[Cefazolin (Kefzol, Eli Lilly) and Cefazolin (Astra)].
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Bacterial Infections↗
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Double-blind comparison of pefloxacin and cefazolin as prophylaxis in elective cardiovascular surgery.
A total of 162 patients (134 males and 28 females) scheduled for coronary artery bypass grafting (144) or valve surgery (18) were randomly assigned to receive, under double-blind conditions, either pefloxacin 400 mg iv or cefazolin 1.0 g 30 min before the surgical incision and then post-operatively 12-hourly x 4 or 6-hourly x 8, respectively. Positive per- and post-operative cultures were seen in 27 patients (11 pefloxacin, 16 cefazolin) and 47 micro-organisms were isolated: 34 per-operatively (21 pefloxacin, 13 cefazolin) and 13 post-operatively (4 pefloxacin, 9 cefazolin). There were five failures of prophylaxis (2 pefloxacin, 3 cefazolin): two early (less than 5 days: 1 pefloxacin, 1 cefazolin) and three late (greater than or equal to 5 days, 1 pefloxacin, 2 cefazolin) divided into (i) one major primary failure in the cefazolin group (1 cefazolin resistant Staphylococcus epidermidis mediastinitis); (ii) two minor primary failures, one in each group (Gram-positive sternal incision abscesses) and (iii) two secondary failures (1 cefazolin resistant Enterobacter cloacae and Pseudomonas aeruginosa UTI in the cefazolin group and one culture negative pneumonia in the pefloxacin group). Tolerance to both antibiotics was excellent. In our sample of patients, the efficacy and safety of pefloxacin was not different from those of cefazolin in prophylaxis in cardiovascular surgery.
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Cefuroxime versus cefazolin as prophylaxis in vascular surgery.
Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
Cefazolin↗
Prediction of cefazolin penetration in high- and low-protein-containing extravascular fluid: new method for performing simultaneous studies.
The effect of extravascular fluid protein concentration and drug-protein binding was studied in rabbits with subcutaneously implanted Visking chambers. Chambers containing serum or saline were simultaneously studied in three animals by injecting cefazolin (30 mg/kg) intramuscularly every 4 h for four doses. Five additional animals were then studied for an 8-h period while receiving two doses of cefazolin. Peak and trough serum and chamber fluid were assayed for cefazolin concentration. The three-animal experiment demonstrated that equilibrium in the subcutaneous chambers was reached after two intramuscular injections and that the extravascular fluid levels were stable in comparison to the wide fluctuation of the serum levels. The five-animal experiment demonstrated that after two doses the serum-filled chambers contained 12.9 mug of cefazolin per ml, whereas saline-filled chambers contained 1.8 mug of cefazolin per ml. Ratios of chamber to peak serum for the second study were 12.4% for serum chambers and 1.7% for saline chambers. The cefazolin concentration in high-and low-protein extravascular fluid in both studies could be predicted from the logarithmic mean of the peak and trough serum cefazolin concentration and the antibiotic binding to rabbit serum and extravascular fluid proteins. These observations explain the previously published apparent discrepancies seen in studies of extravascular penetration of highly protein-bound antibiotics such as cefazolin.
Animals↗
Antimicrobial evaluation of cefoxitin: a new semisynthetic cephamycin. Comparative studies with cefazolin and cefalotin.
Antimicrobial activity of 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (cefoxitin), a new semisynthetic cephamycin antibiotic, was studied in comparison with that of cefazolin and cefalotin. Cefoxitin exhibited antibacterial activity against both gramnegative and gram-positive bacteria, and its action was bactericidal. Against gram-negative bacteria, cefoxitin was highly active as well as cefazolin, and more active than cefalotin. Especially, cefoxitin was highly active not only against strains of clinical isolates of indole-positive Proteus and S. marcescens but also against those of E. coli and P. mirabilis which were resistant to cefazolin and/or cefalotin, respectively. In addition, cefoxitin was effective against the strains resistant to beta-lactam antibiotics including cefazolin and cefalotin. Cefoxitin was hardly active against the strains of E. cloacae and P. aeruginosa, similar to cefazolin and cefalotin. Against gram-postive bacteria, cefoxitin was less active than cefazolin and cefalotin. In protection tests in mice, cefoxitin and cefazolin were more effective against infection with E. coli than cefalotin. Furthermore, cefoxitin was more active against infections with S. marcescens and P. morgani than the other antibiotics. Cefoxitin, like cefalotin, was less effective against infection with S. aureus than cefazolin. Cefoxitin was highly resistant to hydrolysis by beta-lactamases derived from the organisms insusceptible to the antibiotic. This fact revealed that the resistance of the organisms to cefoxitin may be in part due to factors other than beta-lactamase inactivation.
Animals↗
Characteristics of biliary excretion of cefazolin and other cephalosporins with reference to the relationship between serum levels and administration conditions.
The biliary excretion of cefazolin was compared with that of cephalothin and cephaloridine in rats and man. In rats, the biliary levels were dose-related with cefazolin and cephalothin but not with cephaloridine. Biliary levels were higher than serum levels after injection of 10--80 mg/kg of cefazolin and cephalothin, whereas serum levels of cephaloridine after injection were higher than biliary levels. The highest biliary levels of cefazolin were obtained by intravenous injection, followed by intramuscular injection and drip infusion. In man, a crossover study was made to compare biliary levels of cefazolin with those of cephaloridine and cephalothin. After a single 1-gram intravenous injection, the peak levels of cefazolin ranged from 0.85 to 21 mug/ml and those of cephaloridine varied from 0.55 to 3.9 mug/ml. After a 3-gram intravenous injection, the peak biliary levels of cefazolin ranged from 35.5 to 270 mug/ml and those of cephalothin from 0.3 to 64 mug/ml. The chemotherapeutic biliary levels of cefazolin able to inhibit susceptible organisms were obtained by 3-gram intravenous injections.
Animals↗
Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery.
Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5-8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery.
Bacterial Infections↗
Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass.
The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery.
Adolescent↗
Pharmacological study of cefazolin during intermittent and continuous infusion: a crossover investigation in humans.
Levels of cefazolin were determined in plasma, urine, bile, and cerebrospinal fluid in humans after a bolus intravenous injection and during a controlled, continuous intravenous infusion. All the patients were studied in a steady-state and crossover fashion. In plasma, the mean peak level after bolus injection (1.5 g) studied in 12 patients was 206.5 mug/ml; during continuous infusion (6 g daily), the mean level remained stable at 52.6 mug/ml. With bolus injection and continuous infusion, respectively, 89.7 and 86.3% of the administered dose of cefazolin were excreted in the urine of nine patients over the 6-h period considered. The levels of cefazolin in common bile duct bile were studied in six cholecystectomized patients. In bile collected during the two 3-h periods of the experiment, the mean concentration of the drug in the bile after bolus injection was 66.9 and 22.0 mug/ml, respectively; during continuous infusion, the corresponding biliary levels were 50.7 and 51.3 mug/ml, respectively. In four neurosurgical patients with an intraventricular catheter, neither bolus injection nor continuous infusion resulted in a demonstrable concentration of cefazolin in the cerebrospinal fluid. The continuous intravenous administration of cefazolin might have some advantage over the intravenous bolus intermittent injections. In plasma, the area under the curve is greater with continuous infusion than with bolus injection. In bile, the levels of cefazolin are more sustained with continuous infusion than with bolus injection. This approach to intravenous administration of cefazolin deserves more pharmacological and clinical trials.
Bile↗
Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin.
The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.
Animals↗
Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin.
