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PubMed1995

Cefazolin is inferior to cefotetan as single-dose prophylaxis for women undergoing elective total abdominal hysterectomy.

The purpose of this prospective, randomized, double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy. A major operative site infection requiring parenteral antimicrobial therapy developed in 46 (9%) of 511 evaluable women: 30 (11.6%) of 258 women given cefazolin prophylaxis and 16 (6.3%) of 253 women given cefotetan prophylaxis (relative risk, 1.84; 95% confidence interval, 1.03 to 3.29; P < .05). Risk factors for major operative site infection were younger age, lower postoperative hemoglobin concentration, and a proliferative endometrium. Ten (3.9%) of 258 women given cefazolin prophylaxis had a postoperative pelvic abscess; two of these women required additional surgical procedures, compared with two (0.8%) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery (relative risk, 4.9; 95% confidence interval, 1.09 to 22.16; P = .04). A greater number of infections and more serious infections occurred following cefazolin prophylaxis; this treatment resulted in 234 additional hospital days for administration of parenteral antimicrobial therapy.

Adult↗
PubMedDate not supplied

Comparison of cefonicid and cefazolin for treatment of soft-tissue infections.

Cefonicid was compared with cefazolin for the treatment of serious infections of soft tissue. According to a randomized, prospective protocol designed to assign twice as many patients to cefonicid, 38 patients were treated with cefonicid and 19 patients, with cefazolin. Dosages used were 1.0 g once daily intramuscularly or intravenously for cefonicid and 0.5-1.0 g three times a day intramuscularly or intravenously for cefazolin. Clinical diagnoses included cellulitis (39 patients), abscesses (14), infected ulcers (3), and bursitis (1). Bacteriologic diagnoses included Staphylococcus aureus alone (8 patients), group A Streptococcus alone (13), combined S. aureus plus streptococci (8), viridans group streptococci alone (1), and mixed anaerobes (1). Gram-negative rods were isolated from 11 patients, all in mixed cultures with gram-positive species. For two patients, gram-negative organisms were thought to be etiologic. All 57 patients responded satisfactorily to treatment. Treatment with either drug was neither interrupted nor discontinued because of toxicity. Both cefonicid and cefazolin appear to be effective for the treatment of infections of skin and soft tissues. Cefonicid has the advantage of once-daily dosing.

Abscess↗
PubMed1987

Efficacy of cefazolin, cefamandole, and gentamicin as prophylactic agents in cardiac surgery. Results of a prospective, randomized, double-blind trial in 1030 patients.

In an effort to develop an improved regimen of antibiotic prophylaxis in cardiac surgery, 1030 patients who were to have elective cardiothoracic surgery involving a median sternotomy were selected at random to receive cefamandole or cefazolin, with or without gentamicin, in a prospective double-blind study. Cefazolin was significantly less effective than cefamandole at both the sternal (1.8% vs. 0.4%, respectively, p less than 0.05) and donor sites (1.3% vs. 0%, respectively, p less than 0.02). Seven Staphylococcus aureus infections occurred among cefazolin recipients as compared with no such infections among the patients receiving cefamandole (p less than 0.01). All five wound infections yielding fungi or gentamicin-resistant gram-negative rods occurred in patients who had received gentamicin as a second prophylactic agent. These data suggest that gentamicin has no role as a prophylactic antibiotic in cardiac surgery and that, compared with cefamandole, cefazolin offers unreliable prophylaxis against deep infection at both the sternal and donor sites.

Cardiac Surgical Procedures↗
PubMed1994

Randomized comparison trial of teicoplanin i.v., teicoplanin i.m., and cefazolin therapy for skin and soft tissue infections caused by gram-positive bacteria.

