Antimicrobial Susceptibility of Neisseria gonorrhoeae in Fukuoka City, Japan, in the Early 1980s and 1997–1998: Emergence of High-Level Fluoroquinolone Resistance

Resistance to fluoroquinolones in gonococcal isolates has recently become a significant problem in Far East Asia including Japan (2). In the present study, we examined the in vitro antimicrobial susceptibilities of gonococcal isolates from 1997 to 1998 in Fukuoka City, Japan, to various agents, in order to investigate the emergence of high-level fluoroquinolone resistance.

A total of 186 strains of Neisseria gonorrhoeae were isolated from men with urethritis attending a sexually transmitted diseases (STD) clinic in Fukuoka City from March 1997 through March 1998. Of the 186 isolates, 157 were included in this study, while the remaining 29 were from patients known to have received fluoroquinolones or other antibiotics and were excluded. For comparative purposes, antimicrobial susceptibilities of 27 N. gonorrhoeae strains, 14 β-lactamase producing and 13 not β-lactamase producing, that were urethral isolates obtained at an STD clinic in the city between 1981 and 1984 were also tested. The MICs for all isolates were determined by an agar dilution technique and twofold dilutions of antibiotic (2). The criterion for high-level ciprofloxacin resistance in N. gonorrhoeae isolates was a MIC of 1 to 16 μg/ml (1). There are no established criteria that define resistance to other fluoroquinolones. Therefore, we set the criteria for high-level resistance as follows: ≥2 μg/ml for norfloxacin, ≥0.5 μg/ml for levofloxacin, ≥0.5 μg/ml for sparfloxacin, and ≥0.25 μg/ml for DU-6859a. The proportions of strains from 1997–1998 with high-level resistance to the five fluoroquinolones were compared with those of strains from 1981 to 1984 by the chi-square test.

Of the 157 strains from 1997–1998, 37 (23.6%) showed high-level resistance to ciprofloxacin (MIC ≥ 1 μg/ml), while none of the 27 strains from 1981 to 1984 showed high-level resistance to ciprofloxacin. The proportions of the 1997–1998 strains showing high-level resistance to norfloxacin (MIC ≥ 2 μg/ml), levofloxacin (MIC ≥ 0.5 μg/ml), sparfloxacin (MIC ≥ 0.5 μg/ml), and DU-6859a (MIC ≥ 0.25 μg/ml) were 32.5, 28.7, 21.7, and 8.3%, respectively. On the other hand, none or only one of the 27 isolates from 1981 to 1984 were highly resistant to these fluoroquinolones (Table 1). These differences in prevalence of high-level resistance to the five fluoroquinolones between the strains from 1997–1998 and those from 1981 to 1984 were statistically significant (P < 0.0001). In the present study, the emergence of high-level resistance not only to older fluoroquinolones such as norfloxacin and ciprofloxacin but also to newer ones such as levofloxacin and sparfloxacin was found in N. gonorrhoeae isolates obtained in 1997–1998 in Fukuoka City. However, no significant reductions in the susceptibilities of the 1997–1998 strains to β-lactams, tetracycline, azithromycin, or spectinomycin were observed.

TABLE 1.

Distribution of antimicrobial susceptibilities of N. gonorrhoeae isolates to fluoroquinolones

Agent	No. of strains for which the MIC (μg/ml) was:													No. of highly resistanta strains (%)
	≤0.008	0.016	0.031	0.063	0.125	0.25	0.5	1	2	4	8	16	32
Ciprofloxacin
1997–1998	66	5	18	9	11	5	6	2	5	14	11	5		37 (23.6)
1981–1984	15	5	3	3		1								0
Norfloxacin
1997–1998		26	40	3	4	15	11	7	6	6	8	28	3	51 (32.5)
1981–1984	4	4	5	3	7	3			1					1 (3.7)
Levofloxacin
1997–1998	61	9	5	17	10	10	7	2	6	11	18	1		45 (28.7)
1981–1984	11	9	6		1									0
Sparfloxacin
1997–1998	72	8	14	8	17	4	7	2	11	8	6			34 (21.7)
1981–1984	1	9	7	5	4		1							1 (3.7)
DU-6859a
1997–1998	98	13	9	6	18	12	1							13 (8.3)
1981–1984	26		1											0

^aDefined as ≥1 μg/ml for ciprofloxacin, ≥2 μg/ml for norfloxacin, ≥0.5 μg/ml for levofloxacin, ≥0.5 μg/ml for sparfloxacin, and ≥0.25 μg/ml for DU-6859a.