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IV cefuroxime plus oral clarithromycin or IV erythromycin for the treatment of community-acquired pneumonia in hospitalised patients: a pilot study |
Gotfried M H, Killian A D, Servi R J, Danziger L H, Rodvold K 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 use of IV cefuroxime together with either oral clarithromycin (group A) or IV erythromycin (group B) for the treatment of community-acquired pneumonia (CAP).
Economic study type Cost-effectiveness analysis.
Study population The study population was male and female inpatients with mild to moderate community-acquired pneumonia between 16 and 85 years of age. Exclusion criteria included: pregnancy, nursing mothers, known hypersensitivity to one of the three drugs or to penicillin, use of terfenadine within 1 week prior to enrolment or anticipated use within 2 weeks of study completion, hospital-acquired pneumonia, or any other abnormal findings on baseline history, clinical or laboratory evaluation that would jeopardise patient safety or the study objectives.
Setting Hospital. The study was carried out at a community hospital in Phoenix, Arizona, USA.
Dates to which data relate Effectiveness and resource use data were collected between January and December 1994. The price dates were not stated.
Source of effectiveness data 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 20 patients were randomised in a 1:1 ratio between the two treatment groups. Patients were stratified into low- and high-risk groups. Power calculations were not used to determine sample size. However, given the sample size, statistical power to detect a difference in clinical cure between the two groups was calculated. Of the 20 patients, 2 in group B were excluded from the efficacy analysis since they both received less than the required period of therapy. All patients were included in the tolerability analysis. One patient was excluded from the cost analysis since cancer was considered to be the likely cause of the patient's fever.
Study design Randomised, open-label controlled trial.
Analysis of effectiveness The analysis of the clinical study was based on intention to treat. The primary health outcomes used were the number of patients who experienced complete resolution of signs and symptoms at the convalescent visit, (presumed) microbiological eradication of organism(s) at discharge, the number of patients who had a fully resolved infiltrate at the convalescent visit, the concentration of serum theophylline and length of stay. No statistically significant differences were found between the two groups with respect to demographic variables, gender, history of pneumonia in the preceding year, history of smoking, previous antibiotic usage, presence of underlying chronic pulmonary diseases, diabetes, use of concomitant immunosuppressants, baseline CAPSI score, oxygenation, severity of illness or dosage of parenteral cefuroxime.
Effectiveness results After controlling for risk factors, both groups demonstrated comparable responses to treatment, although complete resolution of signs and symptoms at the convalescent visit was more common in group A (8/10 versus 1/10, p=0.006).(Presumed) microbiological eradication of organism(s) at discharge was not different between groups (4/4 versus 3/4, p=0.285). 50% of group A and 63% of group B has fully resolved infiltrate at the convalescent visit (p=0.596). There were no clinically significant changes in vital signs or routine laboratory tests between the two groups, but there were significant increases in serum theophylline concentrations in 3 patients in group B (concentrations increased by 120%, 138% and 33%). The average length of hospital stay was 4 days in group A and 3.8 days in group B,(p=0.872).
Clinical conclusions The efficacy and tolerability analyses demonstrate that the two treatments are equally effective for the treatment of patients hospitalised with mild to moderate community-acquired pneumonia. Bacteriological and radiographic responses were similar, however clinical cure at the 2-week follow-up visit was superior for group A.
Measure of benefits used in the economic analysis The number of patients who had complete resolution of signs and symptoms at the 2-week follow-up visit.
Direct costs Direct costs included costs of antibiotic therapy and hospitalisation costs. Costs of antibiotic therapy were calculated based on the total number of doses of the three drugs received during the entire course of treatment. Hospitalisation costs were calculated by multiplying hospitalisation length by the average daily cost of hospitalisation for different types of pneumonia. Data to calculate average daily hospitalisation costs came from 70 university hospitals in the USA. Costs were not discounted. Quantities/costs were not reported separately. The quantity/cost boundary adopted was that of the hospital. The estimation of quantities and costs was based on actual data. Quantities of resources were measured between January and December 1994.
