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The diffusion of cefotaxime compared with that of cefazolin, cefoxitin and cefamandole in the interstitial fluid has been studied in rabbits. The different antibiotics were administered intramuscularly at a dose of 30 mg/kg by injection. Serum concentrations were determined at 30 minutes, 2, 4, 8 and 12 hours following the injection.
Patients undergoing cholecystectomy were randomly divided into two groups. The effects of a single injection of one gram of cefazoline given thirty minutes before operation to 30 patients were compared with those obtained in a second group of 29 untreated cases. The efficiency of the second generation cephalosporins in preventing postoperative complications of this type was confirmed. Prophylactic administration of this antibiotic therapy before uncomplicated biliary tract surgery can significantly reduce the incidence of postoperative parietal infections and therefore the duration of hospitalization.
Our study shows that prophylactic use of an adequate antibiotic appears to be warranted in osteoarticular surgery, during the immediate pre and post-operative periods. The mechanism by which this prophylaxis is effective remains under debate. Surgeons should be encouraged to abandon the use of wide-spectrum antibiotics or combinations of several antibiotics for prophylactic purposes. The only useful prophylaxis is the prescription of one antibiotic effective against the most common agent i.e. staphylococcus aureus. Our results suggest an early action of the antibiotic, as soon as the leukocytes and microorganisms make contact. Selection of highly resistant microorganisms by polyvalent antibiotic therapy is precluded by the prophylactic regimen advocated here. Use of cefazolin during a very short period appears to be a satisfactory solution to prophylactic problems in osteoarticular surgery.
In a randomized comparison, concentrations of cefazolin were found to exceed those of cefamandole in serum, atrial appendage, and sternal bone in patients undergoing cardiopulmonary bypass. No postoperative infections and no antibiotic-related complications occurred in either patient group.
A single intravenous dose of one gram of cefazolin was administered prophylactically to forty-eight patients undergoing total joint replacement. The serum half-life of the antibiotic was 1.8 hours, the same value found in normal volunteers. The mean concentration in bone during surgery was 5.7 micrograms per gram of bone. The mean concentration in synovial fluid during surgery was 24.4 micrograms per milliliter of fluid.
A three drug regimen of carbenicillin, cefazolin and gentamicin was used for the treatment of patients with solid tumors, who developed fever while granulocytopenic following chemotherapy. Thirty-five (8%) of 426 cancer patients receiving various combinations of antineoplastic chemotherapy qualified for the antibiotic treatment. Nine patients (26%) had bacteriologically confirmed infections, all with gram negative microorganisms. Twenty-four patients (69%) recovered and eleven (31%) died. All deaths occurred within five days of antibiotic therapy; in patients who recovered, the fever subsided within six days. Mortality was not influenced by the presence of a positive bacterial culture, age, or the cytotoxic agents used. It was, however, strongly related to metastatic spread: nine out of 14 patients with liver metastases (64%) died from the infection, while only two of 11 patients (18%) with other metastatic sites failed to respond to the antibacterial therapy. No death occurred in 10 patients who had local disease or received adjuvant therapy. This combined antibiotic therapy was as effective as reported for other combinations, with no serious side effects.
Four beta-lactam antibiotics, cefazolin, cefamandole, cefoxitin, and cefuroxime, were tested for their ability to penetrate the bacterial cell wall, to inhibit target proteins, and to resist degradation by beta-lactamase enzymes. Cefuroxime was the only tested antibiotic that performed well in all three categories.
Patients with ischemic extremities were administered 2 g of cefazolin sodium (CEZ) intravenously from the unaffected extremity. Blood samples were periodically taken from both affected and unaffected extremities and concentrations of CEZ in both samples were compared. No statistically significant difference was observed in the concentration of CEZ in affected and unaffected extremities, which suggested that systematic administration of CEZ has satisfactory effects on ischemic extremities.
