Menthol Pretreatment Alleviates Campylobacter jejuni-Induced Enterocolitis in Human Gut Microbiota-Associated IL-10-/- Mice.

Human Campylobacter jejuni infections are of worldwide importance and represent the most commonly reported bacterial enteritis cases in middle- and high-income countries. Since antibiotics are usually not indicated and the severity of campylobacteriosis is directly linked to the risk of developing post-infectious complications, non-toxic antibiotic-independent treatment approaches are highly desirable. Given its health-promoting properties, including anti-microbial and anti-inflammatory activities, we tested the disease-alleviating effects of oral menthol in murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10-/- mice were orally subjected to synthetic menthol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas menthol pretreatment did not improve campylobacteriosis symptoms, it resulted in reduced colonic C. jejuni numbers and alleviated both macroscopic and microscopic aspects of C. jejuni infection in pretreated mice vs. controls. Menthol pretreatment dampened the recruitment of macrophages, monocytes, and T lymphocytes to colonic sites of infection, which was accompanied by mitigated intestinal nitric oxide secretion. Furthermore, menthol pretreatment had only marginal effects on the human fecal gut microbiota composition during the C. jejuni infection. In conclusion, the results of this preclinical placebo-controlled intervention study provide evidence that menthol application constitutes a promising way to tackle acute campylobacteriosis, thereby reducing the risk for post-infectious complications.

Postmortem examination of equids >1-year-old with enterotyphlocolitis in Ontario: a retrospective descriptive study.

Equine enterotyphlocolitis is an inflammatory process of the intestinal tract of horses that is associated with multiple etiologic agents and risk factors. Most clinical cases do not have an etiologic diagnosis. We describe here the pathogens detected and the histologic lesions found in horses with enterotyphlocolitis in Ontario that were submitted for postmortem examination, 2007-2019. We reviewed the medical records of 208 horses that fulfilled inclusion criteria. Cultures were positive in 67 of 208 (32%) equids for Clostridium perfringens, in 16 of 208 (8%) for Clostridioides difficile, and in 14 of 208 (7%) for Salmonella spp.; 6 of 208 (3%) were positive for Neorickettsia risticii by PCR assay. One horse was positive in a Rhodococcus equi PCR assay. All horses tested by PCR assay for equine coronavirus and Lawsonia intracellularis were negative. The histologic lesions were characterized as follows: 6 of 208 (3%) enteritis, 5 of 208 (2%) typhlitis, 104 of 208 (50%) colitis, 37 of 208 (18%) enterocolitis, 45 of 208 (22%) typhlocolitis, and 11 of 208 (5%) enterotyphlocolitis. We strongly recommend standardized testing of diarrheic horses during and/or after postmortem examination, as well as standardized reporting of histologic lesions in enterotyphlocolitis cases.

Gut Microbiota Mediates Lactobacillus rhamnosus GG Alleviation of Deoxynivalenol-Induced Anorexia.

Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; Lactobacillus rhamnosus GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of Lactobacillus and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.

Methicillin-resistant Staphylococcus aureus enterocolitis in a 16-month-old boy: a case report.

BACKGROUND: Methicillin-resistant Staphylococcus aureus enterocolitis is a rare disease that typically affects immunocompromised adults. Most cases of pediatric enterocolitis are caused by Gram-negative bacteria, Gram-positive Clostridiodes difficile, or viruses. This is the first published case report of a toddler with methicillin-resistant Staphylococcus aureus enterocolitis. CASE PRESENTATION: A 16-month-old non-Hispanic White boy with no past medical or psychosocial history initially presented to the emergency room with abdominal pain and emesis. Past family history was pertinent only for his father having a history of constipation. He was diagnosed with intussusception and underwent successful contrast reduction on hospital day 0. The following day, the patient had recurrent symptoms and a repeat contrast enema showed no evidence of recurrent intussusception. A computed tomography scan was obtained, which was concerning for possible recurrence with compromised bowel. He was taken to the operating room for operative reduction and underwent an ileocecetomy with primary handsewn end-to-end anastomosis. His postoperative course was complicated by an anastomotic leak on hospital day 6 necessitating reoperation and creation of an end ileostomy with mucous fistula. He received intravenous metronidazole, ceftriaxone, and ceftazidime antibiotics during his hospital course. On postoperative day 12, the patient developed a sudden increase in ileostomy output, and stool cultures were obtained. His symptoms persisted despite diet modifications, stopping antibiotics, and initiating loperamide. Three days later, stool cultures resulted negative for Escherichia coli, Salmonella, Shigella, Campylobacter species, and Clostridiodes difficile but were positive for methicillin-resistant Staphylococcus aureus. The patient was started on a 10-day course of oral vancomycin and discharged home in good condition 4 days later. After 12 weeks, the patient underwent reversal of the ostomy and is doing well at the 1 month postoperative follow-up, now 5 months from his initial surgery. CONCLUSIONS: To our knowledge, this is the first published report of a toddler being diagnosed with methicillin-resistant Staphylococcus aureus enterocolitis. Because methicillin-resistant Staphylococcus aureus enterocolitis is rare and has overlapping symptoms with more common gastrointestinal pathologies, it is often misdiagnosed. When a patient presents with diarrhea or high ostomy output along with fecal cultures negative for Clostridiodes difficile and other common pathogenic agents, methicillin-resistant Staphylococcus aureus should be considered.

