Evaluation of Drugs with Therapeutic Potential for Susceptibility of Neisseria Gonorrhoeae Isolates from 8 Provinces in China from 2018

Figures & data

Table 1 Antimicrobial Susceptibility Testing Results for 451 Clinical N. Gonorrhoeae Isolates and Breakpoints Used in This Study

Antimicrobial Agent	MIC (mg/L)				MIC Interpretation Used for Analysis in this Study (mg/L)			Percentage of Resistant Isolates
	Range	Mode	MIC50	MIC90	Susceptible	Intermediately Susceptible	Resistant
Meropenem*^a	≤0.004–0.125	0.03	0.03	0.06	≤ 1	2	≥ 4	0
Fosfomycin^b	4-≥256	32	32	64	≤ 64	128	≥ 256	0.2
Berberine hydrochloride^c	2-≥256	16	16	64	NA	NA	NA	-
Doxycycline^d	≤0.125–64	2	2	16	≤ 0.25	0.5–1	≥ 2	60.1

Notes: *415 isolates had efficient MIC results for meropenem. ^aThe MIC interpretation of meropenem according to CLSI breakpoint in testing and reporting for Escherichia coli; ^bThe MIC interpretation of fosfomycin according to CLSI breakpoint in testing and reporting for Escherichia coli and Enterococcus faecalis urinary isolates; ^cThe MIC interpretation of Berberine hydrochloride is not available; ^dThe MIC interpretation of doxycycline according to CLSI breakpoint in tetracycline for N. gonorrhoeae.Abbreviation: NA, not available.

Figure 1 Geographic locations of the provinces where 451 N. gonorrhoeae isolates for antimicrobial susceptibility tests were collected and the number of isolates collected from each province.

Abbreviation: n, number.

Figure 2 The percentage of N. gonorrhoeae isolates with different MICs (mg/L) for four evaluated agents, by province. (A) meropenem; (B) fosfomycin; (C) berberine hydrochloride; (D) doxycycline. The MIC₅₀ (yellow-dotted line), MIC₉₀ (red-dotted line) and number of isolates per province was shown in each Figure.

Abbreviations: BJ, Beijing; GD, Guangdong; GX, Guangxi; LN, Liaoning; SC, Sichuan; SX, Shaanxi; TJ, Tianjin; YN, Yunnan; n, number.

Figure 3 (A–D) Correlation between MICs of meropenem, fosfomycin, berberine hydrochloride, doxycycline and ceftriaxone. Each symbol represents one or multiple isolates, which is indicated by specific numbers and colors. The regression line was calculated using log₂-transformed MIC data. r value and its corresponding P value are indicated. For MICs determined as ≤ or ≥ a specific value, this specific value was used for calculating linear regression of log₂-transformed MIC data.

Figure 4 (A–D) Correlation between MICs of meropenem, fosfomycin, berberine hydrochloride, doxycycline and azithromycin. Each symbol represents one or multiple isolates, which is indicated by specific numbers and colors. The regression line was calculated using log₂-transformed MIC data. r value and its corresponding P value are indicated. For MICs determined as ≤ or ≥ a specific value, this specific value was used for calculating linear regression of log₂-transformed MIC data.

Table 2 MIC Distribution of Selected Antimicrobial Agents for 24 Isolates of N. gonorrhoeae with Decreased Susceptibility to Ceftriaxone (MIC ≥ 0.25mg/L)^a

Number (%) of Isolates for Which the Antimicrobial Agent MIC (mg/L) Was
Antimicrobial Agent	0.03	0.06	0.125	0.25	0.5	1	2	4	8	16	32	64	128	≥256
Ceftriaxone				7 (29.2)	4 (16.7)	13 (54.2)
Meropenem	3 (12.5)	12 (50.0)	9 (37.5)
Fosfomycin									1 (4.2)	9 (37.5)	10 (41.7)	3 (12.5)	1 (4.2)
Berberine hydrochloride									2 (8.3)	6 (25.0)	12 (50.0)	3 (12.5)		1 (4.2)
Doxycycline					1 (4.2)	10 (41.7)	11 (45.8)				2 (8.3)
Azithromycin			1 (4.2)	6 (25.0)	14 (58.3)	1 (4.2)		1 (4.2)	1 (4.2)

Notes: ^aThe breakpoint of ceftriaxone (MIC < 0.25mg/L, susceptible) is based on the guidelines for laboratory testing of sexually transmitted diseases in China Guidelines for laboratory testing of sexually transmitted diseases, 2019.

Table 3 MIC Distribution of Selected Antimicrobial Agents for 87 Isolates of N. gonorrhoeae Resistance to Azithromycin (MIC ≥ 1mg/L)^a

Number (%) of Isolates for Which the Antimicrobial Agent MIC (mg/L) Was
Antimicrobial Agent	≤0.004	0.008	0.015	0.03	0.06	0.125	0.25	0.5	1	2	4	8	16	32	64	128	≥256
Azithromycin									54 (62.1)	10 (11.5)	4 (4.6)	19 (21.8)
Meropenem*	1 (1.2)	8 (9.4)	25 (29.4)	41 (48.2)	7 (8.2)	3 (3.5)
Fosfomycin											1 (1.1)	2 (2.3)	18 (20.7)	52 (59.8)	12 (13.8)	2 (2.3)
Berberine hydrochloride												5 (5.7)	33 (37.9)	39 (44.8)	6 (6.9)	2 (2.3)	2 (2.3)
Doxycycline								5 (5.7)	18 (20.7)	28 (32.2)	1 (1.1)	7 (8.0)	8 (9.2)	14 (16.1)	6 (6.9)
Ceftriaxone		7 (8.0)	23 (26.4)	22 (25.3)	22 (25.3)	10 (11.5)	1 (1.1)	1 (1.1)	1 (1.1)

Notes: *There were 2 isolates without MIC data for meropenem. ^aThe breakpoint of azithromycin (MIC ≤ 0.25 g/L, susceptible; 0.5 mg/L, intermediate susceptible; ≥ 1mg/L, resistance) is based on the guidelines for laboratory testing of sexually transmitted diseases in China Guidelines for laboratory testing of sexually transmitted diseases, 2019.