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PubMed1997

Sequential therapy with cefuroxime followed by cefuroxime axetil in acute exacerbations of chronic bronchitis.

A prospective, multicentre, randomized, open-label, parallel group study compared the efficacy, safety and tolerability of cefuroxime 750 mg iv administered either twice daily (bd) or three times daily (tds) for 48-72 h, followed by oral cefuroxime axetil 500 mg bd for 5-7 days in a sequential therapy regimen for the treatment of acute exacerbations of chronic bronchitis. A total of 628 adult patients entered the study; 323 in the cefuroxime tds group and 305 in the cefuroxime bd group. For clinically evaluable patients, the post-treatment clinical response rate was 86% and 88% in the cefuroxime tds and bd groups, respectively. Cure was maintained at follow-up (14-28 days after treatment completion) in 85% of the cefuroxime tds group and 84% of patients in the cefuroxime bd group. A total of 189 pathogens was isolated, the most common being Haemophilus influenzae (17%), other Haemophilus spp. (15%), Streptococcus pneumoniae (15%) and Enterobacteriaceae (23%). At the post-treatment assessment, 66% and 70% of pathogens were cleared in the cefuroxime tds and bd groups, respectively. Both treatment regimens were well tolerated. The incidence of drug-related adverse events was 7% in the cefuroxime tds group and 6% in the cefuroxime bd group; the most common side-effects were gastrointestinal. Qualitative and quantitative markers were used to determine the optimal time to switch from iv to oral therapy and, of these, peak expiratory flow rate was shown to be the most useful in the present study. In conclusion, the findings of this study support the use of a bd dosing schedule of cefuroxime in a sequential therapy regimen with oral cefuroxime axetil, demonstrating it to be clinically equivalent to the standard tds dosage currently used, as well as being simpler and more convenient to administer at a lower cost.

Adolescent↗

PubMed1996

Evaluation of the use of cefuroxime and cefuroxime axetil in an intravenous-oral stepdown program.

OBJECTIVE: To characterize cefuroxime and cefuroxime axetil use under the influence of a parenteral-to-oral (iv-po) stepdown program. DESIGN: Open single-center retrospective review. SETTING: Tertiary care teaching and referral Canadian hospital with 1100 beds. PATIENTS: A random sample of 78 patients receiving cefuroxime was compared with a random sample of 50 patients receiving iv-po cefuroxime stepdown. RESULTS: During the first 6 months following formulary introduction, 1535 patients received cefuroxime. Stepdown to any oral antibiotic occurred in 22% of patients. Cefuroxime axetil was used as the stepdown agent in 64% of these cases. In a comparison of nonstepdown courses with stepdown courses, some differences were apparent. Nonstepdown treatment courses were primarily prophylactic, whereas stepdown courses were typically initiated as primary therapy for the 10-day management of respiratory tract infections (p < 0.001). Conversion to oral therapy typically occurred on day 5 of parenteral therapy and continued for 5 days. Stepdown was considered possible in 46% of treatment courses in which this process did not happen. When stepdown did occur, it was considered timely in 64% of cases, unnecessarily delayed in 32%, and premature in 4% of treatment courses. Stepdown did not appear to be associated with a negative impact on patient outcome. Mean +/- SD cost of drug therapy per day was less for the stepdown group (US $15.78 +/- $5.97) than the nonstepdown group (US $25.47 +/- $7.87; p < 0.001). CONCLUSIONS: As a result of this study we intend to maintain cefuroxime and cefuroxime axetil on the formulary and continue to judiciously promote the timely conversion to oral therapy.

Administration, Oral↗

PubMed1997

Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired pneumonia.

STUDY OBJECTIVES: To compare the efficacy of two sequential therapy regimens of IV cefuroxime followed by oral cefuroxime axetil for the treatment of community-acquired pneumonia (CAP). DESIGN: Prospective, multicenter, randomized, open-label, parallel-group study. SETTING: Sixty-six centers in 11 countries (Belgium, Canada, Czech Republic, Germany, Hungary, Ireland, Israel, Poland, Portugal, South Africa, and the United Kingdom). PATIENTS: Six hundred thirty-six adults with CAP requiring hospitalization and initial IV antibiotic treatment. INTERVENTIONS: Cefuroxime, 1.5 g IV tid or bid for 48 to 72 h followed by oral cefuroxime axetil, 500 mg bid for 7 days. MEASUREMENTS AND RESULTS: For clinically evaluable patients, the clinical response rates were equivalent for cefuroxime tid and bid groups posttreatment (cure/improvement, 79% and 84%, respectively) and at follow-up (maintained cure, 87% and 82%, respectively). All signs and symptoms of pneumonia showed improvement at the time of switch from IV to oral therapy. A total of 111 pathogens were isolated, the most common being Streptococcus pneumoniae (23%), Haemophilus influenzae (18%), and Enterobacteriaceae (15%). Bacteriologic clearance was obtained posttreatment in 47 of 49 and 36 of 42 of bacteriologically evaluable patients in the cefuroxime tid and bid groups, respectively. Both regimens were well tolerated with a low incidence of drug-related adverse events, the most common being GI. CONCLUSIONS: Twice daily IV cefuroxime followed by oral cefuroxime axetil is a simple and effective sequential therapy regimen for the treatment of CAP. It offers potential cost savings and can replace the current tid regimen in this indication.

