PubMed Health⌕ Search

Biomedical subjects

G P Bodey

Publications and source records attributed to G P Bodey.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effectiveness of an oral triazole for opportunistic mold infections in patients with cancer: experience with SCH 39304.

Fungal infections are the most common infectious cause of death among patients with hematologic malignancies. Conventional antifungal agents have limited activity and a narrow therapeutic index. In an open-label study we assessed the activity of an oral triazole, SCH 39304, in the treatment of refractory life-threatening mold infections in 50 patients with cancer, most of whom had previously received amphotericin B and/or fluconazole. SCH 39304 was given at a daily dose of 200-400 mg for a median of 8 weeks. The overall rate of response was 79% among 34 evaluable patients, with a complete response in 22 instances and a partial response in 5. Some patients responded despite persistent, profound immunosuppression. Three patients developed relapses, and two developed fungal superinfections. SCH 39304 was well tolerated. We conclude that oral triazoles such as SCH 39304 may represent effective and safe treatment of mold infections in immunosuppressed patients, at least after standard antifungal chemotherapy. Unfortunately, the carcinogenic potential of SCH 39304 in animals has precluded its development. Our hope is that analogues with similar efficacy but without carcinogenic potential can be developed.

Administration, Oral↗
PubMed1993

Empirical antibiotic therapy for fever in neutropenic patients.

The necessity for administering empirical antibiotic therapy to febrile neutropenic patients has been well-established; however, no single regimen has been uniformly accepted. During the past decade, gram-positive organisms, often methicillin-resistant, have emerged as significant pathogens. The routine use of vancomycin may be appropriate at some institutions, but its widespread use may lead to resistance. The role of aminoglycosides as part of routine empirical regimens is controversial, and single extended-spectrum beta-lactam agents are often adequate therapy. Not all beta-lactam agents are equally effective, and some gram-negative pathogens, such as Xanthomonas maltophilia, are resistant to many of them. Pneumonia is frequent, the infecting pathogen is often undetermined, and therapy is unsatisfactory. Outpatient antibiotic therapy can be used in selected neutropenic patients. Empirical antibiotic regimens should be selected on the basis of knowledge about predominant pathogens and antibiotic susceptibilities at each institution as much as on the basis of studies from other institutions reported in the literature.

Anti-Bacterial Agents↗
PubMed1993

Emerging fungal pathogens in immunocompromised patients: classification, diagnosis, and management.

Fungi such as Fusarium species, Trichosporon species, Curvularia species, and Alternaria species previously were thought to represent contamination or harmless colonization when isolated from immunocompromised patients. More recently, the pathogenic role of these and other fungi has been clearly established. Three diverse groups of fungi are responsible for these emerging infections: the agents of phaeohyphomycosis and hyalohyphomycosis and certain yeasts. Reports of the emergence of these organisms as significant pathogens may be ascribed to increasing awareness by physicians and microbiologists, aggressive culture of patient specimens, increasingly cytotoxic chemotherapy, and selection of resistant organisms by the widespread empirical use of amphotericin B. Infections with these fungi tend to be disseminated and are frequently fatal in immunocompromised hosts. Treatment of these infections is not standardized. Experimental therapy in murine models of fungal infections suggests a role for newer agents, combination antifungal chemotherapy, and immunotherapy.

Fungi↗
PubMed1993

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↗
PubMed1993

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections. Fifty-one (61%) of the 83 episodes pneumonia and 74 (64%) of the 115 episodes of bacteraemia responded. Only 39 (58%) of the 67 infections caused by Gram-positive bacteria responded compared with 55 (86%) of 64 Gram-negative infections which included seven of eight caused by Pseudomonas aeruginosa. Eighteen (67%) of 27 polymicrobial infections responded to the regimen. Response rates were significantly lower amongst the 125 patients whose neutrophil counts decreased during therapy than amongst the 158 patients whose neutrophil counts increased. Adverse events which were possibly or probably related to antibiotic therapy were observed during 73 of the episodes; the most commonly reported side-effects were diarrhoea and skin rash. Six patients developed a coagulopathy without haemorrhage and two experienced anaphylactic reactions. In this open trial cefoperazone plus sulbactam proved to be an effective regimen for initial therapy of fever in cancer patients. It should be combined with a glycopeptide in those institutions where infections caused by methicillin-resistant staphylococci are frequently encountered.

