Search

Cefotiam (SCE 963), a new, broad-spectrum, third generation cephalosporin was used in the treatment of 136 patients suffering from respiratory tract infections, urinary tract infections, septicemia, meningitis, biliary tract infections and osteoarthritis infections. Cefotiam was administered in monotherapy to 98 patients at the mean posology of two grams per day (extreme doses: 1 to 6 g). The following clinical effectiveness was noted: 83 successes and 18 failures on 101 available clinical reports. The general, biological tolerance and renal tolerance was good in all patients.

The MIC (agar dilution method) and the zone diameter (disk diffusion) were determined for two hundred and sixteen of the most frequently bacterial strains found in hospitals in order to establish the regression curves for four new cephalosporins : cefotaxime, cefoperazone, cefotiam, moxalactam. The dta (MIC, zone size) were represented by a series of points (Mi (Xi Yi) in semilogarithmic rectangular co-ordinates expressed as : Xi = log2 MIC + 7 ; Yi = zone diameter. Firstly, we tried to fit a regression polynomial to this series of points progressing from degree 1, simple equation (standard regression line) 2, 3, etc. in order to reduce if need be, the deviation between the model (polynomial) and the empirical data. For these four cephalosporins a regression polynomial was obtained. Secondly, the global series was divided into three series of points Mi corresponding to three ranges of MIC : MIC less than or equal to 4 microgram/ml ; 4 less than or equal to 16 micrograms/ml; MIC greater than or equal to 16 microgram/ml. A regression line was obtained for each series and compared with each other and each one with the global regression line (they do not coincide statistically). Concerning these antibiotics, it is better to use a regression polynomial rather than apply a standard regression line.

The large apparent volume of distribution of cefotiam (reported by Fourtillan et al. [4]), prompted an investigation of cefotiam diffusion into ascitic fluid. Eight patients with non-infected ascites were each given a single intravenous bolus of 2 gr cefotiam. Samples of blood and ascitic fluid were collected 0.5, 1, 2, 3, 4, 6 and 8 hours after the injection. Plasma and ascitic fluid concentrations of unchanged cefotiam were determined using HPLC. Peak concentration in ascitic fluid averaged 18 micrograms/ml and was reached at two hours. Concentrations were still high (approximately 13 micrograms/ml) at 8 hours, leading to further assays 12 and 24 hours after the injection in three subjects. Cefotiam concentrations achieved in ascitic fluid seem adequate for the treatment of infected ascites, given the antibiotic's MICs for the organisms most commonly involved.

The cefotiam (CFT) penetration in infected ascitic fluid was investigated in 12 cirrhotic patients. CFT (1 g every 8 h) was given intravenously and measured by HPLC in plasmatic and ascitic samples. The mean ascitic concentrations (+/- SEM), 1 h, 3 h and 8 h after the first injection (J1) were 14.6 +/- 4.6, 11.8 +/- 3 and 8.4 +/- 2.9 micrograms/ml respectively. These values were 38, 62 and 88% of the corresponding mean plasmatic concentrations and higher than the MIC's for the organisms most commonly involved. The mean plasmatic and ascitic concentrations, a few days later (4.5 or 6 days) (Jn) were not significantly different from the corresponding values at J1. A significant decrease of polymorphonuclear cell count was observed between J1 and Jn. These results suggest that CFT diffusion into ascitic fluid is independent of inflammation and CFT is an adequate antibiotic in cirrhotic patients with infected ascitic fluid.

We report on the results of a randomized study of 1 g céfotiam flash pre-operative antibioprophylaxis to prevent post-operatory infection complications in non-endoscopic urologic surgery. Thirty-seven patients (17 controls and 20 treated) have had a prostatic adenomectomy: treatment has lead to decrease the number of post-operatory wall complications (47% vs 20%) and hospitalisation staying (p less than 0.03). Seventy-eight patients have had a urologic surgery with lumbar or abdominal incision (37 treated and 41 controls). In this group, there was not gain on post-operatory infections complications nor on hospital staying, since this surgery has a little number of infections complications. During the study, we have not noted an abnormal part of cefotiam resistant germs.

