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PubMed1989

Effect of primary fluids and dilutional volumes on the delivery of cefazolin sodium by a membrane infusion device.

The influence of primary fluids and dilutional volumes on the accuracy of in vitro delivery of cefazolin sodium by gravity flow through a new controlled-release membrane infusion device was studied. For primary fluid studies, cefazolin 1 g (as the sodium salt) in 10 mL of sterile water for injection was injected into the drug chamber, which is separated by a membrane from the fluid chamber; the entire dose passes into the fluid chamber over a set time. The inlet port of the fluid chamber was connected to the 1-L primary fluid bag, and the outlet port was connected to an administration set. The primary fluids included 0.9% sodium chloride injection; 5% dextrose injection; 10% dextrose injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose, 0.45% sodium chloride, and potassium chloride 20 meq/L injection; and 2.2% amino acids with electrolytes in 25% dextrose injection. For dilutional volume studies, cefazolin sodium 1 g diluted in 5, 10, and 15 mL of sterile water for injection was infused with 0.9% sodium chloride injection. The flow rate was set at 1 mL/min. Serial samples were collected in triplicate every five minutes over a 90-minute period and analyzed by high-performance liquid chromatography. The time needed to deliver more than 95% of the cefazolin doses ranged from 35 to 50 minutes using various primary fluids and from 35 to 55 minutes using various dilutional volumes. The manufacturer recommends that a cefazolin dose be delivered completely within 30-60 minutes. The solutes in the primary fluids and the volume injected did not appear to affect the delivery of cefazolin by a controlled-release membrane device.

Cefazolin↗

PubMedDate not supplied

Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man.

In the present study, the physiologically based pharmacokinetic model, which succeeded previously in predicting the pharmacokinetics of beta-lactam antibiotics in rats [A. Tsuji, T. Yoshikawa, K. Nishide, H. Minami, M. Kimura, E. Nakashima, T. Terasaki, E. Miyamoto, C.H. Nightingale, and T. Yamana: Physiologically based pharmacokinetic model for beta-lactam antibiotics. I: tissue distribution and elimination in rats. J. Pharm. Sci. 72, 1239-1252 (1983)], was applied to cefazolin pharmacokinetics in rabbits and man. After iv bolus dosing in normal rabbits, the time courses of cefazolin concentration in plasma and various tissues (lung, heart, muscle, skin, bone, gut, liver, and kidney) were found to be very similar to those in rats. The values of physiological parameters (tissue plasma flows, tissue volumes, tissue/plasma albumin ratio) and biochemical parameters determined in this study (for nonlinear plasma protein binding, intrinsic renal clearance of active secretion and reabsorption) were incorporated into mass balance equations derived from the model. There was reasonable agreement between the model predictions and the observed data for cefazolin and inulin in rabbits. The model was also successful in the prediction of cefazolin disposition in rabbits with renal failure. Using available information reported for cefazolin in man, a preliminary extrapolation from the present model was attempted, and the overall predicted results after iv administration of 1 g cefazolin in man were compared with the serum and bone tissue data. The length of the effective antibacterial period for the drug is also discussed in terms of its predicted concentration unbound with proteins in various tissue interstitial fluids in man.

Animals↗

PubMed1988

Cefazolin versus cefamandole for prophylaxis during total joint arthroplasty.

A prospective, randomized, double-blind comparison of cefazolin versus cefamandole was carried out to evaluate safety and efficacy and to determine bone and serum antibiotic concentrations in patients undergoing total joint arthroplasty. Dosages were 1 g of cefazolin before surgery followed by 500 mg every eight hours for six doses, versus 2 g of cefamandole before surgery followed by 1 g every eight hours for six doses. Intraoperative doses were given during prolonged procedures. No significant adverse drug reactions were clearly attributable to either drug. Among 48 patients receiving cefazolin there was one postoperative wound infection and one distant site infection. Among 49 patients receiving cefamandole, there were two postoperative wound infections and two distant site infections. No deep wound infections occurred in either group during at least 48 months of follow-up study. In hip specimens removed at surgery, the mean antibiotic concentrations were 1.6 +/- 1.4 micrograms/g for cefazolin recipients, compared with 5.7 +/- 5.9 micrograms/g for cefamandole recipients (p less than .001). In knee specimens, the mean antibiotic concentrations were 0.64 +/- 0.57 microgram/g for cefazolin recipients compared to 3.8 +/- 3.4 micrograms/g for cefamandole recipients (p = .004). Cefazolin given at one-half the dose of cefamandole appeared to be equally safe and effective but resulted in lower bone concentrations of antibiotic.

