Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance.

Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Bacteria that are resistant to antibiotics are a growing global health crisis. One type of antibiotic resistance arises when certain bacteria that can produce enzymes called extended-spectrum beta-lactamases (or ESBLs for short) become more common in the gut. These enzymes stop important antibiotics, like penicillin, from working. However, exactly which antibiotics and treatment durations contribute to the emergence of this antibiotic resistance remain unknown. Now, Niehus et al. find certain antibiotics that are associated with an increase in the number of gut bacteria carrying antibiotic resistance genes for ESBL enzymes. First, rectal swabs collected from 133 patients from three European hospitals were analysed to measure the total gut bacteria and the number of genes for ESBL enzymes. These samples had been collected at several time points including when the patient was first admitted to hospital, then every two to three days during their stay, and finally when they were discharged. Combining the analysis of the samples with details of the patients’ charts showed that treatment with two antibiotics: cefuroxime and ceftriaxone, was linked to an increase in ESBL genes in the gut bacteria. Other antibiotics – namely, meropenem, piperacillin-tazobactam and oral ciprofloxacin – were associated with a decrease in the number of bacteria with ESBL genes. Niehus et al. then performed further analysis to see if different treatment regimens affected how long patients were carrying gut bacteria with ESBL genes. This predicted that a longer course of meropenem, 14 days rather than 5 days, would shorten the length of time patients carried ESBL-resistant bacteria in their guts by 70%, although this effect will likely depend on the location of the hospital and the local prevalence of other types of antibiotic resistance. This analysis reveals new details about how antibiotic treatment can affect ESBL resistance genes. More studies are needed to understand how antibiotics affect other antibiotic resistance genes and how resistant bacteria spread. This will help scientists understand how much specific antibiotic regimens contribute to antibiotic resistance. It may also help scientists develop new antibiotic treatment strategies that reduce antibiotic resistance.

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© 2020, Niehus et al.

Déclaration de conflit d'intérêts

RN, Ev, YM, AT, CL, YC, HG, ET, BC, LP, SM No competing interests declared, BC Reviewing Editor, eLife