Antibiotic plus probiotic combination may kill off superbugs

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Every year, over 2 million people in the United States develop infections that are resistant to treatment, and approximately 23,000 people die as a result.

These statistics have prompted the Centers for Disease Control and Prevention (CDC) to deem drug resistance “one of the biggest public health challenges of our time.”

Therefore, researchers are hard at work trying to develop ingenious ways of tackling so-called superbugs — bacteria that have become immune to antibiotic treatment.

Lately, researchers have added probiotics to their arsenal against superbugs. Probiotics are beneficial bacteria found in foods, such as yogurt, kefir, pickles, or miso soup.

Only a month ago, for example, a study suggested that simply consuming probiotics on a regular basis could reduce the need for antibiotics, thus helping to curb the drug resistance crisis. Continue reading Antibiotic plus probiotic combination may kill off superbugs

For Cystic Fibrosis Lung Infections, How Well Antibiotics Work May be Affected by pH, Oxygen

By Heather Buschman, PhD

People living with cystic fibrosis (CF) spend their entire lives battling chronic lung infections that are notoriously resistant to antibiotic therapy. Yet a one-size-fits all approach to wiping out the offending bacterium may not be the best approach for all patients with the disease, according to a new study by researchers at University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. Continue reading For Cystic Fibrosis Lung Infections, How Well Antibiotics Work May be Affected by pH, Oxygen

Newfound airway cells may breathe life into tackling cystic fibrosis

By Aimee Cunningham

Meet the ionocyte. This newly discovered cell may be the star of future cystic fibrosis therapies. Researchers have found that the gene tied to the disease is very active in the cells, which line the air passages of the lungs.

While the cells are rare, making up only 1 to 2 percent of cells that line the airways, they seem to play an outsized role in keeping lungs clear. The identification of the ionocyte “provides key information for targeting treatments,” says medical geneticist Garry Cutting of Johns Hopkins School of Medicine in Baltimore, who was not involved in the research. Two teams, working independently, each describe the new cell online August 1 in Nature.

The ionocyte shares its name with similar cells found in fish gills and frog skin. This type of cell regulates fluid movement at surfaces — skin, gills, airways — where air and water meet. In people, special proteins that tunnel across cell membranes lining the airways allow chloride ions (half of what makes salt) to move into the airway. This causes water to move into the airway through a different channel to moisten mucus along the lining, which helps it remove bacteria and inhaled particles from the body.

The tunnel protein that allows chloride ions through is made by a gene called CFTR. In cystic fibrosis patients, that gene is flawed. Airways can’t regulate water movement properly and get clogged with thick mucus that traps bacteria and leads to persistent infections and lung damage. The genetic disease affects at least 70,000 people worldwide, according to the Cystic Fibrosis Foundation in Bethesda, Md.

Researchers had suspected CFTR was most active in ciliated cells — cells with brushlike projections that work along with the mucus in airways to move invaders out. But the new work found very little gene activity in those cells, compared with the ionocytes.

In experiments with laboratory samples of mouse cells from the airway lining, cell biologist Jayaraj Rajagopal of Massachusetts General Hospital in Boston and his colleagues found that the gene was very active in ionocytes: out of all the instructions for building the tunnels detected in the cells, 54 percent came from ionocytes. Aron Jaffe, a respiratory disease researcher at Novartis Institutes for Biomedical Research in Cambridge, Mass., and his colleagues reported that, in laboratory samples of human airways cells, ionocytes were the source of 60 percent of the activity of the tunnels.

The discovery of the new cells raises a lot of questions. Jaffe wonders where ionocytes are positioned in the lining of the airways, and how that placement supports the coordination of water movement and mucus secretion by other cells. “You can imagine the distribution [of ionocytes] is really important,” he says.

A question Rajagopal has: “How does a rare cell type do all of this work?” In fish and frogs, ionocytes are loaded with mitochondria, the so-called cellular energy factories, he notes. Maybe that will be true for human ionocytes, too, giving them lots of energy to do the lion’s share of regulating the movement of water.

Both researchers say the ionocyte’s discovery should lead to a better understanding of cystic fibrosis. “It will let us think about creative new ways to approach the disease,” Rajagopal says.

Original article here.

AIT’s Inhaled Nitric Oxide Shows Potential in Fighting Bacterial Infection Prevalent in CF Patients

By Alice Melao

Inhaled nitric oxide (NO) was shown to be an effective antibacterial agent against Mycobacterium abscessus infection in preclinical studies, as well as in a pilot clinical trial, according to AIT Therapeutics.

The company discussed the latest data on its NO product in two poster presentations during the 3rd Annual World Bronchiectasis Conference held recently at Georgetown University in Washington, D.C.

NO is a small molecule that is an important mediator of immune defense mechanisms against infections. The compound has been shown to have broad-spectrum antibacterial activity against several strains of bacteria that often infect patients with underlying lung diseases, including cystic fibrosis (CF).

