Dietary Indole-3-Carbinol Alleviated Spleen Enlargement, Enhanced IgG Response in C3H/HeN Mice Infected with Citrobacter rodentium.

Enteropathogenic and enterohemorrhagic Escherichia coli are important enteric pathogens that induce hemorrhagic colitis or even fatal hemolytic uremic syndrome. Emerging evidence shows that some bio-actives derived from fruits and vegetables may serve as alternatives to antibiotics for overcoming multidrug resistant E. coli infections. In this study, the Citrobacter rodentium (Cr) infection model was utilized to mimic E. coli-induced acute intestinal inflammation, and the effects of a cruciferous vegetable-derived cancer protective compound, indole-3-carbinol (I3C), on the immune responses of Cr-susceptible C3H/HeN mice were investigated. Dietary I3C significantly inhibited the loss of body weight and the increase in spleen size in Cr infected mice. In addition, I3C treatment reduced the inflammatory response to Cr infection by maintaining anti-inflammatory cytokine IL-22 mRNA levels while reducing expression of other pro-inflammatory cytokines including IL17A, IL6, IL1ß, TNF-α, and IFN-γ. Moreover, the serum cytokine levels of IL17, TNF-α, IL12p70, and G-CSF also were down-regulated by I3C in Cr-infected mice. Additionally, dietary I3C specifically enhanced the Cr-specific IgG response to Cr infection. In general, dietary I3C reduced the Cr-induced pro-inflammatory response in susceptible C3H/HeN mice and alleviated the physiological changes and tissue damage induced by Cr infection but not Cr colonization.

A case of Raoultella ornithinolytica urinary tract infection in a pediatric patient.

Raoultella ornithinolytica is a Gram-negative, non-motile, encapsulated, biofilm producing, facultative aerobic bacillus and is found in natural environment. Human infections with R.ornithinolytica is rare in children with only five cases having been reported previously. The present case report describes an urinary tract infection caused by R. ornithinolytica that was identified by MALDI-TOF MS and successfully treated with antibiotic therapy in a 6.5-year-old female child.

CNF1-like deamidase domains: common Lego bricks among cancer-promoting immunomodulatory bacterial virulence factors.

Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic Escherichia coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer. In particular, through in silico analysis of the distribution of the CNF1-like deamidase active site Gly-Cys-(Xaa)n-His sequence motif in bacterial genomes, we unveil the wide distribution of the super-family of CNF-like toxins and CNF-like deamidase domains among members of the Enterobacteriacae and in association with a large variety of toxin delivery systems. We extent our discussion with recent findings concerning cellular systems that control activated Rac1 GTPase stability and provide protection against cancer. These findings point to the urgency for developing holistic approaches toward personalized medicine that include monitoring for asymptomatic carriage of pathogenic toxin-producing bacteria and that ultimately might lead to improved public health and increased lifespans.

Colonization With Levofloxacin-resistant Extended-spectrum ß-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients.

Background: Bacteremia caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for ß-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. Results: We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. Conclusions: HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.

A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 µg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.

[Monitoring and antibiotic resistance profile of tracheal aspirate microbiota in ICU children with severe craniocerebral trauma].

Nosocomial infections and their rational antibiotic treatment represent a major challenge for the healthcare nowadays. In this context, gramnegative bacteria including Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae spp. are etiologically important and characterized by a significant level of antibiotic resistance. To examine dynamics of the respiratory tract colonization by hospital flora, tracheal aspirates obtained at three time points from 69 children with severe craniocerebral trauma during their stay in ICU were analysed. Colonization was observed on the 4th day of the ICU stay with predomination of K. pneumoniae (45%) and A. baumanii (27-37%). P. aeruginosa was detected after the 8th day of the ICU stay with the isolation rate of 33%. Substantial proportions of P. aeruginosa (61%), A. baumanii (78%) and K. pneumoniae (25%) were resistant to carbapenems. In 65 carbapemen resistant isolates, the presence of carbapenemases was examined using PCRs. OXA-48 carbapenemase was detected in 11 out of 14 (78%) K. pneumoniae isolates. Among the A. baumanii isolates, 30/31 (97%) carried OXA-40 and 1/31 (3%) had OXA-23 carbapenemases. None of the examined A. baumanii and K. pneumoniae isolates produced metallo-betalactamases (MBL). In contrast, all 20 carbapenem resistant P. aeruginosa isolates produced a MBL, and in 12 out of 20 (60%) of theme VIM-2 was detected. Thus, gramnegative nosocomial microflora rapidly colonizes ICU patients and has a high level of resistance to antibiotics, including carbapenems.

