ÇAĞLA BOZKURT GÜZEL, Zayre ERTURAN, Paul B. SAVAGE, Ayşe Alev GERÇEKER

Katyonik steroid antibiyotik csa-13’ün, kolistin ve çeşitli antibiyotiklerle kombinasyonlarının kistik fibrozlu hastalardan izole edilen pseudomonas aerugınosa suşlarına karşı üçlü sinerjistik etkileri

Bu çalışmada, yeni bir katyonik steroid antibiyotik olan CSA-13’ün kolistin ve çeşitli antibiyotiklerle kombinasyon halinde kistik fibrozlu hastalardan izole edilen Pseudomonas aeruginosa suşlarına karşı oluşturduğu ikili ve üçlü sinerjistik etkisi araştırılmıştır. MİK ve MBK değerleri, CLSI’nın önerdiği mikrodilüsyon tekniği ile saptanmıştır. Antibiyotiklerin ikili ve üçlü kombinasyonlarının etkileri mikrodilüsyon “checkerboard” ve zamana bağlı öldürme yöntemleri kullanılarak ölçül- müştür. Antibiyotiklerin MİK değerleri 0.5-2 μg/ml arasında değişmektedir. MBK değerleri ise MİK değerlerine eşit yada iki katı değerindedir. Mikrodilüsyon “checkerboard” tekniği kullanılarak yapılan ikili kombinasyon çalışmalarında en fazla siner- jistik etki CSA-13-kolistin kombinasyonu ile elde edilmiştir. Zamana bağlı öldürme deneylerinin sonuçlarına göre CSA-13, hızlı bir bakterisidal etki göstermiştir. Zamana bağlı öldürme yöntemine göre kolistinin tobramisin ve siprofloksasin ile olan ikili kombinasyonlarının aditif etkili olduğu saptanmıştır. Bu ikili kombinasyonlara CSA-13’ün üçüncü antibiyotik olarak eklenmesi ile sinerjistik etki ortaya çıkmıştır. Sonuç olarak, kolik asitten türemiş olan yeni bir katyonik steroid yapıda molekül olan CSA-13’ün de içinde bulunduğu bu üçlü kombinasyonların, kistik fibrozlu hastalardaki P.aeruginosa infeksiyonlarının tedavisine yeni bir bakış açısı kazandıracağı düşüncesindeyiz.

Investigation of triple synergistic activities of the novel cationic steroid antibiotic csa-13, with colistin and various antibiotics against pseudomonas aeruginosa strains ısolated from cystic fibrosis patients

In this study, in vitro double and triple synergistic activities of the novel cationic steroid antibiotic CSA-13, with colistin, tobramycin and ciprofloxacin were assessed against Pseudomonas aeruginosa strains isolated from cystic fibrosis (CF) patients. MICs and MBCs were determined by microdilution technique according to CLSI guidelines. Combinations of CSA- 13 plus colistin, together with tobramycin and ciprofloxacin were measured using checkerboard and the time-kill curve (TKC) method. Susceptibility testing demonstrated that the MICs were ranging 0.5-2 μg/ml. The MBCs were equal to or two-fold greater than those of the MICs. According to the double combination studies using the microdilution checkerboard method, synergistic interactions were most frequent with CSA-13-colistin combination. The results of TKC analysis demonstrated rapid bactericidal activity of CSA-13. Combination TKC analysis demonstrated additive effect with colistin plus tobramycin and colistin plus ciprofloxacin. The addition of CSA-13 as a third antibiotic to these combinations, led to a synergistic effect. We showed that triple combination of CSA-13, a new cationic steroid molecule derived from cholic acid offers new perspectives as a new treatment option for P.aeruginosa infections in CF patients

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