azlocillin and Hematologic-Diseases

The authors report treatment of eighteen haematologic patients (twelve male, six female, age between 21 and 78 years), suffering from upper respiratory tract (ten patients) and/or lower urinary tract (eight patients) infections caused by Gram-negative germs, with a combination of ciprofloxacin-azlocillin in the ratio 1:10. Before treatment, the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Fractional Inhibitory Concentration (FIC) index of Gram-negative isolates from patients for the ciprofloxacin-azlocillin combination were evaluated. The in vitro experiments revealed a synergistic activity of the combination for 85% of isolates, while at the same concentration ciprofloxacin alone was 100% effective, and azlocillin alone was 50% effective. The combination was administered to patients as follows: ciprofloxacin: 750 mg "per os" every 12 h; azlocillin 5 g intravenously every 8 h for a therapeutic cycle of 8 days. Seventeen of the eighteen patients that were treated with the combination showed complete eradication of the causative pathogen, sixteen of the eighteen patients recovered fully, whereas the other two showed significant improvements. The tolerability of the combination was excellent in seventeen patients and only one patient developed symptoms of mild gastric intolerance. The results presented here warrant further interest in studies of this antibiotic combination.

Topics: Adult; Aged; Azlocillin; Ciprofloxacin; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Diseases; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Opportunistic Infections; Prospective Studies

One hundred and two patients with neutropenia (less than 1 x 10(9)/L) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospectively randomised, upon the development of fever or other signs of infection, to receive empirical antibiotic treatment with either ceftazidime (+/- flucloxacillin) (n = 52) or azlocillin plus amikacin (+/- flucloxacillin) (A&A, n = 50). The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25% of the patients in each group on the clinical suspicion of Gram positive infection. When assessed at 96 hours, the complete response rates were 59.6% for the ceftazidime treated patients and 44% for A&A treated patients. Partial response rates were 17% and 20% respectively. This difference was not statistically significant. Eight patients died whilst on the trial, three of those initially randomised to ceftazidime and five initially randomised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group (p less than 0.01), whilst other parameters of toxicity were equivalent. No primary or acquired resistance to ceftazidime was encountered. Separate analysis of those patients who did not receive flucloxacillin yielded identical results. We conclude that ceftazidime (+/- flucloxacillin) is as efficacious as azlocillin plus amikacin (+/- flucloxacillin) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Amikacin; Azlocillin; Bacterial Infections; Ceftazidime; Drug Therapy, Combination; Female; Fever; Floxacillin; Hematologic Diseases; Humans; Male; Middle Aged; Neutropenia; Randomized Controlled Trials as Topic; Remission Induction; Therapeutic Equivalency

The safety of azlocillin was evaluated in 631 patients treated for urinary tract or systemic infections in U.S.A. clinical trials. The mean azlocillin dose was 260 mg/kg/day and the mean duration of treatment was 11.1 days. Twenty patients (3.2%) experienced adverse local reactions and 92 patients (14.6%) experienced adverse systemic reactions. In thirty-one instances (4.9%) they led to premature termination of therapy, but only 14 of 135 reactions were classified as severe. All adverse reactions were reversible if adequate follow-up was done. Hypersensitivity reactions, manifest by rash, fever or eosinophilia occurred in 4.4%, 0.3% and 1.1% respectively. Hypokalaemia was noted in only three instances (0.5%). Hepatotoxicity occurred in 1.7%, diarrhoea in 1.9% and leukopenia in 0.3%. Transient chest discomfort was seen on rapid infusion on three occasions. Overall, azlocillin appeared well tolerated, and had no evident unique toxicity.

Topics: Adolescent; Adult; Aged; Azlocillin; Bacterial Infections; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Drug Hypersensitivity; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Kidney Diseases; Male; Middle Aged; Penicillins; Water-Electrolyte Imbalance