143 Impact of sepsis and antibiotics on the microbiome Although less frequently studied, the long-term effects of antibiotics on the microbiome have been described [103, 104]. One study evaluated the effects of a 10-day course of ciprofloxacin on the microbiome over the course of a year with faecal samples collected a total of six times [104]. Based on culture-based techniques, a decrease in the number of gram-negative aerobes was observed, consistent with the results of the studies described above. However, when molecular techniques were utilized, the impact of ciprofloxacin on the microbiota occurred for the entire study period of 12 months [104]. Another study assessed the gut microbiome of three people via daily faecal sampling over a 10-month period in subjects who received two 5-day courses of ciprofloxacin separated by six months [103]. A notable change in the composition of the microbiota was observed in as little as 3 days after the start of the treatment course. Due to the aggressive faecal sampling, intersubject variability was captured and noted to be considerable. Importantly, up to 50% of the organisms that made up the gut microbiota prior to exposure were eliminated by the ciprofloxacin exposure. Despite having a stable microbiota composition by the eighth month of the study, each subject’s microbiota make-up was altered compared to the composition noted prior to any ciprofloxacin exposure. The authors also noted that this stable change is likely due to multiple disturbances, as one subject did have a complete recovery after the first treatment course. Conclusion The disruptions on the microbiome from early development are known to have lasting effects far into adulthood and can even shape the response to other medical interventions such as chemotherapy. The molecular data describing the faecal microbiota shifts suggest that outside of the changes after birth and inflammatory manifestations of gastrointestinal diseases such as Crohn’s disease, the significant changes observed with antimicrobial exposures was the only other situation where these discernable microbiota alterations are evident [105, 106]. Given the microbiome and sepsis are closely intertwined, future research should expand our knowledge regarding the importance of a homeostatic microbiome and its therapeutic potential. Although life-saving, antimicrobial interventions have significant effects on gut microbiota that weigh very little in the acute phase of treating fatal infections. Many studies, mostly using culture-based methods, have been done to help better understand the effects of specific antimicrobials on the faecal microbiota. However, the clinical translation of these studies is more challenging. Patients often receive multiple cocktails of therapies, are in an inflammatory state, and have confounding issues that make it difficult to delineate a direct association. Molecular-based methods may provide another level of granularity that is missed by culture-based methods. As a part of judicious stewardship, rapid technologies that identify organisms and their predicted response to antibiotic treatment (many of which do so directly from a specimen) can facilitate stewardship efforts. While it is not desirable to halt early intervention of antimicrobial therapy for patients with signs and symptoms of infection, efforts to support earlier targeted therapy should be incorporated to avoid the use of unnecessary exposure to these agents, as many of these agents disrupt the microbiome in as little as a single dose and can take up to several weeks for recovery. Much like cancer chemotherapy 6
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