Antibiotics and antimicrobial resistance. The role of gut microbiota

Although the phenomenon of antibiotic resistance can be attributed to many factors, there is a well-established relationship between antibiotic prescribing practices and the emergence of antimicrobial resistant pathogens. It is well know that selective pressure from antibiotics accelerates the spread of resistant bacteria.

Knowledge of the gut microbiota, an extraordinarily complex community of organisms, has improved dramatically in recent years.

The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance genes to potential pathogenic bacteria.

Changes in the composition of the gut flora, due in particular to antibiotics, can happen silently, leading to the selection of resistant bacteria and Candida species. The resistant organisms may remain for months in the gut of the carrier without causing any symptoms or translocate through the gut epithelium, induce healthcare-associated infections or undergo cross-transmission to other individuals.

The indigenous bacteria of the colon provide an important host-defense mechanism by inhibiting colonization by potentially pathogenic microorganisms. Under normal conditions, the gut “receives” a large amount of bacteria from the hands, pharyngeal and nasal secretions, water, food, and beverages. This defense mechanism can be applied to the prevention of overgrowth by indigenous potential pathogens and the inhibition of colonization by exogenously introduced organisms. Escherichia coli, a member of the indigenous colonic microflora, is normally maintained at relatively low population densities by the predominant anaerobic microflora.

While, the indigenous intestinal microbiota provides an important host-defense mechanism by preventing colonization of potentially pathogenic microorganisms, however, the intestinal tract is also an important reservoir for antibiotic-resistant bacteria. Evidence is accumulating to support the hypothesis that intestinal bacteria not only exchange resistance genes among themselves but might also interact with bacteria that are passing through the colon, causing these bacteria to acquire and transmit antibiotic resistance genes.

Antibiotics exert undue selective pressure on bacteria in the intestine. Most antibiotics exert a dramatically disruptive effect on the gut microbiome. Antibiotics very rapidly kill susceptible bacteria, including E. coli and the chiefly anaerobic micro-organisms responsible for the barrier function. This favors bacteria within the intestine that are already resistant, have become resistant through mutation or through the acquisition of exogenous DNA (e.g. plasmids) from cells colonized in, or passing through, the intestinal tract. Antibiotics can select gut micro-organisms initially present in very small amounts, such as Clostridium difficile, ESBL-producing E. coli, P. aeruginosa, Candida spp, or even Acinetobacter spp.

The gut epithelium is very fragile and can be profoundly altered in the most severely ill ICU patients. An increase in gut permeability allows the translocation of micro-organisms into the bloodstream with bacteraemia or candidaemia. Endotoxins and other toxins can also cross the gut barrier. Selection of resistant micro-organisms may occur in the gut even after successful treatment of the primary focus of infection. During broad-spectrum antibiotic therapy, the gut may contain high concentrations of most of the resistant Gram-negative and –positive bacteria. Most of the time, these organisms do not result in clinical symptoms and their presence is therefore overlooked. In the most severely ill patients (often in the ICU) some of the gut micro-organisms can induce healthcare-associated infections.

Finally, the risk of dissemination of multi-resistant bacteria coming from the gut is probably very high, since bacteria are found in high concentrations in the rectum. The very low compliance with hand hygiene rules in most hospitals worldwide is a major obstacle to preventing the cross-transmission of resistant and susceptible micro-organisms.