Evidence supported second- or third- generation cephalosporins for cardiac surgery prophylaxis, and suggested there may be an advantage to prophylaxis prolongation up to 48 hours postoperatively. The authors' conclusions reflected only a subset of the findings. They should therefore be interpreted with caution as they do not reliably reflect the overall evidence, particularly in terms of the primary outcome.

To compare different antibiotic prophylaxis strategies in cardiac surgery according to type, duration and dosing.

The Cochrane Library, PubMed and LILACS were searched until December 2010 with no language or date restrictions; search terms were reported. Conference proceedings and bibliographies of included studies were handsearched to locate further published and unpublished literature.

Eligible for inclusion were randomised controlled trials (RCTs) that compared any systemic single or combination antibiotic prophylaxis versus a different regimen, different dose, or different durations of prophylaxis. The primary outcome of interest was deep sternal wound infections. Trials had to contain at least 10% of patients undergoing coronary artery bypass graft, valve, aortic or other cardiac surgery (excluding heart transplantation). Secondary outcomes included: wound and surgical site infections; surgical site infections requiring surgical intervention; surgical site infections caused by Gram-negative or Gram-positive bacteria; methicillin-resistant Staphylococcus aureus (MRSA); pneumonia; endocartitis; bacteraemia; all-cause mortality; and adverse events.

Mean participant age per trial arm ranged from 28.6 to 70.1 years (where reported); three trials contained children. Trials took place between 1964 and 2008 (where reported). A wide range of antibiotics and regimens were included (reported fully in paper). Duration of postoperative surveillance ranged from 0 to 168 hours (where reported). Surgical site infection definitions varied widely (where reported).

Two reviewers independently selected studies for inclusion.

Risk of bias was assessed according to adequacy of description for allocation concealment, allocation generation, double-blinding and intention-to-treat analysis. Descriptions were classified as adequate, not reported or inadequate.

The authors did not explicitly state how many reviewers performed the quality assessment.

Number of events for the outcomes were extracted to calculate risk ratios with 95% confidence intervals. Data were extracted up to three months postoperatively; authors were contacted for any missing data.

Two reviewers independently extracted the data.

Risk ratios (RRs) were pooled with 95% confidence intervals (CIs) using the Mantel-Haenszel fixed-effect method. Heterogeneity was assessed using Χ² and Ι² (where p below 0.1 indicated significant heterogeneity and Ι² values above 50% indicated inconsistency).

Meta-analyses were conducted to compare antibiotics that contained additional Gram-negative coverage versus mainly Gram-positive coverage (stratified by type of Gram-negative coverage for pneumonia and all-cause mortality); short (24 or less hours and over 24 hours) versus longer prophylaxis duration; glycopeptides versus β-lactam; cephalosporin- versus penicillin-based regimens; and low versus higher antibiotic dosing for surgical site infections. Two-tailed Pearson correlation analyses were performed to assess the relationships between various outcomes.

Where studies were not included in the meta-analyses, these were presented narratively.

Funnel plots were constructed to examine small study effects for meta-analyses including more than ten trials.

Fifty-nine RCTs (24,083 participants) were included in the review; trial sample size ranged from 30 to 3047 participants. Double-blind procedures were reported by 21 trials and low risk of bias for allocation concealment was reported by nine trials. Concealment methods were not reported by 41 trials; high risk of bias was reported for nine trials. Assessment for the use of intention-to-treat data was not reported.

Additional Gram-negative coverage versus mainly Gram-positive coverage: Compared to mainly Gram-positive coverage, statistically significant lower risks of postoperative pneumonia (RR 0.66, 95% CI 0.51 to 0.86, 24 trials) and all-cause mortality (RR 0.69, 95% CI 0.50 to 0.93, 18 trials) were found for antibiotics with additional Gram-negative coverage. The effect was statistically strongest for pneumonia when Gram-negative coverage was provided by a β-lactam (second or third-generation cephalosporin in most studies). No statistically significant heterogeneity or small-study effects were observed.

Prophylaxis duration: Statistically significant differences were found for trials that compared the same or different antibiotics in the long versus short-duration study arms for the following outcomes: deep sternal wound infection (RR 1.49, 95% CI 1.08 to 2.06, 15 trials); any sternal wound infection (RR 1.37, 95% CI 1.14 to 1.64, 20 trials); Gram-positive surgical site infection (RR 1.30, 95% CI 1.01 to 1.66, 12 trials); and surgical intervention for surgical site infection (RR 1.48, 95% CI 1.04 to 2.09, seven trials). Subgroup analyses by short duration arms indicated that the significant differences were due to short prophylaxis durations 24 or less hours post-operation but not short durations over 24 hours post-operation.

Glycopeptide versus β-lactam: Compared to β-lactams of the same duration, the risk for any surgical site infection was lower with glycopeptides but this was of borderline statistical significance (RR 0.74, 95% CI 0.56 to 0.99, six trials). Risk of surgical intervention for surgical site infection was statistically significantly lower with glycopeptides than with β-lactams of the same duration (RR 0.20, 95% CI 0.07 to 0.52, two trials).

Glycopeptides statistically significantly increased risks for deep sternal wound infection compared to β-lactams of a longer duration (RR 1.90, 95% CI 1.14 to 3.19, 3 trials), any sternal wound infection compared to β-lactams overall (RR 1.33, 95% CI 1.08 to 1.64, 9 trials) and to β-lactams of a longer duration (RR 1.77, 95% CI 1.36 to 2.32, three trials).

Cephalosporin-based versus penicillin-based prophylaxis regimen: Weak statistical significance was found for a lower risk of bacteraemia with cephalosporin-based prophylaxis regimens (RR 0.48, 95% CI 0.24 to 0.99, three trials, Ι²=52%).

Antibiotic dosing: No statistically significant differences were found (reported fully in paper).

Other analyses were reported in the review. Two studies were reported narratively.

Evidence supported second- or third-generation cephalosporins for cardiac surgery prophylaxis, and suggested that there may be an advantage to prophylaxis prolongation up to 48 hours postoperatively.

The review question was clear and the inclusion criteria appeared sufficiently replicable. Relevant data sources were searched and study selection was not restricted by language or publication status, which reduced the risks of language and publication biases. Attempts were made to minimise error and bias during study selection and data extraction, but this was unclear for the quality assessment stage. Suitable quality assessment criteria were used and results were variable.

Study details were presented and no significant statistical heterogeneity between trials was indicated in any of the meta-analyses reported. However, clinical and methodological differences did exist between the studies, which suggested that a fixed-effect model may not have been appropriate for the meta-analyses shown. Most studies assessed cephalosporins so it was uncertain whether there were sufficient data to assess the effects of other antibiotics, and so adequately answer the review question. Subgroup analyses may have been underpowered because they were often based on small numbers of trials. The authors stated that the included trials spanned a long time period (over 40 years), and findings may have been influenced by changes in practice and bacterial resistance over time.

The authors' conclusions reflected only a subset of the findings. They should therefore be interpreted with caution as they do not reliably reflect the overall evidence, particularly in terms of the primary outcome.

Practice: The authors stated that second- or third-generation cephalosporins should be the preferred agents for perioperative cardiac surgery prophylaxis. Glycopeptides might be warranted in locations with prevalent MRSA, and were non-inferior to β-lactams.

Research: The authors stated that all future trials should report surgical site infections by the Centres for Disease Control and Prevention criteria to allow comparability, and report on pneumonia and all-cause mortality. Further research to confirm the advantages of prophyaxis for treatment of pneumonia and mortality, and advantages of longer prophylaxis duration, and pre-/intra-operation administration were suggested.

This review was internally funded.

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.