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PubMed1990

Transfer of ceftizoxime surpasses that of cefoperazone by the isolated human placenta perfused in vitro.

The transfer of cefoperazone and ceftizoxime across the human placenta was compared using the in vitro, bidirectionally perfused human placental lobule. The mean (+/- SEM) clearance indices for ceftizoxime and cefoperazone were 0.124 +/- 0.02 and 0.037 +/- 0.01, respectively (P = .0013). Cefoperazone concentration plateaued at a fetal concentration of 4-5 micrograms/mL in a recirculating perfusion system. No evidence of a decreasing slope of ceftizoxime transfer to the fetal compartment was noted after 60 minutes of perfusion. In a closed-closed perfusion system with equal concentrations of ceftizoxime in each compartment, a 1.1:1 fetal gradient was noted. These data indicate that ceftizoxime crosses the placenta significantly better than does cefoperazone and support our in vivo study documenting preferential concentration of ceftizoxime in the fetal compartment.

Biological Transport↗

PubMed1986

Pharmacokinetics of cefoperazone in healthy volunteers.

Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two-compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller.

Adolescent↗

PubMed1986

[Comparative study of cefoperazone and cotrimoxazole in kidney stone surgery via percutaneous approach].

The effectiveness and drawbacks of cefoperazone and cotrimoxazole in the prevention of postoperative infections following percutaneous removal of renal stones were studied comparatively. 60 patients were divided at random into two groups. 30 subjects were given 1 g cefoperazone IV every 8 hours for 5 consecutive days starting on the day before the procedure. The 30 other patients had an infusion of 800 mg sulfamethoxazole and 160 mg trimethoprim every 12 hours on the same 5 days. Age, sex and type of surgical procedure were comparable in both groups. Results were as follows: in the cefoperazone group, one patient had intraoperative septic shock due to a stone infected by a resistant Pseudomonas aeruginosa; in the cotrimoxazole group, 2 patients had postoperative fever due to stones infected by resistant Gram negative rods (Pseudomonas aeruginosa) and three patients had a urinary tract infection (Candida albicans in 1 case, Escherichia coli in 1 and Pseudomonas aeruginosa in 1). Tolerance was satisfactory for both regimens. The authors conclude that intravenous cefoperazone in the more effective drug and should be continued throughout the first three postoperative days.

Adolescent↗

PubMed1986

Pharmacokinetics of cefoperazone after single and multiple doses.

The pharmacokinetics of cefoperazone was determined following single and multiple intravenous and intramuscular administrations in man. Ten subjects at each dose level were given eleven successive doses, at 12 h intervals of 500 and 1000 mg i.m. and i.v.. Serum concentrations and urinary excretion were determined in all subjects after the first, fifth and eleventh doses. The first i.m. doses yielded mean peak serum levels of 37 micrograms/ml and 76 micrograms/ml at 1.0 h after injection. The first i.v. doses yielded mean serum levels of 93 and 180 micrograms/ml at 5 min after the injection. No tendency toward drug accumulation was observed on multiple dosage. The pharmacokinetics could be described by a linear, open, two-compartment model of drug distribution. The terminal serum half-life (2.1-2.4 h after i.v. doses and 2.6-2.8 h after i.m. doses) remained essentially constant over the period of the study by dose levels. The no-significant differences of areas under the curve between the two routes, at two doses, show the absolute bioavailability of cefoperazone was about 95% following i.m. administration. The high binding to serum proteins (90%) influences favourably the pharmacokinetic parameters of cefoperazone. It yielded high and prolonged serum concentrations and has very useful distribution properties. These favourable properties, together with its good antibacterial activity, suggest that cefoperazone will be effective in treating bacterial infections in human beings.

Adult↗

PubMed1985

[Severe liver damage as a drug-allergy reaction to cefoperazone].

A 20 year old man was treated with cefoperazone for 25 days because of a local infection after an open fracture complicated by pseudarthrosis. Severe liver damage was noted on 25th day of cefoperazone treatment. There was extreme elevation of transaminases and alkaline phosphatasis as well as jaundice and prolonged prothrombin time. Upper GI bleeding, fever and acute renal failure developed. All symptoms disappeared after cessation of cefoperazone. A causal relationship between the drug and liver damage seems likely because of a positive lymphocyte stimulation test, the time relation between cefoperazone therapy and change in liver function as well as the development of eosinophilia. Other causes of liver damage could be excluded. The pathogenesis of liver damage, upper GI bleeding and acute renal failure is discussed.

