Multidrug-resistant Neisseria Gonorrhoeae Research Articles

Two cases of multidrug-resistant Neisseria gonorrhoeae related to travel in south-eastern Asia, France, June 2019.

We report two cases of multidrug-resistant Neisseria gonorrhoeae urogenital infection with ceftriaxone resistance in a heterosexual couple in south-western France who were successfully treated with a single, high dose of intramuscular ceftriaxone (1 g). Whole genome sequencing of isolate F91 identified MLST13871, NG-MAST1086, NG-STAR233. Patient history revealed the isolate F91 was most likely acquired during a trip to Cambodia and belongs to the successful multidrug-resistant FC428 Asian clone.

Complement alone drives efficacy of a chimeric antigonococcal monoclonal antibody.

Multidrug-resistant Neisseria gonorrhoeae is a global health problem. Monoclonal antibody (mAb) 2C7 recognizes a gonococcal lipooligosaccharide epitope that is expressed by >95% of clinical isolates and hastens gonococcal vaginal clearance in mice. Chimeric mAb 2C7 (human immunoglobulin G1 [IgG1]) with an E430G Fc modification that enhances Fc:Fc interactions and hexamerization following surface-target binding and increases complement activation (HexaBody technology) showed significantly greater C1q engagement and C4 and C3 deposition compared to mAb 2C7 with wild-type Fc. Greater complement activation by 2C7-E430G Fc translated to increased bactericidal activity in vitro and, consequently, enhanced efficacy in mice, compared with “Fc-unmodified” chimeric 2C7. Gonococci bind the complement inhibitors factor H (FH) and C4b-binding protein (C4BP) in a human-specific manner, which dampens antibody (Ab)-mediated complement-dependent killing. The variant 2C7-E430G Fc overcame the barrier posed by these inhibitors in human FH/C4BP transgenic mice, for which a single 1 μg intravenous dose cleared established infection. Chlamydia frequently coexists with and exacerbates gonorrhea; 2C7-E430G Fc also proved effective against gonorrhea in gonorrhea/chlamydia-coinfected mice. Complement activation alone was necessary and sufficient for 2C7 function, evidenced by the fact that (1) “complement-inactive” Fc modifications that engaged Fc gamma receptor (FcγR) rendered 2C7 ineffective, nonetheless; (2) 2C7 was nonfunctional in C1q−/− mice, when C5 function was blocked, or in C9−/− mice; and (3) 2C7 remained effective in neutrophil-depleted mice and in mice treated with PMX205, a C5a receptor (C5aR1) inhibitor. We highlight the importance of complement activation for antigonococcal Ab function in the genital tract. Elucidating the correlates of protection against gonorrhea will inform the development of Ab-based gonococcal vaccines and immunotherapeutics.

Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018.

We describe a multidrug-resistant Neisseria gonorrhoeae urethritis case with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Ireland, August 2018. Whole-genome sequencing showed that the isolate IR72 belongs to the internationally spreading multidrug-resistant ceftriaxone-resistant FC428 clade, initially described in Japan in 2015. IR72 was assigned MSLT ST1903, NG-MAST ST17842 and NG-STAR type 1133, including the ceftriaxone resistance-mediating penA-60.001. Global awareness of spreading ceftriaxone-resistant gonococcal strains that threaten recommended dual therapies is essential.

Human Factor H Domains 6 and 7 Fused to IgG1 Fc Are Immunotherapeutic against Neisseria gonorrhoeae.

