Figure 1 summarises the search and review process. Among the 74 articles reviewed in detail, 39 studies on independent populations reported data that contributed to the meta-analyses. Among the 39 studies that met the inclusion criteria, 17 assessed the effectiveness of nasal decolonization compared with standard of care,24
15 compared glycopeptide prophylaxis with β lactam prophylaxis,41
and seven assessed a bundle in which patients were screened for nasal colonization with S aureus
, decolonized, and MRSA carriers given glycopeptide prophylaxis and all other surgical patients given β lactam prophylaxis.56
Of the 15 study authors who we attempted to contact, 12 responded. Three authors did not have the necessary data, but nine shared their data.
Fig 1 Literature search for articles on nasal decolonization or glycopeptide prophylaxis for preventing surgical site infections (SSIs) caused by Gram positive bacteria
Of the 39 studies included in the meta-analysis, 13 were randomized controlled trials and 26 were observational studies. Thirty six of these studies were published in peer reviewed journals, whereas three were presented in abstract form only (see supplementary table 1). Overall, the randomized controlled trials included in this meta-analysis had a fairly low risk of bias (fig 2). Table 1 presents the Downs and Black subscale scores for each observational study. In general, the observational studies had good external validity but poor internal validity.
Fig 2 Risk of bias assessment for randomized controlled trials. + indicates low risk of bias, − indicates high risk of bias, and ? indicates unclear risk of bias
Table 1 Risk of bias among observational studies as measured by Downs and Black subscales. Values in brackets are total scores achievable
Bundle including decolonization and glycopeptide prophylaxis meta-analysis
Seven quasi-experimental studies assessed infection prevention bundles that utilized both nasal decolonization and glycopeptide prophylaxis. Two studies decolonized MRSA carriers only, two decolonized MRSA carriers and MSSA carriers, and three decolonized all patients in the intervention group; in one of the latter studies, mupirocin treatment was stopped if the results of nares cultures were negative. MRSA carriers received vancomycin for prophylaxis in four studies, vancomycin and cefazolin in two studies, and teicoplanin in one study (see supplementary table 1a). Two of these studies included cardiac operations, three included total joint arthroplasties, and two included general orthopedic surgical procedures (see supplementary table 1a). All of these studies were sufficiently homogeneous and thus could be included in the meta-analyses to assess all outcomes (I2=0%, P>0.30).
In this meta-analysis, the decolonization and prophylaxis bundle was significantly protective against surgical site infections caused by both Gram positive bacteria (fig 3) and S aureus (table 2). Although this bundle was shown to be significantly protective against MRSA and MSSA surgical site infections, the effect estimate for MRSA surgical site infections was stronger than for MSSA surgical site infections, possibly because glycopeptide prophylaxis was used to prevent the MRSA surgical site infections (table 2).
Fig 3 Forest plot of bundle intervention to prevent surgical site infections caused by Gram positive bacteria. All studies were observational
Nasal decolonization meta-analysis
Of the 17 studies that assessed nasal decolonization, five were randomised controlled trials and 12 were quasi-experimental studies. Ten studies included cardiac operations and three assessed total joint arthroplasties. Since the number of studies that assessed total joint arthroplasty was small, we also included the seven studies that assessed nasal decolonization for general orthopedic operations. The decolonization regimen varied across studies. However, 16 of 17 studies used mupirocin ointment to decolonize the nares and one study used nasal chlorhexidine gluconate. (See supplementary table 1b for details of these studies.)
The meta-analysis of these 17 studies found that nasal decolonization was associated with a decreased rate of Gram positive surgical site infections and that these studies were significantly heterogeneous (fig 4). When surgical site infections caused by S aureus were assessed as the outcome among the 17 studies, the results were homogenous (I2=12%; P=0.32) and nasal decolonization was associated with a significantly lower risk of S aureus surgical site infections (table 2). The pooled relative risks were similar when study results were stratified by surgical site infections caused by MRSA or MSSA, suggesting decolonization was protective against either. Additionally, nasal decolonization was significantly protective against S aureus surgical site infections among patients who underwent orthopedic or cardiac surgical procedures (table 2). When only randomized controlled trials were assessed, nasal decolonization was associated with a statistically significant decline in S aureus surgical site infections, but this protective association was not statistically significant for all Gram positive surgical site infections (table 2).
Fig 4 Forest plot of nasal decolonization to prevent surgical site infections caused by Gram positive bacteria, stratified by study design
In 11 studies, all patients in the intervention group were decolonized with an intranasal antimicrobial agent regardless of whether they carried S aureus in their nares. When the effects of these studies were pooled, nasal decolonization was associated with a significant decrease in S aureus surgical site infections (pooled relative risk 0.40, 95% confidence interval 0.29 to 0.55). In contrast, six other studies decolonized only patients who carried S aureus in their nares. The pooled effect estimate of these six studies indicated that this approach was also associated with a significant decrease in S aureus surgical site infections (0.36, 0.22 to 0.57).
