Davey P, Barza M, Stuart M
Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Boston, MA 02111.
J Antimicrob Chemother. 1988 Apr;21(4):395-404. doi: 10.1093/jac/21.4.395.
In the rat croton oil pouch model, treatment with ciprofloxacin, gentamicin or imipenem caused a sharp reduction in the numbers of Pseudomonas aeruginosa when applied 24 h after infection but treatment had little or no effect when delayed until 48 h after infection. Surviving bacteria from treated animals were fully susceptible on subculture in vitro. Between 24 h and 48 h after infection there was an increase in the concentration of magnesium and a decrease in the concentration of oxygen but no significant change in the pH of the pouch fluid. In-vitro, the MBC of gentamicin was increased four-fold by the addition of magnesium ions and eight-fold under anaerobic conditions whereas these variables had no significant effect upon the MBC of ciprofloxacin and imipenem. However, cells of P. aeruginosa incubated in batch culture for 4, 24 and 48 h became progressively more tolerant to killing by all three drugs. We conclude that the tolerance of P. aeruginosa in vivo was only partly explained by biochemical changes at the site of infection. The stationary growth phase was associated with progressive tolerance to killing by ciprofloxacin, gentamicin and imipenem both in vivo and in vitro.
在大鼠巴豆油袋模型中，感染24小时后应用环丙沙星、庆大霉素或亚胺培南治疗可使铜绿假单胞菌数量急剧减少，但如果延迟至感染48小时后治疗则效果甚微或没有效果。经治疗动物体内存活的细菌在体外传代培养时仍对药物敏感。感染后24小时至48小时之间，袋内液体中镁离子浓度升高，氧浓度降低，但pH值无显著变化。在体外，添加镁离子可使庆大霉素的最低杀菌浓度（MBC）增加4倍，在厌氧条件下增加8倍，而这些变量对环丙沙星和亚胺培南的MBC没有显著影响。然而，在分批培养中培养4小时、24小时和48小时的铜绿假单胞菌细胞对这三种药物杀菌作用的耐受性逐渐增强。我们得出结论，铜绿假单胞菌在体内的耐受性仅部分可由感染部位的生化变化来解释。静止生长期与体内外对环丙沙星、庆大霉素和亚胺培南杀菌作用的耐受性增强有关。
