Two retrospective subgroup analyses of ventilated and non-ventilated patients with MRSA [56, 57] from nosocomial pneumonia clinical trials [58, 59] showed that linezolid-treated patients had higher survival and clinical cure rates than vancomycin-treated patients. It has been suggested that this may be due to the favourable intrapulmonary distribution of linezolid . However, the viability and validity of these subset analyses has been questioned [61, 62], such that further trials are required before linezolid can be recommended to be used preferentially over vancomycin for the treatment of MRSA pneumonia. A recent trial of patients with MRSA-VAP, which was designed and powered to demonstrate "non-inferiority" of linezolid to vancomycin demonstrated numerically better values for linezolid-treated patients compared with van-comycin-treated patients with respect to microbiological eradication (56.5% and 47.4%, respectively), clinical cure (66.7% and 52.9%, respectively), survival rate (86.7% and 70.0%, respectively) and length of hospitalization (18.8 and 20.1 days, respectively), ventilation (10.4 and 14.3 days, respectively) and ICU stay (12.2 and 16.2 days, respectively) . For the small number of subjects in this study these differences were not statistically significant.
A recent meta-analysis including 9 trials comparing glycopeptides (7 vancomycin and 2 teicoplanin) with linezolid found that the linezolid versus glycopeptide analysis showed a clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I(2) = 0%) and a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98-1.22; p = 0.10) . In contrast, they found that the risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = 0.001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = 0.02) were higher with linezolid, but they did see no differences for renal dysfunction or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = 0.63). The authors therefore concluded that linezolid was not superior to vancomycin in pneumonia. However, only 3 of these studies enrolled exclusively patients with pneumonia .
Despite using the same trials for calculation, a second meta-analysis found also no difference in treatment success for patients pneumonia (OR = 1.16, 95% CI 0.85-1.57) but a trend for better eradication rates in all microbiologically assessed patients for linezolid (OR = 1.33, 95% CI 1.03-1.71). In contrast to Kalil et al. they found no difference in total adverse effects (OR = 1.14, 95% CI 0.82-1.59) but more nephrotoxicity in patients receiving vancomycin (OR = 0.31, 95% CI 0.13-0.74) .
As clinical data on linezolid in HAP/VAP are inconclusive so are the recommendations of current guidelines. The ATS/IDSA guideline on HAP/VAP does not advocate to preferred use of linezolid in patients with HAP/VAP . In contrast, the German sepsis guideline recommends linezolid in proven MRSA pneumonia and expressively warns to rely on vancomycin mono-therapy in such cases .