Insufficient antibiotics available for cystic fibrosis patients: Study

Turns out, the majority of patients with cystic fibrosis may not achieve blood concentrations of antibiotics sufficiently high enough to effectively fight bacteria responsible for pulmonary exacerbations, thus leading to worsening pulmonary function.

Cystic fibrosis, a genetic condition that affects about 70,000 people worldwide, is characterised by a buildup of thick, sticky mucus in patients’ lungs. There, the mucus traps bacteria, causing patients to develop frequent lung infections that progressively damage these vital organs and impair patients’ ability to breathe.

A recent study led by researchers at Children’s National Health System shows that it’s impossible to predict solely from dosing regimens which patients will achieve therapeutically meaningful antibiotic concentrations in their blood. The findings were published online in the Journal of Pediatric Pharmacology and Therapeutics.

These infections, which cause a host of symptoms collectively known as pulmonary exacerbations, are typically treated with a combination of at least two antibiotics with unique mechanisms. One of these drugs is typically a Beta-lactam antibiotic, a member of a family of antibiotics that includes penicillin derivatives, cephalosporins, monobactams and carbapenems.

Although all antibiotics have a minimum concentration threshold necessary to treat infections, Beta-lactam antibiotics are time-dependent in their bactericidal activity. Their concentrations must exceed a minimum inhibitory concentration for a certain period. However, study’s lead author Andrea Hahn explained that blood concentrations of Beta-lactam antibiotics aren’t typically tracked while patients receive them.

Since antibiotic dosing often doesn’t correlate with cystic fibrosis patients’ clinical outcomes, Dr. Hahn and other researchers examined whether patients actually achieved serum antibiotic concentrations that are therapeutically effective.

In addition, all the patients underwent pulmonary function tests at the start of their exacerbations and about once weekly until their antibiotic therapy ended.

Using the data points, the researchers constructed a model to determine which patients had achieved therapeutic concentrations for the bacteria found in their respiratory secretions. They then correlated these findings with the results of patients’ pulmonary function tests. Just 47 per cent of patients had achieved therapeutic concentrations. Those who achieved significantly high antibiotic exposure had more improvement on their pulmonary function tests compared with patients who didn’t.

Paradoxically, they discovered that although each patient received recommended antibiotic doses, some patients had adequately high serum antibiotic concentrations while others did not.

Another way to ensure patients receive therapeutically meaningful levels of antibiotics is to develop new models that incorporate variables such as age, gender, and creatinine clearance–a measure of kidney function that can be a valuable predictor of metabolism–to predict drug pharmacokinetics.

Using findings from this research, Dr. Hahn adds, Children’s National already has implemented an algorithm using different variables to determine antibiotic dosing for patients treated at the hospital.

Original article here.

As Both Patient and Scientist, I’m Putting Nature’s Medicine to the Test

By Ella Balasa

I peered into one of the incubators that stored my petri dishes for 24 hours, anxious to see whether I would discover discoloration and unevenness on the surface, which would have indicated that my experiment produced favorable results. I wanted to see a visual representation of whether manuka honey kills the stubborn Pseudomonas bacterium, which dwells in nearly half of the lungs affected by CF.

I’m a microbiology lab scientist, plus an inquisitive writer. I also consider myself an informed, self-advocating realist. Life experiences have taught me that I am solely responsible for my health. I strive to keep my health stable through prescribed medications, healthy diet, and some natural supplements.

During my college years, I focused on the environment, especially the living parts that we can’t see but that are essential to the cycle of life — bacteria. It just so happens that certain ones are, understatedly, little pests for people with CF. The lung bacteria of people with CF birth many symptoms and infections.

I continually fight Pseudomonas aeruginosa, my nemesis bacterium that spikes fevers within days of overwhelming my immune system and that has caused countless infections, leaving my lungs with pockets of dead tissue. I take antibiotics frequently, but I also believe that naturally derived compounds can have positive effects. So, despite my disdain and nausea, I sometimes supplement garlic, which contains the antibacterial compound ajoene. I’ve also consumed manuka honey; this I’ve done more religiously, as it tastes more like candy than any “medication.” Manuka honey contains the natural antibiotic methylglyoxal, a compound that fights relentless Pseudomonas by causing its cells to burst and die. I took a spoonful a day for a few years until recently. Maybe I stuck to this exorbitantly priced, palatable remedy merely because of its taste and the flawed logic that expensiveness is indicative of effectivity.

