Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae

References

• Newman L, Rowley J, Vander Hoorn S, et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One. 2015;10(12):e0143304.
   PubMed Web of Science ®Google Scholar
• Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev. 2014;27(3):587–613.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva (Switzerland): World Health Organization; 2012.
   Google Scholar
• World Health Organization. WHO guidelines for the treatment of Neisseria gonorrhoeae. Geneva (Switzerland): World Health Organization; 2016.
   Google Scholar
• Lindbäck E, Rahman M, Jalal S, et al. Mutations in gyrA, gyrB, parC, and parE in quinolone-resistant strains of Neisseria gonorrhoeae. APMIS. 2002;110(9):651–657.
   PubMed Web of Science ®Google Scholar
• Trees DL, Sandul AL, Peto-Mesola V, et al. Alterations within the quinolone resistance-determining regions of GyrA and ParC of Neisseria gonorrhoeae isolated in the Far East and the United States. Int J Antimicrob Agents. 1999;12(4):325–332.
   PubMed Web of Science ®Google Scholar
• Ng LK, Martin I, Liu G, et al. Mutation in 23S rRNA associated with macrolide resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2002;46(9):3020–3025.
   PubMed Web of Science ®Google Scholar
• Chisholm SA, Dave J, Ison CA. High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. Antimicrob Agents Chemother. 2010;54(9):3812–3816.
   PubMed Web of Science ®Google Scholar
• Unemo M, Golparian D, Hellmark B. First three Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Sweden: a threat to currently available dual-antimicrobial regimens for treatment of gonorrhea? Antimicrob Agents Chemother. 2014;58(1):624–625.
   PubMed Web of Science ®Google Scholar
• Roberts MC, Chung WO, Roe D, et al. Erythromycin-resistant Neisseria gonorrhoeae and oral commensal Neisseria spp. carry known rRNA methylase genes. Antimicrob Agents Chemother. 1999;43(6):1367–1372.
   PubMed Web of Science ®Google Scholar
• Cousin S Jr., Whittington WL, Roberts MC. Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between 1940 and 1987. Antimicrob Agents Chemother. 2003;47(12):3877–3880.
   PubMed Web of Science ®Google Scholar
• Lindberg R, Fredlund H, Nicholas R, et al. Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime and ceftriaxone: association with genetic polymorphisms in penA, mtrR, porB1b, and ponA. Antimicrob Agents Chemother. 2007;51(6):2117–2122.
   PubMed Web of Science ®Google Scholar
• Ohnishi M, Golparian D, Shimuta K, et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother. 2011;55(7):3538–3545.
   PubMed Web of Science ®Google Scholar
• Ameyama S, Onodera S, Takahata M, et al. Mosaic-like structure of penicillin-binding protein 2 gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob Agents Chemother. 2002;46(12):3744–3749.
   PubMed Web of Science ®Google Scholar
• Osaka K, Takakura T, Narukawa K, et al. Analysis of amino acid sequences of penicillin-binding protein 2 in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime and ceftriaxone. J Infect Chemother. 2008;14(3):195–203.
   PubMedGoogle Scholar
• Ochiai S, Sekiguchi S, Hayashi A, et al. Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2 for oral cephalosporins in Neisseria gonorrhoeae. J Antimicrob Chemother. 2007;60(1):54–60.
   PubMed Web of Science ®Google Scholar
• Lahra MM, Ryder N, Whiley DM. A new multidrug-resistant strain of Neisseria gonorrhoeae in Australia. N Engl J Med. 2014;371(19):1850–1851.
   PubMed Web of Science ®Google Scholar
• Ohnishi M, Saika T, Hoshina S, et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis. 2011;17(1):148–149.
   PubMed Web of Science ®Google Scholar
• Unemo M, Golparian D, Nicholas R, et al. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012;56(3):1273–1280.
   PubMed Web of Science ®Google Scholar
• van Dam AP, van Ogtrop ML, Golparian D, et al. Verified clinical failure with cefotaxime 1g for treatment of gonorrhoea in the Netherlands: a case report. Sex Transm Infect. 2014;90(7):513–514.
