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PubMed1988

Estimation of the degree of crystallinity of cefazolin sodium by X-ray and infrared methods.

The pentahydrate (alpha form) of cefazolin sodium (CEZ) exhibited sharp X-ray diffraction peaks, while the dehydrated alpha form showed weak but distinct diffraction peaks. As expected the amorphous form exhibited a diffuse and halo diffraction pattern. The X-ray procedure to estimate the degree of crystallinity of CEZ was based upon the measurement of the total scattering and the scattering from the crystalline region of the drug. The major difference in the infrared (IR) spectra among the three forms of CEZ was the absence of a spectral band at 1542 cm-1 in the amorphous form. The IR procedure was based upon the measurement of the peak percentage area ratio between the bands at 1542 and 1760 cm-1, where the latter was used as a normalizing peak. The degree of crystallinity of CEZ samples, obtained by either freeze-drying aqueous CEZ solutions or storing the crystalline forms under different humidity conditions, was determined by these two methods. Although the correlation of results by the two methods was good, the X-ray procedure appears to be superior since it can differentiate among the three solid CEZ forms, whereas IR could distinguish between only crystalline and amorphous CEZ, reproducibly.

Cefazolin↗
PubMed2003

Effect of experimental renal failure and hypotonic hyponatremia on the pharmacodynamics of cefazolin-induced seizures in rats.

PURPOSE: The purpose of this study was to investigate the effect of experimental renal failure and hypotonic hyponatremia on the pharmacodynamics of cefazolin (CEZ)-induced seizures. METHODS: Rats received an intravenous infusion of CEZ until the onset of seizures. Renal failure was produced by bilateral ureteral ligation (UL) or uranyl nitrate (UN) injection. Hypotonic hyponatremia was produced by intravenous infusion of 5% dextrose in water or intraperitoneal infusion of distilled water after arginine vasopressin injection. RESULTS: The serum and brain concentrations of CEZ at the onset of seizures increased with increasing infusion rate, but the CSF concentration of CEZ at the onset of seizures was not affected by the infusion rate. The concentration of CEZ in CSF at the onset of seizures was significantly lower in UL rats than control rats, whereas there was no difference between UN rats and their controls. Serum concentrations of Na+ and serum tonicity were lower in UL rats than UN rats. Hypotonic hyponatremia had no apparent effect on the CSF concentration of CEZ. The CSF concentration of CEZ at the onset of seizures was significantly lower in UN rats with hypotonic hyponatremia than their controls. CONCLUSION: Renal failure with severe hypotonic hyponatremia is associated with increased central nervous system sensitivity to CEZ-induced seizures.

Animals↗
PubMed1983

Cefazolin and cephalexin kinetics in continuous ambulatory peritoneal dialysis.

We studied single-dose cefazolin (CFZ) and cephalexin (CPX) kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients to establish therapeutic guidelines for two cephalosporins commonly used to treat peritonitis in these patients. CFZ, 10 mg/kg, was given intravenously and intraperitoneally, while CPX, 500 mg, was given orally. CFZ led to serum concentrations of 25 microgram/ml at 24 hr, with a half-life (t 1/2) of 33 hr. CAPD accounted for only 20% of total body clearance. When CFZ was given intraperitoneally, 74% of the dose was absorbed and similar serum concentrations had much the same t 1/2. CPX, on the other hand, had a serum t 1/2 of 8.6 hr and resulted in much lower peritoneal concentrations than CFZ. The kinetic principal of superposition provided a model for the prediction of plasma concentrations after repeated intraperitoneal doses of CFZ. The model predicts that a 10-mg/kg intraperitoneal loading dose, followed by 5-mg/kg doses in each exchange the first day and 2.5-mg/kg doses thereafter, will lead to steady-state plasma concentrations of 50 to 65 microgram/ml. The data suggest that CFZ needs be given only intraperitoneally at doses lower than those in current use. CPX probably adds little to the treatment of peritonitis.

Administration, Oral↗
PubMed1977

[Investigation of the c. s. fluid levels of two newer antibiotics; cefazolin and sisomicin (author's transl)].

