A pharmacoeconomic comparison of amoxicillin/clavulanate and cefpodoxime proxetil in the treatment of acute otitis media.

This report describes the results of a review that was done to compare, from the patients' and their parents' perspective, costs involved in treating acute otitis media in children with amoxicillin/clavulanate potassium or cefpodoxime proxetil. The following costs were included in the analysis: average wholesale price of the initial antibiotic prescribed, cost of initial and follow-up physician visits for additional treatment, antibiotics for treatment failures, and medications and products required to manage side effects. The amount of time that parents were required to take off work or school to deal with treatment failures or side effects in their children and the number of times that parents phoned the physician about side effects were also monitored. The acquisition costs of the initial antibiotics were slightly higher for patients who received cefpodoxime proxetil than for those who were given amoxicillin/clavulanate. However, the total costs were greater with amoxicillin/clavulanate therapy. In addition, the time that parents were required to take to deal with treatment failures or side effects in their children was greater in the amoxicillin/clavulanate group. More parents from the amoxicillin/clavulanate group also phoned their physicians about side effects. The results of this review confirm that there are many factors in addition to acquisition cost that must be considered when determining the total cost of treating a patient with a specific drug.

Cefpodoxime proxetil. An appraisal of its use in antibacterial cost-containment programmes, as stepdown and abbreviated therapy in respiratory tract infections.

Cefpodoxime proxetil is an orally administered prodrug which is converted in vivo to the third generation cephalosporin cefpodoxime. Cefpodoxime has a similar spectrum of antibacterial activity to the parenteral cephalosporins ceftriaxone and cefotaxime and a long elimination half-life, which allows once- or twice-daily administration. Cefpodoxime proxetil has proven efficacy in the treatment of community-acquired pneumonia and upper respiratory tract, skin and soft tissue and urinary tract infections. It has been evaluated for use in cost-containment programmes, as stepdown (parenteral-to-oral conversion) therapy in the treatment of community-acquired pneumonia and as abbreviated therapy in upper respiratory tract infections. Substituting oral for parenteral therapy can achieve considerable savings (in acquisition, delivery and labour costs). Moreover, oral administration has advantages for the patient in terms of comfort and mobility, avoids the hazards of parenteral delivery and may allow earlier discharge from hospital, or even allow home treatment from the outset in low-risk patients. As hospitalisation is usually the major cost component in treating serious infections, considerable savings can be made in this way. Pharmacy-driven stepdown programmes in 2 US hospitals have achieved cost savings by targeting patients with community-acquired pneumonia for early conversion from intravenous ceftriaxone therapy to oral cefpodoxime proxetil. Costs were compared with those from a control group of patients who continued to receive intravenous ceftriaxone until physicians deemed that oral therapy (with various agents) was appropriate. In one study, duration of parenteral therapy in the cefpodoxime proxetil group was reduced from 6.18 to 3.82 days and duration of hospitalisation was reduced from 10.06 to 6.23 days (p < 0.02), with corresponding hospitalisation cost reductions of $US7300 per patient. However, clinical trial data relating to the efficacy of cefpodoxime proxetil as stepdown therapy in patients initially requiring parenteral antibacterials are lacking. Abbreviated (4-to 7-day) cephalosporin regimens appear to be as effective as traditional 10-day penicillin regimens in the treatment of upper respiratory tract infections. Short regimens may improve patient compliance and tolerability, thereby reducing the costs of adverse effects and treatment failures. Data from preliminary clinical studies suggest that a 5-day course of cefpodoxime proxetil is as effective as an 8-day course of amoxicillin/clavulanic acid in treating either acute otitis media or sinusitis, and as effective as a 10-day course of amoxicillin/ clavulanic acid and more effective than a 10-day course of phenoxymethyl- penicillin in the treatment of pharyngotonsillitis. Cefpodoxime proxetil tended to be better tolerated and was associated with better compliance than penicillin-based regimens. Indeed, a pharmacoeconomic study showed that a 10-day regimen of cefpodoxime proxetil was associated with lower costs for treating adverse effects and treatment failures than a 10-day regimen of amoxicillin/clavulanic acid in the treatment of acute otitis media in children. A 5-day course of cefpodoxime proxetil had a lower cost per patient treated per month free of recurrence than a 10-day course of phenoxymethylpenicillin (non-generic) or amoxicillin/clavulanic acid in the treatment of recurrent pharyngotonsillitis. Thus, evidence to date suggests that cefpodoxime proxetil has potential for use as stepdown therapy in community-acquired pneumonia and in abbreviated therapy courses in upper respiratory tract infections. These preliminary observations require confirmation in well designed studies.

Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults. A prospective general practice study.

A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program.

OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital.

The importance of wound infection in antibiotic failures in the therapy of postpartum endometritis.

A prospective, randomized, double-blind trial was done to compare the efficacy of cefoxitin (2 grams given intravenously every six hours) with ceftizoxime (2 grams given intravenously every 12 hours) in the treatment of postpartum endometritis. Thirty-eight patients received cefoxitin and 43 received ceftizoxime. Demographic variables (age, gravidity, parity and estimated gestational age) and risk factors (cesarean section, operating time, duration of ruptured membranes and labor, number of vaginal examinations and internal monitoring) were not statistically different in the two antibiotic groups. In the cefoxitin group, eight of 38 patients failed initial antibiotic therapy and six of 43 patients in the ceftizoxime group failed (p = 0.399). In the univariate analysis, abdominal wound infection (p = 0.003) and higher gestational age (p = 0.008) were associated with failure of the antibiotic. With multiple logistic regression, only abdominal wound infection was associated with failure of the antibiotic (p = 0.0002). We conclude that cefoxitin and ceftizoxime are equally effective in the therapy of postpartum endometritis and that abdominal wound infection is primarily responsible for persistent fever and, therefore, failure of the antibiotic in patients with postpartum endometritis.

Effect of replacing cefotaxime with ceftizoxime in a hospital where penicillin-resistant pneumococcal disease is prevalent.

Ceftizoxime and cefotaxime demonstrate very similar activities in vitro against a broad range of bacteria. To reduce costs, our hospital pharmacy implemented an automatic substitution policy whereby ceftizoxime was dispensed and administered whenever cefotaxime was ordered. This policy was modified when penicillin-resistant Streptococcus pneumoniae isolates were found to be markedly less susceptible to ceftizoxime than to cefotaxime, of concern considering the prevalence and virulence of this pathogen. We compared clinical findings among 179 adult patients treated with ceftizoxime for any indication during the substitution months with 200 patients treated with cefotaxime during the previous year. The ceftizoxime group had a shorter mean length of stay, which paralleled a hospital-wide trend toward more efficient discharge planning. After adjusting for this trend, we observed no significant difference in duration of study drug, number of other intravenous antibiotics, likelihood of receiving additional antibiotics after study drug completion, or patient survival. Fortuitously, no penicillin-resistant pneumococcal infections were documented in ceftizoxime-treated patients. This study suggests that cefotaxime and ceftizoxime are comparable. The choice of one versus the other may be dictated by price, provided ceftizoxime is not used for proven or suspected penicillin-resistant pneumococcal infections.

Double-blind comparison of cefazolin and ceftizoxime for prophylaxis against infections following elective biliary tract surgery.