   PubMed Web of Science ®Google Scholar
• Unemo M, Golparian D, Potocnik M, et al. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill. 2012;17:25.
   Google Scholar
• Unemo M, Golparian D, Stary A, et al. First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhoea treatment failure in Austria, 2011. Euro Surveill. 2011;16:43.
   Google Scholar
• Chen SC, Yin YP, Dai XQ, et al. Antimicrobial resistance, genetic resistance determinants for ceftriaxone and molecular epidemiology of Neisseria gonorrhoeae isolates in Nanjing, China. J Antimicrob Chemother. 2014;69(11):2959–2965.
   PubMed Web of Science ®Google Scholar
• Lee H, Unemo M, Kim HJ, et al. Emergence of decreased susceptibility and resistance to extended-spectrum cephalosporins in Neisseria gonorrhoeae in Korea. J Antimicrob Chemother. 2015;70(9):2536–2542.
   PubMed Web of Science ®Google Scholar
• Lee SG, Lee H, Jeong SH, et al. Various penA mutations together with mtrR, porB and ponA mutations in Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime or ceftriaxone. J Antimicrob Chemother. 2010;65(4):669–675.
   PubMed Web of Science ®Google Scholar
• Olsen B, Pham TL, Golparian D, et al. Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011. BMC Infect Dis. 2013;13:40.
   PubMed Web of Science ®Google Scholar
• Sigmund CD, Ettayebi M, Morgan EA. Antibiotic resistance mutations in 16S and 23S ribosomal RNA genes of Escherichia coli. Nucleic Acids Res. 1984;12(11):4653–4663.
   PubMed Web of Science ®Google Scholar
• Unemo M, Golparian D, Skogen V, et al. Neisseria gonorrhoeae strain with high-level resistance to spectinomycin due to a novel resistance mechanism (mutated ribosomal protein S5) verified in Norway. Antimicrob Agents Chemother. 2013;57(2):1057–1061.
   PubMed Web of Science ®Google Scholar
• Ilina EN, Malakhova MV, Bodoev IN, et al. Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae. Front Microbiol. 2013;4:186.
   PubMed Web of Science ®Google Scholar
• Hagman KE, Pan W, Spratt BG, et al. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system. Microbiology. 1995;141(Pt 3):611–622.
   PubMed Web of Science ®Google Scholar
• Lee EH, Shafer WM. The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids. Mol Microbiol. 1999;33(4):839–845.
   PubMed Web of Science ®Google Scholar
• Rouquette-Loughlin C, Dunham SA, Kuhn M, et al. The NorM efflux pump of Neisseria gonorrhoeae and Neisseria meningitidis recognizes antimicrobial cationic compounds. J Bacteriol. 2003;185(3):1101–1106.
   PubMed Web of Science ®Google Scholar
• Rouquette-Loughlin CE, Balthazar JT, Shafer WM. Characterization of the MacA-MacB efflux system in Neisseria gonorrhoeae. J Antimicrob Chemother. 2005;56(5):856–860.
   PubMed Web of Science ®Google Scholar
• Veal WL, Nicholas RA, Shafer WM. Overexpression of the MtrC-MtrD-MtrE efflux pump due to an mtrR mutation is required for chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. J Bacteriol. 2002;184(20):5619–5624.
   PubMed Web of Science ®Google Scholar
• Zarantonelli L, Borthagaray G, Lee EH, et al. Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations. Antimicrob Agents Chemother. 1999;43(10):2468–2472.
   PubMed Web of Science ®Google Scholar
• Lucas CE, Balthazar JT, Hagman KE, et al. The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae. J Bacteriol. 1997;179(13):4123–4128.
   PubMed Web of Science ®Google Scholar
• Gill MJ, Simjee S, Al-Hattawi K, et al. Gonococcal resistance to beta-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus. Antimicrob Agents Chemother. 1998;42(11):2799–2803.
