Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce β-lactamase

Akasaka, Soichiro; Muratani, Tetsuro; Yamada, Yoji; Inatomi, Hisato; Takahashi, Koichi; Matsumoto, Testsuro

doi:10.1007/s101560170034

Cited by 64 publications

(39 citation statements)

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“…In Japan, ceftriaxone was not endorsed for gonorrhea treatment from the 1990s to the early 2000s. Consequently, many oral cephalosporins and dose regimens, including some with suboptimal efficacies, were prescribed for monotherapy, but if resistance was identified, cefodizime or spectinomycin was administered (139,140). Multiple low-dose regimens of oral cephalosporins were frequently used, which could have resulted in subinhibitory cephalosporin concentrations and, accordingly, may have selected for cephalosporin resistance (5,(140)(141)(142)(143).…”

Section: Figmentioning

confidence: 99%

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

2014

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SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae , including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection.

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Section: Figmentioning

confidence: 99%

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

2014

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“…As alternatives to fluoroquinolones, cephalosporins are potent antibiotics that are commonly used in the oral form for the treatment of gonococcal infections in Japan. However, decreases in the susceptibilities of present clinical isolates of N. gonorrhoeae to oral cephalosporins, including cefixime, have also been observed (1,17).…”

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confidence: 99%

Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan

Ito¹,

Deguchi²,

Mizutani³

et al. 2005

Antimicrob Agents Chemother

190

192

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Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were >0.125 g/ml and randomly selected 15 isolates for which cefixime MICs were <0.06 g/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were >0.5 g/ml and the cefdinir MICs were >1 g/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.

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“…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.…”

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confidence: 99%

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

Muratani

Akasaka

Kobayashi³

et al. 2001

Antimicrob Agents Chemother

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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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Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce β-lactamase

Cited by 64 publications

References 4 publications

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

Emergence and Spread of Neisseria gonorrhoeae Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan

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

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