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PubMed2001

Maternal and transplacental pharmacokinetics of cefazolin.

OBJECTIVE: To evaluate the intrapartum pharmacokinetics of cefazolin, including delivery to amniotic fluid (AF) and fetal compartments, and to ascertain that adequate cefazolin concentrations are attained to exceed the mean concentration inhibiting 90% (MIC(90)) of group B streptococcus strains. METHODS: Cefazolin (1 g) was administered intravenously at five separate time intervals (0.5, 1, 2, 4, and 6 hours) before elective cesarean at term to 26 women with intact membranes and with no significant infections or cardiovascular, liver, or renal disease. Samples of maternal blood, cord blood, and AF were obtained at the time of delivery. Exact collection times relative to cefazolin infusion were noted. Amniotic fluid contaminated with blood or meconium was excluded. Cefazolin concentration was measured by high-pressure liquid chromatography. RESULTS: All maternal and cord plasma cefazolin levels, except one, were above the MIC(90) for Streptococcus agalactiae (group B streptococcus). For AF, all cefazolin levels, except two, were above the MIC(90). CONCLUSIONS: Cefazolin concentrations greater than or equal to the MIC(90) for group B streptococcus were attained in nearly all maternal, fetal, and AF samples. This information, together with the knowledge that there is rare resistance of group B streptococcus to cefazolin, supports the use of cefazolin as a better alternative than clindamycin or erythromycin for group B streptococcus prophylaxis in patients with a nonanaphylactic penicillin allergy.

Adult↗

PubMed2002

A pilot study to determine the feasibility of continuous cefazolin infusion.

BACKGROUND: Animal studies have shown that continuous infusion of beta-lactam antibiotics is more effective than intermittent dosing. We studied several dosing regimens of cefazolin in humans to determine safety and whether or not adequate serum and tissue antibiotic concentrations could be achieved in patients undergoing cardiac bypass. METHODS: A prospective, randomized pilot study was conducted at a university-affiliated teaching hospital over a 2-year period in patients undergoing first-time coronary artery bypass grafting. One hundred and thirty-seven patients were randomized to one of three groups. Group 1 (n = 64) received 1 g of cefazolin intravenously before operation and 1 g intravenously at the end of cardiopulmonary bypass. Group 2 (n = 35) received 2 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 20 mg/min throughout surgery. Group 3 (n = 38) received 3 g of cefazolin intravenously before operation, followed by a continuous intravenous infusion of cefazolin at 15 mg/min throughout surgery. Venous blood and subcutaneous fat samples were obtained from the sternal wound in a subset of 34 patients at incision, 0.25 h, 0.5 h, and 1 h; at the end of cardiopulmonary bypass; and at wound closure. Venous blood was sampled in the recovery room and on postoperative day 1. Cefazolin concentrations in the samples were determined by reverse-phase high-performance liquid chromatography using a C18 column. RESULTS: Serum cefazolin concentrations were higher for group 3 when compared with group 1 at all six intraoperative intervals (p < 0.02) and for group 2 when compared with group 1 at four of six intraoperative intervals (p < 0.04). When compared with group 1, tissue cefazolin concentrations were higher for group 3 at all intraoperative intervals (p < 0.02). No related toxicity or adverse events were observed. CONCLUSION: Cefazolin administered as a large preoperative bolus with continuous intraoperative infusion resulted in higher serum and tissue concentrations when compared with conventional intermittent dosing. Pharmacodynamically, continuous infusion of beta-lactam antibiotics may be superior to intermittent dosing when used for perioperative prophylaxis against wound infection, especially for cases in which the antibiotic is not redosed intraoperatively.

Anti-Bacterial Agents↗

PubMedDate not supplied

Influence of peritoneal dialysate flow rate on the pharmacokinetics of cefazolin.

