By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: A man in Las Vegas with gonorrhea was infected with the first ceftriaxone-resistant strain of Neisseria gonorrhoeae identified in the United States.

SOURCE: Picker MA, Knoblock RJ, Hansen H, et al. Notes from the Field: First case in the United States of Neisseria gonorrhoeae harboring emerging mosaic penA60 allele, conferring reduced susceptibility to cefixime and ceftriaxone. MMWR Morb Mortal Wkly Rep 2020;69:1876-1877.

An HIV-negative heterosexual man in Las Vegas received the standard treatment of ceftriaxone plus azithromycin for symptoms of urethritis in October 2019. He had been informed by his main sexual partner, who was staying with family in China, that she had been treated for gonorrhea.

Culture of his urethral discharge performed at the Southern Nevada Public Health Laboratory of the Southern Nevada Health District (SNHD) yielded Neisseria gonorrheae. As a participant in the Gonococcal Isolate Surveillance Project (GISP), SNHD regularly sends a selection of isolates to a laboratory member of the Centers for Disease Control and Prevention’s (CDC) Antibiotic Resistance Laboratory Network.

The patient’s isolate was among those sent and, although susceptible to azithromycin, was found by the laboratory to have reduced susceptibility to cefixime and to ceftriaxone, with minimum inhibitory concentrations (MICs) of 2.0 mcg/mL and 1.0 mcg/mL, respectively. The Clinical & Laboratory Standards Institute (CLSI) breakpoint for susceptibility for both is ≤ 0.25 mcg/mL. The CDC laboratory identified the presence in the isolate of penA60, which encodes a mosaic PBP2 that accounts for the reduced susceptibility to these cephalosporins.

One of two casual partners was located and was negative by nucleic acid amplification test (NAAT) and culture for N. gonorrhoeae.

SNHD provided the CDC with all 257 N. gonorrhoeae NAAT-positive swabs from September 2019 to November 2019, but none were found to carry penA60. All of the approximately 5,500 N. gonorrhoeae culture nationwide isolates submitted to GISP from January 2019 to December 2019 had cefixime and ceftriaxone MICs lower than did the Nevada isolate.

COMMENTARY

GISP began monitoring antimicrobial susceptibilities in 1986. The ceftriaxone MIC of 1.0 mcg/mL in this case was the highest they had ever detected in N. gonorrhoeae in the United States. Fortunately, there has been no evidence of spread in southern Nevada, and there have been no recorded failures of treatment in the United States with the use of the recommended regimen of ceftriaxone plus azithromycin. The Las Vegas patient was cured with this regimen, presumably because his isolate remained susceptible to azithromycin.

Reduced susceptibility to ceftriaxone or to azithromycin has been reported in a number of countries. Combined resistance is even rarer, although it has been identified in, e.g., China.1 In that case, a ceftriaxone-resistant FC428 clonal strain carrying penA60 had acquired azithromycin resistance. The penA60 allele was first identified in Japan in 2016 and it has taken four years for its first identification in the United States. Although to date it been recognized only in a single isolate, its presence is a harbinger of what is likely to come — increasing cephalosporin resistance of N. gonorrhoeae.

REFERENCE

  1. Yuan Q, Li Y, Xiu L, et al. Identification of multidrug-resistant Neisseria gonorrhoeae isolates with combined resistance to both ceftriaxone and azithromycin, China, 2017-2018. Emerg Microbes Infect 2019;8:1546-1549.