Novel therapeutics against multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococcal lipooligosaccharide often expresses lacto-N-neotetraose (LNnT), which becomes sialylated in vivo, enhancing factor H (FH) binding and contributing to the organism's ability to resist killing by complement. We previously showed that FH domains 18-20 (with a D-to-G mutation at position 1119 in domain 19) fused to Fc (FHD1119G/Fc) displayed complement-dependent bactericidal activity in vitro and attenuated gonococcal vaginal colonization of mice. Gonococcal lipooligosaccharide phase variation can result in loss of LNnT expression. Loss of sialylated LNnT, although associated with a considerable fitness cost, could decrease efficacy of FHD1119G/Fc. Similar to N. meningitidis, gonococci also bind FH domains 6 and 7 through Neisserial surface protein A (NspA). In this study, we show that a fusion protein comprising FH domains 6 and 7 fused to human IgG1 Fc (FH6,7/Fc) bound to 15 wild-type antimicrobial resistant isolates of N. gonorrhoeae and to each of six lgtA gonococcal deletion mutants. FH6,7/Fc mediated complement-dependent killing of 8 of the 15 wild-type gonococcal isolates and effectively reduced the duration and burden of vaginal colonization of three gonococcal strains tested in wild-type mice, including two strains that resisted complement-dependent killing but on which FH6,7/Fc enhanced C3 deposition. FH/Fc lost efficacy when Fc was mutated to abrogate C1q binding and in C1q-/- mice, highlighting the requirement of the classical pathway for its activity. Targeting gonococci with FH6,7/Fc provides an additional immunotherapeutic approach against multidrug-resistant gonorrhea.

Development of complement factor H based immunotherapeutic molecules against multidrug-resistant Neisseria gonorrhoeae

Development of complement factor H based immunotherapeutic molecules against multidrug-resistant Neisseria gonorrhoeae

Repositioning of 8-hydroxyquinoline derivatives as a new promising candidate for combating multidrug resistant Neisseria gonorrhoeae.

The multidrug resistance of Neisseria gonorrhoeae becomes a public health problem worldwide, especially the strain H041 that showed the decrease susceptibility to ceftriaxone which is the last resort for gonorrhea treatment. Therefore, the simultaneous discovery and development of a new compound to fight this pathogen is urgently required. In this study, 8-hydroxyquinoline (8HQ) and derivatives were evaluated for their antimicrobial activities against the gonococcal pathogen using spectinomycin as the reference drug. The results showed that 8HQ derivatives gave an excellent antimicrobial potency. Particularly, the dihalogenated 8HQ (iodoquinol, clioquinol and 5,7-diCl-8HQ) exerted the high activity with MIC range of 0.08-0.15 μM, 0.10-0.20 μM and 0.28-0.56 µM, respectively, compared with the reference drug (MIC = 16 μg/mL or 48.14 μM). Moreover, these compounds were also shown to be non-cytotoxic/very high safety index. The findings reveal that these three compounds could be further developed as a new antimicrobial agent for fighting the gonorrheal disease.

Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic.

The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC-3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community-acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans. Lefamulin exhibits a unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA for peptide transfer. Lefamulin displays activity against gram-positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains) and vancomycin-resistant Enterococcus faecium. Lefamulin was also shown to retain activity against multidrug-resistant Neisseria gonorrhoeae and Mycoplasma genitalium. Lefamulin exhibits time-dependent killing, and the pharmacodynamic target best associated with antibacterial activity is ƒAUC0-24 /MIC (minimum inhibitory concentration [MIC]). Preclinical and phase II trials indicate that lefamulin concentrates in lung tissue are well tolerated at an IV dose of 150mg twice/day over 1hour or a PO dose of 600mg twice/day, and preliminary phase III data suggest similar efficacy when compared with moxifloxacin with or without linezolid in CABP. Documented resistance and cross-resistance with other gram-positive antibacterials remains low. Additional published invitro, invivo, and preclinical trial data suggest further exploration of lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for lefamulin.

