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

• Published in: International journal of antimicrobial agents Vol. 39; no. 1; pp. 27 - 32
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.01.2012; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; anti-infective agents; antibacterial properties; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial resistance; Bacterial Infections - microbiology; beta-lactamase; Biological and medical sciences; Burkholderia cepacia complex; Burkholderia cepacia complex - drug effects; Burkholderia cepacia complex - isolation & purification; cystic fibrosis; Cystic Fibrosis - microbiology; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Infectious Disease; Medical sciences; Microbial Sensitivity Tests - standards; Minimum inhibitory concentration; multiple drug resistance; patients; Pharmacology. Drug treatments; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - isolation & purification; Staphylococcus aureus; Stenotrophomonas maltophilia; Susceptibility testing; Thiourea - analogs & derivatives; Thiourea - chemical synthesis; Thiourea - chemistry; Thiourea - pharmacology; virulent strains; Pseudomonas aeruginosa; Susceptibility testing; Antimicrobial resistance; Minimum inhibitory concentration; Pseudomonadales; Drug susceptibility test; In vitro; Biological activity; Antimicrobial agent; Hydrochlorides; Burkholderia cepacia; Multiple resistance; Pseudomonadaceae; Bacteria
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.08.015

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.