I had the idea to test the effectiveness of the honey on my sputum. My mucus grows many species of bacteria, but Pseudomonas is a primary component, so it’s easy to propagate in the lab setting.

Yes, I took a sputum cup of mucus into work. When inoculating the vials with the bacteria, I was slightly anxious that my lab mates might freak out at the sight of the hazardous and vile-looking green blobs. Then again, they work with wastewater from treatment plants, so it really shouldn’t phase them.

I tested a concentration of 15 percent weight per volume of manuka honey, a choice informed by published studies. I tested half of the petri dishes with honey mixed into the nutrients for the bacteria and the other half without the honey. The dishes with the honey should have less bacterial growth if the treatment works. (If you want more detail on the process, drop a comment below this column.)

The yellow dish has the honey added and the white dish doesn’t. (Photo by Ella Balasa)

After the 24-hour incubation period, I was excited to see the results of science that we as patients typically do not participate in. We provide our sputum samples during doctor’s appointments, then labs perform antibiotic resistance tests, and results are returned as values on a piece of paper indicating resistance or susceptibility. We don’t see the process. I was doing this same research on my own, and in a sense, taking the utmost control of my health.

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Monitoring Pulmonary Exacerbation in Cystic Fibrosis: The Hunt for Urine-based Biomarkers Begins

By Michele Wilson PhD

The buildup of mucus in the lungs is an ongoing challenge faced by people with cystic fibrosis, and knowing whether they should seek medical attention is not always clear.

Recently, Mologic – a developer of personalized diagnostics – have developed a tool which they hope will help guide people with cystic fibrosis so they can avoid unnecessary stays in hospital.

The app-embedded algorithm converts data collected from a urinary test to a traffic light result, which indicates whether a patient is stable or in need of medical intervention.

Recently, Mologic, announced that they are launching a clinical trial to assess the company’s urine-based diagnostic tool, ‘HeadsUp’.

To learn more about how this point-of-care diagnostic tool could help improve healthcare for people with cystic fibrosis, we spoke with Gita Parekh, Head of R&D at Mologic.

How do you define pulmonary exacerbation, and why is it important that it is monitored in people with cystic fibrosis? Continue reading Monitoring Pulmonary Exacerbation in Cystic Fibrosis: The Hunt for Urine-based Biomarkers Begins

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. 

Cinnamon Oil Compound Might Block Bacteria Like P. aeruginosa from Forming Biofilms

By: Alice Melao

A natural component found in cinnamon oil, known as cinnamaldehyde or CAD, may be able to prevent Pseudomonas aeruginosa bacteria from spreading in an organism and inhibit their ability to form antibiotic-resistant biofilms, researchers show.

These findings may support further study into anti-microbial medications that can help control the behavior of these so-called superbugs, or treatment-resistant bacteria, which represent a serious healthcare problem for people with cystic fibrosis and other diseases.

The discovery was reported in “Cinnamaldehyde disrupts biofilm formation and swarming motility of Pseudomonas aeruginosa,” published in the journal Microbiology.

“Humans have a long history of using natural products to treat infections, and there is a renewed focus on such antimicrobial compounds,” Sanjida Halim Topa, PhD, a researcher at Swinburne University of Technology in Australia, and lead study author, said in a university news release. “Natural products may offer a promising solution to this problem.”

Cinnamaldehyde, one of the major components of cinnamon oil, is responsible for its characteristic flavor. This compound is known to have antimicrobial activity against many bacteria, including P. aeruginosa; a stomach ulcer-causing bacteria called Helicobacter pylori; and Listeria monocytogenes, which is responsible for the food-borne infection listeriosis.

“We hypothesized that using natural antimicrobials, such as essential oils, might interfere in [drug-resistant] biofilm formation,” Topa said. “Though many previous studies have reported antimicrobial activity of cinnamon essential oil, it is not widely used in the pharmaceutical industry.”

