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In Vitro Activities of Antibiotic Combinations Against Clinical Isolates of Pseudomonas Aeruginosa

台灣綠膿桿菌臨床菌株對不同抗生素組合的感受性之研究

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摘要


綠膿桿菌是全世界院內感染常見之菌種,且其抗藥性也是目前之重要課題。目前臨床上對於此感染,一般建議採用兩種以上之抗生素合併療法,但台灣地區尚無相關之體外感受性報告。本研究是針對台灣一醫學中心於 2001 年所收集之 100 株臨床菌株進行數種抗生素單獨及合併使用之體外藥物感受性試驗。在單一藥物感受性試驗方面,本研究之綠膿桿菌除對 aztreonam 之不敏感性較低外,其他藥物之不敏感性都較亞洲地區之平均值高,顯示台灣地區之綠膿桿菌抗藥性的嚴重。在藥物組合中,以 piperacillin 合併 amikacin 表現出最高程度之加乘效果 (59/100),而 amikacin 合併其他 beta-lactam 類藥物 (cefepime 或 aztreonam) 也有不錯之加乘效果 (7/100 或 16/100)。此外,合併兩種 beta-lactam 類之藥物於本研究中亦可見其加乘效果。近來,ciprofloxacin 已成為治療綠膿桿菌感染相當重要之藥物,但本研究發現其和其他類藥物合併使用並沒有產生相當明顯之加乘作用。關於具 piperacillin 抗藥性之綠膿桿菌,合併 amikacin 及 beta-lactam (含 piperacillin) 仍具有相當程度之加乘作用,但兩種 beta-lactam 類藥物之合併則無加乘作用。本研究並未發現任何藥物組合對綠膿桿菌具有互相拮抗之作用。整體而言,以 amikacin 合併 beta-lactam 類藥物對綠膿桿菌表現出最好之加乘效果;而這些結果可進一步提供高抗藥地區之臨床醫師用藥的重要參考資料。

並列摘要


Combination therapy has been recommended to treat Pseudomonas aeruginosa infections worldwide. The purpose of the present study was to determine the in vitro activities of piperacillin, cefepime, aztreonam, amikacin, and ciprofloxacin alone and in combination against 100 clinical isolates of P. aeruginosa from one medical center in southern Taiwan. The combination susceptibility assay was performed using the checkerboard technique. The percentage of resistance of P. aeruginosa to single agents in our study was relatively high for the Asia-Pacific area, except to aztreonam. Piperacillin plus amikacin exhibited the highest potential for synergy (59/100) in this study. Moreover, a high percentage of synergism was also noted with amikacin combined with cefepime (7/100) or aztreonam (16/100). The combination of two beta-lactams, such as cefepime with piperacillin, and aztreonam with cefepime or piperacillin, showed synergistic effects against some P. aeruginosa isolates. Although ciprofloxacin is a good anti-pseudomonal agent, a very low potential for synergy with other antibiotics was demonstrated in this study. No antagonism was exhibited by any combination in our study. Among piperacillin-resistant strains, there was synergy with a beta-lactam plus amikacin, including the combination of piperacillin and amikacin. However, the combination of two beta-lactams, such as piperacillin and cefepime or aztreonam, did not have any synergistic activity against these strains. In summary, the combinations of amikacin with the tested beta-lactams (piperacillin, aztreonam, cefepime) had a greater synergistic effect against P. aeruginosa, even piperacillin-resistant strains, than other combinations. Understanding the synergistic effect on clinical strains may help clinicians choose better empirical therapy in an area with high prevalence of multidrug-resistant P. aeruginosa.

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