The concern for development of new resistance to central lines coated with antimicrobial combinations was not validated by current clinical and experimental evidence, according to a review published in the Journal of Antimicrobial Chemotherapy-Antimicrobial Resistance.

Central line-associated bloodstream infections (CLABSIs) are one of the most persistent postinsertion adverse events and cause significant morbidity, mortality, and have a substantial economic impact. In order to reduce the risk for CLABSIs, central lines coated with antimicrobial agents were introduced; however, the use of these central lines introduces other risk including, irritation and inflammatory responses to the antimicrobial agents, breakthrough infections by virulent, resistant organisms, and prolonged exposure to the antimicrobial agents that could induce antimicrobial resistance.

Currently, there are 2 antimicrobial catheter treatments that comprise combinations of different agents that are widely used and recommended by the Centers for Disease Control and Prevention: chlorhexidine/silver sulfadiazine and minocycline/rifampicin. However, there remains a concern that antimicrobial medical devices may induce resistance. Therefore, this systemic review evaluated the evidence for induced antimicrobial resistance caused by exposure to antimicrobial medical devices.

In total, 44 publications that were published between 1983 and 2019 were included. These publications were selected from 4 electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature [CINAHL], and Scopus) and were studies regarding assessment of microbial resistance with use of medical devices containing chlorhexidine, minocycline, rifampicin, or combinations. Of the 44 included publications, 18 were in vitro studies, 3 were in vivo studies, and 24 were clinical studies. The development of new resistance, selection for tolerant organisms, and “no change in resistance” were assessed.


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A majority of studies (13 in vitro, 2 in vivo, and 20 clinical) reported no change in resistance after exposure to antimicrobial medical devices. Multiple studies reported the development of new resistance with the use of rifampicin as a single agent, which may be due to the fact that only a single point mutation in RNA polymerase is required for resistance to occur. In human studies, the development of new resistance against minocycline or chlorhexidine in devices was not confirmed, and although there were slight increases in minimum inhibitory concentration, they were not clinically relevant. The development of new resistance to minocycline or chlorhexidine single-agent devices was less likely because the expression of new proteins and acquisition of genes was required for new resistance to occur. Furthermore, the development of new resistance to double combinations of chlorhexidine/silver sulfadiazine or minocycline/rifampicin were not confirmed in any clinical trials.

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Overall, the review authors concluded that, “The risk of development of new resistance to these antimicrobial combinations appears more fear-based than substantiated by clinical and experimental evidence but warrants continued surveillance.”

Reference

Reitzel RA, Rosenblatt J, Gerges BZ, Jarjour A, Fernández-Cruz, Raad II. The potential for developing new antimicrobial resistance from the use of medical devices containing chlorhexidine, minocycline, rifampicin and their combinations: a systemic review. JAC Antimicrob Resist. 2020;2(1):dlaa002.