Sparing anti-pseudomonas antibiotics in intraabdominal infections.

The progress of surgery allowed the timely source control of the intraabdominal infections (IAIs); the availability and use of the broad-spectrum antibiotics resulted in an important reduction of the morbidity and mortality over the last century. Nevertheless, this pathology remains a major challenge for surgeons, internists, infectious diseases and microbiology specialists. The increased bacterial resistance and its spread within institutions limits the antibiotic treatment options and patients'outcome. This phenomenon is more obvious in Gram-negative bacilli which are the main cause of the IAIs. This paper brings into discussion the criteria which would help reducing the use of anti-pseudomonas antibiotics in the initial empirical treatment when they are not necessary, and also outlines the available therapies for these infections.

Efficacy of human simulated exposures of ceftaroline against phenotypically diverse Enterobacteriaceae isolates.

Ceftaroline fosamil, a new broad-spectrum cephalosporin, exhibits potent bactericidal activity against common Gram-negative pathogens, including Enterobacteriaceae, and Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The purpose of this study was to evaluate the efficacy of a human simulated dose of ceftaroline fosamil against clinical Enterobacteriaceae in both neutropenic and immunocompetent mouse thigh infection models. Thirty-five Enterobacteriaceae isolates with ceftaroline MICs ranging from 0.25 to 32 µg/ml were selected for the neutropenic model, and five Escherichia coli isolates were also tested in the immunocompetent model. Two hours after inoculation, the ceftaroline fosamil human simulated regimen of 600 mg intravenously (i.v.) every 12 h was administered. The change in log(10) CFU after 24 h was compared to that in 0 h controls. The human simulated regimen produced predictable efficacy against 18 of 20 isolates with a MIC of ≤ 1 µg/ml. Similar efficacy was seen in the immunocompetent model against isolates with a MIC of ≤ 2 µg/ml, and enhanced efficacy was observed against the isolate with a MIC of 4 µg/ml. Human simulated exposures to ceftaroline fosamil at 600 mg every 12 h provided predictable efficacy against Enterobacteriaceae with MICs of ≤ 1 µg/ml and enhanced efficacy within the immunocompetent model, supporting the clinical utility of ceftaroline fosamil against these organisms.

A prospective, randomized trial of 3 or 14 days of ciprofloxacin treatment for acute urinary tract infection in patients with spinal cord injury.

BACKGROUND: Urinary tract infection (UTI) is common among patients with spinal cord injury. The optimal duration of treatment for symptomatic UTI has not been determined. METHODS: A randomized, double-blind, placebo-controlled trial compared 3-day and 14-day regimens of ciprofloxacin, 250 mg twice daily, for the treatment of acute UTI in patients with spinal cord injury. Patients with pyelonephritis, struvite stones, hydronephrosis, or long-term indwelling catheters were excluded from the trial. RESULTS: Sixty patients with spinal cord injury were enrolled in the trial, with 30 patients assigned to each study arm. The most common infecting organisms were Klebsiella species (30%), Enterococcus species (22%), and Escherichia coli (22%); 33% of the infections were polymicrobial. Microbiological cure at long-term follow-up was significantly better among patients who received therapy for 14 days than among patients who received therapy for 3 days. By 6 weeks of follow-up, microbiological relapse (in 11 [37%] of 30 patients vs. 2 [7%] of 30 patients; 95% confidence interval [CI], 1.38-3.18; P=.01) and symptomatic relapse (in 7 [23%] 30 patients vs. 0 of 30 patients; 95% CI, 1.69-3.13; P=.01) both occurred more frequently in patients treated for 3 days. Reinfection occurred with similar frequency in patients in the 2 study arms. Six of 7 evaluable patients with treatment failure had a fluoroquinolone-resistant organism isolated at enrollment. CONCLUSIONS: For patients with spinal cord injury, treatment of acute symptomatic UTI for 14 days leads to improved clinical and microbiological outcomes, compared with short-course therapy.

