Details

Autor(en) / Beteiligte

• Nicholson, Audrey
• Perry, John D
• James, Arthur L
• Stanforth, Stephen P
• Carnell, Sonya
• Wilkinson, Kathryn
• Anjam Khan, C.M
• De Soyza, Anthony
• Gould, F. Kate

Titel

In vitro activity of S -(3,4-dichlorobenzyl)isothiourea hydrochloride and novel structurally related compounds against multidrug-resistant bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia complex

Ist Teil von

• International journal of antimicrobial agents, 2012-01, Vol.39 (1), p.27-32

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract The aim of this study was to establish the antimicrobial activities of S -(3,4-dichlorobenzyl)isothiourea hydrochloride (A22) and a series of structurally related compounds against multidrug-resistant (MDR) bacteria. The minimum inhibitory concentrations (MICs) of 21 compounds were determined against 18 strains of pathogenic bacteria in addition to Pseudomonas aeruginosa ( n = 19) and Burkholderia cepacia complex (BCC) ( n = 20) isolated from the sputa of cystic fibrosis patients. Selected compounds were tested against further isolates, including P. aeruginosa ( n = 100), BCC ( n = 12) and Stenotrophomonas maltophilia ( n = 19). The interaction of S -(4-chlorobenzyl)isothiourea hydrochloride ( C2 ) in combination with conventional antimicrobials was examined against 10 P. aeruginosa strains. Selected compounds were also tested against Enterobacteriaceae producing NDM-1 carbapenemase ( n = 64) and meticillin-resistant Staphylococcus aureus (MRSA) ( n = 37). Of the 21 compounds, 14 showed antimicrobial activity that was generally more pronounced against Gram-negative bacteria. Against P. aeruginosa , the most active compound was C2 [MIC for 50% of the organisms (MIC50 ) = 32 μg/mL]. This compound was also the most active against BCC, with all isolates inhibited by 64 μg/mL. For all ten strains of P. aeruginosa subjected to combination testing with C2 and conventional antimicrobials, a bactericidal effect was achieved with at least one combination. C2 and A22 both showed strong activity [MIC for 90% of the organisms (MIC90 ) = 4 μg/mL] against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S -(4-chlorobenzyl)- N -(2,4-dichlorophenyl)isothiourea hydrochloride showed good activity (MIC90 = 8 μg/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.