8 INTERNATIONAL RESEARCH & OPINION

Antibacterials and infections - news from ISPOR

At the Third Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) [Philadelphia, US; May 1998] one session was devoted to presentations of pharmaco­economic studies of antibacterials in the treatment of infection. The results of a selection of studies presented at the session are outlined below. Researchers in 3 Spanish studies investigated the economic impact of tazobactam/piperacillin in neutropenia and intra­abdominal infection, and the impact of teicoplanin vs vancomycin in neutropenia. In another study, German researchers compared 4 antibacterial regimens for the treatment of skin and soft tissue infections.

Febrile neutropenia Tazobactam/piperacillin is more cost effective than

ceftazidime when used as adjunctive therapy with amikacin for the treatment of chemotherapy-induced febrile neutropenia. 1 This is the finding of a modelling study that was conducted by researchers from the Hospital Universitario de Salamanca and Wyeth­Lederle, Spain, using data from 2 large clinical trials.

Patients in the EORTC* trial were randomised to receive treatment with amikacin 1.5 g/day plus either tazobactam/piperacillin 4g 4 times daily or ceftazidime 2g 3 times daily. Those in the GAF** trial were randomised to receive amikacin 0.75g twice daily plus tazobactam/piperacillin 4g 4 times daily or amikacin 0.75g 3 times daily plus ceftazidime 1g 3 times daily. In total, 493 patients received tazobactam/piperacillin and 498 received ceftazidime.

Tazobactam/piperacillin favoured Efficacy data from the clinical trials showed the

following episodes of success with tazobactam/ piperacillin vs ceftazidime: 228 (57%) vs 202 (50%) in the EORTC trial and 57 (60%) vs 42 ( 44%) for the GAF trial, respectively. These values represent a total of 285 and 244 'units of effectiveness' for tazobactam/ piperacillin and ceftazidime, respectively. Per-patient treatment costs in the clinical trials totalled $US3035 and $US2883 for tazobactam/piperacillin and ceftazidime, respectively. Multiplying per-patient treatment costs by the number of patients ( 493 and 498, respectively) generated total costs of $US 1.5 million and $US 1.4 million for tazobactam/ piperacillin and ceftazidime, respectively.

This generates cost-effectiveness values of $US5250 and $US5884 per unit of treatment success for the 2 regimens, respectively. Therefore, tazobactam/ piperacillin 'presented a better cost-effectiveness relation' to ceftazidime in the treatment of patients with febrile neutropenia, reducing the cost per unit of treatment success by $US635.

Intra-abdominal infections Tazobactam/piperacillin is more cost effective than

imipenem/cilastatin in the treatment of intra-abdominal infections when its clinical efficacy is higher than, or similar to, that for imipenem/cilastatin.2 So say 2 of

PharmacoEconomics& OutcomesNews4Jul1998 No.169

the Spanish researchers involved in the previous study who also assessed the pharmacoeconomics of tazobactam/piperacillin in this second indication.

Their decision-analytical model used data obtained from 2 randomised clinical trials comparing 10 days of antibacterial therapy for intra-abdominal infection. One trial compared tazobactam/piperacillin 4g/0.5g 3 times daily with imipenem/cilastatin 1g/1g (high dose) 3 times daily in 86 patients. Under an intention­to-treat analysis, clinical success rates in this study were 55.3 and 51.3%, respectively. The other trial compared tazobactam/piperacillin 4g/0.5g 3 times daily with imipenem/cilastatin 0.5g/0.5g (low dose) 3 times daily in 134 patients. Clinical success rates were 74 and 61.5%, respectively.

Tazobactam/piperacillin wins again

Information on treatment patterns and resource use was obtained from 5 expert physicians in Spain, and information on treatment costs was obtained from published articles, government publications and hospital price lists. All costs were expressed in 1995 Spanish pesetas (Pta).

Intention-to-treat analysis showed that tazobactam/ piperacillin was cost saving compared with both high­and low-dose imipenem/cilastatin in the treatment of intra-abdominal infection [see table 1]. Furthermore, incremental cost-effectiveness analysis showed that, compared with high- and low-dose imipenem/cilastatin, tazobactam/piperacillin would save an additional Pta2.04 million and Pta265 736 per additional patient with treatment success, respectively.