OBJECTIVE: To determine the impact of dialysate flow rate (DFR) on cefazolin pharmacokinetics (PK) in peritoneal dialysis (PD) patients. METHODS: A meta-analysis of published reports, identified by MEDLINE search (1966-2002) and other sources, containing information on cefazolin PK data in PD patients was conducted. Data were analyzed based upon low DFR (< or = 5.50 mL/minute) or high DFR (> 5.50 mL/minute). Data available were from North American (NA) (n = 45) and Singaporean (n = 10) patients. Complete data sets were available for 33 patients (CDS patients). Data were analyzed with respect to data origin and data set completeness: all patients (ALL), NA, and CDS. Analysis of log-transformed cefazolin PK data was performed to determine coefficient of determination (r2) between DFR and cefazolin elimination rate constant (kel), clearance total (ClT), and clearance peritoneal (ClPD). Clearance total data were extrapolated to DFR observed in continuous flow PD. RESULTS: Published literature provided data on 55 PD patients (12 high DFR, 43 low DFR). Regardless of data origin (ALL, NA, or CDS), a prominent coefficient of determination (p < 0.0001) existed between DFR and all cefazolin PK data except ClPD. The p value for DFR correlation to ClPD was 0.953, 0.011, and 0.036 for ALL, NA, and CDS patients, respectively. Cefazolin ClT and ClPD increased at higher DFRs. CONCLUSION: These findings demonstrate that an increased DFR leads to an increased rate of cefazolin clearance in NA PD patients. The impact of Asian descent on cefazolin ClPD warrants further investigation. Clinicians dosing cefazolin in PD patients using a higher DFR than that used to determine cefazolin PK should use increased doses or prescribe lower/comparable DFRs. Data are not yet available for patients prescribed very high DFRs (e.g., continuous flow PD); extrapolation of our results demonstrates significant influences on clearance and risk for underdosing.

Adult↗

PubMedDate not supplied

Stability of cefazolin sodium in four heparinized and non-heparinized dialysate solutions at 38 degrees C.

BACKGROUND: Intraperitoneal administration of antibiotics is often required in the treatment of peritoneal dialysis-associated peritonitis. Extended use and heating may affect drug stability. The objective of our study was to determine the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non-heparinized dextrosecontaining peritoneal dialysis solution (Dianeal PD-2; Baxter Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose, or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38 degrees C for 4 days. METHODS: Three poly-vinyl chloride containers of each dialysis fluid were stored at 38 degrees C for 4 days. Samples were taken after the bags were mixed and allowed to stand for 2 minutes. Two 500-microL samples were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96. Samples were then analyzed by high-performance liquid chromatography (HPLC) in our laboratory. In order to establish the stability-indicating nature of the method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH) hydrolysis, oxidation (H(2)O(2) 0.3%), and heat at 80 degrees C. Samples were analyzed every 30 minutes until approximately 25% of the drug's peak disappeared. The drug was considered stable if its concentration exceeded 90% of the original. RESULTS: For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%, and 4.25% dextrose, cefazolin sodium was considered stable at 38 degrees C for 60 hours at low cefazolin concentrations (125 mg/L), both with and without heparin, and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 48 hours at low cefazolin concentrations in heparinized and non-heparinized solutions, and at high concentrations only in non-heparinized dialysate, not in heparinized dialysate. Cefazolin sodium was considered stable at 38 degrees C in icodextrin for 60 hours at high concentrations when heparinized. CONCLUSION: Cefazolin sodium was stable in all four nonheparinized dialysate fluids for at least 48 hours at 38 degrees C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium were not stable for extended periods of time. Extended use and heating of dialysate containing cefazolin may adversely affect patient outcome.

Cefazolin↗

PubMed1980

[Double-blind comparison of cefamandole and cefazolin in the therapy of respiratory tract infections (author's transl)].

