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Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from symptomatic men attending the Nanjing sexually transmitted diseases clinic (2011-2012): genetic characteristics of isolates with reduced sensitivity to ceftriaxone.

Li S, Su XH, Le WJ, Jiang FX, Wang BX, Rice PA - BMC Infect. Dis. (2014)

Bottom Line: Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid.The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type.Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent.

View Article: PubMed Central - PubMed

Affiliation: STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China. wslisai@163.com.

ABSTRACT

Background: Evolving gonococcal antimicrobial resistance (AMR) poses a serious threat to public health. The aim of this study was to: update antimicrobial susceptibility data of Neisseria gonorrhoeae recently isolated in Nanjing, China and identify specific deteminants of antimicrobial resistance and gentoypes of isolates with decreased sensitivity to ceftriaxone.

Methods: 334 N. gonorrhoeae isolates were collected consecutively from symptomatic men attending the Nanjing STD Clinic between April 2011 and December 2012. The minimum inhibitory concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone were determined by agar plate dilution for each isolate. Penicillinase-producing N. gonorrhoeae (PPNG) and tetracycline-resistant N. gonorrhoeae (TRNG) were examined and typed for β-lactamase and tetM encoding plasmids respectively. Isolates that displayed elevated MICs to ceftriaxone (MIC ≥0.125 mg/L) were also tested for mutations in penA, mtrR, porB1b, ponA and pilQ genes and characterized by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST).

Results: 98.8% (330/334) of N. gonorrhoeae isolates were resistant to ciprofloxacin; 97.9% (327/334) to tetracycline and 67.7% (226/334) to penicillin. All isolates were susceptible to ceftriaxone (MIC ≤0.25 mg/L) and spectinomycin (MIC ≤32 mg/L). Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid. Elevated MICs for ceftriaxone were present in 15 (4.5%) isolates; multiple mutations were found in penA, mtrR, porB1b and ponA genes. The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type.

Conclusions: N. gonorrhoeae isolates in Nanjing generally retained similar antimicrobial resistance patterns to isolates obtained five years ago. Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent. Ceftriaxone and spectinomycin remain treatments of choice of gonorrhea in Nanjing, however, decreased susceptibility to ceftriaxone and rising MICs for spectinomycin of N. gonorrhoeae isolates underscore the importance of maintaining surveillance for AMR (both phenotypic and genotypic).

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Distribution of spectinomycin MICs ofNeisseria gonorrhoeaeisolates: Nanjing, 2006 (n = 198) and 2011–12 (n = 334).
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Fig2: Distribution of spectinomycin MICs ofNeisseria gonorrhoeaeisolates: Nanjing, 2006 (n = 198) and 2011–12 (n = 334).

Mentions: It is encouraging to note that the percentage of gonococci isolates with decreased susceptibility to ceftriaxone (MIC ≥0.125 mg/L) declined significantly from 9.1% (18/198) in 2006 [39] to 4.5% (15/334) in 2011–12 (p = 0.04); a one dilution decrease of the modal MIC for ceftriaxone was also observed (0.06 mg/L in 2006 to 0.03 mg/L in 2011–12) (Figure 1). In Europe [32,60-63], Australia [64], Africa [65-67], the western hemisphere [33,58,59,68-70] and the South-East Asia Region [31], MICs to ceftriaxone have risen during this period. Nonetheless, it is of concern that the distribution of spectinomycin MICs shifted upward in Nanjing during the same interval, between 2006 and 2011–12 (Figure 2) [39]. In 2006, an MIC = 32 mg/L to spectinomycin was observed in 1.0% of strains, rising to 18.3% in 2011–12 (p < 0.01), coinciding with a significant decrease in the percentage of strains whose MICs ≤8 mg/L (p < 0.01). Opposing trends in resistance of gonococcal isolates to ceftriaxone and spectinomycin may, in part, result from the greater use of spectinomycin in the Nanjing STD clinic. Ninety-eight percent of gonococcal urethritis cases in men were prescribed spectinomycin as recently as in 2012, in large part because of the lower price of Chinese-manufactured spectinomycin vs. imported ceftriaxone and the requirements for cefriaxone skin testing prior to administration. Resistance of N. gonorrhoeae to spectinomycin, although rarely reported [31,33,65,71], because of limited access to and use of this antibiotic in many countries outside of China, may be the “cautionary tale” of clinical failure when it is used as primary treatment of gonorrhea [72].Figure 1


Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from symptomatic men attending the Nanjing sexually transmitted diseases clinic (2011-2012): genetic characteristics of isolates with reduced sensitivity to ceftriaxone.

