Victor Fainstein

The emerging role of Fusarium infections in patients with cancer.

Infection due to Fusarium species is an increasing cause of serious potentially fatal disease in patients with cancer. We described 9 patients with infection caused by Fusarium species during a 4-year period at the M. D. Anderson Hospital. The spectrum of infections included disseminated disease in 4 patients, skin or soft-tissue infections in 3, pneumonia in 1, and fungemia in 1. All 4 patients with disseminated infection had culture- and biopsy-proven skin lesions caused by Fusarium species and the blood cultures yielded the organism in 3 of these 4 patients. Maxillary sinusitis was the presenting manifestation of Fusarium infection in 2 of these 4 patients, suggesting that paranasal sinuses are potential portals of entry for the infection. Eight patients had a hematological malignancy and 7 were neutropenic at the onset of their infection. Patients with deep-seated infections remained neutropenic and died from infection despite treatment with amphotericin B. All 5 isolates tested in vitro showed resistance to ketoconazole and miconazole, whereas 3 were susceptible to amphotericin B. Fusarium species could play a role in producing myelosuppression and fungal cultures are required to differentiate it from the more commonly encountered Aspergillus species. Fusarium species are emerging as a serious, potentially fatal, pathogen in patients with cancer.

Nosocomial infection caused by Xanthomonas maltophilia: a case-control study of predisposing factors.

Factors predisposing to clinically significant nosocomial infection with Xanthomonas maltophilia were examined in a matched case-control study using multivariate techniques. Sixteen cases occurred among cancer patients in a six-month period, including an apparent cluster of three cases in an intensive care unit. These infections were unusually serious; eight patients had disseminated infection caused by X maltophilia and six died as a result of their infections. Among the 64 factors that were examined, therapy with broad-spectrum antibiotics and central venous catheterization were found to significantly increase susceptibility to infection. Therapy with imipenem was more than ten times more frequent among cases than among controls (p less than .001). All fatal infections occurred in patients who had received imipenem, including two patients who died before the organism could be identified and appropriate therapy instituted. Infection with X maltophilia should be suspected in patients who develop superinfection while receiving imipenem, and prompt therapy should be instituted to improve chances of survival. Because a common environmental source of X maltophilia was not identified, further study is necessary to determine specific preventive measures.

Clostridial bacteremia in cancer patients. A 12-year experience

Over 12 years, 136 episodes of bacteremia caused by clostridial species were documented. Eighty‐three were monomicrobial, and 53 were polymicrobial. Gastrointestinal, genitourinary carcinomas, and acute leukemia were the most common underlying malignancies. Septic shock occurred in 29% of monomicrobial bacteremias and 45% of polymicrobial bacteremias and was associated with a high mortality rate. Acute hemolysis, gas gangrene, and diffuse spreading cellulitis occurred infrequently but were associated with a 100% fatality rate. Many infections caused by Clostridium perfringens and C. septicum were associated with abdominal disease. The most commonly isolated organism was C. perfringens, followed by C. septicum and C. sporogenes. Overall survival was 58%, but it was 66% for monomicrobial episodes and 45% for polymicrobial infections. All of the patients with bacteremia due to an aerobic gram‐negative bacillus in addition to the clostridial species died of their infection. The most effective antibiotics were clindamycin, penicillin, metronidazole, and moxalactam. Surgical drainage of abscesses was an important component of therapy.

Polymicrobial septicemia in the cancer patient.

The medical records of 507 patients with polymicrobial septicemia were examined to determine prognostic and descriptive factors. Over 50% of the episodes occurred in patients with solid tumors and 80% originated during hospitalization. Invasive procedures and immunosuppressive therapy frequently preceded development of polymicrobial septicemia, and infection was often accompanied by shock and pneumonia. A majority of infections were caused by at least 1 aerobic gram-negative bacillus (76%) and anaerobic infections were not infrequent. Overall response among these patients was 50%, with poorest response seen among patients with persistent neutropenia (25%), pneumonia (19%), and gram-negative bacillary infection (46%). Therapy with an antibiotic regimen to which all causative organisms were sensitive was of greatest prognostic significance. Response to appropriate therapy was 58%, whereas only 10% of those who received inappropriate therapy were cured (p less than .0001).

Aztreonam therapy in neutropenic patients with cancer

Combinations of aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin were compared in a prospective randomized trial as empiric therapy for febrile neutropenic cancer patients. Vancomycin was added to aztreonam to provide coverage against gram-positive organisms. Of 535 febrile episodes included in the study, 455 were evaluable. The aztreonam/vancomycin and aztreonam/vancomycin/amikacin combinations were both more effective than the moxalactam/ticarcillin combination in a total of 244 episodes of documented infection. The difference was due to the fact that both aztreonam-containing combinations were more effective than the moxalactam/ticarcillin combination in documented gram-positive infections. The three regimens were equally effective in 67 documented infections due to a single gram-negative bacterial species. (The response rates were 87, 86 and 94 percent for the aztreonam/vancomycin, aztreonam/vancomycin/amikacin, and moxalactam/ticarcillin combinations, respectively.) Aztreonam was effective as the single active antibiotic in the treatment of gram-negative infections in neutropenic patients; however, it must be used in combination with another antibiotic to provide gram-positive coverage.

Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients

A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients. The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one. Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response. Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01). The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash. Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients. This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.

β‐Lactam regimens for the febrile neutropenic patient

A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin‐clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram‐negative infections, and infections in patients with persistent severe neutropenia (< 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive.

Foscarnet-ganciclovir cytomegalovirus retinitis trial: 5. Clinical features of cytomegalovirus retinitis at diagnosis

PURPOSE To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis. METHODS Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS. RESULTS The systemic characteristics marginally associated with the percentage of retina affected by CMV in a patients worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV. CONCLUSIONS The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions.

Central nervous system histoplasmosis: An unappreciated complication of the acquired immunodeficiency syndrome

Involvement of the central nervous system (CNS) by Histoplasma capsulatum is a rare event. It is usually not included in the differential diagnosis of CNS lesions in patients with acquired immunodeficiency syndrome (AIDS). Herein are described four patients with AIDS and progressive disseminated histoplasmosis who had CNS involvement. Histoplasmosis in the CNS may produce meningitis, single or multiple brain abscesses, and may present with either a clinical picture of obtundation or a deteriorating space-occupying CNS lesion. Three of the four patients were treated with amphotericin B and had initial clinical response, but ultimately, all experienced a relapse and died from their infection.

Pseudomonas putida: newly recognized pathogen in patients with cancer

Pseudomonas putida was recovered from blood culture specimens between 1980 and 1985 in 15 patients with cancer. No isolates were found in specimens obtained before 1980. Eight patients were considered to have septicemia (more than one positive blood culture result plus clinical signs of infection). Septicemia was monomicrobial in three of those eight patients and polymicrobial in five. Of these eight patients, one had pneumonia and three had phlebitis, cellulitis, or both at the site of the venous catheter. The infection appeared to be catheter-related in these three patients, with response to catheter removal in one patient, response to catheter removal and antibiotics in one patient, and response to antibiotics alone in one patient. P. putida was isolated from the site of insertion and the tip of the catheter in one of these three patients. Following therapy, all patients had a rapid recovery from their infection. In vitro susceptibility testing revealed that 90 percent of the isolates were susceptible to piperacillin, ceftazidime, imipenem, and ciprofloxacin.