Rationale for a Neisseria gonorrhoeae Susceptible-only Interpretive Breakpoint for Azithromycin

• Type of Material: Article
• Authors: Ellen N. Kersh, Centers for Disease Control and Prevention; Vanessa Allen, Public Health Ontario; Eric Ransom, Association of Public Health Laboratories; Matthew Schmerer, Centers for Disease Control and Prevention; Sancta St. Cyr, Centers for Disease Control and Prevention; Kimberly Workowski, Emory University; Hillard Weinstock, Centers for Disease Control and Prevention; Jean Patel, Centers for Disease Control and Prevention; Mary Jane Ferraro, Harvard University
• Language: English
• Date: 2020-03-01
• Publisher: Oxford University Press Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Published by Oxford University Press for the Infectious Diseases Society of America 2019.
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciz292
• Title of Journal or Parent Work: Clinical Infectious Diseases
• Volume: 70
• Issue: 5
• Start Page: 798
• End Page: 804
• Grant/Funding Information: APHL (Association of Public Health Laboratories) (ER), and by the Massachusetts General Hospital (MJF).; This work was supported by CDC (Centers for Disease Control and Prevention) and in part made possible through support from CDC’s Advanced Molecular Detection (AMD) and Combating Antibiotic Resistant Bacteria (CARB) programs (ENK, MS, SSC, HW, JP)
• Keywords: Science & Technology; Pharmacokinetics; Immunology; No longer; Infectious Diseases; Genomic epidemiology; Surveillance; Infection; antimicrobial resistance; breakpoints; Neisseria gonorrhoeae; Efficacy; Resistance; Uncomplicated gonorrhea; United States; Microbiology; Life Sciences & Biomedicine; Diseases treatment guidelines; interpretive criteria
• Research Categories: Health Sciences, Immunology; Health Sciences, Pharmacology; Biology, Genetics; Biology, Microbiology

Abstract

BACKGROUND: Azithromycin (AZI) is recommended with Ceftriaxone (CRO) for treatment of uncomplicated gonococcal urethritis and cervicitis in the United States (US) and an AZI susceptibility breakpoint is needed. Neither the FDA (Food and Drug Administration) nor the CLSI (Clinical and Laboratory Standards Institute) has set interpretive breakpoints for AZI susceptibility. As a result, AZI antimicrobial susceptibility testing (AST) cannot be interpreted using recognized standards. This has contributed to increasingly unavailable clinical laboratory AST, although gonorrhea is on the rise with over 550,000 US gonorrhea cases reported to the CDC in 2017, the highest number of cases since 1991. METHODS: This document summarizes the rationale data reviewed by the CLSI in June 2018. RESULTS: CLSI decided to set a susceptible only interpretive breakpoint at the MIC (Minimum Inhibitory Concentration) of and below 1 μg/ml. This is also the epidemiological cut-off value (ECV), i.e., the end of the wild-type susceptibility distribution. This breakpoint presumes that AZI (1 gm single dose) is used in an approved regimen that includes an additional antimicrobial agent (i.e. CRO 250 mg, intramuscular [IM] single dose). CONCLUSION: Having a breakpoint can improve patient care and surveillance, and allow future development and FDA regulatory approval of modernized AST to guide treatment. The breakpoint coincides with a EUCAST (European Committee on AST) decision to remove previously established, differing AZI breakpoints and use the ECV as guidance for testing. The CLSI breakpoint is now the recognized standard that defines AZI susceptibility for gonococcal infections.