ࡱ> rbjbj884RR8)NN8dX#"L$$$$$%Z?&[&$v0&%%&&$$\f\f\f\& $$f\&f\f\j$P < D K2qr0}&P d k&&f\& &Yk&k&k&[k&k&k&&&&&k&k&k&k&k&k&k&k&k&N n:Guidelines 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults M Unemo1, JDC Ross2, AB Serwin3, M Gomberg4, M Cusini5 and JS Jensen6 1WHO Collaborating Center for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, rebro University Hospital and Faculty of Medicine and Health, rebro University, rebro, Sweden 2University Hospital Birmingham NHS Foundation Trust, Birmingham, UK 3Department of Dermatology and Venereology, Medical University of BiaBystok, BiaBystok, Poland 4Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology, Moscow, Russia 5Department of Dermatology, Fondazione IRCCS Ca' Granda Ospedale Policlinico, Milano, Italy 6Infection Preparedness, Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark Abstract Gonorrhoea, including its severe complications and sequelae, is a major public health concern globally. In many European countries, increasing incidence and sporadic cases of ceftriaxone resistance, including treatment failures, is a growing concern. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea in Europe. Compared to the outdated 2012 European gonorrhoea guideline, the updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured NAATs and culture; dual antimicrobial therapy including high dose of ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance (identification, verification and reporting) of treatment failures with recommended treatment regimens. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. For detailed background, evidence base and discussions, see the background review for the present 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020). Keywords Neisseria gonorrhoeae, gonorrhoea, sexually transmitted infection, Europe, management, diagnosis, antimicrobial resistance, treatment Corresponding author: M Unemo, WHO Collaborating Center for Gonorrhoea and other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, rebro University Hospital, rebro, Sweden. Email: magnus.unemo@regionorebrolan.se The present evidence-based guideline represents an updated version of the 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults.1 For detailed background, evidence base and discussions, see the background review for the present 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020). Aetiology, transmission, and epidemiology Gonorrhoea is caused by the obligate human pathogenic, Gram-negative bacterium Neisseria gonorrhoeae;2 Infection predominantly involves the columnar epithelium of the urethra, endocervix, rectum, oropharynx, and conjunctivae. Infection can ascend to the upper genital tract to cause pelvic inflammatory disease (PID) and epididymo-orchitis;1-3 Transmission is by direct inoculation of infected secretions from one mucosa to another, i.e., genital-urogenital, urogenital-anorectal, oro-urogenital, or oro-anal contact, or by mother-to-child transmission at birth;1-7 In the European Union (EU)/European Economic Area (EEA), gonorrhoea is the second (after Chlamydia trachomatis infections) most frequently reported bacterial STI, and the incidence has increased by (240% since 2008.8 In 2018, 76% of gonorrhoea cases were reported in men,8 reflecting the high prevalence in men who have sex with men (MSM) and the higher proportion of diagnosed symptomatic urogenital infections in men. In 2018, the highest incidence of gonorrhoea in the EU/EEA was among 25-34 year olds, closely followed by 15-24 year olds and, in many countries, there is a disproportionate burden of infection in MSM and/or ethnic minority groups.8-10 Clinical features1-3,11-16 Symptoms and physical signs of gonorrhoea reflect localised inflammation of infected mucosal surfaces in the urogenital tract and several other STIs cause similar symptoms. Symptoms In men, acute urethritis is predominant with symptoms of urethral discharge (>80%) and dysuria (>50%), usually starting within 2-8 days of exposure. Asymptomatic urethral infection in men is rare (<10% of infections); In women, endocervical and urethral infection include symptoms such as increased or altered vaginal discharge (d"50%), lower abdominal pain (d"25%), dysuria (10-15%), and occasionally intermenstrual bleeding or menorrhagia. Endocervical infection is frequently asymptomatic (e"50%); Rectal and oropharyngeal infections in men and women are usually asymptomatic. Rare symptoms include anal discharge and perianal/anal pain, or discomfort and sore throat, respectively. Physical signs In men, mucopurulent urethral discharge is most common, which may be accompanied by erythema of the urethral meatus; In women, urogenital examination may be normal or a mucopurulent discharge may be evident from the cervix, sometimes accompanied with hyperaemia and contact bleeding of the endocervix. Complications and sequelae PID in women, potentially resulting in ectopic pregnancy and infertility, and epididymo-orchitis in men are complications of infection ascending to the upper genital tract; Gonococcal bacteraemia is generally rare,17,18 but can be more common in high-prevalent gonorrhoea areas and may be expected to increase when the gonorrhoea incidence increases.19 This is usually manifested by skin lesions, fever, arthralgia, acute arthritis, and tenosynovitis (disseminated gonococcal infection [DGI]).3,17-21 Indications for testing [2C] Symptoms or signs of urethral discharge in men; Cervical or vaginal discharge with risk factor for STI (age <30 years, new sexual contact in the last