Antibiotics have been shown to reduce the incidence of wound infections after elective biliary tract procedures. Cefazolin and cefoxitin are among the agents most commonly promoted for this purpose. Cefoxitin has been substituted with ceftizoxime in many institutions; however, the role of ceftizoxime as a prophylactic agent in this setting has not been determined. To assess the comparative prophylactic efficacies of cefazolin and ceftizoxime in biliary tract surgery, we conducted a double-blind, randomized prospective clinical trial in a tertiary-care teaching hospital. Adult patients were randomized to one of two treatment groups and received a 30-min preoperative dose of study drug and as many as two postoperative doses at 12 and 24 h, depending on hospitalization status. Cefazolin and ceftizoxime were given as 1,000-mg doses. Patients with infections, those receiving prior antibiotics, or those with beta-lactam allergies were excluded. Over the 19-month study tenure, 167 patients were enrolled. Seventeen patients were excluded from analysis because of protocol violations. Of the 150 evaluable patients (72 and 78 receiving cefazolin and ceftizoxime doses, respectively), there was no significant difference among groups regarding sex, age, weight, preoperative Apache II score, baseline chemistry, and hematological parameters. Groups were also equivalent regarding the surgeon, type of procedure, characteristics (blood loss, drains, organ injury, and complications), and duration of hospital stay (mean, 5.6 versus 4.3 days [P = 0.31]). No clinical evidence of infection (7-day hospital stay and 30-day follow-up) was identified in 93% of cefazolin and 92% of ceftizoxime patients (P = 1.0). Microbiological confirmation was found in only 18% of primary-site infections. In conclusion, cefazolin and ceftizoxime appear to be equivalent for the prevention of infection in biliary tract surgery with the dosage regimens studied.

Prospective randomized study of antibiotic prophylaxis for nonlaparotomy surgery in benign conditions.

BACKGROUND: Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis. METHODS: This prospective randomized trial was conducted to investigate the prevention of major operating site infections after nonlaparotomy surgery, with treatment regimens as follows: the first group of patients received 2 g of intravenous cefotiam dihydrochloride (CTM) on the induction of anesthesia, while the second group received 100 mg of oral cefpodoxime proxetil (CPDX- PR) twice daily, from day 0 to day 2. RESULTS: Nineteen of the 207 patients enrolled developed postoperative infections diagnosed by our simple criteria for postoperative infection. The frequency of febrile morbidity was not significantly less in patients who received CTM (9 cases; 8.6%) as compared with those in the CPDX-PR group (10 cases; 9.8%) (p = 0.56). CONCLUSION: The administration of oral CPDX-PR (100 mg, twice daily, for 3 days) appears to be a safe, cost-saving, convenient prophylaxis which reduces overall expense.

Pharmacoeconomic benefit of antibiotic step-down therapy: converting patients from intravenous ceftriaxone to oral cefpodoxime proxetil.

OBJECTIVE: To evaluate the economic benefit associated with the early conversion of therapy from intravenous ceftiaxone to the comparable oral third-generation cephalosporin, cefpodoxime proxetil. DESIGN: Open-label, unblind, nonrandomized clinical trial. SETTING: A 360-bed Veterans Affairs Medical Center. PATIENTS: Forty patients who began receiving intravenous ceftriaxone for either a community-acquired pneumonia or a complicated urinary tract infection. INTERVENTION: twenty patients were selected, based on clinical assessment, to be converted from intravenous ceftriaxone to oral cefpodoxime proxetil. Twenty other comparable patients who would have been appropriate for step-down therapy, did not receive pharmacy intervention and were used as a control group. MEASUREMENTS: Both groups were assessed and compared for length of ceftiaxone therapy, length of oral follow-up therapy (if any), length of hospitalization, results of culture and sensitivity testing, treatment success and readmissions, and cost of respective therapeutic regimens. RESULTS: In the cefpodoxime study group, the average time receiving intravenous and oral antibiotics was 9.1 days at a total cost of $3040.26 for the 20 patients. In the control group, the average time receiving intravenous and oral antibiotics was 11.9 days at a total cost of $3961.26. A savings of $46.05 per patient was achieved. Patients receiving step-down therapy averaged 1 fewer day of hospitalization. CONCLUSION: Pharmacist intervention and cefpodoxime step-down therapy were associated with decreased overall antibiotic costs in our intravenous-to-oral program.