Table 1. Costs* of tazobactam/piperacillin vs imipenem/cilastatin in intra-abdominal infection using an intention-to-treat analysis

TnNitment coats Tazobactarn/ lmlpenem/ Difference I raciliin cilastatln

High dose imipenem/cilastatln:

I Cost per treatment success 408 260

Cost per treatment failure 709 964

581 315

670552

1 Total treatment costs 543 122 624 773 11 Low-dose imipenem/cilastatin:

Cost per treatment success 409 255 463 620

I. Cost per treatment failure 71 o 959 612 437

. Total treatment costs 487 698 520 915

i • 1995 pesetas (Pta); negative values equal cost savings with i tazobactam/piperacillin

-173055

39412

-81 651

-54 365

98522

-33217 i

Teicoplanin vs vancomycin in neutropenia

The direct costs and efficacy associated with teicoplanin and vancomycin are similar in the second­line treatment of febrile neutropenia, suggest other researchers from the Hospital Universitario de Salamanca, Spain.3

*European Organization for Research and Treatment of Cancer **Groupe d'etude des Aplasies Febriles

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INTERNATIONAL RESEAR CH & OPI NION

Their prospective randomised study involved 38 patients who received teicoplanin and 38 who received vancomycin after failing first-line empirical treatment with tazobactam/piperacillin plus amikacin for neutropenia. Clinical response was defined as apyrexia after 48 hours, after 7 days, or at conclusion of aplasia. Treatment costs included those associated with drug price, preparation and administration, monitoring, treatment of adverse effects, and treat­ment failure.

Comparable costs 18 teicoplanin recipients and 17 vancomycin

recipients experienced treatment success, and there were no differences between the 2 treatment groups in terms of drug-related renal or hepatic toxicity. The total treatment costs for the 2 respective groups were $US17 414 and $US19 124 which, according to the researchers, represented average per-patient costs of about $US450 and $US473. Administration and monitoring costs were lower in the teicoplanin group. The researchers also commented that teicoplanin is an attractive alternative as it is a once-daily regimen -the use of which can improve compliance and quality of life.

Skin and soft tissue infections Amoxicillinlclavulanic acid appears to be more

cost effective than tazobactam/piperacillin, which in tum is more cost effective than ceftriaxone and cefotaxime for inpatient treatment of skin and soft tissue infections.4 This is the finding of Yvonne Bruchhausen and B Rappenhoner from the Institute of Empirical Health Economics in Odenthal , Germany.

They constructed a decision-analytical model using data from 3 clinical trials of antibacterials for skin and soft tissue infections. One study involved 114 patients who received tazobactam/piperacillin for 6-7 days, another involved I 00 patients who received either ceftriaxone or amoxicillin/clavulanic acid for 7 days and the third involved 50 patients who received cefotaxime for 12.3 days. The IV antibacterial dosages received in these analyses were tazobactam/piperacillin 0.5gl2g 3 times daily, a single daily dose of ceftriaxone 2g or 3g, amoxicillinlclavulanic acid lgl2g 4 times daily or 2g/2g 4 times daily, and cefota.xime 2g 3 times daily.

Cost data incorporated into the model included those for drug acquisition, hospitalisation, hospital consuma-

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bles (e.g. dressings), treatment of adverse drug reactions, and lost productivity. The study was conducted from the perspective of the national economy.

Amoxicillin/clavulanic acid more cost effective

The success rates associated with these 4 regimens in the treatment of skin and soft tissue infections were 98% for cefotaxime, 95% for tazobactam/piperacillin, 94% for amoxicillinlclavulanic acid, and 90% for ceftriaxone. The direct, indirect and total costs, as well as the cost effectiveness associated with these treatments, are shown in table 2. Amoxicillinlclavulanic acid was the most cost effective alternative, followed by tazobactamlpiperacillin, ceftriaxone and cefotaxime. These result proved to be robust under sensitivity analysis.

Table 2. Total cost• and cost effectiveness of ~~ens for skin and soft tissue infections m ermany

AntlbM:t111181 onctc:oet lndlnct Tot.l c:oet COet c:oet ~ ..

Tazobactamf 2431 1026 3457 3639 piper8cllln

Amoxlcinlnl 2093 1061 3154 3355 c:lavulanlc acid

Celtr1axone 2703 1096 3799 4221 Cefotaxlme 4517 1828 6345 6474 • Deutschmarl<s

•• ~usted fof the rate ol treatment success

A flaw in this analysis, according to one of the delegates at the meeting, was that the 3 clinical trials included in the decision-analytical model did not compare all of the drugs under investigation. As a result, the random samples that received the drugs were from different populations. This highlights the need for prospective economic studies.

1. Dominguez-Gil A, eta!. Cost-effectiveness of piperacillin-ta.zobactam versus ceftazidime in patients with febrile neutropenia. Value in Health 1: 68, May-Jun 1998 2. Dominguez-Gil A, et al. Cos! -effectiveness analysis of piperacillin-tazobactam versus imipenem-cila.statin in the treatment of intra-abdominal infections. Value in Health I: 68-69, May-Jun 1998 3. Dominguez-Gil A, et a!. Randomised prospective srudy comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients. Value in Health 1: 37, May-Jun 1998 4. Bruchhausen Y, et al. Socio-economic relevance of inpatient treaunent of skin and soft tissue infections with ta.zobactamlpiperacillin 0.5g12.0g in comparison with amoxicillin/clavulanic acid, ceftriaxone, and cefotaxime. Value in Health I : 39, May-Jun 1998 aoomll2

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