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Quantitation of carbenicillin disodium, cefazolin sodium, cephalothin sodium, nafcillin sodium, and ticarcillin disodium by high-pressure liquid chromatography.

High-pressure liquid chromatographic (HPLC) methods for the quantitation of carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin were developed. The stability of 2% solutions of the antibiotics in normal saline and in 5% dextrose in water were studied at 24 and 5 degrees. The assays were conducted using a previously reported colorimetric method, and some assays also were performed using HPLC. For discolored solutions of cephalothin, the colorimetric method was not stability indicating. The percent relative standard deviations by HPLC based on six injections were 1.69, 0.94, 1.30, 1.59, and 1.6 for carbenicillin, cefazolin, cephalothin, nafcillin, and ticarcillin, respectively. Both carbenicillin and ticarcillin apparently may be mixtures of two isomers at equilibrium with each other. The shelflives recommended by the manufacturers at 5 degrees may be too conservative.

Carbenicillin↗

Flucloxacillin compared with cefazolin in short-term prophylaxis for clean orthopedic surgery.

Two-hundred and fifty-two patients were included in a prospective, randomized, double-blind trial comparing the efficacy of flucloxacillin with that of cefazolin for clean orthopedic surgery. The preventive antibiotic regimen consisted of three 1-g injections perioperatively. There were 126 patients in each group, and the follow-up period was at least 6 months. Two deep (1.6%) and five superficial (4.0%) infections occurred in the flucloxacillin group. Three deep (2.4%) and five superficial (4.0%) infections developed in the cefazolin group.

Adolescent↗

Dosage adjustments of cefazolin according to the pharmacokinetics of this new cephalosporin.

Serum and urine levels of cefazolin were studied: 1. following a single 500mg intra-muscular dose of the drug in normal subjects (n = 10), in patients with renal impairment (n = 12) and in patients undergoing maintenance hemodialysis (n = 10); 2. following a single 500 mg intra-venous dose of the drug in normal subjects (n = 10). In normal subjects, serum half-lives averaged 1.75 hour after intravenous injection (Ke = 0.395) and 2.22 hours after intra-muscular injection (Ke = 0.312); urinary recovery of cefazolin over a six hours period amounted to 61% after intra-venous injection and to 47.5% after intra-muscular injection. The renal clearance of the drug approximated 40 ml/mn. A linear correlation (Ke = 0.022 + 0.0028 CrCl) was established between the overall elimination rate-constants and the creatinine clearances in the subjects under investigation. The various pharmacokinetic constants thus obtained can be used to calculate the maintenance doses, loading doses and dosage intervals adjusted according to creatinine clearances. These data actually yield dosage regimes adapted to each individual case according to the degree of renal function.

Cefazolin↗

Cefazolin and cephradine: relationship between serum concentrations and tissue contents in mice.

The relationship between serum concentrations and tissue levels of various doses of cefazolin and cephradine was determined in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the right hind leg, antibiotics were administered 1 h later. At 15-minute intervals mice were killed by exsanguination after a blood sample was taken, and the infected thigh was taken out and homogenized. The total amount of antibiotic per gram thigh muscle tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between blood concentrations and total tissue contents it may be concluded that the thigh was easily accessible for both cephalosporins. The ratio between the total tissue content and the free serum concentrations was the same for both antibiotics despite the difference in protein binding between cefazolin and cephradine in mouse serum. This implies that the discrepancy between the relative antibacterial activity of the cephalosporins in vitro and in vivo found in earlier experiments cannot be explained by differences in accessibility of the tissue.

Animals↗

Cefazolin-induced pseudomembranous colitis resulting in perforation of the sigmoid colon.

The seventh case of probable cefazolin-induced pseudomembranous colitis is reported. Perforation of the colon necessitated sigmoid resection. The postoperative course was protracted, and illustrates the difficulty of managing advanced pseudomembranous colitis when the oral route of antibiotic administration is not available. Although rare, pseudomembranous colitis related to cefazolin administration is a potentially fatal complication. The routine use of prophylactic antibiotics must be weighed against this possibility.

