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PUBLICATION DATE: AUGUST 02, 2023

 

Thirty-five to forty years is the average lifespan of a patient with Cystic Fibrosis (CF) in the U.S. and U.K. 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 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). It suggests in a press release, that, “The presence of multidrug resistant bacteria in the airways of patients with CF is associated with decreased microbial diversity and decreased pulmonary function.

Antimicrobial Resistance in Cystic Fibrosis Patients

The hallmark symptom of Cystic Fibrosis is chronic lung congestion with persistent coughing, frequent lung infections, wheezing, and shortness of breath. Cystic Fibrosis is a progressive genetic disorder in which patients inherit two defective copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene—one from each parent. The mutated genes cause the CFTR protein to malfunction, and the result is that the normal mucus in various organs, including the lungs, becomes thick and sticky.

The mucus clogs the patient’s airways and traps germs that lead to infections and other complications, including the growth of bacterial colonies called “biofilms” in the lungs. Bacterial biofilms are structured bacterial communities that produce a polymer matrix that protects the colony. Biofilm bacteria behave differently than single bacteria with various members, developing different morphology and functionalities.

Crucially, biofilm bacteria are more resistant to antibiotics than single bacteria. That is why strategies to fight CF infections need 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 measures.”

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.

Leveraging Diagnostic Tools to Fight Antimicrobial Resistance (AMR) and Inform Treatment for Cystic Fibrosis Patients

Limiting the overuse and misuse of antibiotics is essential in the fight against AMR, and it necessitates the use of rapid diagnostic tools to support accurate and timely prescribing decisions. While antibiotic utilization may be necessary, responsible use is vital. “We can’t stop using antibiotics,” Dr. Hahn said, “but we can learn to use them better.” To do that, Dr. 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 to.

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,” Dr. Hahn says. “By genetically sequencing these samples, we can see everything that’s there.” Rapid molecular testing of CF patient samples can be lifesaving, particularly since many patients have more than one species of microbe causing an infection.

A paper in the MDPI journal, Antibiotic Resistance in Patients with Cystic Fibrosis: Past, Present, and Future, discusses the ways that advanced tools and whole genome sequence (WGS) data generated from next-generation sequencing (NGS) platforms can be especially helpful. NGS tools have proven to be less time consuming and more effective than traditional molecular techniques. NGS platforms also offer the possibility for horizontal resistome analysis, including “detection of acquired resistance genes and relevant chromosomal mutations”. Although modern research and technology have helped lead to better treatment for patients with CF, additional research is needed to continue the progress.

 

Research priorities should comprise the establishment of better diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, that may directly detect AMR in the microbial communities colonizing the airways in patients with CF,” explain authors of the MDPI study. “The presence of AMR remains a critical health issue in patients with CF. In this regard, both management and monitoring of antibiotics usage are obligatory and more relevant than ever.”

 

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

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