Influenza Virus Infection Impairs the Gut's Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids.

Along with respiratory tract disease per se, viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders. In IAV-infected mice, the signs of intestinal injury and inflammation, altered gene expression, and compromised intestinal barrier functions peaked on day 7 postinfection. As a likely result of bacterial component translocation, gene expression of inflammatory markers was upregulated in the liver. These changes occurred concomitantly with an alteration of the composition of the gut microbiota and with a decreased production of the fermentative, gut microbiota-derived products short-chain fatty acids (SCFAs). Gut inflammation and barrier dysfunction during influenza were not attributed to reduced food consumption, which caused in part gut dysbiosis. Treatment of IAV-infected mice with SCFAs was associated with an enhancement of intestinal barrier properties, as assessed by a reduction in the translocation of dextran and a decrease in inflammatory gene expression in the liver. Lastly, SCFA supplementation during influenza tended to reduce the translocation of the enteric pathogen Salmonella enterica serovar Typhimurium and to enhance the survival of doubly infected animals. Collectively, influenza virus infection can remotely impair the gut's barrier properties and trigger secondary enteric infections. The latter phenomenon can be partially countered by SCFA supplementation.

Early Bacterial Infections After Pediatric Liver Transplantation in the Era of Multidrug-resistant Bacteria: Nine-year Single-center Retrospective Experience.

BACKGROUND: Early bacterial infection is a major and severe complication after liver transplantation (LT). The rise of antimicrobial resistance, especially extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), is a growing concern for these patients. This study aimed to assess the epidemiology of early bacterial infections in a pediatric population, including those caused by multidrug-resistant (MDR) pathogens, and to identify risk factors for infection. METHODS: We conducted a monocentric retrospective study including 142 consecutive LTs performed in 137 children between 2009 and 2017. RESULTS: Ninety-three bacterial infections occurred after 67 (47%) LTs. Among the 82 isolated pathogens, the most common was Klebsiella pneumoniae (n = 19, 23%). Independent risk factors for early bacterial infection were low weight [odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.9-0.99; P = 0.03] and the presence of a prosthetic mesh (OR = 2.4; 95% CI: 1.1-5.4; P = 0.046). Sixty-one children (45%) carried MDR bacteria and 16 infections were caused by MDR pathogens, especially ESBL-producing K. pneumoniae (n = 12). ESBL-PE stool carriage was associated with ESBL-PE infection (OR = 4.5; 95% CI: 1.4-17.4; P = 0.02). Four children died from an infection, three due to ESBL-producing K. pneumoniae. CONCLUSIONS: This study confirmed a shift toward a predominance of Gram-negative early bacterial infections after pediatric LT. The risk factors for infection were low weight and the presence of a prosthetic mesh. ESBL-PE stool carriage was associated with ESBL-PE infection. Adapted antimicrobial prophylaxis and personalized antibiotherapy are mandatory to reduce infection prevalence and mortality.

Subchronic (90-day) toxicity assessment of Somacy-FP100, a lipopolysaccharide-containing fermented wheat flour extract from Pantoea agglomerans.

Pantoea agglomerans is a Gram-negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide-containing fermented wheat flour extract from P. agglomerans (Somacy-FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with Somacy-FP100 reported its lack of genotoxicity in vitro, but a subchronic toxicity study has not yet been performed. Therefore, to demonstrate the safety of Somacy-FP100 for use as a food ingredient, a 90-day oral (gavage) toxicity study in rats was conducted. Male and female Han Wistar rats were administered vehicle (control) or Somacy-FP100 at 500, 1500, or 4500 mg/kg body weight/day at a dose volume of 10 mL/kg body weight, for at least 90 days. No test article-related adverse clinical signs or effects on body weight, food consumption, or clinical pathology were observed, and there were no macroscopic or microscopic findings related to the test article. Therefore, 4500 mg/kg body weight/day (the highest dose tested and highest feasible dose) was established as the no-observed-adverse-effect level. This absence of subchronic toxicity, in addition to the previously reported lack of genotoxicity, demonstrates the safety of Somacy-FP100 for use as a food ingredient.

