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PubMed1984

Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.

Aged↗
PubMed1987

Alteration of gentamicin and cefazolin kinetics with control of the hypothyroid state in humans.

We studied the effect of the control of the hypothyroid state in humans on the pharmacokinetic parameters of cefazolin and gentamicin after a single intravenous injection. These two antibiotics were chosen because of their different patterns of binding to serum albumin (0% for gentamicin and 82% for cefazolin). In hypothyroidism, the behavior of cefazolin only was altered, with a decrease in the total body clearance, possibly due to reduced urinary excretion, and a decrease in the volume of distribution without a significant alteration of cefazolin binding to serum protein.

Cefazolin↗
PubMed1988

Penetration of cefpiramide and cefazolin into peritoneal capsular fluid in rabbits.

Penetration of cefpiramide and cefazolin into a specific extravascular fluid was measured with rabbits bearing capsules in the peritoneal cavity. A general feature of slow accumulation and elimination of drugs from extravascular sites having low surface area/volume ratios has also been observed in this study. The capsular concentration-time profiles were well expressed by the following equation: C(CF) = A(CF)[e-kel(CF)(t-to)-e-kp(CF)(t-to)], where C(CF), A(CF), kp(CF), kel(CF), and to indicate capsular concentration at time t, constant for the dimension of concentration, capsule penetration rate constant, capsule elimination rate constant, and lag time before penetration occurs, respectively. The kp(CF), kel(CF), and to were 0.139 h-1, 0.059 h-1, and 0.45 h, respectively, for cefpiramide, and 0.448 h-1, 0.0145 h-1, and 0.14 h, respectively, for cefazolin. A(CF) was 22.7 micrograms/ml for cefpiramide and 4.53 micrograms/ml for cefazolin, being parallel to the area under the plasma concentration-time curve for free drug from to to infinity (20.1 micrograms.h/ml for cefpiramide and 3.43 micrograms.h/ml for cefazolin). In conclusion, it is suggested that as well as kp(CF) and kel(CF), the area under the plasma concentration-time curve for free drug from to to infinity may play an important role regarding the circulating reservoir of drugs in determining capsular concentration-time profiles in experimental models for particular extravascular sites of infection, like abscesses into which drugs cannot easily penetrate.

Animals↗
PubMed1988

Comparison of cefazolin, cefamandole, vancomycin, and LY146032 for prophylaxis of experimental Staphylococcus epidermidis endocarditis.

We evaluated antibiotic prophylaxis in the rabbit model of experimental endocarditis with three strains of Staphylococcus epidermidis of differing susceptibility patterns. For the first strain, which was highly susceptible to methicillin and cephalosporins, vegetations grew S. epidermidis for all 15 untreated rabbits compared with 1 of 20 rabbits receiving cefazolin, 3 of 20 receiving cefamandole, none of 20 receiving vancomycin, and none of 20 receiving LY146032. For the second strain, which was methicillin resistant but cephalosporin susceptible, vegetations were positive for 14 of 15 untreated controls, 4 of 20 receiving cefazolin, 5 of 22 receiving cefamandole, none of 20 receiving vancomycin, and none of 20 receiving LY146032. For the third strain, which was methicillin resistant and only intermediately susceptible to cephalosporin antibiotics, vegetation cultures were positive for 15 of 17 untreated controls, 14 of 21 receiving cefazolin, 11 of 20 receiving cefamandole, 5 of 20 receiving vancomycin, and 0 of 22 receiving LY146032. In conclusion, these studies in the endocarditis model indicate that cefazolin and cefamandole have some protective value against certain strains of S. epidermidis. Vancomycin and LY146032, however, were more active than cephalosporins for all three strains included in this analysis. These findings support the need for trials of vancomycin and LY146032 prophylaxis in patients undergoing placement of prosthetic heart valves.

Animals↗
PubMed1998

Synergism between poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan and cefazolin in prophylaxis of staphylococcal wound infection in a guinea pig model.

To determine whether the infection-preventing capability of the neutrophil-activating agent poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan (PGG-glucan) can be enhanced with antibiotic prophylaxis, we administered PGG-glucan and cefazolin, alone and in combination, to guinea pigs inoculated with isolates of staphylococci. Guinea pigs receiving both PGG-glucan and cefazolin had 50% infective doses that were 8- to 20-fold higher than those obtained with cefazolin alone and 100- to 200-fold higher than those obtained with PGG-glucan alone. PGG-glucan and cefazolin are synergistic in their ability to prevent staphylococcal wound infection.

Adjuvants, Immunologic↗
PubMed2002

Effects of neutrophils on cefazolin activity and penicillin-binding proteins in Staphylococcus aureus abscesses.