Adolescent↗
PubMed1993

Prospective evaluation of effects of broad-spectrum antibiotics on gastrointestinal yeast colonization of humans.

This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad-spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract.

Adult↗
PubMed1993

In vitro activities of antimicrobial agents against clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer.

We evaluated the in vitro activities of 21 different antimicrobial agents against nine clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer. The organisms were susceptible to most agents commonly used for the empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, monobactams, and carbapenems) and prevention of infections (quinolones and trimethoprim-sulfamethoxazole) in this patient population.

Anti-Bacterial Agents↗
PubMed1993

Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice.

The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 x 10(6) CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 10(6) CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80% when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 10(6) CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50% was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 10(5) and 1 x 10(5) intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 10(5) C. albicans. Mice infected with 10(5) C. albicans and treated with cilofungin (25 mg/kg) twice a day for 10 days had no organisms in the kidney, spleen, and liver at days 8, 2, and 8, respectively. There was 1-log-unit reduction in C. albicans counts in brain tissue from mice of one of the treated groups between 2 h and 2 days postinfection, after which the numbers of organisms remained the same until day 12. These data demonstrate the efficacy of cilofungin in the treatment of disseminated C. albicans infections in normal and granulocytopenic mice. The treatment regimen used in this study was able to clear C. albicans from the kidneys, spleen, and liver but not from brain tissue.

Agranulocytosis↗
PubMed1993

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↗
PubMed1993

What's new in fungal infection in leukemic patients.

Fungal infections have become an important cause of mortality in patients with hematological malignancies. In recent years, fungi such as Candida tropicalis, Aspergillus spp, Fusarium spp and Trichosporon spp have emerged as important pathogens. Amphotericin B remains the antifungal agent with the broadest spectrum of activity, although some of the newer pathogens may be resistant. The administration of this drug in lipid vehicles reduces the toxicities, permitting the administration of higher doses that may be more effective. The new agents, fluconazole and itraconazole, have activity against some fungal pathogens, although their role in therapy has not been fully determined. Fluconazole has been shown to be effective for prophylaxis of Candida infections.

Amphotericin B↗
PubMed1993

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↗
PubMed1992

Serious complications of vascular catheter-related Staphylococcus aureus bacteremia in cancer patients.

Over the period 1986 to 1989, 53 cancer patients were identified with catheter-related Staphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23%) patients and was suspected in another 3 (6%). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p < 0.01). Fever persisted for more than three days after antibiotic initiation in 52% of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19% of those without complications (p < 0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p < 0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-related Staphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks.

Adult↗
PubMed1992

Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia.

OBJECTIVE: To determine the impact of catheter management on the acute and long-term outcome of catheter-related coagulase-negative staphylococcal bacteremia. DESIGN: Retrospective surveillance of catheter-related sepsis using quantitative blood and catheter cultures. SETTING: University-affiliated tertiary cancer center. PATIENTS AND METHODS: Seventy patients with catheter-related coagulase-negative staphylococcal bacteremia were studied by retrospective chart review. The clinical characteristics of the patients and the management of the bacteremias were determined. The impact of immunosuppressive risk factors, antibiotic therapy, and catheter management on the recurrence of the bacteremia was investigated. RESULTS: Acute sepsis-related morbidity and mortality were not related to catheter management. However, during a 12-week followup period, the bacteremia recurred in 20% of the patients whose catheters remained in place, compared with only 3% of those whose catheters were removed (p less than .05). By multivariate analysis, patients whose catheters remained in place were 2.9 times more likely to experience a recurrence than those whose catheters were removed (odds ratio = 2.9, 95% confidence interval = 1.2-8.8, p = .03). All other potential risk factors were equally distributed between patients, with and without a recurrence. CONCLUSIONS: Although patients with catheter-related coagulase-negative staphylococcal bacteremia could be treated successfully while the catheter remains in place with the majority remaining free of recurrence, catheter retention results in a significantly higher risk for the recurrence of the bacteremia.

Adolescent↗
PubMed1992

Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors.

Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = .0005). The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than .0001) and with profound neutropenia (P less than .0001). Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than .001), while sucralfate therapy did not increase risk (P = .65). Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist-induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry. In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid-sparing regimen should be considered to preserve the natural acidic barrier to infection.

Bacteremia↗
PubMed1992

Azole antifungal agents.

The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.

Animals↗