Aged↗

PubMedDate not supplied

Perioperative antimicrobial prophylaxis in cardiovascular surgery. A prospective randomized trial comparing two day cefuroxime prophylaxis with four day cefazolin prophylaxis.

In a randomized prospective study, two different regimens of antibiotic prophylaxis have been tested: four-day cefazolin prophylaxis (Kefzol 0.5 gr every 6 h) compared with two-day cefuroxime administration (Zinacef 1.5 gr every 12 h). A total of 569 patients in the two groups were studied in a 10 month period. Haematological, liver function, serum creatinine and urea measurement were made preoperatively and repeated daily for the first four days and after one week. At least five chest X-rays were taken during the hospitalisation. Body temperature was measured regularly every two hours in the ICU and a least twice a day thereafter. The wounds were examined daily and the patients were carefully observed for other infections. Bacteriological examinations of the tips of all inserted catheters and pacemaker wires were undertaken on removal in the first four months of the trial. Swabs of any tracheal or wound secretion or pus taken for bacteriological examinations as also blood cultures in any suspected septicaemia. Of the 569 patients three had to be withdrawn from the study. Of the assessable ones 285 received cefuroxime and 281 were given cefazolin. Seven patients (1.2%) died postoperatively. The total infection rate was 5.5%: 5.7% in the cefazolin group and 5.3% in the cefuroxime group. The overall wound infection rate was 1.8%: 2.5% in the cefazolin group and 1.1% in the cefuroxime group. Septicaemia occurred in 0.5% of the cases. Pneumonia occurred in 11 (1.9%) patients; 1.5% in the cefazolin and 2.5% in the cefuroxime group. Seven patients (1.2%) developed a urinary tract infection; 1.4% in the cefazolin group and 1.1% in the cefuroxime group.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

PubMed1987

Cost analysis of using premixed frozen versus hospital-reconstituted cefazolin sodium injection.

The costs of preparing cefazolin sodium 1-g small-volume injections (SVIs) by each of two reconstitution methods were compared with the costs of using premixed frozen cefazolin SVIs at two hospitals. Both hospitals routinely used premixed cefazolin 1-g SVIs. Each converted to its previous reconstitution system for approximately two weeks. One hospital used a once-weekly "batch" system, and the other hospital used the twice-daily "extemporaneous" system. Pharmacist and technician time involved in both systems was determined using time-and-motion methods. A total of 40 preparation cycles of 10 SVIs each were monitored to determine labor costs. Hospital purchase-contract prices were used for determining material costs per SVI, and waste was calculated based on the number of SVIs that could not be recycled. The total time required for preparation of 10 cefazolin 1-g SVIs by each method was comparable (6.2 minutes for the batch method, 5.8 minutes for the extemporaneous method); labor costs contributed minimally to overall costs of each reconstituted SVI. Approximately 5% of reconstituted SVIs were wasted in each system. The conversion to premixed cefazolin SVIs resulted in an annual cost increase of more than $5000 at each hospital, compared with the reconstitution methods. However, subjective evaluations indicated that use of the premixed admixtures resulted in increased efficiency of i.v. preparation by allowing pharmacy personnel to devote more time to other labor-intensive duties. The results of this study allowed the pharmacies to negotiate more equitable prices for premixed cefazolin sodium injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefazolin↗

PubMed1985

Pharmacokinetics and bioavailability of cefazolin in horses.

The pharmacokinetics and bioavailability of cefazolin given (IV, IM) to horses at the dosage of 11 mg/kg were investigated. The disposition of cefazolin given by IV route was characterized by a rapid disposition phase with a half-life of 5 to 10 minutes and a subsequent slower elimination phase with a half-life of 35 to 46 minutes. The total plasma clearance of cefazolin averaged 5.51 ml/min/kg and was due mainly to renal clearance (5.39 ml/min/kg) of unchanged drug. The volume of distribution at steady-state averaged 188 ml/kg. Plasma protein binding of cefazolin at a concentration of 10 micrograms/ml averaged 8.1 +/- 1.9%. Given by the IM route, cefazolin was rapidly absorbed; the extent of bioavailability was 78.4 +/- 18.8%, and the terminal half-life ranged from 49 to 99 minutes. Thus, cefazolin was extensively absorbed, but was eliminated more slowly than after IV administration.