Diet-derived galacturonic acid regulates virulence and intestinal colonization in enterohaemorrhagic Escherichia coli and Citrobacter rodentium.

Enteric pathogens sense the complex chemistry within the gastrointestinal tract to efficiently compete with the resident microbiota and establish a colonization niche. Here, we show that enterohaemorrhagic Escherichia coli and Citrobacter rodentium, its surrogate in a mouse infection model, sense galacturonic acid to initiate a multi-layered program towards successful mammalian infection. Galacturonic acid utilization as a carbon source aids the initial pathogen expansion. The main source of galacturonic acid is dietary pectin, which is converted to galacturonic acid by the prominent member of the microbiota, Bacteroides thetaiotamicron. This is regulated by the ExuR transcription factor. However, galacturonic acid is also sensed as a signal through ExuR to modulate the expression of the genes encoding a molecular syringe known as a type III secretion system, leading to infectious colitis and inflammation. Galacturonic acid acts as both a nutrient and a signal directing the exquisite microbiota-pathogen relationships within the gastrointestinal tract. This work highlights that differential dietary sugar availability influences the relationship between the microbiota and enteric pathogens, as well as disease outcomes.

"Double carbapenem" and oral fosfomycin for the treatment of complicated urinary tract infections caused by blaNDM -harboring Enterobacteriaceae in kidney transplantation.

Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplant patients with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin.

Travel to Asia and traveller's diarrhoea with antibiotic treatment are independent risk factors for acquiring ciprofloxacin-resistant and extended spectrum ß-lactamase-producing Enterobacteriaceae-a prospective cohort study.

Travel to (sub)tropical countries is a well-known risk factor for acquiring resistant bacterial strains, which is especially of significance for travellers from countries with low resistance rates. In this study we investigated the rate of and risk factors for travel-related acquisition of extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E), ciprofloxacin-resistant Enterobacteriaceae (CIPR-E) and carbapenem-resistant Enterobacteriaceae. Data before and after travel were collected from 445 participants. Swabs were cultured with an enrichment broth and sub-cultured on selective agar plates for ESBL detection, and on plates with a ciprofloxacin disc. ESBL production was confirmed with the double-disc synergy test. Species identification and susceptibility testing were performed with the Vitek-2 system. All isolates were subjected to ertapenem Etest. ESBL and carbapenemase genes were characterized by PCR and sequencing. Twenty-seven out of 445 travellers (6.1%) already had ESBL-producing strains and 45 of 445 (10.1%) travellers had strains resistant to ciprofloxacin before travel. Ninety-eight out of 418 (23.4%) travellers acquired ESBL-E and 130 of 400 (32.5%) travellers acquired a ciprofloxacin-resistant strain. Of the 98 ESBL-E, predominantly Escherichia coli and predominantly blaCTX-M-15, 56% (55/98) were resistant to gentamicin, ciprofloxacin and co-trimoxazole. Multivariate analysis showed that Asia was a high-risk area for ESBL-E as well as CIPR-E acquisition. Travellers with diarrhoea combined with antimicrobial use were significantly at higher risk for acquisition of resistant strains. Only one carbapenemase-producing isolate was acquired, isolated from a participant after visiting Egypt. In conclusion, travelling to Asia and diarrhoea combined with antimicrobial use are important risk factors for acquiring ESBL-E and CIPR-E.

First Report of a Foodborne Providencia alcalifaciens Outbreak in Kenya.

