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New Class of Adjuvants Enables Lower Dosing of Colistin Against Acinetobacter baumannii
journal contribution
posted on 2018-06-11, 00:00 authored by Bradley M. Minrovic, David Jung, Roberta J. Melander, Christian MelanderAntibiotic resistance
has become increasingly prevalent over the past few decades, and this
combined with a dearth in the development of new classes of antibiotics
to treat multidrug resistant Gram-negative infections has led to a
significant global health problem and the increased usage of colistin
as the last resort antibiotic. Colistin, however, presents dose dependent
toxicity in the clinic. One potential approach to combatting this
problem is the use of an antibiotic adjuvant, a compound that is nontoxic
to the bacteria that enhances the potency of colistin and ultimately
allows for reducing dosing. Herein, we present a new urea-containing
class of 2-aminoimidazole-based adjuvants that potentiates colistin
activity against colistin-sensitive Acinetobacter baumannii. Lead compounds enabled 1000-fold reduction in the minimum inhibitory
concentration of colistin in vitro and showed efficacy in a Galleria mellonella infection model, representing the first
step toward validating the potential of employing these adjuvants
to lower colistin dosage.
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Colistinresort antibiotic2- aminoimidazole-based adjuvantsLead compoundsNew Classurea-containing classGram-negative infectionscolistin dosagehealth problempotentiates colistin activityAdjuvants Enablesantibiotic adjuvantGalleria mellonella infection modelAcinetobacter baumannii Antibiotic resistancecolistin-sensitive Acinetobacter baumannii