The medical records of patients with hematogenous candidiasis at M. D. Anderson Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed. There were 491 episodes of infection (6 per 1,000 admissions), 79% of which occurred outside the intensive care unit setting. A significant decrease in incidence was observed among patients with leukemia over the study period, together with a relative decrease in Candida albicans and Candida tropicalis infections and an increase in Candida krusei and possibly Candida glabrata infections. In the multivariate analysis, fluconazole prophylaxis provided strong protection against the development of C. tropicalis infection (odds ratio [OR] = 0.08) and C. albicans infection (OR = 0.15), in comparison with protection against infections due to other species, but it was the single most important determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata (OR = 5.08) infections. In conclusion, there has been a substantial shift in the epidemiology of hematogenous candidiasis caused by different Candida species in recent years. Fluconazole appears to be playing a major role in this observed shift.

Aspergillus spores are ubiquitous in the environment and may become concentrated in hospital ventilation systems. Colonization in normal hosts can lead to allergic diseases ranging from asthma to allergic bronchopulmonary aspergillosis. Normal hosts rarely develop invasive disease, which is primarily an infection of severely immunocompromised patients. The major predisposing factors for infection include prolonged neutropenia, chronic administration of adrenal corticosteroids, the insertion of prosthetic devices, and tissue damage due to prior infection or trauma. Since Aspergillus spp. are respiratory pathogens, the most common form of infection is pneumonia followed by sinusitis. Patients with preexistant cavitary disease may develop noninvasive aspergillomas. Most infections are caused by Aspergillus fumigatus. The organism is capable of invading across all natural barriers, including cartilage and bone. It has a propensity for invading blood vessels causing thrombosis and infarction. The diagnosis of pulmonary infection is usually difficult to establish because the organism is seldom cultured from sputum and can represent contamination in some cases. Therapy is immunocompromised hosts is less than satisfactory and amphotericin B is the only agent with significant activity. There is anecdotal evidence to suggest that the addition of 5-fluorocytosine to amphotericin B may be beneficial.

Iron is tightly controlled in mammalian tissues and regulates virulence factors in various pathogenic organisms. The influence of Fe availability upon production of cryptococcal capsular polysaccharide was studied. Polysaccharide, measured as cell-bound glucuronyl residues, increased more than threefold as available Fe in the culture medium was varied from repletion to tight sequestration and depletion in five incremental steps. Since physiologic CO2 concentration may serve as stimulus for cryptococcal polysaccharide synthesis, the combined effect of Fe availability and CO2 on encapsulation was studied. Addition of dissolved, loosely chelated Fe moderated the effect of CO2. Tight chelation of dissolved Fe potentiated the CO2 effect. Tissue from infected mice showed heavily encapsulated organisms, consistent with results with physiologic CO2 concentration and Fe deprivation. In conclusion, cryptococcal polysaccharide synthesis is increased by limitation of ferric iron availability to the cell and by dissolved CO2, and the two effects are additive.

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.

The in vitro susceptibilities of 130 Xanthomonas maltophilia isolates to 12 antibiotics-trimethoprimsulfamethoxazole, 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 ticarcillinclavulanate, 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 used in the treatment of serious X. maltophilia infections.Xanthomonas maltophilia has emerged as a significant cause of morbidity and mortality in cancer patients (5,6,18). This organism is capable of causing life-threatening infections (5, 25) and is usually resistant to multiple antimicrobial agents, particularly to those of the beta-lactam class (25). The standard therapy for infections by this organism is trimethoprimsulfamethoxazole. The newly developed quinolones, which have broad antimicrobial activity, are now being used in both prophylaxis and therapy of infections in cancer patients. However, at The University of Texas M. D. Anderson Cancer Center, we have cared for patients with serious X maltophilia infections that developed during quinolone prophylaxis. Because of our concern for the emergence of resistance of X. maltophilia to quinolones and the limited therapeutic options available to treat this potentially life-threatening infection, we studied the in vitro activities of various antimicrobial agents, including quinolones, against 130 clinical isolates of X. maltophilia.The strains of X maltophilia used in this study were single patient isolates from the clinical microbiology laboratory at M. D. Anderson Cancer Center. Eighty-nine of the cultures were isolated from patients' bloodstreams, 24 were from urine, 12 were from sputum or the throat, and 5 were from miscellaneous sources. These isolates had been collected in the infectious disease laboratories since 1981 for their clinical significance. The bacteria were identified as X. maltophilia by various biochemical tests using the API 20C system (Analytab Products, Plainview, N.Y.). Organisms were stored in the laboratory at -70°C.All antimicrobial agents were obtained in the form of standard laboratory powders and were stored at -70°C before use. The drugs tested were trimethoprim-sulfamethoxazole (Hoffmann-La Roche, Montclair, N.J.); minocycline (Lederle, Pearl River, N.Y.); ciprofloxac...

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Mucocutaneous and soft tissue infections caused by X. maltophilia are not uncommon, and X. maltophilia can cause metastatic nodular skin lesions that mimic disseminated fungal infections. It also causes serious morbidity and high mortality in patients with metastatic skin nodules and can cause superinfections in patients receiving broad-spectrum beta-lactam or quinolone antibiotics to which the organisms are susceptible when the infections develop. Catheter removal contributes to a favorable outcome in patients with catheter-associated cellulitis without bacteremia. Xanthomonas maltophilia infection should be added to the differential diagnosis of mucocutaneous or soft tissue infection in patients with cancer. Trimethoprim-sulfamethoxazole with or without ticarcillin-clavulanate is the current treatment of choice for culture-proven infections, but early empiric therapy may improve outcome.

Neutropenia-related fungal infections can be life-threateningand efficacy of rG-CSF-elicited WBC transfusions in patients despite antifungal therapy. We evaluated the role of recombiwith neutropenia-related fungal infections that were refractory nant granulocyte colony-stimulating factor (rG-CSF)-elicited to therapy with amphotericin B. acute branching septated hyphae but the culture evaluation