Identification of a Bacteria-produced Benzisoxazole with Antibiotic Activity against Multi-drug Resistant Acinetobacter baumannii

The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml−1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole

Management of wet ascitic type of peritoneal tuberculosis: single center experience

OBJECTIVE: We aimed to present our experience with the management of 17 patients with ascites who underwent diagnostic laparoscopy or laparotomy, and histologic confirmation of wet ascitic type of peritoneal tuberculosis (TB). PATIENTS AND METHODS: Between January 2008 and March 2019, 17 patients whose ascites were investigated by a gastroenterologist and who were thought to have non-cirrhotic ascites were referred to our Surgery clinic for peritoneal biopsy. The clinical, biochemical, radiological, microbiological, and histopathological data of the patients who underwent diagnostic laparoscopy or laparotomy were analyzed retrospectively. Histopathological examination of peritoneal tissue samples in hematoxylin-eosin-stained preparations revealed necrotizing granulomatous inflammation with caseous necrosis and Langhans type giant cells. Ehrlich-Ziehl-Neelsen (EZN) staining was studied with the suspicion of TB. Acid-fast bacilli (AFB) were detected in EZN stained slide. Histopathological findings were also considered. RESULTS: Seventeen patients aged 18 to 64 years were included in this study. The most common symptoms were ascites and abdominal distention, weight loss, night sweats, fever and diarrhea. Radiological examination revealed peritoneal thickening, ascites, omental cacking, and diffuse lymphadenopathy. Histopathologically, necrotizing granulomatous peritonitis consistent with peritoneal TB were detected. While direct laparoscopy was preferred in sixteen patients, laparotomy was preferred in the remaining one due to previous surgical procedures.  However, seven were converted to open laparotomy. CONCLUSIONS: Diagnosis of abdominal TB requires high index of suspicion, and the treatment should be prompt to reduce the morbidity and mortality associated with delay in treatment