year, or more than one partner in the last year); Mucopurulent cervicitis; Persons newly diagnosed with other STI; Sexual contact of persons with an STI or PID; Acute epididymo-orchitis in a male aged <40 years or with risk factors for STIs; Acute pelvic pain or signs of PID; When performing a STI screen in young adults (<25 years of age) or MSM; When performing a STI screen in individuals with new or multiple recent sexual contacts; Purulent conjunctivitis in a neonate or adult; Mother of a newborn with ophthalmia neonatorum; Unplanned termination of pregnancy in areas or populations of high gonorrhoea prevalence; Any intrauterine interventions or manipulations in areas or populations of high gonorrhoea prevalence.22,23 Testing and diagnosis Diagnosis of uncomplicated gonorrhoea is established by identification of N. gonorrhoeae in urogenital, rectal, oropharyngeal, or ocular secretions;2,24 N. gonorrhoeae can be detected by nucleic acid amplification tests (NAATs) or culture. The bacterium can also be visualized by microscopy of a stained anogenital tract smear to facilitate rapid diagnosis in symptomatic patients; Microscopy (1000) using Gram or methylene blue staining for identification of characteristic intracellular diplococci within polymorphonuclear leukocytes offers adequate sensitivity (90-95%) and specificity (>99%) as a rapid diagnostic test in symptomatic men with urethral discharge [1C].1-3,12,24,25 Microscopy has a low sensitivity in asymptomatic men (50-75%) and from endocervical (16-50%) or rectal (d"40%) sites, and microscopy is not recommended as a test of exclusion in these patients [1C].1-3,12,14,24-28 Microscopy is also not recommended for detection of oropharyngeal gonorrhoea due to low specificity and sensitivity; Culture, including appropriate species confirmation, is a highly specific test, and relatively sensitive for urogenital specimens, providing that specimen collection, transport, storage, and culture procedures are optimised. However, the sensitivity of culture for rectal and oropharyngeal specimens is significantly lower.1,2,24,29 Diagnostic culture is appropriate for endocervical, urethral, rectal, oropharyngeal and conjunctival specimens but not for urine or vaginal swabs.1,2,24 Ideally, all gonococcus-positive individuals diagnosed by NAAT should have cultures performed before initiation of gonorrhoea treatment to permit antimicrobial resistance (AMR) testing and surveillance to be performed. Selective culture media containing antimicrobials such as vancomycin, colistin, nystatin, and trimethoprim are recommended [1C].2,24,27 Culture (ideally supplemented with a NAAT for optimal sensitivity) should also be performed for AMR testing in patients with proven infection (i.e. positive test of cure [TOC]) or in the presence of symptoms following treatment with recommended regimen;1-3,24,30 NAATs are the recommended diagnostic tests for symptomatic and asymptomatic individuals,1,2,31-35 however, culture of individuals with urogenital symptoms and in gonococcal NAAT-positive individuals prior to treatment to obtain isolates for AMR testing is also encouraged. NAATs are more sensitive than culture (particularly for oropharyngeal and rectal specimens); less demanding in specimen quality, transportation and storage; offer testing on a wider range of specimen types; and show high sensitivity (>95%) in both symptomatic and asymptomatic gonorrhoea.1,2,24,29-49 In men, urine (up to 20 mL sampled >1 h after previous micturition) is preferable it provides high sensitivity and non-invasive sampling.1,2,33,39,49 In women, vulvo-vaginal swabs (health care worker- or self-collected) are recommended due to their superior sensitivity and being less invasive since they do not require a speculum examination [1A].1,2,31-35,41,48-52 NAATs are significantly more sensitive than culture for detection of rectal and oropharyngeal gonorrhoea,1,2,24,29,32-35,43,46,47,53-59 and appropriate, validated and quality-assured NAATs are recommended for testing and/or screening for infections at these sites.1,2,32-35,60,61 However, most commercially available gonococcal NAATs are not licensed for testing oropharyngeal and rectal specimens, and differ in their sensitivity and especially specificity,1,2,24,32,34,62-66 particularly when examining oropharyngeal specimens due to the frequent presence of non-gonococcal Neisseria species. NAAT confirmatory testing: The positive predictive value (PPV) of the NAAT testing to detect N. gonorrhoeae should exceed 90%. The PPV is highly influenced by the gonorrhoea prevalence in the tested population and of the specificity of the NAAT.1,2,24,62-64 If the diagnostic NAAT used does not display a PPV exceeding 90%, positive specimens should be confirmed, i.e. by repeat testing with a NAAT targeting another genetic sequence, particularly if oropharyngeal specimens are tested [1C];1,2,24,32,33,60,61,63,64,67-69 Point-of-care tests (POCTs): rapid, validated and quality-assured POCTs for diagnosis of gonorrhoea with sufficient sensitivity compared to NAATs are still lacking, however, several NAAT-based POCTs with high sensitivity and specificity are in late development (https://www.who.int/reproductivehealth/topics/rtis/Diagnostic-Landscape-for-STIs-2019.pdf).2,70,71 Testing of rectal and oropharyngeal specimens should be routine in all MSM, in women when there is a history of direct exposure at the site [1C], and be considered based on sexual history, risk and symptoms or signs in all other patients.1,33,72-79 Testing of pooled specimens (oropharyngeal, rectal, and urine) is not recommended, due to potentially decreased sensitivity,1,33,80-82 increased complexity, including risk of cross-contamination of sample, and lack of approval by US Food and Drug Administration (FDA) or other regulatory agency. Management of patients Information, explanation and advice for the patient Patients with gonorrhoea should be advised to abstain from sexual contact (or if this is not possible to consistently use barrier contraception) for 14 days (seven days if ceftriaxone monotherapy)1,33,34 after they and their sexual partners have completed a ceftriaxone plus azithromycin dual treatment and their symptoms have resolved [2D]. This is to limit possible re-exposure in the presence of residual azithromycin; Patients (and their sexual partners) should be given information (verbal and written) about their infection, including details about transmission, prevention, complications, and treatment [1D]; A patient information leaflet is available in different languages from IUSTI (https://www.iusti.org/regions/Europe/PatientInformation.htm). Patients with verified gonorrhoea (and their sexual contacts) should be encouraged to have testing for other STIs, including C. trachomatis, syphilis, HBV, HCV, and HIV [1C]. Therapy1,33,34,83-100 For detailed background, evidence base and discussions regarding gonorrhoea therapy and antimicrobial resistance in N. gonorrhoeae, see the background review for the present guideline (Unemo M, et al. Int J STD AIDS. 2020).1,33,34,83-199 Briefly, ceftriaxone plus azithromycin dual therapy aims to provide cure for all gonorrhoea cases and, accordingly, to delay the emergence and/or spread of multi-drug resistance and particularly ceftriaxone resistance. It has very high cure rates; effectively target both intracellular and extracellular bacteria;110 have likely been involved in decreasing the level of resistance to extended-spectrum cephalosporins (ESCs; mainly ceftriaxone and cefixime) internationally111-115 and inhibiting spread of ESC-resistant and azithromycin-resistant gonococcal strains (because concurrent resistance to ceftriaxone and azithromycin has been exceedingly rare globally (https://www.ecdc.europa.eu/en/publications-data).111,113-115,131 This dual therapy also effectively eradicates concomitant C. trachomatis infections1,34,116 and a proportion of Mycoplasma genitalium infections, and adherence appears high.117 Ceftriaxone 1 g effectively cures ceftriaxone-susceptible anogenital and oropharyngeal gonorrhoea.92-94 However, failures to treat ceftriaxone-resistant infections, particularly oropharyngeal gonorrhoea, have occurred also with ceftriaxone 1 g,131 and additional treatment failures can be expected when using ceftriaxone monotherapy for currently circulating gonococcal strains.131-141,143 ESCs combined with another anti-gonococcal antimicrobial, including azithromycin, can more effectively cure gonorrhoea, including oropharyngeal infection.1,86,99,100,112,131,145-147 Azithromycin 2 g, but not azithromycin 1 g, effectively cures azithromycin-susceptible gonococcal infections, including in the oropharynx.1,33,87,119,120,146,147 Nevertheless, azithromycin 2 g single oral dose may also result in more gastrointestinal side effects, particularly if taken on empty stomach,88,89,147 although the reported incidence of gastrointestinal side effects varies widely between studies.146,155,156 Dividing the dose of azithromycin to give it over a longer period of time reduces the high and sustained tissue concentration, but also reduces the risk of gastrointestinal side effects.110,148-154 Recent published randomised controlled clinical trials (RCTs) on the treatment of gonorrhoea are few and do not address the rapidly evolving situation of gonococcal AMR. Treatment regimens recommended in this guideline are based on early clinical efficacy trials, pharmacokinetic/pharmacodynamic (PK/PD) considerations,145 in vitro AMR surveillance data,111,113-115,131 case reports of verified treatment failures,103,104,131 and expert judgements. Significant variations between different European countries in STI health care, patient and partner management, including follow up, and gonococcal AMR and AMR surveillance exist. Accordingly, national adoption of the European gonorrhoea guideline based on comprehensive, recent, quality-assured AMR data and an effective patient management strategy, e.g. including mandatory TOC, locally can be reasonable.1,159,200 Indications for therapy [1C] Identification of characteristic intracellular diplococci within polymorphonuclear leukocytes in a sample from a urogenital site, by Gram-stained or methylene blue-stained microscopy; Positive culture or confirmed NAAT from any site for N. gonorrhoeae (or unconfirmed NAAT from urogenital specimens in settings where PPV>90%); On epidemiological grounds, if a recent sexual contact has confirmed gonorrhoea,201 mother of neonate with verified gonorrhoea, and can be considered following sexual assault. When giving treatment based on epidemiological grounds, specimen(s) for laboratory testing should be collected; On demonstration of a purulent urethral discharge in men or mucopurulent cervicitis in women when rapid diagnostic tests such as microscopy are not available and after specimen collection for laboratory testing. In this circumstance, empirical treatment covering also C. trachomatis infection should be considered. Recommended treatment for uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum in adults and adolescents when the antimicrobial susceptibility