Bacteria survive within abscesses despite antimicrobial therapy, usually necessitating drainage. Our previous work showed that bacterial killing is diminished within the neutrophils of animals with abscesses. To further assess the role of neutrophils in Staphylococcus aureus survival and the poor activities of beta-lactams in abscesses, tissue cage abscess-bearing rats were given polymorphonuclear leukocyte (PMN)-depleting antibody prior to and several times following inoculation of the tissue cages with S. aureus. Cefazolin (300 mg/kg of body weight/day) was administered to all animals in appropriately divided doses. After 7 days of antimicrobial therapy, the 17 animals that received anti-PMN serum had significantly fewer abscess neutrophils than the 18 controls and fewer abscess bacteria (5.55 versus 3.79 log(10) CFU/ml [P = 0.04]) than the 18 controls. The data were consistent with the premise that cefazolin is more effective in abscesses depleted of neutrophils. To investigate further, S. aureus was incubated with rat peritoneal neutrophils; and bacterial cell membrane proteins were isolated, labeled with biotinylated ampicillin, separated by electrophoresis, blotted onto nitrocellulose, and stained for biotin reactivity. PBP 2 expression was consistently and significantly decreased after a brief, nonkilling PMN exposure. These experiments showed that PMN depletion enhanced the activity of cefazolin in the abscess milieu. Furthermore, altered bacterial cell wall cefazolin targets may be the mechanism by which the PMN diminishes antimicrobial activity, suggesting the importance of the staphylococcus-PMN interaction in the outcome of established infections.

Abscess↗
PubMed1974

Biliary tract excretion of cefazolin, cephalothin, and cephaloridine in the presence of biliary tract disease.

The biliary tract excretion of three cephalosporins, cefazolin, cephaloridine, and cephalothin, was compared in patients with biliary tract disease. In the absence of obstruction, mean antibiotic levels in bile from gall bladder and common duct in patients undergoing cholecystectomy were highest for cefazolin (17 and 31 mug/ml, respectively) than either cephaloridine (7 and 9 mug/ml) or cephalothin (1 and 4 mug/ml). Biliary tract levels generally paralleled serum levels. In no patient with cystic duct obstruction were any of the cephalosporins detectable in appreciable amounts in gall bladder bile. In patients with T-tube drainage given each of the three different cephalosporins on separate days, concentrations of cefazolin in bile were many-fold higher than either cephaloridine or cephalothin. Peak levels of cefazolin in T-tube bile averaged 51 mug/ml after intravenous and 26 mug/ml after intramuscular administration, whereas mean peak levels of cephalothin and cephaloridine were only 6 and 16 mug/ml, respectively. Here, too, T-tube levels reflected serum concentrations and obstruction to biliary flow impaired excretion of each of the drugs.

Biliary Tract↗
PubMed1975

Comparative pharmacokinetics and clinical experience with a new cephalosporin-derivative: cefazolin.

In a cross-over study in 12 normal individuals, the pharmacokinetic parameters of cefalotin, cefradine and cefazolin were determined after intravenous injection of 1,000 mg of each substance. The microbiological activities in urine and serum were determined using the agar diffusion test; the pharmacokinetic data were calculated by a computer system on the basis of a Fortran programme. Cefazolin has significantly higher serum concentrations than the other two cephalosporins, distinctly longer serum half-lives, higher protein binding, and smaller apparent volumina of distribution. In 36 inpatients with mainly chronical and acute infections of the urinary tract, we tested the antibacterial effectivity, the compatibility, and the application modalities of cefazolin. In 29 patients we had a satisfactory clinical result, in 25 cases we achieved the elimination of bacteria by the end of the therapy. The compatibility of cefazolin was good; apart from a minor, reversible, liver-specific increase in enzymes in 6 patients, no side effects could be detected.

Adult↗
PubMed2003

Antimicrobial prophylaxis in laparoscopic gynecologic surgery: a prospective randomized study comparing amoxicillin-clavulanic acid with cefazolin.

Numerous studies have been published in recent years about antimicrobial prophylaxis in gynecologic surgery, but the optimal drug and schedule for the different surgical procedures is still a matter of debate. The aim of the present study was to compare two ultra-short term antimicrobial prophylaxis regimens (amoxicillin-clavulanic acid and cefazolin) in preventing infections following laparoscopic gynecologic operations. Three hundred sixty women hospitalized for a laparoscopic gynecologic surgery procedure were included in the study between January 1999, and December 2001. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] as a single dose 30 minutes before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract and respiratory tract. In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 164 and 172 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both groups with febrile morbidity occurring in only one patient (0.6%) in the amoxicillin-clavulanic group. No sign of infections at the surgical site, urinary tract and respiratory tract was observed in either group. No death due to sepsis was recorded. It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective laparoscopic gynecologic surgery.

