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Double-blind randomized comparison of single-dose ciprofloxacin versus intravenous cefazolin in patients undergoing outpatient endourologic surgery.

OBJECTIVES: To compare the efficacy of single-dose oral ciprofloxacin with intravenous cefazolin as a prophylactic agent in patients undergoing outpatient endourologic surgery. METHODS: One hundred patients were enrolled in a double-blind, randomized study to receive either ciprofloxacin (500 mg) or cefazolin (1 g) before surgery. A postoperative clinical evaluation and urine cultures were performed 5 to 10 days after surgery. Patients undergoing ureteral stent insertion or exchange, ureteroscopy, bladder biopsy, retrograde pyelography, collagen injection, and internal urethrotomy were included. RESULTS: Postoperative urinary tract infection occurred in 7 (9.1%) of 77 patients, including 3 (8.1%) of 37 and 4 (10.0%) of 40 of those who received ciprofloxacin and cefazolin, respectively (P = 0.77). There were no episodes of sepsis, and no patient with infection required hospitalization. The total cost associated with the administration of prophylactic antibiotics in the study population was $3657 less in those 50 patients who received ciprofloxacin than in the 50 patients who received cefazolin. CONCLUSIONS: A single oral dose of ciprofloxacin in patients undergoing outpatient endourologic surgery was equally effective as cefazolin in preventing postoperative urinary tract infection, but was associated with markedly lower overall costs.

Adult↗

Randomised clinical trial of perioperative cefazolin in preventing infection after hysterectomy.

To determine the efficacy of perioperative cefazolin in preventing pelvic and wound infections after elective non-radical hysterectomy, a randomised, placebo-controlled, double-blind clinical trial was done. Among 86 patients undergoing vaginal hysterectomy, those who received three perioperative 1 g doses of cefazolin (44) had significantly fewer pelvic infections (21% vs. 2%); less standard febrile morbidity (31% vs. 14%); shorter length of stay (LOS); and fewer courses of antibiotics postoperatively. There was no reduction in rate of urinary-tract infection (UTI) (21% vs. 23%). Among 429 women having abdominal hysterectomy, the 206 who received cefazolin had significantly lower rates of wound and pelvic infections (21% vs. 14%), UTI (21% vs. 9%), and febrile morbidity (20% vs. 14%). They also had shorter LOS and received fewer courses of antibiotics postoperatively. Use of perioperative cefazolin was not accompanied by more side-effects. Three doses of perioperative cefazolin seem to be safe, efficacious, and cost-effective in preventing infection after vaginal or abdominal hysterectomy.

Adult↗

Ceftriaxone versus cefazolin with probenecid for severe skin and soft tissue infections.

To evaluate the hypothesis that a single daily administration of cefazolin and probenecid and a single daily administration of ceftriaxone and probenecid would be equally effective, in combination with oral antibiotics, for the outpatient treatment of skin and soft tissue infections, a randomized, double-blind study was completed. Patients presenting to the Emergency Department with the primary diagnosis of cellulitis or soft tissue infection, excluding patients requiring immediate hospital admission, received either 2 g of ceftriaxone or 2 g of cefazolin, each with 1 g of probenecid, on a daily basis as outpatients from the Emergency Department. The patients were given a prescription for oral penicillin and cloxacillin for independent procurement. Outcome was assessed based on reduction in the size of the infected area, and the need for additional treatment (other antibiotics or hospital admission). A total of 194 patients were randomized to receive ceftriaxone (96) or cefazolin (98). There was no statistical difference in cause of infection, site of infection, duration of treatment, noncompliance or need for incision or drainage of the wound. The outcome, as determined by the ratio of the involved infected area on initial and last treatment day, and the frequency of failure were similar. The single daily administration of 2 g of either cefazolin, in combination with probenecid, or ceftriaxone are equivalent in efficacy in the outpatient treatment of skin and soft tissue infections. There is the potential for significant cost savings in utilizing outpatient cefazolin therapy over ceftriaxone for treatment of these infections.

Ambulatory Care↗

Comparison of topical 0.3% ofloxacin with fortified tobramycin plus cefazolin in the treatment of bacterial keratitis.