A cooperative study in 46 institutions and clinics in Tohoku and Hoddaido districts in Japan was carried out to compare the efficacy, usefulness and safety of cefamandole and cefazolin in treatment of repiratory tract infections by randomized double blind technique. Two grams of either of the two cephalosporins were given by intravenous drip infusion to the two groups of patients aged over 16 years twice a day for 14 days. Of a total of 232 patients included in the study, 120 patients were treated with cefamandole and 122 patients with cefazolin. Of these patients treated with either of the both drugs, 27 patients were excluded from evaluation for efficacy. All 232 patients were adopted for analysis of side effects. Characteristics of the population, sex and age distribution, severity of infections and infecting organisms before treatment were similar in each treatment group and no statistically significant differences could be found between the two groups. Both groups included nearly equal numbers of patients with underlying diseases or with complications. The patients pre-treated with other antibiotics before the start of the study or treated simultaneously with anti-inflammatory drugs were equally distributed in the both treatment groups. Clinical cure rate was 69.2% in groups of the patients treated with cefamandole, whereas that in cefazolin treatment group was 62.2%. Thus, there was a difference of 7% in clinical cure rate between two treatment groups, though it was not statistically significant. In groups of patients with acute bacterial pneumonia or lung abcess, clinical cure rate with cefamandole was 76.7%, whereas that with cefazolin was 67.7%. Thus, the clinical cure rate was 9% higher in the group of patients treated with cefamandole, though the difference was again statistically not significant. In the group of patients with infections associated with chronic respiratory diseases, cefamandole cured 50% of the patients treated, whereas cefazolin cured 48.1%. Comparison of the curves of cumulative distribution of MICs of cefamandole and cefazolin proved the superiority of cefamandole to cefazolin in antimicrobial activities against strains of various species isolated from the patients in the study. Rate of eradication of potential pathogenic microorganisms was 82.4% in the patients with pneumonia or lung abscess who were treated with cefamandole, whereas that with cefazolin was 83.3%. Taking efficacy and adverse effects into consideration, usefulness of the two cephalosporins in the treatment of respiratory tract infections was evaluated by doctors in charge. In 33.3% of patients treated, cefamandole was evaluated as quite useful in the treatment of pneumonia or lung abscess. In contrast, cefazolin was evaluated as quite useful in only 18.3% of patient treated. This difference was statistically significant (P smaller than 0.1). In treatment of patients with infections associated with chronic respiratory disease, cefamandole and cefazolin were evaluated as quite useful or useful in 53.1% and in 51...

Adult↗

PubMed1980

Seizures associated with high cerebrospinal fluid concentrations of cefazolin.

Three cases of generalized seizures in patients with high cerebrospinal fluid (CSF) concentrations of cefazolin are reported. Patient 1, a 60-year-old woman with impaired renal function and a Klebsiella pneumoniae infection, was treated with 70 mg every eight hours of i.v. gentamicin sulfate and 1.5 g every four hours of i.v. cefazolin sodium. Gentamicin was discontinued on day 11. On day 12, the patient had a generalized tonic-clonic seizure. Serum and CSF concentrations of cefazolin one day later were 470 and 64 micrograms/ml, respectively. Patient 2, a 70-year-old man with impaired renal function, was given i.v. cefazolin, 1 g every 12 hours; the dosage interval was shortened later to every six hours. Two days later, the patient had two tonic-clonic seizures. Serum and CSF concentrations eight hours after the last dose of cefazolin were 360 and 34 micrograms/ml, respectively. Patient 3, a 67-year-old woman with renal vein thrombosis, received 55 mg every eight hours of i.v. gentamicin and 2 g every six hours of i.v. cefazolin. The antibiotics were discontinued after eight days when the patient had two tonic-clonic seizures. Serum and CSF concentrations of cefazolin measured 28 hours later were 1000 and 106 micrograms/ml, respectively. Previous reports of cefazolin-associated seizures are reviewed. In patients with renal failure, cefazolin may obtain high CSF concentrations. To avoid seizures, cefazolin doses should be adjusted in these patients.

Aged↗

PubMedDate not supplied

Pharmacokinetics of cefazolin administered as a new drug delivery system in healthy volunteers.

A study was made of the pharmacokinetic behaviour in plasma and urine of cefazolin in seven healthy volunteers following parenteral administration of sodium cefazolin (1250 mg) and a sustained release formulation containing sodium cefazolin: cefazolin-dibenzylamine (1:4) at a total dose of 1250 mg, both formulations being administered over 1 week by the i.m. route. Cefazolin concentrations in plasma and urine were determined by a HPLC technique. Kinetic analysis of the experimental results was performed using an open single-compartment kinetic model and a sustained release model for the drug administered as standard formulation and the sustained release formulation, respectively. The results obtained point to significant variations in the pharmacokinetic profile of the drug when administered in the DDS. The time of cefazolin at levels greater than 1 microgram ml-1 was 16.03 +/- 2.51 and 47.76 +/- 14.18 h-1 after administration of the standard formulation and the DDS, respectively. The urinary excretion rate curves also show the existence of sustained drug levels in the urine following administration of the DDS. The renal clearance of the drug did not show statistically significant differences between the two formulations administered. The process of release of cefazolin from the cefazolin-dibenzylamine complex proved to be a first order kinetic process. The release constant of the antibiotic was calculated according to three different methods: the Wagner-Nelson method; the statistical moments method; and the fitting of the plasma levels curves to a compartmental model considering release and absorption. The values obtained for this constant ranges from 0.026 +/- 0.02 h-1 calculated with the method of statistical moments to 0.094 +/- 0.03 h-1 as calculated by the equation derived for the plasma fitting of cefazolin administered as DDS.