Aged↗

Single-dose cephalosporin for prevention of major pelvic infection after vaginal hysterectomy: cefazolin versus cefoxitin versus cefotaxime.

Antimicrobial overutilization accelerates the development of bacterial resistance. A prospective, randomized, blinded clinical trial of vaginal hysterectomy prophylaxis was designed to compare the efficacy, safety, and costs of cefazolin with those of cefoxitin and cefotaxime. Sixteen women (7.5%) developed febrile morbidity only, 10 (4.7%) developed major pelvic infection requiring parenteral antimicrobial therapy, and neither clinical nor laboratory adverse reactions of significance were observed. Anemia, diabetes, and additional surgical procedures were associated with a significantly increased incidence of postoperative infection; no regimen was more protective for women with or without these risk factors. Infections almost doubled hospital stay and the charges for health care. Diagnosis-related group reimbursement would have been more than $1,300 less than the mean hospital charge for women who developed infection. Utilizing cefazolin for prophylaxis and reserving cefoxitin and cefotaxime for therapy is cost and antimicrobial efficient.

Adult↗

Single-dose cefazolin prophylaxis for cesarean section.

In a prospective, randomized trial, the efficacy of a single-dose, first-generation, long-acting cephalosporin was compared with a three-dose regimen in a group of 100 women undergoing cesarean section who were at high risk for postoperative febrile morbidity. Fifty women received a single 1 gm intravenous dose of cefazolin and 50 received 1 gm of the drug followed by two additional doses, 8 hours apart, to complete a three-dose regimen. Another 50 women, considered to be at low risk for postoperative febrile morbidity, were not given antibiotic prophylaxis. Outcomes of febrile morbidity (18% vs 12%) and particularly morbidity caused by endometritis (6% vs 8%, respectively) were similar for single-dose and three-dose groups. In the untreated low-risk group there were no cases of endometritis and the febrile morbidity was comparable to that of the prophylactically treated groups (14% vs 15%). Single-dose cefazolin prophylaxis appears to be comparable to multidose prophylaxis in reducing febrile morbidity after cesarean section.

Adult↗

Noncovalent bonding of penicillin and cefazolin to dacron.

Dacron grafts treated with the surfactant, benzalkonium chloride or TDMAC bind significant quantities of penicillin-14C or cefazolin-14C. The treated grafts showed strong antibacterial activity which indicated that bound radioactivity corresponds to the reversible adsorption of biologically active molecules. Bound penicillin-14C or cefazolin-14C slowly dissociates when the grafts are placed in a surgically prepared muscle pouch in the rat. This slow release of antibiotic produces therapeutic levels of antibiotic in the adjacent tissue. Binding can also be achieved by in situ irrigation of surfactant treated grafts with antibiotic or by injection of the antibiotic.

Adsorption↗

Randomized trial of one-dose versus six-dose cefazolin prophylaxis in elective general thoracic surgery.

The objective of this study was to compare the efficacy of one to six doses of cefazolin as prophylaxis in general thoracic surgery using a randomized, double-blind design. Two-hundred eight consecutive patients admitted to a regional thoracic surgery unit for elective thoracotomy and lung resection were eligible for the trial. There were no wound infections in the one-dose group and two in the six-dose group (95% confidence intervals [CI]: -0.008, +0.048 [The positive number refers to the largest possible difference in favor of the one-dose group and the negative number, the largest possible difference in favor of the six-dose group]). Each group had eight postoperative chest infections (CI: -0.075, +0.077) and three empyemas (CI: -0.004, +0.050). Thirty-day mortality was 5% in the one-dose group and 4% in the six-dose group (CI: -0.053, +0.069). Postoperative duration of hospital stay, requirement for antibiotics, and the need for reoperation were comparable. These results suggest that six doses of cefazolin do not confer clinically important benefit beyond that obtained from a single dose for prophylaxis of wound infection in elective general thoracic surgery.

