azlocillin and Neoplasms

In the four EORTC International Antimicrobial Therapy Cooperative Group trials, the frequency of gram-positive isolates has increased significantly from 29% of single-organism bacteraemias in trial I (1973-1976) to 41% in trial IV (1983-1985). In trial IV febrile and neutropenic (less than 1000 polymorphonuclear lymphocytes per microliter) cancer patients were randomized prospectively to receive either azlocillin plus a long course (at least 9 days) of amikacin, or ceftazidime plus a short course (3 days) of amikacin, or ceftazidime plus a long course of amikacin. Without modification of the allocated antibiotics, the overall response rates for gram-positive bacteraemias were similar for all three regimens (19/37 [51%], 8/23 [35%] and 14/30 [47%]), respectively. However, in patients with prolonged and severe neutropenia, treatment with azlocillin plus amikacin was significantly more effective than with ceftazidime plus 3 days' amikacin (7/10 vs. 0/7). The overall response rate for these infections was significantly lower than that observed in trial I (46% vs. 74%), but this was not associated with increased mortality. The response to treatment was significantly influenced by the susceptibility of the infecting strain to the beta-lactam. Multivariate analysis revealed that increasing age, presence of a central venous catheter and resistance to beta-lactam adversely affected outcome. Future studies should be designed to improve the outcome of gram-positive bacteraemia in neutropenic patients with cancer.

Topics: Agranulocytosis; Amikacin; Azlocillin; Bacterial Infections; Ceftazidime; Drug Therapy, Combination; Gram-Positive Bacteria; Humans; Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Sepsis

Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children.

Topics: Adolescent; Agranulocytosis; Azlocillin; Bacteria; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Fever; Humans; Infant; Neoplasms; Netilmicin; Neutropenia; Randomized Controlled Trials as Topic

To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia, we conducted a randomized multicenter trial comparing ceftazidime plus a short course (three days) of amikacin, ceftazidime plus a long course (nine days) of amikacin, and azlocillin plus a long course (nine days) of amikacin. Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients. Without a change in antibiotics, the response rates were 81 percent with ceftazidime and long-course amikacin, 48 percent with ceftazidime and short-course amikacin (P = 0.002), and 40 percent with azlocillin and long-course amikacin (P less than 0.001). Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy, the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin (P = 0.03). Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection, whereas the presence of leukemia or shock was the least favorable. We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside (amikacin) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Amikacin; Azlocillin; Ceftazidime; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Humans; Leukemia; Leukocyte Count; Male; Middle Aged; Neoplasms; Prognosis; Random Allocation; Regression Analysis; Sepsis

Topics: Agranulocytosis; Azlocillin; Child; Clinical Trials as Topic; Escherichia coli Infections; Female; Fever; Humans; Male; Neoplasms; Neutropenia; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Ticarcillin

A multicentre clinical trial was organized by the International Antimicrobial Therapy Project Groups of the European Organisation for Research on the Treatment of Cancer (E.O.R.T.C.) to compare the effectiveness of three combinations of antibiotics (azlocillin + amikacin; cefotaxime + amikacin and ticarcillin + amikacin) in patients with malignant leukopenic and febrile diseases (polymorphonuclears less than 1000/mm3; temperature greater than 38.5 degrees C). Some 800 patients from 20 centres entered the study. Preliminary results in 421 assessable patients showed a 62% positive response rate. The response rate in patients with bacteraemia was twice as high in the azlocillin group than in the other groups, the difference being significant at p less than 0.02. This difference does not seem to be due to a distribution bias, since the responsible micro-organisms, the severity of granulopenia, the incidence of bacterial-resistant strains, etc., were similar in all three groups. Similarly, the death rate was 12% in the azlocillin-amikacin group as against 15% and 17% respectively in the other groups. It would appear from this trial that the azlocillin-aminoglycoside treatment is superior to the other antibiotic combinations tested in this category of patients.

