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Inoculum effect on growth-delay time of oxacillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis exposed to cefamandole, cefazolin, and cefuroxime.

Cephalosporins have been recommended as prophylactic antibiotics in patients undergoing cardiovascular surgery. The major function of these antibiotics is to protect patients against Staphylococcus aureus and Staphylococcus epidermidis infections. The lowest inoculum amount responsible for infection during surgery is unknown but is probably low. To determine the comparative activities of cefazolin, cefuroxime, and cefamandole against S. aureus and S. epidermidis for prophylactic purposes, we selected five strains of S. aureus and S. epidermidis that presented homogeneous resistances to oxacillin. A continuously monitored turbidimetric method was used to evaluate cultures with variable inoculum sizes ranging from 10(6) to 1 CFU/ml and exposed to cefazolin, cefuroxime, and cefamandole at concentrations of 0.5, 1, 2, 4, 8, 16, and 32 micrograms/ml. Growth was defined as an increase of 0.1 optical density unit. The relationship between the time required for growth, the antibiotic concentration, and the initial bacterial density showed that cefamandole was more active than cefazolin, which, in turn, was revealed to be more active than cefuroxime against S. aureus and S. epidermidis.

Cefamandole↗

Simulation of human serum pharmacokinetics of cefazolin, piperacillin, and BRL 42715 in rats and efficacy against experimental intraperitoneal infections.

Studies were performed to determine the effects of BRL 42715, a potent beta-lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats. Compounds were administered to rats as a continuous infusion of an exponentially diluted solution to simulate in rat plasma the concentration-versus-time curves obtained for humans following intravenous bolus administration. A simulated 1-g dose of cefazolin was ineffective in reducing the bacterial counts in blood and peritoneal fluid samples of animals infected with S. marcescens US20, which produced class Ia beta-lactamase, and as a result, mortality was similar to that of infected controls. Similarly, a simulated 2-g dose of piperacillin was ineffective in reducing bacterial numbers and mortality in animals infected with E. coli 41548, producing a TEM-1 beta-lactamase. However, when the antibiotics were coadministered with BRL 42715, bacterial numbers were reduced significantly and all animals survived at least 16 h after infection. These data demonstrate the ability of BRL 42715 to potentiate the activity of cefazolin and piperacillin against beta-lactamase-producing bacteria that would otherwise be resistant to these antibiotics and illustrate the application of a model to simulate human serum concentrations in conscious rats.

Animals↗

Quinolones potentiate cefazolin-induced seizures in DBA/2 mice.

The behavioral and convulsant effects of cefazolin, a beta-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvulsant effects of some quinolones on seizures evoked by intraperitoneal administration of cefazolin were also evaluated in DBA/2 mice. Our study also demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin > enoxacin > ofloxacin > rufloxacin > norfloxacin > cinoxacin > ciprofloxacin > nalidixic acid. The relationships between the chemical structures and proconvulsant activities of quinolone derivatives were studied. The relationship between lipophilicity and proconvulsant activity was also investigated.

Animals↗

Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an in vitro peritoneal dialysate model.

Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the antibacterial activity of cell wall-active agents. By use of an in vitro static model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of 10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25 mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S. sanguis) and PDF at pHs of 5.5 and 7.4. The pH had no effect on antibacterial activity. Neither cefazolin nor vancomycin produced a bactericidal or a bacteriostatic effect versus MRSA, MSSA, MSSE, or S. sanguis in PDF, while all concentrations of daptomycin were bactericidal against all organisms in PDF. Daptomycin did not exhibit concentration-dependent activity in PDF. Daptomycin appears to be a promising agent for use in peritoneal dialysis-associated peritonitis, producing bacterial kill to a greater extent and at a higher rate than cefazolin or vancomycin in PDF.

Anti-Bacterial Agents↗

Extended-spectrum cephalosporin compared to cefazolin for treatment of Klebsiella pneumoniae-caused liver abscess.