In ten patients continuous estimations of the C.S.F. and serum levels were performed after the administration of a Cephalosporin derivative (Cefazolin - 4 cases) and a new alpha-amino-glycoside antibiotic (Sisomicin - 6 cases). After the evaluation of the results some doubts must be cast on the value of both these antibiotics for the treatment of meningitis or for per-operative chemo-prophylaxis in neurosurgical procedures. The values found were compared with those well-known in the literature, regarding the cephalosporins and the alpha-amino-glycoside Gentamycin.

Adolescent↗
PubMed1998

Beta-lactamase production diminishes the prophylactic efficacy of ampicillin and cefazolin in a guinea pig model of Staphylococcus aureus wound infection.

Clinical trials in surgery suggest that some failures of antibiotic prophylaxis are related to the in vivo degradation of beta-lactams by Staphylococcus aureus beta-lactamase. To explore this issue further, isogeneic isolates of S. aureus differing only in whether they contained the structural gene for type A staphylococcal beta-lactamase were constructed and compared for their ability to establish an abscess in a guinea pig model. With ampicillin prophylaxis, the ID50 was 870 cfu for the beta-lactamase-negative isolate VK7114 and 240 cfu for the beta-lactamase-producing isolate VK7115 (P < .001). Similarly, the ID50 was greater for the beta-lactamase-negative isolate when cefazolin prophylaxis was administered (599 vs. 128 cfu, VK7114 and VK7115; P < .001). In the setting of prophylaxis with beta-lactamase-susceptible antibiotics, beta-lactamase contributes to the pathogenesis of S. aureus wound infections.

Abscess↗
PubMed1983

A comparative study of the efficacy of ceftazidime versus cefazolin and tobramycin in patients with acute exacerbations of chronic bronchitis.

Fifty-nine adult patients have entered this study. The initial pathogens were eradicated from the infection sites and all except two of the patients who were assessed clinically in the ceftazidime group and 4 cases in the comparative group were cured or improved. No adverse reactions were connected to ceftazidime or to tobramycin and cefazolin.

Adolescent↗
PubMed1983

Safety and tolerance comparison of imipenem-cilastatin to cephalothin and cefazolin.

Imipenem-cilastatin was compared, in two multicentre clinical trials, with cefazolin or cephalothin, in their efficacy, safety, and tolerance. Safety and tolerance for imipenem-cilastatin was similar to that of these two cephalosporins. There were more transient liver function test changes in the imipenem-cilastatin group, but the frequency was similar to that for beta-lactams in general. There were similar numbers of cases of transient neutropenia in each group. Clinical side effects were few for the treatment groups and all drugs were well tolerated.

Cefazolin↗
PubMed1990

Beta-lactam antibiotics (aztreonam, ampicillin, cefazolin and ceftazidime) in the control and eradication of Salmonella typhimurium in naturally resistant and susceptible mice.

This study was undertaken to investigate the efficacy of different beta-lactam antibiotics in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c (Itys) and resistant CBA (Ityr) mice were used to investigate the efficacy of one monocyclic (aztreonam) and three bicyclic (ampicillin, cefazolin, ceftazidime) beta-lactam antibiotics in controlling systemic salmonella infections when given for brief or prolonged periods. The present study confirms and amplifies earlier reports on ampicillin therapy, demonstrates marked differences in the efficacy of the different antibiotics and shows that aztreonam is not only very effective but can completely eradicate the salmonellae from the RES when given early in the infection.

Ampicillin↗
PubMed1999

Treatment of hospitalized patients with complicated gram-positive skin and skin structure infections: two randomized, multicentre studies of quinupristin/dalfopristin versus cefazolin, oxacillin or vancomycin. Synercid Skin and Skin Structure Infection Group.

Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic available for the treatment of complicated gram-positive skin and skin structure infections, was compared with standard comparators (cefazolin, oxacillin or vancomycin) in one USA and one international trial. These two randomized, open-label trials of virtually identical design enrolled a total of 893 patients (450 quinupristin/dalfopristin, 443 comparator). The majority of patients had erysipelas, traumatic wound infection or clean surgical wound infection. Staphylococcus aureus was the most frequently isolated pathogen in both treatment groups and polymicrobial infection was more common in the quinupristin/dalfopristin group than in the comparator group. The clinical success rate (cure plus improvement) in the clinically evaluable population was equivalent between the two treatment groups (68.2% quinupristin/dalfopristin, 70.7% comparator; 95% CI, -10.1, 5.1) despite a shorter mean duration of treatment for quinupristin/dalfopristin patients. In the bacteriologically evaluable population, by-patient and by-pathogen bacteriological eradication rates were somewhat lower for quinupristin/dalfopristin (65.8% and 66.6%, respectively) than for the comparator regimens (72.7% and 77.7%, respectively). The lower bacteriological response rates in the quinupristin/dalfopristin group were, in part, due to a higher rate of polymicrobial infections and a higher incidence of patients classified as clinical failure, a category which included premature discontinuation of treatment because of local venous adverse events. The bacteriological eradication rate for quinupristin/dalfopristin was higher in monomicrobial infections than in polymicrobial infections (72.6% versus 63.3%, respectively), whereas the corresponding rate for the comparator regimens was lower for monomicrobial infections than polymicrobial infections (70.8% versus 83.1%). This finding was not unexpected, since the spectrum of quinupristin/dalfopristin is focused on gram-positive pathogens and additional antibiotics to treat gram-negative bacteria were not required per protocol. The systemic tolerability of both treatment regimens was qualitatively similar. A higher rate of drug-related venous adverse events was reported for quinupristin/dalfopristin (66.2%) than for the comparator regimen (28.4%). Premature discontinuation of study drug was primarily due to adverse clinical events for quinupristin/dalfopristin (19.1%), whereas the most common reason for discontinuation among those receiving the comparator regimens was treatment failure (11.5%). Quinupristin/dalfopristin is an effective alternative for the treatment of hospitalized patients with complicated skin and skin structure infections due to quinupristin/ dalfopristin-susceptible gram-positive organisms, including methicillin- and erythromycin-resistant S. aureus.

Adolescent↗
PubMedDate not supplied

Combined effects of ticarcillin and cefazolin on blood coagulation and platelet function.

Combined intravenous infusions of ticarcillin and cefazolin given to normal volunteers resulted in a functional platelet defect which appeared to be determined primarily by the dose and duration of treatment with the penicillin component. No effect on soluble blood coagulation factors was evident. Acute administration of corticosteroids did not influence the prolonged bleeding times induced by extended ticarcillin infusions.

Blood Coagulation↗
PubMed1987

The comparative influence of prophylactic antibiotics on the prothrombin response to warfarin in the postoperative prosthetic cardiac valve patient. Cefamandole, cefazolin, vancomycin.

A prospective randomized trial was conducted comparing the effect of three antibiotics: cefamandole (CM), cefazolin (CZ), and vancomycin (V), used as prophylaxis for prosthetic valve surgery, on the prothrombin (PT) response to warfarin (W) on the third day of anticoagulant therapy. Twenty patients, with normal preoperative PTs, were randomized to each antibiotic. Their PTs were not significantly different at 2 hours after operation and the morning before W was begun. The three groups received similar W doses for 2 days, and the PT, as percentage of activity, on the morning of the third day demonstrated that V (51 +/- 18%) was significantly greater (p less than 0.005) than CM (29 +/- 14%) or CZ (38 +/- 18%). CM had a significantly greater percentage of change in PT (64 +/- 14%, p less than 0.0001) from the first to third day than either CZ (51.1 +/- 18%) or V (44.6 +/- 19%). CM also had a greater number of patients (6) with PTs greater than or equal to 30 seconds on day 3 than either CZ (1) or V (1). The antibiotic influence on the PT response to W in this study is ranked as CM greater than CZ greater than V.

Aged↗
PubMed1994

Nocardial necrotizing scleritis after trauma. Successful outcome using cefazolin.