4th meeting of the EU research network EUROME: from the identification of genes and cellular networks in murine models of arthritis to novel therapeutic intervention strategies in rheumatoid arthritis, London, UK, 9 March 2004.

Rheumatoid arthritis (RA) is a common human disease with a prevalence of about 1% in most parts of the world. At the time of symptom onset it is difficult to predict the severity of subsequent disease course. After 2 years joint erosions are seen in most patients, and most patients become clinically disabled within 20 years. A recent meeting at the Kennedy Institute of Rheumatology (Imperial College, London) brought together representatives from several European centres of excellence, to discuss research funded by the EU Framework 5 Quality of Life Programme. This research network combines gene and protein expression profiling with different animal models of RA to identify cells, genes and pathways contributing to arthritis initiation, progression and chronicity. The studies discussed highlight the reality that collaboration between different research groups is the basis of groundbreaking research and, it is hoped, eventual new therapies for RA.

Treatment of infectious diarrhea in children.

Diarrheal diseases remain an important cause of childhood morbidity and death in developing countries, although diarrheal deaths have significantly declined in recent years, mostly due to successes in the implementation of oral rehydration therapy (ORT), which is the principal treatment modality. Diarrhea may occur for varied reasons; however, most episodes of diarrhea in developing countries are infectious in origin. Three clinical forms of diarrhea (acute watery diarrhea, invasive diarrhea, and persistent diarrhea) have been identified to formulate a management plan. Acute diarrhea may be watery (where features of dehydration are prominent) or dysenteric (where stools contain blood and mucus). Rehydration therapy is the key to management of acute watery diarrhea, whereas antimicrobial agents play a vital role in the management of acute invasive diarrhea, particularly shigellosis and amebiasis. In persistent diarrhea, nutritional therapy, including dietary manipulations, is a very important aspect in its management, in addition to rehydration therapy. Rehydration may be carried out either by the oral or intravenous route, depending upon the degree of dehydration. Oral rehydration salts (ORS) solution (World Health Organization formula) is recommended for ORT. Intravenous fluid is recommended for initial management of severe dehydration due to diarrhea, followed by ORT with ORS solution for correction of ongoing fluid losses. Antimicrobial therapy is beneficial for cholera and shigellosis. Antiparasitic agents are indicated only if amebiasis and giardiasis are present. Appropriate feeding during diarrhea is recommended for nutritional recovery and to prevent bodyweight loss. Antidiarrheal agents do not provide additional benefit in the management of infectious diarrhea. Although some probiotics have been shown to be beneficial in the treatment of acute diarrhea due to rotavirus, their use in the treatment of diarrhea is yet to be recommended, even in developed countries. The children of developing countries might benefit from zinc supplementation during the diarrheal illness, but its mode of delivery and cost effectiveness are yet to be decided.

The importance of Bi-Digital O-Ring Test in the treatment of multiple hepatic abscesses: a case history.

The Bi-Digital O-Ring Test has been very useful in the identification of bacterial and viral infections, as well as other etiological agents, in difficult clinical cases. Case report of a patient with multiple hepatic abscesses (pylephlebitis induced hepatic abscess is the most difficult abscess to treat), in which the etiological agent was suggested through Bi-Digital O-Ring Test with excellent clinical evolution after modification of previously ineffective multi anti-microbial treatment is presented. 45 years old, female with a history of pain at right hypochondria for 15 days, with jaundice, oscillating fever and shivering. Computerized tomography showed liver with multiples nodules in the parenchyma with additional appendicitis. An appendectomy was performed with drainage of intra abdominal abscesses. Treatment with metronidazol, ceftazidim and amicacine was performed with no improvement while the general condition of the patient was deteriorating progressively in the following 3 weeks. Bi-Digital O-Ring Test was then performed to determine the etiological agent and the drug compatibility test among effective antimicrobial agents. Based on the Bi-Digital O-Ring Test, the main etiological agent was found to be Enterobacter aerogenes. Amongst the three antibiotics that were being used, only metronidazol was effective and the other 2 was cancelled its effect. Based on Bi-Digital O-Ring Test findings two new antibiotics (cefadroxil and imipenen), were added to metronidazol and additional cilantro tablets by Hayashibara, Japan was given, and Selective Drug Uptake Enhancement Method performed, with excellent clinical, laboratory testing and tomography improvement within 10 days. Bi-Digital O-Ring Test suggested the etiological agent, and effective and mutually compatible antibiotics for treating the abscesses which resulted in a good clinical evolution, characterized by relief of fever and reduction of the hepatic abscesses in a short period and followed complete disappearance of hepatic abscess.