PURPOSE: Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular penetration. We compared ofloxacin 3% solution with a combination of fortified tobramycin sulphate and cefazolin sodium solutions in the treatment of culture-proven bacterial keratitis. METHODS: Thirty eyes with culture-proven bacterial corneal ulcers were enrolled in a prospective randomised, controlled, double-masked study for comparison. The ofloxacin drop and saline were decanted into two identical-looking bottles to the tobramycin and cefazolin. The cases were randomly allocated into treatment with 0.3% ofloxacin solution or a combination of fortified antibiotics (1.5% tobramycin and 10% cefazolin solutions; control group) along with supportive cycloplegic, vitamins and anti-glaucoma therapy. Student's t-test was used to compare the results. RESULTS: Staphylococcus aureus and coagulase-negative staphylococci were the two most common organisms isolated. Resolution of the ulcer was achieved in 93% and 87% of cases in the ofloxacin and control groups respectively. The mean time required for symptomatic relief was 7.8 +/- 1.54 days and for epithelial healing 15.0 +/- 3.86 days in ofloxacin group, compared with 8.33 +/- 1.54 days for symptomatic relief and 15.46 +/- 3.86 days for epithelial healing in the control group. Post-resolution best corrected visual acuity of 20/200 or better was achieved in all but one eye in both groups. CONCLUSIONS: Ofloxacin and combined fortified tobramycin and cefazolin topical drops were comparable for treating cases of bacterial corneal ulcer. However, considering its easy availability and cost-effectiveness, monotherapy with ofloxacin is preferred over the combined fortified tobramycin and cefazolin therapy.

Adolescent↗

Stability of cefazolin sodium eye drops.

OBJECTIVE: Assessing the stability of cefazolin sodium in preservative-free and preservative-containing eye drops. METHOD: Extemporaneous formulations of eye drops were prepared from a commercially-available parenteral product of cefazolin sodium: eye drops 'A' contained 50mg/ml of cefazolin sodium in 0.45% w/v sodium chloride solution, and eye drops 'B' contained 50 mg/ml, 0.005% w/v thiomersal and 1% w/v glycerol in water-for-injection. Cefazolin sodium concentrations in these eye drops were monitored by a stability-indicating HPLC assay method. Measurements of pH and osmolality, as well as tests for microbial contamination, were conducted. RESULTS: The eye drops stored at 4 degrees C were stable for 42 days with minimal changes in pH and osmolality, but eye drops stored at room temperature were only stable for a few days with greater increments in pH and osmolality. None of the samples cultured had bacterial or fungal growth after 7 days of incubation. CONCLUSION: Extemporaneously prepared formulations of cefazolin are unstable at room temperature and should be stored in a refrigerator.

Bacteriological Techniques↗

Antibiotic prophylaxis with cefazolin and gentamicin in cardiac surgery for children less than ten kilograms.

OBJECTIVE: Antibiotic prophylaxis is recommended in pediatric cardiac surgery, but no data concerning the current antibiotic regimen were available. DESIGN: Prospective study from April to June 2000. SETTING: University hospital operating room and postoperative intensive care unit. PARTICIPANTS: Nineteen consecutive infants less than 10 kg with normal renal function undergoing cardiac surgery with cardiopulmonary bypass longer than 30 minutes. INTERVENTIONS: Intravenous administration of cefazolin, 40 mg/kg, and gentamicin, 5 mg/kg, at induction of anesthesia; followed by cefazolin, 35 mg/kg every 8 hours, and gentamicin, 2 mg/kg every 12 hours, over 48 hours. MEASUREMENTS AND MAIN RESULTS: Levels of serum antibiotics were measured: cefazolin (microbiologic) and gentamicin (fluorescence immunoassay) with 8 intraoperative and 5 postoperative samplings. Intraoperatively, cefazolin levels decreased from 166 +/- 44 (mean +/- standard deviation) down to 54 +/- 16 microg/mL and gentamicin from 20.8 +/- 9.5 down to 5.9 +/- 1.5 microg/mL. The postoperative trough levels were 12 +/- 7, 15 +/- 10, and 19 +/- 22 microg/mL for cefazolin and 1.1 +/- 0.5, 0.8 +/- 0.4, and 0.8 +/- 0.9 microg/mL for gentamicin. CONCLUSIONS: Antibiotic serum levels are consistent with satisfactory efficacy, but intraoperative gentamicin peak levels appeared too high.

Anti-Bacterial Agents↗

Relapse of type A beta-lactamase-producing Staphylococcus aureus native valve endocarditis during cefazolin therapy: revisiting the issue.

