Antibiotics are increasingly unable to fight bacteria as resistance develops.

For 70 years, antimicrobial agents, known as antibiotics, have been successfully fighting infectious diseases, dramatically reducing rates of illness and death worldwide.

However, their widespread use has led to adaptations in the infectious organisms that they are designed to kill, reducing the drugs' effectiveness.

In the US, antibiotic-resistant bacteria cause at least 2 million cases of disease and 23,000 fatalities annually.

As a result, the Centers for Disease Control and Prevention (CDC) have outlined the top 18 drug-resistant threats to the US and categorized them based on level of concern: urgent, serious or concerning. Health professionals have been encouraged to limit the use of antibiotics.

Those in the "urgent" category are currently:

• Clostridium difficile (C. difficile), which causes life-threatening diarrhea
• Carbapenem-resistant Enterobacteriaceae (CRE), mostly occurring in medical facilities, where it causes bloodstream infections that prove fatal in almost 50% of cases
• Neisseria gonorrhoeae that cause gonorrhea, a sexually transmitted disease, affecting 820,000 people a year.

The current study, led by Egija Zaura, PhD, an associate professor in oral microbial ecology at the Academic Centre for Dentistry in Amsterdam, the Netherlands, looked at 66 healthy adults from the UK and Sweden who were prescribed different antibiotics.

Participants were randomly assigned to receive a full course of one of four antibiotics: ciprofloxacin, clindamycin, amoxicillin or minocycline, or a placebo.

The researchers collected fecal and saliva samples from participants at the start of the study, immediately after taking the antibiotics, and 1, 2, 4 and 12 months after finishing the course.

Single antibiotic course has long-term impact

A laboratory technique called 16S rRNA gene amplicon sequencing identified the presence of bacteria on 389 fecal and 391 saliva samples.

Another lab technique, metagenomic shotgun sequencing, highlighted the largest differences before and after antibiotic usage, which enabled researchers to study the emergence of antibiotic resistance.

The drugs were found to enrich genes associated with antibiotic resistance and to severely affect microbial diversity in the gut for months after exposure. By contrast, microorganisms in the saliva showed signs of recovery in as little as a few weeks.

The microorganisms in participants' feces were severely affected by most antibiotics for months. In particular, researchers saw a decline in the abundance of health-associated species that produce butyrate, a substance that inhibits inflammation, cancer formation and stress in the gut.

Microbiome diversity in feces was significantly reduced for up to 4 months in participants taking clindamycin and up to 12 months in those taking ciprofloxacin. In contrast, diversity in the oral cavity microbiome was only altered for up to a week after drug exposure.

Amoxicillin had no significant effect on microbiome diversity in either the gut or oral cavity, but it was associated with the greatest number of antibiotic-resistant genes.

'Antibiotics should only be used when really necessary'

Researchers are not sure why the oral cavity returns to normal sooner than the gut, but it could be because the gut is exposed to a longer period of antibiotics.

Alternatively, the oral cavity may be intrinsically more resilient toward stress because it is exposed to different stressors every day.

UK participants started the study with more antibiotic resistance than those from Sweden, possibly due to different attitudes toward antibiotics. Sweden has seen a significant decline in antibiotic use over the last 2 decades.

Zaura says:

"Antibiotics should only be used when really, really necessary. Even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome. Certainly we cannot live or survive without antibiotics; that's out of the question. But there are situations when we should not use them, like when there are no evidence-based reasons."

Medical News Today recently reported that hospital treatments in the US are severely hampered by antibiotic resistance.