Analysis of Emergence of Quinolone-Resistant Gonococci in Greece by Combined Use of Neisseria gonorrhoeae Multiantigen Sequence Typing and Multilocus Sequence Typing

Mavroidi, Angeliki; Tzelepi, E.; Siatravani, Eirini; Godoy, Daniel; Miriagou, Vivì; Spratt, Brian G.

doi:10.1128/jcm.02233-10

Cited by 20 publications

(13 citation statements)

References 25 publications

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“…Furthermore, all gonococcal lineages resistant to ciprofloxacin were positioned at the edges of the minimum spanning tree, indicating a very distant genetic relatedness to the major gonococcal lineages, and further suggesting that ciprofloxacin resistance was most likely introduced from outside the province. Mavroidi et al (17) found that the emergence and rapid recent increase of a quinolone-resistant strain of N. gonorrhoeae in Greece were due to the importation of a quinolone-resistant strain, ST-1901, from other countries. Although resistance to ciprofloxacin in Saskatchewan is presently low, it may emerge and spread, as we already observed the importation of several quinolone-resistant N. gonorrhoeae strains within this province.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Vidović¹,

Thakur²,

Horsman

et al. 2012

J Clin Microbiol

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A longitudinal study combining multilocus sequence typing with molecular evolutionary analysis determined the distribution, population structure, and evolution of antibiotic resistance in Neisseria gonorrhoeae isolates in Saskatchewan that were collected between 2005 and 2008. Of 195 gonococcal isolates examined, 29 sequence types (STs) were identified with 3 major circulating strains (ST-1 through ST-3) comprising 52% of all gonococcal isolates studied. The prevalences, persistence, distribution patterns, and clonalities of these isolates strongly suggest that gonorrhea endemicity within this broad geographic region was driven by these 3 circulating strains. ST-1 exhibited a significantly (P ‫؍‬ 0.001) higher prevalence throughout the study than did the others, accounting for ϳ25% of the tested isolates each year. The spatial distributions of the gonococcal strains indicated that ST-1 in 2007 entered a linear component of the sexual network, reaching the remote north and resulting in the further spread and maintenance of infection. Ciprofloxacin and azithromycin resistances were observed in distantly related gonococcal lineages, clearly indicating the convergent acquisition of these antibiotic-resistant phenotypes. In addition, all ciprofloxacinand azithromycin-resistant lineages were found at the edges of the minimum spanning tree, far from the major lineages, suggesting that these antibiotic phenotypes were most likely introduced into the province. In contrast, resistance to penicillin was found mostly in the endemic gonococcal lineages, suggesting that penicillin resistance was probably acquired in Saskatchewan as a result of spontaneous mutations in already-established lineages. Tetracycline resistance was present in all STs except one, indicating its ubiquitous nature in the gonococcal population studied. N eisseria gonorrhoeae, a fastidious Gram-negative diplococcus, is an obligate human pathogen that causes the disease gonorrhea. Complications from the spread of the organism along the mucosal surfaces may result in endometritis, salpingitis, and peritonitis in females (3), which can lead to infertility or ectopic pregnancy (27). In Canada, between 1999 and 2008, the overall rate of gonococcal infection increased by 116.5%, from 17.6 to 38 cases per 100,000 (20). Saskatchewan has had the highest infection rate of all the Canadian provinces, with an increase from 45.2 cases per 100,000 in 2000 to 131.3 cases per 100,000 in 2008, resulting in a 290.4% increase (173.4% above the national average) (20). Antimicrobial resistance in N. gonorrhoeae is a major public health problem, as treatment options are becoming increasingly limited. Recently, N. gonorrhoeae isolates with decreased susceptibilities (MIC Ն 0.25) to third-generation cephalosporins (cefixime and ceftriaxone) have been identified in Japan, Europe, the United States, and Canada (4,15,16,19,29,30). These antibiotics are the last remaining options for treating gonorrhea in a single-dose fashion, a preferred mode of treatment for gonococcal infection...

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Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Vidović¹,

Thakur²,

Horsman

et al. 2012

J Clin Microbiol

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“…Based on this two-locus-combined profile, the isolates were equally assigned as ST225, which indicates a shared ancestral origin for these isolates. The ST225 seems to be an emerging multi-resistant clone that has been recently identified in many countries such as Australia (Todd et al 2007), Scotland (Palmer et al 2008), France (Monfort et al 2009), Portugal (Florindo et al 2010) and Greece (Mavroidi et al 2011). In fact, ST225 was the most prevalent ST in Scotland and France and has been reported as the second major genotype among QRNG isolates that were collected between 1997-2007 in Greece.…”

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Genotyping of two Neisseria gonorrhoeae fluroquinolone-resistant strains in the Brazilian Amazon Region