Adolescent↗
PubMed2006

Serum sickness-like reaction associated with cefazolin.

BACKGROUND: Although rare, serum sickness-like reactions have been documented to occur following the administration of many antibiotics. Cefazolin, a first generation cephalosporin, is a commonly prescribed antibiotic which is considered to be generally safe and well tolerated. There have been no prior reports linking this drug with sickness-like reactions. We report a probable case of serum sickness-like reaction following a single dose of cefazolin. CASE PRESENTATION: A 23 year old man with no significant past medical history was admitted to undergo a laparoscopic donor nephrectomy as part of a living-related renal transplant. One gram of intravenous cefazolin was administered perioperatively. The surgery was completed without complication and the remainder of his hospital course was uneventful. Ten days following discharge the patient developed fevers, painful and swollen joints, and a cutaneous eruption overlying his trunk and extremities. There was no evidence of systemic vasculitis. These clinical findings were most consistent with a serum sickness-like reaction. A brief course of corticosteroids and antihistaminergic therapy was initiated, and complete resolution of the patient's symptoms followed. The Naranjo probability scale indicated that this adverse drug event was probable. CONCLUSION: Serum sickness-like reaction may be associated with cefazolin therapy.

Adult↗
PubMed2002

Effect of water content on the solid-state stability in two isomorphic clathrates of cephalosporin: cefazolin sodium pentahydrate (alpha form) and FK041 hydrate.

This study clearly demonstrates that clathrated water molecules can contribute to both chemical stabilization and destabilization of clathrates. The solid-state stabilities for two isomorphic clathrates of cephalosporin, cefazolin sodium and FK041, were investigated in terms of the effects of water content. The isomorphic ranges of water content were estimated to be 3.5-5 mol/mol for alpha-form cefazolin sodium and 2-4 mol/mol for FK041 hydrate. Upon the isomorphic dehydration, alpha-form cefazolin sodium was destabilized as the water content decreased below 4.25 mol/mol owing to the disruption of hydrogen bonding network in lattice channels. In this case, the hydration of clathrated water up to 4.25 mol/mol contributed to the physical and chemical stability of the crystals. On the contrary, the isomorphic hydration in FK041 hydrate contributed to the chemical destabilization owing to the high water activity. The difference in water activity between alpha-form cefazolin sodium and FK041 hydrate could be attributed to the size of water channels.

Cefazolin↗
PubMed1994

Prophylaxis against infection in total joint arthroplasty. One day of cefuroxime compared with three days of cefazolin.

The efficacy of cefuroxime was compared with the efficacy of cefazolin for prophylaxis against postoperative wound infection in a prospective, double-blind, multicenter study of 1354 patients who had had elective primary or revision total hip or knee arthroplasty. The patients were randomly assigned to receive either 1.5 grams of cefuroxime followed by 750 milligrams eight and sixteen hours later (for a total of one day of antibiotic treatment), or one gram of cefazolin every eight hours for nine doses (for a total of three days of antibiotic treatment). The first dose of each drug was administered fifteen to sixty minutes before the operative incision was made (for a primary operation) or after tissue samples had been obtained for culture (for a revision procedure). After the operation, the patients were assessed daily while hospitalized and then at two to three months and one year after the operation. Demographic characteristics and risk factors were similar in the two groups. For the patients who had had a primary hip arthroplasty, the rate of deep wound infection was 0.5 per cent (one of 187) for those who had received cefuroxime and 1.2 per cent (two of 168) for those who had received cefazolin. For the patients who had had a primary knee arthroplasty, the rate of deep wound infection was 0.6 per cent (one of 178) for those who had received cefuroxime and 1.4 per cent (three of 207) for those who had received cefazolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Absorption↗
PubMed1978

Cefazolin.

After 5 years of use, cefazolin can be considered similar to cephalothin as a therapeutic agent and in its potential for adverse reactions. When cefazolin and cephalothin are compared by appropriately designed clinical trials, neither cefazolin's slightly greater in-vitro susceptibility to staphylococcal beta-lactamase inactivation, nor its slightly greater microbiologic activity for some enterobacteraciae has been shown to result in any readily apparent therapeutic differences. The important differences between cefazolin and cephalothin--and this is also probably true with respect to cephapirin and cephradine--are not in therapeutic effectiveness, microbiologic activity, or toxicity but rather in pharmacokinetics and cost-effectiveness.

Agranulocytosis↗
PubMed1989

The effect of an education program on cefazolin prescribing.

