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PubMed2006

Cefazolin induced seizures in hemodialysis patients.

Cephalosporins are epileptogenic drugs, especially when excessive dosages are used or when the drugs are used in patients with decreased renal clearance. The present case report showed that a chronic kidney patient receiving hemodialysis developed generalized tonic clonic seizures when an inappropriate high dose cefazolin was given. Cefazolin 2 g iv q 8 h was given for 25 days continuously to treat fever of unknown origin in a patient who was a severe renal impairment patient. In a severe renal impairment patient, the maintenance dose of cefazolin should be reduced by half and the interval for administration should be extended to 24 h. Even though hemodialysis could remove cefazolin from the blood circulation, in the presented case the very high dose of cefazolin given was far beyond the ability of hemodialysis to clear the drug. The accumulation ofcefazolin, therefore, induced three episodes of seizures on days 14, 21 and 25. More precaution should be taken when prescribing medication to a patient with predisposing factors.

Adult↗

PubMed1988

Prophylaxis in gynaecological and obstetric surgery: a comparative randomised multicentre study of single-dose cefotetan versus two doses of cefazolin.

Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Multidisciplinary program for promoting single prophylactic doses of cefazolin in obstetrical and gynecological surgical procedures.

A multidisciplinary cost-containment program for promoting the use of single prophylactic doses of cefazolin for obstetrical and gynecological surgical procedures is described. Following a one-month review of patient charts to identify the antimicrobial regimens used most frequently for prophylaxis in obstetrical and gynecological surgical procedures, the department of pharmacy services, with the cooperation of the pharmacy and therapeutics (P&T) committee and the departments of obstetrics and gynecology and infectious diseases, implemented an educational program to promote the use of single doses of cefazolin for surgical prophylaxis. The program included inservice education and distribution of letters of support and a therapeutics newsletter. Drug stocking patterns in the operating and delivery rooms were changed to make cefazolin more accessible, and the P&T committee formally restricted the use of prophylactic antimicrobial agents in obstetrical and gynecological surgical procedures to single doses of cefazolin unless a consulting infectious-disease physician recommended otherwise. Compliance with the program increased as each step was implemented; data collected 16 months after the program was initiated demonstrated a compliance rate of 78.8%. Based on comparison of data collected before initiation and six months after initiation of the program, an actual cost savings of +7,125 was realized, which extrapolates to +14,250 annually. No apparent adverse effects on patient care were noted. The multidisciplinary approach to promoting the use of single doses of cefazolin was effective.

Cefazolin↗

PubMed1979

Clinical pharmacology phase I of cefazedone, a new cephalosporin, in healthy volunteers. II. Pharmacokinetics in comparison with cefazolin.

In two consecutive cross-over studies, each involving 10 healthy volunteers, the pharmacokinetics of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamindo)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) in comparison with cefazolin were investigated after single i.v. and i.m. administration. The doses were: i.v. cefazedone 500 mg and 1000 mg; cefazolin 1000 mg; i.m. cefazedone 500 mg, cefazolin 500 mg. The pharmacokinetic parameters were analysed by applying an open two-compartment model. The pharmacokinetics of cefazedone are nearly identical with those of cefazolin. In particular, it must be noted that cefazedone has a relatively long serum elimination half-life (1.64 +/- 0.23 h after i.v. and 1.85 +/- 0.51 h after i.m. administration) and that cefazedone exhibits, in comparison with cefazolin, a more favourable concentration ratio of central vs. peripheral (= tissue) compartment (1:2).

Adult↗

PubMed1980

Behavioral and electrocortical effects after intrastriatal cefazolin in rats are antagonized by drugs enhancing GABA-ergic transmission.