Working with researchers at Nanyang Technological University in Singapore, the team conducted several experiments to evaluate the impact of different concentrations of cinnamaldehyde on P. aeruginosa biofilms.

They found that non-lethal amounts of the essential oil compound could disrupt by 75.6 % antibiotic-resistant, preformed P. aeruginosa biofilms. Cinnamaldehyde was found to prevent the production of a bacterial-signaling protein essential for bacteria communication and biofilm formation. [Biofilms, or microbe communities whose growth is facilitated by the thick and sticky mucus that marks CF, are known to promote antibiotic resistance in P. aeruginosa lung infections.]

In a concentration-dependent manner, cinnamaldehyde also could reduce the motility of the bacteria, preventing them from spreading elsewhere, the scientists reported.

These findings, the researchers wrote, show “CAD can disrupt biofilms and other surface colonization phenotypes through the modulation of intracellular signaling processes.”

They are now investigating the use of cinnamaldehyde embedded-wound dressings as a way to treat skin infections.

Original article here.

Positive Data from the CARE CF 1 Clinical Study of Oral Lynovex in Cystic Fibrosis Exacerbations

NovaBiotics Ltd (“NovaBiotics”) announces that its oral therapy for cystic fibrosis (CF), Lynovex®, has met the study objectives of the CARE CF 1 clinical trial.

CARE CF 1 assessed the effects of two weeks of Lynovex treatment as an adjunct to standard of care therapy (SOCT) in CF, compared to placebo plus SOCT. This trial was designed to determine whether the inclusion of Lynovex capsules alongside SOCT lessened the clinical impact of exacerbations in adults with CF, as measured by symptom severity and levels of bacteria and inflammatory mediators in sputum and blood.  CARE CF 1 was a 6-arm study with the primary objectives of determining the optimal dose and regimen of Lynovex in patients with exacerbations of CF-associated lung disease and to further evaluate the safety and tolerability of Lynovex in exacerbating CF patients.  Continue reading Positive Data from the CARE CF 1 Clinical Study of Oral Lynovex in Cystic Fibrosis Exacerbations

Surviving Home IVs As a Mom

By Janeil Whitworth

I’m no stranger to home IV antibiotics.

Actually, if I am being completely honest, I think we have gotten a little too friendly over the past decade or so. I prefer to do home IVs because I am one of those patients who goes a little nuts after being trapped in the hospital for too long. Seclusion and unlimited access to cable are not beneficial to my physical or mental well-being. I need the opportunity to be with people just as much as I need the comfort of my own bed to rest and heal completely. I’ve even gone as far as learning to access my own port-a-cath to create even further distance between the hospital and me. Plus, I enjoy the luxuries of home IVs such as creating my own schedule, eating my own food, using my own toilet paper, and coming and going as I please.

Releasing control

I’m positive I’m not the only one who struggles to release control over my disease while experiencing an exacerbation. Feeling the façade of freedom slipping away post-IV-talk, I involuntarily tighten my grip on my independence in a desperate attempt at normalcy.

In-patient admission? No way. Home IVs? Ok, I can do that. Thankfully, you can travel on home IVs, celebrate your bachelorette party on home IVs, and even graduate college on home IVs. But is it possible to successfully care for a 9-month-old baby on home IVs?

After the past few weeks of increased shortness of breath and unwavering fatigue, I agreed it was time for IVs. The reality of home IVs as a mom suddenly hit me as I exhaustedly said for the millionth time that day, “Please, don’t eat mommy’s IVs, buddy.”

I knew this was not going to be easy with a mobile, energetic baby crawling every which way, leaving a trail of alcohol pads in his path. (I think this might be the fatigue talking, but the crunchy hospital bed and one-ply toilet paper are starting to seem a little better right now.)

The last time I did home IVs, my son was 4 months old, so it made it a tad easier as he was just a chubby and adorable blob. I would set him down, hook myself up to the antibiotic-filled Eclipse ball, and he wouldn’t move. Those were the days.

