Cefodizime Research Articles

Immunopharmacological activity of cefodizime in young and elderly subjects: In vitro and ex vivo studies

The biological response modifying activities of cefodizime (CDZ), a new third-generation cephalosporin, were investigated in vitro and ex vivo. In vitro investigations using cells isolated from the blood of young healthy donors showed no stimulating activity of CDZ on peripheral blood lymphocytes, natural killer cell activity, IL-1 production by adherent mononuclear cells, PMN chemiluminescence or PMN chemotaxis. A slight but statistically insignificant increase in PMN phagocytosis and phagocytic index was observed in the same population. IL-1 production was increased in three subjects with low resting state values. In a controlled ex vivo study, 20 healthy elderly subjects selected on the basis of depressed phagocytic function were treated with CDZ 1 g i.m. b.i.d. or placebo for eight days. PMN function was determined at baseline and on the day after the last dose. In the CDZ group a significant increase in both phagocytosis and phagocytic index was found, while there were no changes in the placebo group. In conclusion, CDZ restored depressed PMN phagocytic function in a population of elderly subjects. Patients with impaired PMN function who require antibiotic treatment may benefit from this activity of CDZ.

Review of effectiveness of cefodizime in the treatment of lower respiratory tract infections with parenchymal involvement.

The efficacy of cefodizime (CDZ) in lower respiratory tract infections (LRTI) with parenchymal involvement was assessed by the analysis of data from 919 patients who participated in four controlled, randomized studies and three open studies. Sputum bacteriology and a chest x-ray were performed at baseline and after therapy. A total of 778 patients were evaluable for clinical efficacy and 451 for bacteriological efficacy. The most frequent pathogen was Streptococcus pneumoniae, followed by Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. CDZ 1 g b.i.d., 2 g b.i.d. and 2 g once daily achieved clinical and bacteriological cure rates above 90%, which matched those observed with the comparators (cefuroxime 1.5 g t.i.d. and cefotaxime 2 g b.i.d.). No significant differences in clinical and bacteriological outcome were detected when the various CDZ dosage regimens were compared. 1 g CDZ b.i.d. is therefore recommended as the regimen of choice for the treatment of LRTI with parenchymal involvement, with CDZ 2 g once daily as an alternative.

Cefodizime: enhancement of depressed phagocytosis-associated respiratory burst activity in chronic uremic patients.

Patients with renal failure are highly susceptible to infection, in part because uremia decreases the killing capacity of phagocytic leucocytes. Phagocytosis-associated respiratory burst activity was investigated at different stages of renal impairment by measuring the 14CO2 production during metabolism of labeled glucose by phagocytic cells. Non-dialyzed end-stage renal failure and haemodialysis patients showed a decrease in phagocytosis to about 50% of normal (p less than 0.05). In a second phase of the study, six haemodialysis patients received 2 g cefodizime (CDZ) i.v. after dialysis for ten days (five doses). Phagocytosis was determined at baseline and was followed until day 29. A clear, long-lasting stimulatory effect of CDZ on phagocytosis after both latex and zymosan challenge was found. It is concluded that a usual CDZ dosage regimen stimulates depressed phagocytosis in haemodialysis patients, and that this stimulatory effect persists for at least two weeks after the end of treatment. Uremic patients with infection may benefit from this additional property of CDZ.

Pharmacokinetic profile of cefodizime.

The pharmacokinetics of cefodizime (CDZ) were determined after i.v. and i.m. administration of single doses of up to 2 g and after i.v. administration of 2 g b.i.d. for six days. Serum concentrations were adequately described by three exponential functions, with a terminal half-life of about 4 h. Serum and urine levels and amounts excreted were dose-proportional, and derived pharmacokinetic characteristics were dose-independent. Steady state was established after the second dose (b.i.d.). CDZ is 100% bioavailable after i.m. administration. Concomitant administration of lidocaine did not alter either bioavailability or pharmacokinetic characteristics. Following administration of 1 and 2 g i.m., Cmax was reached after 1.2 h and amounted to 60 and 140 mg/l, respectively. CDZ is 88% bound to plasma proteins. CDZ was predominantly eliminated by the kidneys (80% of dose), a further 20% being excreted in the bile. Metabolites were not detectable in serum or urine. Dose adjustment does not seem warranted in the elderly. For renally impaired patients with CLcr between 30 and 10 ml/min, the daily dose should not exceed 2 g. For patients with CLcr below 10 ml/min, individual adjustment is suggested. CDZ showed good penetration into tissues and biological fluids (lung, bronchial secretions, pleural fluid, kidney, prostate, urine, bone, muscle, skin, Fallopian tube) with long-lasting concentrations. In urine, therapeutic concentrations were present for more than 24 h after administration of 1 and 2 g. Thus, on the basis of its pharmacokinetic profile, cefodizime is appropriate for effective treatment with once-daily administration.

Cefodizime given once daily for the treatment of upper urinary tract infections and complicated lower urinary tract infections.

