Clinical analysis of nontyphoidal salmonellosis in children and mechanisms of Salmonella resistance to bile

• Main Authors: Ming Han Tsai, 蔡明翰
• Other Authors: C. H. Chiu
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/97430037122776249507

博士 === 長庚大學 === 臨床醫學研究所 === 99 === Salmonella is one of the most important pathogens. Most people with Salmonella infections have self-limited gastroenteritis; however, it can also cause bacteremia or extraintestinal focal infections without overt diarrheal illness. In children with nontyphoidal salmonellosis, most of them present as self-limited gastroenteritis and few for nontyphoidal Salmonella bacteremia. So we characterized the clinical features of previously healthy children with nontyphoidal Salmonella bacteremia. Our results revealed that nontyphoidal Salmonella bacteremia was relatively benign and extraintestinal infections were infrequently seen. Less than 10 days of appropriate antibiotic treatment is probably adequate for those without a suppurative focal infection. In the treatment of children with nontyphoidal enteric infection, antimicrobial therapy is not recommended for routine treatment of nontyphoidal salmonellosis and effective antibiotic treatment is essential if NTS infection spreads beyond the intestine such as bacteremia or other extraintestinal infections. Although some reports revealed that antimicrobial therapy may be beneficial for shortening the clinical courses of severe NTS enteritis, most of them were not based on the objective studies. Thus, we evaluated and reassessed the indications of parenteral antimicrobial therapy in children with nontyphoidal enteric infection. We found that antibiotics which can reach high tissue concentrations in the intestinal mucosa (i.e., 3rd generation cephalosporins), may be clinically beneficial to a subset of patients with high CRP (≧100 mg/L) and longer duration of fever (≧2 days) among children with NTS enteritis. To prevent the induction of antibiotic resistance from this therapy, we suggest a short course (3–5 days) of intravenous ceftriaxone for such patients, which will lead to a faster clinical recovery. Increased antimicrobial resistance in nontyphoidal Salmonella species is a serious problem for public health worldwide. In order to improve our understanding of antimicrobial resistance and the choice of proper antimicrobial therapies, it is important to recognize how Salmonella can endure environmental extremes in the intestinal tracts, such as the presence of bile. Besides the major role of emulsification and solubilization of lipids, bile also acts as a detergent with potent antimicrobial activity. So if Salmonella can survive in the intestinal tract, they must defend themselves against the toxic action of bile. Our study showed that mutations in genes for lipopolysaccharide (rfaP and dam) synthesis and efflux pump-related genes (tolC), and regulatory genes (marAB and phoPQ) would impair Salmonella resistance to bile. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. So we recommended that the efflux pump inhibitor in combination with fluoroquinolones may be an effective strategy for dealing with the increasing resistance in Salmonella infection. Besides the resistance mechanisms to bile previously described, biofilm may be another cause for Salmonella to exist in an asymptomatic carrier state in the human intestines and gallbladders. Biofilms are defined as communities of organisms attached to a surface and producing an extracellular matrix, in which the bacteria are imbedded. Our study indicated that biofilm formation is dependent on the presence of bile because Salmonella organisms cultured without bile do not readily form biofilms. Then we utilized 2-D gel electrophoresis to analyze the effect of bile on the biofilm formation at the global proteomic level. The results revealed that mutants with incomplete capsule (ompA mutant), defective flagella (fljB or flgE mutant) and mutants deficient in quorum sensing (luxS mutant) were shown to be defective in biofilm formation. It may conclude that the flagellar-mediated motility provides mechanisms enabling Salmonella to reach surfaces. Besides, both external environmental cues (i.e., bile) and bacterial signaling molecules have been shown to be important in triggering the initiation of biofilm formation. Throughout the study, we hope to increase our understanding on the mechanisms of how Salmonella tolerate the high levels of bile and the occurrence of chronic infections. Information obtained from bile and biofilm research may be exploited in the devising of novel antibacterial and preventive therapies.