Cefazolin, a semisynthetic cephalosporin, reported to reproduce in several animal species an experimental model of epilepsy, was microinjected into the head of the caudate nucleus in rats. The effects on behavior, electrocortical activity and the antagonism by GABA receptor agonists and GABA-transaminase activity inhibitors were studied. Cefazolin given into the III cerbral ventricle produced an intense pattern of behavioral and locomotor stimulation culminating into several episodes of wild-running crisis, myoclonic jerks of the limbs and in some occasions generalized clonic seizures, these effects lasting over 2 h. At the same time bursts of electrocortical high-voltage spikes followed bu intermittent high-voltage single spikes were recorded. Similarly cefazolin, given into the caudate nucleus produced contralateral circling, an increase locomotor activity, myoclonic jerks of contralateral limbs, intense stereotyped behavior and occasionally generalized clonic convulsions. In addition postural changes consisting in tonic contralateral head-neck deviation were observed. This picture was accompanied by epileptic electrocortical changes, i.e. high-voltage spikes, spike-waves complexes, recruiting polyspikes. The subsequent intraventricular or intrastriatal infusion of GABA, GABOB, muscimol or of GABA-transaminase inhibitors, ethanolamine-o-sulphate and GABA-vinyl-GABA was able to antagonize clinical and electrocortical changes evoked by cefazolin. In conclusion, the present results suggest that cefazolin motor and electrocortical effects are due to an impairment of GABA-ergic transmission.

Animals↗

PubMed1978

[Experimental studies on the passage of antibiotics into cerebrospinal fluid in staphylococcal meningitis in rabbits. II. Cephaloridine, cephalothin and cefazolin (author's transl)].

Passage of cephaloridine, cephalothin and cefazolin into cerebrospinal fluid (CSF) was evaluated in Staphylococcus aureus meningitis in rabbits and the following results were obtained. 1. Concentration in CSF (microgram/ml) [CSF/serum ratio (%)] was determined 1/2, 1 and 2 hours after a single intravenous injection of 100 mg/kg of each antibiotic, respectively; cephaloridine-7.5 [8.9], 9.7 [13.8], 9.1 [22.6]; cephalothin-0.42 [3.6], 0.23 [6.4], not detectable [0]; cefazolin-7.5 [11.8], 5.2 [19.3], 2.0 [17.5]. 2. When results with cefazolin after an intravenous injection 100 mg/kg and 200 mg/kg were compared, a definite dose response was noted in blood concentration but not in CSF concentration. 3. A standard error of CSF concentrations of each antibiotic was larger than that of penicillins, and "Unpredictability" of their passage into CSF was considered to be one of the characteristics common to these three drugs in respect of their passage into CSF. 4. There was no significant difference noted in antibiotic passage into CSF between cephaloridine of low protein binding rate and cefazolin of very high binding rate. Cephalothin, of which binding rate was intermediate, showed a remarkably lower passage into CSF. These results indicate that a correlation does not always exist between protein binding rate of the antibiotics and their passage into CSF. 5. Based on the above results, a review of the literature was made on clinical applicability of these three antibiotics in the treatment of bacterial meningitis. Low transport rate of cephalothin into CSF and nephrotoxicity of cephaloridine make them to be unsuitable for bacterial meningitis. Cefazolin is considered to be suitable in the treatment of ampicillin-resistant Escherichia coli meningitis and Gram-positive coccal meningitis in which penicillins are not applicable.

Animals↗

PubMed1981

Effect of multidose therapy on cerebrospinal fluid penetration of cefazolin.

The relationship between serum concentrations and cerebrospinal fluid (CSF) concentrations of cefazolin, and the association between these concentrations and neurotoxic reactions, were investigated. Samples of serum and spinal fluid were drawn simultaneously from six patients at the steady state on various dosages of cefazolin sodium for different conditions. The dose, dosing interval, number of doses, results of renal function tests, and signs of neurotoxicity, such as muscle twitches, confusion, and seizures, were recorded. The concentrations of cefazolin in the serum and CSF, total serum protein, and percent albumin were determined. Five of the six patients given multiple doses of cefazolin sodium had notable CSF accumulation of the drug (11.3 +/- 2.7% of the serum concentration). Three patients experienced generalized focal-motor seizures during their therapy. Neurotoxicity was found to be associated with renal dysfunction and multiple-dose therapy leading to serum concentrations greater than 360 micrograms/ml and CFS concentrations greater than 34 micrograms/ml. Cefazolin will penetrate into the CSF in patients receiving multiple-dose therapy of the drug. To avoid neurotoxicity, careful attention should be paid to the recommended dosage regimens, the impact of renal dysfunction on drug clearance should be recognized, and serum assays should be performed when necessary.

Adult↗

PubMed1993

Antibiotic prophylaxis in cardiovascular surgery: a prospective randomized comparative trial of one day cefazolin versus single dose cefuroxime.

