The efficacy and safety of linezolid and glycopeptides in the treatment of Staphylococcus aureus infections

Abstract

To assess the effectiveness and safety of linezolid in comparison with glycopeptides (vancomycin and teicoplanin) for the treatment of Staphylococcus aureus infections, we conducted a meta-analysis of relevant randomized controlled trials. A thorough search of Pubmed and other databases was performed. Thirteen trials on 3863 clinically assessed patients were included. Linezolid was slightly more effective than glycopeptides in the intent-to-treat population (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10), was more effective in clinically assessed patients (OR 95% CI: 1.38, 1.17-1.64) and in all microbiologically assessed patients (OR 95% CI: 1.38, 1.15-1.65). Linezolid was associated with better treatment in skin and soft-tissue infections (SSTIs) patients (OR 95% CI: 1.61, 1.22-2.12), but not in bacteraemia (OR 95% CI: 1.24, 0.78-1.97) or pneumonia (OR 95% CI: 1.25, 0.97-1.60) patients. No difference of mortality between linezolid and glycopeptides was seen in the pooled trials (OR 95% CI: 0.98, 0.83-1.15). While linezolid was associated with more haematological (OR 95% CI: 2.23, 1.07-4.65) and gastrointestinal events (OR 95% CI: 2.34, 1.53-3.59), a significantly fewer events of skin adverse effects (OR 95% CI: 0.27, 0.16-0.46) and nephrotoxicity (OR 95% CI: 0.45, 0.28-0.72) were recorded in linezolid. Based on the analysis of the pooled data of randomized control trials, linezolid should be a better choice for treatment of patients with S. aureus infections, especially in SSTIs patients than glycopeptides. However, when physicians choose to use linezolid, risk of haematological and gastrointestinal events should be taken into account according to the characteristics of the specific patient populations.

Figure 1. Flow diagram of the randomized controlled trials (RCTs) for meta-analysis.

Figure 2. Meta-analyses of treatment success for clinically assessed patients.

Test of all studies for overall effect: Z = 3.65 P = 0.000; test of blinded RCTs for overall effect: Z = 2.11 P = 0.035; test of Non-blinded RCTs for overall effect: Z = 3.03 P = 0.002; test of RCTs in adults for overall effect: Z = 3.64 P = 0.000.

Figure 3. Meta-analyses of treatment success for clinically assessed patients with skin and soft-tissue infections, bacteraemia, and pneumonia.

Test of SSTI for overall effect: Z = 3.37 P = 0.001; test of bacteraemia for overall effect: Z = 0.91 P = 0.364; test of pneumonia for overall effect: Z = 1.73 P = .083.

Figure 4. Meta-analyses of treatment success for microbiologically assessed patients.

Test of all studies with microbiological assessment for overall effect: Z = 3.46 P = 0.001; test of S.aureus eradication for overall effect: Z = 4.43 P = 0.000; test of MRSA eradication for overall effect: Z = 3.78 P = 0.000.

Figure 5. Meta-analyses of adverse effects related to studied regimens.

Test of total adverse effects for overall effect: Z = 1.58 P = 0.113; test of patients withdrawn because of adverse effects for overall effect: Z = 1.41 P = 0.159; test of nephrotoxicity for overall effect: Z = 3.36 P = 0.001.

Figure 6. Meta-analyses of haematological, gastrointestinal, and skin adverse effects related to studied regimens.

Test of haematological adverse effects for overall effect: Z = 2.56 P = 0.010; test of gastrointestinal adverse effects for overall effect: Z = 7.74 P = 0.000; test of skin system adverse effects for overall effect: Z = 6.27 P = 0.000.

Figure 7. Meta-analysis of mortality in this pooled data.

Test of mortality for overall effect: Z = 0.29 P = 0.771.