Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales

Chisholm, Stephanie; Neal, Timothy; Alawattegama, A B; Birley, Humphrey; Howe, Robin; Ison, Catherine

doi:10.1093/jac/dkp188

Cited by 111 publications

(64 citation statements)

References 18 publications

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“…Emerging resistance to extended-spectrum cephalosporins (19,29,30), as well as resistance to fluoroquinolone (15,41) and macrolide (8,10,13,23) antibiotics, among gonococcal isolates is an ongoing challenge for the treatment and control of gonorrhea infections. In this study, we have provided insight into the antimicrobial profiles of N. gonorrhoeae isolates collected over a large geographic area using past and present antimicrobial agents recommended for gonococcal treatment (5,6).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Vidović¹,

Thakur²,

Horsman

et al. 2012

J Clin Microbiol

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A longitudinal study combining multilocus sequence typing with molecular evolutionary analysis determined the distribution, population structure, and evolution of antibiotic resistance in Neisseria gonorrhoeae isolates in Saskatchewan that were collected between 2005 and 2008. Of 195 gonococcal isolates examined, 29 sequence types (STs) were identified with 3 major circulating strains (ST-1 through ST-3) comprising 52% of all gonococcal isolates studied. The prevalences, persistence, distribution patterns, and clonalities of these isolates strongly suggest that gonorrhea endemicity within this broad geographic region was driven by these 3 circulating strains. ST-1 exhibited a significantly (P ‫؍‬ 0.001) higher prevalence throughout the study than did the others, accounting for ϳ25% of the tested isolates each year. The spatial distributions of the gonococcal strains indicated that ST-1 in 2007 entered a linear component of the sexual network, reaching the remote north and resulting in the further spread and maintenance of infection. Ciprofloxacin and azithromycin resistances were observed in distantly related gonococcal lineages, clearly indicating the convergent acquisition of these antibiotic-resistant phenotypes. In addition, all ciprofloxacinand azithromycin-resistant lineages were found at the edges of the minimum spanning tree, far from the major lineages, suggesting that these antibiotic phenotypes were most likely introduced into the province. In contrast, resistance to penicillin was found mostly in the endemic gonococcal lineages, suggesting that penicillin resistance was probably acquired in Saskatchewan as a result of spontaneous mutations in already-established lineages. Tetracycline resistance was present in all STs except one, indicating its ubiquitous nature in the gonococcal population studied. N eisseria gonorrhoeae, a fastidious Gram-negative diplococcus, is an obligate human pathogen that causes the disease gonorrhea. Complications from the spread of the organism along the mucosal surfaces may result in endometritis, salpingitis, and peritonitis in females (3), which can lead to infertility or ectopic pregnancy (27). In Canada, between 1999 and 2008, the overall rate of gonococcal infection increased by 116.5%, from 17.6 to 38 cases per 100,000 (20). Saskatchewan has had the highest infection rate of all the Canadian provinces, with an increase from 45.2 cases per 100,000 in 2000 to 131.3 cases per 100,000 in 2008, resulting in a 290.4% increase (173.4% above the national average) (20). Antimicrobial resistance in N. gonorrhoeae is a major public health problem, as treatment options are becoming increasingly limited. Recently, N. gonorrhoeae isolates with decreased susceptibilities (MIC Ն 0.25) to third-generation cephalosporins (cefixime and ceftriaxone) have been identified in Japan, Europe, the United States, and Canada (4,15,16,19,29,30). These antibiotics are the last remaining options for treating gonorrhea in a single-dose fashion, a preferred mode of treatment for gonococcal infection...