of the infection is unknown.1,33,34,84,86,110,90-97 Ceftriaxone 1 g intramuscularly (IM) as a single dose together with azithromycin 2 g as a single oral dose [1C] If gastrointestinal side effects are anticipated: ceftriaxone 1 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used to limit gastrointestinal side effects110,154 NOTE: Azithromycin tablets should not be taken on empty stomach due to possible gastrointestinal side effects. If required, snack or crackers can be given to patients before taking the azithromycin tablets.146,147 For patients perceived to be at risk of vomiting, an anti-emetic can be provided.84 OR Ceftriaxone 1 g IM as a single dose [2C] NOTE: Only recommended in settings where: i. comprehensive, recent and quality-assured local in vitro ceftriaxone susceptibility testing has shown lack of ceftriaxone resistance; ii. TOC is mandatory; iii. the patient is considered very likely to return for TOC; iv. doxycycline 100 mg oral dose twice daily for 7 days is administered at the same time to cover any concomitant C. trachomatis infection, if C. trachomatis infection has not been excluded by NAAT. In other settings, ceftriaxone 1 g IM monotherapy is only an alternative option if azithromycin is not available or patient is unable to take oral medication. Treatment when patient has history of severe hypersensitivity (e.g. anaphylaxis) to any -lactam antimicrobial (penicillins, cephalosporins, monobactams or carbapenems)1,33,34 Third-generation cephalosporins, such as ceftriaxone, show negligible cross-allergy with penicillins and allergy to these cephalosporins is rare.160-164 Recommended treatment Spectinomycin 2 g IM as a single dose [1B] together with azithromycin 2 g as a single oral dose [1C] If gastrointestinal side effects are anticipated: spectinomycin 2 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Alternative treatment For susceptible gonococcal infections, early clinical trials demonstrated that ciprofloxacin (500 mg) had high efficacy.90,91,165 Accordingly, this is an alternative treatment when the infection has been confirmed to be susceptible to ciprofloxacin; using phenotypic AMR testing or validated and quality-assured molecular gyrA-based fluoroquinolone resistance testing (only for anogenital samples due to potential cross-reactions with commensal Neisseria species in pharyngeal samples)60,166-169,202-204: Ciprofloxacin 500 mg as a single oral dose [1B] Gentamicin 240 mg IM as a single dose together with azithromycin 2 g as a single oral dose [1B] If gastrointestinal side effects are anticipated: gentamicin 240 mg IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: The European Medicines Agency (EMA) has alerted a risk of serious side effects associated with the use of quinolone/fluoroquinolone antibiotics.170 Ciprofloxacin should be avoided in people who have previously had serious side effects with any quinolone, and it should be used with caution in those >60 years, taking a corticosteroid, having kidney disease, and who have had an organ transplantation. However, single ciprofloxacin 500 mg oral dose likely limits the risk of side effects. See note regarding use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Treatment when administration of an intramuscular injection is contraindicated or refused Multiple reports of cefixime treatment failures, PK/PD investigations, and in vitro resistance levels have raised serious concerns over the adequacy of 400 mg of cefixime for treatment, particularly for monotherapy and treatment of oropharyngeal gonorrhoea (https://www.ecdc.europa.eu/en/publications-data).103,104,131,145,171-173 Recommended treatment Cefixime 400 mg as a single oral dose together with azithromycin 2 g as a single oral dose [1B] If gastrointestinal side effects are anticipated: cefixime 400 mg single oral dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Alternative treatment When the infection has been confirmed before treatment to be susceptible to ciprofloxacin; using phenotypic AMR testing or validated and quality-assured molecular gyrA-based fluoroquinolone resistance testing (only for anogenital samples)60,166-169,202-204: Ciprofloxacin 500 mg as a single oral dose [1B]. NOTE: Co-infection with C. trachomatis is common in young (<30 years) heterosexual patients and MSM with gonorrhoea.1,8,9,33,34 If treatment for gonorrhoea does not include azithromycin, doxycycline 100 mg oral dose twice daily for 7 days should be considered for possible C. trachomatis co-infection unless co-infection has been excluded with NAAT testing.1,33,34 Treatment for gonococcal infection of the pharynx or when such infection has not been excluded Many antimicrobials, including ceftriaxone, have a lower efficacy in curing oropharyngeal gonorrhoea compared to urogenital and anorectal infection.1,33,34,90,91,98,103,104,119,131,142,157,171-180 Recommended treatment Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose [1D] If gastrointestinal side effects are anticipated: ceftriaxone 1 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Alternative regimens Ceftriaxone 1 g IM as a single dose [2D] NOTE: This regimen is only an option if azithromycin is not available or patient is unable to take oral medication. Ciprofloxacin 500 mg as a single oral dose [1B] NOTE: This regimen is only an alternative for treatment when the infection has been confirmed before treatment to be susceptible; using phenotypic AMR testing or validated and quality-assured molecular gyrA-based fluoroquinolone resistance testing (only for anogenital samples)60,166-169,202-204 Recommended treatment for genital, anorectal and oropharyngeal gonococcal infection when ceftriaxone resistance identified1,85,146,147 The management of patients with ceftriaxone-resistant gonorrhoea or verified treatment failures following other recommended antimicrobial regimens requires advice from specialist STI clinicians and microbiologists, and should include sexual contact notification and follow-up with TOC. Three-site testing for N. gonorrhoeae, including culture and AMR testing, is recommended for all patients with ceftriaxone-resistant gonorrhoea. AMR testing, when available, should inform further treatment. Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose [1D], i.e. when ceftriaxone monotherapy, a lower ceftriaxone dose, or another treatment regimen was given initially. High-level azithromycin resistance should preferably be excluded first Spectinomycin 2 g IM as a single dose [1B] together with azithromycin 2 g as a single oral dose [1C] Gentamicin 240 mg IM as a single dose together with azithromycin 2 g as a single oral dose [1B] The high efficacy (100% [95%CI 95-100%]) of this regimen for treatment of anogenital and oropharyngeal gonorrhoea was confirmed in two recent RCTs.146,147 Notable, gentamicin 240 mg IM combined with azithromycin 1 g orally is suboptimal to eradicate rectal (90%) and oropharyngeal gonorrhoea (82%).119 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Ertapenem 1 g IM once daily for three days [2D] This treatment has only been used in a very small number of patients with oropharyngeal gonorrhoea resistant to a regimen of ceftriaxone with or without azithromycin.131,139,142 Treatment for gonococcal infections in pregnancy or when breastfeeding193-195 Recommended treatment Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose [1D] If gastrointestinal side effects are anticipated: ceftriaxone 1 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 Alternative regimen Spectinomycin 2 g IM as a single dose together with azithromycin 2 g as a single oral dose [1D] If gastrointestinal side effects are anticipated: spectinomycin 2 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Ceftriaxone 1 g IM as a single dose [2D] NOTE: Pregnancy does not significantly affect the efficacy of treatment. Pregnant and breastfeeding women should not be treated with fluoroquinolones or tetracyclines. The safety of azithromycin 2 g in pregnancy cannot be completely guaranteed but clinical experience indicates that it can be used safely. However, it should only be used under medical supervision if the expected benefit to the mother is thought to be greater than the possible risk to the foetus.196 Treatment for upper genital tract gonococcal infection Epididymo-orchitis See the European guideline on the management of epididymo-orchitis (www.iusti.org/regions/Europe/euroguidelines.htm). Pelvic inflammatory disease See the European guideline for the management of pelvic inflammatory disease (http: https://www.iusti.org/regions/Europe/euroguidelines.htm). Recommended treatment for disseminated gonococcal infection [2D] There have been no clinical trials on the treatment of DGI since the progressive development of gonococcal AMR. Recommended treatment is based on current AMR data, observational data from case series, and the principals of treating septicaemia. Hospitalization is recommended for initial therapy,1,17,20,33,34,197,198 and gonococcal culture and AMR testing should be performed. Initial therapy: Ceftriaxone 1 g IM or intravenously (IV) every 24 hours OR Cefotaxime 1 g IV every 8 hours OR Spectinomycin 2 g IM every 12 hours. Therapy should continue for 7 days, but may be switched 24-48 hours after substantial clinical improvement to one of the following oral regimens guided by AMR testing: Cefixime 400 mg oral dose twice daily OR Ciprofloxacin 500 mg oral dose twice daily. NOTE: Ciprofloxacin should only be used when the infection has been confirmed before treatment to be susceptible; using phenotypic AMR testing or validated and quality-assured molecular gyrA-based fluoroquinolone resistance testing (only for anogenital samples)60,166-169,202-204 Recommended treatment for gonococcal conjunctivitis1,33,34,199 There is a lack of recent clinical data for treatment of gonococcal conjunctivitis. The eye should be irrigated frequently with sterile saline solution. Ceftriaxone 1 g IM as a single dose together with azithromycin 2 g as a single oral dose [2D] If gastrointestinal side effects are anticipated: ceftriaxone 1 g IM single dose plus azithromycin 1 g oral dose followed by azithromycin 1 g oral dose 6-12 h later may be used110,154 NOTE: See use of azithromycin 2 g for treatments of uncomplicated N. gonorrhoeae infections of the urethra, cervix and rectum. Recommended treatment for ophthalmia neonatorum (gonococcal neonatal conjunctivitis)1,33,34 The eye should be irrigated frequently with sterile saline solution. Ceftriaxone 25-50 mg/kg IV or IM as a single dose, not to exceed 125 mg Recommended treatment for HIV-positive individuals1,33,34 HIV-positive individuals with gonorrhoea should be treated in an identical way to HIV-negative individuals. Recommended treatment for uncomplicated Neisseria meningitidis infection of the urethra205-207 Individuals with uncomplicated urethritis caused by N. meningitidis should be treated in an identical way to patients with gonococcal urethritis. Sexual contact notification and management of sex contact(s) Sexual contact notification should be performed and documented by appropriately