Gonococcal MtrE and its surface-expressed Loop 2 are immunogenic and elicit bactericidal antibodies

The rise in multidrug resistant Neisseria gonorrhoeae poses a threat to healthcare, while the development of an effective vaccine has remained elusive due to antigenic and phase variability of surface-expressed proteins. In the current study, we identified a fully conserved surface expressed protein and characterized its suitability as a vaccine antigen. An in silico approach was used to predict surface-expressed proteins and analyze sequence conservation and phase variability. The most conserved protein and its surface-exposed Loop 2, which was displayed as both a structural and linear epitope on the oligomerization domain of C4b binding protein, were used to immunize mice. Immunogenicity was subsequently analyzed by determination of antibody titers and serum bactericidal activity. MtrE was identified as one of the most conserved surface-expressed proteins. Furthermore, MtrE and both Loop 2-containing fusion proteins elicited high protein-specific antibody titers and particularly the two Loop 2 fusion proteins showed high anti-Loop 2 titers. In addition, antibodies raised against all three proteins were able to recognize MtrE expressed on the surface of N. gonorrhoeae and showed high MtrE-dependent bactericidal activity. Our results show that MtrE and Loop 2 are promising novel conserved surface-expressed antigens for vaccine development against N. gonorrhoeae.

In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

BackgroundRecent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro synergy of 21 dual combinations including current and alternative WHO recommended treatment regimens and other dual combinations.Methods and findingsThe potential utility of in-vitro interactions of 21 combinations was investigated against 95 N. gonorrhoeae strains including 79 MDR and one XDR strain collected during March 2013 to July 2017 and fractional inhibitory concentration index (FICI) was calculated. These 21 combinations comprised of two WHO currently recommended (cefixime+azithromycin, ceftriaxone+azithromycin); two WHO recommended in treatment failure cases (azithromycin+gentamicin, spectinomycin+azithromycin) and other 17 combinations.ResultsFICI of the four WHO recommended antimicrobial combinations were higher (>1.0) than the five novel combinationbreeds (FICI range 0.603–0.951) in the study i.e. gentamicin+ertapenem, moxifloxacin+ertapenem, spectinomycin+ertapenem, azithromycin+ moxifloxacin, cefixime+gentamicin. No antagonistic effect of the above four WHO recommended combinations except spectinomycin+azithromycin (FICI = 4.25) was observed for the XDR strain. Out of above five novel combinations, four combinations produced high synergistic effects in overall 95 strains and also for the XDR strain with FICI of 0.13 to 0.38. Antagonistic effects varying from 3.2 to 12.6% were observed for 10 out of 21 tested combinations (azithromycin in combination with gentamicin and spectinomycin; ceftriaxone with moxifloxacin, gentamicin, spectinomycin and ertapenem; spectinomycin with moxifloxacin and gentamicin; cefixime and gentamicin combination with moxifloxacin).ConclusionWHO recommended cefixime+azithromycin, ceftriaxone+azithromycin combinations having no antagonism indicates their continuing clinical utility. Highest antagonism without any synergistic effect for the WHO recommended spectinomycin+azithromycin in treatment failure cases suggests that this combination should be evaluated further both in vitro and in vivo. Highest synergistic or additive effect without any antagonistic effect of the above five novel combinations suggests that these may be recommended for treatment in future.

In Vitro Synergy Testing of Gentamicin, an Old Drug Suggested as Future Treatment Option for Gonorrhoea, in Combination With Six Other Antimicrobials Against Multidrug-Resistant Neisseria gonorrhoeae Strains.

Emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Neisseria gonorrhoeae is a serious concern and combination therapy has been recommended to delay the onset of treatment failures. Gentamicin, an old and inexpensive antibiotic, is recommended in combination with azithromycin for treatment failures cases with the first-line regimen as per the latest Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines. However, not much literature is available on in vitro and in vivo efficacy of this combination. Therefore, this study was carried out to evaluate the in vitro synergy of gentamicin in combination with azithromycin and 5 other antimicrobials. In vitro synergy of gentamicin in combination with cefixime, ceftriaxone, spectinomycin, azithromycin, moxifloxacin, and ertapenem was determined by Etest for 75 N. gonorrhoeae strains, of which 65 were MDR and one was XDR. Fractional inhibitory concentration index (FICI) of ≤0.5 and >4.0 denoted synergy and antagonism respectively. Maximum efficacy of gentamicin was observed in combination with ertapenem (geometric mean FICI, 0.56) followed by cefixime (FICI, 0.87). There was no antagonism for both these combinations. However, antagonism was demonstrated in 5.3%, 8%, 8%, and 10.7% strains when gentamicin was paired with spectinomycin (FICI, 1.34), ceftriaxone (FICI, 1.13), azithromycin (FICI, 1.49), and moxifloxacin (FICI, 1.30), respectively. The findings suggest that gentamicin significantly enhances the in vitro therapeutic potency of ertapenem and cefixime which will be potentially effective to control the spread of MDR and XDR N. gonorrhoeae. The study warrants more in vitro studies and clinical trials for gentamicin + azithromycin and other 3 combinations because of considerable antagonism.

Refinement of immunizing antigens to produce functional blocking antibodies against the AniA nitrite reductase of Neisseria gonorrhoeae.

The emergence of multi-drug resistant Neisseria gonorrhoeae has generated an urgent need for novel therapies or a vaccine to prevent gonococcal disease. In this study we investigate the potential of targeting the surface exposed nitrite reductase, AniA, to block activity by producing functional blocking antibodies. AniA activity is essential for anaerobic growth and biofilm formation of N. gonorrhoeae and functional blocking antibodies may prevent colonisation and disease. Seven peptides covering regions adjacent to the active site were designed based on the AniA structure. Six of the seven peptide conjugates generated immune responses. Peptide 7, GALGQLKVEGAEN, was able to elicit antibodies capable of blocking AniA activity. Antiserum raised against the peptide 7 conjugate detected AniA in 20 N. gonorrhoeae clinical isolates. Recombinant AniA protein antigens were also assessed in this study and generated high-titre, functional blocking antibody responses. Peptide 7 conjugates or truncated recombinant AniA antigens have potential for inclusion in a vaccine against N. gonorrhoeae.

Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis

Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted therapy with antibiotics previously thought to be ineffective, made possible by rapid molecular assays to predict susceptibility. Previous studies have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro resistance to ciprofloxacin. We conducted a systematic review of studies comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial susceptibility testing results. We identified 31 studies meeting inclusion criteria, among which 7 different loci for mutations in the gyrA gene were identified, from 16 countries between the years of 1996 and 2016. We then performed a meta-analysis among those studies stratifying by use of real-time polymerase chain reaction (PCR) or non-real-time PCR technique, and compared the summary receiver operating characteristic curves between the 2 PCR methods. Among studies using real-time PCR, the pooled estimate of sensitivity and specificity of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5-99.1%) and 98.6% (95% CI, 97.0-99.3%), respectively. The summary operating characteristic curves for studies using real-time PCR techniques were well separated from those using non-real-time PCR techniques, with only slight overlap in the CIs, suggesting that real-time PCR techniques were a more accurate approach. GyrA genotype testing is a novel approach to combating the emergence of multidrug-resistant N. gonorrhoeae and is a sensitive and specific method to predict in vitro ciprofloxacin susceptibility.

Listerine for Gonorrhea

In the era of multi-drug–resistant Neisseria gonorrhoeae and increasing rates of gonorrhea particularly among MSM, we urgently need new prevention and

Implementation of a Rapid Genotypic Assay to Promote Targeted Ciprofloxacin Therapy of Neisseria gonorrhoeae in a Large Health System

Multidrug-resistant Neisseria gonorrhoeae is a top threat to public health. In November 2015, UCLA Health introduced a rapid gyrase A (gyrA) genotypic assay for prediction of Neisseria gonorrhoeae susceptibility to ciprofloxacin. We found a significant reduction in ceftriaxone use with a concomitant increase in targeted therapy.

