Background Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC <= 0.06 mu g/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC <= 0.25 mu g/mL. Conclusions Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials. A single genetic marker, gyrA codon 91, correctly predicted ciprofloxacin susceptibility in a global collection of Neisseria gonorrhoeae isolates with genome sequences and phenotypic antimicrobial susceptibility data. For other antimicrobials, multiple molecular markers are needed to accurately predict antimicrobial susceptibility.
[1]Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[2]Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.
[3]Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[4]Univ Washington, Dept Allergy & Infect Dis, Seattle, WA 98195 USA.
[5]Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA.
[6]Social & Sci Syst, Silver Spring, MD USA.
[7]Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA.
[8]Univ Saskatchewan, Dept Biochem Microbiol & Immunol, Saskatoon, SK, Canada.
[9]Natl Hosp Venereol & Dermatol, Dept Microbiol Mycol & Parasitol, Hanoi, Vietnam.
[10]Hanoi Med Univ, Dept Clin Microbiol & Parasitol, Hanoi, Vietnam.
[11]Hanoi Med Univ, Dept Dermatol & Venereol, Hanoi, Vietnam.
[12]Lab Nacl Dr Defillo, Santo Domingo, Dominican Rep.
[13]Univ KwaZulu Natal Durban, Durban, South Africa.
[14]Natl Hlth Lab Serv, Johannesburg, South Africa.
[15]Ctr AIDS Programme Res South Afr CAPRISA, Durban, South Africa.
[16]WHO, Geneva, Switzerland.
[17]Pentara Corp, Salt Lake City, UT USA.
[18]Univ Southern Calif, Keck Sch Med, Dept Populat & Publ Hlth Sci, Los Angeles, CA 90007 USA.
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