Teicoplanin, a glycopeptide antibiotic chemically related to the vancomycin-ristocetin group of antibiotics, has potent activity against aerobic and anaerobic gram-positive bacteria. In this study, we examined the efficacy and safety of teicoplanin for parenteral treatment of skin and soft tissue infections caused by gram-positive bacteria. Ninety-six hospitalized adults with moderate to severe skin and soft tissue infections were randomized to receive either teicoplanin intravenously (i.v.) once a day, teicoplanin intramuscularly (i.m.) once a day, or cefazolin i.v. every 8 hours. We evaluated patients' clinical and microbiologic status and assessed clinical and laboratory adverse events. Of 76 clinically assessable patients, 26 of 26 (100%) given teicoplanin i.v., 21 of 22 (95%) given teicoplanin i.m., and 26 of 28 (93%) given cefazolin showed improvement or cure. Of 60 microbiologically assessable patients, 22 of 22 (100%) given teicoplanin i.v., 16 of 18 (89%) given teicoplanin i.m, and 18 of 20 (90%) given cefazolin were cured. Of 96 patients assessable for adverse events, 7 of 34 (21%) given teicoplanin i.v., 4 of 31 (13%) give teicoplanin i.m., and 1 of 31 (3%) given cefazolin had adverse events. In this study, once daily teicoplanin appeared to be safe and effective therapy for skin and soft tissue infections.

Cefazolin↗
PubMed1997

Ceftriaxone versus cefazolin in peripheral arterial operations: a randomized, prospective trial.

Serious morbidity and mortality are associated with postoperative wound infections in peripheral vascular surgery. The use of prophylactic antibiotics is considered the standard of care, with attention focused on the most efficacious agent. A prospective, randomized study was conducted to evaluate the efficacy of ceftriaxone versus cefazolin in prevention of postoperative wound infections in a group of patients who had peripheral arterial operations between October 1991 and February 1993. Patient characteristics associated with an increased risk of postoperative wound infection were evaluated. Prophylaxis was provided for 105 operations with cefazolin and 103 operations with ceftriaxone. The overall wound infection rate was 3.85%. Six operations (5.7%) in the cefazolin group were complicated by wound infection versus 2 operations (1.9%) in the ceftriaxone group. Diabetes (6 infections/64 operations; infection rate, 9%) and a personal history of previous aortocoronary bypass (5 infections/49 operations; infection rate, 10%) were characteristics associated with an increased chance for postoperative wound infection. Ceftriaxone is therapeutically equivalent to cefazolin in the prevention of postoperative wound infections in peripheral vascular surgery.

Aged↗
PubMed2003

Cefazolin prophylaxis in neurosurgery monitored by capillary electrophoresis.

Prophylactic use of antibiotics to prevent postoperative infections is a routine method in neurosurgery. Little is known about the period of effectiveness of antibiotics applied only for the purposes of operation. The actual concentration of cefazolin was determined in the serum, in the contents of wound drains, and in the cerebrospinal fluid in a 24-hour postoperative period after the administration of 1 g of cefazolin just prior to skin incision in 8 patients undergoing lumbar discectomy and 11 patients undergoing craniectomy. The concentration of the antibiotic was then compared with the minimal inhibitory concentration values of cefazolin for 10 different bacterial species. For evaluating the concentration of cefazolin, capillary electrophoresis was used, which is a new clinical application of this separation technique. Results showed that the antibiotic was effective against bacterial breeding in the serum and in the drainage up to 12 hours. The drug concentration in the cerebrospinal fluid remained less than the value of the serum, and it exceeded the minimal inhibitory concentration values only for approximately 5 hours.

Adult↗
PubMed1994

Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection.

The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injections of 250 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 min and fluctuated between 54.7 +/- 11.0 micrograms/ml (mean +/- SEM) and 73.2 +/- 13.2 micrograms/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration-time curves followed first-order one-compartment model decay in most of the animals with an elimination half-life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area.

Animals↗
PubMedDate not supplied

Pharmacokinetic disposition of cefazolin in serum and tissue during canine total hip replacement.

Intraoperative cefazolin concentrations were measured in serum, joint capsule, cancellous bone of the acetabulum, and proximal cancellous bone of the femur in 15 dogs undergoing total hip replacement. Cefazolin (22 mg/kg intravenously [IV]) was administered every hour for three doses. The mean peak serum concentrations (+/- SEM) were 387.79 +/- 27.56 micrograms/mL, 521.71 +/- 28.00 micrograms/mL, and 542.20 +/- 30.91 micrograms/mL, respectively. Mean serum concentrations just before administration of doses 2 and 3 were 51.77 +/- 2.39 micrograms/mL, and 64.84 +/- 3.46 micrograms/mL, respectively. The mean cefazolin concentrations in the joint capsule, cancellous bone of the acetabulum, and cancellous bone of the femur were 34.71 +/- 2.50 micrograms/g, 28.70 +/- 7.40 micrograms/g, and 36.20 +/- 3.80 micrograms/g, respectively. The minimum inhibitory concentration of cefazolin for 90% of the common contaminants (MIC90) in this clinic is less than or equal to 2 micrograms/mL or per gram of tissue. Serum concentrations never fell below 15 times the MIC90 (lowest trough, 35.93 micrograms/mL), and the lowest tissue concentration (6.57 micrograms/mL in cancellous bone from the acetabulum) was still more than 3 times the MIC90. The mean tissue concentration was 15 times the MIC90.