Animals↗

PubMed1984

[A prospective, randomized comparative study between cefazolin and cefuroxime as perioperative antibiotic prevention in cardiovascular surgery].

In a randomized prospective study, two different regimens of antibiotic prophylaxis have been tested: 4-day cefazolin prophylaxis (Kefzol, 0.5 g every 6 h) compared with 2-day cefuroxime administration (Zinacef, 1.5 g every 12 h). A total of 569 patients in the two groups were studied over a 10 months' period. Hematological, liver-function, serum creatinine and urea measurements were performed preoperatively and repeated daily for the first four days and after one week. At least five chest X-rays were taken during the hospitalization. Body temperature was measured regularly every two hours in the ICU and at least twice daily thereafter. The wounds were examined daily and the patients were carefully observed for other infections. Bacteriological examinations of the tips of all inserted catheters and pacemaker wires were undertaken on removal in the first four months of the trial. Swabs of any tracheal or wound secretion or pus were taken for bacteriological examinations, and blood cultures were performed for any suspected septicemia. Of the 569 patients, 3 had to be withdrawn from the study. Of the assessable patients, 285 received cefuroxime and 281 were given cefazolin. Seven patients (1.2%) died intra- or postoperatively. The total infection rate was 5.5%; 5.7% in the cefazolin group and 5.3% in the cefuroxime group. The overall wound infection rate was 1.8%; 2.5% in the cefazolin group and 1.1% in the cefuroxime group. Septicemia occurred in 0.5%, pneumonia in 11 patients (1.9%); 1.5% in the cefazolin and 2.5% in the cefuroxime group. Seven patients (1.2%) developed a urinary tract infection; 1.4% on the cefazolin group and 1.1% in the cefuroxime group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1973

Clinical and in vitro evaluation of cefazolin, a new cephalosporin antibiotic.

Cefazolin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 26 patients. Cefazolin had activity equivalent to cephalothin against Streptococcus pneumoniae, Staphylococcus aureus, group A streptococci, and Proteus mirabilis. Cefazolin was four- to eightfold more active against Escherichia coli and slightly more active against Klebsiella pneumoniae, whereas cephalothin was slightly more active against indole-positive Proteus species. After a 500-mg dose of cefazolin intramuscularly, peak concentrations in the serum were high enough to inhibit all strains of S. pneumoniae, S. aureus, group A streptococci, E. coli, K. pneumoniae, and P. mirabilis, as well as 60% of strains of Proteus species other than P. mirabilis. All of 26 patients (18 with pneumonia, 6 with urinary tract infection, and 2 with skin infections) responded clinically and bacteriologically to cefazolin therapy. There were no major side effects of therapy, and no patient complained of pain at the site of intramuscular injection. Cefazolin is an effective cephalosporin which can be used intramuscularly for therapy of serious bacterial infections. Its major advantages over other cephalosporins are higher, more sustained concentrations in the blood and apparent lack of pain on intramuscular injection.

Adult↗

PubMed1973

Bactericidal activity and pharmacology of cefazolin.

The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against Escherichia coli and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 mug/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.

Adult↗

PubMed1974

Disk susceptibility studies with cefazolin and cephalothin.

Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The cephalothin antibiotic class disk by the standard Bauer-Kirby method failed to detect susceptibility to cefazolin in a significant percentage of Escherchia coli, Enterobacter species, and Enterococcus isolates. A separate cefazolin disk with a susceptibility cut-off point of 18 mm is recommended. An alternative to a separate cefazolin disk would be a reinterpretation of the cephalothin susceptibility disk zone diameters so that it would more adequately predict cefazolin activity.

Cephalosporins↗

PubMed2026

The inoculum effect of methicillin-susceptible Staphylococcus aureus on cefazolin and other antimicrobial agents.