Nocardial necrotizing scleritis is uncommon, but potentially sight threatening. We report the occurrence of necrotizing scleritis in a 58-year-old farm worker after he sustained trauma with vegetable matter. Microbiological studies isolated Nocardia asteroides, sensitive only to cefazolin. Clinically the patient responded well to this drug, attaining a final visual acuity of 20/40, with complete resolution of the scleritis. Early isolation and testing for antibiotic sensitivity were responsible for the successful management of this patient.

Cefazolin↗
PubMed1995

Anaphylactic reaction to cefazolin in pregnancy.

Anaphylaxis is a rare event in pregnancy, but is one that can have serious implications for both the mother and fetus. We report a case of severe anaphylactic reaction to intravenous (i.v.) cefazolin (CEZ) given during labor with premature rupture of membranes. Maternal shock and prolonged fetal bradycardia occurred. Both the maternal and fetal outcomes were good following treatment with ephedrine, glucocorticoids, and emergency caesarean section.

Adult↗
PubMedDate not supplied

Antiepileptic effects of a calcium antagonist (nimodipine) on cefazolin-induced epileptogenic foci in rabbits.

The epileptogenic properties of cefazolin (CFZ) were utilized to induce an electrophysiological pattern of epilepsy in the rabbit. CFZ, cortically applied in different concentrations (2 or 4%), produced epileptic activity in a degree proportional to the concentration of the substance. In this experimental epilepsy model, we evaluated the effects of increasing doses (0.025, 0.05, and 0.1 mg/kg i.v.) of the calcium antagonist nimodipine (Bay e 9736). In the evaluation of nimodipine effects, the spike-and-wave burst frequency per minute was taken into account. These data were compared with those of placebo-treated (Bay e 9736 control test) control groups and statistically evaluated by two-tailed t test. In 2% CFZ-induced epilepsy, nimodipine at the 0.025- and 0.05-mg/kg doses did not produce significant changes in the EEG pattern. A statistically significant reduction (p less than 0.001) in epileptic activity was observed at the 0.1-mg/kg nimodipine dose. This reduction was seen first in the contralateral focus leads and persisted for the entire time of observation. In the more intense epileptic form (4% CFZ), nimodipine at the doses employed did not induce noteworthy EEG modifications. These data indicate that nimodipine exerts an antiepileptic effect. The possible mechanisms involved in this activity of a calcium antagonist are discussed.

Animals↗
PubMed1979

Intravenous use of cephradine and cefazolin against serious infections.

The relative efficacy and safety of cephradine and cefazolin were compared in 180 patients with a variety of serious infections caused by susceptible organisms. The patients were randomly assigned to one of two groups of 90 patients each. Most patients received 2 to 4 g per day, administered by intravenous injection in four equally divided doses, for a minimum of 4 days. Based on the clinical and microbiological results, the two cephalosporins were found to be comparable in therapeutic effectiveness. Toxicity was not a problem with either drug.

Adolescent↗
PubMed1980

Comparison of in vitro activity of moxalactam (LY127935) with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin against 420 blood culture isolates.

To compare the in vitro activity of moxalactam (LY127935), a new broad-spectrum antimicrobial agent, with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin, each drug was tested against 420 bacterial isolates from the blood of septic patients. Standard broth dilution methods were used to determine minimum inhibitory and bactericidal concentrations. LY127935 was as active as the aminoglycosides against aerobic gram-negative organisms, including Pseudomonas aeruginosa, and was at least 10-fold more active than the other beta-lactam agents against these bacteria. LY127935 was the most active agent tested against Bacteroides fragilis; its activity against all other anaerobic bacteria and Staphylococcus aureus was similar to those of the other agents tested. All streptococci, however, grew at higher concentrations of LY127935 than any other drug, and Streptococcus faecalis and Listeria monocytogenes were not inhibited at the highest concentration tested (minimum inhibitory concentration, > 64 microgram/ml). Although a greater proportion of blood culture isolates were susceptible to LY127935 than to any other drug tested, LY127935 does not have a sufficiently broad spectrum of in vitro activity to be recommended safely alone for empirical treatment of sepsis of unknown etiology.

Amikacin↗