Acetabulum↗
PubMed1988

Rate-controlled absorption enhancement of rectally administered cefazolin in rats by a glyceride mixture (MGK).

The enhancing effect of the medium chain glyceride preparation MGK on the rectal absorption of the cephalosporin antibiotic cefazolin sodium was evaluated in relation to the rate of delivery. Cefazolin sodium proved to be absorbed to a small extent (15 to 27%) after rectal administration without MGK. Bolus administration with MGK enhanced rate and extent of cefazolin sodium absorption, resulting in a bioavailability of 57 +/- 26%. Linear infusion of 3 mg cefazolin sodium with MGK in 32 min produced complete absorption of the antibiotic (102 +/- 7%), but absorption occurred slower in comparison with bolus delivery. The rate of administration proved to be an important variable of the absorption enhancing effect of MGK.

Administration, Rectal↗
PubMed1976

Cefazolin in the treatment of acute enteric fever.

Cefazolin was used in the treatment of nine patients with acute enteric fever proven by positive blood cultures. In seven patients the causative organism was Salmonella typhi and in two it was Salmonella paratyphi B. Minimal inhibitory and minimal bactericidal concentrations of cefazolin against the nine isolates ranged between 1.95 and 3.90 mug/ml. Cefazolin was administered either intramuscularly or intravenously in a daily dose of 3 to 6 g for 11 to 16 days. The mean peak serum antibiotic concentration after a 0.5-g intravenous injection was 64.4 mug/ml, and the mean trough concentration, 3 h later, was 12.7 mug/ml. The highest serum inhibitory dilution at peak level was frequently 1/64, and at trough level it was 1/16 to 1/32. The acute infection was satisfactorily controlled in all patients. Phlebitis, complicating intravenous therapy, in five out of eight patients, was the only side effect observed. Relapse of typhoid fever, as documented by positive blood culture, occurred in one patient 11 days after treatment course was completed. More extensive clinical studies are required before drawing any conclusions regarding the efficacy of cefazolin in acute enteric fever.

Adolescent↗
PubMed1977

Rapid analysis of cefazolin in serum by high-pressure liquid chromatography.

A high-pressure liquid chromatography (HPLC) method has been developed for the analysis of cefazolin in serum. Serum was deproteinized by the addition of 6% trichloroacetic acid and injected onto a reverse-phase column with a mobile phase of 10 to 15% methanol in 1% aqueous acetic acid. Cefazolin chromatographed without interference from ultraviolet-absorbing components of serum, with a retention time of 3.1 min. Standard curves comparing peak area with concentration prepared from dog or human sera were linear over a range of 1.6 to 200 mug/ml. Results from the HPLC assay were compared with microbiological assays (cylinder plate method) on both standard serum samples and sera from dogs and human subjects receiving intramuscular cefazolin. The HPLC method was somewhat more accurate in comparison with the microbiological assay performed on serum samples of known concentration. The comparison of results from an analysis of serum levels of dogs or human subjects receiving cefazolin indicated that the two methods would lead to identical conclusions concerning pharmacokinetics or the achievement of therapeutic serum levels. The HPLC assay method presents an alternative to conventional microbiological assays, with marked improvement in speed (30 min) and considerable potential for future development.

Animals↗
PubMed1977

Penetration of cefazolin, cephaloridine, and cefamandole into interstitial fluid in rabbits.