A study was conducted to identify cefazolin prescribing practices prior to a pharmacy based educational program and to assess the effect of the educational program on cefazolin prescribing and costs. The educational program consisted of the circulation of a drug information bulletin, a letter from the Chairman of the Pharmacy and Therapeutics Committee to all medical staff and pharmacists plus personal communications with physicians by pharmacists. The assessment involved a retrospective review of all cefazolin orders written during two 25-day periods, before and after the educational program. The results demonstrated a statistically significant reduction (p less than 0.05 by Z-test of proportions) in the number of cefazolin orders more frequent than every eight hours as well as the total number of doses given at more frequent regimens. This improvement in appropriate prescribing resulted in cost savings of $1,727.71 for the post education study period. This saving extrapolated to 12 months would lead to a $25,224.57 annual saving. This study suggests the effectiveness of a multifaceted educational program in optimizing prescribing.

Cefazolin↗
PubMed1999

[Enzymatic synthesis of beta-lactam antibiotics. I. Cefazolin].

Production of cefazolin by acyl transfer enzymatic synthesis with immobilised cefazolin synthetase from Escherichia coli as a biocatalyst acting in accordance with the mechanism including formation of the acyl-enzyme complex was shown possible. The process kinetic parameters and the ratio of the maximum conversion of the key amino acid and the initial concentrations of the substrate and nucleophile were determined. Correlation of the calculated and experimental data on the cefazolin yield in the enzymatic synthesis was good. The main physico-chemical properties of the substrates and the reaction products i.e. dissociation constants and solubility were investigated. The complex of the physico-chemical studies makes it possible to design a highly efficient technological process for production of cefazolin including not only the stage of the enzymatic synthesis but also the stage of separation of the reaction mixture components.

Acylation↗
PubMedDate not supplied

Effective treatment of peritoneal dialysis-associated peritonitis with cefazolin and ceftazidime in children.

OBJECTIVE: To evaluate the use of the combination of cefazolin and ceftazidime for initial treatment of peritoneal dialysis (PD)-related peritonitis in pediatric patients. DESIGN: Retrospective nonrandomized study. SETTING: Pediatric dialysis units of the University Medical Center of Utrecht and Nijmegen, The Netherlands. PATIENTS: 40 children (median age 5.4 years) who were treated with PD during the study period of 4.5 years. INTERVENTIONS: All 50 episodes of peritonitis that occurred during the study period were evaluated by review of medical records. Patients were given intraperitoneal ceftazidime 500 mg/L dialysis fluid, and cefazolin 500 mg/L as a loading dose, followed by a maintenance dose of ceftazidime 125 mg/L and cefazolin 100 mg/L, intraperitoneally, 4 times daily. Antibiotics were continued for 14 days. RESULTS: After identification of the causative microorganism, one of the antibiotics was discontinued in 34 cases, and the antibiotic schedule was adapted in 2 cases. All cases were initially cured within 3 days. In 5 cases (10%), there was a peritonitis with the same organism recurring within 2 weeks after completion of treatment. There were 4 cases of PD-related peritonitis caused by pseudomonas, all of which were cured. CONCLUSIONS: The antibiotic combination of cefazolin and ceftazidime is effective for the initial therapy of PD-related peritonitis in children. The toxic complications of aminoglycosides are avoided with this combination.

Adolescent↗
PubMedDate not supplied

Treatment and outcome of peritonitis in automated peritoneal dialysis, using a once-daily cefazolin-based regimen.

OBJECTIVE: We determined the effectiveness of a once-daily cefazolin-based regimen in treating automated peritoneal dialysis (APD) peritonitis. DESIGN: We carried out a retrospective analysis of all APD peritonitis episodes treated with a once-daily cefazolin protocol. SETTING: The study was performed in a peritoneal dialysis unit in a tertiary care hospital. PATIENTS AND METHODS: We studied 60 episodes of primary peritonitis in 40 patients on APD. Each patient was treated with a vancomycin-free regimen consisting of intraperitoneal cefazolin (1.5 g IP) with gentamicin IP administered in the daytime exchange. The main outcome measures were successful treatment of peritonitis, removal of peritoneal catheter, relapse of peritonitis, and patient death. RESULTS: Gram-positive infections occurred in 35 episodes (58.3%), gram-negative Infections in 10 episodes (16.7%), culture-negative infections in 14 episodes (23.3%), and a yeast infection in 1 episode (1.7%). Of the 60 episodes, 47 (78.3%) were successfully treated. In 10 episodes (16.7%), catheters were removed (9 for treatment failure, 1 for yeast infection). Four patients (8%) had a relapse of infection within 4 weeks of completing antibiotic therapy. One patient (1.7%) died. CONCLUSIONS: Our results demonstrate that once-daily cefazolin with gentamicin IP is an effective treatment for APD peritonitis, with the advantage of being easy to administer and enabling patients to remain on APD during treatment.

Adult↗