Microbiology Department, Freeman Hospital, Newcastle upon Tyne, UK.
Int J Antimicrob Agents. 2012 Jan;39(1):27-32. doi: 10.1016/j.ijantimicag.2011.08.015. Epub 2011 Oct 10.
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 (MIC(50))=32μg/mL]. This compound was also the most active against BCC, with all isolates inhibited by 64μg/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 (MIC(90))=4μg/mL] against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S-(4-chlorobenzyl)-N-(2,4-dichlorophenyl)isothiourea hydrochloride showed good activity (MIC(90)=8μg/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.
本研究旨在确定 S-(3,4-二氯苄基)异硫脲盐酸盐（A22）和一系列结构相关化合物对多药耐药（MDR）细菌的抗菌活性。除了从囊性纤维化患者痰液中分离出的铜绿假单胞菌（n=19）和伯克霍尔德菌复合群（BCC）（n=20）外，还测定了 21 种化合物对 18 种病原菌的最低抑菌浓度（MIC）。选择的化合物进一步针对其他分离株进行了测试，包括铜绿假单胞菌（n=100）、BCC（n=12）和嗜麦芽窄食单胞菌（n=19）。还研究了 S-(4-氯苄基)异硫脲盐酸盐（C2）与常规抗菌药物联合使用对 10 株铜绿假单胞菌的相互作用。还测试了所选化合物对产 NDM-1 碳青霉烯酶的肠杆菌科（n=64）和耐甲氧西林金黄色葡萄球菌（MRSA）（n=37）的抗菌活性。在 21 种化合物中，有 14 种具有抗菌活性，通常对革兰氏阴性菌的活性更强。对铜绿假单胞菌而言，最有效的化合物是 C2[半数抑菌浓度（MIC50）为 32μg/mL]。该化合物对 BCC 的活性也最强，所有分离株均被 64μg/mL 抑制。在对 10 株铜绿假单胞菌进行 C2 与常规抗菌药物联合测试的所有菌株中，至少有一种组合产生了杀菌作用。C2 和 A22 对产 NDM-1 碳青霉烯酶的肠杆菌科均表现出较强的活性[MIC90 为 4μg/mL]。最后，S-(4-氯苄基)-N-(2,4-二氯苯基)异硫脲盐酸盐对 MRSA 表现出良好的活性（MIC90=8μg/mL）。本研究确定了异硫脲衍生物对广泛的临床重要 MDR 细菌的活性。