UNLABELLED: The inoculum effect (IE) refers to a reduced susceptibility of methicillin-susceptible Staphylococcus aureus (MSSA) to certain antibiotics under high bacterial inocula and may contribute to treatment failure. This exploratory study assessed IE prevalence among 234 nonduplicate MSSA isolates across 11 agents spanning major therapeutic classes, including cefazolin, and characterized IE-positive clones via whole-genome sequencing to inform clinical strategies. Minimum inhibitory concentrations (MICs) were determined by broth microdilution at standard and high inocula. Whole-genome sequencing was performed on IE-positive strains to identify β-lactamase types and conduct multilocus sequence typing. The highest prevalence of IE was observed for trimethoprim-sulfamethoxazole (9.4%), followed by erythromycin (8.8%), linezolid (6.8%), penicillin (6.1%), clindamycin (5.5%), vancomycin (3.8%), cefazolin (3.0%), levofloxacin (1.5%), tetracycline (0.5%), and oxacillin and gentamicin (0.0%). All cefazolin IE-positive strains carried blaZ type A, and ST25 was the most common sequence type (42.9%). For trimethoprim-sulfamethoxazole, erythromycin, and clindamycin IE, ST7 was the most common sequence type (22.7%, 26.7%, and 33.3%, respectively). ST1281 and ST188 were the predominant sequence types among strains exhibiting linezolid IE and vancomycin IE (25.0% and 33.3%, respectively). Among the 234 MSSA strains, 66.7% of ST59, 60.0% of ST25, 58.3% of ST5, and 54.2% of ST7 strains exhibited IE to at least one antimicrobial agent. Cefazolin IE was associated with blaZ type A, and ST5, ST7, ST59, and ST25 were the major sequence types associated with IE across the antimicrobial classes tested. IMPORTANCE: Methicillin-susceptible Staphylococcus aureus (MSSA) can show an inoculum effect on multiple antimicrobial agents, which may reduce antibiotic activity under high-burden conditions. In this study, MSSA isolates from Shanghai exhibited inoculum effects on several commonly used agents, although the overall detection rates were low. Cefazolin inoculum effect was specifically associated with blaZ type A, and several major sequence types were more likely to exhibit this phenotype. These findings improve our understanding of the epidemiology of the inoculum effect in MSSA and may help guide laboratory detection and antimicrobial treatment decisions.

Cefazolin↗

PubMed1982

Toxicity, efficacy, and clearance of intravitreally injected of cefazolin.

The intravitreal injection of cefazolin sodium was evaluated with respect to its potential toxicity, efficacy, and clearance in the treatment of bacterial endophthalmitis in the rabbit model. Toxicity evaluation included indirect ophthalmoscopy, scotopic electroretinogram, and light microscopy of histopathologic specimens. Rabbits given doses up to and including 2.25 mg of cefazolin sodium showed no evidence of toxic reaction by these criteria after two weeks of observation. When injected within 24 hours of inoculation, 2.25 mg of cefazolin sodium sterilized five of six rabbit eyes infected with Staphylococcus aureus. Following intravitreal injection of 2.25 mg of cefazolin sodium, vitreous concentrations in excess of the minimum inhibitory concentration for S aureus were maintained for five days. A 2.25-mg dose of cefazolin sodium appears to be nontoxic, effective, and biologically active against susceptible organisms during a prolonged period, when injected into the vitreous cavity of the pigmented rabbit in vivo.

Animals↗

PubMed1982

Rifampin and cefazolin as prophylactic agents. A comparison in an animal model of vascular graft infection.

We investigated rifampin and cefazolin sodium as prophylactic agents in a dog model of vascular graft infection. A 1-cm segment of 3-mm-diameter polytetrafluoroethylene (Gore-tex) graft was sewn into the right carotid artery of each dog, and prior to closure, 10(3) Staphylococcus organisms sensitive to both cefazolin and rifampin were injected over the graft. The dogs were killed five days after surgery and the grafts cultured. Infection occurred in 100% of controls, 58% of cefazolin-pretreated dogs, and 17% of rifampin-pretreated dogs. Mean blood levels of antibiotics were assayed as follows: cefazolin, 50.1 micrograms/mL; rifampin, 2.9 micrograms/mL. Both were well above the minimal inhibitory concentration. Thus, rifampin proved to be more effective than cefazolin in this animal model.

Animals↗

PubMedDate not supplied

Pharmacokinetic study of cefazaflur compared to cephalothin and cefazolin.

A single 1-Gm dose of cefazaflur, a new semisynthetic cephalosporin derivative, was compared in a crossover study to the same dose of cephalothin and cefazolin by intramuscular injection in seven healthy volunteers. Serum concentrations were measured at several time intervals during 6 hours following each administration. The mean peak serum levels obtained after 30 minutes were 25.2, 17.2, and 62.3 mug/ml, respectively, for cefazaflur, cephalothin, and cefazolin. In each of the seven subjects, serum concentrations were higher at each sampling time with cefazolin than with the other two cephalosporins. The percentage of total administered dose recovered in urine in a microbiologically active form for the 0-24-hour collection was, respectively, 92.7, 59.2, and 94.9 per cent with cefazaflur, cephalothin, and cefazolin, the largest part being excreted during the first 6 hours. Neither drug appeared to have any pronounced effect on various laboratory tests. Local reactions at the site of intramuscular injection were minor with cefazaflur and cefazolin, but were more pronounced with cephalothin.