With the intention of reducing prophylactic antibiotic dosage, previous studies in the Zurich University Hospital have shown that a one/day prophylactic antimicrobial regimen with cefazolin was as effective as a single dose of ceftriaxone. In this prospective randomized study one day cefazolin prophylaxis (1 g q 8 h i.v.) was compared with a single dose of cefuroxime prophylaxis (1.5 g). In cases of cardiopulmonary bypass 0.75 g was added in the priming solution. In case of re-operation prophylaxis was repeated. 496 patients were enrolled in the study protocol; 78 patients were subsequently excluded. Of the remaining patients 224 (158 male, 66 female, mean age 61) were in the cefazolin group and 194 (142 male and 52 female, mean age 60) in the cefuroxime group. Mean duration of the intensive care unit (ICU) stay was three days in both groups and mean hospital stay was 16 days in the cefazolin group and 15 days in the cefuroxime group. The overall postoperative infection rate was 15.3%; 18.8% in the cefazolin group and 11.3% in the cefuroxime group. The statistical differences were found as in trend (p = 0.095). The lower incidence of infectious complications in the single cefuroxime dose group may indicate an improvement in effectiveness of antimicrobial prophylaxis: it offers patients a reliable antimicrobial protection. In addition, the single dose prophylaxis has the advantage of easier handling, reduced dosage frequency and lower cost.

Bacterial Infections↗

PubMed1993

Cefazolin antibacterial activity and concentrations in serum and the surgical wound in dogs.

An antibiotic selected for surgical antimicrobial prophylaxis must be present in the surgical site throughout the operation in concentration sufficient to prevent growth of contaminating pathogens. The antimicrobial spectrum, minimal toxicity, and low cost of cefazolin make this first-generation cephalosporin a logical choice for antimicrobial prophylaxis in small animal surgical procedures in which the normal microbiologic flora of skin and gastrointestinal tract are the most likely pathogens. Pharmacokinetic variables of cefazolin were determined in serum and surgical wounds in dogs. Drug concentration in interstitial fluid of muscle biopsy specimens taken at random from wound surfaces and in postoperative wound fluid samples were determined. Effective surgical wound concentration of cefazolin was defined as 4 micrograms/ml, a concentration that inhibited the growth in vitro of 100% of staphylococcal and 80% of Escherichia coli clinical isolates. After IV and SC administrations, cefazolin equilibrated rapidly between serum and the surgical wound, and concentrations in the 2 sites decreased in parallel. With a bolus dose of 20 mg/kg of body weight given IV at the beginning of surgery and repeated by SC administration at 6 hours, cefazolin concentration in the surgical wound remained > 4 micrograms/ml for longer than 12 hours.

Animals↗

PubMed1996

Effect of cefazolin and vancomycin on osteoblasts in vitro.

The effect of cefazolin and vancomycin on osteoblast-like cells was studied. Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 microg/ml. For cefazolin, a second interval was performed between 100 and 1000 microg/ml to define toxic levels more accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined. The results of this study show that local levels of vancomycin of 1000 microg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 microg/ml cause cell death. Concentrations of cefazolin of 100 microg/ml and less have little or no effect on osteoblast replication, 200 microg/ml significantly decrease cell replication, and 10,000 microg/ml cause cell death. The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections.

Anti-Bacterial Agents↗

PubMed1999

Teicoplanin for skin and soft tissue infections: An open study and a randomized, comparative trial versus cefazolin.

An open trial and a multicenter, three-group, randomized trial versus cefazolin were performed to study the use of teicoplanin in the treatment of serious skin and soft tissue infections caused by Gram-positive bacteria. A total of 418 patients were entered into the randomized trial, 293 of whom were available for efficacy analysis, and 262 patients were entered in the open trial. The randomized trial had three arms: intramuscular (125 patients) vs intravenous (148 patients) teicoplanin vs cefazolin (145 patients). In both trials teicoplanin was administered once daily, originally as 3 mg/kg per day, with the option of higher doses in the open trial. Cefazolin was given at a dose of 1.5-4 g/day, in three divided doses. In the randomized trial, teicoplanin and cefazolin showed similar overall efficacy. The higher dose of teicoplanin (6 mg/kg) was significantly more effective than the lower dose (3 mg/kg), particularly in patients with diabetes. In the open trial, teicoplanin had a clinical success rate of 93%. There was no significant difference in the incidence of adverse events between the cefazolin and teicoplanin groups. Outpatient ambulatory therapy was shown to be a practical method of administering teicoplanin. Once-daily dosing with teicoplanin may allow physicians to treat skin and soft tissue infections on a totally outpatient basis.

