Jordi Vila

Bacterial translocation of enteric organisms in patients with cirrhosis

BACKGROUND/AIMS The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

Bacterial infections in cirrhosis: A position statement based on the EASL Special Conference 2013

Bacterial infections are very common and represent one of the most important reasons of progression of liver failure, development of liver-related complications, and mortality in patients with cirrhosis. In fact, bacterial infections may be a triggering factor for the occurrence of gastrointestinal bleeding, hypervolemic hyponatremia, hepatic encephalopathy, kidney failure, and development of acute-on-chronic liver failure. Moreover, infections are a very common cause of repeated hospitalizations, impaired health-related quality of life, and increased healthcare costs in cirrhosis. Bacterial infections develop as a consequence of immune dysfunction that occurs progressively during the course of cirrhosis. In a significant proportion of patients, infections are caused by gram-negative bacteria from intestinal origin, yet gram-positive bacteria are a frequent cause of infection, particularly in hospitalized patients. In recent years, infections caused by multidrug-resistant bacteria are becoming an important clinical problem in many countries. The reduction of the negative clinical impact of infections in patients with cirrhosis may be achieved by a combination of prophylactic measures, such as administration of antibiotics, to reduce the occurrence of infections in high-risk groups together with early identification and management of infection once it has developed. Investigation on the mechanisms of altered gut microflora, translocation of bacteria, and immune dysfunction may help develop more effective and safe methods of prevention compared to those that are currently available. Moreover, research on biomarkers of early infection may be useful in early diagnosis and treatment of infections. The current manuscript reports an in-depth review and a position statement on bacterial infections in cirrhosis.

Mechanisms of Resistance in Multiple-Antibiotic-Resistant Escherichia coli Strains of Human, Animal, and Food Origins

ABSTRACT Seventeen multiple-antibiotic-resistant nonpathogenic Escherichia coli strains of human, animal, and food origins showed a wide variety of antibiotic resistance genes, many of them carried by class 1 and class 2 integrons. Amino acid changes in MarR and mutations in marO were identified for 15 and 14 E. coli strains, respectively.

The global threat of antimicrobial resistance: science for intervention

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

Salmonella enterica Serovar Typhimurium Skills To Succeed in the Host: Virulence and Regulation

SUMMARY Salmonella enterica serovar Typhimurium is a primary enteric pathogen infecting both humans and animals. Infection begins with the ingestion of contaminated food or water so that salmonellae reach the intestinal epithelium and trigger gastrointestinal disease. In some patients the infection spreads upon invasion of the intestinal epithelium, internalization within phagocytes, and subsequent dissemination. In that case, antimicrobial therapy, based on fluoroquinolones and expanded-spectrum cephalosporins as the current drugs of choice, is indicated. To accomplish the pathogenic process, the Salmonella chromosome comprises several virulence mechanisms. The most important virulence genes are those located within the so-called Salmonella pathogenicity islands (SPIs). Thus far, five SPIs have been reported to have a major contribution to pathogenesis. Nonetheless, further virulence traits, such as the pSLT virulence plasmid, adhesins, flagella, and biofilm-related proteins, also contribute to success within the host. Several regulatory mechanisms which synchronize all these elements in order to guarantee bacterial survival have been described. These mechanisms govern the transitions from the different pathogenic stages and drive the pathogen to achieve maximal efficiency inside the host. This review focuses primarily on the virulence armamentarium of this pathogen and the extremely complicated regulatory network controlling its success.

The Acinetobacter baumannii Oxymoron: Commensal Hospital Dweller Turned Pan-Drug-Resistant Menace

During the past few decades Acinetobacter baumannii has evolved from being a commensal dweller of health-care facilities to constitute one of the most annoying pathogens responsible for hospitalary outbreaks and it is currently considered one of the most important nosocomial pathogens. In a prevalence study of infections in intensive care units conducted among 75 countries of the five continents, this microorganism was found to be the fifth most common pathogen. Two main features contribute to the success of A. baumannii: (i) A. baumannii exhibits an outstanding ability to accumulate a great variety of resistance mechanisms acquired by different mechanisms, either mutations or acquisition of genetic elements such as plasmids, integrons, transposons, or resistant islands, making this microorganism multi- or pan-drug-resistant and (ii) The ability to survive in the environment during prolonged periods of time which, combined with its innate resistance to desiccation and disinfectants, makes A. baumannii almost impossible to eradicate from the clinical setting. In addition, its ability to produce biofilm greatly contributes to both persistence and resistance. In this review, the pathogenesis of the infections caused by this microorganism as well as the molecular bases of antibacterial resistance and clinical aspects such as treatment and potential future therapeutic strategies are discussed in depth.

Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs.

The mutations in the quinolone resistance-determining region of the gyrA and gyrB genes from 27 clinical isolates of Escherichia coli with a range of MICs of ciprofloxacin from 0.007 to 128 micrograms/ml and of nalidixic acid from 2 to > 2,000 micrograms/ml were determined by DNA sequencing. All 15 isolates with ciprofloxacin MICs of > or = 1 micrograms/ml showed a change in Ser-83 to Leu of GyrA protein, whereas in clinical isolates with a MIC of > or = 8 micrograms/ml (11 strains), a double change in Ser-83 and Asp-87 was found. All isolates with a MIC of nalidixic acid of > or = 128 micrograms/ml showed a mutation at amino acid codon Ser-83. Only 1 of the 27 clinical isolates of E. coli analyzed showed a change in Lys-447 of the B subunit of DNA gyrase. A change in Ser-83 is sufficient to generate a high level of resistance to nalidixic acid, whereas a second mutation at Asp-87 in the A subunit of DNA gyrase may play a complementary role in developing the strains high levels of ciprofloxacin resistance.

Are Quinolone-Resistant Uropathogenic Escherichia coli Less Virulent?

The prevalence of hemolysin, type 1 fimbriae, P fimbriae, cytotoxic necrotizing factor-1 (CNF-1), aerobactin, and autotransporter toxin (sat) was analyzed by polymerase chain reaction and phenotypic assays of 42 epidemiologically unrelated Escherichia coli strains causing acute pyelonephritis in women (21 nalidixic acid-susceptible and 21 nalidixic acid-resistant strains) and 58 E. coli strains causing cystitis in women (29 nalidixic acid-susceptible and 29 nalidixic acid-resistant strains). Hemolysin and CNF-1 were less prevalent (P<.05) in nalidixic acid-resistant than in nalidixic acid-susceptible E. coli strains from patients with either pyelonephritis (14.3% vs. 52.4%) or cystitis (0% vs. 31.0%). Among E. coli strains causing cystitis, type 1 fimbriae expression was less prevalent (P<.05) in the nalidixic acid-resistant group (55.2%) than in the nalidixic acid-susceptible group (86.2%). None of the nalidixic acid-resistant and 20.7% of the nalidixic acid-susceptible strains causing cystitis showed the proteolytic toxin Sat (P<.05). These results suggest that resistance to quinolones may be associated with a decrease in the presence or the expression of some virulence factors in uropathogenic E. coli.

Mutation in the gyrA gene of quinolone-resistant clinical isolates of Acinetobacter baumannii.

The gyrA gene mutations associated with quinolone resistance were determined in 21 epidemiologically unrelated clinical isolates of Acinetobacter baumannii. Our studies highlight the conserved sequences in the quinolone resistance-determining region of the gyrA gene from A. baumannii and other bacteria. All 15 isolates for which the MIC of ciprofloxacin is > or = 4 micrograms/ml showed a change at Ser-83 to Leu. Six strains for which the MIC of ciprofloxacin is 1 microgram/ml did not show any change at Ser-83, although a strain for which the MIC of ciprofloxacin is 1 microgram/ml exhibited a change at Gly-81 to Val. Although it is possible that mutations in other locations of the gyrA gene, the gyrB gene, or in other genes may also contribute to the modulation of the MIC level, our results suggest that a gyrA mutation at Ser-83 is associated with quinolone resistance in A. baumannii.

Aeromonas spp. and traveler's diarrhea: clinical features and antimicrobial resistance.

Traveler’s diarrhea is the most common health problem of international travelers. We determined the prevalence of Aeromonas spp. associated with traveler’s diarrhea and analyzed the geographic distribution, clinical features, and antimicrobial susceptibility. Aeromonas spp. were isolated as a cause of traveler’s diarrhea in 18 (2%) of 863 patients. A. veronii biotype sobria was isolated in nine patients, A. caviae in seven patients, and A. jandai and A. hydrophila in one patient each. Aeromonas spp. were isolated with a similar prevalence in Africa, Latin America, and Asia. Watery and persistent diarrhea, fever, and abdominal cramps were common complaints. All strains were resistant to ampicillin; showed variable resistance to chloramphenicol, tetracycline, and cotrimoxazole; and were susceptible to cefotaxime, ciprofloxacin, and nalidixic acid. The persistence of symptoms made antimicrobial treatment necessary.