Identification and characterization of novel isothiazolones with potent bactericidal activity against multi-drug resistant Acinetobacter baumannii clinical isolates.

Acinetobacter baumannii has emerged as a globally important nosocomial pathogen characterized by an increased multi-drug resistance (MDR), leaving limited options for treating its infection. To identify novel antibacterial compounds with activity against clinical isolates of A. baumannii, we performed high-throughput screening against a chemical library of 42,944 compounds using nonpathogenic Escherichia coli MG1655 and identified 55 hit compounds. The antibacterial activities of 30 pure compounds were determined against MDR clinical isolates of A. baumannii obtained from Los Angeles County hospitals. Two isothiazolones identified, 5-chloro-2-(4-chloro-3-methylphenyl)-4-methyl-3(2H)-isothiazolone (Compound 6) and 5-chloro-2-(4-chlorophenyl)-4-methyl-3(2H)-isothiazolone (Compound 7), possess novel structure and exhibited consistent, potent and cidal activity against all 46 MDR A. baumannii clinical isolates and reference strains. Additionally, structure-activity relationship analysis involving several additional isothiazolones supports the link between a chloro-group on the heterocyclic ring or a fused benzene ring and the cidal activity. Attempts to obtain isothiazolone resistant mutants failed, consistent with the rapid cidal action and indicative of a complex mechanism of action. While cytotoxicity was observed with Compound 7, it had a therapeutic index value of 28 suggesting future therapeutic potential. Our results indicate that high-throughput screening of compound libraries followed by in vitro biological evaluations is a viable approach for the discovery of novel antibacterial agents to contribute in the fight against MDR bacterial pathogens.

[Clinical analysis on hepatic hydatid disease in Yili river valley].

OBJECTIVE: To analyze the clinical diagnosis and treatment of hepatic hydatid disease and its epidemiological characteristics in Yili river valley. METHODS: Retrospective investigation was carried out on 2049 cases collected in 1993-2003. Clinical diagnosis was made by ways of intradermal test, serological test, ultrasound, X-ray, CT and/or MRI, majority of them received surgical operation. RESULTS: Among the 2049 cases, cystic hydatidosis occupied 96% (1965/2049), while 4% (84/2049) were alveolar hydatidosis. 99% (2034/2049) accepted surgery including hepatolobectomy, endocystomy and hydatidostomy in 302 cases (14.7%) without relapses. 754 cases (36.7%) received chemotherapy (praziquantel, albendazole) after surgical operation. The disease distributed in agri-pastoral areas along the valley. Local residents from different minorities had a close contact with dogs, 54% of the cases were females and 48% of the cases were in the group of 25-49 years old. The incidence tends to decline in the years. CONCLUSION: Hydatidosis is still an important health problem in the region. Further practices for improving treatment especially surgical intervention and for epidemiological investigation are needed.