From January 1995 to May 2000, a total of 107 adults with liver abscess due to Klebsiella pneumoniae admitted at a large medical center in northern Taiwan were reviewed. Patients were considered to have received cefazolin or an extended-spectrum cephalosporin if they received at least 3 days of that antibiotic within the first 5 days of hospitalization. Fifty-nine (55.1%) patients received cefazolin, and 48 (44.9%) patients received an extended-spectrum cephalosporin. The demographic data, clinical features, severities of illness, and rates of early drainage for the two groups were comparable. However, the rates of developing complications for the two groups were significantly different (37.3 versus 6.3%, respectively; P < 0.001). Furthermore, six independent factors preventing severe complications following liver abscess due to K. pneumoniae were identified: normal platelet count, alkaline phosphatase less than 300 U/liter, no gas formation in the abscess, APACHE III score less than 40, use of an extended-spectrum cephalosporin, and early drainage. In conclusion, cefazolin therapy may be suboptimal for patients with liver abscess due to K. pneumoniae despite active in vitro susceptibility. Use of an extended-spectrum cephalosporin and early drainage for patients with liver abscess due to K. pneumoniae are suggested.

APACHE↗

Cefatrizine (SK&F 60771), a new oral cephalosporin: serum levels and urinary recovery in humans after oral or intramuscular administration--comparative study with cephalexin and cefazolin.

Cefatrizine (SK&F 60771), a new broad-spectrum cephalosporin, was administered in a 0.5-g dose either orally or intramuscularly to volunteers in a crossover study. After oral administration, the average peak serum levels were 5.6 and 22.1 mug/ml for cefatrizine and cephalexin, respectively. The serum half-life of cefatrizine appeared to be more extended than that of cephalexin. Urinary recovery of cefatrizine (35%) was approximately half that of cephalexin (68%) after oral administration. After intramuscular injection of 0.5 g, the average peak serum level of cefatrizine (12.0 mug/ml) was approximately one-fourth that of cefazolin (44.0 mug/ml). The serum half-life after intramuscular injection was 86 min for cefatrizine and 118 min for cefazolin. Urinary recovery was 45% of the intramuscularly administered dose, as compared with cefazolin, which was 74%.

Administration, Oral↗

Efficacy of cefazolin in promoting ovine tracheal epithelial repair.

Inhalation of toxic materials has been shown injurious to the upper airways. Because secondary infection can slow the repair process, we undertook this study to determine the efficacy of antibiotic therapy in promoting the healing process of acute tracheal wounds. In 18 anesthetized sheep, a portion of the cervical trachea was exposed to smoke from smoldering cotton cooled to 38 degrees C. Nine received the broad-spectrum antibiotic, cefazolin, while none received saline placebo. At 13 days after injury, nonciliated and ciliated cell counts were 75% and 33% respectively of noninjured trachea receiving placebo, while in those receiving cefazolin, nonciliated and ciliated cell counts increased to 93% and 114% of paired noninjured trachea, respectively. We suggest that cefazolin therapy allows cell proliferation and differentiation to proceed more rapidly than observed with placebo therapy and thus may be a helpful augmentor to the healing of an acute airway injury.

Animals↗

Relationships between in vitro susceptibility and efficacy in experimental mouse infection-protection assay of cefazolin and cephalothin using Escherichia coli strains.

The disc sensitivity and minimal inhibitory concentrations (MIC) of cefazolin and cephalothin were compared against a series of Escherichia coli isolates. These data were correlated with the mouse protective doses of the 2 cephalosporins in animals infected with E. coli strains selected according to their various degrees of in vitro sensitivity to the 2 cephalosporins. The overwhelming majority of E. coli strains showed a significantly higher degree of susceptibility and lower MIC values for cefazolin than for cephalothin. There has been found a good correlation between the inhibition zones and especially the MIC values and the ED50 results for both cephalosporins. Using E. coli clinical isolates, cefazolin was found to be superior to cephalothin not only in vitro experiments but also more potent in protecting the experimentally infected mice.

Animals↗

Differential susceptibility of indole-positive and -negative strains of Klebsiella pneumoniae to cefazolin, choramphenicol and tetracycline.

Biochemical properties and antibiotic susceptibilities of 168 clinical isolates of Klebsiella pneumoniae were tested. On the basis of the indole reaction, 30 isolates (18%) were indole-positive and 138 isolates (82%) were indole-negative. A significant difference in antibiotic susceptibility was found in each of the two groups of isolates. Of the indole-negative isolates, 82.6% were susceptible to cefazolin at 6.25 microgram/ml or lower, while the indole-positive isolates varied in susceptibility to cefazolin. All of the indole-positive isolates were susceptible to chloramphenicol and tetracycline, but the indole-negative isolates varied in their susceptibility to these antibiotics. Whereas there was no relationship between indole production and susceptibility to cephalothin among the K. pneumoniae isolates studied, it appeared that there was a correlation between the indole reaction and susceptibility to cefazolin, chloramphenicol and tetracycline.