Providencia alcalifaciens is an emerging bacterial pathogen known to cause acute gastroenteritis in children and travelers. In July 2013, P. alcalifaciens was isolated from four children appearing for diarrhea at Kiambu District Hospital (KDH) in Kenya. This study describes the outbreak investigation, which aimed to identify the source and mechanisms of infection. We identified seven primary and four secondary cases. Among primary cases were four mothers who had children and experienced mild diarrhea after eating mashed potatoes. The mothers reported feeding children after visiting the toilet and washing their hands without soap. P. alcalifaciens was detected from all secondary cases, and the isolates were found to be clonal by random amplified polymorphic DNA (RAPD) fingerprinting. Our study suggests that the outbreak was caused by P. alcalifaciens, although no fluid accumulation was observed in rabbit ileal loops. The vehicle of the outbreak was believed to be the mashed potato dish, but the source of P. alcalifaciens could not be confirmed. We found that lack of hygiene, inadequate food storage, and improper hand washing before food preparation was the likely cause of the current outbreak. This is the first report of a foodborne infection caused by P. alcalifaciens in Kenya.

Non-surgical management of thyroid abscess with ultrasound-guided fine-needle application of an antibiotic followed by sclerotization with absolute alcohol.

Thyroid abscess is a relatively rare yet dramatic condition of the thyroid gland requiring immediate therapeutic intervention. Traditionally, more or less aggressive surgical approaches and administration of broad-spectrum antibiotics have been used. Clinically less severe disease allows non-surgical treatment as well. The case report describes successful treatment of a large abscess of iatrogenic origin after biopsy of a cystic cavity. A combination of broad-spectrum antibiotics was used based on culture results, administered both orally and by repeated application directly into the abscess cavity using an ultrasound-guided fine-needle approach. Concurrent repeated evacuation of the cavity replaced drainage. Ultimately, a small residual cavity with sterile contents was managed by sclerotization with absolute alcohol. Clinical condition permitting, thyroid abscess may be successfully treated by repeated application of a targeted antibiotic, using a fine needle and ultrasound guidance, directly into the abscess cavity, with repeated evacuation replacing drainage.

New Delhi Metallo-beta lactamase-1 containing enterobacteriaceae: origin, diagnosis, treatment and public health concern.

One of the biggest problems associated with the antibiotic therapy is resistance. Recently published studies have revealed that enterobacteriaceae, like E. coli and Klebsiella, isolated from several Indian centers are resistant to many antibiotics including some highly potent antibiotics like carbapenems. It has been proposed that this resistance is because of a carbapenemase enzyme called NDM-1 (New Delhi Metallo-betalactamase-1). This carbapenemase is class B carbapenemase also called metallolactamases as they require zinc at their active site. This enzyme is coded by a gene called bla-NDM-1 or gene NDM-1. NDM-1 containing enterobacteriaceae can be screened in laboratory by few techniques. Metallolactamase production can be detected by disk approximation test or Modified Hodge test and NDM-1 gene can be detected by polymerase chain reaction by the use of specific primer targeting the gene. Infections caused by such bacteria are associated with high morbidity and mortality. Two classes of antibiotics i.e., polymyxins (colistin) and glycylcyclines (tigecyclines), have shown in vitro activity against NDM-1 harboring enterobacteriaceae. The safety profile of both of these antibiotics is questionable. There is a need for active screening of microorganisms for NDM-1 and research should be directed towards the development of safe antibiotics for the treatment of these kinds of infections.

[Pyogenic spondylitis by Enterobacter cloacae as a postoperative complication of TURP: a case report].

We report a case of pyogenic spondylitis caused by Enterobacter cloacae as a rare complication of transurethral resection of the prostate (TURP). A 79-year-old man underwent TURP. Immediate after removal of urethral catheter on postoperative day (POD) 7, he developed high fever > 40 degrees C with increased acute inflammatory reaction. Urine and blood culture detected E. cloacae and methicillin-resistant Staplylococcus aureus. He complained of lumbago since POD 9. Two-week administration of imipenem and teicoplanin resulted in resolution of fever as well as laboratory data, so intravenous antibiotics were changed to oral gatifloxacin. However, his lumbago worsened and gait disturbance appeared. On POD 39, diagnosis of pyogenic spondylitis was finally obtained by Ga-scintigraphy and magnetic resonance imaging. Aspiration of the intervertebral disk (L4-5) revealed E. cloacae as the causative organism of pyogenic spondylitis. His condition improved after conservative treatment with teicoplanin, meropenem and ciplofloxacin for 9 weeks.