Cefoxitin (Mefoxitin), Cephaloridin, Cephalothin and Cefazolin were tested in vitro against 380 clinical isolates of Staph. aureus and Enterobacteriaceae using the tube dilution procedure. Of the gramnegative microorganisms a selection of 150 strains was examined regarding susceptibility to the antibiotic combinations cefoxitin/gentamicin and cefoxitin/sisomicin in comparison to cephalothin/gentamicin and cephalothin/sisomicin. Cefoxitin has a broad antimicrobial spectrum and a high beta-lactamase-resistance. Cefoxitin was more active than the other antibiotics tested against E. coli, Klebsiella, Serratia, Enterobacter, indole-negative and -positive Proteus species. The high effectiveness of cefoxitin against anaerobic bacteria such as Bacteroides fragilis and Clostridium perfringens is discussed. Cefoxitin has an excellent bactericidal potency. Among the combinations tested cefoxitin/sisomicin was most active and obtained synergistic effects in most species. The resistance rate of cefoxitin of 8.7% was reduced to 0.7% with cefoxitin/sisomicin.
Cefmetazole (CMZ) was compared to cefazolin (CEZ) for efficacy and safety in the treatment of suppurative otitis media (including acute otitis media and chronic otitis media in acute aggravating stage) under well controlled clinical trials. The therapeutic effects were analyzed statistically in 172 patients (82 administered CMZ, 90 administered CEZ). The adverse reactions were also analyzed statistically in 199 patients (CMZ 99, CEZ 100) in whom the judgement was possible. 1. The efficacy rate of CMZ (72.3% for good to excellent response) was assessed by physicians in charge to be similar to that of CEZ (59.3%). This was the same being assessed by the committee, too (CMZ 64.6%, CEZ 56.7%). 2. When patients were classified into 2 groups (acute otitis media, chronic otitis media in acute aggravating stage) with respect to diagnosis, statistically significant difference in clinical efficacy assessed by physicians in charge was observed in the cases with chronic otitis media (CMZ, CEZ). In addition, the improvements of flares on the drum membrane and the mucous membrane of eardrum were significantly better in the CMZ group than in the CEZ group. 3. Bacteriologically, 16 cases (19.8%) of S. aureus were resistant to CEZ, while only 1 case (1.2%) to CMZ. CMZ was judged to be effective in 5 of the 6 cases in which CEZ-resistant strains were detected. 4. Side effects were found in 2 cases (2.0%) treated with CMZ: one complained of retching and abdominal pain and the other developed skin eruption. On the other hand, only 1 case (1.0%) developed skin eruption in the CEZ group. These results suggest that CMZ is a new antibiotic agent which is highly valuable in the treatment of suppurative otitis media.
Study of the pharmacokinetics of kanamycin and cefazolin in various types of experimental infarction of the small intestine showed their satisfactory penetration capacity with respect to the body fluids (blood, lymph, peritoneal exudate) and tissues (small and large intestine, parietal peritoneum, small intestine mesentery, gastrocolic omentum). This capacity was also shown with respect to the small intestine and its mesentery affected by infarction. Tissues traumatized during surgical operations were saturated with the antibiotics in concentrations equal to those in the control animals. The maximum concentrations of the antibiotics in the biosubstrates studied were observed by the 1st hour from the moment of their intramuscular injection. For prophylaxis of postoperative infections it is recommended that the antibiotics be applied not later than 1 hour before operation. This time is considered to be optimal.
A single intramuscular dose of one gram of cefazoline was administered to fifty eight patients undergoing total hip replacement. The elimination of the antibiotic in femoral head is parallel to the blood elimination but ten times lower. Twelve hours after injection, levels of 0.5 microgram/g (i.e. higher than MIC of Staphylococcus aureus normally isolated from post surgery infections) are still detected in capsule and femoral head.
Many strains of cefazolin (CEZ)-resistant Staphylococcus aureus of recent clinical isolates were also resistant to gentamicin (GM). In addition, the antibacterial activity of NTL was found to be stronger than that of GM and stronger than that of CEZ for those resistant strains and especially for those moderately resistant to GM.
In a randomized cross over study Cefazoline and Cefazedone were administered i.v. as injection of 2 minutes duration and as infusion of 30 minutes duration. The concentrations in blood plasma and the excretion with the urine were similar for both substances and differed only with regard to their levels during the first 60 minutes, depending on the mode of administration.
In a prospective randomized and controlled double-blind trial the effect of prophylactic systemic administration of Cefazolin in elective colorectal surgery on postoperative wound infection was investigated. The incidence of wound infection was significantly reduced (P less than 0.01) from 32% in the control group to 10% in the treated group. Furthermore there was a significant reduction (P less than 0.05) in hospital stay of about 3 days.
Cefazolin (CEZ) concentration in the bone marrow of tibia was examined 1, 2 and 3 hours after intramuscular injection of 1 g. CEZ concentration in the bone marrow of tibia 1 hour after injection was 59.9+/-10.31 microgram/ml. Ratio to serum was 101.7%. CEZ concentration in the bone marrow of tibia 2 hours after injection was 42.5+/-7.77 microgram/ml. Ratio to serum was 102.7%. CEZ concentration in the bone marrow of tibia 3 hours after injection was 33.9+/-7.75 microgram/ml. Ratio to serum was 102.7%. Penetration capacity of CEZ into the bone marrow of tibia was excellent.
The kinetics of splitting out the substitute at C3 in the molecule of beta-lactam antibiotics such as cefazolin, cefaclor, cefazedone and others as well as that of splitting out the chlorine atom in the side radical of the cefazedone molecule was studied within wide ranges of pH and temperature. The destruction processes for all the investigated compounds were shown to be described by the 1st order equations. The values of the activation energy, pre-exponential factors and reaction order by the hydrogen ions were measured. This provided the mathematical description of the destruction processes within wide ranges of pH and temperature. An unusual mechanism of synchronous splitting out the substitute at C3 and one of the chlorine atoms in the side radical of the cefazedone molecule was observed.
In order to elucidate the usefulness of cephacetrile (CEC), comparative trials with cefazolin (CEZ) were carried out in the patients with complicated infections of the urinary tract, and the following results were obtained: 1. There were no statistically significant differences or tendencies observed between the groups given CEC and CEZ in either of the global effects, bacteriological effects, rate of superinfection, relapse, relapse with bacterial alternation, drug usefulness, rate of improvements in symptoms and findings in all the cases. 2. According to a result of stratified analyses, there were statistically significant differences observed, showing more inferior results of CEC than CEZ in either stratum of "below 50" in the age, "acute" in the disease phase, "infections of the upper urinary tract" in the disease pattern, and "E. coli including mixed infections with gram-positive organisms" in the pathogenic strains. However, it should be taken into consideration that certain background factors influence greatly in the effects and there were some problems on deviated backgrounds in these strata. On the other hand, CEC displayed better bacteriological effects than those of CEZ in higher stratum of "chronic" in the disease phase and "Klebsiella, Proteus, Citrobacter, Enterobacter including mixed infections" in the pathogenic strains, and statistically significant differences were not observed. 3. In consequence of bacteriological studies, CEC showed stronger resistance than CEZ against beta-lactamase produced in all the strains of gram-negative bacilli. Particularly there were significant differences or tendencies observed in those of Proteus, Cirtobacter, and Enterobacter, and at the same time there were great differences in the activity of beta-lactamase between CEC and CEZ as the substrate. 4. In correlation of the MIC and effects, CEC showed weaker actions than CEZ against susceptible organisms, but slightly stronger actions against moderately or highly resistant strains. A study of the relationship between the MIC of pathogenic strains, beta-lactamase, and bacteriological effects, showed possibilities that even the high activity of beta-lactamase results in remarkable effects in susceptible strains and the drugs with stronger resistance against beta-lactamase given better results in moderately or highly resistant organisms. 5. The incidence rate of adverse reactions was 2 out of 51 cases in the CEC group (3.9%) and 3 out of 50 cases in the CEZ group (6.0%), showing no significant difference, and those symptoms were similar. In conclusion, when the usefulness of CEC in complicated infections of the urinary tract is compared with that of CEZ, the former is said to be equal to the latter without significant difference as a whole...