Molecular Epidemiology, Antimicrobial Surveillance, and PK/PD Analysis to Guide the Treatment of Neisseria gonorrhoeae Infections.

Rodrigo Alonso,Aitor Artetxe,Javier Garaizar,Ilargi Martínez-Ballesteros,Andrés Canut,Amaia Aguirre-Quiñonero,Alicia Rodríguez-Gascón,Ainara Rodríguez-Achaerandio

doi:10.3390/pharmaceutics13101699

Abstract

The aim of this study was to apply molecular epidemiology, antimicrobial surveillance, and PK/PD analysis to guide the antimicrobial treatment of gonococci infections in a region of the north of Spain. Antibiotic susceptibility testing was performed on all isolates (2017 to 2019, n = 202). A subset of 35 isolates intermediate or resistant to at least two antimicrobials were selected to search for resistance genes and genotyping through WGS. By Monte Carlo simulation, we estimated the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the antimicrobials used to treat gonorrhea, both indicative of the probability of treatment success. In total, 2.0%, 6.4%, 5.4%, and 48.2% of the isolates were resistant to ceftriaxone, cefixime, azithromycin, and ciprofloxacin, respectively. Twenty sequence types were identified. Detected mutations were related to antibiotic resistance. PK/PD analysis showed high probability of treatment success of the cephalosporins. In conclusion, multiple populations of N. gonorrhoeae were identified. We can confirm that ceftriaxone (even at the lowest dose: 250 mg) and oral cefixime are good candidates to treat gonorrhea. For patients allergic to cephalosporins, ciprofloxacin should be only used if the MIC is known and ≤0.125 mg/L; this antimicrobial is not recommended for empirical treatment.

Highlights

Transmitted infections (STIs) are a serious global health problem [1]
Non-duplicated N. gonorrhoeae isolates from patients attending to the Emergency, Infectious Disease, and Primary Care services were included in the study
A total of 202 isolates of N. gonorrhoeae were collected in the study period (2017–2019)

Summary

Introduction

Transmitted infections (STIs) are a serious global health problem [1]. The prevalence of gonorrhea has increased significantly in recent years. Organization (WHO) estimates that there are 87 million new cases of gonorrhea each year [2]. The most frequently prescribed antibiotics for the treatment of gonorrhea have become less effective, in part due to the inexorable progression of gonococcal antimicrobial resistance [3,4]. In 2018, the WHO reported the expansion of multidrugresistant strains of N. gonorrhoeae worldwide [5]. In Europe, the Euro-GASP (depending on the European Centre for Disease Prevention and Control) provides important data at the European level on antimicrobial resistance, which are used to inform treatment guidelines [6]. The determination of antimicrobial susceptibility to identify isolates

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