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Antimicrob Agents Chemother. 2018 Jul 27;62(8). pii: e00689-18. doi: 10.1128/AAC.00689-18. Print 2018 Aug.

Activity of RX-04 Pyrrolocytosine Protein Synthesis Inhibitors against Multidrug-Resistant Gram-Negative Bacteria.

Author information

1
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, United Kingdom.
2
Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, United Kingdom d.livermore@uea.ac.uk.
3
Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.

Abstract

Pyrrolocytosines RX-04A to -D are designed to bind to the bacterial 50S ribosomal subunit differently from currently used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A-the most active analog-inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa at 0.5 to 4 μg/ml, with no MICs of >8 μg/ml. MICs for multidrug-resistant (MDR) carbapenemase producers were up to 2-fold higher than those for control strains; values were highest for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs.

KEYWORDS:

50S ribosomal subunit; blasticidin; mcr-1; pyrrolocytosine

PMID:
29914946
PMCID:
PMC6105809
[Available on 2019-01-27]
DOI:
10.1128/AAC.00689-18

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