ANTIRESDEV

The effects of antibiotic administration on the emergence and persistence of antibiotic-resistant bacteria in humans and on the composition of the indigenous microbiotas at various body sites

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'The objective of the HEALTH-2009-2.3.1-2 call is to study the impact of different antibiotics on the prevalence of resistant bacteria in the human host. In ANTIRESDEV we will achieve this objective using the approaches suggested in the call as follows. We will use culture-based and culture-independent approaches to investigate the impact of four different types of antibiotics (with different modes of action, antimicrobial spectra and pharmacokinetic properties) on the emergence of antibiotic-resistant organisms and their persistence at several body sites. Disruption of the indigenous microbiota is recognized as an important factor in the persistence and transmission of antibiotic-resistant organisms, therefore we will also study the ecological impact of the antibiotics on the indigenous microbiotas of several body sites using culture-dependent and -independent techniques. We will then identify, using state-of-the-art microarrays, the genes responsible for resistance in the antibiotic-resistant organisms isolated. The genetic elements involved in resistance transfer by a number of these organisms will also be determined as knowledge of these elements is essential to fully understand the mechanisms underlying resistance transmission. By using state-of-the-art 454 pyrosequencing we will determine the full complement of resistance genes (the “resistome”) present in cultivable and not-yet-cultivated members of the oral and faecal microbiotas and the effect on these resistomes of antibiotic administration. Another important aspect of the dynamics and transmission of resistance is the fitness cost associated with resistance acquisition by an organism and we will investigate this in a variety of clinically-important organisms. We will ensure that the results of this study are made available to appropriate governmental and healthcare agencies so that they can be used to help in the formulation of measures designed to reduce the spread of antibiotic resistance.'

Introduzione (Teaser)

The growing ability of microorganisms to withstand antibiotic treatment has resulted in a serious health concern. Given that very few new antibiotics are in the development pipeline, the emergence of antibiotic-resistant bacteria has reduced our ability to treat many infectious diseases.

Descrizione progetto (Article)

Antibiotics inhibit the growth of bacteria or kill them. Their widespread misuse has put a strong selective pressure on microorganisms, leading to the emergence of bacterial strains resistant to a variety of antibiotics.To limit the development and spread of such resistant strains, the mechanisms involved in antibiotic action and the emergence of resistance need to be elucidated.

Scientists from the EU-funded http://www.ucl.ac.uk/antiresdev (ANTIRESDEV) project therefore studied the effects of administering a range of antibiotics (amoxicillin, minocycline, ciprofloxacin, clindamycin) to healthy volunteers. They examined the impact of the antibiotics on the emergence of resistance in their indigenousmicrobiotas. The rationale was that the distinct chemical nature, pharmacokinetics and antimicrobial spectrum of each antibiotic is likely to cause different patterns of resistance emergence and persistence.

Four cohorts of healthy individuals were recruited. After being administered a specific antibiotic, they were screened for the presence of antibiotic-resistant bacterial species at various body sites using culture-dependent and molecular techniques. Samples were collected before treatment and at certain time points (upto one year) after treatment.

Soon after antibiotic administration there was a transient increase in the proportions of antibiotic-resistant bacteria for all tested antibiotics, with the exception of amoxicillin. In the case of ciprofloxacin and clindamycin, increased proportions of some resistant species were observed up to one year after antibiotic administration.. None of the four antibiotics appeared to create selection pressure for the emergence of several pathogens of major clinical importance including Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter species.

Culture-independent analysis revealed that administration of minocycline, clindamycin and ciprofloxacin, but not amoxicillin, had a profound effect on the oral and intestinal microbiotas. However, after one month, the oral microbiota was similar to that which existed prior to antibiotic administration. One month after the administration of amoxicillin or minocycline, the intestinal microbiota was similar to that found prior to antibiotic administration. In contrast, a return to pre-administration values took 4 months in the case of ciprofloxacin and between 4 months and one year for clindamycin.

Taken together, the ANTIRESDEV study demonstrated the new potential of some antibiotics to induce the emergence of resistant strains in healthy individuals. It also revealed their potential to disrupt the protective indigenous microbiotas at various body sites. This information could help clinicians to select the appropriate antibiotic to minimise both the emergence of antibiotic resistance and the disruption of the human microbiota.