Bi-Directional Regulation by Chinese Herbal Formulae to Host and Parasite for Multi-Drug Resistant <i>Staphylococcus aureus</i> in Humans and Rodents

Abstract

A decline in the immunopotential of the host plays acritical factor(s) in the occurrence of infections with methicillin-resistant Staphylococcus aureus (MRSA) or microorganisms by opportunistic infection. In such an infection, no way out for therapeutic concept, therefore bi-directional trial was the final choice. So we selected aformula, Dang Gui Liu Huang Tang (dLHT), which could both augmentimmune factorsin host and exert bacteriostatic effect. We sought to break through the epidemic by MRSA especially in elderly patient, by the fundamental and clinical trial by employing minor TCM, characterizing bidirectional ability of the decoction by western methods. Animal Experiment: Mitomycin-C (MMC)-treated mice with or without the infection of MRSA were made. The experimental design was made up to examine the bacteriostatic action as well as the immunopo-tentiating bias of the promising Chinese herbal medicine, dLHT, which was first proved for its immune potentiating activities as well as their sensitivity to antibiotics, but not direct aseptic effect was clear for MRSA. Both basic and clinical data showed that this formula was effective on repelling from the infectious focus after the treatment of MRSA infection. After the administration of dLHT, the number of white blood cells in MMC-treated mice recovered to 80% of the normal level. In addition, the phagocytic activity of macrophages increased to 70% in the dLHT-treated group, while that of the non-treated group was only 20%. The bactericidal activity also recovered to the level close to the normal value by dLHT. The ratio of neutrophils in the dLHT-administered group increased to 2.2% (normal mice, 2.6%), whereas that in the non-terated group was only 0.5%. The bacterial count in the liver of MRSA-challenged mice reached the peak at six hours after the challenge in both dLHT-treated and non-treated mice. However, the number of bacteria in dLHT group was much greater than that in the non-treated group. The bacterial count in the blood showed an increase 12 and 24 hours after the challenge. Even 24 hours after the challenge, a significant number of bacteria existed in the blood of dLHT-administered group, whereas only a small number of bacteria detectable 6 hours after the challenge and the number gradually decreased thereafter in the dLHT-administered group. MRSA-challenged MMC-treated mice were treated by dLHT, vancomycin, or dLHT and vancomycin. All of non-treated mice died 8 days after the MRSA challenge, whereas the survival rates were 60% after dLHT treatment, 40% after vancomycin treatment, and 80% after dLHT and vancomycin treatment. All of MMC-treated mice, to which the phagocytic cells prepared from MMC-treated mice with dLHT administration had adoptively been transferred, survived from MRSA challenge. On the other hand, the survival rate of MMC-treated mice, to which the lymphocytes prepared from the same mice had adoptively been transferred, was 40%. Clinical Trial: All cases with dLHT treatment showed negative culture results for MRSA after the dLHT administration. The culture generally became negative less than 50 days after the initial administration, whereas one control case needed more than 100 days and the other was dead of the infection. One representative case, who was a 78-year-old woman suffering from hypertension, atrial fibrillation, and cerebral bleeding in the right occipital lobe, infected with MRSA during the antibiotic therapy for Streptococcus pneumoniae. The antibiotic therapy was halted and the dLHT administration started. Three weeks later, the culture result became negative. In addition, serum protein and albumin values also returned to the level that they had had before the infection of MRSA.