Continue reading AIT’s Inhaled Nitric Oxide Shows Potential in Fighting Bacterial Infection Prevalent in CF Patients

Phage-Coated Microparticles Treats Lung Conditions like CF

By SterlingAdmin

The methods available to treat bacterial infections are many. But among those with any real and lasting effectiveness, their usage is limited. Antibiotics were once the Holy Grail of medicine to deal with devastating diseases that wiped out entire populations. With them, these suffering conditions were almost entirely wiped out and the populace began to learn how to live without the fear of most children dying at a young age. But, as is well known, the age of antibiotic cure-alls is ending and the time of antibiotic resistance is beginning to reach its peak. So, medical researchers are hard at work on all the other opportunities for dealing with bacteria that don’t require these specific groups of compounds.

The Medicine of Viruses

Phage therapy is one such alternative that has begun to see more extensive use over the past two decades.Bacteriophages are lifeforms that have crafted over evolutionary time a niche focused on using bacteria as their reproductive hosts, killing said host in the process. And since they are living beings as well, they actively engage in the selective pressures of finding ways around resistance against them, rather than being a static attack on bacteria like antibiotics are. This means that even the most feared multi-drug resistant bacterial strains have little to no protection against phages.

The primary downside to this treatment is that phages are highly specialized, having formed themselves to only target a particular host species. Therefore, to deal with certain bacteria, one also has to find and be able to cultivate a certain type of phage. Once that step is accomplished, however, it has been found that they can be altered fairly easily to give them variable methods of attack, so as to minimize any potential side effects on the human body while they are killing the bacteria. They can even be set up to synergistically interact with the human immune system to work together to wipe out the bacterial invasion.

With the right phage strain, the largest remaining issue is how to get them into the human body and to the right type of location and system that the bacteria are also attacking from. A large proportion of phage research has gone into finding new ways to do this very thing, as it is one of the inefficient areas of the therapy and, if improved, can drastically heighten the success rates of the treatment and the types of bacterial diseases that can be combated.

It is difficult and time consuming to produce modified phage, with many of them dying in this fabrication. For bacterial diseases of the lungs, such as the kinds that like to colonize those suffering from cystic fibrosis, there is currently no true delivery method of getting phage into the deep lung tissues. And, of course, getting any single treatment approved requires showing success in some sort of animal model, even though the phages may not translate well or at all to anything other than humans. This is one of the major problems this author has with the current approval setup by governments for medical trials.

Microparticles For A Micro World

Scientists at the Georgia Institute of Technology have been seeking a new method for just such a delivery system. Dry powder formulations has seen some positive benefits for effectiveness in recent years, but there lingers the issue of how to use such a powder to delivery living phages to the right spot. To do so would require a very carefully made powder indeed.

The engineering techniques they brought into play were used to make phage-loaded microparticles (phage-MPs), hollow molecular structures formed using water-oil-water emulsion to keep them stable. The bacteria being combated was the opportunistic pathogen Pseudomonas aeruginosa and several strains of phage against it were chosen for the experiment.

The microparticles were housed in a phage-containing solution, allowing them to be filled with the phage after incubation. Though they were filled in a different way than the usual method of them being inside the MPs. Instead, they cover the exterior in this method after the MPs are made, meaning no phage are lost due to solvent usage during MP fabrication from the prior ways other studies used. Three to five phages were contained on the MPs in order to reduce the likelihood of any possible bacterial resistance.

This delivery mechanism also reduces endotoxin production by the phage, thereby minimizing side impacts of their use, with the reduction bringing them down to 0.078 endotoxin units (EUs), far below the accepted FDA limit of 20 EU in treatments. The technique was first tested on petri dishes containing the bacteria to which the phage-MPs were applied. The P. aeruginosa were modified to express green fluorescent protein (GFP) to identify their living location on the plates.

A Complete Victory

After 16 hours of co-incubation, large patches of non-fluorescence showed where the phage had successfully killed off the bacteria, while the control group MPs without a phage coating had no deaths. These zones were also far larger than the applied MP area, showing that the phage were able to spread and extend to other bacteria in the dishes. The same test was done using synthetic sputum to mimic the environment of an animal lung and the bacteria and phages were applied at the same time. There was no visible growth of bacteria after application, showing that the phages were able to both control and wipe them out. A further test showed the phage are also able to get past the protective biofilms of the bacteria that they make under environmental emergencies.

The dry powder formulations were also seen to have a large burst of phages initially, with slow release for two weeks after, the perfect way to allow consistent application and treatment against the bacteria. The final experiment involved using mice infected with the bacteria. A control test using just phage-MPs showed no negative effects on the mice or their lungs after application. Fluorescent phage-MPs also showed that they were only localized to the lungs and nowhere else in the body, as desired. The control using free form phages without microparticles revealed how the dry powder still didn’t allow them to be properly applied, with no major phage levels detected in those mouse lungs, proving that the MPs as a transport vector were required.