Our experience with a patient with methicillin-susceptible Staphylococcus aureus aortic native valve endocarditis, who had a relapse involving fever and positive blood culture results while receiving cefazolin, led us to evaluate this organism's ability to hydrolyze cefazolin at high inocula, a previously well-documented phenomenon. Analysis of the infecting strain disclosed a high minimum inhibitory concentration of cefazolin when a large inoculum was used, as well as rapid and complete cefazolin degradation, which was associated with regrowth in a time-kill experiment. DNA sequencing of the beta-lactamase gene showed that it was identical to that of the S. aureus type A beta-lactamase, known to efficiently inactivate cefazolin. A word of caution is given regarding the use of this antibiotic for treatment of endocarditis caused by this type of S. aureus isolate.

Anti-Bacterial Agents↗

Cefoxitin versus erythromycin, neomycin, and cefazolin in colorectal operations. Importance of the duration of the surgical procedure.

Perioperative parenteral cefoxitin was compared with oral erythromycin, neomycin and parenteral cefazolin in a prospective, double-blind, randomized evaluation of 119 patients undergoing colorectal operations. Patients receiving cefoxitin had a higher wound infection rate than patients receiving erythromycin-neomycin-cefazolin (12.5% v 3.2%, respectively, p = .06). A direct correlation existed between the duration of the operation and the infection rate. Cefoxitin prophylaxis was as effective as erythromycin-neomycin-cefazolin in patients undergoing surgical procedures of 4 hours or less (infection rates of 4.8% and 4.0%, respectively). However, for surgical procedures lasting more than 4 hours, 5 of 14 patients (37.5%) receiving cefoxitin developed a wound infection v 0 of 13 patients receiving erythromycin-neomycin-cefazolin (p less than .05). It is speculative as to whether frequent two-gram doses of cefoxitin given during the operation would provide prophylaxis equivalent to erythromycin-neomycin-cefazolin.

Cefazolin↗

Intravenous cefazolin in penetrating eye injuries. Treatment of experimental posttraumatic endophthalmitis.

The use of intravenous antibiotics as prophylaxis in penetrating eye injuries is strictly empiric and not based on scientific data supporting their use. To determine the efficacy of prophylactic intravenous cefazolin in penetrating eye injuries, a rabbit model of posttraumatic endophthalmitis was developed. Forty rabbits received penetrating eye injuries followed immediately by an intravitreal inoculum of live Staphylococcus epidermidis. The rabbits then were randomly divided into four groups: group 1 received three doses of intravenous cefazolin; group 2 received six doses, and group 3 received nine doses; group 4 received no treatment and served as controls. All control rabbits developed 4+ vitreitis; rabbits receiving three doses of the antibiotic developed 2+ vitreitis, and those receiving six or nine doses of cefazolin showed no vitreous inflammation (P < or = 0.0001). Histologic examination of control eyes showed an exuberant reaction with formation of retrolental membranes, vitreous abscess, and retinal detachment. Eyes treated with nine doses of cefazolin were devoid of inflammatory cells. These findings suggest that intravenous cefazolin is effective in preventing the development of posttraumatic endophthalmitis in a rabbit model.

Animals↗

Intravenous cefazolin in penetrating eye injuries. A swine model.

PURPOSE: A swine model of penetrating ocular trauma was used to determine the delivery of systemically administered cefazolin to the vitreous cavity of traumatized and nontraumatized eyes. METHODS: Thirty-one pigs received a scleral laceration to the right eye under anesthesia and then were given intravenous cefazolin every 8 hours. Seven pigs received nine doses at 17 mg/kg. Seven animals received three doses of 36 mg/kg, and six others received nine doses of this regimen. Six pigs received three doses of 79 mg/kg and five others received three doses of 190 mg/kg. RESULTS: Vitreous levels of cefazolin averaged 15.6 micrograms/mL in traumatized eyes but were less than 1 microgram/mL in control eyes of animals receiving three doses at 190 mg/kg (P < or = 0.025). Mean serum concentration in these animals was 49.3 micrograms/mL. Vitreous levels were less than 1 microgram/mL in traumatized and control eyes in animals given lower doses of cefazolin (range, 17-79 mg/kg) despite multiple treatments over 2 and 3 days. CONCLUSIONS: These data demonstrate that systemically delivered cefazolin achieves levels ten times the minimum inhibitory concentration for Staphylococcus epidermidis in injured eyes. Therapeutic intraocular levels can be obtained through intravenous dosing, provided that therapeutic serum concentrations are achieved.

Animals↗

Human intradiscal levels with cefazolin.

