The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

Anaerobic adaptation of Mycobacterium avium subspecies paratuberculosis in vitro: similarities to M. tuberculosis and differential susceptibility to antibiotics.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease in ruminants and is associated with Crohn's disease (CD) in humans, although the latter remains controversial. In this study, we investigated the ability of MAP to adapt to anaerobic growth using the "Wayne" model of non-replicating persistence (NRP) developed for M. tuberculosis. RESULTS: All strains adapted to anaerobiosis over time in a manner similar to that seen with MTB. Susceptibility to 12 antibiotics varied widely between strains under aerobic conditions. Under anaerobic conditions, no drugs caused significant growth inhibition (>0.5 log) except metronidazole, resulting in an average decrease of ~2 logs. CONCLUSIONS: These results demonstrate that MAP is capable of adaptation to NRP similar to that observed for MTB with differential susceptibility to antibiotics under aerobic versus anaerobic conditions. Such findings have significant implications for our understanding of the pathogenesis of MAP in vivo and the treatment of CD should this organism be established as the causative agent.

Treatment of refractory Crohn's disease and pyoderma gangrenosum with a combination regimen of rifaximin, gentamicin and metronidazole.

The etiology of Crohn's disease (CD) remains controversial. It is hypothesized that CD is the result of an abnormal immune response to the gut flora in genetically susceptible hosts. However, an infectious etiology has not been completely ruled out. Antibiotics have been utilized with some success to modify the course of the disease. Here, we report a patient with CD and pyoderma gangrenosum refractory to standard therapy, including biologics, who achieved remission with a combination of rifaximin, gentamicin and metronidazole.

Iron deficiency anemia in patients with inflammatory bowel disease.

Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD) are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%-76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient's quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented.

Guidewire embolization and right ventricular perforation visualized by cardiac CT.

A 60-year-old physician with a history of septic arthritis presented with chest pain. Initial studies including an electrocardiogram, chest x-ray, and transthoracic echocardiogram were non-diagnostic. Cardiac CT demonstrated perforation of the right ventricle from a retained wire stylus. Our case highlights the clinical utility of CT in diagnosing migration of devices through the cardiac chambers, evaluating for associated sequelae, including hemopericardium and other perforated structures, and defining the complete course of the device, thereby facilitating safe extraction.

Continuous high-solids corn liquefaction and fermentation with stripping of ethanol.

Removal of ethanol from the fermentor during fermentation can increase productivity and reduce the costs for dewatering the product and coproduct. One approach is to recycle the fermentor contents through a stripping column, where a non-condensable gas removes ethanol to a condenser. Previous research showed that this approach is feasible. Savings of $0.03 per gallon were predicted at 34% corn dry solids. Greater savings were predicted at higher concentration. Now the feasibility has been demonstrated at over 40% corn dry solids, using a continuous corn liquefaction system. A pilot plant, that continuously fed corn meal at more than one bushel (25 kg) per day, was operated for 60 consecutive days, continuously converting 95% of starch and producing 88% of the maximum theoretical yield of ethanol. A computer simulation was used to analyze the results. The fermentation and stripping systems were not significantly affected when the CO(2) stripping gas was partially replaced by nitrogen or air, potentially lowering costs associated with the gas recycle loop. It was concluded that previous estimates of potential cost savings are still valid.

Absence of mycobacterium avium subsp. paratuberculosis in Crohn's patients.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) has been suspected of involvement in Crohn's disease (CD). We investigated this potential association by testing whole blood from CD patients and healthy controls for the presence of MAP by culture and molecular methods. In addition, each blood sample was analyzed for polymorphisms in the NOD2/CARD15 gene previously associated with CD. METHODS: Four 4-mL K(2)-EDTA tubes of whole blood were drawn from each subject (n = 260, 130 CD patients and 130 healthy controls). Two tubes of blood were cultured for MAP by the following methods: Mycobacterial Growth Indicator Tube, Herrold's Egg Yolk Agar, BACTEC 460, and Hungate. The remaining 2 tubes of blood were tested for MAP DNA and polymorphisms in the NOD2/CARD15 gene by polymerase chain reaction (PCR). RESULTS: One healthy control patient was positive for MAP via PCR; however, no viable MAP was cultured from this individual. All blood cultures were negative for MAP. One CD patient's blood was culture-positive for M. tuberculosis complex. CD patients exhibited a higher rate of polymorphism in the NOD2/CARD15 gene than healthy control patients. CONCLUSIONS: In this study MAP was not recovered from the blood of CD patients or healthy controls. However, CD patients showed higher mutation rates in the NOD2/CARD15 gene, compared with healthy controls, supporting the findings of other investigators. No correlation between these polymorphisms and MAP bacteremia in CD patients could be identified in this study.

Clopidogrel-induced hepatotoxicity and fever.

A 59-year-old woman developed fever and elevated hepatic enzyme levels within days of starting clopidogrel, which had been prescribed in conjunction with a percutaneous coronary intervention. When she discontinued the clopidogrel, her liver enzyme levels returned to baseline and her fever disappeared. These signs and symptoms returned after rechallenge with clopidogrel. Monitoring for fever and elevation of liver enzyme levels in patients taking clopidogrel may be warranted. If a patient has signs of hepatotoxicity with or without fever, discontinuation of clopidogrel should be considered, along with substitution with ticlopidine if clinically warranted.