When tested on mice infected with P. aeruginosa, the bacterial count dropped by an entire order of magnitude and 100% of the mice survived their pneumonia, while the untreated control group only had 13% survive. For mice with a cystic fibrosis genetic mutation, the same test saw their bacterial counts drop by three orders of magnitude, approaching the limit of what could be detected. The phage-MPs also saw the same effectiveness against multiple strains of the bacteria, meaning that even genetic variance in a population wasn’t enough to defend against them.

A last point of importance is that when testing against a mouse group exposed to phage-MPs long before being infected and later treated, there was no reduction in effect and no antibodies against the phages seemed to develop. So there is likely no performance loss to the treatment if used multiple times.

The New Antibiotics

As a conclusion, the researchers were able to engineer specialized biomaterials made of microparticles that, when coated with bacteriophages, were highly effective at reducing bacterial counts for lung-related diseases, including those resulting from the lowered immune system responses of cystic fibrosis. These phage-MPs are stable and can be stored for a fair amount of time with no loss in phage amounts and can be administered through simple inhalation, meaning younger patients can be treated with less complications.

For lung-related diseases, and likely for broader conditions at large in the medical community, this breakthrough might serve as a major way to allow phage therapy to become more common and used in replacement of or as a sought after alternative to antibiotics. The number of lives this should be able to save in the long run is likely incalculable.

Press Article Link

Study Link

Original article Link

Antioxidant-Enriched Multivitamin May Decrease Respiratory Illnesses

MedicalResearch.com Interview with:

Scott D Sagel MD PhD
Professor of Pediatrics
University of Colorado School of Medicine
Aurora, Colorado

MedicalResearch.com: What is the background for this study?

Response: Inflammation is an important feature of cystic fibrosis (CF) lung disease and contributes to lung damage and lung function decline in CF. We need safe and effective anti-inflammatory treatments in CF. Anti-oxidant therapy has been an area of promise, but with mixed results in CF.

This clinical trial, conducted at 15 CF centers affiliated with the cystic fibrosis Foundation Therapeutics Development Network, enrolled 73 patients who were 10 years and older (average age 22 years), with pancreatic insufficiency, which causes malabsorption of antioxidants. Subjects were randomized to either a multivitamin containing multiple antioxidants including carotenoids such as beta(β)-carotene, tocopherols (vitamin E), coenzyme Q10 (CoQ10), and selenium or to a control multivitamin without antioxidant enrichment. The antioxidants used in the study were delivered in a capsule specifically designed for individuals with difficulties absorbing fats and proteins, including those with cystic fibrosis.

MedicalResearch.com: What are the main findings?

Response: Antioxidant supplementation was safe and well-tolerated. Supplemental antioxidants increased antioxidant concentrations in the bloodstream in treated subjects and temporarily reduced inflammation in the blood at four weeks but not 16 weeks. Airway inflammation, as measured in sputum, did not change significantly with antioxidant treatment. Importantly, antioxidant treatment appeared to both prolong the time to the first respiratory illness requiring antibiotics and reduce the frequency of respiratory illnesses they experienced.

MedicalResearch.com: What should readers take away from your report?

Response: Taking a specially formulated antioxidant-enriched multivitamin, containing multiple dietary antioxidants, may decrease respiratory illnesses in people with cystic fibrosis. While more research needs to be done to find a treatment that delivers a sustained anti-inflammatory effect, we believe the prolonged time patients had before their first respiratory illness is clinically meaningful. Also, the cost of a dietary antioxidant-enriched multivitamin is relatively modest compared to other currently available therapies that have been proven to reduce pulmonary exacerbations in cystic fibrosis.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We still don’t know the optimal dosing of these various dietary antioxidants. We also don’t know the added benefit of antioxidant supplementation in the era of CFTR modulator therapy, emerging treatments that get at the basic protein defect in cystic fibrosis.

MedicalResearch.com: Is there anything else you would like to add?

Response: This clinical trial, funded by a grant from the Cystic Fibrosis Foundation, was an investigator-initiated study led by Scott D. Sagel, MD, PhD, a Professor of Pediatrics at Children’s Hospital Colorado and Director of the University of Colorado Cystic Fibrosis Center. It was not an industry initiated or funded trial. Callion Pharma manufactured the antioxidant-enriched and control multivitamins and provided them at no charge for this study.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial
Scott D Sagel , Umer Khan , Raksha Jain , Gavin Graff , Cori L Daines , Jordan M Dunitz , Drucy Borowitz , David M Orenstein , Ibrahim Abdulhamid , Julie Noe , John P Clancy , et al
https://doi.org/10.1164/rccm.201801-0105OC PubMed: 29688760
American Journal of Respiratory and Critical Care Medicine

Published Online: April 24, 2018

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

Original interview article here.