Cefazolin↗

Effect of controlled hemorrhage on tissue and serum cefazolin clearance.

Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.

Animals↗

The effect of scrubbing and irrigation with normal saline, povidone iodine, and cefazolin on wound bacterial counts in a guinea pig model.

This study examines the effects of povidone iodine, normal saline, and cefazolin alone and after scrubbing on bacterial counts in contaminated animal lacerations. Twelve albino guinea pigs each received four lacerations inoculated with a standard inoculum of Staphylococcus aureus. Twelve hours after inoculation, each wound was biopsied to ensure contamination and then either treated or left as an untreated control. One wound on each animal was an untreated control. The remaining three lacerations on six pigs were irrigated with cefazolin (CZ) solution, normal saline, or 1% (wt/vol) povidone iodine solution (PI). Three lacerations on another six pigs were treated with 20% poloxamer 188 scrub (scrub) alone, scrub followed by PI irrigation (SCR/PI), or scrub followed by CZ irrigation (SCR/CZ). Quantitative bacteriology was performed on tissue biopsies 2 hours (time 1), 7 hours (time 2), and 12 hours (time 3) after irrigation. Posttreatment counts for PI, CZ, and normal saline irrigation were not different from control or one another (P > .05). Bacterial counts for SCR/PI were significantly lower than control (P < .05) for all posttreatment biopsies (1.8 to 2.9 mean log(10) decrease). SCR/CZ was significantly lower than control (P < .05) at times 2 and 3 only (1.7 to 2.0 mean log(10) decrease). In this guinea pig model, cleansing 12-hour-old lacerations contaminated with S aureus using SCR/PI or SCR/CZ significantly reduced bacterial counts over 12 hours.

Animals↗

Effects of cefotetan disodium, cefoxitin, cefazolin, and cefotaxime in vitro on polymorphonuclear leukocytes from patients with leukopenia and severe pelvic inflammatory disease.

The effects of cefotetan, cefoxitin, cefazolin, and cefotaxime on polymorphonuclear leukocyte chemotaxis and chemiluminescence were determined in 10 patients with pelvic inflammatory disease and 10 oncologically treated patients. It was found that cefotetan enhanced both chemotaxis and chemiluminescence, with the favorable effects more pronounced in the oncologically treated patients with leukopenia. Cefotaxime depressed polymorphonuclear leukocyte functions. Cefoxitin and cefazolin had no significant effects. It would be logical, when treating empirically, to choose a regimen that enhances and not depresses host defenses in all patients but more expressly in leukopenic and other immunologically compromised patients.

Cefazolin↗

Antibiotic prophylaxis in open-heart surgery: a comparison of cefamandole, cefuroxime, and cefazolin.

We undertook a prospective randomized evaluation of cefamandole nafate, cefuroxime sodium, and cefazolin sodium as prophylaxis in open-heart operations. A total of 903 patients having an elective procedure were enrolled in the study, and 620 of them were eventually considered evaluable. There were no significant differences between the three study groups. The overall rate of infection and the rate of infection according to demographic variables was not significantly different between the three antibiotics. Serious complications and deaths were also similar between the three agents. The presence of multiple severe underlying conditions was a risk factor for infection, independent of the antibiotic used. We conclude that there are no differences in the efficacies of the three agents in preventing postoperative infections in patients having open-heart operation. Cefuroxime, principally because of its every-12-hour dose, is far less expensive than cefamandole or cefazolin.

Cardiac Surgical Procedures↗

Determinants of wound infection incidence after isolated coronary artery bypass surgery in patients randomized to receive prophylactic cefuroxime or cefazolin.