Bacterial and viral enterocolitis in horses: a review.

Enteritis, colitis, and enterocolitis are considered some of the most common causes of disease and death in horses. Determining the etiology of these conditions is challenging, among other reasons because different causes produce similar clinical signs and lesions, and also because some agents of colitis can be present in the intestine of normal animals. We review here the main bacterial and viral causes of enterocolitis of horses, including Salmonella spp., Clostridium perfringens type A NetF-positive, C. perfringens type C, Clostridioides difficile, Clostridium piliforme, Paeniclostridium sordellii, other clostridia, Rhodococcus equi, Neorickettsia risticii, Lawsonia intracellularis, equine rotavirus, and equine coronavirus. Diarrhea and colic are the hallmark clinical signs of colitis and enterocolitis, and the majority of these conditions are characterized by necrotizing changes in the mucosa of the small intestine, colon, cecum, or in a combination of these organs. The presumptive diagnosis is based on clinical, gross, and microscopic findings, and confirmed by detection of some of the agents and/or their toxins in the intestinal content or feces.

Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice.

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10-/- mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.

Secretion of c-di-AMP by Listeria monocytogenes Leads to a STING-Dependent Antibacterial Response during Enterocolitis.

Stimulator of interferon genes (STING) acts as a cytoplasmic signaling hub of innate immunity that is activated by host-derived or bacterially derived cyclic dinucleotides. Listeria monocytogenes is a foodborne, facultative intracellular pathogen that secretes c-di-AMP and activates STING, yet the in vivo role of the STING pathway during bacterial pathogenesis remains unclear. In this study, we found that STING-deficient mice had increased weight loss and roughly 10-fold-increased systemic bacterial burden during L. monocytogenes-induced enterocolitis. Infection with a L. monocytogenes mutant impaired in c-di-AMP secretion failed to elicit a protective response, whereas a mutant with increased c-di-AMP secretion triggered enhanced protection. Type I interferon (IFN) is a major output of STING signaling; however, disrupting IFN signaling during L. monocytogenes-induced enterocolitis did not recapitulate STING deficiency. In the absence of STING, the intestinal immune response was associated with a reduced influx of inflammatory monocytes. These studies suggest that in barrier sites such as the intestinal tract, where pathogen-associated molecular patterns are abundant, cytosolic surveillance systems such as STING are well positioned to detect pathogenic bacteria.

Predictive Factors for the First Recurrence of Clostridioides difficile Infection in the Elderly from Western Romania.

Background and objectives: At present, Romania and parts of the European Union are facing an increasingly challenging public health problem consisting of nosocomial Clostridioides difficile infection (CDI), mostly in the elderly. Relapse cases have become more frequent, which present higher morbidity and mortality rates than the initial CDI infection. The aim of this study is to determine the predictive factors for recurrence, with the purpose of reducing the exposure of patients diagnosed with CDI, as well as aiming to initiate early treatment. Materials and Methods: In this retrospective descriptive study, we analyze a database from the First Department of Infectious Diseases at the Dr. Victor Babes Clinical Hospital for Infectious Diseases and Pulmonology in Timisoara, looking for patient history of CDI recurrences. We analyzed CDI recurrence in patients aged ≥65 years from 1 January 2016 to 31 December 2019, identifying 77 cases of CDI recurrence. The determination of predictive factors for recurrence involved the formation of a randomized control group, consisting of 74 patients aged ≥65 years who were diagnosed with C. difficile enterocolitis, but did not suffer a recurrence and survived ≥2 weeks after symptom onset. Results: Immunocompromised status, pre-existing gastrointestinal disease, and fever on initial hospitalization for CDI were all found to be significant independent positive predictive factors for the condition recurring in elderly Romanian patients. Conclusions: As the geriatric population in Romania grows, the national health system becomes increasingly overburdened, both from a financial standpoint and a human resources perspective. The analysis of factors predictive for CDI recurrence is, thus, of the utmost importance, particularly for the early identification of patients most at risk of CDI recurrence. Our findings could help physicians to identify recurrence early, consequently benefitting patients by a rapid intervention with a potential decrease in the associated complications and mortality.