We compared the penetration of three cephalosporins into interstitial fluid. Interstitial fluid was obtained in rabbits from Silastic tissue cages. Cefazolin, cephaloridine, and cefamandole were administered by the intramuscular route (30 mg/kg per injection). Peak blood levels and interstitial concentrations were studied after a single injection. Interstitial levels were also compared in a three-injection study (one injection every 12 h) and in a cumulative effect study (six injections), in which the interval between injections was established for each drug on the basis of its common therapeutic use. After a single injection, cephaloridine activity was detected more rapidly and attained higher levels than the other two drugs within the first 4 h. However, 2 h after the third injection, cefazolin levels in tissue fluid were higher than with cephaloridine. Cefamandole consistently gave the lowest interstitial levels. With all three drugs, detectable concentrations were present in interstitial fluid at a time when no detectable antibiotic was found in serum. In the six-injection study, the interstitial levels obtained with cefazolin were significantly higher than those observed with the other drugs. Our data suggest that cefazolin is a drug of choice due to its high extravascular levels.

Animals↗
PubMed1977

Exudate levels and bactericidal activity of cefazolin in a new local infection system using rat granuloma pouches.

An experimental local infection system has been developed in which exudates are induced with croton oil in granuloma pouches of rats. This system provided a suitable model for the evaluation of the therapeutic effect of two antibiotics, cefazolin and cephalothin. Exudate levels of cefazolin were found to be higher than those of cephalothin, and these levels correlated with the higher serum level of cefazolin. The therapeutic effect of cefazolin, after intramuscular injection of 20 mg of each antibiotic per kg, was superior to that of cephalothin in eradicating both Staphylococcus aureus and Escherichia coli.

Animals↗
PubMed1978

Pharmacology of intraperitoneal cefazolin in patients undergoing peritoneal dialysis.

Cefazolin was added to dialysis fluid in nine patients with renal failure undergoing peritoneal dialysis with 2 liters/h per exchange. With 50 mg/liter (three patients), the first measurable mean serum concentration was 3.7 mug/ml (range, 2.4 to 4.9 mug/ml) after three exchanges and was 30.3 mug/ml (range, 13.3 to 44.3 mug/ml) after 24 exchanges. After 18 to 24 more exchanges without cefazolin, the mean serum concentration was 12.3 mug/ml (range, 3.8 to 24.6 mug/ml). The mean concentration in the dialysis outflow was 26.9 mug/ml (range, 2.5 to 58.5 mug/ml). With 150 mg/liter (six patients), the mean serum concentration was 5.2 mug/ml (range, 3.6 to 7.8 mug/ml) after the first exchange and 8.4 (range, 6.1 to 14.0 mug/ml), 15.0 (range, 8.2 to 23.5 mug/ml), and 71.9 (range, 26.2 to 142.1 mug/ml) mug/ml after the second, third, and twenty-fourth exchanges, respectively. After 17 to 24 more exchanges without cefazolin, the mean serum concentration was 38.2 mug/ml (range, 15.4 to 65.7 mug/ml). The mean concentration in the dialysis outflow was 71.4 mug/ml (range, 21.9 to 150.8 mug/ml). After 1 g of cefazolin was given intraperitoneally with no more dialysis, serum concentrations rose by a mean of 62.5 mug/ml (range, 18.9 to 107.8 mug/ml). The maximum rise occurred within 2 h with two-thirds of the rise occurring within 30 min. During the subsequent 22 h levels dropped to 65.4% of the peak.

Acute Kidney Injury↗
PubMed1980

Failure of single doses of cefazolin and cefamandole to penetrate experimental chronic Escherichia coli abdominal abscesses.

Four perforated capsules were implanted into the abdominal cavity of each of three rabbits. After 4 to 5 weeks, single doses of cefazolin (30 mg/kg) or cefamandole (90 mg/kg) were administered intramuscularly. Peak levels of the respective drugs in serum were 104 +/- 10 and 127 +/- 5 micrograms/ml (mean +/- standard error); corresponding peak levels in capsule fluid were 6.3 +/- 2.3 micrograms/ml. Sixteen weeks after implantation, 2 X 10(6) colony-forming units of a strain of Escherichia coli susceptible to cefazolin (minimum inhibitory concentration, 1.0 microgram/ml) and cefamandole (minimum inhibitory concentration, less than 0.125 microgram/ml) was introduced into each of the 12 capsules. Chronic infection was established in seven of the capsules. At 4 to 6 weeks after infection, cefazolin and cefamandole were again administered. Peak serum concentrations were 102 +/- 3.3 micrograms/ml for cefazolin and 148 +/- 6.7 micrograms/ml for cefamandole. Peak concentrations in noninfected capsules were 7.5 +/- 3.4 and 12.1 +/- 2.1 micrograms/ml, respectively, not statistically different from the first study (P greater than 0.2). However, peak concentrations in infected capsules (less than 0.3 microgram/ml) were strikingly lower than in uninfected capsules (P less than 0.002). In keeping with the latter finding, quantitative cultures of E. coli in the infected capsules remained unchanged. Administration of [14C]cefamandole indicated that low drug levels were a result of poor drug penetration rather than drug inactivation or binding. Lack of vascularity and capsule wall necrosis may be responsible for poor drug penetration.

