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Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost |
Angeli P, Guarda S, Fasolato S, Miola E, Craighero R, Del Piccolo F, Antona C, Brollo L, Franchin M, Cillo U, Merkel C, Gatta A |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study compared switch therapy with ciprofloxacin to intravenous ceftaxidime in the treatment of spontaneous bacterial peritonitis (SBP).
The switch therapy regimen involved intravenous ciprofloxacin (Ciproxin; Bayer Sp.A., Milan) administered at a dose of 200 mg twice daily (b.i.d.) for a serum creatine (SCR) level of 2.5 mg/dL, and 200 mg every 24 hours for an SCR level of greater than 2.5 mg/dL. Intravenous ciprofloxacin was followed by oral ciprofloxacin if and when clinical signs of infection had disappeared; the polymorphonuclear (PMN) count in the ascitic fluid and in blood had significantly decreased. Oral ciprofloxacin was administered at doses of 500 mg b.i.d. and 205 mg b.i.d. for SCR levels of 2.5 mg/dL and greater than 2.5 mg/dL, respectively.
Intravenous ceftazidime (Spectrum; Sigma-Tau Sp.A., Pomezia, Rome) was administered at doses of 2 g b.i.d. (SCR <1.5 mg/dL), 1 g b.i.d. (SCR 1.5 to 2.5 mg/dL) and 1 g every 24 hours (SCR >2.5 mg/dL).
After randomisation, the patients received ceftazidime or cipropfloxacin for 8 days, resolution of SBP being established when all clinical signs of the infection had disappeared, the PMN count in the ascitic fluid had decreased to less than 205/mm3, the total and differential white blood count had normalised, and ascitic fluid cultures were negative.
Economic study type Cost-effectiveness analysis.
Study population Patients were included in the study if they had a diagnosis of ascites and SBP. The exclusion criteria were:
antibiotic treatment within 1 month of inclusion;
a history of hypersensitivity to quinolones or beta-lactam antibiotics;
age younger than 18 years and older than 75 years;
evidence of other bacterial or fungal infections;
evidence of organic nephropathy; and
the presence of shock, gastrointestinal bleeding, dehydration, hepatocellular carcinoma, cardiac failure, extrahepatic neoplasis at the diagnosis of SBP.
Setting The setting was secondary care. The economic study was carried out in Italy.
Dates to which data relate The dates to which the effectiveness data, resource use data and prices related were not reported.
Source of effectiveness data The effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the effectiveness study.
Study sample Power calculations, assuming similar efficacy for both antibiotic treatments and based on the possibility of discharging patients before the end of antibiotic treatment, were used to calculate the sample size. An early discharge was assumed in 25% of patients in the ciprofloxacin groups and in no patients in the ceftazidime groups. This led to a minimum requirement of 50 patients per group, with a two-sided Type I error rate of 5% and a Type II error rate of 20%.
A total of 165 patients with cirrhosis and ascites with SBP were evaluated. Of these, 116 were randomised to the intravenous ceftazidime arm (n=55) and to the switch therapy with ciprofloxacin arm (n=61). Forty-nine patients were excluded from the study. Reasons for exclusion were hepatocellular carcinoma (16), treatment with antibiotics at diagnosis of SBP (9), organic nephropathy (5), gastrointestinal bleeding (5), aged older than 75 (3), hypersensitivity to beta-lactam antibiotics (2), cardiac failure (2), extrahepatic neoplasia (2), other bacterial infections (2) and cardiac failure (3).
Study design The study was a randomised controlled trial that was carried out in four hospitals. The randomisation was performed with sealed envelopes containing the treatment options, prepared using random numbers. Randomisation was independent for each hospital. The duration of follow-up was 3 months after inclusion, death or liver transplantation.
Analysis of effectiveness The analysis of the effectiveness study was conducted on an intention to treat basis. The primary heath outcome was the resolution of infection. Other outcomes such as complications were also reported. The groups were shown to be comparable as far as the age, gender, and presentation and aetiology of SBP were concerned.