Li S, Su XH, Le WJ, Jiang FX, Wang BX, Rice PA - BMC Infect. Dis. (2014)

Distribution of spectinomycin MICs ofNeisseria gonorrhoeaeisolates: Nanjing, 2006 (n = 198) and 2011–12 (n = 334).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4263019&req=5

Fig2: Distribution of spectinomycin MICs ofNeisseria gonorrhoeaeisolates: Nanjing, 2006 (n = 198) and 2011–12 (n = 334).
Mentions: It is encouraging to note that the percentage of gonococci isolates with decreased susceptibility to ceftriaxone (MIC ≥0.125 mg/L) declined significantly from 9.1% (18/198) in 2006 [39] to 4.5% (15/334) in 2011–12 (p = 0.04); a one dilution decrease of the modal MIC for ceftriaxone was also observed (0.06 mg/L in 2006 to 0.03 mg/L in 2011–12) (Figure 1). In Europe [32,60-63], Australia [64], Africa [65-67], the western hemisphere [33,58,59,68-70] and the South-East Asia Region [31], MICs to ceftriaxone have risen during this period. Nonetheless, it is of concern that the distribution of spectinomycin MICs shifted upward in Nanjing during the same interval, between 2006 and 2011–12 (Figure 2) [39]. In 2006, an MIC = 32 mg/L to spectinomycin was observed in 1.0% of strains, rising to 18.3% in 2011–12 (p < 0.01), coinciding with a significant decrease in the percentage of strains whose MICs ≤8 mg/L (p < 0.01). Opposing trends in resistance of gonococcal isolates to ceftriaxone and spectinomycin may, in part, result from the greater use of spectinomycin in the Nanjing STD clinic. Ninety-eight percent of gonococcal urethritis cases in men were prescribed spectinomycin as recently as in 2012, in large part because of the lower price of Chinese-manufactured spectinomycin vs. imported ceftriaxone and the requirements for cefriaxone skin testing prior to administration. Resistance of N. gonorrhoeae to spectinomycin, although rarely reported [31,33,65,71], because of limited access to and use of this antibiotic in many countries outside of China, may be the “cautionary tale” of clinical failure when it is used as primary treatment of gonorrhea [72].Figure 1

Bottom Line: Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid.The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type.Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent.

View Article: PubMed Central - PubMed

Affiliation: STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China. wslisai@163.com.

ABSTRACT

Background: Evolving gonococcal antimicrobial resistance (AMR) poses a serious threat to public health. The aim of this study was to: update antimicrobial susceptibility data of Neisseria gonorrhoeae recently isolated in Nanjing, China and identify specific deteminants of antimicrobial resistance and gentoypes of isolates with decreased sensitivity to ceftriaxone.

Methods: 334 N. gonorrhoeae isolates were collected consecutively from symptomatic men attending the Nanjing STD Clinic between April 2011 and December 2012. The minimum inhibitory concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone were determined by agar plate dilution for each isolate. Penicillinase-producing N. gonorrhoeae (PPNG) and tetracycline-resistant N. gonorrhoeae (TRNG) were examined and typed for β-lactamase and tetM encoding plasmids respectively. Isolates that displayed elevated MICs to ceftriaxone (MIC ≥0.125 mg/L) were also tested for mutations in penA, mtrR, porB1b, ponA and pilQ genes and characterized by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST).

Results: 98.8% (330/334) of N. gonorrhoeae isolates were resistant to ciprofloxacin; 97.9% (327/334) to tetracycline and 67.7% (226/334) to penicillin. All isolates were susceptible to ceftriaxone (MIC ≤0.25 mg/L) and spectinomycin (MIC ≤32 mg/L). Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid. Elevated MICs for ceftriaxone were present in 15 (4.5%) isolates; multiple mutations were found in penA, mtrR, porB1b and ponA genes. The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type.

Conclusions: N. gonorrhoeae isolates in Nanjing generally retained similar antimicrobial resistance patterns to isolates obtained five years ago. Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent. Ceftriaxone and spectinomycin remain treatments of choice of gonorrhea in Nanjing, however, decreased susceptibility to ceftriaxone and rising MICs for spectinomycin of N. gonorrhoeae isolates underscore the importance of maintaining surveillance for AMR (both phenotypic and genotypic).

Show MeSH
Related in: MedlinePlus