Molecular characterization of a ceftriaxone-resistant Neisseria gonorrhoeae strain found in Switzerland: a case report

Abstract

Background The resistance of Neisseria gonorrhoeae to ceftriaxone is unusual in Switzerland. The underlying genotype responsible for resistance is suspected to be novel. Generally, resistance in Neisseria gonorrhoeae (Ng) involves a comprehensive set of genes with many different mutations leading to resistance to different β-lactams and fluoroquinolones. Case presentation A patient had a positive result from specific PCR for Ng. We routinely culture all clinical specimens with a positive NG-PCR. In this particular case, we isolated a strain with resistance to ceftriaxone in Switzerland. A total of seven different genes (penA, ponA, porinB, mtr, gyrA, parC, 23S rRNA gene) in this strain were partially sequenced for comparison with phenotypic susceptibility testing. Interestingly, two different mutations in the porinB gene were observed, and data on this gene are limited. Information on the identified allele type of the penA gene is very limited as well. Three different mutations of parC and gyrA that correlate with ciprofloxacin resistance were found. The combination of ceftriaxone and ciprofloxacin resistance makes an appropriate treatment difficult to obtain due to multidrug resistance. Conclusion The combined results for all genes show the appearance of new mutations in central Europe either due to worldwide spread or the emergence of new genetic combinations of mutations.

Rapid Molecular Phenotypic Antimicrobial Susceptibility Test for Neisseria gonorrhoeae Based on Propidium Monoazide Viability PCR

“…16,22 Relying on a single resistance marker can easily blindside complex and evolving resistance mechanisms. 14 The use of high-throughput genomic analysis, such as whole genome sequencing (WGS), has been suggested as a suitable alternative to address this limitation. However, WGS could only be used to detect known resistance determinants and cannot reliably provide the minimum inhibitory concentration necessary for surveillance purposes.…”

“…In the era where NG diagnosis is predominately made via nucleic-acid-based molecular testing (e.g., PCR), standard phenotypic AST which is time-consuming (24–48 h) and laborious and requires viable cultures is not routinely performed. Methods that rely on detecting a single mutation as a marker of resistance have been explored; however, ongoing monitoring of resistance patterns is required. , Relying on a single resistance marker can easily blindside complex and evolving resistance mechanisms . The use of high-throughput genomic analysis, such as whole genome sequencing (WGS), has been suggested as a suitable alternative to address this limitation.…”

Rapid molecular phenotypic antimicrobial susceptibility test forNeisseria gonorrhoeaebased on propidium monoazide viability PCR

“…Methods that rely on detecting a single mutation as a marker of resistance 5 m T y, tic ce ng ot ce have been explored, however ongoing monitoring of resistance patterns is required 15,20 . Relying on a single resistance marker can easily blindside complex and evolving resistance mechanisms 13 . The use of high-throughput genomic analysis, such as whole genome sequencing (WGS), has been suggested as a suitable alternative to address this limitation.…”

“…Both the CDC and WHO have labelled NG as a top-tier AMR threat. Increase in ceftriaxone resistance has been reported in Asia, Australia, and the UK 13,14 .…”

“…Both the CDC and WHO have labelled NG as a top-tier AMR threat. Increase in ceftriaxone resistance has been reported in Asia, Australia, and the UK 13,14 . With only ceftriaxone as the first and last line NG therapy, rapid and reliable susceptibility test is needed to monitor emergence of NG strains with decreased susceptibility to ceftriaxone and anticipate potential outbreaks.…”