FQ, especially later generation ones, have a very wide spectrum of activity. Their excellent bioavailability and seemingly favourable tolerability led to widespread use and, like other antimicrobials, misuse. Not surprisingly resistance predictably followed. Resistance is mediated by both chromosomal and plasmid gene mutations with resultant altered DNA targets and/or reduced drug permeation. Unfortunately, clinical laboratories are challenged to detect low level resistance which is associated with poorer clinical outcomes. It also appears that continued treatment of bacteria with low level FQ resistance promotes the development of high level FQ resistance.
Another ominous development associated with quinolone use has been the occurrence of some serious adverse reactions leading to the removal of several agents from the market. Black box warnings about the risks of serious side effects accompany the agents that remain on the market. The FDA took the unusual step of advising that serious side effects associated with FQ generally outweigh the benefits for treating sinusitis, AECB and uncomplicated urinary tract infections in patients who have other treatment options.
Hopefully, emerging antimicrobial stewardship programs will improve FQ utilization and thereby preserve and protect this class of antimicrobials. It also hoped that research and development within this class will yield new FQ with better safety profiles and with expanded spectrum against the emerging multi-drug resistant microorganisms.
We would like to thank Dr. John Galbraith for his contribution to our newsletter.
Dr. Galbraith is a microbiologist and infectious diseases specialist with the Vancouver Island Health Authority, Victoria, BC; and a member of the Clinical Microbiology Proficiency Testing (CMPT) Microbiology Subcommittee.
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