Topics: Agranulocytosis; Amikacin; Azlocillin; Bacterial Infections; Cefotaxime; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Neoplasms; Penicillins; Ticarcillin

Fifty consecutive episodes of fever in neutropenic children with malignant disease or aplastic anaemia were randomized to treatment with either ceftazidime alone or a combination of azlocillin and tobramycin, pending the results of bacteriological investigation. More than 90% of organisms isolated from these episodes were sensitive to ceftazidime, which appears to be a non-toxic alternative to aminoglycosides in such circumstances.

Topics: Adolescent; Agranulocytosis; Anemia, Aplastic; Azlocillin; Bacterial Infections; Ceftazidime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Fever; Humans; Infant; Neoplasms; Neutropenia; Penicillins; Random Allocation; Tobramycin

Although the semisynthetic broad-spectrum acylureido-penicillin, azlocillin has been demonstrated to have significant antibiotic activity in leukemic patients, its role in combination therapy of febrile granulocytopenic patients with chemotherapy-treated solid tumors has not been clearly delineated. Thirty-five solid tumor patients with chemotherapy-induced absolute granulocytopenia (less than 1000 granulocytes/ml) associated with fever (greater than 38.3 degrees C) were treated on a prospective study with a combination of azlocillin 4 g intravenously (IV) every 6 hours, cephalothin 2 g IV every 6 hours, and tobramycin 80 to 100 mg IV every 8 to 12 hours. Prior chemotherapy included doxorubicin combinations in 18 patients and other combinations in 17 patients. Granulocyte counts preantibiotic therapy were greater than 100 granulocyte/ml in 14 patients, 100 to 499 in nine patients, and 500 to 1000 in 12 patients. Granulocyte nadirs were less than 100 in 20 patients, 100 to 499 in nine patients, and 500 to 1000 in six patients. Times for granulocytes to rise towards normal were 1 to 3 days in eight patients, 4 to 6 days in 18 patients, and 7 or more days in nine patients. Tobramycin levels were primarily in the peak range of 3 to 6 micrograms/ml and trough range of 0 to 1.9 micrograms/ml. The site and pathogen were identified in nine patients, the infection site clinically documented without isolated pathogen in three patients, and no site or pathogen identified in 23 patients. Of the 35 patients, 34 had good responses to the antibiotic combination (complete disappearance of fever and other evidence of infection). Serum creatinine rose 0.4 to 0.6 mg/dl in nine patients, 0.7 to 1.5 in four patients, and 1.5 in one patient (obstructive uropathy). The only other noted antibiotic-related side effect was hypokalemia. This antibiotic combination had little toxicity with marked efficacy.

Topics: Adult; Aged; Aged, 80 and over; Azlocillin; Bacterial Infections; Cephalothin; Drug Evaluation; Drug Therapy, Combination; Female; Fever; Humans; Leukopenia; Male; Middle Aged; Neoplasms; Tobramycin

At the present time, gram-negative bacillary bacteremia in patients with neutropenia will respond favorably in 60% to 70% of the patients when carbenicillin-ticarcillin or cephalothin-cefazolin combined with aminoglycosides (gentamicin, tobramycin, sisomicin, netilmicin, or amikacin) are given. Piperacillin alone will cure 20/34 (59%) of bacteremic episodes in patients without granulocytopenia who have a severe underlying disease. In patients with neutropenia, the combination of piperacillin with amikacin was found to be associated with a favorable response in 76/121 patients (63%). These results are thus as good as those obtained with other broad-spectrum, beta-lactam antibiotics whether used alone in patients without granulocytopenia or in combination with aminoglycosides in patients with neutropenia. It seems likely that in patients with severe underlying disease and/or granulocytopenia, antibiotic combinations have reached an optimal efficacy. More attention should be paid to the correction of the basic predisposing factors to infection (granulocytopenia and immunodepression) and to infections caused by nonbacterial pathogens.

Topics: Amikacin; Azlocillin; Bacterial Infections; Drug Therapy, Combination; Humans; Mezlocillin; Neoplasms; Penicillins; Piperacillin