Poeppl Wolfgang, Lingscheid Tilman, Bernitzky Dominik, Schwarze Uwe Y, Donath Oliver, Perkmann Thomas, Kozakowski Nicolas, Plasenzotti Roberto, Reznicek Gottfried, Burgmann Heinz
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Department of Oral Surgery, Bernhard Gottlieb University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Antimicrob Agents Chemother. 2014 Sep;58(9):5111-6. doi: 10.1128/AAC.02720-13. Epub 2014 Jun 16.
Fosfomycin monotherapy was compared to therapy with vancomycin for the treatment of implant-associated methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis in an experimental rat model. The proximal tibiae were inoculated with 15 μl of a suspension containing 1×10(8) to 5×10(8) CFU/ml of a clinical isolate of MRSA with simultaneous insertion of a titanium wire. Four weeks later, treatment was started for 28 days with either 50 mg/kg of body weight vancomycin intraperitoneally twice daily (n=11) or 75 mg/kg fosfomycin intraperitoneally once daily (n=10). Eleven animals were left untreated. After treatment, quantitative cultures from bone were found to be positive for MRSA in all animals in the untreated group (median, 3.29×10(6) CFU/g of bone) and the vancomycin group (median, 3.03×10(5) CFU/g of bone). In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42×10(2) and 1.51×10(3) CFU/g of bone). Vancomycin was superior to the no-drug control (P=0.002), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). The cultures from the wires were positive in all untreated animals (median, 2.5×10(3) CFU/implant), in 10 animals in the vancomycin group (median, 1.15×10(3) CFU/implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P=0.324), and fosfomycin was superior to the no-drug control and vancomycin (P<0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.
在实验性大鼠模型中，将磷霉素单药疗法与万古霉素疗法用于治疗植入物相关的耐甲氧西林金黄色葡萄球菌（MRSA）骨髓炎进行了比较。将含有1×10⁸至5×10⁸CFU/ml MRSA临床分离株的15μl悬液接种到大鼠胫骨近端，同时插入一根钛丝。四周后，开始治疗28天，治疗方式为：每天两次腹腔注射50mg/kg体重的万古霉素（n = 11）或每天一次腹腔注射75mg/kg磷霉素（n = 10）。11只动物未接受治疗。治疗后，未治疗组所有动物（中位数，3.29×10⁶CFU/g骨）和万古霉素组所有动物（中位数，3.03×10⁵CFU/g骨）的骨定量培养均发现MRSA呈阳性。在磷霉素组中，10只动物中有2只（20%）可检测到MRSA（3.42×10²和1.51×10³CFU/g骨）。万古霉素优于未用药对照组（P = 0.002），磷霉素优于未用药对照组和万古霉素（P < 0.001）。未治疗动物的钛丝培养均呈阳性（中位数, 2.5×10³CFU/植入物），万古霉素组10只动物呈阳性（中位数, 1.15×10³CFU/植入物）, 磷霉素组所有动物均为阴性。基于植入物的细菌计数，万古霉素并不优于未用药对照组（P = 0.324），磷霉素优于未用药对照组和万古霉素（P < 0.00）。未观察到耐药性的出现。总之，结果表明磷霉素单药疗法对治疗实验性植入物相关的MRSA骨髓炎非常有效。