Adult↗

PubMed1982

[Minimal inhibitory and bactericidal concentrations of cefoperazone, cefotaxime, cefuroxime and cefalotin against 90 bacterial strains].

In this work, the sensitivity in vitro of cefoxitin, cefuroxime, cefotaxime, cefoperazone and cephalothin have been examined. Test of sensitivity in vitro have been performed as by Kirby-Bauer method as by measurement of MIC and MBC. Then the regression lines have been determined. Cefotaxime and cefoperazone provided nearly complete coverage of all Enterobacteriaceae; 80% were inhibited at less than or equal to 2 mcg./ml. This value is far below therapeutically attainable serum concentrations. Cefotaxime has MIC lower than cefoperazone. It has a significant spectrum of activity against Pseudomonas aeruginosa, nonenterococcal Streptococcus sp, non Enterobacteriaceae Gram-negative bacilli. Only enterococci and Acinetobacter species were relatively resistant to cefoperazone and cefotaxime. The cephalothin and the cefoxitin included excellent antimicrobial coverage of the staphylococci and the anaerobic bacteria respectively.

Acinetobacter↗

PubMed1980

Comparative pharmacokinetics of cefoperazone and cefotaxime.

The pharmacokinetics of cefoperazone and cefotaxime were compared in a crossover, randomized study in ten healthy volunteers (5 males, 5 females). Each subject received 2.0 gm of the study drug administered by an IV infusion over 30 minutes. Serum concentrations of cefoperazone and cefotaxime at the end of the infusion (zero time) were 254 mg/liter and 144 mg/liter, respectively. Comparative results at other times were the following: four hours, 20 mg/liter and 3 mg/liter; eight hours, 4.4 mg/liter and 0.3 mg/liter; and 12 hours, 1.2 mg/liter and 0.0 mg/liter. Twenty-one percent of the 2.0-gm single dose of cefoperazone was recovered in the urine during the first 24 hours following dosing, compared to 52% for cefotaxime. The renal clearance of cefoperazone was also determined in three patients during four hours. The results of the investigations will be discussed in view of the clinical relevance.

Adult↗

PubMed1980

A study of cefoperazone alone and in combination with tobramycin against Pseudomonas aeruginosa.

The minimum inhibitory concentrations (MICs) of cefoperazone for 507 clinical isolates of Pseudomonas aeruginosa were measured by plate dilution technique. On a cumulative percentage basis, 81% of isolates were inhibited by less than or equal 3.13 microgram/ml of cefoperazone. The minimum bactericidal concentration (MBC) was found to be generally twice the MIC. Synergy occurred between cefoperazone and tobramycin, judged by a lowering of the MIC in 69% of isolates, for which the MIC of cefoperazone alone was less than or equal to 6.2 microgram/ml.

Anti-Bacterial Agents↗

PubMed1984

Cefoperazone in the treatment of postsurgical wound infection, sepsis, and abscess of the spinal cord and brain.

Cefoperazone was used in the treatment of 23 cases of serious bacterial infection in 20 patients. Ten postoperative scalp wound infections, five infections at the site of tracheostomy, four cases of extradural spinal cord abscess, three cases of sepsis, and one abscess of the cerebellopontine angle were treated with cefoperazone (1 to 2 gm BID, usually for seven to 27 days). There were excellent or good clinical responses in 87% (20/23) of the cases (14 of the 15 postsurgical wound infections, three of the four cases of spinal cord abscess, and all three cases of sepsis). Most of the organisms isolated from the patients' cultures were sensitive to cefoperazone. Excellent or good responses occurred in ten of the 12 infections due to Staphylococcus aureus, in all three infections due to Pseudomonas sp, all three due to Citrobacter freundii, the two due to Serratia marcescens, one of the two due to Klebsiella sp, and the one due to Escherichia coli. Two patients with ventriculitis were clinically improved by three 1-gm infusions, via a shunt, of cefoperazone. No adverse effects of the antibiotic therapy were reported.

Abscess↗

PubMed1984

Evaluation of cefoperazone in the treatment of bacterial infections in patients with hematological diseases.