Cefazolin↗

Treatment of twelve burn wound infections and eight other serious infections with cefazolin and tobramycin: in vitro and in vivo evaluation.

20 patients with serious infections were treated with cefazolin and tobramycin for 9--64 days. Minimal inhibitory concentration (MIC) values and minimal bactericidal concentration (MBC) values were determined for each of the 112 clinical bacterial isolates. The median cefazolin MIC/MBC was 1.56/12.5 micrograms/ml, and the median tobramycin MIC/MBC was 6.25/25.0 micrograms/ml for all organisms studied. Median cefazolin doses of 49.0 mg/kg/day gave median peak/trough serum levels of 43.0/11.0 micrograms/ml. Median tobramycin doses of 4.3 mg/kg/day gave median peak/trough serum levels of 5.0/1.4 micrograms/ml. Checkerboard studies revealed synergy with 65% of strains. Bacteriologic and clinical success was obtained in 17 of 20 patients.

Acute Kidney Injury↗

In vitro activity of cefmenoxime, cefotaxime, latamoxef, cefazolin, nafcillin and vancomycin against 53 endocarditis and bacteremic strains of Staphylococcus aureus.

Antistaphylococcal activity of newer beta-lactam antibiotics, cefmenoxime, cefotaxime and latamoxef was compared with that of the more conventional antistaphylococcal agents, nafcillin, cefazolin and vancomycin. 53 strains of Staphylococcus aureus, 40 from patients with endocarditis and 13 from patients with bacteremia from other causes were tested in vitro against each antibiotic using agar dilution methods. Minimal concentration of antibiotic to inhibit 90% of strains tested was 2 micrograms/ml for cefmenoxime and cefotaxime, 8 micrograms/ml for latamoxef and only 0.5 microgram/ml for nafcillin, cefazolin and vancomycin. The newer beta-lactam antibiotics may not be preferred to nafcillin, cefazolin or vancomycin in the treatment of serious staphylococcal infections.

Anti-Bacterial Agents↗

Effect of cefazolin on the corneal endothelium. An experimental study.

Cefazolin sodium was injected into the anterior chamber of the rabbit eye in order to evaluate its effect upon the corneal endothelium. Endothelial toxicity was evaluated by contact specular microscopy and transmission electron microscopy 48 h after injection. The results suggest that doses of 1 and 2 mg of cefazolin are nontoxic to the corneal endothelium. Endothelial toxicity occurred when 5 and 10 mg of cefazolin were injected.

Animals↗

Comparison of cefonicid and cefazolin prophylaxis in abdominal hysterectomy.

One hundred and sixty-four patients undergoing abdominal hysterectomy for benign diseases were prospectively evaluated. The efficacy and safety of surgical prophylaxis with a single dose of the long-acting cefonicid was compared to the standard three dose regimen of cefazolin. Prophylaxis was successful in 82 of 85 (96.5%) patients receiving cefonicid and in 77 of 79 (97.5%) patients receiving cefazolin. No serious adverse effects were encountered with both drugs. It is concluded that single dose intravenous cefonicid, when given preoperatively, is as safe and effective as the standard multiple dose regimen of cefazolin in patients undergoing elective abdominal hysterectomy.

Adult↗

Cefazolin: a valid model of experimental epilepsy?

In various animal species (chicks, rats and rabbits) the intravenous injection of high doses of cefazolin, a cephalosporin not hitherto reported to produce epileptic seizures, was found to produce epileptiform electrocortrical changes similar to those evoked by intravenous benzylpenicillin. Similar phenomena as those reported after systemic injection were also observed after microinjection of cefazolin into the III cerebral ventricle. In fact, both in chicks and rats cefazolin given by the latter route produced wild running crisis, myoclonic jerks of the limbs and in some instances generalized clonic convulsions. Concomitantly, bilateral electrocortical high voltage bursts of spikes were observed, followed during the intercritic period by periodic bilateral or unilateral single spikes.

Animals↗

Cefazolin prophylaxis in head and neck cancer surgery.

This study evaluated the prophylactic use of cefazolin in reducing the incidence of infection in patients undetgoing cancer surgery where the upper aerodigestive tract was entered from the neck. A prospective, randomized, double-blind design was conducted in a single hospital. The patient was given placebo or cefazolin, 1 gm intramuscularly with the preoperative medications, then 0.5 gm every six hours for four doses. Of 55 determinate patients, 32 received antibiotics and 23 placebo. Infection rate was 38% (12/32) and 87% (20/23) respectively, representing a statistically significant reduction in infection (P less than 0.001/. There were 30 wound and two nonwound (sinusitis and pneumonia) infections. In conclusion, the perioperative use of cefazolin in patients undergoing cancer surgery where the oral cavity or pharynx has been entered from the neck is useful in reducing the incidence of wound infection.