trained professionals at the time of diagnosis to prevent reinfection and reduce onwards transmission [1B]; Sexual contacts should be contacted and offered (and encouraged to have) testing for gonorrhoea (and other STIs) together with antimicrobial treatment if appropriate (i.e. if positive N. gonorrhoeae test or clinician considers contacts will not return for treatment after testing results are available) and receive counseling for gonorrhoea and other STIs [1D]; All sexual contact(s) within the preceding 3 months of onset of symptoms or diagnosis should be tested and treated if positive [2D].1,33,34,201 See the European guidelines for the management of partners of persons with sexually transmitted infections (www.iusti.org/regions/Europe/euroguidelines.htm). Follow up and test of cure Assessment after treatment is recommended to confirm eradication of infection, compliance with therapy, enquire about adverse effects, resolution of symptoms and signs, take a sexual history to explore the possibility of re-infection, and pursue partner notification and health promotion [1D]; A TOC is recommended in all cases to identify persisting infection (possible treatment failure) and emerging AMR.1,30,131,200 When symptoms and/or signs persist after treatment, culture is recommended to identify persisting infection and for AMR testing, and should be performed 3-7 days after completion of therapy, possibly supplemented a week later with a NAAT for increased sensitivity if culture is negative. TOC in asymptomatic patients can be performed with a NAAT 2 weeks after completion of treatment and ideally, all positive patients should be cultured and AMR testing performed before further treatment is given.29,208,209 A positive TOC can be due to treatment failure, but also reinfection or, when NAATs are used, residual nucleic acid from non-viable gonococci, and needs to be followed up and interpreted in the clinical context [2C].29,208,209 Identification, confirmation and reporting of treatment failures The surveillance of possible and confirmed failures with recommended treatment regimens should be enhanced, as detailed in the ECDC Response Plan.200 As much clinical and laboratory data as feasible should be collected and reported on treatment failures, including a detailed clinical history (including all antimicrobial treatments given), the exclusion of reinfection, whole genome sequencing of pre-treatment and post-treatment gonococcal isolates or other highly discriminative molecular epidemiological typing of NAAT specimens (identifying indistinguishable isolates/genetic variants) and phenotypic and/or molecular assessment of resistance (AMR determinants) to the prescribed treatment using the gonococcal isolates or NAAT specimens.200,210 Notification Gonorrhoea cases should be notified to local, regional and national authorities as mandated by statute. The ECDC is responsible for the EU/EEA-wide gonorrhoea surveillance. Authors note A list of contributing organisations can be found at: https://www.iusti.org/regions/Europe/euroguidelines.htm Acknowledgements The authors are grateful to Chris Bignell for being the first author of the outdated 2012 European gonorrhoea guidelines,1 which formed the basis of the present guideline, and for valuable input on the present guideline to Fabian Kong, xx,xx. Declaration of Conflicting Interests JR reports personal fees from GSK Pharma, Mycovia, and Nabriva Therapeutics as well as ownership of shares in GSK Pharma and AstraZeneca Pharma. The other author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Composition of the European STI Guidelines Editorial Board The current composition of the European STI Guidelines Editorial Board can be found at: https://www.iusti.org/regions/Europe/euroguidelines.htm. Search strategy The present guideline was produced according to the protocol for production and revision of European STI guidelines, which has been written and approved by the IUSTI European STI Guidelines Editorial Board (https://www.iusti.org/regions/Europe/pdf/2017/ProtocolForProduction2017.pdf). A Medline search was conducted in February 2020 using PubMed for articles published since the development of the 2012 European gonorrhoea guideline.1 Search headings were kept broad (i) gonorrhoea, iii) gonorrhea or ii) Neisseria gonorrhoeae to include epidemiology, diagnosis, antimicrobial susceptibility/resistance, therapy, clinical trials, prevention, and control. Only publications and abstracts in the English language were considered. The Cochrane Library was searched for all entries related to gonorrhoea/gonorrhea or Neisseria gonorrhoeae. Relevant STI guidelines produced by the WHO (www.who.int), US Centers for Disease Control and Prevention (www.cdc.gov/std/) and the British Association for Sexual Health and HIV (www.bashh.org) were also reviewed. Levels of evidence and grading of recommendations Levels of evidence and grading of recommendations that were used in the present guideline can be found in the protocol for production and revision of European STI guidelines at: https://www.iusti.org/regions/Europe/pdf/2017/ProtocolForProduction2017.pdf Qualifying statement Decisions to follow these recommendations must be based on professional clinical judgement, consideration of individual patient circumstances and available resources. All possible care has been undertaken to ensure publication of the correct dosage of medication and route of administration. However, it remains the responsibility of the prescribing clinician to ensure the accuracy and appropriateness