Adult↗

PubMed2003

Cefazolin does not accelerate gastric emptying in the critically ill.

OBJECTIVE: To evaluate the effect of intravenous cefazolin on gastric emptying measured by the C-13 octanoic acid breath test. DESIGN: Prospective, double-blind, cross-over, randomised, placebo-controlled trial. SETTING: Mixed multidisciplinary intensive care unit in a university hospital. PATIENTS: Fourteen critically ill, mechanically ventilated patients. INTERVENTIONS: After a 4-h fast patients received either 50 mg cefazolin or 20 ml saline over 20 min immediately prior to measurement of gastric emptying. The next day the study was repeated with the alternative therapy. MEASUREMENTS AND RESULTS: Breath samples were analysed for the concentration of (13)CO2 by mass spectrometer, and the gastric emptying coefficient (GEC) and half-emptying time (t(50)) were calculated. Results are mean (standard deviation). Data were analysed with the paired t-test (saline vs cefazolin). Two patients were excluded for technical problems. Twelve patients remained (six male/six female), aged 57 (+/-16) years, with an APACHE II score of 20 (+/-8). Both GEC and t(50) were unchanged after administration of cefazolin compared with placebo (t(50) cefazolin, 138 (+/-54) vs saline 122 (+/-46) min, P=0.32; GEC cefazolin 3.27 (+/-0.83) vs saline 3.55 (+/-0.6), P=0.24). Two patients had abnormal t(50) after saline and five after cefazolin. There was no order effect of the study day. CONCLUSION: In mechanically ventilated patients, cefazolin had no effect on gastric emptying. These data do not support the use of low-dose cefazolin as a pro-kinetic agent in critically ill patients.

Adult↗

PubMed1980

Application of cephalosporins to obstetrics and gynecology: transfer of cefazolin and cephalothin to uterine tissue.

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In tthe perimetrium, levels were 154 microgram/gm for cefazolin and 24.1 microgram/gm for cephalothin; in the myometrium, 109.5 microgram/gm for cefazolin, and 15.5 microgram/gm for cephalothin; and in the endometrium, 98.9 microgram/gm for cefazolin and 10.4 microgram/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 microgram/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40-70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.

Adult↗

PubMed1988

Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs.

This paper describes the protein binding of cefazolin to human serum and to human serum albumin (HSA) using equilibrium dialysis. The drug is exclusively bound to HSA with a moderate affinity, Ka = 16,600 +/- 1600 M-1, and one saturable binding site, n = 0.73 +/- 0.02. Moreover cefazolin shows a dose-dependent binding leading a possible increase of the free fraction (when its total concentration increases). This antibiotic is displaced by free fatty acids (FFA) and bilirubin. Cefazolin binding to human serum and human serum albumin (HSA) was studied in presence of acidic drugs. At low concentrations clofibric acid and phenylbutazone both exhibiting high affinity for HSA displace strongly cefazolin. Valproic and salicylic acids, sulfamethoxazole, cefoperazone which have approximately the same affinity as cefazolin, must be used at higher concentrations to displace this antibiotic. A particular phenomenon was observed with cefazolin on HSA when associated with furosemide. A low concentration (5-25 microM) of this drug induces a positive cooperativity of binding between cefazolin and HSA. But at a molar ratio of furosemide to albumin greater than one, such cooperative interaction disappears and a competitive inhibition of cefazolin binding occurs. For all drugs studied, a competitive inhibition was found except for tryptophan. Finally, it is concluded that cefazolin shares the warfarin binding site on HSA.

Bilirubin↗

PubMed2001

Cefazolin dialytic clearance by high-efficiency and high-flux hemodialyzers.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Adult↗

PubMed2001

Another look at differences in the susceptibility of Escherichia coli and Klebsiella pneumoniae to cephalothin and cefazolin.