   PubMed Web of Science ®Google Scholar
• Shafer WM, Folster JP. Towards an understanding of chromosomally mediated penicillin resistance in Neisseria gonorrhoeae: evidence for a porin-efflux pump collaboration. J Bacteriol. 2006;188(7):2297–2299.
   PubMed Web of Science ®Google Scholar
• Magooa MP, Muller EE, Gumede L, et al. Determination of Neisseria gonorrhoeae susceptibility to ciprofloxacin in clinical specimens from men using a real-time PCR assay. Int J Antimicrob Agents. 2013;42(1):63–67.
   PubMed Web of Science ®Google Scholar
• Peterson SW, Martin I, Demczuk W, et al. Molecular assay for detection of ciprofloxacin resistance in Neisseria gonorrhoeae isolates from cultures and clinical nucleic acid amplification test specimens. J Clin Microbiol. 2015;53(11):3606–3608.
   PubMed Web of Science ®Google Scholar
• Zhao L, Zhao S. TaqMan real-time quantitative PCR assay for detection of fluoroquinolone-resistant Neisseria gonorrhoeae. Curr Microbiol. 2012;65(6):692–695.
   PubMed Web of Science ®Google Scholar
• Pond MJ, Hall CL, Miari VF, et al. Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy. J Antimicrob Chemother. 2016;71(4):897–902.
   PubMed Web of Science ®Google Scholar
• Buckley C, Trembizki E, Donovan B, et al. A real-time PCR assay for direct characterization of the Neisseria gonorrhoeae GyrA 91 locus associated with ciprofloxacin susceptibility. J Antimicrob Chemother. 2016;71(2):353–356.
   PubMed Web of Science ®Google Scholar
• Hemarajata P, Yang S, Soge OO, et al. Performance and verification of a real-time PCR assay targeting the gyrA gene for prediction of ciprofloxacin resistance in Neisseria gonorrhoeae. J Clin Microbiol. 2016;54(3):805–808.
   PubMed Web of Science ®Google Scholar
• Siedner MJ, Pandori M, Castro L, et al. Real-time PCR assay for detection of quinolone-resistant Neisseria gonorrhoeae in urine samples. J Clin Microbiol. 2007;45(4):1250–1254.
   PubMed Web of Science ®Google Scholar
• Trembizki E, Buckley C, Donovan B, et al. Direct real-time PCR-based detection of Neisseria gonorrhoeae 23S rRNA mutations associated with azithromycin resistance. J Antimicrob Chemother. 2015;70(12):3244–3249.
   PubMed Web of Science ®Google Scholar
• Goire N, Freeman K, Lambert SB, et al. The influence of target population on nonculture-based detection of markers of Neisseria gonorrhoeae antimicrobial resistance. Sex Health. 2012;9(5):422–429.
   PubMed Web of Science ®Google Scholar
• Ochiai S, Ishiko H, Yasuda M, et al. Rapid detection of the mosaic structure of the Neisseria gonorrhoeae penA gene, which is associated with decreased susceptibilities to oral cephalosporins. J Clin Microbiol. 2008;46(5):1804–1810.
   PubMed Web of Science ®Google Scholar
• Gose S, Nguyen D, Lowenberg D, et al. Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA. BMC Infect Dis. 2013;13:570.
   PubMed Web of Science ®Google Scholar
• Peterson SW, Martin I, Demczuk W, et al. Molecular assay for detection of genetic markers associated with decreased susceptibility to cephalosporins in Neisseria gonorrhoeae. J Clin Microbiol. 2015;53(7):2042–2048.
   PubMed Web of Science ®Google Scholar
• Goire N, Lahra MM, Ohnishi M, et al. Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain. Euro Surveill. 2013;18(14):20444.
   PubMedGoogle Scholar
• Goire N, Ohnishi M, Limnios AE, et al. Enhanced gonococcal antimicrobial surveillance in the era of ceftriaxone resistance: a real-time PCR assay for direct detection of the Neisseria gonorrhoeae H041 strain. J Antimicrob Chemother. 2012;67(4):902–905.
