In this study, vancomycin presented favorable efficacy outcomes compared with teicoplanin, although the rate of discontinuation of the study drugs due to side effects was higher in the vancomycin group. Treatment outcome, including mortality and discontinuation of the study drugs due to treatment failure, was considered a clinical failure of the study drugs. Although concerns regarding the possibility of overestimation of the clinical failure rate were noted, there were significant differences in the mortality and discontinuation rates due to treatment failure between vancomycin and teicoplanin. Furthermore, the clinical cure rate was favorable in the vancomycin group, although no statistical significance was noted. Thus, the clinical cure rate may be insufficient to retrospectively evaluate the efficacy and safety of vancomycin and teicoplanin with a relatively small number of patients because linezolid could be actively considered as an alternative for patients with MRSA pneumonia after Wunderink’s study.[20, 26] Furthermore, the clinicians in the present study changed the study drugs to linezolid in 27.6% (32/116) of patients because they suspected treatment failure of the study drugs in nine patients in the vancomycin group and 23 patients in the teicoplanin group. More side effects were noted, leading to the discontinuation of the study drugs in the vancomycin group compared with that in the teicoplanin group. We selected clinical failure as the primary outcome owing to treatment failure because these changes could lead to the underestimation of treatment efficacy. Moreover, the treatment efficacy of vancomycin and teicoplanin were analyzed after excluding patients with adverse effects, as shown in Additional file 1. To the best of our knowledge, this is the first study to show that the outcomes of vancomycin are more favorable than those of teicoplanin in patients with MRSA pneumonia.
Glycopeptides are reported to present relatively lower lung penetration. Although teicoplanin presented a higher lung penetration ratio than vancomycin in previous studies, no clear evidence was presented.[13, 27–31] The penetration of various antibiotics into the lungs of patients with HAP and VAP was found to be variable.[32–34] Furthermore, the protein-binding rate of teicoplanin was variable in critically ill patients. Therefore, clinicians could not agree that patients with MRSA pneumonia individually took adequate teicoplanin doses. Physicians could individually adjust the vancomycin dose based on therapeutic drug monitoring levels. The efficacy of vancomycin and teicoplanin depends on the trough drug concentration. Therefore, variability possibly affected the efficacy of teicoplanin. Recently, the importance of therapeutic drug monitoring of teicoplanin has been increasingly emphasized.
Another possible cause of unfavorable teicoplanin outcomes in this study was that more than 50% of the patients in the teicoplanin group were prescribed a low-dose regimen. Mimoz et al. indicated that patients with VAP required a high-dose teicoplanin regimen to maintain adequate trough levels in the lungs. However, there was no difference in the clinical failure rate (60.0% vs. 61.7%, p = 0.906), clinical cure rate (40.0% vs. 36.2%, p = 0.789), and adverse event rate (0.0% vs. 2.1%, p > 0.999) between the high-dose and low-dose groups (Additional file 3). Even in multivariate analysis for clinical failure, there was no significant difference between the two groups, although high-dose teicoplanin presented a lower aOR. Another possible cause was that more patients with underlying respiratory or cardiovascular disease were enrolled in the teicoplanin group. Although previous medical history did not affect the composite events in the Cox proportional hazard model, further studies are needed to evaluate the effects of teicoplanin dose and these covariates because a relatively small number of patients were included in this study.
In this study, more patients in the vancomycin group had to discontinue the study drugs due to adverse effects. Azotemia was the most common adverse effect in this study, which is similar to the results of other studies.[8, 37] The nephrotoxicity of vancomycin is a well-known side effect. Various risk factors are associated with vancomycin-induced nephrotoxicity, including vancomycin trough level of ≥16.2 µg/mL. [38, 39] Furthermore, nosocomial pneumonia is regarded as a possible risk factor for vancomycin-induced nephrotoxicity because MRSA pneumonia usually requires a higher dose of vancomycin because of poor lung penetration and lower susceptibility to antibiotics if they are associated with hospital-acquired infection.[39, 40] The mean vancomycin trough levels were >16.2 µg/mL at days 6 and 9 during the therapeutic period in this study because most of the clinicians attempted to maintain the trough level between 15 and 20 µg/mL. Relatively high concentrations may affect azotemia. Conversely, only one case of adverse effect was noted in the teicoplanin group. Bacteremia is also considered an important factor in nephrotoxicity as it may be a sign of a more serious disease that is prone to complications due to bacteremia. However, no obvious difference was found between the groups with and without bacteremia. Thrombocytopenia is a well-known complication of teicoplanin administration. Because vancomycin presented unfavorable outcomes owing to side effects and poor prognosis was reported in pneumonia patients with acute kidney injury in a previous study, teicoplanin could be considered as an alternative, especially in patients with risk factors associated with vancomycin-induced nephrotoxicity. In our study, among the 13 patients who discontinued vancomycin due to adverse effects, vancomycin was replaced with teicoplanin in 12 patients. The rate of each side effect was relatively lower than that reported in other studies because only adverse effects leading to the discontinuation of study drugs were included.[37, 41, 43]
This study had several limitations. First, the study was conducted at a single referral center using a retrospective design with relatively small populations. Additionally, patients for whom vancomycin or teicoplanin was initiated at other hospitals or who were transferred to other facilities were excluded, which might have led to selection bias. Further randomized controlled studies with a large number of patients with MRSA pneumonia would be needed to clarify the results of this study. Second, MRSA pneumonia was defined to be based on the physicians’ judgments. Although the medical records to confirm the clinical diagnosis and exclude patients with other possible causative pathogens were reviewed, there were possibilities indicating that pneumonia was caused by microorganisms other than MRSA. Third, the discontinuation of the study drugs due to adverse events as outcomes independent of clinical failure and clinical cure were analyzed. As discontinuation of the study drugs due to side effects occurred more in the vancomycin group, the clinical failure rate could be overestimated, which makes it difficult to apply our results to real clinical practice. If physicians could identify patients at high risk for vancomycin-induced adverse effects, our results could effectively help physicians in real practice. Finally, the two-dose teicoplanin regimen was included in this study. Thus, the dose effects for the efficacy of teicoplanin could not be confirmed. Further studies may be needed to evaluate each dose regimen of teicoplanin and vancomycin.