Extravascular diffusion of cefotiam was studied by a suction blister technique. Maximal cefotiam concentration in blister fluid (18.4 +/- 6.4 micrograms X ml-1) was found one hour after intravenous injection of a 1 g bolus. The area under the curve (AUC) of blister fluid concentrations was 35.4 micrograms X ml-1. Apparent elimination half-life from blister fluid was 0.72 hour. The AUC plasma/AUC blister fluid ratio approximated 1.

Simultaneous administration by the intravenous route of 1 g of cefotiam and 1 g of cefsulodin does not alter the pharmacokinetic parameters of either compound.

In vitro activity of a new cephalosporin, cefodizime, was investigated by comparison with cefotiam, cefoperazone, cefotetan and cefotaxime. 291 Enterobacteriaceae strains belonging to 6 cephalosporin-resistance phenotypes and 32 strains of oxidative Gram negative bacilli were tested. With modal MICs of 0.25 to 4 mg/l, cefodizime is active on most phenotypes of resistance to first or second generation cephalosporins demonstrated in vitro in Enterobacteriaceae, including strains resistant to cefamandole and intermediate to cefoxitin. Cefodizime fails to inhibit strains resistant to third generation cephalosporins (E. cloacae, C. freundii, P. stuartii), except for those strains of S. marcescens belonging to this phenotype whose modal MIC is 4 mg/l. 85% of all tested Enterobacteriaceae are inhibited by 4 mg/l and 91% by 8 mg/l. Cefodizime exhibits little activity against A. calcoaceticus and P. aeruginosa. Comparison of activities of the five cephalosporins against Enterobacteriaceae shows that cefodizime out-strips cefotiam, cefoperazone and cefotetan as a result of its broader spectrum of activity against tested species. Cefotaxime, on the contrary, proves superior to cefodizime and is still the most potent drug against. A. calcoaceticus whereas cefoperazone has the greatest effectiveness against P. aeruginosa.

20, 30 and 90 minutes after a single intravenous injection of 2 g of cefotiam prostatic tissue and serum samples were taken from 12 patients who underwent transabdominal prostatectomy for prostatic adenoma. Cefotiam was assayed by HPLC. Mean serum and prostatic concentrations were respectively 157 +/- 39 mg/ml and 42 +/- 23 mg/g at 20 mn, 77 +/- 52 mg/ml and 54 +/- 2 mg/g at 30 mn, 36 +/- 21 mg/ml and 16 +/- 18 mg/g at 90 mn. Elimination half-life of cefotiam was 1 h 39 mn for serum and 1 h 10 mn for prostatic tissue. These findings confirm the satisfactory diffusion of cefotiam within prostatic tissue, although saturation occurs after 30 mn. Treatment of prostatitis by cefotiam can be expected to give excellent results.

Antibacterial activity of cefotiam associated with gentamicin, tobramycin, netilmicin, or amikacin against Enterobacteriaceae strains either moderately susceptible (MIC = 4 to 32 micrograms/ml, 14 strains) or resistant (MIC = 64 to 512 micrograms/ml, 22 strains) to cefotiam was studied using the checkerboard method. High rates of synergic associations (FIC index less than or equal to 0.5) were found, with variations according to the aminoglycoside: 65% for tobramycin and netilmicin, 76% for amikacin, and 81% for gentamicin. Activity of cefotiam is increased by the synergic effect of these associations: of the 36 strains tested, 83, 78 and 76% became susceptible to cefotiam (MIC less than or equal to 4 micrograms/ml) associated with tobramycin, netilmicin or gentamicin, and amikacin respectively.

