Outbreak of Cefozopran (Penicillin, Oral Cephems, and Aztreonam)-Resistant Neisseria gonorrhoeae in Japan

Abstract

We have previously reported that the Neisseria gonorrhoeae isolates from clinical failure cases treated with cefdinir and aztreonam, ␤-lactams exhibited high MICs. These resistant isolates were clearly separated from the isolates exhibiting a low level of resistance to ␤-lactams as shown by the MIC distribution of cefozopran. Restriction fragment length polymorphism DNA typing revealed that the outbreak of cefozopran-resistant isolates in Kitakyushu, Japan, occurred as a result of clonal spread.As a result of the absence of strains of Neisseria gonorrhoeae resistant to the expanded spectrum of cephems, the National Committee for Clinical Laboratory Standards (NCCLS) (8) has not defined the breakpoint MICs of expanded-spectrum cephems such as cefixime (CFM), cefpodoxime (CPD), cefepime (FEP), etc. A previous study reported the incidence of clinical failures in gonococcal urethritis treated with cefdinir (CDR) or aztreonam (ATM) (1). For the N. gonorrhoeae isolates from such clinical failure cases, high-level MICs of CDR, ATM, and other ␤-lactams were observed. In order to investigate the prevalence of these resistant isolates in Kitakyushu, Japan, we examined 54 N. gonorrhoeae isolates from different cases occurring during 1999 for susceptibility to a variety of antimicrobial agents. Forty of 54 strains were isolated from male patients with gonococcal urethritis, while the remaining isolates were from female patients with gonococcal cervicitis. Identification of N. gonorrhoeae and testing for production of ␤-lactamase were performed by ID-test-HN-20 Rapid (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) using colonies cultured on Thayer-Martin Agar Base, Modified (Nissui Pharmaceutical Co.). The MICs of various antimicrobials were determined by the twofold serial agar dilution method on BBL GC Agar Base (Becton Dickinson and Co., Cockeysville, Md) with 1% BBL IsoVitalX enrichment (Becton Dickinson Europe, Meylan, France) according to the guidelines of the NCCLS (8). The antimicrobial agents used in this study were purchased from or provided by the corresponding companies.The MIC distribution of cefozopran (CZO) for N. gonorrhoeae isolates was divided into two groups. The MICs for the high-level resistance group (8 to 16 g/ml) were more than 16 times greater than the MICs for the susceptible and low-level resistance groups (Ͻ0.5 g/ml). The MICs of CZO were correlated with those of CDR, CPD, cefpirome (CPI), FEP, ATM, cefuroxime, cefotiam, ceftizoxime (ZOX), CFM, and cefcapene (CPN). The MICs of CZO correlated poorly with those of penicillin (PEN), cefmetazole, flomoxef, and cefodizime (CDZ) despite the fact that all 17 CZO-resistant isolates for these four agents belonged to the high-level MIC group. CFM, CDZ and ceftriaxone (CRO) exhibited lower MICs but the resistant isolates belonged to the group with reduced susceptibility to these three agents. These new resistant strains were clearly divided into two groups by the MIC distribution of CZO, with all of the CZO-resistant isolates exhibiting either resistance or ...

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