Evidence for Clonally Associated Increasing Rates of Azithromycin Resistant Neisseria gonorrhoeae in Rio de Janeiro, Brazil.

Késia T Barros Dos Santos,Sergio E L Fracalanzza,Livia H Justo-Da-Silva,Raphael C Medeiros,Raquel R Bonelli,Larissa B Skaf,Maria Cristina A Caniné,Ronaldo Da S Francisco Junior

doi:10.1155/2019/3180580

Abstract

Azithromycin is one of the drugs used in the combined therapy for syndromic treatment of gonorrhoea in many countries, including Brazil. Our research group, which receives isolates from clinical laboratories since 2006, has detected, after 2016, a tendency of rising rates of azithromycin resistance, with isolates showing higher minimal inhibitory concentrations (MICs) than those previously reported in this country. In this study, we report the susceptibility to azithromycin of 93 N. gonorrhoeae isolates obtained between 2014 and 2017. Strains with MIC ≥2 μg/mL were characterized according to azithromycin resistance mechanisms and strain typing. Results indicate that azithromycin resistance has emerged in all these years in unrelated MLST-STs, but after 2016 a clonal complex connected with ST1901 has been more frequently detected, grouping isolates with MIC varying from 2 to 64 μg/mL, with DelA mutations at the mtrR promoter region associated or not with mutations at rrl alleles. High rates of azithromycin resistance may compromise the use of this drug in the combined therapy with ceftriaxone. Inclusion of Rio de Janeiro in the Brazilian gonococcal surveillance program is important to evaluate if this data indicates an epidemiological phenomenon in the country.

Highlights

Neisseria gonorrhoeae, the agent of gonorrhoea, has come to world attention due to a high capacity to become resistant to antimicrobial agents [1, 2]
We describe the increase of azithromycin resistance rate and azithromycin minimal inhibitory concentrations (MICs) among N. gonorrhoeae isolates received by our research laboratory from 2014 to 2017
We evaluated the azithromycin susceptibility of 93 N. gonorrhoeae isolates obtained in Rio de Janeiro between 2014 and 2017 and characterized the genetic diversity and main resistance mechanisms of isolates with MIC ≥2 μg/mL for this antimicrobial agent

Summary

Introduction

The agent of gonorrhoea, has come to world attention due to a high capacity to become resistant to antimicrobial agents [1, 2]. Empiric treatment for gonorrhoea is based on ceftriaxone combined with azithromycin in most countries [3,4,5]. Combined therapy is a strategy to mitigate the dissemination of resistant strains to any of the drugs used [6]. In many countries, including Brazil, monotherapy with 2 g azithromycin is used to treat gonorrhoea in patients allergic to beta lactams [3, 7]. The minimal inhibitory concentration (MIC) breakpoint that defines azithromycin resistance in N. gonorrhoeae is not under consensus. Whereas EUCAST classifies isolates with MIC >0.5 μg/mL as resistant to azithromycin, CLSI indicates the epidemiological cutoff value (ECV) ≥2 μg/mL as an alert value to recognize isolates carrying resistance mechanisms to this drug [8, 9]. Mutations in one to four alleles of rrl, which encodes the target of azithromycin 23S rRNA, usually exert greater impact in the azithromycin MIC, in some cases reaching 256 μg/mL [10,11,12]

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Results

Discussion

Conclusion