Raad Issam, Hanna Hend, Jiang Ying, Dvorak Tanya, Reitzel Ruth, Chaiban Gassan, Sherertz Robert, Hachem Ray
The University of Texas M D Anderson Cancer Center, Department of Infectious Diseases, Infection Control and Employee Health, Houston, TX 77030, USA.
Antimicrob Agents Chemother. 2007 May;51(5):1656-60. doi: 10.1128/AAC.00350-06. Epub 2007 Mar 12.
In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.
在与导管相关的血流感染情况下,管腔内抗生素封管疗法可能有助于挽救血管导管。在这项体外研究中,我们研究了新型抗生素达托霉素、利奈唑胺和替加环素与万古霉素、米诺环素和利福平相比,对生物膜中耐甲氧西林金黄色葡萄球菌(MRSA)的疗效。我们还评估了在每天进行4小时导管封管治疗后,单独或与利福平联合使用这些抗生素时,耐这些抗生素的MRSA菌株的出现情况。在接触这些抗生素的第一天后,米诺环素、达托霉素和替加环素在抑制生物膜中的MRSA方面比利奈唑胺、万古霉素和阴性对照更有效(P < 0.001),其中米诺环素活性最强,其次是达托霉素,然后是替加环素,而万古霉素和利奈唑胺缺乏活性,与阴性对照相似。在每天4小时暴露3天后,达托霉素从生物膜中根除MRSA的速度最快,其次是米诺环素和替加环素,它们比利奈唑胺、利福平和万古霉素更快(P < 0.001)。当单独使用利福平时,在每天4小时暴露5天后,它从生物膜中根除MRSA的效果最差,因为它与耐利福平的MRSA的出现有关。然而,当利福平与其他抗生素联合使用时,该联合用药在比每种抗生素单独使用更快地消除生物膜中的MRSA定植方面显著有效。总之,达托霉素、米诺环素和替加环素应进一步考虑用于抗生素封管治疗,利福平应考虑用于增强抗葡萄球菌活性,但不作为单一药物使用。