Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jun 9;12(6):e1001838; discussion e1001838.
doi: 10.1371/journal.pmed.1001838. eCollection 2015 Jun.

Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras

Mingliang Chen  1 , Qinglan Guo  2 , Ye Wang  3 , Ying Zou  4 , Gangyi Wang  3 , Xi Zhang  3 , Xiaogang Xu  2 , Miao Zhao  2 , Fupin Hu  2 , Di Qu  5 , Min Chen  3 , Minggui Wang  2
Affiliations

Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras

Mingliang Chen et al. PLoS Med. .

Abstract

Background: Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC) prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.

Methods and findings: A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84%) in 1965-1973 to serogroup A CC1 (58%) in 1974-1985, then to serogroup C or B CC4821 (62%) in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37) in 2005-2013 (p < 0.001). Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31) were assigned to either CC4821 (n = 20) or CC5 (n = 7). The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31) of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31) of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15) among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available and that only a small sample of convenience isolates from 1965-1985 were available.

Conclusions: The increasing prevalence of ciprofloxacin resistance since 2005 in Shanghai was associated with the spread of hypervirulent lineages CC4821 and CC5. Two resistant meningococcal clones ChinaCC4821-R1-C/B and ChinaCC5-R14-A have emerged in Shanghai during the quinolone era. Ciprofloxacin should be utilized with caution for the chemoprophylaxis of N. meningitidis in China.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Annual incidence of reported cases of meningococcal disease in Shanghai from 1950 to 2013.
The trend was analyzed using regression splines (red dotted line).
Fig 2
Fig 2. Case fatality rate of reported cases of meningococcal disease in Shanghai from 1950 to 2013.
The trend was analyzed using regression splines (red dotted line).
Fig 3
Fig 3. Minimum spanning tree analysis of multi-locus sequence types of N. meningitidis from patients.
Isolates were obtained from patients during the periods 1965–1973, 1974–1985, and 2005–2013. STs are displayed as circles. The size of each circle indicates the number of isolates of this particular type. Serogroup is distinguished by different colors. The shaded halo surrounding the STs encompasses related STs that belong to the same CC. Heavy solid lines represent SLVs, and light solid lines represent DLVs.
Fig 4
Fig 4. Dendrogram of 51 ciprofloxacin-nonsusceptible N. meningitidis strains from patients and carriers in Shanghai, China, 2005–2013, constructed using pulsed-field gel electrophoresis—NheI.
The clones ChinaCC4821-R1-C/B and ChinaCC5-R14-A are indicated in grey shading, with the relatedness values marked on the roots. ●The PFGE data for the Anhui outbreak strain 053442 were obtained from PulseNet China. §Clonal dissemination between patients and their close contacts was observed. †Imported cases. NG, non-groupable.
Fig 5
Fig 5. Timeline for the introduction of fluroquinolones and vaccines, and clonal waves of N. meningitidis in China.
SG, serogroup.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jafri RZ, Ali A, Messonnier NE, Tevi-Benissan C, Durrheim D, Eskola J, et al. Global epidemiology of invasive meningococcal disease. Popul Health Metr. 2013;11:17 10.1186/1478-7954-11-17 - DOI - PMC - PubMed
    1. Bratcher HB, Bennett JS, Maiden MC. Evolutionary and genomic insights into meningococcal biology. Future Microbiol. 2012;7:873–885. 10.2217/fmb.12.62 - DOI - PMC - PubMed
    1. Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, Paul M, Leibovici L. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2011;10:CD004785. - PubMed
    1. Wu HM, Harcourt BH, Hatcher CP, Wei SC, Novak RT, Wang X, et al. Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America. N Engl J Med. 2009;360:886–892. 10.1056/NEJMoa0806414 - DOI - PubMed
    1. Lapadula G, Vigano F, Fortuna P, Dolara A, Bramati S, Soria A, et al. Imported ciprofloxacin-resistant Neisseria meningitidis . Emerg Infect Dis. 2009;15:1852–1854. 10.3201/eid1511.090833 - DOI - PMC - PubMed

Publication types

Grants and funding

This study was funded by grants (81120108024 to MW and 81102509 to QG) from the National Natural Science Foundation of China, a grant (2013ZX10004216-001-004 to MC) of the National Key Programs for Infectious Diseases of China, and a grant (12JC1401700 to MW) of Shanghai Municipal Science and Technology Committee. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.