European journal of cancer & clinical oncology最新文献

The results of the four EORTC trials conducted over the past 15 years suggest: (1) early empiric therapy with broad spectrum antibiotics directed against gram-negative bacterial bacteremia (GNBB) is a reasonable approach in febrile granulocytopenic patients (GCP); (2) the level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; severely and/or persistently neutropenic patients are the true tests of antibiotic efficacy and they benefit from antimicrobial synergism; (3) mortality from GNBB in GCP is not related directly to a given empiric antimicrobial regimen which may 'buy time' and allow appropriate therapeutic alterations; (4) only microbiologically documented infections and especially bacteremias are useful to compare responses to antimicrobial regimens; (5) the response rate of GNBB is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen and emergence of resistance to some antibiotics (cephalothin, carbenicillin, ticarcillin, azlocillin) has rendered some combinations less effective. The combination of an anti-Pseudomonas beta-lactam plus an aminoglycoside is recommended as the 'standard' for empiric therapy in febrile GCP; (6) gram-positive pathogens have become a common cause of bacteremia in GCP and although the response rate to empiric regimens may be marginal, the associated mortality is low. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.

In order to evaluate bacterial factors which might predispose to P. aeruginosa colonization or bacteremia in the granulocytopenic patient, 132 isolates recovered from 44 oncology patients were evaluated for antigenic serotype, iron correctable sensitivity to pooled human serum, antibiotic susceptibility, production of lecithinase, elastase, protease, gelatinase, pyocyanin and pyoverdin. Similarly, potential host factors, primarily total iron binding capacity, were evaluated in a subpopulation of acute leukemia patients composed of 13 control patients without P. aeruginosa cultured during their hospital course, 11 colonization only patients and 15 P. aeruginosa bacteremia patients. No significant differences were observed between strains recovered from bacteremia vs. colonization patients for extracellular enzyme activity, pigment production, serum sensitivity and antigenic serotype. Significant differences were observed between bacteremia and colonizing strains for antibiotic susceptibility to ticarcillin, 40% vs. 76% (P less than 0.002); piperacillin, 44% vs. 86% (P less than 0.006); and cefsulodin, 60% vs. 90% (P less than 0.02). Of the host factors evaluated in the acute leukemia patients, significant differences were observed between the TIBC nadir of control patients and both colonization patients (P less than 0.0002) and bacteremia patients (P less than 0.0004). P. aeruginosa bacteremia was associated with the temporal occurrence of TIBC nadir and the detection of the organism. These data suggest a possible role for beta-lactam antibiotic resistance and host iron binding capacity as determinants and possible predictors of P. aeruginosa sepsis in the granulocytopenic patient.

Recurrent episodes of salmonellosis, including recurrent life-threatening bacteremias, have been well-described in patients with AIDS. Because of the need to avoid sensitization to trimethoprim-sulfamethoxazole (TMP-SFX) in AIDS patients and the high frequency of ampicillin resistance of Salmonella isolates, alternative therapies must be sought. We report the treatment of nine AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral fluoroquinolone which has excellent in vivo activity against Salmonella sp. Each patient had two to three prior distinct clinical episodes of salmonellosis which had failed to be eradicated with standard courses of ampicillin, TMP-SFX, ceftriaxone or cefotaxime. Microbiologic relapse had occurred in each patient within 2-4 weeks. Each of the enteric pathogens was susceptible in vitro to norfloxacin. Patients were treated with norfloxacin 400 mg bid orally for 30 days. Stool cultures were negative at 1 week in all patients. Nausea and headache were the only adverse reactions to norfloxacin noted. One patient had a clinical and microbiologic relapse of Salmonella 1 week after norfloxacin was stopped but responded to retreatment with norfloxacin. Norfloxacin appears effective in the treatment of enteric infections in AIDS patients and may be more useful than standard agents in eradicating the organism and preventing clinical and microbiologic relapse. Oral administration and twice daily dosing are significant advantages.

In view of the activity of Cisplatin in bladder cancer a multicentre study of its less toxic analogue Carboplatin was carried out in 48 patients with metastatic transitional cell carcinoma, of whom 30 had received no previous cytotoxic chemotherapy. No complete remissions and only 3 partial responses were observed, suggesting that Carboplatin has only minimal activity in this disease.