Clinical use of colistin induces cross-resistance to host antimicrobials in Acinetobacter baumannii. MBio 2013

ABSTRACT The alarming rise in antibiotic resistance has led to an increase in patient mortality and health care costs. This prob-lem is compounded by the absence of new antibiotics close to regulatory approval. Acinetobacter baumannii is a human patho-gen that causes infections primarily in patients in intensive care units (ICUs) and is highly antibiotic resistant. Colistin is one of the last-line antibiotics for treating A. baumannii infections; however, colistin-resistant strains are becoming increasingly com-mon. This cationic antibiotic attacks negatively charged bacterial membranes in a manner similar to that seen with cationic anti-microbials of the innate immune system.We therefore set out to determine if the increasing use of colistin, and emergence of colistin-resistant strains, is concomitant with the generation of cross-resistance to host cationic antimicrobials. We found that there is indeed a positive correlation between resistance to colistin and resistance to the host antimicrobials LL-37 and lysozyme among clinical isolates. Importantly, isolates obtained before and after treatment of individual patients demonstrated that colis-tin use correlated with increased resistance to cationic host antimicrobials. These data reveal the overlooked risk of inducing cross-resistance to host antimicrobials when treating patients with colistin as a last-line antibiotic