Abdomen↗
PubMed1981

beta-Lactam resistance in Serratia marcescens: comparison of action of benzylpenicillin, Apalcillin, Cefazolin, and ceftizoxime.

The intrinsic mechanisms of resistance to beta-lactam antibiotics in Serratia marcescens IFO 12648 were investigated, comparing the action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. The minimal inhibitory concentrations for this strain were 1,600, 3.13, 6,400, and 0.05 microgram/ml, respectively. The addition of ethylenediaminetetraacetic acid markedly reduced the minimal inhibitory concentrations of benzylpenicillin and cefazolin, whereas those of apalcillin and ceftizoxime were not influenced. S. marcescens IFO 12648 produced only a low level of beta-lactamase activity constitutively, and the production was considerably increased by the addition of benzylpenicillin. Cefazolin was hydrolyzed rapidly by beta-lactamase activity, whereas benzylpenicillin, apalcillin, and ceftizoxime were poorly hydrolyzed. Peptidoglycan synthesis in ether-treated strain IFO 12646 cells was inhibited by a concentration of ceftizoxime markedly lower than that of cefazolin and by a concentration of apalcillin moderately lower than that of benzylpenicillin.

Ampicillin↗
PubMed1982

Penetration of moxalactam and cefazolin into atrial appendage after simultaneous intramuscular or intravenous administration.

This study compared the penetration of moxalactam and cefazolin into the human atrial appendage after simultaneous administration of both drugs by two routes. Nineteen adult patients scheduled for coronary vein bypass surgery randomly received 10 mg of moxalactam and cefazolin per kg by either the intramuscular or intravenous (bolus) route on administration of anesthesia. Concentrations of cefazolin in serum were significantly greater than concentrations of moxalactam at all times for both routes of administration. There were no significant differences, however, in the concentration of these drugs in atrial appendages, although concentrations of both agents administered intravenously were significantly greater than of drugs administered intramuscularly. (19.3 +/- 10.3 and 21.0 +/- 11.0 micrograms intravenously versus 8.3 +/- 3.6 and 10.1 +/- 3.2 micrograms/g intramuscularly for moxalactam and cefazolin, respectively).

Aged↗
PubMed1982

Therapeutic activities of cefazolin, cefotaxime, and ceftazidime against experimentally induced Klebsiella pneumoniae pneumonia in rats.

The efficacies of several dosage schedules of cefazolin, cefotaxime, and ceftazidime, started 12 or 36 h after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae in rats. The therapeutic activities of the cephalosporins were compared with the antibacterial activities in vitro and the serum concentration curves. The course of experimental pneumonia was rapid and characterized by tissue necrosis. Response to antimicrobial treatment was evaluated with respect to mortality and numbers of bacteria in lung (left lobe), blood, and pleural fluid. When antibiotic treatment was started early, i.e., 12 h after bacterial inoculation, cefotaxime and ceftazidime were equally effective and superior to cefazolin. Eleven doses of 10 mg of cefotaxime or ceftazidime per kg or 11 doses of 60 mg of cefazolin per kg were required to improve the survival rate. With a delay in administration to 36 h after inoculation, the efficacy of the cephalosporins decreased markedly. In the three dosages tested, cefazolin was ineffective. Survival improved with the administration of nine doses of 60 mg of cefotaxime per kg or nine doses of 10 mg of ceftazidime per kg. These results are not in accordance with the ratio of in vitro activities of cefotaxime and ceftazidime or the serum concentration curves.

Animals↗