This review found that topical ampicillin was effective for the prevention of infection in surgical wounds, but that no additional benefits were seen when ampicillin was used with systemic antibiotics. In view of the limitations in the current evidence, the authors' advice on the need to conduct further research to clarify the role of ampicillin in clinical practice appears appropriate.

To assess whether topical ampicillin given prophylactically can reduce the rate of wound infections in clean contaminated and contaminated surgical wounds.

MEDLINE and the Cochrane Controlled Trials Register were searched from 1960 to 2001; the search terms were given. The references of retrieved articles were also checked in order to locate further trials. Studies published in languages other than English were excluded from the review. Only published material was included in the review.

Study designs of evaluations included in the review

To be included in the review, the studies needed to be randomised controlled trials (RCTs).

Specific interventions included in the review

The interventions needed to compare topical ampicillin given with or without systemic antibiotic treatment against no topical agents or an inert agent. The doses of ampicillin ranged from 500 mg to 2 g.

Participants included in the review

The participants were those undergoing colorectal or appendectomy surgery.

Outcomes assessed in the review

The outcomes were documented infection rates in intervention and control groups.

How were decisions on the relevance of primary studies made?

Two reviewers independently assessed the titles, abstracts and full papers of identified studies.

Quality was assessed through an investigation of the following trial characteristics: method of randomisation, blind outcome assessment, written definition of surgical wound infection, loss to follow-up, and whether an intention-to-treat analysis was undertaken. The authors did not state how the papers were assessed for quality, or how many reviewers performed the quality assessment.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

How were the studies combined?

Separate meta-analyses were conducted to obtain odds ratios (ORs) for the following categories: topical ampicillin versus no antibiotic prophylaxis in clean contaminated wounds; topical ampicillin versus no antibiotic prophylaxis in contaminated wounds; and topical ampicillin combined with systemic antibiotics versus systemic antibiotics alone. Studies that included both clean and contaminated wounds had the appropriate subgroup of patients included in the above categories.

How were differences between studies investigated?

Statistical heterogeneity was investigated within each pooled group of studies.

Nine RCTs with a total of 1,773 participants were included in the review.

Based on 5 trials (n=886), topical ampicillin resulted in a statistically significant reduction in wound infection associated with clean contaminated wounds (OR 0.084, 95% confidence interval, CI: 0.044, 0.164, P<0.0001). There was evidence of statistically significant heterogeneity (chi-squared 55.72, P<0.001).

Based on 3 trials (n=188), topical ampicillin showed a statistically significant reduction in surgical wound infections associated with contaminated wounds (OR 0.262, 95% CI: 0.136, 0.505, P<0.0001). There was evidence of statistically significant heterogeneity (chi-squared 17.53, P<0.001).

Based on 4 trials (n=669), there was no statistically significant difference in wound infections between topical ampicillin combined with systemic antibiotic prophylaxis and systemic antibiotic prophylaxis used alone (OR 0.927, 95% CI: 0.271, 1.716). There was no evidence of statistical heterogeneity in this group of studies (chi-squared 1.482, P>0.1)

Topical ampicillin was effective for the prevention of infection in clean contaminated wounds, but no incremental benefit was seen with systemic antibiotics.

The review had a defined question with stated inclusion criteria for the participants, interventions, outcomes and study designs. The search for studies was based on two databases with some additional reference checking. However, unpublished data and foreign language studies were not included in the review, thus raising the possibility of publication and language bias. Aspects of the review process, such as the methods of data extraction and quality assessment, were not described in full so it was not possible to ascertain whether any bias might have been introduced into the review. The quality of the trials was assessed, but the influence of trial quality on the results was not fully explored in the meta-analyses. The data were pooled despite observed statistical heterogeneity.

In view of these methodological issues and methodological limitations in the primary studies, the authors' advice on the need to conduct a large trial investigating any incremental benefit of ampicillin over and above systemic antibiotics appears appropriate.

Practice: The authors stated that an in vitro analysis of common infecting organisms would be required before the use of ampicillin could be authorised in current practice. They also stated that the combination of ampicillin and systemic antibiotics cannot be supported by the current evidence.

Research: The authors stated that a large clinical trial would be required to identify any potential incremental benefit of ampicillin when used with systemic antibiotics.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.