Seven Years of Culture Collection of Neisseria gonorrhoeae: Antimicrobial Resistance and Molecular Epidemiology

Abstract

The emergence of Neisseria gonorrhoeae isolates displaying resistance to antimicrobials, in particular to ceftriaxone monotherapy or ceftriaxone plus azithromycin, represents a global public health concern. This study aimed to analyze the trend of antimicrobial resistance in a 7-year isolate collection retrospective analysis in Italy. Molecular typing on a subsample of gonococci was also included. A total of 1,810 culture-positive gonorrhea cases, collected from 2013 to 2019, were investigated by antimicrobial susceptibility, using gradient diffusion method, and by the N. gonorrhoeae multiantigen sequence typing (NG-MAST). The majority of infections occurred among men with urogenital infections and 57.9% of male patients were men who have sex with men. Overall, the cefixime resistance remained stable during the time. An increase of azithromycin resistance was observed until 2018 (26.5%) with a slight decrease in the last year. In 2019, gonococci showing azithromycin minimum inhibitory concentration above the EUCAST epidemiological cutoff value (ECOFF) accounted for 9.9%. Ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae (PPNG) percentages increased reaching 79.1% and 18.7% in 2019, respectively. The most common sequence types identified were 5,441, 1,407, 6,360, and 5,624. The predominant genogroup (G) was the 1,407; moreover, a new genogroup G13070 was also detected. A variation in the antimicrobial resistance rates and high genetic variability were observed in this study. The main phenotypic and genotypic characteristics of N. gonorrhoeae isolates were described to monitor the spread of drug-resistant gonorrhea.

Keywords: N. gonorrhoeae multiantigen sequence typing (NG-MAST); antimicrobial resistance; genogroup; gonorrhea.

FIG. 1.

Percentages of resistance of cefixime, azithromycin, ciprofloxacin, and PPNG, from 2013 to 2019. PPNG, penicillinase-producing Neisseria gonorrhoeae.

FIG. 2.

(A) Number of STs identified among N. gonorrhoeae collected from 2013 to 2019 (only ST comprising at least four gonococci are reported in the Figure). (B) Genogroups (G) among N. gonorrhoeae isolates by year. ST, sequence type.

FIG. 3.

Phylogenetic tree based on the porB and tbpB sequences (n = 144) concatenated of each NG-MAST type, (excluding the singletone STs unless they belong to a genogroup), identified among isolate collected from 2013 to 2019 in Italy. The tree was built using the maximum likelihood method (kimura 2-parameter), and bootstrapped with 100 repetitions. * = presence of HLR for azithromycin. Year, genogroup and ciprofloxacin, azithromycin, and cefixime resistance are indicated. HLR, high level of resistance; NG-MAST, Neisseria gonorrhoeae multiantigen sequence typing.