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A prospective, randomised comparison of single-vs. multiple-dose antibiotic prophylaxis in penetrating trauma |
Schmidt-Matthiesen A, Roding H, Windolf J, Sommerfeldt D, Gutt C, Pannike A, Encke 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 Early-stage antibiotic prophylaxis with single-dose ceftriaxone 2g in the prevention of infection in patients with a penetrating trauma.
Economic study type Cost-effectiveness analysis.
Study population Patients with a penetrating injury to only one part of the body, who reached the hospital within 2 hours of being injured and who received adequate surgical care within 16 hours of being injured. Exclusion criteria were as follows: aged under 18 years, pregnancy, antibiotic treatment in the previous treatment, clinically important bacterial infection requiring antibiotic treatment, severe craniocerebral trauma, burns, pre-existing fatal disease or immunodeficiency, kidney failure, liver dysfunction, mechanical ventilation required for greater than 24 hours, hypersensitivity to cephalosporins or penicillin, patients with injuries likely to cause death within 10 days of admission to hospital, planned multiple major surgical procedures in the 3 days after admission, and haemorrhage which could not be controlled by surgical means.
Setting Hospital. The economic study was carried out in Germany.
Dates to which data relate Effectiveness and resource use data corresponded to patients treated between January 1993 and July 1995. The price year was not explicitly reported.
Source of effectiveness data The evidence for the final clinical outcomes was derived from a single study.
Link between effectiveness and cost data Costing was prospectively undertaken on the same patient sample as that used in the effectiveness analysis.
Study sample Power calculations were used to determine the sample size (with an assumption of 10% infection for the comparator drug and 24% for the intervention drug, one-sided alpha=0.05, and beta=0.2, a total of 150 patients in each study group was required). The study could only recruit a total of 206 patients; 102 were randomised to the ceftriaxone group with a median age of 39 years and 104 to the cefoxitin group with a median age of 36 years.
Study design This was an open-label, randomised, comparative, phase IV study, carried out in two centres. The duration of the follow-up was for 10 days after admission or until discharge or reoperation. Loss to follow-up consisted of 5 patients in the ceftriaxone group and 6 in the cefoxitin group. Randomisation was carried out separately for each study site, and stratified for abdomen, thorax and limbs, using computer-generated lists with blocks of 6 patients each. Because of the unexpected shortage of patients, the sample size of 150 for each study group could not be realised at the end of 24 months of the pre-planned time period adopted for the study; consequently stratification by type of injury was not possible.
Analysis of effectiveness The principle used in the analysis of effectiveness was both intention to treat and treatment completers only (per protocol). The main health outcome was the frequency of postoperative bacterial infections up to the trial end point (or percentage of patients who were infection-free). Other postoperative outcomes such as periods of central venous catheterisation, endotracheal intubation, wound drainage, frequency and duration of episodes of fever, and hospital stay, were also reported. The study groups were comparable in terms of demographic features and injuries (per-protocol basis).
Effectiveness results The prevention of infection in the first 10 days after admission (fully effective cases) was achieved in 96% of the ceftriaxone and 95% of the cefoxitin group. The groups were found not to be significantly different in terms of other postoperative outcomes.
Clinical conclusions It was concluded that, provided medication is given early and surgery is performed early, both single-dose ceftriaxone and a 3-day course of cefoxitin 3 times a day provide a high degree of primary protection from infection.
Measure of benefits used in the economic analysis No summary benefit measure was identified in the economic analysis since, with equivalent efficacy of the antibiotic modalities in terms of primary end-point of the study, the economic analysis was reduced to a cost-minimisation analysis.
Direct costs Costs were not discounted due to the short time frame of the cost analysis. Quantities were reported separately from the costs only in terms of staff time for intravenous administration and hospital stay. Cost items were reported separately. Cost analysis covered the costs of antibiotic treatment consisting of the purchase price, preparation and administration of the study medication and the antibiotics given to treat an infection up to the time of discharge from hospital or trial completion. The average personnel costs were estimated using an average staff time of 10 minutes for each intravenous administration. Cost data were obtained from a German source for pharmacological information (GPI). Neither the perspective adopted in the cost analysis nor the price year was explicitly reported. No adjustments for inflation appear to have been made.
Statistical analysis of costs A statistical analysis was performed on cost components, however the statistical test used was not specifically reported.
Estimated benefits used in the economic analysis Cost results Based on intention to treat analysis, the average cost was $42.69 for ceftriaxone and $107.69 for cefoxitin.
Synthesis of costs and benefits Costs and benefits were not combined since with comparative efficacy of the preventive alternatives, the economic study was a cost-minimisation analysis; the intervention single-dose drug being the less costly approach.
Authors' conclusions Prophylaxis in penetrating trauma with a single dose of ceftriaxone is safe and has considerable practical and economic advantages.
CRD COMMENTARY - Selection of comparators The use of cefoxitin was regarded as the comparator since it had proven efficacy in preventing infection in penetrating trauma. You, as a database user, should consider whether this is a widely used health technology in your own setting.
Validity of estimate of measure of effectiveness The effectiveness results are likely to be internally valid given the randomised nature of the study design; it should be borne in mind that the study could not achieve the full sample size required by the prospective power calculations. The study groups were found to be comparable in terms of demographic features and injuries. The patient sample appears to have been representative of the population of patients with penetrating trauma treated in the hospital emergency department.
Validity of estimate of measure of benefit The analysis of benefits was based upon therapeutic equivalence of treatment alternatives. The economic analysis therefore included only costs.
Validity of estimate of costs Some quantities were reported separately from the costs and adequate details of methods of cost estimation were given. It is not clear whether, in the cost calculations, true costs as opposed to charge data were used. The price year was not specified and no adjustment appeared to be made for inflation. The effects of alternative antibiotic modalities on indirect costs were not explicitly discussed; although it can be argued that the groups were not statistically different in terms of hospital stay or of being free from infection. The conversion rate from German currency to US dollars was not reported.
Other issues The authors' conclusion appears to be justified given the uncertainties in the data. Although the issue of generalisability to other settings or countries was not addressed, appropriate comparisons were made with other studies. The study sample consisted of patients with penetrating trauma treated in hospital emergency department and the authors' general comments appear to reflect that.
Implications of the study The administration of multiple doses of antibiotics over several days becomes unnecessary, reducing the risk of selecting undesirable nosocomial problem pathogens and avoiding treatment "gaps" resulting from missed or delayed dosing of antibiotic medication. Together with timely, thorough surgical care, administration of antibiotics within a short time after injury is a major contributory factor to the prevention of infection in patients with penetrating trauma.
Bibliographic details Schmidt-Matthiesen A, Roding H, Windolf J, Sommerfeldt D, Gutt C, Pannike A, Encke A. A prospective, randomised comparison of single-vs. multiple-dose antibiotic prophylaxis in penetrating trauma. Chemotherapy 1999; 45(5): 380-391 Indexing Status Subject indexing assigned by NLM MeSH Abdominal Injuries /complications /surgery; Adult; Antibiotic Prophylaxis; Bacterial Infections /drug therapy /etiology; Cefoxitin /administration & Ceftriaxone /administration & Cephalosporins /administration & Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination /administration & Extremities /injuries; Female; Humans; Male; Prospective Studies; Pseudomonas Infections /drug therapy; Staphylococcal Infections /drug therapy; Thoracic Injuries /complications /surgery; Wound Healing; Wounds, Penetrating /complications /economics /surgery; dosage; dosage /economics; dosage /economics; dosage /economics AccessionNumber 21999001729 Date bibliographic record published 31/10/2000 Date abstract record published 31/10/2000 |
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