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

Nicholson, Audrey, Perry, John, James, Arthur, Stanforth, Stephen, Carnell, Sonya, Wilkinson, Kathryn, Khan, Anjam, de Soyza, Anthony and Gould, Kate (2012) 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. International Journal of Antimicrobial Agents, 39 (1). pp. 27-32. ISSN 0924-8579

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Abstract

The aim of this study was to establish the antimicrobial activities of S-(3,4-dichlorobenzyl)isothioureahydrochloride (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 cepaciacomplex (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 [1]g/mL]. This compound was also the most activea gainst BCC, with all isolates inhibited by 64 [1]g/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 [1]g/mL]against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S-(4-chlorobenzyl)-N-(2,4 dichlorophenyl)isothiourea hydrochloride showed good activity (MIC90 = 8 [1]g/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.

Item Type:	Article
Uncontrolled Keywords:	Susceptibility testing Minimum inhibitory concentration Antimicrobial resistance Pseudomonas aeruginosa
Subjects:	F100 Chemistry
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Linda Barlow
Date Deposited:	21 Dec 2012 13:13
Last Modified:	12 Oct 2019 18:27
URI:	http://nrl.northumbria.ac.uk/id/eprint/10862

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