The administration of prophylactic antibiotics for the prevention of discitis is common in the field of spinal surgery. The purpose of this study was to determine 1) whether cefazolin administered intravenously would result in detectable intradiscal levels; and 2) if so, what the proper timing of the antibiotic bolus should be to achieve optimal intradiscal concentrations. Forty human lumbar discs were obtained during the study period. All subjects received a preoperative bolus infusion of 2 g of cefazolin during a 3-5 minute period. Serum and intradiscal samples were obtained at intervals ranging from 6 to 220 minutes after the antibiotic infusion. The respective intradiscal concentrations of cefazolin were then determined, and the findings were as follows: 1) cefazolin does diffuse into the human disc in detectable concentrations; and 2) a critical time relationship exists (15-80 minutes after a bolus administration of cefazolin) for the optimal level of intradiscal antibiotics to be achieved.

Cefazolin↗

The use of intradiscal antibiotics for discography: an in vitro study of gentamicin, cefazolin, and clindamycin.

STUDY DESIGN: In vitro determination of minimum inhibitory concentrations (MICs) of gentamicin, cefazolin, and clindamycin, alone and in combination with iohexol against laboratory strains of Eschericia coli B, Staphylococcus aureus, and Staphylococcus epidermidis. OBJECTIVE: To study the effects of iohexol on the efficacy of gentamicin, cefazolin, and clindamycin. SUMMARY OF BACKGROUND DATA: Prophylactic antibiotics have been advocated to prevent discitis following discography. Intravenous cefazolin administered before discography has been shown to penetrate the intervertebral disc. However, the use of systemic antibiotics for prophylaxis may lead to bacterial resistance. Intradiscal antibiotic administration is an attractive alternative to systemic antibiotic prophylaxis before discography, but there is no data documenting the efficacy of commonly used antibiotics in the presence of iohexol. METHODS: MICs were determined by adding standard concentrations of bacteria to serial dilutions of antibiotic with and without the addition of iohexol in Todd-Hewitt Broth medium. MICs were determined as the lowest concentration well that demonstrated inhibition of cell growth. RESULTS: Gentamicin, cefazolin, and clindamycin remain efficacious in the presence of iohexol. MICs were lower for cefazolin and gentamycin than for clindamycin. Iohexol alone also demonstrated some inhibition of cell growth. CONCLUSION: This study supports the use of intradiscal antibiotics for prophylaxis of disc space infection during discography. lntradiscal placement of antibiotic should obviate the need for systemic antibiotic prophylaxis and its attendant risk of generating antimicrobial resistance.

Anti-Bacterial Agents↗

Prospective randomized comparison of single-dose versus 1-day cefazolin for prophylaxis in gynecologic surgery.

BACKGROUND: The purpose of this prospective, randomized study was to compare the efficacy of single-dose versus 1-day cefazolin prophylaxis for the prevention of postoperative gynecologic infections. METHODS: From June 2001 to January 2003, 548 patients were randomized to receive either single-dose (1 g of cefazolin intravenously before surgery, 273 patients) or 1-day cefazolin (1 g intravenously before surgery and three more doses every 6 hr after surgery, 275 patients) prophylaxis. RESULTS: A total of 531 (267 patients in the single-dose group and 264 in the 1-day group) completed the study. Only one of 267 (0.37%) patients in the single-dose group developed a trocar wound infection and one of 264 (0.37%) patients in the 1-day group developed a vaginal cuff infection. Had a single dose of prophylactic antibiotics been administered to all patients, the antibiotic cost would have been reduced by 75-80%. CONCLUSIONS: The use of single-dose preoperative cefazolin prophylaxis was as effective as four doses of cefazolin for preventing serious infectious morbidity among our patients. Shortening the duration of antibiotics prophylaxis also reduced medical costs and microorganism resistance.

Adult↗

Effects of cephalothin, cefazolin, and cefmetazole on the hemostatic mechanism in normal dogs: implications for the surgical patient.

Twenty-six female beagles were used to evaluate the effects of intravenous and long-term subcutaneous administration of cephalothin, cefazolin, and cefmetazole on platelet function and the coagulation cascade. Platelet aggregation in response to an adenosine diphosphate (ADP) agonist, bleeding time, platelet count, platelet size, prothrombin time (PT), and activated partial thromboplastin times (aPTT) were evaluated before and 90 minutes after two intravenous doses (22 mg/kg) of cephalothin, cefazolin, and cefmetazole given at 90-minute intervals. Dogs given saline injections were used as controls. Platelet count, platelet size, PT, and aPTT were evaluated after 7 days of subcutaneous administration of saline, cefazolin, and cefmetazole (22 mg/kg every 8 hours). A significant decrease in platelet aggregation in response to ADP was detected 90 minutes after intravenous administration of cephalothin. Bleeding time was increased significantly 90 minutes after intravenous administration of cefmetazole. Platelet size was decreased significantly 24 hours after onset of the study in all animals, including controls. No significant changes in platelet count, platelet size, PT, or aPTT were detected after 7 days of subcutaneous administration. Cefazolin had no adverse effects on platelet aggregation in response to ADP, bleeding time, platelet count, platelet size, PT, or aPTT. Therefore, cefazolin should be considered as a perioperative antibiotic in dogs with conditions predisposing to hemostatic complications.

