Microbiological Analysis from a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae

DOI: 10.1128/AAC.01221-18

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FIG 1
Frequency distribution of gepotidacin MICs against baseline urogenital N. gonorrhoeae isolates (N = 69).

TABLE 1

Antimicrobial activity of gepotidacin and comparator antimicrobial agents against urogenital N. gonorrhoeae isolates at baseline (N = 69)

↵a Susceptibility interpretations were per M100-S27 Clinical and Laboratory Standards Institute breakpoints.
↵b —, no breakpoint was available.

TABLE 3

Microbiological response by gepotidacin MIC against N. gonorrhoeae at baseline^a

Specimen source	Gepotidacin MIC (µg/ml)	Gepotidacin 1,500 mg (N = 30)				Gepotidacin 3,000 mg (N = 39)
Specimen source	Gepotidacin MIC (µg/ml)	n	MS (n)^b	MF (n)^c	Success (%)	n	MS (n)	MF (n)	Success (%)
Urogenital	≤0.06	8	8	0	100	9	9	0	100
	0.12	10	10	0	100	10	10	0	100
	0.25	7	7	0	100	15	15	0	100
	0.5	3	3	0	100	2	2	0	100
	1	2	1	1	50	3	1	2	33
Pharyngeal	≤0.06	0	0	0	0	1	1	0	100
Pharyngeal	0.12	0	0	0	0	1	0	1	0
Rectal	0.12	1	1	0	100	1	1	0	100
Rectal	0.25	0	0	0	0	1	1	0	100

↵a Participants were only required to have a urogenital N. gonorrhoeae isolate at baseline to qualify for the microbiologically evaluable population. Pharyngeal or rectal N. gonorrhoeae isolates at baseline were not required for this population. Therefore, the n values for the pharyngeal and rectal data are each a subset of the full population (i.e., of the overall 69 participants in this population, 2 had a baseline pharyngeal N. gonorrhoeae isolate and 3 had a baseline rectal N. gonorrhoeae isolate).
↵b MS, microbiological success.
↵c MF, microbiological failure.

TABLE 5

Baseline urogenital N. gonorrhoeae isolates with a ParC D86N mutation

Participant no.	Mutation^a		MIC (µg/ml)^b								GEP dose (mg)	Microbiological response	fAUC/MIC^c
Participant no.	GyrA	ParC	GEP^d	CRO	AZI	CIP	CFM	PEN	SPT	TET	GEP dose (mg)	Microbiological response	fAUC/MIC^c
1	S91F D95G	D86N	≤0.06	0.015	0.12	2	0.03	0.25	8	0.5	1,500	Success	200
2	S91F D95A	D86N	0.25	0.008	0.25	2	0.008	0.25	16	0.5	3,000	Success	100
3	S91F D95A	D86N	0.25	0.008	0.25	2	0.015	16	32	1	3,000	Success	97
4	S91F D95G	D86N	1	0.06	0.5	8	0.06	4	8	2	3,000	Failure	24
5	S91F D95G	D86N	1	0.004	0.25	4	0.004	0.25	8	1	3,000	Success	24
6	S91F D95G	D86N	1	0.06	0.5	4	0.06	1	16	2	3,000	Failure	24
7	S91F D95A	D86N	1	0.03	2	16	0.03	2	8	2	1,500	Failure	12
8	S91F D95A	D86N	1	0.008	0.5	2	0.015	0.5	32	0.5	1,500	Success	12

↵a Sequencing of quinolone resistance-determining region only.
↵b AZI, azithromycin; CFM, cefixime; CIP, ciprofloxacin; CRO, ceftriaxone; GEP, gepotidacin; PEN, penicillin; SPT, spectinomycin; TET, tetracycline.
↵c fAUC/MIC, ratio of the area under the free-drug concentration-time curve to the MIC.
↵d No breakpoints are currently available for GEP.