Reactive Arthritis Provoked by Campylobacter jejuni Enterocolitis Mimicking Prosthetic Joint Infection: A Case Report.

CASE: A 59-year-old man with previously well-functioning partial knee replacement was admitted with a warm, swollen, and painful knee. The clinical presentation was consistent with prosthetic joint infection (PJI), but the synovial fluid analysis was negative for microbial growth. Further discussion revealed earlier Campylobacter jejuni enterocolitis that subsequently provoked reactive arthritis (ReA) mimicking PJI. The patient was treated with oral naproxen and intra-articular injection of triamcinolone and recovered completely without antibiotics or surgery. After 29 months, the knee is functioning normally. CONCLUSION: ReA is rare but should be included in the differential diagnosis of PJI.

Effects of Colonization of Gnotobiotic Swiss Webster Mice with Helicobacter bilis.

Helicobacter bilis (Hb) causes hepatitis in some strains of inbred mice. The current study confirmed that Hb directly causes portal hepatitis in outbred gnotobiotic Swiss Webster (SW) mice, as we previously reported for conventional SW mice. Hbmonoassociated SW mice also developed mild enterocolitis, expanded gut-associated lymphoid tissue (GALT), and tertiary lymphoid tissue in the lower bowel. At 1 and 10 mo after infection, Hb-induced GALT hyperplasia exhibited well-organized, ectopic germinal centers with increased mononuclear cell apoptosis, MHC class II antigen presentation, and pronounced endothelial venule formation, consistent with features of tertiary lymphoid tissue. In the lower bowel, Hb induced mainly B220+ cells as well as CD4+ IL17+, CD4+ IFNγ+, and CD4+ FoxP3+ regulatory T cells and significantly increased IL10 mRNA expression. This gnotobiotic model confirmed that Hb causes portal hepatitis in outbred SW mice but stimulated GALT with an antiinflammatory bias. Because Hb had both anti- and proinflammatory effects on GALT, it should be considered a 'pathosymbiont provocateur' and merits further evaluation in mouse models of human disease.

Chronic high-level multidrug-resistant Campylobacter coli enterocolitis in an agammaglobulinemia patient: Oral gentamicin efficacy.

BACKGROUND: Campylobacter is the most common cause of infectious diarrhea in agammaglobulinemia patients. These infections can be severe, prolonged, and recurrent in such patients. PATIENT AND METHODS: We report a 29-year-old male patient with X-linked agammaglobulinemia with Campylobacter coli enterocolitis that persisted for nine months despite multiple 10- to 14-day courses of oral ciprofloxacin and azithromycin. RESULTS: The isolate was highly resistant to ciprofloxacin, erythromycin, tetracycline, and fosfomycin. The patient failed to respond to intravenous ertapenem, 1.0g/day for two weeks, to which the pathogen was susceptible. He was finally cured with oral gentamicin, 80mg four times daily, and stool cultures remained negative during the seven-month follow-up. CONCLUSION: Oral aminoglycoside might be the most appropriate choice for eradication of persistent Campylobacter in the intestinal tract for macrolide- and fluoroquinolone-resistant isolate in agammaglobulinemia patients with chronic diarrhea or relapsing systemic infections.

Clinical Characteristics of Campylobacter Enterocolitis in Korean Adults: A Retrospective Study at a Single Center.