In this open-label, randomized drug study, we compared two cephalosporin prophylactic regimens, one using cefazolin and one using cefuroxime, in 100 patients having coronary bypass surgery. Additional epidemiological data were collected to identify the patient at higher risk for acquiring an infection. Patients were categorized into four groups: (1) no infection; (2) clinically determined infection without a culture or prescription of additional antibiotics; (3) clinical infection with no or negative wound culture and prescription of additional antibiotics; and (4) clinical infection with positive culture and need for additional antibiotics. Seven cefuroxime patients (13.5%) and 9 cefazolin patients (18.8%; p = 0.471) had a wound that became clinically infected (Groups 2-4). In a univariate analysis, 11 variables were statistically associated with the development of a wound infection. A logistic regression model defined 3 variables at an alpha level of 0.05 and 3 at an alpha level of 0.10 that predicted a wound infection. Patients were identified at high risk of wound infection if they had postoperative weight gain, long operative hospitalization, prolonged use of a Foley catheter, postoperative use of blood products, and operation performed by two specific surgeons. Our results indicated that closer observation of the high-risk patients and a definition of the mechanism of the infections are needed.

Cefazolin↗

Cefazolin in children with renal insufficiency.

Cefazolin (7 mg/kg) were administered to 11 children with renal insufficiency and to ten children on hemodialysis. The serum half-life of the drug was progressively prolonged as glomerular filtration rate fell. The serum half-life of cefazolin was variably prolonged in those children on hemodialysis, but their serum levels of cefaxolin had dropped by 35 to 65% during dialysis. Most had no measurable level prior to the next dialysis. Dosage recommendations are made for both groups of patients.

Adolescent↗

Prophylactic cefazolin versus placebo in total hip replacement. Report of a multicentre double-blind randomised trial.

The effect of five days of antibiotic prophylaxis with cefazolin injections (beginning just before surgery) on postoperative infections (beginning just before surgery) on postoperative infectious complications was evaluated in a double-blind, randomised, placebo-controlled trial in nine centres on 2137 patients undergoing hip replacement. Antibiotic prophylaxis reduced the number of hip infections significantly from 3.3% (placebo) to 0.9% (cefazolin). Positive peroperative blood samples and positive bacteriological examination of the drain were risk factors for hip infection but the prognostic value of obesity, diabetes, or previous hip surgery was not confirmed. Development of a urinary infection was not related to hip infection. Hip infections were less common in the four centres with hypersterile operating theatres, and the benefits of prophylactic antibiotics were restricted to patients having hip replacement operations in conventional theatres.

Aged↗

Structural relationship and desolvation behavior of cromolyn, cefazolin and fenoprofen sodium hydrates.

The hydrated crystal structures of cromolyn, cefazolin, and fenoprofen sodium salts are reported. The former two compounds are non-stoichiometric hydrates, whereas the fenoprofen lattice maintains its stoichiometry over a broad range of relative humidity. The relationship between composition, lattice parameters, and relative humidity is studied using a combination of moisture sorption isotherms and variable humidity X-ray powder diffraction. The dehydration properties of the sodium salts are related to the ion coordination and hydrogen bonding of the water molecules in the structures. Anisotropic lattice contraction is observed during dehydration of the cromolyn and cefazolin sodium and is related to the closeness of intermolecular contacts in the hydrated structures.

Cefazolin↗

Cyclic and linear sweep voltammetry of cefazolin and cefmetazole: electroanalytical applications.

A study of the variables influencing the voltammetric behaviour of cephalosporins and cefamycins bearing substituents of the S-R' type (R' = non-electroactive group) has been carried out in order to determine the most suitable conditions for obtaining reproducible peaks for the determination of both types of antibiotic and the calculation of kinetic and thermodynamic parameters. The voltammetric behaviour of cefazolin and cefmetazole has also been studied. The voltammetric peak yielded by these two antibiotics at high sweep rates and low concentrations is due solely to the reduction of adsorbed molecules as the contribution of those molecules moving to the electrode through diffusion to the current is negligible. The peak current of cefazolin varies linearly with its concentration in the range 10(-9)-10(-7) M, whereas the linear range for cefmetazole is between 10(-8) and 5 X 10(-7) M, which allows the electroanalytical determination of the two antibiotics at these concentrations.

Cefazolin↗