Ferreira

Naveca

et al. 2011

Mem. Inst. Oswaldo Cruz

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(S91F and D95G in GyrA and S87R in ParC). Both isolates were genotyped using N. gonorrhoeae multi-antigen sequence typing and the analysis showed that the ST225 which represented an emerging widespread multi-resistant clone that has also been associated with reduced susceptibility to ceftriaxone. We recommend continued surveillance of this pathogen to assess the efficacy of anti-gonococcal antibiotics in Brazil.Key words: Neisseria gonorrhoeae -fluroquinolone resistance -gyrA and parC -genotyping -MAST Two male patients, a 24-year-old and a 32-year-old, were treated at the sexually transmitted diseases (STD) clinic after presenting with urethral discharge and dysuria. The patients provided urethral culture swabs for Neisseria gonorrhoeae and were treated with a single oral dose of ciprofloxacin (500 mg). Because the symptoms persisted, a single dose of ceftriaxone (250 mg) intramuscular was administrated, which cured all of the symptoms. Tests later confirmed that both culture swabs were positive for N. gonorrhoeae. Both patients were human immunodeficiency virus-negative, although one of them was venereal disease research laboratory-reactive (1/4). One patient reported sexual contact with 10 casual partners in the last three months before infection, whereas the other patient reported two casual partners. It was not possible to know if patients had sexual contact in another state of Brazil or country.The gonococci were screened using several tests, including beta-lactamase BD BBL TM (BD, Franklin Lakes, NJ, USA), Serovar (Phadebact ® GC Serovar Test, Bactus AB, Huddinge, Sweden) and E-test ® (AB Biodisk, Solna, Sweden). The E-test ® was performed using a media containing a GC Medium Base (BD-Difco TM ) and 1% defined growth supplements to ciprofloxacin, ofloxacin, chloramphenicol, ceftriaxone, azithromycin, penicillin and tetracycline. Reference values for sensitivity, reduced sensitivity or resistance were set according to the Clinical and Laboratory Standards Institute + Corresponding author: wianfe@yahoo.com.br WAF, CMF and FGN contributed equally to this work. Received 24 September 2010 Accepted 6 June 2011 (CLSI 2005a) and (Van Dick et al. 1999), specifically to chloramphenicol. The ATCC 49226 strain was used as a control for antibiotic quality.The strains were not beta-lactamase producers and were classified in the WII-III serogroup with Bo, Bp, Br, Bs and Bt serotypes. The isolates showed resistance to ciprofloxacin, ofloxacin (> 32.00 µg/mL) and chloramphenicol (3 µg/mL and 2 µg/mL). One strain was classified as having chromosomally-mediated resistance to penicillin [non-PPNG, non-TRNG with penicillin, minimal inhibitory concentrations (MIC) of ≥ 2 µg/mL and tetracycline MIC of ≤ 2 µg/mL] and reduced susceptibility to tetracycline (0.75 µg/mL and 0.500 µg/mL). Both strains were susceptible to azithromycin (0.125 µg/ mL and 0.190 µg/mL). MIC values were 0.064 µg/mL and 0.032 µg/mL. The agar dilution method was used to confirm MICs of ciprofloxacin and ofloxacin at > 32.00 µg/mL. The major difference (p...

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“…Treatment failures with cefixime have been verified in Japan (10,41,55) for many years, but recently, treatment failures have also been reported in Norway (46), Austria (45), and the United Kingdom (16). It appears that a few very successful gonococcal lineages (clones), e.g., the multilocus sequence typing (MLST) sequence type 7363 (ST7363) and ST1901, which most likely originated in Japan, are spreading globally and account for a substantial proportion of the isolates showing decreased susceptibility and resistance to ESCs and multidrug resistance in many countries (12,15,23,29,38,42,53; http://pubmlst.org/neisseria/; M. Ohnishi and M. Unemo, unpublished data). The recent gonorrhea treatment failures with cefixime in Norway (46), Austria (45), and the United Kingdom (16) were caused by the MLST ST1901 clone, which appears to have evolved into multiple different N. gonorrhoeae multiantigen sequence typing (NG-MAST) STs.…”

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confidence: 99%

High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure

Unemo

Golparian

Nicholas

et al. 2012

Antimicrob Agents Chemother

568

549

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Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA, and pilQ). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC ‫؍‬ 4 g/ml) and ceftriaxone (MIC ‫؍‬ 1 to 2 g/ml) and resistance to most other antimicrobials examined. A novel penA mosaic allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance, as determined by transformation into a set of recipient strains. N. gonorrhoeae appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness and enhanced understanding and monitoring of the ESCresistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a vaccine are essential to develop for efficacious gonorrhea management.

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Analysis of Emergence of Quinolone-Resistant Gonococci in Greece by Combined Use of Neisseria gonorrhoeae Multiantigen Sequence Typing and Multilocus Sequence Typing

Cited by 20 publications

References 25 publications

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Genotyping of two Neisseria gonorrhoeae fluroquinolone-resistant strains in the Brazilian Amazon Region

High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure

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