Lingscheid Tilman, Poeppl Wolfgang, Bernitzky Dominik, Veletzky Luzia, Kussmann Manuel, Plasenzotti Roberto, Burgmann Heinz
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Division for Biomedical Research, Medical University of Vienna, Vienna, Austria.
Antimicrob Agents Chemother. 2015 Feb;59(2):859-63. doi: 10.1128/AAC.04246-14. Epub 2014 Nov 17.
The aim of this study was to evaluate the combination of daptomycin and fosfomycin in experimental chronic implant-associated osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA). Infection was induced in the tibiae of rats by the insertion of a bacterial inoculum (1 to 5×10(8) CFU/ml) of a clinical MRSA isolate and a titanium wire. Four weeks after infection, each animal was assigned to a treatment group: daptomycin monotherapy at 60 mg/kg of body weight once daily (n=10), fosfomycin monotherapy at 40 mg/kg once daily (n=10), or daptomycin and fosfomycin combined at 60 mg/kg and 40 mg/kg, respectively, once daily (n=9). Ten animals were left untreated. After a 3-week treatment period, the animals were euthanized, and the infected tibiae and implants were processed for quantitative bacterial cultures. The bacterial cultures from bones were positive for MRSA in all animals in the untreated group, the daptomycin group, and the fosfomycin group, with median bacterial counts of 2.34×10(6) CFU/g bone, 1.57×10(6) CFU/g bone, and 3.48×10(2) CFU/g bone, respectively. In the daptomycin-fosfomycin group, 6 out of 9 animals were positive for MRSA, with a median count of 7.92 CFU/g bone. Bacterial cultures derived from the titanium wires were negative in the fosfomycin- and daptomycin-fosfomycin-treated groups. Based on bacterial counts in bones, treatment with daptomycin-fosfomycin was statistically significantly superior to all that of the other groups (P≤0.003). Fosfomycin was superior to daptomycin and no treatment (P<0.0001). No development of resistance was observed in any treatment arm. The combination of daptomycin and fosfomycin demonstrated synergism against MRSA in experimental implant-associated osteomyelitis.
本研究的目的是评估达托霉素和磷霉素联合用药对耐甲氧西林金黄色葡萄球菌（MRSA）所致实验性慢性植入物相关骨髓炎的疗效。通过植入临床MRSA分离株的细菌接种物（1至5×10⁸CFU/ml）和一根钛丝，在大鼠胫骨中诱导感染。感染四周后，将每只动物分配到一个治疗组：每日一次给予60mg/kg体重的达托霉素单药治疗（n = 10），每日一次给予40mg/kg的磷霉素单药治疗（n = 10），或分别每日一次给予60mg/kg和40mg/kg的达托霉素和磷霉素联合治疗（n = 9）。十只动物未接受治疗。经过3周的治疗期后，对动物实施安乐死，并对感染的胫骨和植入物进行定量细菌培养。未治疗组、达托霉素组和磷霉素组所有动物的骨细菌培养MRSA均呈阳性，骨细菌计数中位数分别为2.34×10⁶CFU/g骨、1.57×10⁶CFU/g骨和3.48×10²CFU/g骨。在达托霉素 - 磷霉素组中，9只动物中有6只MRSA呈阳性，计数中位数为7.92CFU/g骨。在磷霉素组和达托霉素 - 磷霉素治疗组中，源自钛丝的细菌培养均为阴性。基于骨细菌计数，达托霉素 - 磷霉素治疗在统计学上显著优于其他所有组（P≤0.003）。磷霉素优于达托霉素和未治疗组（P<0.0001）。在任何治疗组中均未观察到耐药性的产生。在实验性植入物相关骨髓炎中，达托霉素和磷霉素联合用药对MRSA表现出协同作用。