Animals↗

Cephalothin and cefazolin in vitro antibacterial activity and pharmacokinetics in dogs.

The periods of time that cephalothin and cefazolin serum concentration remained above minimum inhibitory concentration (MIC) for beta hemolytic, coagulase positive staphylococcal, and Escherichia coli clinical isolates were compared. Cephalothin and cefazolin were similarly very effective in vitro against staphylococcal isolates, with an MIC90 of 0.12 microgram/mL and 0.25 microgram/mL, respectively. In contrast, cefazolin was more effective than cephalothin against E coli isolates; the cefazolin MIC90 for E coli was 16 micrograms/mL and for cephalothin 64 micrograms/mL. Cefazolin (20 mg/kg intravenously [i.v.]) serum concentration remained more than MIC90 for E coli isolates significantly longer than serum concentration of cephalothin (40 mg/kg i.v.) (P < .001).

Animals↗

Penetration of cefazolin into pleural fluid.

Single doses of cefazolin, 500 mg intramuscularly and 1 g intravenously, were administered to 16 patients having lung pathology who were scheduled for thoracic fluid aspiration. Pleural fluid and serum samples were taken at intervals of 30 to 240 min for determination of cefazolin levels. The levels obtained were variable; however, the levels of cefazolin in pleural fluid generally exceeded the reported minimal inhibitory concentration values for Staphylococcus pneumoniae and Staphylococcus, and group A beta-hemolytic streptococcus. In addition, the pleural fluid levels exceeded the minimal inhibitory concentration for cefazolin against most of the Klebsiella and Haemophilus influenzae strains. These data show that cefazolin, despite its comparative high protein binding, produces levels in the pleural fluid capable of inhibiting the organisms commonly found in respiratory tract infections.

Adult↗

Treatment of osteomyelitis and septic arthritis with cefazolin.

Sixteen cases of severe osteomyelitis and septic arthritis caused by staphylococci, streptococci, gonococci, and a variety of gram-negative bacilli were treated with 4 to 8 g of parenteral cefazolin per day; nine received subsequent therapy with oral cephalexin or ampicillin. Of 16 infections, 15 were apparently cured. Cefazolin concentrations in those patients were: serum (peak), 25 to 216 micrograms/ml; synovial fluid, 24 to 46 micrograms/ml; and bone, 3.2 to 10.6 micrograms/g. Bacterial pathogens had minimal inhibitory concentrations of cefazolin of 2 micrograms or less per ml and seemed to be eradicated from foci of infection during therapy. One infection in a diabetic patient did not respond; despite high concentrations of cefazolin in serum, no detectable antibiotic was present in her infected metatarsal, and the infecting Escherichia coli (minimal inhibitory concentration, 16 micrograms/ml) was not eradicated during therapy. Concentrations of cefazolin in bone in 10 uninfected patients who received 1-g intramuscular doses prophylactically before surgery were also measured. Concentrations in bones from those who had normal renal function ranged from less than 0.6 to 2.8 micrograms/g.

Adolescent↗

Excretion of cefamandole, cefazolin, and cephalothin into T-tube bile.

The biliary tract excretion of cefamandole, cefazolin, and cephalothin was measured in eight patients with T-tubes inserted into their common ducts after ductal exploration for biliary tract stones. Each patient received 1.0 g intravenously of each cephalosporin on 3 separate days; T-tube bile and serum were collected at selected time intervals thereafter. In seven patients, bile and urine were collected for 6 h after the administration of each drug. Mean peak levels of cefamandole, cefazolin, and cephalothin in bile were 352, 46, and 12 mug/ml, respectively. The respective mean peak serum levels were 55.0, 92.8, and 32.4 mug/ml. Despite the fact that peak serum levels of cefazolin were 1.5 times those of cefamandole, levels in bile of cefamandole were about 8 times those of cefazolin. Over a 6-h period, almost three times as much cefamandole was excreted into bile as was cefazolin. Therefore, in those patients with biliary tract sepsis, in whom a cephalosporin is indicated for therapy, cefamandole appears to be the drug of choice.

Adult↗