Antibiotics Make Bacteria More Resistant by Lowering Microbial Diversity in Lungs, Study Suggests

Antibiotics lessen the diversity of microbes in the lungs of cystic fibrosis (CF) patients, and make these people more susceptible to infections with bacteria that are highly resistant to antibiotics, researchers reported.

The study “Antibiotic multidrug resistance in the cystic fibrosis airway microbiome is associated with decreased diversity” was published in the journal Heliyon.

Acute and chronic lung infections in CF patients require the use of multiple antibiotics to manage and prevent the exacerbations, or disease worsening, they cause. However, excessive antibiotic use can lead to the development of bacteria that are multi-drug resistant, making treatment difficult. Antibiotics can also kill non-pathogenic bacteria in the lungs, reducing the diversity of the microbial community there that is important to lung health.

Researchers assessed the diversity of the lung microbiome (the genomes of microbes that live in the lungs) and the presence of drug-resistant bacteria in CF patients after antibiotic use following an exacerbation episode using sensitive molecular biology techniques.

Six patients, with a mean age of 12, participated in the 18-month study. All were recruited from the Children’s National Health System in Washington D.C., where they were undergoing treatment. For the study, either sputum samples or fluid from the lungs were collected from the patients at four different time points:

• at a routine visit (baseline), before starting treatment with intravenous (IV) antibiotics
• when they were hospitalized for an exacerbation (exacerbation visit), which needed IV antibiotic treatment
• at the end of their antibiotic course (treatment visit), and,
• over 30 days after completion of antibiotic therapy (recovery visit).

Through these visits, a total of 19 samples were obtained for testing.

In addition to the classic laboratory analysis of sputum samples that enables bacterial identification, researchers also used genetic analysis to identify antibiotic resistance genes in the bacterial genomes.

“Laboratory cultures are designed to grow certain types of bacteria that we know are problematic, but they don’t show everything,” Andrea Hahn, MD, pediatric infectious diseases specialist at Children’s National Health System and the study’s first author, said in a press release.

“By genetically sequencing these samples, we can see everything that’s there,” Hahn added.

Researchers found multi-drug resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA; a particularly difficult-to-treat bacteria) in seven samples. Of those seven, three came from exacerbation visits, two were taken at treatment visits, and two at recovery visits.

In addition to MRSA, other resistant bacteria found included those from the Streptococci and Alcaligenes genus. The role of Alcaligenes in CF is not yet known, the researchers noted.

These resistant bacterial samples showed markedly less diversity in types of bacteria, compared to patients without antibiotic-resistant bacteria, suggesting poorer microbiome diversity in the lungs of those affected. Lung function was measured by the patient’s ability to forcefully and quickly exhale a deep breath of air, a measure called forced vital capacity (FVC; the greater the FVC, the better is the patient’s lung function).

Patients with multi-drug resistant bacteria showed significantly poorer lung function (FVC of 64.5) compared to those without MDR bacteria (FVC of 91.6), the team found.

The researchers concluded that the use of antibiotics appears to promote the development of antibiotic resistance, lower microbial diversity in the lung, and to hamper lung function.

“Decreasing diversity has been associated with both prolonged antibiotic use,” the researchers noted, “however, no prior studies have tried to associate the presence of antibiotic resistance within the microbial community of the airway to community diversity.”

Still, antibiotics are needed after each episode of disease worsening to help CF patients. “We can’t stop using antibiotics,” Hahn concluded, “but we can learn to use them better.”