of the medication they prescribe. Proposed date of revision: 2023 REFERENCES Bignell C, Unemo M; European STI Guidelines Editorial Board. Int J STD AIDS 2013;24:85-92. Unemo M, Seifert HS, Hook EW 3rd, Hawkes S, Ndowa F, Dillon JR. Gonorrhoea. Nat Rev Dis Primers 2019;5:79. doi:10.1038/s41572-019-0128-6 Hook EW III, Handsfield HH. Gonococcal infections in the adult. In Holmes KK, Sparling PF, et al (eds.), Sexually Transmitted Diseases 4th ed. New York, NY. McGraw Hill 2008; 627-45. Cornelisse VJ, Williamson D, Zhang L, et al. Evidence for a new paradigm of gonorrhoea transmission: cross-sectional analysis of Neisseria gonorrhoeae infections by anatomical site in both partners in 60 male couples. Sex Transm Infect 2019;95:437-42. Cornelisse VJ, Zhang L, Law M, et al. Concordance of gonorrhoea of the rectum, pharynx and urethra in same-sex male partnerships attending a sexual health service in Melbourne, Australia. BMC Infect Dis 2018;18(1):95 Cornelisse VJ, Bradshaw CS, Chow EPF, et al. Oropharyngeal gonorrhea in absence of urogenital gonorrhea in sexual network of male and female participants, Australia, 2018. Emerg Infect Dis 2019;25:1373-6. Fairley CK, Cornelisse VJ, Hocking JS, Chow EPF. Models of gonorrhoea transmission from the mouth and saliva. Lancet Infect Dis 2019;19:e360-6. European Centre for Disease Prevention and Control. Surveillance Atlas of Infectious Diseases. http://atlas.ecdc.europa.eu/public/index.aspx GRASP Steering Group. Antimicrobial resistance in Neisseria gonorrhoeae in England and Wales. Key findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2018). https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/834924/GRASP__2018_report.pdf Risley CL, Ward H, Choudhury B, et al. Geographical and demographic clustering of gonorrhoea in London. Sex Transm Infect 2007;83:481-7. Reddy BSN, Khandpur S, Sethi S, Unemo M. Gonococcal infections. In Gupta S and Kumar B (eds), Sexually Transmitted infections 2nd ed. New Delhi, India. Elsevier 2012; 473-93. Sherrard J, Barlow D. Gonorrhoea in men: clinical and diagnostic aspects. Genitourin Med 1996;72:422-6. Lewis DA, Bond M, Butt KD, Smith CP, Shafi MS, Murphy SM. A one-year survey of gonococcal infection seen in the genitourinary medicine department of a London district general hospital. Int J STD AIDS 1999;10:588-94. Barlow D, Phillips I. Gonorrhoea in women: diagnostic, clinical and laboratory aspects. Lancet 1978;1:761-4. Kent CK, Chaw JK, Wong W, Liska S, Gibson S, Hubbard G, Klausner JD. Prevalence of rectal, urethral and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California 2003. Clin Infect Dis 2005;41:67-74. Peters RPH, Nijsten N, Mutsaers J, Jansen CL, Morre SA, van Leeuwen AP. Screening of oropharynx and anorectum increases prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection in female STD clinic visitors. Sex Transm Dis 2011;38:783-7. OBrien JP, Goldenberg DL, Rice PA. Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Medicine 1983;62:395-406. Belkacem A, Caumes E, Ouanich J, et al.  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/23920397" Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009-2011. Sex Transm Infect 2013;89:613-5. Birrell JM, Gunathilake M, Singleton S, Williams S, Krause V. Characteristics and impact of disseminated gonococcal infection in the "Top End" of Australia. Am J Trop Med Hyg 2019;101:753-60.  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Bleich%20AT%5BAuthor%5D&cauthor=true&cauthor_uid=22353959" Bleich AT,  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Sheffield%20JS%5BAuthor%5D&cauthor=true&cauthor_uid=22353959" Sheffield JS,  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Wendel%20GD%20Jr%5BAuthor%5D&cauthor=true&cauthor_uid=22353959" Wendel GD Jr,  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Sigman%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22353959" Sigman A,  HYPERLINK "http://www.ncbi.nlm.nih.gov/pubmed?term=Cunningham%20FG%5BAuthor%5D&cauthor=true&cauthor_uid=22353959" Cunningham FG. Disseminated gonococcal infection in women. Obstet Gynecol 2012;119:597-602. Roth A, Mattheis C, Muenzner P, Unemo M, Hauck CR. Innate recognition by neutrophil granulocytes differs between Neisseria gonorrhoeae strains causing local or disseminating infections. Infect Immun 2013;81:2358-70. Grentzer JM, Peipert JF, Zhao Q, McNicholas C, Secura GM, Madden T. Risk-based screening for Chlamydia trachomatis and Neisseria gonorrhoeae prior to intrauterine device insertion. Contraception 2015;92:313-8. Sufrin CB, Averbach SH. Testing for sexually transmitted infections at intrauterine device insertion: an evidence-based approach. Clin Obstet Gynecol 2014;57:682-93. Unemo M, Ison C. Gonorrhoea. In Unemo M, Ballard R, et al (eds), Laboratory Diagnosis of Sexually Transmitted infections, including Human Immunodeficiency Virus 2nd ed. Geneva, Switzerland. World Health Organization 2013; 21-54. Taylor SN, DiCarlo RP, Martin DH. Comparison of methylene blue/gentian violet stain to Grams stain for the rapid diagnosis of gonococcal urethritis in men. Sex Trans Dis 2011;38:995-6. Thorley N, Radcliffe K. The performance and clinical utility of cervical microscopy for the diagnosis of gonorrhoea in women in the era of the NAAT. Int J STD AIDS 2015;26:656-60. Jephcott AE. Microbiological diagnosis of gonorrhoea. Genitourin Med 1997;73:245-52. Forni J, Miles K, Hamill M. Microscopy detection of rectal gonorrhoea in asymptomatic men. Int J STD AIDS 2009;20:797-8. Wind CM, Schim van der Loeff MF, Unemo M, Schuurman R, van Dam AP, de Vries HJC. Test of cure for anogenital gonorrhoea using modern RNA-Based and DNA-based nucleic acid amplification tests: A prospective cohort study. Clin Infect Dis 2016;62:1348-55. Whiley DM, Goire N, Lahra MM, Donovan B, Limnios AE, Nissen MD, Sloots TP. The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae is a public health disaster in waiting. J Antimicrob Chemother 2012;67:2059-61. Cook RL, Hutchison SL, stergaard L, Braithwaite RS, Ness RB. Systematic Review: Non-invasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med 2005;142:914-25. Whiley DM, Garland SM, Harnett G, et al. Exploring best practice for nucleic acid detection of Neisseria gonorrhoeae. Sexual Health 2008;5:17-23. Fifer H, Saunders J, Soni S, Sadiq ST, FitzGerald M. 