Six studies assessed nasal decolonization plus skin decontamination with either chlorhexidine gluconate or triclosan. The pooled effect estimate for this intervention was consistent with a protective effect against S aureus surgical site infections (0.29, 0.19 to 0.44). The meta-analysis of the 11 other studies, which assessed decolonization alone without skin decontamination, also found a statistically significant protective effect against S aureus surgical site infections (0.70, 0.50 to 0.97). However, none of the studies compared nasal decolonization alone with nasal decolonization plus skin decontamination.
Glycopeptide prophylaxis meta-analysis
Of the 15 studies assessing the effectiveness of preoperative glycopeptide prophylaxis, 12 assessed vancomycin and three assessed teicoplanin. Of the 15 studies, eight were randomised controlled trials, four were quasi-experimental studies, and three were retrospective cohort studies; eight studies included cardiac operations, five included total joint arthroplasties, and two assessed both. (See supplementary file table 1c for details of these studies.)
The meta-analysis of the association between glycopeptide prophylaxis and surgical site infections found that this intervention was significantly protective against MRSA surgical site infections compared with β lactam prophylaxis (table 2). Conversely, glycopeptide prophylaxis was a risk factor for MSSA surgical site infections, although this finding was not statistically significant (table 2). However, among all studies and among only randomized controlled trials, glycopeptide prophylaxis was not associated with significantly decreased surgical site infection rates caused by Gram positive bacteria or by S aureus (fig 5).
Fig 5 Forest plot of glycopeptide prophylaxis for all patients to prevent surgical site infections caused by Gram positive bacteria, stratified by study design
Six studies compared the efficacy of prophylaxis with a combination of a glycopeptide plus another antimicrobial agent (for example, rifampin, clindamycin, cefuroxime, cefazolin, ticarcillin/clavulante) and prophylaxis with a β lactam antibiotic only. When those six studies were pooled, the combination prophylaxis was significantly protective against Gram positive surgical site infections (pooled relative risk 0.22, 0.09 to 0.55). Conversely, when the nine studies that compared glycopeptide prophylaxis alone with β lactam prophylaxis were combined, glycopeptide prophylaxis was a risk factor for Gram positive surgical site infections, though this result did not reach statistical significance (1.19, 0.99 to 1.45).
For each meta-analysis we calculated fixed effects relative risks and fixed effects risk differences. The fixed effects relative risks were nearly identical to the random effects relative risks for the associations between nasal decolonization and Gram positive surgical site infections (fixed effects 0.44, 0.36 to 0.54), between glycopeptide prophylaxis and Gram positive surgical site infections (fixed effects 0.89, 0.75 to 1.06), and between the bundle and Gram positive surgical site infections (fixed effects 0.40, 0.30 to 0.54). Nasal decolonization alone and the bundle were both associated with a significantly decreased risk of Gram positive surgical site infections (risk difference −0.0107, 95% confidence interval −0.0134 to −0.0080, and −0.0057, −0.0077 to −0.0038, respectively). Glycopeptide prophylaxis was not associated with a statistically significant decrease in the risk of Gram positive surgical site infections (−0.0036, −0.0088 to 0.0016).
Additionally, to evaluate whether interventions that focused on decreasing S aureus surgical site infections might increase the rate of surgical site infections caused by other organisms, we evaluated the studies to assess the association between the interventions of interest and all surgical site infections and surgical site infections specifically caused by Gram negative bacteria. Nasal decolonization was associated with a significantly protective effect of reducing all surgical site infections (pooled relative risk 0.60, 95% confidence interval 0.49 to 0.73) and Gram negative surgical site infections (0.15, 0.03 to 0.74). Compared with β lactam prophylaxis, glycopeptide prophylaxis was not statistically significantly associated with changes in all surgical site infections (1.00, 0.70 to 1.42) or Gram negative surgical site infections (0.90, 0.50 to 1.61).The bundle was significantly protective against all surgical site infections (0.47, 0.37 to 0.60) but was not significantly associated with changes in Gram negative surgical site infections (0.73, 0.39 to 1.36) nor Gram positive surgical site infections caused by pathogens other than S aureus (1.02, 0.50 to 2.05).
Publication bias assessment
Funnel plots assessing publication bias were visibly symmetrical for studies of nasal decolonization and studies of the decolonization and glycopeptide prophylaxis bundle (see supplementary figure 1). The funnel plot was visibly asymmetrical for studies of glycopeptide prophylaxis, suggesting that small studies that demonstrated the superiority of β lactam prophylaxis over glycopeptide prophylaxis may not have been published. However, if studies showing the superiority of β lactam prophylaxis were published, these studies would add further evidence that glycopeptide prophylaxis is not superior to β lactam prophylaxis for the prevention of surgical site infections.