Effectiveness results Resolution of infection was achieved with initial antibiotic treatment in 46 (84%) of the 55 patients treated with ceftazidime and 49 (80%) of the 61 patients treated with ciprofloxacin, (p not significant).
Clinical conclusions The authors concluded that switch therapy with ciprofloxacin was as effective as the intravenous administration of ceftazidime in the treatment of SBP.
Measure of benefits used in the economic analysis The authors did not specify a summary measure of benefit although the primary outcome was the percentage resolution of infection.
Direct costs The costs and the quantities were not reported separately. The costs included were those of the antibiotic treatment and of hospital stay. The source of the costs and quantities and the dates to which they related were not reported. Discounting was not necessary given the short duration of follow-up.
Statistical analysis of costs The costs were presented as means +/- standard errors. Comparisons between groups were performed using the chi-squared test or Fischer's exact test for categorical data, and Student's t-test for continuous data.
Indirect Costs The indirect costs were not included.
Sensitivity analysis No sensitivity analysis was reported.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The mean cost of antibiotic treatment per patient was EUR 150.70 (+/-7.28) in the ciprofloxacin group and EUR 291.83 (+/-12.22) in the ceftazidime group, (p<0.001).
The cost of hospitalisation per patient was EUR 1,994 (+/- 284) in the ciprofloxacin group and EUR 3,145 (+/- 236) in the ceftazidime group.
Synthesis of costs and benefits Authors' conclusions Switch therapy with ciprofloxacin was more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis (SBP) in cirrhotic patients who are not on prophylaxis with quinolones.
CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator was clear. The comparator was chosen because it represented the 'gold' standard for the antibiotic treatment of patients with SBP. You should consider whether this is a widely used technology in your own setting.
Validity of estimate of measure of effectiveness The estimates of the measure of effectiveness were based on a randomised controlled trial. The randomisation appears to have been well conducted, the sample size appears to have been reasonable although no power calculations were reported, and the patient groups were shown to have been comparable at analysis. These factors suggest that the results are likely to be valid.
Validity of estimate of measure of benefit The authors do not appear to have specified a summary measure of benefit, although the primary clinical outcome was the percentage resolution of infection.
Validity of estimate of costs The perspective of the analysis was not reported. However, given the costs included, it would appear to be that of the health service provider. The unit costs and the resource quantities were not reported separately, which reduces the generalisability of the study's findings. The sources from which the costs and quantities were drawn were not reported.
Other issues The authors noted one important limitation of their analysis, namely that the sample size was calculated on the hypothesis of a similar effectiveness between the two antibiotic treatments. They noted that a larger number of patients should have been enrolled in order to provide statistical evidence that the two antibiotic treatments were equally effective. Although ciprofloxacin was cheaper than ceftazidime, it was also slightly less effective. Thus, it would have been useful had the authors calculated an incremental cost-effectiveness ratio and evaluated the uncertainty.
Implications of the study The authors made no recommendations for policy or further research.
Bibliographic details Angeli P, Guarda S, Fasolato S, Miola E, Craighero R, Del Piccolo F, Antona C, Brollo L, Franchin M, Cillo U, Merkel C, Gatta A. Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost. Alimentary Pharmacology and Therapeutics 2006; 23(1): 75-84 Indexing Status Subject indexing assigned by NLM MeSH Administration, Oral; Albumins /therapeutic use; Anti-Bacterial Agents /administration & Antihypertensive Agents /therapeutic use; Ceftazidime /administration & Ciprofloxacin /administration & Female; Health Care Costs; Hepatorenal Syndrome /drug therapy /mortality; Humans; Infusions, Intravenous; Length of Stay; Liver Cirrhosis /complications; Lypressin /analogs & Male; Middle Aged; Peritonitis /drug therapy /economics; derivatives /therapeutic use; dosage; dosage; dosage AccessionNumber 22006000651 Date bibliographic record published 31/03/2007 Date abstract record published 31/03/2007 |
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