First Three Neisseria gonorrhoeae Isolates with High-Level Resistance to Azithromycin in Sweden: a Threat to Currently Available Dual-Antimicrobial Regimens for Treatment of Gonorrhea?

Unemo, Magnus; Golparian, Daniel; Hellmark, Bengt

doi:10.1128/aac.02093-13

Cited by 60 publications

(57 citation statements)

References 12 publications

(12 reference statements)

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“…Sporadic infections with highly azithromycin-resistant N. gonorrhoeae isolates have been reported since 2001 in Argentina [7], in Scotland (2004) [8], in Wales (2007) [9], in Italy (2007) [10], in the United States (2011) [11] and in Sweden in 2013 [12]. Here we described the first isolate identified and presumably acquired in France.…”

Section: Discussionmentioning

confidence: 85%

“…Here we described the first isolate identified and presumably acquired in France. In previous publications [7,9,11,12], high-level azithromycin resistance was shown to result from the accumulation of mutations in the four rrl alleles at positions 2143 (G instead of A) or 2599 (T instead of C) in the domain V of the 23S rRNA involved in the binding site of azithromycin (NG numbering). In this report, our isolate harboured the C2599T mutation in the four rrl alleles.…”

Section: Discussionmentioning

confidence: 99%

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High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014

et al. 2014

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We report the first case in France of a high-level azithromycin-resistant Neisseria gonorrhoeae (minimum inhibitory concentration (MIC) = 96 mg/L) assigned to MLST7363 (NG-MAST ST6360), also resistant to ciprofloxacin and tetracycline but susceptible to ceftriaxone. The patient was a 51 year-old heterosexual man who returned following 1g azithromycin monotherapy. Mechanisms of azithromycin resistance were a C2599T mutation in the four copies of the rrl gene and a novel mutation in the promoter of the mtrR gene.The surveillance of Neisseria gonorrhoeae (NG) susceptibility to antibiotics in France is based on a voluntary sentinel network of laboratories [1]. In March 2014, the first NG strain showing a high level of azithromycin resistance was isolated from the urine of a 51 year-old man living in the south of France. He had a history of a Chlamydia trachomatis infection 20 years ago. The patient was heterosexual and declared having sex with only two regular female partners (last sexual contact four and ten days before symptoms). Case descriptionAt the first visit, the patient presented with mild symptoms of urethritis. He was in good general state of health and his HIV test was negative. No microbiological analyses were performed and the patient was treated empirically with a single dose of azithromycin (1 g orally) for suspected C. trachomatis infection. The patient presented again with persisting symptoms 48 hours later. At that time, he was treated empirically with a single dose of spectinomycin (2 g intramuscularly) and bacteriological examination was performed with direct microscopic examination and culture. Culture results indicated the presence of an azithromycin-resistant NG isolate. The absence of C. trachomatis infection was determined retrospectively by negative nucleic acid amplification test. At a third visit, one week later the patient was successfully cured and free of clinical symptoms.In France, the first-line treatment of uncomplicated urogenital gonorrhoea is ceftriaxone (500 mg intramuscularly), whereas spectinomycin is used in cases of contraindication to beta-lactams. For our patient, the clinician chose spectinomycin because of his own prescribing practices. Infection with the azithromycinresistant-strain was presumably acquired in France since neither the patient nor his sexual contacts had travelled in the past six months or had other known sexual contacts. In addition, they had not received any antibiotic treatment in the preceding six months.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014

et al. 2014

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“…This was most notable for the MtrC-MtrD-MtrE pump in H041, the first clinical XDR isolate with high-level resistance to ceftriaxone, which was obtained from a ceftriaxone treatment failure (12). However, this was also observed for many MDR clinical gonococcal strains (6,10,24,25), including strains that resulted in ESC treatment failures. Accordingly, a specific efflux pump inhibitor (EPI) of the gonococcal MtrC-MtrD-MtrE pump, particularly coadministered with appropriate antimicrobials, might be a future treatment option for gonorrhea.…”

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confidence: 96%

“…The isolates examined were WHO reference strains WHO F, which is considered to be a wild-type strain susceptible to all of the antimicrobials included, and WHO P (24); four isolates from ESC treatment failures, including the first XDR strain (H041) with high-level ceftriaxone resistance (6,10,12); one isolate displaying high-level azithromycin resistance (25); and three isolates display- ing low-level azithromycin resistance. All of the strains except WHO F contained mtrR mutations known to increase the expression of mtrCDE (21,26) and possessed the mtrCDE-, macAB-, and norM-encoded pumps.…”

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confidence: 99%

Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae

Golparian

Shafer

Ohnishi

et al. 2014

Antimicrob Agents Chemother

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The contribution of drug efflux pumps in clinical isolates of Neisseria gonorrhoeae that express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted.

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“…Past AMR studies using limited numbers of gonococcal strains from specific geographic regions of the globe have mostly focused on a number of representative genes or genetic regions of the genome to elucidate underlying mechanisms of antibiotic resistance (Hagman & Shafer, 1995;Lindberg, Fredlund, Nicholas, & Unemo, 2007;Ohneck et al, 2011;Thakur, Levett, Horsman, & Dillon, 2014;Tomberg, Unemo, Ohnishi, Davies, & Nicholas, 2013;Unemo & Shafer, 2014;Unemo, Golparian, & Hellmark, 2014;Unemo, Golparian, & Nicholas, 2012;Zhao et al, 2009).…”

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confidence: 99%

Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance

Ezewudo

Joseph

Castillo-Ramírez

et al. 2014

Preprint

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Neisseria gonorrhoeae is the causative agent of gonorrhea, a sexually transmitted infection (STI) of major importance. As a result of antibiotic resistance, there are now limited options for treating patients. We collected whole genome sequences and associated metadata data on 76 N. gonorrhoeae strains from around the globe and searched for known determinants of antibiotics resistance within the strains. The population structure and evolutionary forces within the pathogen population were analyzed. Our results indicated a cosmopolitan gonoccocal population mainly made up of five subgroups. The estimated ratio of recombination to mutation (r/m=2.2) from our data set indicates an appreciable level of recombination occurring in the population. Strains with resistance phenotypes to more recent antibiotics (azithromycin and cefixime) were mostly found in two of the five population subgroups.PeerJ PrePrints | http://dx.doi.org/10.7287/peerj.preprints.636v1 | CC-BY 4.0 Open Access |

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First Three Neisseria gonorrhoeae Isolates with High-Level Resistance to Azithromycin in Sweden: a Threat to Currently Available Dual-Antimicrobial Regimens for Treatment of Gonorrhea?

Cited by 60 publications

References 12 publications

High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014

High-level azithromycin-resistant Neisseria gonorrhoeae clinical isolate in France, March 2014

Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae

Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance

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