Çağla BOZKURT GÜZEL
(İstanbul Üniversitesi, Eczacılık Fakültesi, Farmasötik Mikrobiyoloji Anabilim Dalı, İstanbul, Türkiye)
Nevin Meltem AVCI
(İstanbul Üniversitesi, Eczacılık Fakültesi, Farmasötik Mikrobiyoloji Anabilim Dalı, İstanbul, Türkiye)
Paul SAVAGE
(Brigham Young University, Department of Chemistry and Biochemistry, Provo, Utah, USA)
Yıl: 2020Cilt: 17Sayı: 1ISSN: 1304-530X / 2148-6247Sayfa Aralığı: 63 - 67İngilizce

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In Vitro Activities of the Cationic Steroid Antibiotics CSA-13, CSA-131, CSA-138, CSA142, and CSA-192 Against Carbapenem-resistant Pseudomonas aeruginosa
Objectives: Pseudomonas aeruginosa is an important opportunistic pathogen that is difficult to treat because of the antibiotic resistance that has developed in recent years. Increasing carbapenem resistance has led to a rise in hospital infections caused by this bacterium. As a result, researchers have begun to search for new molecules. Ceragenins are the general name for membrane-acting cationic steroid antimicrobial molecules that have activity similar to that of antimicrobial peptides. In this study, we investigated the in vitro activities of the cationic steroid antibiotics (CSAs) CSA-13, CSA-131, CSA-138, CSA-142, CSA-192, and colistin on carbapenem-resistant Pseudomonas aeruginosa (CRPA). Materials and Methods: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by broth dilution method. Results: The MIC50 (µg/mL) values of CSA-13, CSA-131, CSA-138, CSA-142, CSA-192, colistin, and meropenem were 8, 4, 8, 16, 32, 1, and 16, respectively. The MBC values were equal to or twice the MIC values. Conclusion: CSA-131 and CSA-138 appear to be good candidates for CRPA treatment. However, the lack of stability, efficacy, and pharmacokinetic properties of CSA requires further research in the future in vivo and in vitro.
DergiAraştırma MakalesiErişime Açık
  • 1. Bassetti M, Poulakou G, Ruppe E, Bouza E, Van Hal SJ, Brink A. Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach. Intensive Care Med. 2017;43:1464-1475.
  • 2. Davies TA, Marie Queenan A, Morrow BJ, Shang W, Amsler K, He W, Lynch AS, Pillar C, Flamm RK. Longitudinal survey of carbapenem resistance and resistance mechanisms in Enterobacteriaceae and non-fermenters from the USA in 2007-09. J Antimicrob Chemother. 2011:66:2298-2307.
  • 3. El-Mahdy TS. Expression of ampC, oprD, and mexA, outer membrane protein analysis and carbapenemases in multidrug resistant clinical isolates of Pseudomonas aeruginosa from Egypt. J Chemother. 2014:26:379-381.
  • 4. World Health Organization. WHO publishes list of bacteria for which new antibiotics are urgently needed (2017). Accessed: 14 March. 2017. http:// www.who.int/mediacentre/news/releases/2017/bacteria-antibioticsneeded/en/
  • 5. Falagas ME, Bliziotis IA. Pandrug-resistant Gram-negative bacteria: the dawn of the postantibiotic era? Int J Antimicrob Agents. 2007;29:630- 636.
  • 6. Vila-Farrés X, Callarisa AE, Gu X, Savage PB, Giralt E, Vila J. CSA-131, a ceragenin active against colistin-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clinical isolates. Int J Antimicrob Agents. 2015:46:568-571.
  • 7. Smeianov V, Scott K, Reid G. Activity of cecropin P1 and FA-LL-37 against urogenital microflora. Microbes Infect. 2000;2:773-777.
  • 8. Epand RM, Epand RF, Savage PB. Ceragenins (Cationic Steroid Compounds), a novel class of antimicrobial agents. Drug News Perspect. 2008:21:307-311.
  • 9. Chin JN, Jones RN, Sader HS, Savage PB, Rybak MJ. Potential synergy activity of the novel ceragenin, CSA-13, against clinical isolates of Pseudomonas aeruginosa, including multidrug-resistant P. aeruginosa. J Antimicrob Chemother. 2008:61:365-370.
  • 10. Chin JN, Rybak MJ, Cheung CM, Savage PB. Antimicrobial activities of ceragenins against clinical isolates of resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2007:51:1268-1273.
  • 11. Durnaś B, Wnorowska U, Pogoda K, Deptuła P, Wątek M, Piktel E, Głuszek S, Gu X, Savage PB, Niemirowicz K, Bucki R. Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites. PLoS One. 2016;11:e0157242.
  • 12. Epand RF, Pollard JE, Wright JO, Savage PB, Epand RM. Depolarization, bacterial membrane composition, and the antimicrobial action of ceragenins. Antimicrob Agents Chemother. 2010:54:3708-3713.
  • 13. Epand RF, Savage PB, Epand RM. Bacterial lipid composition and the antimicrobial efficacy of cationic steroid compounds (Ceragenins). Biochim Biophys Acta. 2007;1768:2500-2509.
  • 14. Howell MD, Streib JE, Kim BE, Lesley LJ, Dunlap AP, Geng D, Feng Y, Savage PB, Leung DY. Ceragenins: a class of antiviral compounds to treat orthopox infections. J Invest Dermatol. 2009:129:2668-2675.
  • 15. Lara D, Feng Y, Bader J, Savage PB, Maldonado, RA. Anti-trypanosomatid activity of ceragenins. J Parasitol. 2010;96:638-642.
  • 16. Leszczynska K, Namiot D, Byfield FJ, Cruz K, Zendzian-Piotrowska M, Fein DE, Savage PB, Diamond S, McCulloch CA, Janmey PA, Bucki R. Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections. J Antimicrob Chemother. 2013;68:610-618.
  • 17. Polat ZA, Savage PB, Genberg C. In vitro amoebicidal activity of a ceragenin, cationic steroid antibiotic-13, against Acanthamoeba castellanii and its cytotoxic potential. J Ocur Pharmacol Ther. 2011;27:1- 5.
  • 18. Savage PB, Li C, Taotafa U, Ding B, Guan Q. Antibacterial properties of cationic steroid antibiotics. FEMS Microbiol Lett. 2002;217:1-7.
  • 19. Bozkurt-Guzel C, Savage PB, Gerceker AA. In vitro activities of novel ceragenin, CSA-13, alone or combination with colistin, tobramycin and ciprofloxacin against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients. Chemotherapy. 2011;57:505-510.
  • 20. Saha S, Savage PB, Bal M. Enhancement of the efficacy of erythromycin in multiple antibiotic resistant gram-negative bacterial pathogens. J Appl Microbiol. 2008;105:822-828.
  • 21. Guan Q, Li C, Schmidt EJ, Boswell JS, Walsh JP, Allman GW, Savage PB. Preparation and characterization of cholic acid-derived antimicrobial agents with controlled stabilities. Org Lett. 2000;2:2837-2840.
  • 22. Clinical and Laboratory Standards Institute.Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard-(10 th ed). CLSI document. USA; 2015:7-10.
  • 23. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. CLSI document (27th ed). USA; 2016:100-127.
  • 24. National Committee for Clinical Laboratory Standarts. Methods for Determining Bactericidal Activity of Antimicrobial Agents-Approved Guideline, USA; 2005:26.

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