(1010) - Antimicrobial Activity of Cysteamine Against Antibiotic Resistant Pathogens Isolated from Cystic Fibrosis and Non- CF Patients Including Mycobacterium abscessus Complex from Lung Transplant Recipients

Abstract

Lung transplantation for cystic fibrosis (CF) patients colonised with pan resistant bacteria, in particular M abscessus complex (MABSC) may preclude them from lung transplantation due to poor outcomes. Treatment of MABSC generally consists of a 3 drug regime including nephrotoxic/ototoxic amikacin. Oral cysteamine is licenced for treatment of cystinosis and has recently been reported as having good antimicrobial, anti-biofilm and mucolytic activity against CF pathogens. We evaluated the antimicrobial activity of this compound against a collection of 31 strains of CF and non- CF pathogens including isolates from lung transplant recipients. We also evaluated the interaction of cysteamine with 12 anti-pseudomonal agents against 4 strains P aeruginosa (Pa). Microdilution MIC’s against 12 MABSC were performed and bactericidal activity was assessed by subculture. MIC’s were performed against a collection of 19 further strains including: Pa (n=3), Achromobacter spp. (n=2) and 1 each of the following: Burkholderia multivorans, Burkholderia cenocepacia, Ralstonia mannitolylitica, Pandoraea sp. Stenotrophomonas maltophilia, and Inquilinus limosus. NCTC strains of E coli, S aureus; C albicans, E faecalis and 4 carbapenemase-producing Enterobacteriacae (CPE) were also evaluated. The Multiple Combination Bactericidal Test (MCBT) was utilised to assess synergy by incorporating cysteamine at 500 mg/L with 12 agents at the systemic concentration. The 4 strains selected were only susceptible to colomycin. Cysteamine at 500 mg/L was bactericidal against all 4 strains of Pa and no antagonism was observed with antipseudomonal agents. The MIC’s of 12 MABSC were 256-1024 mg/L with bactericidal activity against 9 strains at 1024 mg/L and 512 mg/L for 2 strains. One strain was inhibited at 256 mg/L but no bactericidal activity observed at 1024 mg/L. The MIC’s of the 19 other isolates ranged from 64-1024 mg/L with bactericidal activity ranging from 128-1024 mg/L for all except C albicans. The results of this study demonstrate that cysteamine has potential as an antimicrobial for the treatment of severe infection caused by pan resistant bacteria in lung transplant patients with or without CF and warrants further evaluation.