Adult↗

Outcomes of cefazolin versus ceftriaxone therapy in treating lower respiratory tract infections in adults.

OBJECTIVE: To determine whether choice of a first- versus third-generation cephalosporin as initial therapy for lower respiratory tract infections in hospitalized adults affects the course and duration of care, both of which may influence antimicrobial treatment cost. DESIGN: Retrospective analysis of discharge abstracts and hospital pharmacy records. SETTING: Forty-eight US acute-care hospitals. PATIENTS: One thousand ninety-two hospitalized adults (aged > 17 y) with principal diagnoses of lower respiratory tract infections (DRGs 79-80, 89-90). INTERVENTIONS: Cefazolin or ceftriaxone, given as sole antimicrobial therapy for at least one day. MAIN OUTCOME MEASURES: (1) The number of patients who received another parenteral antibiotic anytime prior to hospital discharge; (2) the number of days during which patients received any parenteral antibiotic while in the hospital; and (3) the number of days patients remained hospitalized following the start of antibiotic therapy. RESULTS: Patients treated with cefazolin (n = 763) were more likely to receive another parenteral antibiotic while in the hospital (30.3 vs. 20.7 percent; p < 0.001) and received more total days of therapy (7.2 vs. 6.7 d; p < 0.05) than those treated with ceftriaxone (n = 329). Although the time to hospital discharge did not differ in the full sample (9.2 d for both groups), it was greater among those receiving cefazolin (8.6 vs. 8.0 d; p < 0.05) when patients with lengths of stay exceeding 24 days were excluded from both groups. CONCLUSIONS: In addition to acquisition cost, differences in course and duration of care should be considered when determining the most cost-effective choice for antimicrobial therapy.

Adolescent↗

Influence of fever on cefazolin pharmacokinetics.

The influence of fever on the pharmacokinetics of cefazolin was investigated in patients with acute febrile diseases. Nine patients were included in the study. Antibiotic serum concentrations were determined using high performance liquid chromatograpy (HPLC). An analog computer and the SIMULINK software package were used to identify the pharmacokinetic model and PCNONLIN software package to obtain the secondary parameters. In 6 patients a two-compartment pharmacokinetic model of cefazolin was observed during fever and after defervescence. In 2 patients a two-compartment model changed to a one-compartment after defervescence, and a one-compartment model was observed in one patient during both periods. Cefazolin-treated patients with a two-compartment model (6/9) had higher Cmax, mean steady state serum concentrations (Css), and area under the plasma concentration-time curve (AUC(0-->infinity)), smaller central compartment volume (V1), and lower clearance (Cl) during fever. The varying distribution of antibiotics during fever probably reflects different hemodynamic responses to fever.

Adult↗

Penetration of nafcillin, methicillin, and cefazolin into human brain tissue.

To determine the penetration of the antistaphylococcal antibiotics, nafcillin, methicillin, and cefazolin, into brain tissue, we gave to each of 27 patients undergoing craniotomy and brain biopsy one of the antibiotics in a 2-g intravenous infusion just before operation. At the time of brain tissue removal (30 to 225 minutes after the start of the infusion), a serum specimen was obtained, and tissue and serum were assayed for antibiotic concentration. Eleven of 13 brain specimens contained detectable nafcillin concentrations between 0.36 and 11 micrograms/g of tissue (mean, 2.7 micrograms/g for all 13 specimens). Fourteen of 18 brain tissue specimens contained detectable methicillin concentrations between 0.56 and 5.0 micrograms/g of tissue (mean, 2.0 micrograms/g for all 18 specimens). Ten of 11 brain tissue specimens contained detectable cefazolin concentrations between 2.0 and 40 micrograms/g of tissue (mean, 10.6 micrograms/g for all 11 specimens). Each antibiotic penetrated "abnormal" brain tissue better than "relatively normal" brain tissue. Because nafcillin is more active against Staphylococcus aureus, we conclude that nafcillin is preferable to methicillin for the therapy of central nervous system staphylococcal infections. Cefazolin achieves higher brain tissue concentrations than the penicillins, but has not been clinically evaluated for the therapy of central nervous system infections.

Brain Chemistry↗