Multidrug-Resistant Neisseria gonorrhoeae Isolates from Nanjing, China, Are Sensitive to Killing by a Novel DNA Gyrase Inhibitor, ETX0914 (AZD0914).

We tested the activity of ETX0914 against 187 Neisseria gonorrhoeae isolates from men with urethritis in Nanjing, China, in 2013. The MIC50, MIC90, and MIC range for ETX0914 were 0.03 μg/ml, 0.06 μg/ml, and ≤0.002 to 0.125 μg/ml, respectively. All isolates were resistant to ciprofloxacin, and 36.9% (69/187) were resistant to azithromycin. Of the isolates, 46.5% were penicillinase-producing N. gonorrhoeae (PPNG), 36% were tetracycline-resistant N. gonorrhoeae (TRNG), and 13% (24 isolates) had an MIC of 0.125 μg/ml for ceftriaxone. ETX0914 may be an effective treatment option for gonorrhea.

P09.10 The potential impact of vaccination on the prevalence of gonorrhoea

Introduction Gonorrhoea, one of the most common sexually transmitted infections worldwide, can lead to serious sequelae, including infertility and increased HIV transmission. Recently, untreatable, multidrug-resistant Neisseria gonorrhoeae strains have been reported. In the absence of new antibiotics, and given the speed with which resistance has emerged to all previously used antibiotics, development of a vaccine would be the ideal solution to this public health emergency. Understanding the desired characteristics, target population, and expected impact of an anti-gonococcal vaccine is essential to facilitate vaccine design, assessment, and implementation. The modelling presented herein aims to fill these conceptual gaps and inform future gonococcal vaccine development. Methods Using an individual-based, epidemiological simulation model, gonococcal prevalence was simulated in a heterosexual population of 100, 000 individuals (with a ~1.7% prevalence rate) after the introduction of vaccines with varied efficacy (10–100%) and duration of protection (2.5–20 years). Results Model simulations predicted that gonococcal prevalence could be reduced by; at least, 90% after 20 years, if all 13-year-olds were given a vaccine with 50% efficacy that does not wane. A comparable reduction in prevalence could be achieved by a vaccine with 100% efficacy that wanes after 7.5 years. A 40% reduction in prevalence would be achieved with a non-waning vaccine of just 20% efficacy. Conclusion A vaccine of moderate efficacy and duration could have a substantive impact on gonococcal prevalence and disease sequelae, if coverage is high and protection lasts over the highest risk period (i.e. most sexual partner change) among youths. Disclosure of interest statement This work was funded by the Australian National Health and Medical Research Council, The Australian Government Department of Health, and the National Institutes of Health USA. No pharmaceutical grants were received in the development of this study.

The potential impact of vaccination on the prevalence of gonorrhea

Gonorrhea, one of the most common sexually transmitted infections worldwide, can lead to serious sequelae, including infertility and increased HIV transmission. Recently, untreatable, multidrug-resistant Neisseria gonorrhoeae strains have been reported. In the absence of new antibiotics, and given the speed with which resistance has emerged to all previously used antibiotics, development of a vaccine would be the ideal solution to this public health emergency. Understanding the desired characteristics, target population, and expected impact of an anti-gonococcal vaccine is essential to facilitate vaccine design, assessment and implementation. The modeling presented herein aims to fill these conceptual gaps, and inform future gonococcal vaccine development. Using an individual-based, epidemiological simulation model, gonococcal prevalence was simulated in a heterosexual population of 100,000 individuals after the introduction of vaccines with varied efficacy (10–100%) and duration of protection (2.5–20 years). Model simulations predict that gonococcal prevalence could be reduced by at least 90% after 20 years, if all 13-year-olds were given a non-waning vaccine with 50% efficacy, or a vaccine with 100% efficacy that wanes after 7.5 years. A 40% reduction in prevalence is achievable with a non-waning vaccine of only 20% efficacy. We conclude that a vaccine of moderate efficacy and duration could have a substantive impact on gonococcal prevalence, and disease sequelae, if coverage is high and protection lasts over the highest risk period (i.e., most sexual partner change) among young people.

