cefmenoxime and Klebsiella-Infections

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Amphotericin B; Animals; Aspergillosis; Aspergillus fumigatus; Cefmenoxime; Disease Models, Animal; Immunocompromised Host; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases, Fungal; Male; Mice; Pneumonia; Rats

We investigated the synergistic effects of romurtide (MDP-Lys [L18]) and cefmenoxime (CMX) in the treatment of experimental Klebsiella pneumonia in mice. Mice were infected with 1 x 10(4) CFU of Klebsiella pneumoniae by inhalation of aerosol bacterial suspension. About 90% of untreated animals died within a week; however, the mortality rate of animals treated with CMX alone at a dose of 40 mg/kg/day was 60% at 7 days after the infection. When one or two doses of L18 were administered before or after the infection concomitantly with CMX, a remarkable improvement in the survival rate was observed. There was no significant improvement in the survival rate of animals treated with L18 alone before or after infection. Histopathological sections of the lungs of mice treated with CMX and L18 showed slower progression of infection than those of mice treated with CMX alone. Significant differences were also found in quantitative cultures of viable bacteria in the lungs 1 to 4 days after the infection. Although viable bacterial counts in the lungs of the control and CMX-treated groups showed a rapid increase 24 to 48 h after the infection, they remained lower than the initial counts (x 10(4)) in the lungs of mice treated with combination regimens. From these results, it can be concluded that L18 is a useful biological response modifier in the treatment of acute pulmonary bacterial infections.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cefmenoxime; Drug Synergism; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Mice

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered.

Topics: Animals; Biological Assay; Cefazolin; Cefmenoxime; Colony Count, Microbial; Drug Evaluation, Preclinical; Klebsiella Infections; Klebsiella pneumoniae; Lung; Male; Mice; Mice, Inbred Strains; Models, Biological; Models, Statistical; Pneumonia

Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered in an experimental model of murine pneumonia caused by Klebsiella pneumoniae in a way which enabled us to approximate the serum antibiotic concentration time course in humans. Bacterial counts during the experiments were subjected to nonlinear least-squares analyses by using a mathematical model that explained the bacterial killing by the antibiotic concentration time course and other factors associated with antimicrobial potency and bacterial growth. Cefazolin gave a killing curve that changed synchronously with the drug levels in serum; in contrast, cefmenoxime gave a curve that was prolonged as compared with the change in the drug levels in serum. Multiple correlation coefficients were about 0.9, and the model worked well for bacterial count data. Parameters relating to antimicrobial potency of the drugs, bacterial growth rate, and drug distribution into the tissue were estimated numerically.

Topics: Animals; Cefazolin; Cefmenoxime; Cephalosporins; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Mice, Inbred Strains; Models, Biological; Pneumonia

Cefmenoxime (CMX) has been administered under parenteral injection to 39 neonates delivered at term, nearly always by monotherapy in an average dosage of 86.8 mg/kg/day. CMX has been used 31 times in first line therapy and 8 times after failure of association Ampicillin-Gentamicin. 25 strains have been identified: 16 E. coli (9 Ampicillin resistant), 7 P. mirabilis (1 Ampicillin resistant), 1 K. oxytoca and 1 Streptococcus B. The neonates group with septicaemia (1 with arthritis) has been cured without after-effects as urinary tract infections and systemic infections. 2 respiratory tract infections have been improved, the others have been cured. Bacterial samples have always been sterilized within 2 days. Local tolerance (IV or/and IM injection) has been very good. No clinical or biological abnormality has been imputed to treatment. Cefmenoxime appears very effective on enterobacteriaceae (MIC range 0.05-0.5 mg/l) and can be used in newborn infections.

Topics: Bacterial Infections; Cefmenoxime; Drug Tolerance; Escherichia coli Infections; Female; Humans; Infant, Newborn; Klebsiella Infections; Male; Proteus Infections; Proteus mirabilis; Sepsis; Streptococcal Infections