New Insight into Rapid Evolution of AMR in Patients Calls for Shift in Diagnostic Testing Approaches

This could lead to more effective preventative strategies against AMR infections in susceptible individuals. Contrary to the conventional belief that infection typically occurs due to a single strain of bacteria that develops resistance through new genetic mutations, the study suggests that patients often get co-infected by multiple clones of pathogens. In these cases, resistance arises from the selection of already resistant clones rather than new mutations.

In the study led by the University of Oxford (Oxford, UK), the researchers utilized an innovative technique to examine genetic alterations and antibiotic resistance in Pseudomonas aeruginosa, a common hospital-acquired bacterium, particularly among immunocompromised and severely ill individuals. Samples were taken from 35 patients in intensive care units across 12 European hospitals. Approximately two-thirds of the patients were found to be infected by a single strain of Pseudomonas, in some of which AMR developed due to new mutations, as traditionally believed. However, in a surprising revelation, one-third of patients were infected by multiple strains of the bacteria. It was observed that patients with mixed-strain infections exhibited a roughly 20% higher increase in resistance when exposed to antibiotic treatment compared to those with single-strain infections. The spike in resistance was primarily attributed to the selection of pre-existing resistant strains that already existed prior to antibiotic therapy.

Interestingly, the study also found that such resistance could decline rapidly under certain conditions. When samples from single-strain and mixed-strain infections were cultured without antibiotics, the growth rate of AMR strains was slower compared to non-AMR strains. This supports the idea that AMR genes carry fitness trade-offs and are negatively selected when antibiotics are absent. This effect was more pronounced in mixed strain populations, suggesting that a diverse bacterial environment could contribute to resistance loss in the absence of antibiotics.

The findings suggest that strategies focusing on controlling bacterial transmission among patients, such as improved sanitation and infection control measures, might be more effective against AMR compared to efforts to prevent new resistance mutations. This is particularly important in settings with a high infection rate, like immunocompromised individuals. Additionally, the study calls for a shift in clinical testing, emphasizing the importance of considering pathogen strain diversity instead of assuming a singular strain during infection assessments. This approach could aid in making more accurate predictions about antibiotic treatment effectiveness and improve patient outcomes, similar to the use of diversity measurements in cancer cell populations to predict chemotherapy success.

"The diagnostic methods employed for assessing antibiotic resistance in patient samples have undergone slow evolution over time, and our findings highlight the significance of developing new diagnostic approaches that facilitate the assessment of pathogen population diversity in patient samples," said Professor Craig Maclean, the lead researcher from the University of Oxford's Department of Biology.

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