Production of Antimicrobial Substances by Nonpathogenic Neisseria Species

The emergence of multidrug resistant Neisseria gonorrhoeae is a serious public health concern. Compounds known as bacteriocins represent one novel approach to antimicrobial development. Bacteriocin...

Potent and rapid antigonococcal activity of the venom peptide BmKn2 and its derivatives against different Maldi biotype of multidrug-resistant Neisseria gonorrhoeae

The emergence of multidrug-resistant strains of Neisseria gonorrhoeae constitutes a serious threat to public health and necessitates the discovery of new types of antimicrobial agents. Among the 18 clinical isolates of N. gonorrhoeae with susceptible to spectinomycin, ceftriaxone and cefixime, 14 isolates were resistance to penicillin, tetracycline and ciprofloxacin, while 2 isolates were susceptible to tetracycline and another was penicillin intermediate isolate. Significant differences between laboratory strain and multidrug resistant strains were revealed by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling and bioinformatics examination using the MALDI BioTyper software. However, Maldi Biotyper was not successfully separated ciprofloxacin-penicillin resistance and ciprofloxacin-tetracycline resistance from ciprofloxacin-penicillin-tetracycline resistant N. gonorrhoeae isolates. BmKn2 is a basic, alpha-helical peptide with no disulfide-bridge venom peptides that was first isolated from Buthus martensii Kasch. A panel of BmKn2 scorpion venom peptide and its derivatives of varying length and characteristics were synthesized chemically and evaluated for their ability to inhibit the growth of clinical N. gonorrhoeae isolates. Synthetic BmKn2 displayed potent activity against 18 clinical isolates of N. gonorrhoeae with MIC50 values of 6.9–27.6μM. BmKn2 exerted its antibacterial activity via a bactericidal mechanism. Cyclic BmKn1 did not show antigonococcal activity. Decreasing the cationicity and helix percentage at the C-terminus of BmKn2 reduced the potency against N. gonorrhoeae. Taken together, the BmKn1 peptide can be developed as a topical therapeutic agent for treating multidrug-resistant strains of N. gonorrhoeae infections.

Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain

The aim of this study was to characterize the first two extended-spectrum cephalosporin-resistant and multidrug-resistant (MDR) Neisseria gonorrhoeae isolates collected from two sexually related patients (men who have sex with men) in Spain. Antimicrobial susceptibility was studied by Etest. Genes involved in quinolone, ceftriaxone and multidrug resistance were amplified by PCR and sequenced in both directions. The isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST). The two isolates had the same MDR profile, showing resistance to penicillin (MIC 0.094 mg/L; β-lactamase negative), ceftriaxone (MIC 1.5 mg/L), cefixime (MIC 1.5 mg/L), cefotaxime (MIC 1 mg/L), ciprofloxacin (MIC >32 mg/L) and tetracycline (MIC 1.5 mg/L). NG-MAST showed that both isolates belonged to sequence type (ST) 1407 (porB-908 and tbpB-110). Ciprofloxacin resistance was due to amino acid substitutions in GyrA (S91F and D95G) and ParC (S87R). An A deletion in the promoter of the MtrCDE efflux pump (mtrR) was detected. No changes were detected in the pilQ gene. The outer membrane protein PorB showed two substitutions at G120K and A121N. An L421P substitution was observed in the PBP1A (ponA) sequence. The sequence of PBP2 (penA) showed a mosaic structure related to genotype XXXIV with a single additional amino acid substitution (A501P). This genotype was identical to a recently described French isolate (F89). This is the first reported case of high-level extended-spectrum cephalosporin-resistant N. gonorrhoeae transmission. The molecular typing and MDR genotype suggest possible European spread of this strain, highlighting the need for surveillance and the importance of testing the susceptibility of N. gonorrhoeae to extended-spectrum cephalosporins.