There’s been very little rest this week, and admittedly, I tried my hardest to do it all even if I was feeling absolutely poisoned. In my defense, I felt my independence as a mom was slipping away once again, and the impulse to hold on tighter completely crept up on me. This way of thinking will not benefit me in the long run, neither as a mother, nor as a patient. A week has passed since I accessed my port to begin treatment, and I can see more clearly now that I am in desperate need of a different rhythm.

Finding a different rhythm

I am going to attempt to take my own advice for the remainder of treatment, including: 1) Ask for help; 2) Be easy on myself when it comes to everything else; 3) Remain grateful for the privilege of staying home. My normalcy in the coming weeks will look a little different. My parenting style will be altered as well. I need to accept that this is the price for staying home with my baby, while simultaneously being the nurse and patient. Everything needs to be taken in stride as I release my grasp and let the rest, antibiotics, and baby hugs heal me. I think this is the key to surviving home IVs with my health, sanity, and pride intact. I hope.

This blog was originally published on CF News Today.

Cystic Fibrosis Disease Severity Linked to Immune Overreaction to Fungus, Study Reports

By Ana Pena

Disease severity in cystic fibrosis (CF) may be associated with an overreaction of the immune system to the fungus Aspergillus fumigatus, particularly due to a type of white blood cell called a phagocyte — which ingests and kills invading organisms — a study suggests.

U.K. researchers found that phagocytes from CF patients release higher amounts of harmful reactive oxygen species in response to Aspergillus fumigatus, a common cause of lung infection in these patients.

The study, “Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity,” was published in the journal ERC Open Research.

Recent studies have supported the idea that the widespread environmental fungus Aspergillus fumigatus may play a critical role in CF lung disease.

Up to 58% of CF patients are colonized with this fungus, and an estimated 47.7% of adult patients are affected by either allergic reactions or infection caused by the fungus.

Persistent infections with A. fumigatus are also known to be adversely correlated with lung function and hospitalization in CF patients.

Researchers hypothesized that the anti-fungal defense mechanism in CF patients might be altered and have an impact on the progression of lung disease.

To investigate this hypothesis, the team compared the immune response of phagocytes from CF patients with those of healthy individuals used as controls, and tried to correlate them to clinical metrics of disease severity.

For original article please visit CF News Today.

Antioxidant Supplement Helps Cystic Fibrosis Patients, Study Finds

By Carolina Henriques

A special formulation of an antioxidant-enriched multivitamin helped decrease the frequency of pulmonary exacerbations in patients with cystic fibrosis (CF), according to a new study.

The findings, by researchers at Children’s Hospital Colorado and the University of Colorado School of Medicine, were published in the American Journal of Respiratory and Critical Care Medicine under the title “Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis: Randomized, Controlled, Multicenter Trial.”

Inflammation is an important contributor to lung damage and to progressive lung function decline in CF. In the study, researchers looked at the effects of a “cocktail” of multiple antioxidants on inflammation and health outcomes in CF patients.

“Single oral antioxidant formulations have been tested previously in CF with mixed results. However, there had not been a well-designed, randomized controlled trial of an antioxidant ‘cocktail’ that included multiple antioxidants in a single formulation,” Scott Sagel, MD, PhD, said in a University of Colorado news story. Sagel is the study’s first author and a pediatric pulmonologist at Children’s Colorado.

The 16-week study (NCT01859390) was conducted from September 2013 to October 2015 at 15 U.S. CF centers affiliated with the CF Foundation’s Therapeutics Development Network.

The study included 73 pancreatic-insufficient CF patients, 10 years and older (average age 22), who could not adequately absorb important dietary antioxidants such as beta-carotene, coenzyme Q10 (CoQ10), tocopherols (vitamin E), and selenium, which help neutralize inflammation in the body.

Participants received either capsules of antioxidant-enriched multivitamins, or control multivitamins without antioxidant enrichment. The capsules were designed specifically for people with difficulties in absorbing fats and proteins, like CF patients.

The investigational antioxidant-enriched multivitamin supplement, called AquADEKs-2, contains standard amounts of fat-soluble vitamins (A, D, E, K) plus several antioxidants, including beta-carotene, mixed tocopherols, CoQ10, mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium.

