About AMR: Antimicrobial drug selection has a ripple effect on multidrug-resistant infections

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A recent study published in PNAS modelled the sequence of events that increases the risk of colonization and infection with multidrug-resistant (MDR) bacteria. Using longitudinal surveillance data and diagnostic records from a patient population, the modeling reveals that antimicrobial use influences subsequent colonization and infection with bacteria that may be resistant to unrelated classes of antibiotics, a finding with important implications for the improvement of antimicrobial stewardship programs.

Antimicrobial stewardship programs are one strategy to help limit the emergence of MDR bacteria in a hospital setting. These programs include limiting the use of antimicrobials associated with a high risk of increasing the prevalence of corresponding resistant bacteria, in favour of using antimicrobials with a lower risk of promoting drug-resistant infections. Yet, this drug-centric strategy does not consider the consequence of drug selection on the overall prevalence of colonization and infection with MDR bacteria.

In a recent study published in PNAS, Wang and colleagues reveal the secondary consequences of drug selection on the overall colonization of and infection with MDR bacteria. The authors analyzed longitudinal surveillance data collected from patients that were catheterized in a long-term care facility, and asked whether antimicrobial use influences the risk for subsequent infection with unrelated MDR bacteria.

The authors demonstrated that antimicrobial treatment influenced the acquisition of unrelated MDR bacteria, indicating there are consequences of antimicrobial treatment that extend beyond the primary consequence – emergence of bacteria with resistance related to the target specificity of the antimicrobial. For example, multiple antimicrobial classes were associated with increased vancomycin-resistant E. coli (VRE) acquisition, and a single antimicrobial class increased the risk of acquiring multiple unrelated MDR bacteria.

The authors also found that colonization with some MDR bacteria increased the risk of secondary colonization with MDR bacteria, indicating that there are microbial factors influencing the prevalence of MDR colonization. For example, colonization with Proteus mirabilis increased the risk of acquiring Acetobacter baumanii, methicillin-resistant S. aureus (MRSA), and VRE.

Next, the authors analyzed whether these factors influenced the occurrence of catheter-associated urinary-tract infections (CAUTIs). Unexpectedly, pre-existing monocolonization of the MDR bacteria that was detected in the urine was not associated with an increased risk of infection. Rather, co-colonization with the MDR bacteria detected in the urine and a second MDR bacteria increased the risk for CAUTIs, indicating that microbial interactions influence the prevalence of MDR infections.

The interactions identified in this study reveal sequences of events that influence the occurrence of MDR colonization and infection. The networks revealed in the study suggest that antimicrobial treatment can increase the risk for colonization with unrelated MDR bacteria, which can then increase the risk for colonization with additional MDR bacteria and in turn increase the risk for an MDR infection. Understanding the factors that influence these sequences of events has the potential to improve antimicrobial stewardship strategies and reduce the prevalence of MDR infections.

Sources: Wang J, Foxman B, Mody L, Snitkin ES. Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms. Proc. Natl Acad. Sci. USA 114(39), 10467–10472 (2017)

About the author

Julie Kaiser is a Ph.D. candidate in Microbiology at the University of Western Ontario in London, Canada. Her research interests range from the impact of microbial communities on human health, to the molecular basis of drug-resistant bacterial infections. Julie enjoys sharing her love for the microbial world through science communication and is the author of Microbiology for Dummies. Follow her on twitter at @jukais.

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