Characterization of Neisseria gonorrhoeae isolates detected in Switzerland (1998-2012): emergence of multidrug-resistant clones less susceptible to cephalosporins

Abstract

Background: The spread of Neisseria gonorrhoeae (Ng) isolates resistant to the clinically implemented antibiotics is challenging the efficacy of treatments. Unfortunately, phenotypic and molecular data regarding Ng detected in Switzerland are scarce.

Methods: We compared the characteristics of Ng detected during 1998-2001 (n = 26) to those detected during 2009-2012 (n = 34). MICs were obtained with the Etest and interpreted as non-susceptible (non-S) according to EUCAST criteria. Sequence type (ST) was achieved implementing the NG-MAST. BlaTEM, ponA, penA, mtrR, penB, tet(M), gyrA, parC, mefA, ermA/B/C/F, rplD, rplV, and 23S rRNA genes were analyzed.

Results: The following susceptibility results were obtained (period: % of non-S, MIC90 in mg/L): penicillin (1998-2001: 42.3%, 3; 2009-2012: 85.3%, 16), cefixime (1998-2001: 0%, ≤0.016; 2009-2012: 8.8%, 0.125), ceftriaxone (1998-2001: 0%, 0.004; 2009-2012: 0%, 0.047), ciprofloxacin (1998-2001: 7.7%, 0.006; 2009-2012: 73.5%, ≥32), azithromycin (1998-2001: 11.5%, 0.25; 2009-2012: 23.6%, 0.38), tetracycline (1998-2001: 65.4%, 12; 2009-2012: 88.2%, 24), spectinomycin (1998-2001: 0%, 12; 2009-2012: 0%, 8). The prevalence of multidrug-resistant (MDR) isolates increased from 7.7% in 1998-2001 to 70.6% in 2009-2012. International STs and genogroups (G) emerged during 2009-2012 (G1407, 29.4%; G2992, 11.7%; G225, 8.8%). These isolates possessed distinctive mechanisms of resistance (e.g., G1407: PBP1 with L421, PBP2 pattern XXXIV, GyrA with S91F and D95G, ParC with S87R, PorB with G120K and A121N, mtrR promoter with A deletion).

Conclusions: The prevalence of penicillin- ciprofloxacin- and tetracycline-resistant Ng has reached dramatic levels, whereas cefixime and ceftriaxone show MICs that tend to increase during time. International MDR clones less susceptible to cephalosporins are rapidly emerging indicating that the era of untreatable gonococcal infections is close.

Figure 1

MIC values distribution for the eight antibiotics tested against theNg isolates detected during the two different periods (1998–2001versus2009–2012). “S”, indicates the cut-off of susceptibility, whereas “R” indicates the isolates intermediate or resistant according to the EUCAST criteria [26]. The results clearly show that the MICs for cephalosporins increased over time (i.e., CRO: from MIC₉₀ of 0.004 mg/L to 0.047 mg/L; CFX: from MIC₉₀ ≤ 0.016 to 0.125 mg/L with also 8.8% of the isolates resistant) and that the prevalence of PEN-, CIP-, and TET-resistant isolates reached dramatic levels.

Figure 2

Sequencing types (STs) of theNg isolates detected during the two different periods (1998–2001 and 2009–2012). STs with more than one isolate are indicated in colors and with their percentages. Hyperepidemic clones are indicated in bold and STs included in the same genogroup (G) are underlined. The results show that international lineages reported in other countries (G1407, G2992, and G225) are also emerging and spreading in Switzerland. With the exception of two isolates of G25, these STs/Gs were not present during the previous decade. Notably, most of the hyperepidemic clones were MDR (i.e., resistant to ≥ 3 antibiotics).