Munson Erik L, Heard Stephen O, Doern Gary V
Department of Anesthesiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA.
Chest. 2004 Nov;126(5):1628-35. doi: 10.1378/chest.126.5.1628.
Use of central venous catheters (CVCs) impregnated with minocycline and rifampin reduces the density of bacterial growth on catheters and decreases the incidence of catheter-related bloodstream infections. Questions have been raised over the possibility that the use of these catheters will lead to the emergence of antibiotic-resistant organisms. In this study, we sought to determine if in vitro exposure of four test organisms to catheter segments impregnated with minocycline and rifampin would lead to the development of antibiotic resistance.
Catheter segments (1.0 cm) were placed on the surface of agar plates previously inoculated with bacterial suspensions, such that a subconfluent lawn of colony growth would be apparent after 24 h incubation at 35 degrees C in air. Test organisms included American Type Culture Collection strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Zones of inhibition of colony growth surrounding catheters were measured at 24-h intervals up to 7 days (two catheter segments per test). Colonies on agar surfaces located at varying distances from catheter segments were examined for minocycline and rifampin resistance following various periods of exposure (six catheter segments per test). In addition, selected colonies were subsequently exposed to minocycline and rifampin in broth and examined for selection of minocycline and rifampin resistance (> 28 colonies per selection test).
Inhibitory zones of 14 to 47 mm were observed with S aureus, S epidermidis, E faecalis, and E coli. Growth of P aeruginosa was not inhibited by CVC segments. Testing of colonies of the first four organisms at various distances from CVC segments after varying periods of exposure revealed only a single instance of the emergence of resistance (eg, S aureus vs rifampin). Recovery of resistant clones was enhanced with minocycline and rifampin broth selection; however, a direct link between CVC exposure and the emergence of resistance was not established.
Our in vitro data suggest that the exposure of Gram-positive cocci to either rifampin or minocycline can lead to the development of resistance. However, exposure of bacteria to these antibiotics in combination does not directly lead to resistance. Clinical investigations will be required to determine the true risk and implications of the development of resistance.
使用含米诺环素和利福平的中心静脉导管（CVC）可降低导管上细菌生长的密度，并减少导管相关血流感染的发生率。对于使用这些导管是否会导致抗生素耐药菌的出现，人们提出了疑问。在本研究中，我们试图确定四种受试微生物在体外接触含米诺环素和利福平的导管段后是否会产生抗生素耐药性。
将导管段（1.0厘米）放置在预先接种了细菌悬液的琼脂平板表面，在35摄氏度空气中培养24小时后，会出现亚汇合的菌落生长。受试微生物包括美国典型培养物保藏中心的金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、大肠杆菌和铜绿假单胞菌菌株。每隔24小时测量导管周围菌落生长的抑制圈，直至7天（每次试验两个导管段）。在不同暴露时间后，检查琼脂表面距导管段不同距离处的菌落对米诺环素和利福平的耐药性（每次试验六个导管段）。此外，随后将选定的菌落在肉汤中暴露于米诺环素和利福平，并检查米诺环素和利福平耐药性的选择情况（每次选择试验>28个菌落）。
金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和大肠杆菌的抑菌圈为14至47毫米。铜绿假单胞菌的生长未被CVC段抑制。在不同暴露时间后，对前四种微生物距CVC段不同距离处的菌落进行检测，仅发现一例耐药性出现（如金黄色葡萄球菌对利福平）。通过米诺环素和利福平肉汤选择可增强耐药克隆的恢复；然而，未确立CVC暴露与耐药性出现之间的直接联系。
我们的体外数据表明，革兰氏阳性球菌暴露于利福平或米诺环素可导致耐药性的产生。然而，细菌同时暴露于这些抗生素不会直接导致耐药性。需要进行临床研究以确定耐药性产生的真正风险和影响。
