Increased Temperature Enhances the Antimicrobial Effects of Daptomycin, Vancomycin, Tigecycline, Fosfomycin, and Cefamandole on Staphylococcal Biofilms

Increased Temperature Enhances the Antimicrobial Effects of Daptomycin, Vancomycin, Tigecycline, Fosfomycin, and Cefamandole on Staphylococcal Biofilms
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DOI:
10.1128/aac.00275-10
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发表时间:
2010-10-01
影响因子:
4.9
通讯作者:
Presterl, Elisabeth
Presterl, Elisabeth
中科院分区:
医学2区
文献类型:
--
作者:
Hajdu, Stefan;Holinka, Johannes;Presterl, Elisabeth

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植入物相关感染是创伤和骨科手术的严重并发症,也是最难治疗的。34株临床葡萄球菌的细菌生物被膜。分离的金黄色葡萄球菌(n=14;凝固酶阴性葡萄球菌,n=19)与达托霉素(DAP;5、25或100 mg/升)、万古霉素(VAN;5、25或100 mg/升)、替加环素(TGC;1、5或25 mg/升)、磷霉素(FOM;100、250或1000 mg/升)和头孢芒多(FAM;50、100或500 mg/L),在35℃、40℃和45℃三种不同的环境温度下作用24 h。为了定量生物量的减少,测定了染色生物膜的光密度比(ODR)和生长细菌的数量。在与FAM、FOM、TGC、VAN或DAP孵育期间,将温度提高到45摄氏度或40摄氏度,与35摄氏度孵育相比,葡萄球菌生物膜的厚度显著但有差异地减少(P<0.05)。35摄氏度、40摄氏度和45摄氏度下100毫克/升的DAP的生长减少量得到加强(对数减少量分别为4、3.6和3.3;P<0.05)。在40℃和45℃下,浓度为500 mg/L的FAM的生长减少了2个对数(P=0.01)。1,000 mg/L的FOM使细菌生长减少1.2个对数值(不显著)。随着环境温度的升高和使用浓度的增加,抗菌剂的抗菌活性显著增强,但不同程度地增强。辅助热疗在生物膜相关种植体相关感染的治疗中可能有价值。
Implant-related infections are serious complications of trauma and orthopedic surgery and are most difficult to treat. The bacterial biofilms of 34 clinical Staphylococcus sp. isolates (Staphylococcus aureus, n = 14; coagulase-negative staphylococci, n = 19) were incubated with daptomycin (DAP; 5, 25, or 100 mg/liter), vancomycin (VAN; 5, 25, or 100 mg/liter), tigecycline (TGC; 1, 5, or 25 mg/liter), fosfomycin (FOM; 100, 250, or 1,000 mg/liter), and cefamandole (FAM; 50, 100, or 500 mg/liter) for 24 h at three different ambient temperatures: 35 degrees C, 40 degrees C, and 45 degrees C. To quantify the reduction of the biomass, the optical density ratio (ODr) of stained biofilms and the number of growing bacteria were determined. Increasing the temperature to 45 degrees C or to 40 degrees C during incubation with FAM, FOM, TGC, VAN, or DAP led to a significant but differential reduction of the thickness of the staphylococcal biofilms compared to that at 35 degrees C (P < 0.05). Growth reduction was enhanced for DAP at 100 mg/liter at 35 degrees C, 40 degrees C, and 45 degrees C (log count reductions, 4, 3.6, and 3.3, respectively; P < 0.05). A growth reduction by 2 log counts was detected for FAM at a concentration of 500 mg/liter at 40 degrees C and 45 degrees C (P = 0.01). FOM at 1,000 mg/liter reduced the bacterial growth by 1.2 log counts (not significant). The antibacterial activity of antimicrobial agents is significantly but differentially enhanced by increasing the ambient temperature and using high concentrations. Adjuvant hyperthermia may be of value in the treatment of biofilm-associated implant-related infections.