The antibacterial activities of 4 cephalosporin antibiotics, cefazolin, cephaloridine, cephalothin and cephalexin, against 330 isolates of bacteria from patients at National Taiwan University Hospital, were determined by an agar plate dilution technique. Cephalosporins possess strong antibacterial activity against gram-positive bacteria except Enterococci. Staphylococcus aureus is the most susceptible among the organisms tested. More than 90% of Staphylococcus aureus strains are suppressed by cefazolin, cephaloridine and cephalothin at the concentrations of 3.13 mug/ml or less, except that 49.1% are suppressed by cephalexin. The relative potency of cephalosporins against Staphylococcus aureus in decreasing order is cephaloridine, cephalothin, cefazolin, and cephalexin. The gram-negative bacilli, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are less susceptible to cephalosporins than the gram-positive cocci. Among the cephalosporins, cefazolin is the most active against the gram-negative pathogens tested. The relative potency of antibacterial activity of cephalosporins against E. coli in decreasing order is cefazolin, cephaloridine, cephalexin, and cephalothin. One hour after the intramuscular injection of 500 mg of cefazolin, the maximum concentration of 33.3 mug/ml is reached in the serum. The sufficient high levels are sustained for 8 hours. Very high concentrations of cefazolin are also found in the urine.
Adult↗
Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime.
A prospective double-blind trial was performed at a tertiary care center to evaluate perioperative cephalosporin prophylaxis in cardiac operations. Patients were randomized to receive either cefazolin (n = 104) or cefuroxime (n = 109), the preoperative dose being given within 1 hour before the initial incision. Drugs were continued for 48 hours (cefazolin, 1 gm intravenously every 8 hours; cefuroxime, 1.5 gm intravenously every 12 hours). Postoperative infections were assessed by trained nurse clinicians, and data were analyzed by the intention-to-treat principle. Sternal wound infections or mediastinitis occurred in one of 104 patients treated with cefazolin and 10 of 109 treated with cefuroxime (p = 0.01). Deep sternal wounds (including mediastinitis and sternal osteomyelitis) occurred in none of the cefazolin-treated patients and five cefuroxime-treated patients (p = 0.06). Although overall nosocomial infection rates were similar (16.3 versus 19.3 per 100), wound infection occurred somewhat more frequently with streptococci (groups B and D) in patients receiving cefazolin (four versus zero, p = 0.110); conversely staphylococcal infections were more frequent in the cefuroxime group (seven versus one, p = 0.066). Mean and median postoperative stay was 1 day shorter in the cefazolin group. In contrast to findings of a previous report, our data indicate that cefazolin prevented more sternal wound infections than cefuroxime, a finding that supports prophylaxis with a first-generation cephalosporin.
Adult↗
Cefazolin in the treatment of pneumonia.
Cefazolin is a semi-synthetic derivative of cephalosporin C that has a lower cross-immunogenicity with penicillins than do the other cephalosporins. This agent was evaluated as an alternative to penicillin in the therapy of patients with pneumococcal pneumonia. Thirty patient were treated with cefazolin, most receiving 125 or 250 mg IM every 12 hours for 5-10 days. Satisfactory clinical responses were obtained in 29 of these 30 patients, and none complained of pain following IM injections. Three patients developed eosinophilia while receiving cefazolin, and one of these also had a maculopapular eruption that may have been an allergic reaction to cefazolin. Serum levels of cefazolin were measured at 1, 6, and 12 hours after administration. Susceptibilities of 100 isolates of Streptococcus pneumoniae, including these patients' organisms, were determined by broth dilution. Both cefazolin and cephalothin were bactericidal for all 100 isolates at concentrations of 2 microgram/ml or less. Cefazolin appears to be an entirely adequate alternative to penicillin for the therapy of pneumococcalpneumonia. This agent is effective in low dosages, and adequate serum levels are maintained for long periods of time, permitting twice-daily administration.
Adult↗
In vitro activity of flomoxef and cefazolin in combination with vancomycin.
207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.
Cefazolin↗
Hemolysis induced by cefazolin and cephalothin in a patient with penicillin sensitivity.
