The Necessity of Innovative Diagnostics in Controlling Antibiotic Resistance in Patients with Cystic Fibrosis

By the bioMérieux Connection Editors

Forty years is the average lifespan of a patient with Cystic Fibrosis (CF) in the U.S. today. “A key to helping patients live even that long—a vast improvement from an average lifespan of 10 years just decades ago—is judicious use of antibiotics,” explains Andrea Hahn, M.D., a pediatric infectious diseases specialist at Children’s National Health System in Washington D.C.

But antibiotics, “are a double-edged sword,” Dr. Hahn adds, “Although they’re necessary to eradicate lung infections, repeated use of these drugs can lead to antibiotic resistance, making it tougher to treat future infections. Also, antibiotic use can kill the nonpathogenic bacteria living in the lungs as well. That decreases the diversity of the microbial community that resides in the lungs, a factor associated with disease progression.”

But exactly how antibiotic resistance impacts the relationship between lung bacterial diversity and CF patients’ pulmonary function is not fully understood.

A team at Children’s National recently published a study designed to investigate that question. Their open-access paper, Antibiotic multidrug resistance in the cystic fibrosis airway microbiome is associated with decreased diversity, quoted in a Children’s National press release, suggests that, “The presence of multidrug resistant bacteria in the airways of patients with CF is associated with decreased microbial diversity and decreased pulmonary function.”

CF is a progressive genetic disorder in which patients inherit two defective copies of the CF gene from both parents, according to the Cystic Fibrosis Foundation (CFF). Since carriers have one defective and one normal copy of the gene, a child born to two carriers has a 25% change of receiving two defective genes and having CF.

The specific gene impacted by the CF genetic mutation encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which normally regulates the flow of salt and fluids in many cells. There are 1,700 known CFTR gene mutations that lead to CF, according to the CFF. Patients with this genetic disease suffer from a thick build-up of mucus in their lungs. Other organs and systems affected include the pancreas, the gastrointestinal tract, and the male reproductive system.

The hallmark symptom of CF is chronic lung congestion with persistent coughing, frequent lung infections, wheezing, and shortness of breath. The limited function of the CF lung leads not only to frequent lung infections, but to permanent bacterial colonies called “biofilm” dwelling within the lungs.

According to Bacteriality.com, bacterial biofilms are structured bacterial communities with the ability to produce a polymer matrix that protects the colony. Biofilm bacteria behave differently than single bacteria with various members, developing different morphology and functionalities. All perform different, but essential, roles within the community. Such adaptation is the norm, not the exception, in biology. It occurs in embryology, wound healing, and many other examples. But it also can be pathological, as seen with biofilms and in cancer as well.

While bacterial colonies are called biofilm, individual bacteria are referred to as, “planktonic.” These free-floating microbes are typically to blame for acute infections of the blood, urine, lung fluid, cerebrospinal fluid, or other bodily fluids. Biofilm colonies remain fixed in a specific location and lead to chronic infections, like pneumonia in CF patients, implant-associated infections, catheter-associated infections, and chronic wound infections.

Since there’s strength in numbers, planktonic bacteria are usually more vulnerable to antibiotics, while biofilm infections are more resistant. That is why strategies to fight deadly CF infections are based on four key goals, “Directed to combat biofilm growth, prevent the emergence of mutational resistance, promote the development of novel antimicrobial agents against multidrug-resistant strains, and implement strict infection control measure.”

In the Children’s National study, researchers closely analyzed the respiratory secretions of 6 CF patients over an 18-month period. They found a wide variety of bacterial species, including methicillin-resistant Staphylococcus aureus, (MRSA). These patients, and the others who carried an antibiotic-resistant infection, had, “significantly lower microbial diversity in their samples and more aggressive disease.”

Long-term antibiotic use probably contributed to both the antibiotic resistance and lowered microbial diversity in these patients, according to lead investigator, Dr. Hahn. However, reducing antibiotic use in CF patients is not the answer, she insisted. Without antibiotics, many CF patients simply would not survive the recurrent pulmonary exacerbations that are a common occurrence.

“We can’t stop using antibiotics,” Hahn said, “but we can learn to use them better.” To do that, Hahn advocates for a more proactive microbiology lab to closely monitor the types of CF infections and to determine which antibiotics each infection is most susceptible. In the Children’s National study, researchers analyzed each sample in two different ways: standard lab culture and molecular testing.

“Laboratory cultures are designed to grow certain types of bacteria that we know are problematic, but they don’t show everything,” she says. “By genetically sequencing these samples, we can see everything that’s there.”

Rapid molecular testing of CF patient samples can be life-saving, particularly since many patients have more than one species of infection.


Opinions expressed in this article are not necessarily those of bioMérieux, Inc.

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