The significance of in vitro susceptibility tests on Enterobacteriaceae to cephalothin and cefazolin has not been exactly defined in the guidelines of the National Committee for Clinical Laboratory Standards. In the hope of clarifying this confusion, we provide additional information from an ancillary study of the Taiwan Surveillance of Antimicrobial Resistance 1998 (TSAR I). There were 505 Escherichia coli and 227 Klebsiella pneumoniae isolates susceptible to cephalothin, reported by 42 participating hospitals. The susceptibility of these isolates were re-tested at the Microbial Infections Reference Laboratory using cefazolin, with the result that 72% of the 252 cephalothin-resistant E. coli isolates and 24% of the 41 cephalothin-resistant K. pneumoniae isolates were found to be susceptible to cefazolin. We further surveyed the availability of cephalothin and cefazolin in Pharmacy Departments; all of the TSAR I hospitals had cefazolin available in their pharmacies. The resistance rate of E. coli was significantly lower for 12 hospitals that had cefazolin in both pharmacy and laboratory compared with 11 hospitals that had cefazolin available in pharmacy but cephalothin in laboratory. In addition, for all the hospitals that had cephalothin available for clinical use, the resistance rate was twice as low in two hospitals reporting cefazolin susceptibility as in the seven hospitals reporting cephalothin susceptibility. Our findings suggest that inappropriate selection of cephalothin and cefazolin for susceptibility testing contribute to inaccurate indications of in vivo activity for first generation cephalosporins in the treatment of E. coli infections.

Cefazolin↗

PubMed1998

Efficacy and pharmacokinetics of site-specific cefazolin delivery using biodegradable implants in the prevention of post-operative wound infections.

PURPOSE: The study objective was to evaluate the efficacy and pharmacokinetics of cefazolin delivered locally as a glyceryl monostearate (GMS) based biocompatible implant for prevention of post-operative wound infection in Sprague Dawley rats subcutaneously inoculated with Staphylococcus aureus. METHODS: For the efficacy and pharmacokinetic studies, 18 rats were subcutaneously inoculated with 4.5 x 10(7) CFU of S. aureus on the dorsum (6 per rat), and randomly assigned into three group of 6 rats each: (1) the control group, in which rats did not receive antibiotics, (2) the intermittent i.m. treatment group, in which rats received i.m. injections of 10 mg/kg cefazolin every 4 hr (total of 180 mg/kg in 3 days), and (3) the implant treatment group, in which rats were implanted subcutaneously with four Cefazolin-GMS implants in the vicinity of the inoculations. The implants were designed to deliver 180 mg/kg cefazolin over a 3 day period. For efficacy evaluation, the rats were euthanized one week post-inoculation and abscess count, weight and size were determined. RESULTS: Rats in the control group had developed 21 abscesses out of the 36 inoculations, indicating validity of the infection model. The local delivery of cefazolin resulted in complete eradication of the infection, since no abscesses formed in the rats in the implant group. In the IM treatment group, only one abscess was formed and no significant difference in efficacy between the two treatment groups was observed. The GMS implants sustained the release of cefazolin for a period of three days with only 3-fold fluctuations in plasma concentration (5.5-17.5 micrograms/ml). However, plasma concentrations after the intermittent IM administration of cefazolin fluctuated 110-fold between 44-0.4 micrograms/ml every 4 hr. The release rate of cefazolin from the implants was nearly zero order for the entire duration. Bioerosion of the implants was determined by examining the condition of the implants six weeks post-implantation. Two of the 12 implants had completely disappeared and the remaining implants were in a pasty form and had lost 20-80% of their weight. Absence of irritation or inflammation around the implants indicated biocompatibility of the GMS implants. CONCLUSIONS: Implantable system that provided a prolonged delivery of cefazolin was found to be effective against S. aureus infection, and demonstrated suitable pharmacokinetics and biocompatibility with significant bioerosion.

Animals↗

PubMed1992

Cefuroxime versus cefazolin as prophylaxis in vascular surgery.