   PubMed Web of Science ®Google Scholar
• Trembizki E, Wand H, Donovan B, et al. The molecular epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in Australia: a nationwide cross-sectional study, 2012. Clin Infect Dis. 2016;63(12):1591–1598.
   PubMed Web of Science ®Google Scholar
• Trembizki E, Smith H, Lahra MM, et al. High-throughput informative single nucleotide polymorphism-based typing of Neisseria gonorrhoeae using the Sequenom MassARRAY iPLEX platform. J Antimicrob Chemother. 2014;69(6):1526–1532.
   PubMed Web of Science ®Google Scholar
• Dona V, Kasraian S, Lupo A, et al. Multiplex real-time PCR assay with high-resolution melting analysis for characterization of antimicrobial resistance in Neisseria gonorrhoeae. J Clin Microbiol. 2016;54(8):2074–2081.
   PubMed Web of Science ®Google Scholar
• Balashov S, Mordechai E, Adelson ME, et al. Multiplex bead suspension array for screening Neisseria gonorrhoeae antibiotic resistance genetic determinants in noncultured clinical samples. J Mol Diagn. 2013;15(1):116–129.
   PubMed Web of Science ®Google Scholar
• Graham RM, Doyle CJ, Jennison AV. Epidemiological typing of Neisseria gonorrhoeae and detection of markers associated with antimicrobial resistance directly from urine samples using next generation sequencing. Sex Transm Infect. 2017;93(1):65–67.
   PubMed Web of Science ®Google Scholar
• Giles J, Hardick J, Yuenger J, et al. Use of applied biosystems 7900HT sequence detection system and Taqman assay for detection of quinolone-resistant Neisseria gonorrhoeae. J Clin Microbiol. 2004;42(7):3281–3283.
   PubMed Web of Science ®Google Scholar
• Palmer HM, Mallinson H, Wood RL, et al. Evaluation of the specificities of five DNA amplification methods for the detection of Neisseria gonorrhoeae. J Clin Microbiol. 2003;41(2):835–837.
   PubMed Web of Science ®Google Scholar
• Goire N, Kundu R, Trembizki E, et al. Mixed gonococcal infections in a high-risk population, Sydney, Australia 2015: implications for antimicrobial resistance surveillance? J Antimicrob Chemother. 2017;72(2):407–409.
   PubMed Web of Science ®Google Scholar
• Siedner MJ, Pandori M, Leon SR, et al. Detection of quinolone-resistant Neisseria gonorrhoeae in urogenital specimens with the use of real-time polymerase chain reaction. Int J STD AIDS. 2008;19(1):69–71.
   PubMed Web of Science ®Google Scholar
• Lahra MM, Trembizki E, Buckley C, et al. Changes in the rates of Neisseria gonorrhoeae antimicrobial resistance are primarily driven by dynamic fluctuations in common gonococcal genotypes. J Antimicrob Chemother. 2017;72(3):705–711.
   PubMed Web of Science ®Google Scholar
• Demczuk W, Martin I, Peterson S, et al. Genomic epidemiology and molecular resistance mechanisms of azithromycin-resistant Neisseria gonorrhoeae in Canada from 1997 to 2014. J Clin Microbiol. 2016;54(5):1304–1313.
   PubMed Web of Science ®Google Scholar
• Grad YH, Kirkcaldy RD, Trees D, et al. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis. 2014;14(3):220–226.
   PubMed Web of Science ®Google Scholar
• Jacobsson S, Golparian D, Cole M, et al. WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014. J Antimicrob Chemother. 2016;71(11):3109–3116.
   PubMed Web of Science ®Google Scholar
• Unemo M, Golparian D, Sanchez-Buso L, et al. The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization. J Antimicrob Chemother. 2016;71(11):3096–3108.