Administration, Oral↗

PubMed1985

Antibiotic treatment during surgery for diffuse peritonitis: a prospective randomized study comparing the effects of cefuroxime and of a cefuroxime and metronidazole combination.

In a prospective randomized open study of patients operated upon for diffuse peritonitis, the effects of two different antibiotic regimens were evaluated. Cefuroxime given as a single drug (Group I; n = 59) was compared with a combination of cefuroxime and metronidazole (Group II; n = 63). Bacteriological cultures, both aerobic and anaerobic, were obtained peroperatively and in the event of any complication. The antibiotic sensitivities of isolated bacteria, and the serum and tissue concentrations of cefuroxime were determined. Postoperative infectious complications occurred in 22 per cent of Group I patients (cefuroxime), and in 17.5 per cent of Group II (cefuroxime plus metronidazole). The mortality rates were 5 per cent for Group I and 8 per cent for Group II. Tissue concentrations of cefuroxime were well above the MIC (minimal inhibiting concentration) values for most of the bacteria isolated. From a few patients in Group I, however, cultures were obtained with isolates sensitive to metronidazole but resistant to cefuroxime. Our findings suggest that, in the antibiotic treatment of patients operated for diffuse peritonitis, an agent which is primarily effective against aerobic bacteria (but not entirely without effect on anaerobes) is as effective as combination therapy covering both aerobic and anaerobic bacteria.

Adolescent↗

PubMed1991

Concentration of cefuroxime in serum and middle ear effusion after single dose treatment with cefuroxime axetil.

Antimicrobial agents play an important role in the treatment of patients with acute otitis media and otitis media with effusion (OME). The study was undertaken to determine the concentrations of cefuroxime in the blood and middle ear effusions (MEE) of children between 6 and 12 years of age with acute otitis media and chronic OME after a single oral dose administration of cefuroxime axetil, the ester prodrug of cefuroxime. Cefuroxime axetil (250 mg) was administered 2 to 6 hours before either myringotomy for acute otitis media or myringotomy and tube insertion for chronic OME. Blood samples and middle ear aspirates were obtained from 31 children and the samples were analyzed by high performance liquid chromatography. Cefuroxime was recovered in measurable concentrations in all serum samples and in 15 (79%) of the 19 MEE specimens analyzed. No correlation was seen between cefuroxime MEE concentrations and effusion type, bacteriology or serum concentrations. This study shows that cefuroxime does penetrate into MEE when OME is present and that therapeutic concentrations can be achieved in some patients.

Acute Disease↗

PubMed1998

[Stepwise therapy of community-acquired pneumonia. Results of cefuroxime and cefuroxime axetil study].

The efficacy of a 7-day switch therapy with parenteral cefuroxime in a dose of 750 mg for 3-5 days followed by the use of oral cefuroxime axetil in a dose of 500 mg every 12 hours was compared with that of a 7-day therapy with parenteral cefuroxime in a dose of 750 mg every 8 hours in hospitalized patients with community-acquired pneumonia. The clinical and bacteriological efficacies and pharmacokinetic properties of both the dosage forms were estimated. It was shown that the clinical and bacteriological effects did not significantly differ in the patients under the parenteral regimen with cefuroxime and under the parenteral-to-oral regimen with cefuroxime and cefuroxime axetil: the cure in 75 and 83 per cent of the patients and the bacteriological response in 100 and 86 per cent of the cases respectively. The results indicated that the cost of the switch therapy was much lower while the efficacy did not decrease.

Administration, Oral↗

PubMed1991

Comparison of the serum and tissue concentrations of cefuroxime from cefuroxime axetil and phenoxymethylpenicillin in patients undergoing tonsillectomy.

In the study described, the pharmacokinetics of two oral betalactams, cefuroxime axetil and phenoxymethylpenicillin, were compared with respect to their penetration into tonsil tissue. Seventeen patients were given cefuroxime axetil 500 mg single dose and 16 patients were given phenoxymethylpenicillin 650 mg single dose, at different time intervals before tonsillectomy. The tonsils were freeze-dried and the drug concentrations in serum and tissue determined by a high performance liquid chromatographic method. Cefuroxime axetil showed a slightly better penetration ratio (mean 35%, median 32%) than phenoxymethylpenicillin (mean 31%, median 24%) however the difference was not statistically significant. The bioavailability of cefuroxime axetil was low due to being administered in the fasting state. The relatively low penetration ratios of both drugs into samples of whole tissue can be explained by the localization of betalactam antibiotics primarily in the extracellular fluid, with low penetration into normal cells. Both drugs were found to reach concentrations in tonsil tissue above the minimum inhibitory concentration for Group A beta-haemolytic streptococci after a single oral dose. In addition to streptococci, Haemophilus influenzae and beta-lactamase producing Staphylococcus aureus were isolated in a significant number of the tonsils. These bacteria may play a pathogenic role, but this was not investigated.