Sagel and his team found that the antioxidant-enriched multivitamin supplement increased the concentration of antioxidants in the bloodstream, and temporarily reduced inflammation at four weeks, even though these results were not sustained through the end of the 16 weeks of the study.

In addition, antioxidant supplementation was found safe and well-tolerated by study participants.

Researchers also observed that antioxidant treatment appeared to prolong the time to the first pulmonary exacerbation requiring antibiotics, and also to reduce the frequency of pulmonary exacerbations altogether.

For the full article, please visit CF News Today.

Toothpaste ingredient may bust up cystic fibrosis biofilms

By Chris Waters and Sarina Gleason

A common antibacterial substance in toothpaste may combat life-threatening diseases such as cystic fibrosis when combined with an with an FDA-approved drug, researchers report.

Researchers have found that when triclosan, a substance that reduces or prevents bacteria from growing, combines with an antibiotic called tobramycin, it kills the cells that protect the CF bacteria, known as Pseudomonas aeruginosa, by up to 99.9 percent.

CF is a common genetic disease with one in every 2,500 to 3,500 people diagnosed with it at an early age. It results in a thick mucus in the lungs, which becomes a magnet for bacteria.

These bacteria are notoriously difficult to kill because a slimy barrier known as a biofilm, which allows the disease to thrive even when treated with antibiotics, protects them.

“The problem that we’re really tackling is finding ways to kill these biofilms,” says Chris Waters, lead author of the study and a microbiology professor at Michigan State University.

According to Waters, there are many common biofilm-related infections that people get, including ear infections and swollen, painful gums caused by gingivitis. But more serious, potentially fatal diseases join the ranks of CF including endocarditis, or inflammation of the heart, as well as infections from artificial hip and pacemaker implants.

Waters and his coauthors grew 6,000 biofilms in petri dishes, added in tobramycin along with many different compounds, to see what worked better at killing the bacteria. Twenty-five potential compounds were effective, but one stood out.

“It’s well known that triclosan, when used by itself, isn’t effective at killing Pseudomonas aeruginosa,” says coauthor Alessandra Hunt, a postdoctoral associate of microbiology and molecular genetics. “But when I saw it listed as a possible compound to use with tobramycin, I was intrigued. We found triclosan was the one that worked every time.”

Triclosan has been used for more than 40 years in soaps, makeup, and other commercial products because of its antibacterial properties. Recently, the FDA ruled to limit its use in soaps and hand sanitizers due to insufficient data on its increased effectiveness and concern about overuse. Clear evidence has shown, though, that its use in toothpaste is safe and highly effective in fighting gingivitis, and it is still approved for use.

“Limiting its use is the right thing to do,” says coauthor Michael Maiden, a graduate student in medicine. “The key is to avoid creating resistance to a substance so when it’s found in numerous products, the chances of that happening increase.”

Tobramycin is currently the most widely used treatment for CF, but it typically doesn’t clear the lungs of infection, Waters says. Patients typically inhale the drug, yet still find themselves chronically infected their whole lives, eventually needing a lung transplant.

“Most transplants aren’t a viable option though for these patients and those who do have a transplant see a 50 percent failure rate within five years,” he says. “The other issue is that tobramycin can be toxic itself.” Known side effects from the drug include kidney toxicity and hearing loss.

“Our triclosan finding gives doctors another potential option and allows them to use significantly less of the tobramycin in treatment, potentially reducing its use by 100 times,” Hunt says.

Within the next year, Waters and his colleagues will begin testing the effectiveness of the combination therapy on mice with hopes of it heading to a human trial soon after since both drugs are already FDA approved.

Just brushing your teeth with toothpaste that has triclosan won’t help to treat lung infections though, Maiden says.

“We’re working to get this potential therapy approved so we can provide a new treatment option for CF patients, as well as treat other biofilm infections that are now untreatable. We think this can save lives,” he says.

The research appears in the journal Antimicrobial Agents and Chemotherapy.

The National Institutes of Health, Cystic Fibrosis Foundation, and Hunt for a Cure in Grand Rapids, Michigan funded the research.

Source: Michigan State University