Vancomycin plus rifampicin for methicillin-resistant Staphylococcus aureus pneumonia benefits only those who have no development of rifampicin resistance during treatment

To the Editor: We read with great interest the article by Jung et al (1) in the January 2010 issue of Critical Care Medicine. In this prospective study of patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, they described that in the modified intention-to-treat population clinical cure rates were evaluated on day 14 of treatment, with 53.7% success for the vancomycin and rifampicin combination therapy group (VR group) and 31.0% success for those treated with vancomycin alone (p .047). They concluded that vancomycin plus rifampicin seemed to be more effective than vancomycin alone in the treatment of nosocomial MRSA pneumonia. However, according to the study by Ju et al (2) and our recent study (3), resistance to rifampicin developed in approximately one-third of MRSA isolates during rifampicin treatment at a median of 12 days (range, 5–58 days) and 9 days (range, 5–18 days) after the commencement of rifampicin treatment, respectively. Therefore, we are worried about whether the rapid emergence of rifampicin-resistant MRSA during rifampicin treatment would affect the clinical outcome of patients with MRSA pneumonia who received dual therapy. Based on the findings of Jung et al’s study, we divided the VR group (41 patients) into two subgroups. The first group had rifampicin-resistant MRSA (14 patients) and the other group had no rifampicin-resistant MRSA (27 patients) develop during rifampicin treatment. The microbiological eradication rate was lower in patients with emergence of rifampicin resistance (38.5%) than in those who has no rifampicin resistance (88.5%; p .002). However, the clinical cure rate did not differ between these two groups, i.e., 50% in patients with rifampicin resistance and 55.6% in patients without rifampicin resistance (p .754). Furthermore, when we compared the clinical outcome of the two subgroups of the VR group and the group treated with vancomycin alone, the favorable outcome in the VR subgroup was only found among those who did not have rifampicin resistance develop (55.6% vs. 31%; p .042). However, there was no significant difference between the subgroup that had rifampicin resistance when compared to the group treated with vancomycin alone (50% vs. 31%; p .198). Regarding microbiological eradication rate, the highest eradication rate was found in the VR subgroup with no rifampicin resistance (88.5%), followed by the group treated with vancomycin alone (61.5%) and the VR subgroup with rifampicin resistance (38.5%). These data suggested that the beneficial clinical and microbiological outcomes of the VR group might have occurred only in patients with no development of rifampicin resistance but not in patients with development of rifampicin resistance during the VR treatment. This finding emphasized the importance of monitoring the emergence of rifampicin resistance during rifampicin-containing therapy for MRSA, which would be helpful in guiding treatment regimens. Furthermore, Jung et al did not mention whether they changed the antibiotics regimen or whether they continued to use rifampicin when rifampicin resistance developed during VR treatment. They also did not explain why 90% of patients had concomitant use of broadspectrum antibiotics for a median of 9–10 days for Gram-negative pathogens, although approximately 88% of them had MRSA as the sole pathogen for their pneumonia. In summary, we believe that the beneficial effect of vancomycin plus rifampicin for nosocomial MRSA pneumonia is limited to the subgroup of patients with no development of rifampicin-resistant MRSA isolates. Regarding patients with subsequent development of rifampicinresistant MRSA isolates, combination therapy with vancomycin and rifampicin is not better than vancomycin alone for treating MRSA pneumonia. The authors have not disclosed any potential conflicts of interest. Che-Kim Tan, MD, Department of Intensive Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan; ChihCheng Lai, MD, Department of Internal Medicine, Cardinal Tien Hospital, Taipei, Taiwan; Sheng-Hsiang Lin, MD, Department of Internal Medicine, Taipei County Hospital, Taipei County, Taiwan; Po-Ren Hsueh, MD, Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan