Machine learning to help cystic fibrosis decision-making

By James Hayes

New research claims to have demonstrated that machine learning techniques can predict with a 35% improvement in accuracy – in comparison to existing statistical methods – whether a cystic fibrosis patient should be referred for a lung transplant.

The research, led by Professor Mihaela van der Schaar of the Alan Turing Institute at the University of Oxford, has been generated through a partnership between The Alan Turing Institute and charity the Cystic Fibrosis Trust. Continue reading Machine learning to help cystic fibrosis decision-making

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

Harmful Bacteria Replace Beneficial Ones in Gut of CF Patients

By Vijaya Iyer

Cystic fibrosis (CF) patients have a higher amount of harmful gut bacteria and increased levels of intestinal inflammation than healthy people, according to researchers.

Their study, “Altered intestinal microbiota composition, antibiotic therapy and intestinal inflammation in children and adolescents with cystic fibrosis,” was published in the journal PLOS One.

CF predominantly affects the lungs, but it can also cause gastrointestinal complications. The CFTR protein defect (the cause of CF) is abundant in the gastrointestinal tract of patients and affects the normal structure of the intestine. This defect could influence the diversity of the bacteria present in the gut (also called the gut microbiome). Continue reading Harmful Bacteria Replace Beneficial Ones in Gut of CF Patients

A Cost-Utility Analysis Of Vertex’s CF Drugs — What It Teaches Us About Trial Design

By Claudia Dall’Osso, Ph.D., Ian Love, Ph.D., and Nuno Antunes, Ph.D., Decision Resources Group (DRG)

Commercial success in the pharmaceutical industry requires that clinical programs, in addition to demonstrating clinical effectiveness, also provide data supporting a drug’s value. The Institute for Clinical and Economic Research (ICER), a U.S.-based cost-effectiveness watchdog, recently released an analysis suggesting that Vertex Pharmaceuticals’ cystic fibrosis (CF) franchise — Kalydeco, Orkambi, and the recently launched Symdeko — while offering meaningful clinical efficacy, would require discounts of approximately 70 percent1 to be cost-effective.

Here, we review ICER’s cost-effectiveness analysis of the Vertex CF franchise to highlight lessons for orphan drug developers related to clinical trial designs and outcome metrics that would facilitate more favorable cost-effectiveness evaluations by stakeholders who employ cost-utility modeling (e.g., ICER, U.K.’s National Institute for Health and Care Excellence [NICE]).

Calculating The Cost-Effectiveness Of Vertex’s Cystic Fibrosis Franchise

In a cost-utility model, health economic analysts strive to calculate the incremental cost to gain an extra quality-adjusted life year (QALY); they estimate a therapy’s impact on the level of utility patients are deriving from their life based on their health status and incorporate these data into a quantitative estimate of QALYs (Figure 1). The goal of the cost-utility analysis is to determine whether a therapeutic intervention changes the QALYs that patients will accumulate over a set time period (e.g., lifetime), and at what added cost. The threshold for what is considered an acceptable incremental cost per QALY varies by stakeholder; ICER typically presents a sensitivity analysis across a range of thresholds (e.g., $50,000 to $500,000 per QALY for an ultra-rare disease like CF).

In our view, data gaps opened the possibility of a potential undervaluation of the Vertex CF transmembrane conductance (CFTR) modulators on several metrics and, ultimately, on overall survival in the context of the ICER model. Vertex’s pivotal clinical trials captured the effect of CFTR modulators on the two organs chiefly affected in CF — the lungs and the pancreas — with outcome metrics for pulmonary function, percent-predicted 1-second forced expiratory volume (ppFEV1), and pulmonary exacerbation rate, as well as pancreatic sufficiency (body weight) (Figure 2). However, data on metrics assessing emerging complications (e.g., CF-dependent diabetes or bacterial infections), impact on use of other medications (e.g., pancreatic enzyme replacement therapy, mucolytics), reduction in healthcare resource utilization, or reduction in disease burden were far more limited, but these attributes were included in ICER’s cost-effectiveness analysis. Lacking clear clinical trial data on the metrics outlined above, health economists relied on arguably conservative assumptions to estimate the impact of the Vertex CFTR modulators on these domains. Because the Vertex CF franchise has a relatively short market history, and the long-term risks/benefits of the drugs are incompletely understood, assumptions to model the long-term impact of these medicines were also necessary.

For instance, to evaluate survival, ICER modeled the impact of CF-related diabetes in its analysis of CF patients’ health status. Owing to the dearth of clinical trial data on CF-related diabetes in the development program for the Vertex drugs, the company’s CFTR modulators were assumed not to impact this outcome (Figure 2). Treatment with the Vertex CFTR modulators was also conservatively assumed to have no long-term impact on weight after an initial increase and, without long-term data, the drugs’ impact on ppFEV1 beyond two years of treatment was modeled as a 50 percent reduction in the rate of ppFEV1 decline.

Notably, several CF experts interviewed by DRG consider it possible that early treatment of newborns could prevent disease development. The potential impact of early treatment with CFTR modulators on disease development and survival was not explored in the ICER analysis; although little data is available to support such an impact of the Vertex drugs, ICER has considered such scenarios largely unsupported in other evaluations (e.g., a cost-effectiveness evaluation of Spark Therapeutics’ Luxturna for the treatment of retinitis pigmentosa).

The translation of clinical trial data to utility is a second area wherein a manufacturer may lose traction in a cost-utility analysis, if the utility calculation isn’t sufficiently comprehensive or if the drug’s data package is insufficient to support its impact on all relevant metrics. In the ICER analysis of the Vertex franchise, health economists used the ppFEV1 metric to derive a utility curve by assigning a level of benefit to a specific ppFEV1 value. Although this is the most straightforward approach, it also results in an assessment of health benefits that relies exclusively on a mechanical respiratory metric, which may not adequately capture the quality of life experienced by patients, especially considering the multi-organ nature of CF. Indeed, at the May 17 presentation of the ICER model, stakeholders from the Cystic Fibrosis Foundation levied this criticism. Furthermore, ICER’s sensitivity analyses showed that changes in the relationship between ppFEV1 and utility could significantly affect the overall cost-effectiveness assessment. Notably, an alternative scenario in which the utility was increased by 5 percent, to account for clinical effects of a drug beyond pulmonary function, led to a 15 percent decrease in the cost-effectiveness ratio.

Similarly, the impact of the Vertex franchise on payer budgets in the ICER model related only to pulmonary supportive care, while other non-pulmonary expenses remained unchanged — an assumption made in the context of available data, but one that may not fully reflect the benefit of the drugs. Furthermore, the CFTR modulators did not impact the burden of supportive care for CF patients in the model, nor did they impact patients’ productivity. Ultimately, suboptimal alignment of clinical trial data with the demands of a comprehensive (e.g., multi-organ) cost-effectiveness model may have diminished the opportunity for the Vertex franchise to perform maximally in this cost-utility analysis.

Key Lessons And Takeaways For Drug Developers

Although clinical outcome data collected by Vertex was sufficient to gain an FDA green light, it was not sufficient to support a comprehensive analysis of cost-effectiveness in this multi-organ disease. As such, assumptions regarding drug impact were necessary in areas not adequately supported by data, opening the possibility for a suboptimal cost-effectiveness evaluation. To support more favorable and data-supported evaluations, developers should design clinical trials with an eye on cost-effectiveness.

  • Prior to initiating clinical trials, manufacturers should consider how a health status model is likely to be designed to assess cost-effectiveness. They should consider enrolling the assistance of academic researchers to understand which metrics may be important in such a model and to aid in the development of a reliable model in an area where none is established. With this analysis in mind, developers should strive to design a clinical program that covers relevant metrics and the durability of a drug’s impact on them. Indeed, an alternative scenario developed by ICER showed that a change in the long-term effectiveness assumption on ppFEV1 would have a profound impact on the final cost-effectiveness assessment; for Kalydeco, assuming no decline in ppFEV1 after the first two years (rather than 50 percent) decreased the incremental cost-effectiveness ratio ($ per QALY) by approximately 35 percent.
  • Developers should work to understand how key clinical metrics in a given disease area are translated into utility. In a disease with an established function, it is prudent to carefully survey the relevant literature. When developing a pioneering treatment, manufacturers should consider investment into the development of a utility curve that accurately accomplishes this, which would likely facilitate a reliable QALY calculation or at least more detailed/specific alternative scenarios and sensitivity analyses.
  • Understand the patient journey and track healthcare resource utilization during a clinical trial to more fully support an accurate assessment of cost of care, as a favorable impact on direct healthcare costs is important to attain widespread reimbursement.
  • Although metrics such as burden of care, caregiver burden, or productivity loss are difficult to rigorously track, they can be immensely valuable in highlighting the favorable indirect effects of disease-modifying drugs beyond the clinical efficacy. Understanding patients’ pain points and, ideally, tracking these metrics when possible (e.g., with real-world data or social media listening analyses) may further strengthen and support conventional metrics from clinical trials.