This study was conducted as a multicenter trial in 12 institutions in the Kyushu region of Japan. The clinical effects of cefoperazone were evaluated in 101 patients with 112 infections complicated by hematological disease. In about half of the patients, the baseline neutrophil count was below 1,000/mm3. Results were excellent in 23 of 101 cases and good in 48, with an efficacy rate of 70.3%. Cefoperazone alone or in combination with other antibiotics was effective in 60.7% of patients who had not responded to previous antibiotic therapy. No serious side effects attributable to cefoperazone were noted. The results indicate that cefoperazone is a useful antibiotic for the treatment of severe infections in patients with hematological diseases.

Adult↗

PubMed1984

[Influence of cefoperazone on the fecal flora in children].

A differential quantitative study was used to evaluate the effects of parenteral cefoperazone upon children's fecal flora. Fecal specimens were obtained from 16 patients, before, during and after therapy. Cefoperazone therapy was associated with major changes in fecal flora. There was marked reduction or suppression to undetectable levels of Enterobacteria, Staphylococci and Streptococci in 13 patients. During therapy, yeasts were selected or acquired in 7 cases. 5 to 10 days after cefoperazone was discontinued, the fecal flora was virtually the same as before treatment. Thus, cefoperazone should prove very useful in the treatment of septicemia due to intestinal overgrowth.

Adolescent↗

PubMed2004

Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection.

BACKGROUND: We compared imipenem, meropenem and cefoperazone-sulbactam against hospital originated A. baumannii strains in terms of bactericidal efficacy and selection of resistant mutants during treatment in a rat thigh abscess model. METHODS: A total of 18 strains were inoculated in 54 animals (one strain for three animals). Randomly selected 10 among these 18 strains were inoculated in another 10 rats as the control group. Imipenem, meropenem and cefoperazone-sulbactam were the antibiotics compared. After four days of treatment, Wistar albino rats (200 to 250 g) were sacrificed and the abscess materials were processed for mean colony counts and for the presence of resistant mutants. RESULTS: The mean CFUs per gram (mean +/- (std. deviation) [x10(4)]) of the abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17), meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The differences were not significant. On the other hand, no resistant mutant was detected in abscess materials. CONCLUSION: This study indicated; first, cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in this particular abscess model and second, emergence of resistance due to spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

Journal Article↗

PubMed2004

Separation of cefoperazone enantiomers using beta-cyclodextrin as chiral additive by capillary zone electrophoresis.

A capillary electrophoresis method was developed to separate the enantiomers of cefoperazone. Different cyclodextrins, including alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD), 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and methyl-beta-cyclodextrin (Me-beta-CD), were tested as chiral additives in the running buffer. The effect of various parameters on enantioseparation such as concentration of NaH(2)PO(4), buffer pH, and CD concentration was also studied. The cefoperazone enantiomers were baseline separated under conditions of 0.04 mmol/L beta-CD, 75 mmol/L NaH(2)PO(4) buffer at pH 4.0. A fused silica capillary (40 cm effective length x 75 microm ID) was used. The applied voltage and capillary temperature were 20 kV and 25 degrees C, respectively. Under these conditions, linear calibration curves were obtained in the 5-500 microg/ml range using UV detection at 280 nm. The limit of detection for both isomers was 0.1 microg/ml. The method was used for the analysis of different pharmaceutical preparations (dose) and biological samples containing cefoperazone.

Anti-Bacterial Agents↗

PubMedDate not supplied

Cefoperazone therapy of bacterial meningitis: a clinical trial.

Sixteen hospitalized patients, aged between 10 and 76 years (mean: 34.3 years), with bacterial meningitis were treated i.v. with cefoperazone at daily doses of 4.5 g to 9 g. In two cases ampicillin was given in combination with cefoperazone during the last four days and the first five days of treatment, respectively. The following organisms were isolated: Neisseria meningitidis (n = 9), Haemophilus influenzae (n = 3), Escherichia coli (n = 2), Streptococcus pneumoniae (n = 2). Fourteen patients completely recovered from infection and the pathogens were eradicated; the treatment failed in only two patients and both were cured with alternative treatment. Furthermore, in 11 patients cefoperazone serum and CSF levels were determined four times during the first week of treatment (1st, 3rd, 5th and 7th days). No important side effects were recorded.