Although cefazolin prophylaxis has proven efficacy in vascular surgery, Staphylococcus aureus wound infections are still an important postoperative complication. In cardiac surgery, cefazolin's susceptibility to hydrolysis by staphylococcal beta-lactamase has been proposed to account for some prophylaxis failures. To determine whether the incidence of vascular wound infections can be reduced by administering a more beta-lactamase-stable cephalosporin, we undertook a prospective, randomized trial of cefuroxime versus cefazolin. Cefuroxime was administered as a 1.5 gm dose before operation and 750 mg every 3 hours during operation. Cefazolin was given as 1 gm before operation and 500 mg every 4 hours during operation. Both agents were continued every 6 hours after operation for 24 hours. Deep wound infections developed in seven of 272 (2.6%) cefuroxime and three of 287 (1.0%) cefazolin recipients (p = 0.2). Staphylococcus aureus wound infections occurred in five cefuroxime versus two cefazolin recipients. In vitro evaluation of six of the study isolates plus an additional eight S. aureus strains from vascular wound infections showed greater susceptibility of the strains to cefazolin than cefuroxime (median minimal inhibitory concentrations of 0.5 and 2.0 micrograms/ml, respectively, p less than 0.05). Furthermore, despite its more frequent intraoperative redosing, cefuroxime exhibited lower trough serum concentrations than cefazolin. Among cefuroxime recipients, infection-associated procedures were significantly longer than infection-free procedures (p less than 0.05), suggesting that low tissue antibiotic concentrations may have contributed to the pathogenesis of these infections. In contrast, the length of the procedure was not a risk factor for infection among cefazolin recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefazolin↗

PubMed1984

Effects of furosemide, piretanide, and water loading on urinary excretion of cefazolin in humans.

Antibiotics and diuretics are often prescribed concomitantly for humans. We compared the effects of two potent loop diuretics, furosemide and piretanide, with those of water loading on the urinary excretion of cefazolin. During a continuous infusion of inulin and cefazolin (10 mg/kg per h), six healthy male volunteers received a single intravenous injection of furosemide (0.3 mg/kg) or piretanide (0.1 mg/kg) or again an oral water load of 15 ml/kg over a 20-min period. In vitro, furosemide at all concentrations tested significantly reduced by about 10% the percentage of cefazolin bound to serum proteins. Piretanide exhibited such an effect only at a concentration of 2 micrograms/ml. Furosemide, piretanide, and water loading significantly and similarly increased the ratio of excreted to infused cefazolin up to 2 h after the injection of diuretic or after oral water intake. In each of the three parts of the experiment, the increase of the urinary flow rate was similar when compared with the control values. Furosemide significantly increased the cefazolin filtered load during the same time. Piretanide significantly enhanced the absolute rate of net cefazolin tubular secretion. Water loading increased the urinary excretion of cefazolin, probably through a reduction in tubular reabsorption. These results suggest that (i) furosemide and piretanide as well as water loading are capable of enhancing renal excretion of cefazolin by different complex mechanisms; (ii) cefazolin undergoes a bidirectional tubular transport; (iii) piretanide might act on the proximal tubule in addition to its main site of action on Henle's loop; and (iv) the effects of both diuretics and of water loading are unlikely to affect in vivo antibiotic activity in humans.

Adult↗

PubMed2005

Pharmacokinetics of intraperitoneal cefazolin and ceftazidime coadministered to CAPD patients.

PURPOSE: Guidelines for empiric treatment of PD-related peritonitis published in 2000 recommend concurrent intraperitoneal (IP) cefazolin and ceftazidime. The pharmacokinetics (PK) of these agents combined have not been studied. This study was designed to determine the PK of combined IP cefazolin and ceftazidime in CAPD patients. DESIGN: Prospective PK study in seven non-infected CAPD patients. PROCEDURES: Patients had a peritoneal equilibration test (PET), then received one IP dose of cefazolin and ceftazidime (15 mg/kg each) co-administered over a 4-hour dwell, then performed three CAPD exchanges over the next 16 hours. Serum and dialysate samples collected over the 20-hour study period were assayed for drug concentrations by HPLC. OUTCOME MEASURES: PK parameters. STATISTICAL METHODS: Correlations were tested between PET and PK parameters using the Pearson-product correlation coefficient. MAIN FINDINGS: Serum cefazolin and ceftazidime levels exceeded the minimum inhibitory concentrations for susceptible organisms (8 mg/L) throughout the 20 hour study period. Mean cefazolin and ceftazidime PK parameters included: bioavailability, 71% and 63%; elimination rate constant, 0.031 and 0.045 h -1 ; total clearance, 5.8 and 16.0 ml/min; peritoneal clearance, 1.6 and 3.9 ml/min; renal clearance, 2.3 and 3.9 ml/min, respectively. Predictive equations suggest that 1000 mg IP of cefazolin and of ceftazidime every 24 hours would produce average steady-state trough serum cefazolin and ceftazidime concentrations of 70 +/- 52 mg/L and 17 +/- 7 mg/L, respectively. There was no correlation between PET and PK parameters. CONCLUSIONS: Co-administration did not adversely affect the PK of either agent. IP cefazolin and ceftazidime (15 mg/kg) produced adequate serum and dialysate concentrations in CAPD patients for 20 hours. PK predictions suggest that most patients would achieve adequate cefazolin and ceftazidime concentrations with 1000 mg IP once-daily. Anuric patients and those with significant residual renal function may require a more individualized approach.