As market access hurdles intensify, and ICER’s analyses increasingly inform payer policy, anticipating and preparing for cost-utility analyses early in the design of a clinical program will be paramount to support a medicine’s value proposition with U.S. insurers.

Original article found 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

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.

FDA approves Proteostasis’s triple combination program for CF

Singapore — Proteostasis Therapeutics, a clinical stage biopharmaceutical company dedicated to the discovery and development of ground-breaking therapies to treat cystic fibrosis (CF) and other diseases caused by dysfunctional protein processing, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for the Company’s triple combination program for the treatment of cystic fibrosis. The Company’s proprietary triple combination includes a novel cystic fibrosis transmembrane conductance regulator (CFTR) amplifier, third generation corrector and potentiator, known as PTI-428, PTI-801 and PTI-808, respectively. The Company announced in January that the protocol for its triple combination clinical study, which the Company plans to initiate in the current quarter, has received endorsement and a high strategic fit score from the Therapeutics Development Network (TDN) and the Clinical Trial Network (CTN), the drug development arms of the Cystic Fibrosis Foundation (CFF) and the European CF Society (ECFS), respectively.

“Fast Track designation represents another positive step for the development of our triple combination therapy and underscores the serious unmet need that remains for the vast majority of CF patients,” said Meenu Chhabra, president and chief executive officer of Proteostasis Therapeutics.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An investigational drug that receives Fast Track program designation is eligible for more frequent communications between the FDA and the company relating to the development plan and clinical trial design and may be eligible for priority review if certain criteria are met.

To read original article click here.

Antibiotic resistance evolution of Pseudomonas aeruginosain cystic fibrosis patients

By Francesca Lucca, Margherita Guarnieri, Mirco Ros, Giovanni Muffato, Roberto Rigoli, and Liviana Da Dalt

Below is a study hoping to define and answer the questions of Pseudomonas aeruginosain, its evolution and the resistance from different antibiotics. The study took place between 2010-2013. Though the study may have some time clauses I believe there are some strong findings for the CF community moving forward.
_________________________________________________________________________________

Introduction

Pseudomonas aeruginosa is the predominant pathogen responsible of chronic colonization of the airways in cystic fibrosis (CF) patients. There are few European data about antibiotic susceptibility evolution of P aeruginosa in CF patients.

Objectives

The aim of this study is to evaluate the evolution of antibiotic resistance in the period 2010‐2013 in CF patients chronically colonized by P aeruginosa and to highlight the characteristics of this evolution in patients younger than 20 years.

Methods

Clinical and microbiological data were extracted from two electronic databases and analyzed. Antibiotic resistance was defined according to European Committee of Antimicrobial Susceptibility Testing for levofloxacin, ciprofloxacin, meropenem, amikacin and ceftazidime. The between‐group comparison was drawn with the Chi‐square test for proportions, with the T‐test for unpaired samples for normally distributed data and with Mann‐Whitney test for non‐normally distributed data. Significancy was defined by P < .05.

Results

Fifty‐seven CF patients, including thirteen subjects aged less than 20 years, were enrolled. P.. aeruginosa antibiotic sensitivity decreased significantly for fluoroquinolones, mainly in patients aged <20 years, while it increased for amikacin and colistin. The analysis of minimum inhibitory concentration confirmed these trends. In pediatric patients treated with more than three antibiotic cycles per year, greater resistance was found, except for amikacin and colistin.

Conclusion

An evolution in P aeruginosa antibiotic resistances is observed in the 4‐year period studied. Responsible and informed use of antibiotics is mandatory in CF.
___________________________________________________________________________________
Read the whole clinical journal here. 

Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013) Francesca Lucca,Margherita Guarnieri,Mirco Ros,Giovanna Muffato,Roberto Rigoli,Liviana Da Dalt. First published: 1 April 2018. https://doi.org/10.1111/crj.12787