Statistical analysis of costs Costs were compared between the two groups using analysis of variance. Significant differences were reported for p < 0.05.
Indirect Costs No indirect costs were included.
Sensitivity analysis No sensitivity analysis was conducted.
Estimated benefits used in the economic analysis After controlling for risk factors, both groups demonstrated comparable responses to treatment, although complete resolution of signs and symptoms at the 2-week follow-up visit was more common in group A (8/10 versus 1/10, p=0.006).
Cost results The mean cost of inpatient macrolide therapy was $19.28 for group A and $76.04 for group B, (p=0.002). Mean antibiotic treatment costs were $125.36 for group A and $159.65 for group B, (p=0.054). Hospitalisation costs were not reported. Total therapy costs were not significantly different between the two groups (group A: $3,125.36 andgroup B: $3,065.9,p=0.92).
Synthesis of costs and benefits Costs and benefits were not combined in a single measure.
Authors' conclusions Oral clarithromycin appears to be a well tolerated and cost-effective alternative to parenteral erythromycin for patients hospitalised with mild to moderate CAP.
CRD COMMENTARY - Selection of comparators The selection of the comparator is straightforward.
Validity of estimate of measure of benefit Measuring clinical cure at two weeks after discharge may be too soon. The authors acknowledged that it is conceivable that the difference in clinical response may not have been maintained if patients were studied over a longer time interval.
Validity of estimate of costs The costs of hospitalisation, management of side effects and drug interactions, and diagnostic and laboratory procedures were not included in the analysis,which might have affected the cost-effectiveness of the two treatment procedures.
Other issues It is difficult to assess the robustness of the results since no sensitivity analysis was carried out. The results may not be generalisable to other countries since average hospitalisation costs were derived from 70 American university hospitals. The study mainly suffered from a small sample size. For instance, only one patient in group B belonged to the high-risk group. Finally, this was an open-label study which means that significant bias could have been introduced during the assessment of antibiotic efficacy.
Implications of the study Further studies should be conducted which have a larger sample size and an extended period of follow-up. Further research should also be able to define better the role of oral clarithromycin in individuals hospitalised with lower respiratory tract infections.
Source of funding Funded by an unrestricted grant from Abbott Laboratories.
Bibliographic details Gotfried M H, Killian A D, Servi R J, Danziger L H, Rodvold K A. IV cefuroxime plus oral clarithromycin or IV erythromycin for the treatment of community-acquired pneumonia in hospitalised patients: a pilot study. Clinical Drug Investigation 1997; 14(1): 23-34 Other publications of related interest Chien S-M, Pichotta P, Siepman N, et al. Treatment of community-acquired pneumonia: a multicenter, double-blind, randomised study comparing clarithromycin with erythromycin. Chest 1993;103:697-701.
Anderson G, Esmonde T S, Coles S, et al. A comparative safety and efficacy study of clarithromycin and erythromycin stearate in community-acquired pneumonia. Journal of Antimicrobial Chemotherapy 1991;27(supplement A):117-124.
Canadian Coordinating Office for Health Technology Assessment. Macrolides in community-acquired pneumonia and otitis media. Technology Overview: Pharmaceuticals 1997:1-14.
Guest J F, Morris A. Community-acquired pneumonia: the annual cost to the National Health Service in the UK. European Respiratory Journal 1997;10(7):1530-1534.
Indexing Status Subject indexing assigned by CRD MeSH Administration, Oral; Adult; Aged; Cefuroxime /therapeutic use /economics; Clarithromycin /therapeutic use /economics; Cost-Benefit Analysis; Erythromycin /therapeutic use /economics; Female; Injections, Intravenous; Macrolides /therapeutic use; Male; Middle Aged; Pneumonia /drug therapy AccessionNumber 21997001068 Date bibliographic record published 31/03/1999 Date abstract record published 31/03/1999 |
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