Current and future antimicrobial treatment of gonorrhoea – the rapidly evolving Neisseria gonorrhoeae continues to challenge

Table 2 Main characteristics of the verified Neisseria gonorrhoeae superbugs and examples of sporadic gonococcal strains with ceftriaxone MIC = 0.5 mg/L

Country, year	Ceftriaxone MIC (mg/L)	fT_>MIC (hours) with ceftriaxone 250 mg × 1 (1 g × 1)^a	MLST	NG-MAST	PBP2 sequence variant [30]
Japan, 2009 “H041” [30]	4 (Etest)	0-0 (0–5.6)	ST7363	ST4220	C (X + 12 amino acid alterations; new key resistance alterations: A311V, T316P, T483S [45]) ^b
France, 2011 “F89” [26]	2 (Etest)	0-0 (0–20.3)	ST1901	ST1407	CI (XXXIV + A501P)^b
Spain, 2011 “F89” [38]^c	2 (Etest)	0-0 (0–20.3)	ST1901	ST1407	CI (XXXIV + A501P)^b
Japan, 2000–2001 [40]	0.5 (Agar dilution)	0-19.8 (11.1-49.8)	ND	ND	X-variant (X + N575Δ + V576A)^b
China, 2007 [41]	0.5 (Agar dilution)	0-19.8 (11.1-49.8)	ND	ST2288	XVII
Austria, 2011 [25]	0.5 (Etest)	0-19.8 (11.1-49.8)	ST1901	ST1407	XXXIV + T534A^b
Australia, 2014 “A8806” [39]	0.5 (Agar dilution)	0-19.8 (11.1-49.8)	ST7363	ST4015^d	C-variant (including two of the three key alterations in H041: A311V and T483S)^b

^aMonte Carlo simulation, taking into account diversity inherent within patient populations, showing 95 % confidence intervals of time (h) of free ceftriaxone above MIC (fT_>MIC). Data from Chisholm et al. [52]
^bMosaic PBP2 sequence variant [30]
^cPossibly identical to the earlier identified French superbug [26] and represented the first international transmission of a high-level ceftriaxone resistant gonococcal strain
^dCompared to the superbug H041 [30], identical tbpB allele (10) and a porB allele (1059) that only differed by 6 %
MIC minimum inhibitory concentration, MLST multilocus sequence typing, NG-MAST Neisseria gonorrhoeae multi-antigen sequence typing, PBP2 penicillin-binding protein 2, ND not determined, ST sequence type

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