Optimization of empirical antibiotic selection for suspected Gram-negative bacteraemia in the emergency department.

A 1-year prospective study of patients with a positive blood culture and admitted through the emergency department (ED), was conducted to detect incidence and risk factors for resistance of Enterobacteriaceae to gentamicin and ciprofloxacin. A total of 245 emergency department-admitted patients had positive blood cultures, of which 131 (54%) grew Enterobacteriaceae. Of these 131 isolates, 32 (24%) were resistant to gentamicin and 37 (28%) to ciprofloxacin. Risk factors, by multivariate analysis, for gentamicin and ciprofloxacin resistance were: male gender (P<0.05 and P<0.01, respectively), nursing home residence (P<0.001), diabetes mellitus (P<0.05) and presence of a foreign body (P<0.05 and P<0.005). An additional risk factor for ciprofloxacin resistance was recent hospitalisation (P<0.05). These data facilitate optimal selection of empirical antibiotic treatment of suspected Gram-negative infections, and may contribute to improved patient outcome and optimal use of antibiotics.

Successful treatment of infected vascular prosthetic grafts in the groin using conservative therapy with povidone-iodine solution.

Four cases of infected vascular prosthetic graft in the groin successfully treated with povidone-iodine solution using a conservative approach are described here. In all patients the same technique was used. After complete debridement, the prosthetic graft in the groin was completely exposed. The wound was cleansed with hydrogen peroxide and then dressed with gauze soaked in 1:10 sterile water-diluted povidone-iodine solution. The dressings were changed twice a day. The patients were supplemented by systemic therapy of an appropriate antibiotic. All patients were observed in the intensive care unit. In all patients this treatment method led to control of infection and healing of the wound. Thus, it was not necessary to remove the prosthetic graft and patients were spared a major surgical intervention. At follow-up, the prosthetic grafts remain patent without any signs of recurrence of infection.

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in an Italian intensive care unit: clinical and therapeutical remarks.

In this study we evaluated the prevalence of Enterobacteriaceae and the epidemiology of ESBL+ microorganisms in an ICU of our Institution over a 5-year period and analyzed the clinical features and outcomes of the infections caused by these microorganisms. The most frequent ESBL+ isolate was Proteus mirabilis (69 isolates, 58%); a high rate of positive results in the double-disk synergy test (DDS) was also recognized for Klebsiella pneumoniae (52 isolates, 51%), whereas this phenomenon was observed less frequently in other species. In 312 cases the isolated microorganism was considered to be the cause of infection; we documented 103 wound infections, 89 UTIs, 62 LRTIs, 30 primary bacteremias, 27 infections of indwelling catheters and 1 CNS infection. The overall mortality rate due to ESBL+ strains was 1%, compared with 10.6% rate caused by ESBL-negative Enterobacteriaceae. This could be explained because ESBL+ strains caused mostly localized infections (wound infections and UTIs), whereas systemic or severe infections were sustained by ESBL-negative strains, and therapy with carbapenems was started promptly after ESBL+ isolation (always within 24h after strain isolation).

Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.