Background/Aims: Although the diarrheal disease caused by Campylobacter bacteria has been continuously increasing in Korea, there has been limited study on the clinical aspects of Campylobacter enteritis in adults in Korea. The purpose of this study was to analyze the clinical features and characteristics of adult patients with Campylobacter enteritis. Methods: This retrospective study included patients diagnosed with Campylobacter enterocolitis at Nowon Eulji University Hopsital between January 2016 and December 2017. Campylobacter enterocolitis was diagnosed through polymerase chain reaction of stools from patients with acute diarrhea. Results: Among 630 hospitalized patients with acute diarrhea, Campylobacter enterocolitis was diagnosed in 88 patients (14.0%). The mean age was 37.9±19.1 years. Campylobacter enterocolitis was most prevalent in the summer (52 patients, 59.1%). Patients exhibited more than 10 times of diarrhea in 36 (40.9%), high fever above 39°C in 19 (21.59%), and abdominal pain above 5 points on the numeric rating scale in 23 (26.14%) cases. In abdominal CT scan, pancolitis was found in 58 patients (65.9%). Small intestine was involved in 37 patients (42.4%). Mean CRP was 10.14 mg/dL (range 0.72-32.27 mg/dL). The duration of diarrhea after antibiotics treatment was 2.34±1.51 days in the ciprofloxacin treatment group and 2.26±1.71 days in the 3rd cephalosporin treatment group. Conclusions: Campylobacter enterocolitis was common during summer. Commonly healthy young adults were hospitalized due to severe symptoms of Campylobacter enterocolitis. Whole colon and small bowel were frequently involved. Most patients were treated with antibiotics, and the efficacy of 3rd cephalosporin treatment was not inferior to that of ciprofloxacin treatment.

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice.

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. The health-beneficial, particularly anti-inflammatory effects of vitamin C (ascorbate) are well known. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10-/- mice developing acute campylobacteriosis similar to humans. Starting 4 days prior peroral C. jejuni-infection, mice received synthetic ascorbate via the drinking water until the end of the experiment. At day 6 post-infection, ascorbate-treated mice harbored slightly lower colonic pathogen loads and suffered from less severe C. jejuni-induced enterocolitis as compared to placebo control animals. Ascorbate treatment did not only alleviate macroscopic sequelae of infection, but also dampened apoptotic and inflammatory immune cell responses in the intestines that were accompanied by less pronounced pro-inflammatory cytokine secretion. Remarkably, the anti-inflammatory effects of ascorbate pretreatment in C. jejuni-infected mice were not restricted to the intestinal tract but could also be observed in extra-intestinal compartments including liver, kidneys and lungs. In conclusion, due to the potent anti-inflammatory effects observed in the clinical murine C. jejuni-infection model, ascorbate constitutes a promising novel option for prophylaxis and treatment of acute campylobacteriosis.

Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis.

The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.

Paeniclostridium (Clostridium) sordellii-associated enterocolitis in 7 horses.

Enteric disease in horses may be caused by a variety of microorganisms, including several clostridial species. Paeniclostridium sordellii (previously Clostridium sordellii) has been frequently associated with gas gangrene in humans and several animal species, including horses. However, its role in enteric diseases of animals has not been fully determined. We describe herein 7 cases of enteric disease in horses associated with P. sordellii infection. Grossly, the small and/or large intestines were necrotic, hemorrhagic, and edematous. Microscopically, there was severe mucosal necrosis and hemorrhage of the small and/or large intestine of all horses. P. sordellii was isolated and/or demonstrated by immunohistochemistry and/or PCR in the intestine of all horses. All other known causes of enteric disease in horses were ruled out in these 7 cases. P. sordellii should be considered among the differential diagnoses in cases of enteric disease in horses.

Infection in cirrhosis: A prospective study.

INTRODUCTION AND OBJECTIVES: Multidrug-resistant (MDR) infections in cirrhosis are associated with poor outcomes. We attempted a prospective study on infections in patients with cirrhosis evaluating microbiology of these infections and how outcomes depended on factors like bacterial resistance, appropriate antibiotics, stage of liver disease and whether outcomes were significantly different from patients who did not have infections. MATERIALS AND METHODS: This was a prospective evaluation involving one hundred and fifty nine patients with cirrhosis who were admitted at Peerless Hospitex Hospital and Research Center, Kolkata, West Bengal, India, during a 24 month period. One hundred and nineteen of these patients either had an infection at the time of admission or developed infection during hospitalization. Forty patients did not have an infection at admission and did not acquire infection while admitted. Data was collected about demographics, etiology of cirrhosis, liver and renal function and microbiology. RESULTS: Infections were community acquired in 27.7% of patients, healthcare associated in 52.9% and nosocomial in 19.3%. Gram negative bacilli (Escherichia coli 47.4% Klebsiella pneumoniae 23%) were common. 84.9% of enterobacteriaceae produced ESBL, AmpC or Carbapenemases. Spontaneous bacteria peritonitis (SBP) and urinary tract infection (UTI) were the most common sites of infection. In hospital mortality was 21.9%. Non-survivors had higher MELD (26 vs 19, p<0.001) and CTP scores (11.7 vs 10.3, p<0.001). The control group had lower MELD (16.65 vs. 20.8, p<0.001) and CTP scores (9.25 vs 10.59, p<0.001). CONCLUSIONS: MDR infections are common in patients with cirrhosis and have serious implications for treatment and outcomes.