Adult↗

PubMed2004

Once-daily cefazolin and probenecid for skin and soft tissue infections.

OBJECTIVE: To review the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections (SSTI). DATA SOURCES: MEDLINE (1966-July 2003), EMBASE (1980-July 2003), and PubMed (1966-July 2003) databases for English language, human reports were searched. Search terms included cefazolin, probenecid, cellulitis, and soft tissue infections. STUDY SELECTION AND DATA EXTRACTION: Studies that described pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in conjunction with probenecid for SSTI were included. All studies were evaluated independently by both authors. For pharmacokinetic studies, the effect of probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical trials, efficacy and safety endpoints were evaluated. For efficacy endpoints, definition of cure was used as defined by each trial. DATA SYNTHESIS: In all 3 pharmacokinetic studies identified, the addition of probenecid to cefazolin therapy prolonged the half-life and increased serum concentrations of cefazolin. This process allowed serum concentrations to be above the minimal inhibitory concentrations (MIC) for the most likely skin pathogens (Staphylococcus aureus, beta-hemolytic streptococci) at the end of the dosing interval. In the first of 2 clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of 98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In the second clinical trial, clinical success was reported in 51 (86%) of 59 patients receiving the same doses of cefazolin and probenecid as above compared with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral placebo daily. CONCLUSIONS: Limited pharmacokinetic and clinical data suggest that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective regimen in the treatment of SSTI.

Anti-Bacterial Agents↗

PubMed1996

Effect of intraoperative blood loss on the serum level of cefazolin in patients managed with total hip arthroplasty. A prospective, controlled study.

The effect of intraoperative blood loss on serum levels of cefazolin in patients being managed with total hip arthroplasty was studied. Eighteen patients, thirteen men and five women, with a mean age of sixty-five years (range, forty to eighty-five years) were enrolled in the study. Fifteen had a primary total hip arthroplasty and three, a revision. Each patient served as his or her own control. Baseline clearance of cefazolin was determined at a minimum of forty-eight hours before the operation. Each patient received one gram of cefazolin intravenously. Serial serum concentrations were determined from specimens drawn at zero, five, ten, twenty, thirty, sixty, 120, 240, and 300 minutes after administration. Fifteen minutes before the skin incision was made, each patient again received one gram of cefazolin intravenously. Serum samples were collected at the same time-intervals, and the serum levels of cefazolin were determined with use of capillary electrophoresis. Data regarding intraoperative blood loss as well as replacement of fluid and blood were recorded. The administration of the antibiotic, retrieval of the serum samples, and estimation of the blood loss were performed by the same person in the same manner for all patients. The preoperative and intraoperative creatinine clearances (mean and standard deviation), estimated with use of the formula of Cockcroft and Gault, were 62.06 +/- 21.28 and 74.02 +/- 24.75 milliliters per minute, respectively. The amount of intraoperative blood loss averaged 1137 +/- 436 milliliters (range, 675 to 2437 milliliters). The preoperative and intraoperative cefazolin clearances averaged 0.49 +/- 0.21 and 0.52 +/- 0.30 milliliter per minute per kilogram, respectively. During joint replacement, the commonly accepted interval between doses of cefazolin is four hours. In the present study, the serum level of cefazolin at four hours was forty-five micrograms per milliliter. This corresponds to an osseous concentration that well exceeds the minimum inhibitory concentration for Staphylococcus aureus, which is 0.5 microgram per milliliter. This study suggests that, with blood losses of less [corrected] than 2000 milliliters, it is not necessary to administer cefazolin at intraoperative intervals of less than four hours in order to maintain a concentration of antibiotics that is higher than the minimum inhibitory concentration for the most common infecting organisms.

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