   PubMed Web of Science ®Google Scholar
• Eyre DW, De Silva D, Cole K, et al. WGS to predict antibiotic MICs for Neisseria gonorrhoeae. J Antimicrob Chemother. 2017.
   PubMed Web of Science ®Google Scholar
• Low N, Unemo M. Molecular tests for the detection of antimicrobial resistant Neisseria gonorrhoeae: when, where, and how to use? Curr Opin Infect Dis. 2016;29(1):45–51.
   PubMed Web of Science ®Google Scholar
• Tomberg J, Unemo M, Davies C, et al. Molecular and structural analysis of mosaic variants of penicillin-binding protein 2 conferring decreased susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae: role of epistatic mutations. Biochemistry. 2010;49(37):8062–8070.
   PubMed Web of Science ®Google Scholar
• Zhao S, Duncan M, Tomberg J, et al. Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2009;53(9):3744–3751.
   PubMed Web of Science ®Google Scholar
• Whiley DM, Limnios EA, Ray S, et al. Diversity of penA alterations and subtypes in Neisseria gonorrhoeae strains from Sydney, Australia, that are less susceptible to ceftriaxone. Antimicrob Agents Chemother. 2007;51(9):3111–3116.
   PubMed Web of Science ®Google Scholar
• Whiley DM, Limnios EA, Ray S, et al. Further questions regarding the role of mosaic penA sequences in conferring reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2007;51(2):802–803.
   PubMed Web of Science ®Google Scholar
• Shimuta K, Watanabe Y, Nakayama S, et al. Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeae clones from 1995 to 2005 in Japan. BMC Infect Dis. 2015;15:378.
   PubMed Web of Science ®Google Scholar
• Allen VG, Farrell DJ, Rebbapragada A, et al. Molecular analysis of antimicrobial resistance mechanisms in Neisseria gonorrhoeae isolates from Ontario, Canada. Antimicrob Agents Chemother. 2011;55(2):703–712.
   PubMed Web of Science ®Google Scholar
• Uehara AA, Amorin EL, Ferreira Mde F, et al. Molecular characterization of quinolone-resistant Neisseria gonorrhoeae isolates from Brazil. J Clin Microbiol. 2011;49(12):4208–4212.
   PubMed Web of Science ®Google Scholar
• Trembizki E, Guy R, Donovan B, et al. Further evidence to support the individualised treatment of gonorrhoea with ciprofloxacin. Lancet Infect Dis. 2016;16(9):1005–1006.
   PubMed Web of Science ®Google Scholar
• Allan-Blitz LT, Klausner JD. Codon 91 Gyrase A testing is necessary and sufficient to predict ciprofloxacin susceptibility in Neisseria gonorrhoeae. J Infect Dis. 2017;215(3):491.
   PubMed Web of Science ®Google Scholar
• Endimiani A, Guilarte YN, Tinguely R, et al. Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998-2012): emergence of multidrug-resistant clones less susceptible to cephalosporins. BMC Infect Dis. 2014;14:106.
   PubMed Web of Science ®Google Scholar
• Bonhoeffer S, Lipsitch M, Levin BR. Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci USA. 1997;94(22):12106–12111.
   PubMed Web of Science ®Google Scholar
• Fingerhuth SM, Bonhoeffer S, Low N, et al. Antibiotic-resistant Neisseria gonorrhoeae spread faster with more treatment, not more sexual partners. PLoS Pathog. 2016;12(5):e1005611.
   PubMed Web of Science ®Google Scholar
• Fingerhuth SM, Bonhoeffer S, Low N, et al. Detection of antibiotic resistance is essential for gonorrhoea point-of-care testing: a mathematical modelling study. BMC Med. 2017;15(1):142.
   Google Scholar
• Allan-Blitz LT, Humphries RM, Hemarajata P, et al. Implementation of a rapid genotypic assay to promote targeted ciprofloxacin therapy of Neisseria gonorrhoeae in a large health system. Clin Infect Dis. 2017;64(9):1268–1270.
   PubMed Web of Science ®Google Scholar