Adolescent↗

PubMedDate not supplied

Vitamin K supplementation during prophylactic use of cefoperazone in urologic surgery.

Cefoperazone, an antibiotic commonly used for prophylaxis of infection, has been associated with hypoprothrombinemia and bleeding. To reduce the risk of bleeding, co-administration of vitamin K has been advised. We reassessed the need for vitamin K use in a retrospective analysis of 50 patients undergoing urologic procedures and who had received cefoperazone for three days to prevent infection. Eleven of 50 patients were given vitamin K because of liver or renal disease. Prothrombin time was not elevated in any of the 50 patients analyzed. We conclude that routine use of vitamin K with cefoperazone for perioperative prophylaxis of infection may be unwarranted in patients without identified risk for bleeding.

Aged↗

PubMed1988

Controlled trials of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients.

The efficacy and safety of double beta-lactam therapy with cefoperazone plus piperacillin in febrile granulocytopenic patients were compared with moxalactam plus piperacillin, ceftazidime plus piperacillin, and imipenem alone in two separate clinical trials. All patients also received prophylactic vitamin K. When National Committee for Clinical Laboratory Standards breakpoints for susceptibility were used, a greater proportion of pretherapy isolates of gram-negative aerobic bacilli and gram-positive organisms were found to be susceptible to cefoperazone (94 percent) and imipenem (91 percent) than to moxalactam (84 percent), ceftazidime (85 percent), or piperacillin (85 percent). In trial I, the overall response rates for documented or possible infections were 78 percent (76 of 97 patients) for cefoperazone/piperacillin and 80 percent (72 of 90 patients) for moxalactam/piperacillin. In trial II, the overall response rates were 86 percent (25 of 29 patients) for cefoperazone/piperacillin, 74 percent (20 of 27 patients) for ceftazidime/piperacillin, and 72 percent (21 of 29 patients) for imipenem alone. There was no nephrotoxicity or hemorrhage related to the study drugs. Diarrhea was more frequent with each of the double beta-lactam regimens, whereas nausea and seizures were more common with imipenem given at a dosage of 1.0 g intravenously every six hours. Seizures occurred in three of 29 imipenem-treated patients but in none of 243 patients treated with the double beta-lactam regimens (p less than 0.001). These results suggest that cefoperazone plus piperacillin provides adequate coverage for most common bacterial pathogens and is safe and effective therapy for febrile granulocytopenic patients.

Adolescent↗

PubMed1988

Effect of dose and schedule on cefoperazone pharmacodynamics in an in vitro model of infection in a neutropenic host.

Previous studies have shown that cefoperazone given in frequent, large doses is effective in the treatment of infection in patients with cancer. The pharmacodynamics of 2- and 4-g doses of cefoperazone administered either as a single dose or at 12-hour intervals were studied in an in vitro model that simulates infection in a neutropenic patient. One strain each of Pseudomonas aeruginosa (minimal inhibitory concentration [MIC] = 2 micrograms/ml), Staphylococcus aureus (MIC = 1 microgram/ml), Escherichia coli (MIC = 0.06 micrograms/ml), and Klebsiella pneumoniae (MIC = 0.25 micrograms/ml) was studied. The initial dose reduced the inoculum by approximately 3 logs for the Pseudomonas and the staphylococci and 3 to 5 logs for the other organisms. No significant differences in killing were found between the 2- and 4-g doses. Regrowth of Pseudomonas and staphylococci occurred with the single dose but not with the every-12-hour regimen. These data support the clinical use of cefoperazone in doses every 12 hours.

Agranulocytosis↗

PubMed1986

Retinal toxicity of intravitreal cefoperazone.

Cefoperazone is a broad spectrum, third-generation cephalosporin with potential usefulness in treating endophthalmitis because of its in vitro activity against Gram-negative organisms. Retinal toxicity was evaluated via serial indirect ophthalmoscopy, electrophysiologic testing and histopathologic examination of 43 Dutch-belted rabbit eyes injected intravitreally with 2, 4, 8, 16 or 32 mg of cefoperazone in a volume of 0.1 cc each. They were compared with seven eyes injected with sterile saline. Results show electroretinographic and histological evidence of retinal toxicity at concentrations of 16 mg or greater, while a single intravitreal dose of 8 mg or less of cefoperazone produced no evidence of retinal toxicity.

Animals↗