Adult↗

PubMed1993

Evaluation of biodegradable cefazolin sodium microspheres for the prevention of infection in rabbits with experimental open tibial fractures stabilized with internal fixation.

Immediate internal fixation of severe open tibial fractures usually is contraindicated due to the high risk of infection. The objective of this study was to evaluate the efficacy of local antibiotic therapy with biodegradable poly-(DL-lactide-co-glycolide) cefazolin-loaded microspheres for the prevention of infection in experimental open fractures stabilized with internal fixation. Rabbits with experimental tibial fractures that were contaminated with Staphylococcus aureus were treated with local application of cefazolin microspheres, an equivalent local dose of free Ancef powder, or systemic Ancef therapy. The bones then were fixed with a four-hole plate, and the animals were observed for 8 weeks. Clinically, deep infection was present in 86% of control animals that received no antibiotics and in 60% of animals that received a 7 day course of systemic Ancef therapy. In contrast, no infections were noted among any of the surviving rabbits that received local therapy with either cefazolin microspheres or free Ancef powder. Significantly higher levels of serum cefazolin were measured at 1 h for animals treated with free Ancef powder (18.7 +/- 6.1 micrograms/ml) than for those treated with cefazolin microspheres (0.57 +/- 0.27 micrograms/ml). Follow-up studies are in progress to evaluate further the potential clinical benefits of local antibiotic therapy for the management of contaminated open fractures in humans.

Animals↗

PubMed1989

Age-related change in tissue-to-plasma partition coefficient of cefazolin for noneliminating organs in the rat.

Age-related changes in tissue distribution characteristics of cefazolin, a cephalosporin antibiotic, were examined for noneliminating organs of rats. The in vivo tissue-to-plasma partition coefficients (Kp,vivo) varied markedly among different ages and organs. In particular, muscle and skin acted as reservoirs for cefazolin distribution. There were also marked differences in interstitial fluid space (IS), determined using [14C]inulin, among different ages and organs. For muscle and bone, the magnitude of the age-related changes in Kp,vivo of cefazolin and IS was in the order of 1-week-old greater than 7-week-old = 100-week-old greater than 50-week-old rats. This is well correlated with the age-related changes in the volume of distribution at the steady state of cefazolin per body weight (Vdss/BW) and the extracellular fluid volume per body weight (Vecw/BW) determined previously using [14C]inulin. The predicted Kp value (Kp,pred) was estimated by incorporating the serum protein binding parameters of cefazolin, the IS values, and an interstitial-to-plasma albumin concentration ratio (AR) into equations derived from an extracellular fluid model. The Kp,pred values exhibited a fairly good correspondence with the Kp,vivo values determined for various organs, except gut, in rats of all four ages. These results suggest that the determinant of the age-related change in Vdss/BW is the difference in the IS value of muscle and bone, while the age-related change in serum protein binding plays only a modest role.

Adolescent↗

PubMed1983

Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.

A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).

Adult↗

PubMed2006

Intracameral cefazolin as prophylaxis against endophthalmitis in cataract surgery.

PURPOSE: To evaluate the efficacy of prophylactic intracameral cefazolin in preventing endophthalmitis in cataract surgery. SETTING: Service of Ophthalmology, St. Joan Hospital, Reus, Spain. METHODS: In this noncontrolled retrospective observational study, all patients had uncombined cataract surgery from January 2001 to December 2004. All cases of postoperative endophthalmitis were related. The patients were classified into 2 groups. The first (n = 3650) had surgery between January 2001 and December 2002, and the second (n = 3618) had surgery between January 2003 and December 2004; the second group received a bolus of intracameral cefazolin instilled at the end of surgery. RESULTS: The rate of postoperative endophthalmitis was lower in the cases with intracameral injection at the end of surgery (0.055%) than in those without cefazolin injection (0.63%). No patients in the group with intracameral cefazoline developed corneal endothelium or retinal toxicity. CONCLUSIONS: Intracameral bolus injection of cefazolin (1 mg in 0.1 mL solution) in cataract surgery demonstrated prophylactic efficacy in diminishing the rate of postoperative endophthalmitis without toxic effects on the cornea or retina.

Aged↗