A patient with penicillin sensitivity, who had never received a cephalosporin antibiotic previously, developed anemia and spherocytosis following the administration of cefazolin. Hemolysis abated when the drug was discontinued on the fourth day, and recurred on day six when cephalothin therapy was begun. IgG and complement components were present on the patient's erythrocytes, and IgG antibodies in her serum reacted with normal red blood cells which had been coated with benzylpenicillin, cefazolin or cephalothin. Antibodies to cephalothin-coated red blood cells were removed partially by incubating her serum with either benzylpenicillin or cefazolin. Complement-fixing IgG antibodies which reacted with red blood cells coated by cefazolin, cephalothin, and benzylpenicillin were considered to be responsible for hemolysis during the administration of cefazolin and, subsequently, cephalothin. The patient recovered completely following discontinuation of antibiotics, transfusion of red blood cells, and treatment with glucocorticoids. It is concluded that hemolysis may occur during therapy with cefazolin, as well as cephalothin, and may develop rapidly in a patient with penicillin sensitivity.
Adult↗
The biliary excretion of cefazolin.
The biliary excretion of cefazolin was studied by perfusion of isolated rabbit livers. Under these conditions, 6.7 percent of the amount of cefazolin added to the circulating blood was excreted in bile, and concentrations of drug in bile were significantly higher than concentrations in serum. Biliary excretion of cefazolin was also studied in humans after the intravenous administration of 500 mg of the drug. In 10 normal subjects, maximal concentrations of cefazolin (17.10 plus or minus 8.5 mug/ml) in the fluid obtained by duodenal tubing were attained 1-2 hr after administration of cefazolin. Concentrations were similar in bile collected by external drainage from five cholecystectomized patients (maximal levels, 14.0 plus or minus 4.7 mug/ml) 1-2 hr after injection. Assays during cholecystectomy showed that 1 hr after injection, cefazolin levels were much higher in common duct bile (31 plus or minus 11 mug/ml) than in gallbladder bile (5 plus or minus 2 mug/ml).
Animals↗
Protein binding and concentrations of cephaloridine and cefazolin in serum and interstitial fluid of dogs.
Percentages of free and protein-bound cefazolin and cephaloridine in serum and interstitial fluid of dogs were determined by ultrafiltration and microbiologic assay. The percentages of cephaloridine and cefazolin bound to protein in serum were 10% and 80%, respectively. In interstitial fluid accumulating within tissue-embedded polypropylene capsules, 29% of cefazolin was bound to protein, and cephaloridine was unbound. Both antibiotics rapidly penetrated the interstitial fluid and attained measurable levels 5 min after intravenous administration. Levels of total cefazolin in the interstitial fluid were generally higher than those of cephaloridine; however, concentrations of free cephaloridine in the fluid exceeded the levels of free cefazolin after the first 15 min. Binding of anitbiotics by serum proteins does not restrict such agents to the intravascular space, since a highly protein-bound compound has been shown to penetrate interstitial fluid as readily as one that is minimally bound. It should be noted, however, that this penetration may be due primarily to the slow rate of binding of cefazolin to serum proteins.
Animals↗
Synergism between amikacin and cefazolin against Klebsiella: in vitro studies and effect on the bactericidal activity of serum.
Synergism between amikacin and cefazolin was studied in vitro in 20 strains of Klebsiella isolated from clinical material. Several techniques for the demonstration of synergism in vitro were employed. The checkerboard technique with use of bactericidal end points and the killing curves method showed synergism between amikacin and cefazolin for 13 and 15 strains, respectively. The two techniques were in accordance in 12 instances. The data obtained in vitro were correlated with the bactericidal activity in sera from 10 subjects who had received the usual doses of amikacin and cefazolin, alone or in combination. The sera of subjects who received amikacin plus cefazolin were bactericidal at significantly higher dilutions than sera of patients who received cefazolin alone. The increased serum bactericidal activity in subjects receiving amikacin plus cefazolin was observed only for strains against which these antibiotics were synergistic in vitro.
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