Emergence of Increased Azithromycin Resistance During Unsuccessful Treatment of Neisseria gonorrhoeae Infection With Azithromycin (Portland, OR, 2011)

Abstract

We describe the emergence of an azithromycin-resistant Neisseria gonorrhoeae variant in a man from Portland, Oregon, during sole treatment with 2 g azithromycin. This report highlights the ease with which gonococcal macrolide resistance can emerge, the threat of multidrug resistant N. gonorrhoeae, and the need for adherence to Centers for Disease Control and Prevention treatment guidelines.

Analysis of Neisseria gonorrhoeae Azithromycin Susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013

“…It is possible that we overestimated the capacity of N. gonorrhoeae to acquire azithromycin resistance. Apart from three case reports that demonstrated azithromycin MIC increases after treatment with azithromycin monotherapy (15,23,24) and studies that selected for macrolide resistance using erythromycin (25, 26), we are not aware of published data on mutational frequency with in vitro azithromycin exposure or on the stability of the mutants. Related to this, reduced azithromycin susceptibility may be acquired at a fitness cost that limits transmissibility, as appears to be the case with Streptococcus pneumoniae and Campylobacter jejuni (27)(28)(29).…”

“…Isolates with high azithromycin MICs have been sporadically detected in the United States, and resistant strains have been detected following azithromycin monotherapy in the United States and elsewhere, suggesting the possibility of within-host selection for azithromycin resistance (15,23,24,33). Thus, gonorrhea treatment with azithromycin monotherapy is discouraged.…”

“…Two mechanisms have been commonly implicated in gonococcal reduced azithromycin susceptibility: overexpression of an efflux pump due to mtrR-coding region mutations (12)(13)(14)(15) and decreased antimicrobial affinity due to mutations in genes encoding the 23S ribosomal subunit (15,16). Because of the importance of azithromycin in the currently recommended treatment regimen and the risk of macrolide resistance, careful monitoring of azithromycin susceptibility trends is important.…”

Failure of Azithromycin 2.0 g in the Treatment of Gonococcal Urethritis Caused by High-Level Resistance in California

“…Antimicrobial susceptibility testing was also conducted using the Clinical and Laboratory Standards Institute–recommended agar dilution method 1 and 7 CDC quality control N. gonorrhoeae strains, as described previously. 2 CA-1461 displayed high-level resistance to AZM (>2048 μg/mL), intermediate susceptibility to penicillin (0.25 μg/mL) and tetracycline (1.0 μg/mL), and susceptibility to spectinomycin (16 μg/mL), gentamicin (4 μg/mL), cefixime (0.015 μg/mL), ceftriaxone (0.008 μg/mL), and ciprofloxacin (0.015 μg/mL). Minimum inhibitory concentrations for all antimicrobials were interpreted using the 2014 Clinical and Laboratory Standards Institute criteria, 3 with the exception of AZM 4 and gentamicin 5 where the referenced criteria were used.…”

“…CA-1461 was characterized by N. gonorrhoeae multiantigen sequence typing 6 and screened for AZM resistance–associated mutations by sequencing the peptidyltransferase region of domain Vof the 23S rRNA rrl gene, 7 the mtrR promoter region, and the mtrR coding region, 2 as described previously. In addition, polymerase chain reaction assays were performed to detect the presence of the efflux pump mef (A) gene and methylase-encoding erm (A), erm (B), and erm (C), as described previously.…”