Antimicrobial susceptibility and genetic characteristics of Neisseria gonorrhoeae isolates from Vietnam, 2011

Abstract

BackgroundAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. In Vietnam, knowledge regarding N. gonorrhoeae prevalence and AMR is limited, and data concerning genetic characteristics of N. gonorrhoeae is totally lacking. Herein, we investigated the phenotypic AMR (previous, current and possible future treatment options), genetic resistance determinants for extended-spectrum cephalosporins (ESCs), and genotypic distribution of N. gonorrhoeae isolated in 2011 in Hanoi, Vietnam.MethodsN. gonorrhoeae isolates from Hanoi, Vietnam isolated in 2011 (n = 108) were examined using antibiograms (Etest for 10 antimicrobials), Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST), and sequencing of ESC resistance determinants (penA, mtrR and penB).ResultsThe levels of in vitro resistance were as follows: ciprofloxacin 98%, tetracycline 82%, penicillin G 48%, azithromycin 11%, ceftriaxone 5%, cefixime 1%, and spectinomycin 0%. The MICs of gentamicin (0.023-6 mg/L), ertapenem (0.002-0.125 mg/L) and solithromycin (<0.016-0.25 mg/L) were relatively low. No penA mosaic alleles were found, however, 78% of the isolates contained an alteration of amino acid A501 (A501V (44%) and A501T (34%)) in the encoded penicillin-binding protein 2. A single nucleotide (A) deletion in the inverted repeat of the promoter region of the mtrR gene and amino acid alterations in MtrR was observed in 91% and 94% of the isolates, respectively. penB resistance determinants were detected in 87% of the isolates. Seventy-five different NG-MAST STs were identified, of which 59 STs have not been previously described.ConclusionsIn Vietnam, the highly diversified gonococcal population displayed high in vitro resistance to antimicrobials previously recommended for gonorrhoea treatment (with exception of spectinomycin), but resistance also to the currently recommended ESCs were found. Nevertheless, the MICs of three potential future treatment options were low. It is essential to strengthen the diagnostics, case reporting, and epidemiologic surveillance of gonorrhoea in Vietnam. Furthermore, the surveillance of gonococcal AMR and gonorrhoea treatment failures is imperative to reinforce. Research regarding novel antimicrobial treatment strategies (e.g., combination therapy) and new antimicrobials is crucial for future treatment of gonorrhoea.

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

“…Possibly, the N512Y alteration perturbs the architecture of the KTG active site motif of the ␤3 strand (204). Finally, introduction of an A501V mutation, which has been found mainly in gonococcal isolates with decreased ESC susceptibility that lack a mosaic penA gene (246,(249)(250)(251), into a mosaic PBP2 increased the MICs of ceftriaxone and cefixime 2-to 4-fold, i.e., resulted in in vitro resistance (204), which further emphasizes the importance of the ␤3-␤4 loop of PBP2 for ESC resistance.…”

Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and Carbapenem Susceptibilities in Neisseria gonorrhoeae

“…Effects of PBP2 variants on carbapenem susceptibility. Ertapenem has been investigated as a potential future treatment for gonorrhea infections (11)(12)(13)(14). Nonmosaic alleles, regardless of the presence of A501V, caused 2-fold decreased susceptibility to ertapenem, raising the MICs from 0.016 mg/liter to 0.032 mg/liter, but had no effect on meropenem MICs.…”

“…The recommended treatment for gonorrhea is an extendedspectrum cephalosporin (ESC), preferably ceftriaxone or, alternatively, cefixime, in combination with the macrolide azithromycin (3-5); however, treatment failures have been reported in many countries (6-10). Ertapenem has recently been explored as a potential treatment for gonorrhea (11)(12)(13)(14). Resistance to ␤-lactam antibiotics, including ESCs and carbapenems, is primarily caused by changes in their cellular target, penicillin-binding protein 2 (PBP2), which is encoded by the penA gene in Neisseria gonorrhoeae.…”

Modern aspects of epidemiological surveillance of gonococcal infection spread

“…Во Вьетнаме в 2011 г. установлена резистент-ность N. gonorrhoeae к ципрофлоксацину -98% штаммов, к тетрациклину -82%, к пенициллину G -в 48%, к азитромицину -11%, к цефтриаксону -5%, цефиксиму -1% штаммов [47].…”