The efficacy of cefodizime (CDZ) in upper urinary tract infections (UUTI) and complicated lower urinary tract infections (LUTI) was assessed by analysis of the combined results of five clinical trials. Doses of CDZ 1 g i.m. daily, 1 x 2 g i.v. or i.m. and 2 x 2 g i.v. were investigated; comparative agents were cefuroxime 3 x 1.5 g and ceftizoxime 1 x 2 g. Median duration of treatment was seven days. A total of 544 patients, 61% of whom had UUTI, entered the studies. Four hundred twenty-two patients were evaluable clinically and 375 bacteriologically. The most frequent pathogen at baseline was Escherichia coli, followed by Proteus mirabilis, Klebsiella spp. and Staphylococcus aureus. Both clinical and bacteriological cure rates were above 90% in all study groups. The dosage of 1 x 2 g CDZ is recommended for the treatment of UUTI and complicated LUTI.

Cefodizime stimulates subpopulations of cells mediating spontaneous or antibody-dependent cytotoxicity in patients with bacterial infections.

The influence of cefodizime (CDZ) on spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) was investigated in nine patients with conditions predisposing to infection (T-cell deficiency, humoral immune deficiency, myeloproliferative syndrome, kidney or liver damage, or chronic pulmonary disease). SCMC, using the K562 and LIK cell lines as targets, and ADCC, using the LIK cell line, were measured at baseline and after ten days of therapy with CDZ for lower respiratory tract infections. Six patients were cured; clinical outcome was not evaluable in the other three. SCMC lysis of K562 cells did not change significantly. SCMC and ADCC lysis of LIK (lymphoblastoid) cells both increased significantly. CDZ selectively stimulated a subpopulation of NK cells in this population of immunocompromised patients with lower respiratory tract infections.

Cefodizime launched in the UK

Cefodizime launched in the UK

Changes in lymphocyte subpopulations in patients treated with cefodizime for acute lower respiratory tract infections

The influence of cefodizime (CDZ) on CD4 and CD8 lymphocytes was investigated in patients with lower respiratory tract infection and underlying respiratory diseases. Ten men and one woman were treated with CDZ 1 g i.m. b.i.d. for ten days. The infecting organisms were Haemophilus influenzae (5), Streptococcus pneumoniae (2) and Escherichia coli (1). No adverse events were reported. Nine patients were clinically cured; two required further antibiotic therapy. Leucocyte counts decreased significantly during treatment. Lymphocyte counts and CD4 cells both increased significantly in absolute and relative numbers, while there was a much smaller increase in CD8 cells. This resulted in a significant increase in the CD4/CD8 ratio. These effects of CDZ might be of benefit for immunocompromised patients with bacterial infections.

呼吸器感染症に対するCefodizime (CDZM) とCefotaxime (CTX) の薬効比較試験

The clinical efficacy and safety of Cefodizime (CDZM), a new cephem antibiotic, was objectively compared with that of Cefotaxime (CTX) in patients with respiratory infections under a well-controlled comparative study. Patients were administered CDZM or CTX by drip infusion b.i.d. for 14 days in principle at a daily dose of two grams. The parameters assessed were clinical efficacy, safety and clinical usefulness. The following results were obtained: 1. On the basis of committee judgement the clinical efficacy rate was 78.1% (125/160) for the CDZM group, 82.7% (124/150) for the CTX group, and no significant difference was observed between the two drug groups. On the other hand, on the basis of judgement by physicians in charge, the clinical efficacy rate was 83.1% (133/160) for the CDZM group, 83.9% (125/149) for the CTX group, and no significant difference was observed between the two groups. 2. The corresponding figures for patients with pneumonia and pulmonary suppuration were 82.4% (70/85) for the CDZM group, 79.7% (59/74) for the CTX group and no significant difference was observed according to the committee judgement. The judgement by physicians in charge also revealed 83.5% (71/85) for the CDZM group and 82.2% (60/73) for the CTX group. No significant difference was noted between the two groups. While, the committee judgement for the clinical efficacy in patients with chronic respiratory tract infections showed 73.3% (55/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups. The corresponding figures were 82.7% (62/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups on the judgement by physicians in charge. Furthermore, the clinical efficacy of both drugs on chronic respiratory tract infections was assessed according to "Criteria for Evaluation of Clinical Efficacy of Chemotherapeutics on Chronic Respiratory Tract Infection". It was 76.8% (53/69) for the CDZM group, 76.3% (58/76) for the CTX group, and no significant difference was observed between the two groups. 3. The bacteriological eradication rate of causative pathogens was 92.4% out of 66 patients treated with CDZM and 95.5% out of 67 patients treated with CTX in whom judgement was possible. No significant difference was observed between the two drug groups. 4. The adverse reactions occurred in 4 (2.2%) patients for the CDZM group and 8 (4.5%) patients for the CTX group respectively, with no significant inter-group difference in frequency of these reactions for all cases.(ABSTRACT TRUNCATED AT 400 WORDS)