Park M K, Muhvich K H, Myers R A, Marzella L
Division of Hyperbaric Medicine, Maryland Institute for Emergency Medical Services Systems, Baltimore.
Antimicrob Agents Chemother. 1991 Apr;35(4):691-5. doi: 10.1128/AAC.35.4.691.
The objective of this study was to determine whether hyperoxia enhances aminoglycoside activity against Pseudomonas aeruginosa. The existence of tobramycin-oxygen synergy was determined by using the in vitro postantibiotic effect (PAE). P. aeruginosa strains were incubated for 1 h in medium containing tobramycin at four times the MIC in the following gas mixtures: normoxia (21% O2), hyperoxia (100% O2, 101.3 kPa), or hyperbaric oxygen (100% O2, 274.5 kPa). Tobramycin was removed after 1 h and bacteria were incubated under normoxic conditions; growth rates were measured for 5 h. Exposure of three P. aeruginosa strains to hyperoxia prolonged the PAE of tobramycin approximately twofold compared with the PAE after exposure to normoxia (P less than 0.05). Exposure of P. aeruginosa ATCC 27853 to tobramycin and hyperbaric oxygen prolonged the time required for bacteria to increase 1 log10 CFU/ml compared with the time after exposure for this increase to occur in tobramycin-treated, normoxic or hyperoxic groups (P less than 0.02). Pulse-chase labeling of bacteria with L-[35S]methionine, immediately after removal of tobramycin, showed that protein synthesis rates were decreased compared with those in controls (P = 0.0001). Moreover, in tobramycin-treated groups, hyperoxia and hyperbaric oxygen induced 2- and 16-fold decreases, respectively, in protein synthesis rates compared with normoxia; these results did not achieve statistical significance. In the absence of tobramycin, hyperoxia increased bacterial growth (134%; P less than 0.01) and protein synthesis (24%; not significant) compared with normoxia. Hyperbaric oxygen, however, delayed the growth recovery of bacteria (P less than 0.05). We conclude that hyperoxia enhances the bacteriostatic effects of tobramycin in a synergistic manner.+
本研究的目的是确定高氧是否能增强氨基糖苷类药物对铜绿假单胞菌的活性。通过体外抗生素后效应（PAE）来确定妥布霉素 - 氧气协同作用的存在。将铜绿假单胞菌菌株在含有四倍MIC妥布霉素的培养基中于以下气体混合物中孵育1小时：常氧（21% O₂）、高氧（100% O₂，101.3 kPa）或高压氧（100% O₂，274.5 kPa）。1小时后去除妥布霉素，细菌在常氧条件下孵育；测量5小时内的生长速率。与暴露于常氧后的PAE相比，三种铜绿假单胞菌菌株暴露于高氧使妥布霉素的PAE延长了约两倍（P小于0.05）。与妥布霉素处理的常氧或高氧组中细菌增加1 log₁₀ CFU/ml所需的时间相比，铜绿假单胞菌ATCC 27853暴露于妥布霉素和高压氧后延长了该时间（P小于0.02）。在去除妥布霉素后立即用L - [³⁵S]甲硫氨酸对细菌进行脉冲追踪标记，结果显示与对照组相比蛋白质合成速率降低（P = 0.0001）。此外，在妥布霉素处理组中，与常氧相比，高氧和高压氧分别使蛋白质合成速率降低了2倍和16倍；这些结果未达到统计学显著性。在不存在妥布霉素的情况下，与常氧相比，高氧增加了细菌生长（134%；P小于0.01）和蛋白质合成（24%；无显著性）。然而，高压氧延迟了细菌的生长恢复（P小于0.05）。我们得出结论，高氧以协同方式增强了妥布霉素的抑菌作用。