Vitamin D in Acute Campylobacteriosis-Results From an Intervention Study Applying a Clinical Campylobacter jejuni Induced Enterocolitis Model.

Human Campylobacter infections are progressively rising and of high socioeconomic impact. In the present preclinical intervention study we investigated anti-pathogenic, immuno-modulatory, and intestinal epithelial barrier preserving properties of vitamin D applying an acute campylobacteriosis model. Therefore, secondary abiotic IL-10-/- mice were perorally treated with synthetic 25-OH-cholecalciferol starting 4 days before peroral Campylobacter jejuni infection. Whereas, 25-OH-cholecalciferol application did not affect gastrointestinal pathogen loads, 25-OH-cholecalciferol treated mice suffered less frequently from diarrhea in the midst of infection as compared to placebo control mice. Moreover, 25-OH-cholecalciferol application dampened C. jejuni induced apoptotic cell responses in colonic epithelia and promoted cell-regenerative measures. At day 6 post-infection, 25-OH-cholecalciferol treated mice displayed lower numbers of colonic innate and adaptive immune cell populations as compared to placebo controls that were accompanied by lower intestinal concentrations of pro-inflammatory mediators including IL-6, MCP1, and IFN-γ. Remarkably, as compared to placebo application synthetic 25-OH-cholecalciferol treatment of C. jejuni infected mice resulted in lower cumulative translocation rates of viable pathogens from the inflamed intestines to extra-intestinal including systemic compartments such as the kidneys and spleen, respectively, which was accompanied by less compromised colonic epithelial barrier function in the 25-OH-cholecalciferol as compared to the placebo cohort. In conclusion, our preclinical intervention study provides evidence that peroral synthetic 25-OH-cholecalciferol application exerts inflammation-dampening effects during acute campylobacteriosis.

MODERN ETIOLOGICAL STRUCTURE OF ACUTE GASTROENTEROCOLITIS IN THE SOUTHERN UKRAINE.

The etiological structure of the acute diarrhoeal infections among the population of the Odessa region during 2015-2017 was analyzed. Based on the registered cases, an assessment of the frequency of hospitalization of sick persons from different age groups was undertaken. The most frequent pathogens from 18 detected bacterial causative agents were St. aureus, Kl. pneumoniae, Ps. aeruginosa, E. coli, Pr. vulgaris, Ent.cloacae. During 2016-2017 the mixed infection was detected in 54 fecal samples. Bacterial-virus associations were detected in 20 samples and were presented in St. aureus, Kl. pneumoniae, Ps. Aeruginosa and Rotavirus. During the summer period of 2016, the detection rate of rota-, noro-, adenovirus antigens in the examined fecal samples of adult patients was 13.60%. According to the results of genotyping of the circulating rotaviruses strains in 2016, strains G1P[8] (46.70%) and G3P[8] (26.70%) are most commonly detected.

Emergence of phylogenetically diverse and fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal Salmonella disease in Ghana.

BACKGROUND: Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages. METHODOLOGY/PRINCIPAL FINDINGS: Twenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region. CONCLUSIONS/SIGNIFICANCE: Extensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures within the region's burgeoning poultry industry are required to protect a human population at high risk of iNTS disease.

Reactive arthritis secondary to Hafnia alvei enterocolitis.

Diagnosis of postenteritic reactive arthritis (ReA) is a challenge and might have a broad range of differential diagnoses. A 50-year-old man was referred to our attention because of persistent inflammatory low back pain and asymmetric oligoarthritis. The clinical history was positive for diarrhoea in the previous 3 months. Inflammatory bowel disease, Whipple and celiac diseases were carefully excluded. In addition, serology, stool cultures, biopsies from the upper gastrointestinal tract yielded negative results for infections. A presumptive diagnosis of ReA was done and a non-steroidal anti-inflammatory drug trial prescribed. Persistence of symptoms prompted us for a second look of the colon. Biopsy collected from the terminal ileum were cultured and surprisingly colonies of Hafnia alvei, a rod-shaped Enterobacteriaceae, were detected. Treatment with ciprofloxacin leads to fast symptoms resolution. Although enterocolitis from H. alvei has been rarely reported, the culture of intestinal specimens might be recommended in the work-up of patients with suspected postenteritic ReA.