Although recommended durations of antimicrobial therapy for ventilator-associated pneumonia (VAP) range from 7 to 21 d, these are not based on prospective studies and little is known about the resolution of symptoms after start of antibiotics. Resolution of these symptoms was investigated in 27 patients. VAP was diagnosed on clinical, radiographic, and microbiological criteria, including quantitative cultures of bronchoalveolar lavage. All patients received appropriate antibiotic therapy. Highest temperatures, leukocyte counts, Pa(O(2))/FI(O(2)) ratios, and semiquantitative cultures of endotracheal aspirates were recorded from start of therapy until Day 14. Resolution was defined as the first day that these parameters fulfilled the following definition: temperature < or = 38 degrees C, leukocytes < or = 10 x 10(9)/L, Pa(O(2))/FI(O(2)) ratio > or = 25 kPa, and no or +1 of bacterial growth of etiologic pathogens in cultures of endotracheal aspirate. VAP was caused by Enterobacteriaceae (n = 14), P. aeruginosa (n = 7), S. aureus (n = 6), H. influenzae (n = 3), and S. pneumoniae (n = 1). H. influenzae and S. pneumoniae were eradicated from tracheal aspirates, whereas Enterobacteriaceae, S. aureus, and P. aeruginosa persisted, despite in vitro susceptibility to antibiotics administered. Significant improvements were observed for all clinical parameters, most apparently within the first 6 d after start of antibiotics. Newly acquired colonization, especially with P. aeruginosa and Enterobacteriaceae, occurred in the second week of therapy. Six patients developed a recurrent episode of VAP, four of them with P. aeruginosa. Clinical responses to therapy for VAP occur within the first 6 d of therapy, endotracheal colonization with Gram-negative bacteria persists despite susceptibility to therapy, and acquired colonization usually occurs in the second week of therapy and frequently precedes a recurrent episode.

Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients.

Prompt empiric antibiotic therapy is of critical importance for patients with neutropenic fever. However, a major concern with important clinical consequences is the emergence of bacterial resistance to antibiotics. After using ceftazidime with a glycopeptide as initial empiric therapy for neutropenic fever, we were confronted with a 75% reduced susceptibility rate to ceftazidime of inducible Enterobacteriaceae collected in 1994. The initial empiric therapy was therefore replaced in May 1995 by a combination of cefepime with amikacin, with addition of a glycopeptide after 48 h if necessary. After this change, we observed a significant decrease in reduced susceptibility of inducible Enterobacteriaceae, not only to ceftazidime, but also to amikacin, cotrimoxazole and ciprofloxacin. There was also a decrease in reduced susceptibility of non-inducible Enterobacteriaceae, such as Klebsiella spp, to ceftazidime. The reduction of resistance may be related at least in part to the combined use of cefepime together with an aminoglycoside. This study shows that it is possible to reverse bacterial resistance by modifying the antibiotic regimen used.

Minocycline and ethylenediaminetetraacetate for the prevention of recurrent vascular catheter infections.

Three patients with recurrent vascular catheter-related bacteremia were successfully treated by allowing a solution of minocycline and ethylenediaminetetraacetate (EDTA) to dwell in the lumen of the indwelling catheter or by coating polyurethane catheters with minocycline/EDTA and flushing the lumen daily with the same solution. In vitro and in vivo experiments showed that minocycline/EDTA may have broad-spectrum antimicrobial activity, may have optimal anticoagulant activity, and may be highly efficacious in preventing catheter colonization.

[Analysis of cases with liver abscess following transcatheter arterial chemoembolization (TAE) for malignant hepatic tumors].

A total of 182 TAE procedures were carried out in 98 patients with malignant hepatic tumors during the last five years. Liver abscess following TAE occurred in 3 cases (3.1%) and in 3 procedures (1.7%). All cases were discharged after successful percutaneous transhepatic abscess drainage. One case had hepatocellular carcinoma. Another case had undergone total gastrectomy and esophagojejunostomy with Roux-Y reconstruction for gastric leiomyosarcoma. The other had undergone right hemicolectomy and pancreatoduodenectomy for colon cancers and carcinoma of the ampulla of Vater. Communication between the abscess and the intrahepatic bile duct was recognized in 2 cases. In the abscess culture, E. coli and Citrobacter freundii were detected. These results suggest the major factor leading to abscess formation is biliary infection. Therefore, a previous bilio-enteric anastomosis should be regarded as a risk factor for liver abscess following TAE.