Adult↗

PubMed1987

A comparison of systemic cefuroxime and cefuroxime loaded bone cement in the prevention of early infection after total joint replacement.

A controlled prospective randomised trial of 295 arthroplasties of the hip and knee joints was carried out to compare the effect of systemic Cefuroxime with Cefuroxime in bone cement in the prevention of early infection. There was no statistical difference in the incidence of early superficial or deep infection between the two groups. Both methods of administering Cefuroxime appear to be satisfactory in the prevention of early infection after total joint replacement.

Adult↗

PubMed1992

Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the treatment of lower respiratory tract infections.

In a large multinational study, the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment of lower respiratory tract infections in hospitalised patients. A total of 512 patients were entered (256 in each treatment group). All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy. The clinical responses in the two treatment groups were very similar: 223 of 256 (87.1%) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9%) with amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44% of the patients. Clearance rates obtained were again similar: 72.8% with cefuroxime/cefuroxime axetil and 70% with amoxicillin/CA. Ten percent of the isolates were beta-lactamase producers, similar numbers of which were cleared in both groups. Both regimens were generally well tolerated, with only 5% of patients treated with the cefuroxime regimen and 4.3% of patients treated with amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime axetil "follow-on" therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA, with the advantage of twice daily oral administration.

Administration, Oral↗

PubMed1992

High pressure liquid chromatographic analysis of the serum concentration of cefuroxime after an intravenous bolus injection of cefuroxime in patients with a coronary artery bypass grafting.

A simple reversed-phase high pressure liquid chromatographic method was developed for the determination of cefuroxime in the serum of patients undergoing coronary artery bypass grafting. The serum was cleaned up with a 3.3% solution of perchloric acid in water. Cefalexine was used as an internal standard. Detection was made by a UV multi-wavelength detector. The optimum wavelength for cefuroxime is 275 nm. The absolute recovery of this method was 90.9%; the limit of quantification was 0.7 mg/l. This analytical method was used in a study to investigate the cefuroxime serum concentration--time curves in 26 patients undergoing coronary artery bypass grafting. It was found that one single dose is sufficient to obtain effective serum concentrations.

Adult↗

PubMed2004

Pharmacokinetic models for the saturable absorption of cefuroxime axetil and saturable elimination of cefuroxime.

Since oligopeptidic drugs such as beta-lactam antibiotics share the same carriers in humans and animals, the absorption and elimination kinetics of cefuroxime (C) were investigated in rats. Plasma C concentrations were measured by liquid chromatography. Pharmacokinetics and bioavailability of C in the rat were examined after intravenous (i.v.) administration at three doses (1.78, 8.9 and 17.8mg) of cefuroxime sodium and oral administration at two doses (2.02 and 8.9mg) of cefuroxime axetil (CA). Preliminary fits using data from intravenous administration of C showed that the drug disposition kinetics were clearly nonlinear, with an increase in plasma clearance as the intravenous dose increased. After oral administration of CA, normalized C(max) was higher for smaller dose than for the largest dose. The population pharmacokinetic parameters were obtained by means of nonlinear mixed effect modelling approach according to a nonlinear elimination and nonlinear absorption two-compartment model. The nonlinear elimination could be attributed to a saturable renal tubular reabsorption of the antibiotic and nonlinear intestinal absorption of CA mediated by carrier system. The oral bioavailability of C, calculated by numeric integration of an amount of CA drug absorbed was 22 and 17% for 2.02 and 8.9mg of prodrug administered orally.

Administration, Oral↗

PubMed1994

Antibiotic prophylaxis in pulmonary surgery. A prospective randomized double-blind trial of flash cefuroxime versus forty-eight-hour cefuroxime.

The aim of this study was to determine whether a 48-hour antibiotic prophylaxis regimen with a second-generation cephalosporin was more efficient than a flash antibiotic prophylaxis regimen in pulmonary operations. All the included patients underwent lung resection. Patients with preoperative infection were excluded. All the patients were given cefuroxime (1.5 gm intravenously) at the time of the anesthetic induction and again 2 hours later. The randomization was done postoperatively: group 1 was given placebo intravenously (n = 102) and group 2 was given cefuroxime intravenously (n = 101), each every 6 hours for 48 hours. The overall rate of infections was 46% in the 48-hour cefuroxime group versus 65% in the flash group (p = 0.005). The difference remained significant even after an adjustment with prognosis variables (p = 0.01). Six empyemas (6%) in the flash group were noted versus one (1%) in the 48-hour group (p = 0.03). From day 3 to day 8 after the operation, chest x-rays films were more often assessed as being normal in the flash group than in the 48-hour group (p = 0.005). On day 3 after operation, white blood cell counts were 13,020 +/- 1,220 elements/mm3 in the flash group versus 11,620 +/- 1,220 elements/mm3 in the 48-hour group (p = 0.03). A 48-hour antibiotic prophylaxis regimen decreases the rate of deep infections and particularly the rate of empyemas.

Bronchopneumonia↗

PubMed1991