Cefotiam, a new broad-spectrum cephalosporin was used for the treatment of 30 cases of urinary-tract infections (UTI). Patients, 20 females, 10 males were between 23 and 76 years old. UTI were 17 cystitis, 9 pyelonephritis and 4 prostatitis. Bacteria isolated from urine were : 24 E. Coli, 3 Proteus mirabilis, 1 Providencia, 3 Klebsiella, 3 Enterobacter, 2 Serratia, 1 Staphylococcus coagulase--, DNAse--. MIC's of cefotiam ranged from 0.003 to 32 micrograms/ml (median MIC : 0.06 microgram/ml). Cefotiam was given intramuscularly in monotherapy, at the daily dosage of 1 and 2 g in two injections during 7 to 28 days. Followup of patients were at least 4 weeks after the end of treatment. Therapeutic results were : 15 cures and 2 failures by relapse in 17 cystitis, 6 cures and 3 failures by relapse in 9 pyelonephritis, 4 cures in 4 prostatitis. General tolerance was excellent in all cases. Intramusculary injections were well tolerated with a 2 p. cent lidocain solution. Biological tolerance and particularly renal tolerance was good in all patients.

Bacteria are usually classified as susceptible (S), intermediate (l) or resistant (R) by comparison of their MICs with two reference MIC cutoff levels. Three sets Sc, Ic and Rc are thus constructed. By using agar diffusion, the same bacteria are classified as Sd, Id or Rd, by comparison of inhibition zone diameters with two reference diameter breakpoints. These Sd, Id and Rd sets are not absolutely identical with Sc, Ic and Rc respectively. Diameter breakpoints were submitted to successive adjustments until minimal differences were achieved, i.e. when the greatest possible number of elements was included in the sets: (Formula: see text) Comparison of this method with more conventional techniques emphasizes its value.

Peritonitis remains the main complication of CAPD. This study demonstrates that most cases can be successfully treated with cefotiam. In 17 patients under CAPD, 33 cases of bacterial peritonitis were observed, with clinical manifestations in 28. The mean cell count in peritoneal dialysis fluid was 2 820/mm3, with 2 200/mm3 polymorphonuclear leukocytes. Causative pathogens were Staphylococcus in 18 cases, Streptococcus in 4, Stomatococcus mucilaginous in 1, Corynebacterium J.K. in 1, Enterobacter in 3, Acinetobacter in 3 and Pseudomonas in 2. Two cultures were negative. First choice treatment was a daily intraperitoneal injection of 1 g cefotiam. 68.80% of patients recovered within 6 days. Failures were due to a methicillin-resistant Staphylococcus epidermidis in 3 cases, a relapsing Stomatococcus mucilaginous infection in 1, a Streptococcus faecalis in 1, an Acinetobacter in 3 and a Pseudomonas in 2. Mean cefotiam concentrations 24 hours after the intraperitoneal injection were 9.4 +/- 7.0 micrograms/ml (range 1.3-26.4 micrograms/ml) in serum and 3.4 +/- 3.3 micrograms/ml (range 0.4-12.2 micrograms/ml) in dialysate. These concentrations are greater than most of cefotiam's MICs for susceptible bacteria, a finding that confirms the value of treatment with a single daily intraperitoneal injection of cefotiam.

Susceptibility to cefotiam of 494 bacterial strains was studied by MIC determination using an agar dilution assay. Activity of cefotiam was also compared with that of six other beta-lactams (ampicillin, mezlocillin, ticarcillin, cefalotin, cefotaxime, and moxalactam) using an agar diffusion method. Cefotiam showed a wide antibacterial spectrum including more than 70% of Enterobacteriaceae (except Serratia), beta-lactamase-producing and non-beta-lactamase-producing Haemophilus influenzae, non-enterococcus streptococci, and penicillinase-producing and non-penicillinase-producing staphylococci susceptible to methicillin. Conversely, cefotiam was inactive against Pseudomonas aeruginosa, Acinetobacter anitratum, Streptococcus faecalis, and methicillin-resistant Staphylococcus aureus.