Journal Article↗

PubMed1973

Evaluation of cefazolin, a new cephalosporin antibiotic.

Cefazolin sodium was tested in vitro against 308 isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, and enterococcus. Broth and agar dilution and disk diffusion techniques were used with at least two sizes of inocula of organisms. Cefazolin was also studied in the treatment of 85 hospitalized patients with a variety of serious infections. In concentations of 5 mug or less/ml, cefazolin inhibited and killed more than 90% of isolates of Enterobacteriaceae with the exception of indole-positive Proteus and Enterobacter species. No isolate of P. aeruginosa and only a few of Enterobacter and enterococci were killed by 25 mug of cefazolin/ml, a concentration readily attainable in serum with a 500-mg dose given intramuscularly. Penicillin-susceptible as well as penicillin-resistant isolates of S. aureus were killed by 1 mug or less of cefazolin per ml; however, 25 mug/ml was required to kill 100% of the strains when the inoculum size was increased 100-fold. Cefazolin treatment appeared effective in 82 of 85 patients, including four with endocarditis. Pain was minimal after intramuscular injection, and thrombophlebitis was not observed in those treated intravenously. No patient developed a positive Coombs test, and no evidence of renal toxicity was apparent in clinical studies.

Adolescent↗

PubMed1973

Clinical studies of cefazolin and comparison with other cephalosporins.

Cefazolin, a new cephalosporin derivative, was studied in the treatment of 105 hospitalized patients with a variety of infections including endocarditis, pneumonia, and urinary and soft tissue infections, and was found to be effective in 104 patients. Cefazolin was also tested in vitro and shown to be effective against staphylococci, pneumococci, Escherichia coli, Klebsiella sp., and Proteus mirabilis by agar dilution method. It was shown to produce high serum levels when administered in a 250- to 1,000-mg intramuscular dose and was well tolerated and free from renal toxicity. Comparison of the results of this study with those from our prior studies on cephaloridine revealed equivalent antibiotic potency, good tolerance to both the agents when given intramuscularly, superior, average blood levels with cefazolin, equal clinical efficacy, and absence of renal toxicity with cefazolin (unlike cephaloridine). Similarly, the results of treatment of pneumococcal pneumonia with intramuscular cefazolin were found to be superior to those for oral cephalexin.

Bacterial Infections↗

PubMed1990

Vitreous cefazolin levels after intravenous injection. Effects of inflammation, repeated antibiotic doses, and surgery.

We devised a standardized rabbit model of intraocular inflammation using heat-killed Staphylococcus epidermidis as the inducing organism. We applied this model to study the effects of (1) inflammation, (2) repeated antibiotic doses, and (3) surgical status of the eye on cefazolin levels in the vitreous cavity after intravenous administration. Intravenous cefazolin sodium, 50 mg/kg, was administered every 8 hours for 48 hours. Eyes were harvested for assay of vitreous cavity antibiotic levels at various intervals from 1 to 49 hours. Drug levels were compared in inflamed and noninflamed eyes under both phakic and aphakic/vitrectomized conditions. At 1 hour, levels in phakic specimens were 3.0 mg/L in inflamed eyes vs undetectable in noninflamed eyes (P less than .01), but progressively increased to 10.6 mg/L at 49 hours (P less than .02) in inflamed eyes only. Levels in aphakic/vitrectomized eyes at 1 hour were 6.7 mg/L in inflamed eyes vs 4.2 mg/L in noninflamed eyes (P less than .1), but progressively increased to 24.9 mg/L at 49 hours (P less than .001) in inflamed eyes only. Levels at 49 hours in inflamed phakic and inflamed aphakic/vitrectomized eyes were well above the minimum inhibitory concentrations for organisms termed sensitive to cefazolin. We would conclude, therefore, that repeated doses of intravenous cefazolin may play an important adjunctive role in the treatment of endophthalmitis.

Analysis of Variance↗

PubMed2000

Prevention of infection with tobramycin-containing bone cement or systemic cefazolin in an animal model.