Aztreonam in the treatment of severe urinary tract infections in pediatric patients.

Aztreonam was administered to 30 patients, ages 0.03 to 15.4 years, with severe and in 21 cases complicated urinary tract infections caused by members of the family Enterobacteriaceae and Pseudomonas aeruginosa which were resistant to ampicillin and susceptible to the study drug in vitro. A mean dose of 47.7 mg/kg was given intramuscularly every 12 h to 26 patients. In four patients with renal insufficiency, the dose was reduced according to pharmacokinetic data. Permanent urine sterilization and clinical cure were achieved in 22 patients, 13 of whom had urological malformations. In two patients with P. aeruginosa and Proteus mirabilis infections, the treatment failed. Another patient had an Escherichia coli reinfection 21 days after the end of therapy. Four patients with various urological abnormalities had gram-positive superinfections, and two patients had gram-negative superinfections during and at the end of therapy: all six had indwelling ureteric splints or pyelostomy as predisposing conditions. No adverse clinical effects were observed. Some transient and slight or moderate alterations were observed at the end of treatment: eosinophilia (nine cases), elevation of hepatic enzymes (eight cases), prolongation of prothrombin time (three cases), and neutropenia (one case). A pharmacokinetic study was performed in six patients with normal renal function and in seven patients with various degrees of renal insufficiency. The elimination half-life of the drug was inversely correlated with the glomerular filtration rate. At the dosage used, aztreonam proved effective for severe urinary tract infections caused by members of the family Enterobacteriaceae in pediatric patients.

Aetiology and pathogenesis of postinfective tropical malabsorption (tropical sprue).

Postinfective tropical malabsorption (TM; tropical sprue) starts with an acute intestinal infection (bacterial, viral, or parasitic) which can affect predominantly the small or the large intestine. Miscellaneous invasive pathogens cause subsequent enterocyte damage affecting the entire small intestine and, to a lesser extent, the colon. Enteroglucagon, a tropic hormone, is then liberated and reaches a high plasma concentration. Small-intestinal stasis results. Further bacterial colonisation (in the lumen and also at the enterocyte surface) is encouraged. Continuing enterocyte damage is worsened by coexistent folate depletion, which is initiated at the onset of disease; body stores of folate reach a low concentration by 3 or 4 months. The cycle continues until the bacterial overgrowth is eliminated with an antibiotic (eg, tetracycline), or mucosal integrity recovers (hastened by oral folic-acid supplements), or both.

Enterobacter cloacae septicemia in a burn center: epidemiology and control of an outbreak.

An outbreak of infections due to Enterobacter cloacae occurred in the burn center at the Medical College of Virginia (Richmond, Virginia) in 1976. Fifteen patients had bacteremia due to E. cloacae; 10 cases of bacteremia occurred during a six-week period in January and February. The development of bacteremia was significantly related to the extent of third-degree burn and to admission to the burn center in January and February but not to the presence of an intravenous cannula, underlying disease, or antimicrobial therapy. E. cloacae was spread by contaminated hands of personnel and by cross-contamination of hydrotherapy water. A shortage of staff appeared to be an important factor in the occurrence of the outbreak. Control measures included an increase in the number of personnel, instruction of personnel in proper aseptic technique, and adoption of a new hydrotherapy protocol.

Infections of cervical disc space after dental extractions.

Two patients with infections of the cervical intervertebral disc space after dental procedures carried out by the same oral surgeon exhibited similar clinical courses and radiographic appearances. Both had bacteriological confirmation of infection by needle aspiration and were treated with appropriate antibiotics and bracing of the neck. The presumed aetiology and the possible pathogenesis are described. Evidence suggests that the two infections were the result of needle injection of a contaminated solution, the organisms of which haematogenously lodged in the intervertebral discs in the cervical region. Lymph drainage from the gums and teeth is suggested as a possible route of inoculation.