cefoxitin and Agranulocytosis

The efficacy of beta-lactam antibiotics and amikacin alone and in various combinations against Pseudomonas aeruginosa was studied in a rabbit model simulating a closed-space infection in a locally neutropenic site. Six strains of P. aeruginosa were studied in semipermeable chambers placed subcutaneously in rabbits. Therapy was begun 4 h after inoculation of 5 X 10(4) CFU of bacteria per ml of pooled rabbit serum into the chambers. Antibiotics were administered intramuscularly every 6 h for 16 doses. Quantitative bacteriology was measured at the start of therapy and at 20, 44, and 92 h thereafter. Antibiotic concentrations were measured in blood and chamber fluid. Results were compared with in vitro tests of susceptibility and synergy. No single-agent therapy eradicated any of the six test organisms. Azlocillin (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated five of six organisms by 92 h, and ceftizoxime (100 mg/kg per dose) plus amikacin (20 mg/kg per dose) eliminated three of six test strains. Azlocillin plus ceftizoxime (each 100 mg/kg per dose) failed to eliminate any of the six strains. To eliminate P. aeruginosa in this model, two drugs were required, with one being an aminoglycoside. In vitro susceptibility tests of synergy were predictive of successful therapy whenever the antibiotic concentrations (free and total) at the infection site exceeded the MBC for both the aminoglycoside alone and the beta-lactam when tested in combination with amikacin.

Topics: Agranulocytosis; Amikacin; Animals; Anti-Bacterial Agents; Azlocillin; Cefotaxime; Cefoxitin; Ceftizoxime; Disease Models, Animal; Drug Combinations; Female; Hydrogen-Ion Concentration; Kanamycin; Microbial Sensitivity Tests; Neutropenia; Penicillins; Protein Binding; Pseudomonas Infections; Rabbits

The authors report 57 febrile episodes in 36 patients with leukemia and lymphoma. Patients with less than 1000 granulocytes and fever above 38.5 degrees C were included in this empirical antibacterial protocol (15 mg amikacin/kg/day/iv, 500 mg carbenicillin/kg/day/iv, 200 mg cefoxitin/kg/day/iv). The criteria for diagnosis of infection were those widely accepted [Schimpff et al. 1971]. Microbiologic documentation of infection was performed in 33.4% of febrile episodes. Antibacterial therapy induced an improvement in 75.1% of cases. Clinical response often occurred in the presence of profound granulocytopenia (in 72% of episodes). Therapy failure was higher in pneumonia (46%) and lower in fever of unknown origin (21%).

Topics: Adult; Aged; Agranulocytosis; Amikacin; Bacterial Infections; Carbenicillin; Cefoxitin; Drug Therapy, Combination; Female; Fever; Humans; Kanamycin; Leukemia; Lymphoma; Male; Middle Aged