We investigated in an animal model the efficacy of tobramycin-containing bone cement and systemic cefazolin for infection prophylaxis. In 18 female rabbits, the femoral cavity was inoculated with Staphylococcus aureus before injection of bone cement. The first group of six rabbits received tobramycin-containing Simplex-P bone cement. Two other groups of six rabbits received plain Simplex-P bone cement. Preoperatively, in one of the two latter groups cefazolin was administered intravenously. The other group served as untreated controls. The rabbits were monitored for clinical signs of infection. At 7 days' follow-up, the femora were harvested and cultures from the bone adjacent to the cement plug were quantified. Cultures from the rabbits which received antibiotic prophylaxis (either cefazolin systemically or tobramycin-containing bone cement) were all negative. In contrast, all rabbits in the untreated control group had positive cultures. These rabbits also had other signs of infection such as an elevated erythrocyte sedimentation rate and loss of body weight. Culture results were confirmed by the absence of bacterial DNA in the polymerase chain reaction hybridization assay. In conclusion, we found that both tobramycin-containing bone cement and systemic cefazolin are effective in preventing implant bed infection in rabbits up to 7 days after contamination with S. aureus.

Animals↗

PubMed2000

Simultaneous determination of cefazolin in rat blood and brain by microdialysis and microbore liquid chromatography.

A sensitive microbore liquid chromatographic method combined with the minimally invasive technique of microdialysis was devised for simultaneously and continuously monitoring the levels of unbound blood and brain cefazolin in rats. Microdialysis probes were inserted into the jugular vein and brain striatum for blood and brain sampling, respectively. Chromatographic conditions consisted of a mobile phase of methanol-acetonitrile-100 mM monosodium phosphoric acid (20:10:70, v/v, pH 4.5) pumped through a microbore reversed-phase column at a flow rate of 0.05 mL/min. The ultraviolet detection wavelength was set at 270 nm. An on-line design allowed direct and continuous analysis of protein-free samples in the dialysate. Microdialysis probes, being home-made, were screened for acceptable in vivo recovery. Chromatographic resolution and detection were validated for response linearity as well as intra-day and inter-day variabilities. This method was then applied to pharmacokinetic profiling of protein unbound cefazolin in both the blood and brain following intravenous administration (10 mg/kg, i.v., n = 6). Rapid appearance of cefazolin in the rat brain striatal dialysate following drug injection suggested good blood-brain barrier penetration. According to a non-compartmental pharmacokinetics model, the area under the concentration (AUC) vs time ratio of cefazolin in rat brain and blood was 6%.

Animals↗

PubMed2001

Tobramycin-containing bone cement and systemic cefazolin in a one-stage revision. Treatment of infection in a rabbit model.

The efficacy of tobramycin-containing bone cement with that of systemic cefazolin for treatment of infection in a one-stage revision model is compared. In addition, the value of detecting bacterial DNA after antibiotic treatment was investigated. An implant was inserted into the right tibia of rabbits after inoculation with Staphylococcus aureus. At 28 days, the implant was removed. Subsequently, either plain bone cement with or without systemic administration of cefazolin, or tobramycin-containing bone cement was injected into the medullary canal. The tibiae were cultured 14 days after revision (Day 42), and showed a significant decrease in bacterial counts for both antibiotic groups compared with the control group (p</=0.05). The rate of infection in the tobramycin-cement group was slightly higher (2/9) than in the cefazolin group (0/8), although the difference was not significant. Persistence of bacterial DNA after antibiotic treatment may be the result of delayed clearance of DNA and not a sign of active infection. This animal model shows that in a one-stage revision tobramycin-containing bone cement can reduce size and rate of infection, although systemic cefazolin may be more efficacious. Therefore, the use of antibiotic-containing bone cement combined with systemic antibiotic might provide optimal treatment.

Animals↗

PubMed1977

[Serum concentrations and kinetics after intravenous infusion of four grams of cefazolin (author's transl)].

The pharmacokinetics of cefazolin were studied in 25 males and females after administration of 4 g infused over 60 minutes. The mean microbiologically active concentration of cefazolin in serum five minutes after discontinuing the infusion was 410 microgram/ml, after 60 minutes 190 microgram/ml and after 8 hours 8.5 microgram/ml. After 8 hours 84% of the drug was eliminated in the urine of four of the volunteers. The mean serum half-life was 87.38 minutes in the one compartment model, and the volume of distribution 9.20 1. The area under the curve was 44626.15 microgram.min.ml-1. The mean value for the clearance was 73.5 ml/min. The importance of high dosages of cefazolin in severe infections caused by cefazolin-sensitive organisms is discussed. Side-effects were not observed.

Adult↗