated with catheter infections and on 26 culture-negative controls. An additional 10 culture-negative CVC obtained after death were also studied by electron microscopy. Ultrastructural colonization and biofilm formation was universal and quantitatively independent of clinical catheter-related infections. Ultrastructural colonization and biofilm formation was predominantly luminal in long-term CVC (> 30 days). Based on a composite definition, the sensitivity of the roll-plate catheter tip culture was 42%-45% compared with 65%-72% for the sonication of the tip. Colonization of indwelling catheters is universal regardless of culture results. For long-term CVC, colonization becomes predominantly luminal and extraluminal quantitative catheter cultures are of limited diagnostic sensitivity.

Bacteria↗

Experimental hematogenous candidiasis caused by Candida krusei and Candida albicans: species differences in pathogenicity.

Hematogenous infections caused by Candida krusei have been noted with increasing frequency, particularly in cancer patients receiving prophylaxis with antifungal triazoles. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of candidiasis to evaluate the pathogenicity of C. krusei in normal and immunosuppressed mice and to compare it with that of Candida albicans. Several inocula (10(6) to 10(8) CFU per animal) of two clinical strains of C. krusei and three American Type Culture Collection strains of C. albicans were tested. Groups of 20 mice each were injected with a single intravenous dose of one inoculum. Animals randomized to receive C. krusei were immunosuppressed by intraperitoneal injection of cyclophosphamide or the combination of cyclophosphamide plus cortisone acetate or they did not receive immunosuppressive agents (normal mice). One hundred percent mortality was observed in normal mice injected with 10(6) CFU of C. albicans per mouse compared with no mortality in normal mice that received 10(8) CFU of C. krusei per mouse (P < 0.01). Resistance to C. krusei infection was markedly lowered by immunosuppression, particularly by the combination of cyclophosphamide plus cortisone acetate, with a significantly shorter survival and a higher organ fungal burden in immunosuppressed than in normal animals (P < 0.01). Tissue infection was documented by culture and histopathologic findings in all examined organs.

Animals↗

Two-site comparison of broth microdilution and semisolid agar dilution methods for susceptibility testing of Cryptococcus neoformans in three media.

This study evaluated the inter- and intralaboratory agreement between results of the semisolid agar dilution and broth microdilution methods of antifungal susceptibility testing of Cryptococcus neoformans. Three media were tested in two laboratories. The drugs tested were amphotericin B, flucytosine, itraconazole, fluconazole, and Schering 39304. Analysis by kappa statistics revealed good agreement between the laboratories for the two methods. The highest level of inter- and intralaboratory agreement was observed in RPMI 1640 with L-glutamine followed by Eagle's minimum essential medium and yeast nitrogen broth. The broth microdilution method appears more suitable than the semisolid agar dilution method for testing cryptococci because of its ease in performance, cost, and simplicity.

Agar↗

Primary Candida pneumonia. Experience at a large cancer center and review of the literature.

We reviewed the experience over 20 years with primary Candida pneumonia among fatal cancer cases at our hospital. Unequivocal evidence of primary Candida pneumonia has been reported in only 55 cases. We report here 31 such cases. Unlike patients with disseminated candidiasis, and contrary to previous studies concentrating on cancer patients, only 9 of our 31 patients had severe neutropenia. In this report, the lack of organ involvement other than the lungs at complete autopsy examination, the exclusion of patients with candidemia, the very high percentage of intrabronchial and intra-alveolar fungal involvement without vascular invasion, and the concomitant presence of candidal esophagitis in some patients suggest that the mechanism of entry of the infectious particles may have been aspiration of oropharyngeal contents. The major clinical manifestations of primary Candida pneumonia are fever and tachypnea. Radiologically, nonspecific patchy infiltrates can be seen. Histopathologically, there is prevalence of bronchopneumonia, hemorrhage, and necrosis. The only accepted criterion for the definitive diagnosis of Candida pneumonia is histologic demonstration of the fungus in lung tissue. In contrast to previous reports, we demonstrated that primary Candida pneumonia can be life-threatening in patients with cancer since it directly contributed to the death of 84% of the patients in the present series. Very little data are available on the therapy and outcome of patients with Candida pneumonia. However, primary Candida pneumonia in the compromised host should be treated as a life-threatening infection with systemic antifungal therapy.

Adolescent↗

Listeriosis in patients with chronic lymphocytic leukemia who were treated with fludarabine and prednisone.

OBJECTIVE: To determine whether therapy with fludarabine plus prednisone in patients with chronic lymphocytic leukemia increases the risk for developing listeriosis. DESIGN: Retrospective cohort study based on hospital surveillance data. SETTING: Referral cancer center. PARTICIPANTS: A total of 795 patients with chronic lymphocytic leukemia who received care at The University of Texas M. D. Anderson Cancer Center between 1980 and 1990. INTERVENTIONS: Patients were treated with fludarabine alone or fludarabine and prednisone. MEASUREMENTS: The listeriosis attack rate was analyzed according to the type of treatment received. RESULTS: Seven of 408 patients in the fludarabine group developed listeriosis (1.7%; 95% Cl, 0.2% to 6%) compared with 0 of 387 patients who received conventional chemotherapy alone (0% to 0.9%; P = 0.015). The 7 patients were among 248 patients who were treated with both fludarabine and prednisone; none of 160 patients treated with fludarabine alone developed listeriosis (P = 0.045 by the Fisher exact test). A dramatic reduction in CD4 counts occurred in patients after fludarabine and prednisone treatment and coincided with the development of listeriosis. CONCLUSION: The administration of fludarabine plus prednisone is associated with an increased incidence of listeriosis in patients with chronic lymphocytic leukemia. The depletion of CD4 cells may underlie the pathogenesis.

Aged↗

Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia.

Thirty-four adults with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m2 intravenously over 1 hour daily for 5 days and cytosine arabinoside (ara-C) 3 g/m2 intravenously over 2 hours every 12 hours for six doses, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 125 microgram/m2 intravenously over 4 hours daily until recovery of granulocytes above 2.0 x 10(3)/microL. Their outcome was compared with 29 prognostically similar historical control patients treated with the identical chemotherapy without GM-CSF. Overall, the complete response rates were similar in the treatment and control groups (13 of 34 [38%] v 11 of 29 [38%]). There was a trend for less remission induction mortality in the GM-CSF-treated patients (2 of 34 [6%] v 6 of 29 [21%]; P = .08), but, conversely, a higher rate of resistant disease (19 of 34 [56%] v 10 of 29 [34%]; P = .09). Recovery of granulocyte counts above 500/microL was significantly faster in the GM-CSF-treated group (25 days v 33 days; P less than .01), but there was no reduction in the incidence of febrile episodes (91% v 93%) or of documented infections (59% v 59%). Survival was prolonged in the GM-CSF-treated patients but was not of clinical relevance (31 v 20 weeks; P = .05). In summary, the addition of GM-CSF to intensive chemotherapy in refractory adult ALL was associated with a reduction in the remission induction mortality, probably secondary to a shorter duration of granulocytopenia, but not with an improvement in complete response rates.

Adult↗

Azole therapy for trichosporonosis: clinical evaluation of eight patients, experimental therapy for murine infection, and review.

We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species.

Adult↗