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Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Vidović¹,

Thakur²,

Horsman

et al. 2012

J Clin Microbiol

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“…Case reports of AZM-resistant N. gonorrhoeae have been described in many countries, including Canada and the United States (10)(11)(12)(13)(14)(15)(16)(17)(18), but only rarely has AZM-resistant N. gonorrhoeae been reported to be associated with concurrent reduced susceptibility to 3GC (16,17). In Canada, AZM-resistant N. gonorrhoeae was first identified in 1997, and the first AZM-resistant isolates were identified in Ontario in 1998 (10).…”

mentioning

confidence: 99%

Azithromycin Resistance Is Coevolving with Reduced Susceptibility to Cephalosporins in Neisseria gonorrhoeae in Ontario, Canada

Allen

Seah

Martín

et al. 2014

Antimicrob Agents Chemother

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d Azithromycin (AZM) is routinely recommended as a component of dual therapy for gonorrhea in combination with third-generation cephalosporins (3GC). In this study, we examined the prevalence of AZM-resistant (AZM r ) Neisseria gonorrhoeae from July 2010 to February 2013, assessed the rate of concurrent cephalosporin resistance under the current treatment recommendations, and analyzed the clonal distribution of AZM r isolates in Ontario, Canada. Nineteen AZM r clinical isolates (one per patient; MIC, >2 g/ml) were included in the study. Susceptibility profiles of these isolates to 11 antibiotics, molecular typing, characterization of macrolide resistance mechanisms, and penicillin-binding protein 2 (PBP2) patterns were determined for all the isolates. Two groups were defined based on AZM r level; group A isolates displayed high-level resistance (MIC, >2,048 g/ml) due to mutations (A2143G) in the four copies of the 23S rRNA rrl gene, and group B isolates had moderate resistance to AZM (MICs, 2 to 8 g/ml, C2599T mutation in the rrl gene), with a subgroup belonging to sequence type 3158 (ST3158) (n ‫؍‬ 8), which also showed reduced susceptibility to 3GC (MICs, 0.12 to 0.25 g/ml, PBP2 pattern XXXIV). This AZM r phenotype was not observed in previous provincial surveillance in 2008 (the ST3158 clone was found, with AZM MICs of 0.25 to 0.5 g/ml associated with mtrR mutations). We hypothesized that the AZM mutant prevention concentration (MPC) in the ST3158 subpopulation we found in 2008 was higher than the MPC in wild-type isolates (AZM MIC, <0.031 g/ml), increasing the chances of additional selection of AZM r mutations. Full AZM resistance is now emerging in this clone together with reduced susceptibility to 3GC, threatening the future efficacy of these antibiotics as therapeutic options for treatment of gonorrhea.

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“…A higher dose of 2 g of new formulations of azithromycin with a lower incidence of gastrointestinal intolerance may be more effective (9), but recent descriptions of gonococcal strains showing azithromycin resistance or high-level azithromycin resistance (AzHLR; MIC of azithromycin, Ͼ256 mg/liter) would make that treatment untenable if strains of this type were to emerge elsewhere and spread (1,2,6).…”

mentioning

confidence: 99%

New Mutation in 23S rRNA Gene Associated with High Level of Azithromycin Resistance in Neisseria gonorrhoeae

Galarza

Abad

Canigia

et al. 2010

Antimicrob Agents Chemother

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Emergence of high-level azithromycin resistance in Neisseria gonorrhoeae in England and Wales

Abstract: High-level azithromycin resistance has emerged in England and Wales. Contact tracing and typing data suggest this may have originated from Scotland. Surveillance of azithromycin resistance will be key in controlling its further dissemination.

Cited by 111 publications

References 18 publications

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Longitudinal Analysis of the Evolution and Dissemination of Neisseria gonorrhoeae Strains (Saskatchewan, Canada, 2005 to 2008) Reveals Three Major Circulating Strains and Convergent Evolution of Ciprofloxacin and Azithromycin Resistance

Azithromycin Resistance Is Coevolving with Reduced Susceptibility to Cephalosporins in Neisseria gonorrhoeae in Ontario, Canada

New Mutation in 23S rRNA Gene Associated with High Level of Azithromycin Resistance in Neisseria gonorrhoeae

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