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

Table 1 Characteristics of verified gonorrhoea treatment failures with ceftriaxone (250–1000 mg × 1) and causing gonococcal strain

Country, year	Ceftriaxone Therapy	Ceftriaxone MIC (mg/L)	fT_>MIC, hours^a	MLST/NG-MAST	Site of failure	Final successful treatment
Australia (n = 2), 2007 [31]	250 mg × 1	0.016-0.03 (Agar dilution)	41.4-50.3	ND/ST5, ST2740	Pharynx	Ceftriaxone 500 mg × 1/ Ceftriaxone 1 g × 1
Japan (n = 1), 2009 [30]	1 g × 1	4.0^b (Etest, XDR)	0	ST7363/ST4220	Pharynx	None^c
Sweden (n = 1), 2010 [34]	250 mg × 1 and 500 mg × 1	0.125-0.25^b (Etest)	15.6-32.8	ST1901/ST2958	Pharynx	Ceftriaxone 1 g × 1
Australia (n = 1), 2010 [32]	500 mg × 1	0.03-0.06 (Agar dilution)	41.3-49.9	ND/ST1407, ST4950 (genogroup 1407)	Pharynx	Azithromycin 2 g × 1
Slovenia (n = 1), 2011 [36]	250 mg × 1	0.125^b (Etest)	24.3	ST1901/ST1407 (genogroup 1407)	Pharynx	Ceftriaxone 250 mg × 1 plus azithromycin 1 g × 1
Australia (n = 2), 2011 [33]	500 mg × 1	0.03-0.06 (Agar dilution)	41.3-49.9	ST1901/ST225, new variant of ST225	Pharynx	Ceftriaxone 1 g × 1 plus azithromycin 2 g × 1 or Ceftriaxone 1 g × 1
Sweden (n = 3), 2013–2014 [35]	500 mg × 1	0.064-0.125^b (Etest)	32.8-41.3	ST1901/ST3149, ST3149, ST4706 (genogroup 1407)	Pharynx	Ceftriaxone 1 g × 1

^aSimulation of time of free ceftriaxone above MIC (fT_>MIC) based on mean pharmacokinetic parameter values. Data from Chisholm et al. [52]
^bGenetic cephalosporin resistance determinants (penA, mtrR, penB) elucidated [3, 5–8]
^cThe infection was considered to have resolved spontaneously within 3 months
MIC minimum inhibitory concentration, MLST multilocus sequence typing, NG-MAST Neisseria gonorrhoeae multi-antigen sequence typing, ND not determined, ST sequence type, XDR extensively drug-resistant [9]

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