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.

Use of intravenous ciprofloxacin or imipenem therapy in the treatment of hospitalised patients with severe pneumonia.

Treatment.

Cost-effectiveness analysis.

Hospitalised patients with severe pneumonia.

Hospital. The economic study was carried out in the USA.

No dates were given.

Effectiveness data were derived from a single study.

Costing was retrospectively performed on the same patient sample as that used in the effectiveness analysis.

Power calculations were not used to determine the sample size. The study sample initially consisted of 32 enrolled patients, 5 of whom were excluded because they were not efficacy-valid (receiving less than 3 days of study drugs). The remaining 27 patients had already been randomly allocated to the ciprofloxacin-treated group (n=13 with a mean age of 32.5 years) or the imipenem-treated group (n=14 with a mean age of 38 years).

This was a retrospective post-treatment single-centre study of patients who had already participated in a prospective, multicentre, double-blind, randomised study. The duration of follow-up was until discharge for a minimum of 37 days after the end of treatment with the study drug. No loss to follow-up was reported except for those who were excluded from the study for being efficacy-invalid.

The principle used in the analysis of effectiveness was treatment completers (efficacy-valid cases) only.

The health outcome measures were:

bacteriological response (classified as eradication, presumed eradication, persistence, superinfection or indeterminate) at the end of therapy (i.e. 3 to 7 days after treatment);

clinical response (categorised as resolution, failure or indeterminate);

post-study subsequent infection requiring post-study drug treatment with antimicrobials;

the incidence of subsequent Gram-negative infection;

the isolation of Pseudomonas aeruginosa.

The two study groups were comparable in terms of demographic and medical characteristics at baseline.

The ciprofloxacin group had a bacteriological eradication of 85% compared to 57% in the imipenem group, (NS). This compared to 69% (ciprofloxacin) and 59% (imipenem) in the original multicentre study. The corresponding rates in terms of clinical resolution were 77% and 50%, (NS), as compared to 69% and 56%, in the multicentre trial. The rate of post-study subsequent infection requiring post-study drug treatment with antimicrobials was 38% in the ciprofloxacin group versus 64% in the imipenem group. The ciprofloxacin group experienced a 15% incidence of subsequent Gram-negative infection compared to 64% for the imipenem group, (p<0.05). The corresponding values in terms of isolation of Pseudomonas aeruginosa were 7.7% and 50%, (p<0.05).

Upon evaluating the isolation of bacteria in persistent or subsequent infections, a significant difference emerged in favour of ciprofloxacin with a lower incidence of P. aeruginosa and total Gram-negative infections. The reasons for the apparent superiority of ciprofloxacin are not clear, but may include greater lung tissue and fluid penetration, preservation of anaerobic and Gram-positive flora in the oral cavity and upper airways, and/or host-immune differences.

The benefit measure was the number of patients cured (cure rate or clinical resolution rate).

Costs were not discounted due to the short follow-up period of the study. Quantities were reported separately from the costs in terms of subsequent length of stay and days on study drugs. Cost items were reported separately. The cost analysis covered the costs of hospitalisation and antimicrobials. The perspective adopted in the cost analysis was not explicitly specified. The acquisition costs to the study institution were used for antimicrobial costs, while the cost per hospital day was estimated. The date of the price data was not specified.

Not considered.

US dollars ($).

No sensitivity analysis was performed.

10 (77%) patients were cured in the ciprofloxacin-treated group compared to 7 (50%) in the imipenem-treated group, (NS).

The ciprofloxacin group had a total cost of $291,269 for 13 patients versus $533,140 for the imipenem-treated group with 14 patients.

Cost per patient cure was calculated as the measure of cost-effectiveness producing a cost per cure of $29,127 for ciprofloxacin compared to $76,163 per cure for imipenem.

Initial treatment of severe pneumonia with ciprofloxacin resulted in significantly less subsequent Gram-negative infection and was associated with substantially lower curative costs.

No health technology was regarded as the comparator.

The internal validity of the estimates of measures of benefit can not be guaranteed due to small sample size (arising from the fact that this study consisted of a subset of the sample involved in a larger multicentre randomised study).

Quantities were reported separately from the costs in general categories. Adequate details of the methods of cost estimation were given. The retrospective nature of the cost analysis may have adversely affected its internal validity. The study lacked a specific price year. The authors noted that the higher incidence of more serious types of post-therapy infections in the imipenem/cilastatin group probably accounted for greater expenditures in comparison with the ciprofloxacin group.

The interpretation of the cost-effectiveness results should be approached with some caution due to the small sample size, the fact that the analysis was based on treatment completers only, and the lack of a comprehensive sensitivity analysis. The issue of generalisability to other settings or countries was not addressed. Appropriate comparisons were made with other studies (which were reported to exist only in small numbers). No dates were specified for the effectiveness, resource use, and price data used in the study.

Future health economic studies are needed to substantiate these findings and to identify whether there are similar cost savings with ciprofloxacin in patients with other serious infections.

None stated.

Comment in: Journal of Antimicrobial Chemotherapy 1999;43 Suppl A:115.