Emergence and Characterization of Neisseria gonorrhoeae Isolates With Decreased Susceptibilities to Ceftriaxone and Cefixime in Canada

Abstract

In Canada, N. gonorrhoeae isolates with decreased susceptibilities to third-generation cephalosporins have increased over the years. The alterations in penA, mtrR, and porB1b (penB alteration) are important determinants identified in these isolates. The most common STs identified among these Canadian isolates have also been reported worldwide.

Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

“…N. gonorrhoeae bacteria have developed resistance against sulfonamides, penicillins, tetracyclines, and fluoroquinolones (3,4), and current treatment options now include third-generation extended-spectrum cephalosporins (ESC), namely, cefixime (CFM) and ceftriaxone (CRO) (5). MIC creep has seen the modal MIC values rise between 2001 and 2010 in Canada from 0.016 g/ml to 0.125 g/ml and 0.063 g/ml for CFM and CRO, respectively (6). These results coincide with recent clinical reports of treatment failures to primarily CFM monotherapy in Canada (7,8) and additional global reports of high-level CRO MICs in isolates from Japan and Europe (9)(10)(11)(12)(13).…”

“…Of interest is the international epidemic clone ST1407 (and related NG-MAST types such as ST3150, ST3158, and ST4985) that has elevated ESC MICs and increased frequency of AZMresistant strains (6,52,60) that threaten the efficacy of currently recommended treatments. The ST1407 clone is thought to have originated in Japan and spread globally, with the first report of a ST1407 strain harboring a penA mosaic XXXIV allele identified in the United States in 2008 (10).…”

A 34-year-old man with urethral discharge

“…3 However, decreasing susceptibility to ceph a losporins among gonococcal isolates has recently been reported in the United States, East Asia and Europe, and is associated with treatment failure. 6,7 This pattern of resistance is seen more commonly in men who have sex with men. 6 A recent Canadian survey of 155 N. gonorrhoeae isolates from 2001 to 2010 found an increase over time in the modal minimum inhibitory concentrations to both cefixime and ceftriaxone.…”

“…6 A recent Canadian survey of 155 N. gonorrhoeae isolates from 2001 to 2010 found an increase over time in the modal minimum inhibitory concentrations to both cefixime and ceftriaxone. 7 In 2011, in response to these changing patterns of resistance, the Public Health Agency of Canada revised its treatment guidelines for gonococcal infection (Table 1). 3 Changes include the use of higher doses of cefixime (800 mg as a single dose) or the use of intramuscular ceftriaxone 250 mg. A single intramuscular dose of ceftriaxone plus oral azithromycin is the preferred treatment of gonococcal infection in men who have sex with men, as well as for pharyngeal infection (Table 1).…”

Using Crude Whole-Genome Assemblies of Neisseria gonorrhoeae as a Platform for Strain Analysis: Clonal Spread of Gonorrhea Infection in Saskatchewan, Canada

“…The MICs of gonococcal isolates to third-generation extended-spectrum cephalosporins (ESCs) (e.g., cefixime and ceftriaxone), the last of the single-dose treatment options for gonorrhea, have been increasing since the early 2000s (4). N. gonorrhoeae isolates with probable resistance (MICs, Ն25 g/ml) to third-generation cephalosporins, linked with treatment failures, have been reported in Japan, Europe, the United States, Canada, and South Africa (5)(6)(7)(8)(9)(10). This global trend in gonococcal resistance to antibiotics may result in the emergence of untreatable strains.…”