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae. Int J STD AIDS 2020;31:4-15. Workowski KA, Bolan GA; CDC. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2015;64(RR-03):1137. Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep 2014;63(RR-02):1-19. Harryman L, Scofield S, Macleod J, Carrington D, Williams OM, Fernandes A, Horner P. Comparative performance of culture using swabs transported in Amies medium and the Aptima Combo 2 nucleic acid amplification test in detection of Neisseria gonorrhoeae from genital and extra-genital sites: a retrospective study. Sex Transm Infect 2012;88:127-31. Van Dyck E, Ieven M, Pattyn S, Van Damme L, Laga M. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by enzyme immunoassay, culture and three nucleic acid amplification tests. J Clin Microbiol 2001;39:1751-6. Van der Pol B, Ferrero DV, Buck-Barrington L, et al. Multicenter evaluation of the BDProbeTec ET system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical and male urethral swabs. J Clin Microbiol 2001;39:1008-16. Moncada J, Schachter J, Hook EW 3rd, et al. The effect of urine testing in evaluations of the sensitivity of the Gen-Probe APTIMA Combo 2 Assay on endocervical swabs for Chlamydia trachomatis and Neisseria gonorrhoeae. Sex Trans Dis 2004;31:273-7. Chernesky MA, Martin DH, Hook EW, et al. Ability of new APTIMA CT and APTIMA GC Assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs. J Clin Microbiol 2005;43:127-31. Schachter J, Chernesky MA, Willis DE, et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Trans Dis 2005;32:725-8. Ison C. GC NAATs: is the time right? Sex Transm Infect 2006;82:515. Cornelisse VJ, Chow EP, Huffam S, et al. Increased detection of pharyngeal and rectal gonorrhea in men who have sex with men after transition from culture to nucleic acid amplification testing. Sex Transm Dis 2017;44:114-17. Van Der Pol B, Hook EW, 3rd, Williams JA, et al. Performance of the BD CTQx and GCQx Amplified Assays on the BD Viper LT compared with the BD Viper XTR System. Sex Transm Dis 2015;42:521-3. Geelen TH, Rossen JW, Beerens AM, et al. Performance of Cobas(R) 4800 and m2000 real-time assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and self-collected vaginal specimen. Diagn Microbiol Infect Dis 2013;77:101-5. Bachmann LH, Johnson RE, Cheng H, Markowitz L, Papp JR, Palella FJ Jr, Hook EW 3rd. Nucleic acid amplification tests for diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis rectal infections. J Clin Microbiol 2010;48:1827-32. Bachmann LH, Johnson RE, Cheng H, Markowitz LE, Papp JR, Hook EW 3rd. Nucleic acid amplification tests for diagnosis of Neisseria gonorrhoeae oropharyngeal infections. J Clin Microbiol 2009;47:902-7. Lunny C, Taylor D, Hoang L, et al. Self-collected versus clinician-collected sampling for chlamydia and gonorrhea screening: A systemic review and meta-analysis. PLoS One 2015;10(7):e0132776. Coorevits L, Traen A, Bing L, et al. Identifying a consensus sample type to test for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis and human papillomavirus. Clin Microbiol Infect 2018;24:1328-32. Stewart CM, Schoeman SA, Booth RA, et al. Assessment of self taken swabs versus clinician taken swab cultures for diagnosing gonorrhoea in women: single centre, diagnostic accuracy study. BMJ 2012;345:e8107. doi: 10.1136/bmj.e8107 Boiko I, Golparian D, Krynytska I, Unemo M. High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine. APMIS 2019;127:627-34. Van Der Pol B, Taylor SN, Liesenfeld O, et al. Vaginal swabs are the optimal specimen for detection of genital Chlamydia trachomatis or Neisseria gonorrhoeae using the Cobas 4800 CT/NG test. Sex Transm Dis 2013;40:247-50. Page-Shafer K, Graves A, Kent C, Bals JE, Zapitz VM, Klausner JD. Increased sensitivity of DNA amplification testing for the detection of pharyngeal gonorrhoea in men who have sex with men. Clin Infect Dis 2002;34:173-6. McNally LP, Templeton DJ, Jin F, et al. Low positive predictive value of a nucleic acid amplification test for nongenital Neisseria gonorrhoeae infection in homosexual men. Clin Infect Dis 2008;47:e25-7. Schachter J, Moncada J, Liska S, Shayevich C, Klausner JD. Nucleic acid amplification tests in the diagnosis of chlamydial and gonococcal infections in the oropharynx and rectum in men who have sex with men. Sex Trans Dis 2008;35:637-42. Ota KV, Tamari IE, Smieja M, et al. Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in pharyngeal and rectal specimens using the BD Probetec ET system, the Gen-Probe Aptima Combo 2 assay and culture. Sex Trans Infect 2009;85:182-6. Mimiaga MJ, Helms DJ, Reisner SL, et al. Gonococcal, chlamydia, and syphilis infection positivity among MSM attending a large primary care clinic, Boston, 2003 to 2004. Sex Transm Dis 2009;36:507-11. Cosentino LA, Danby CS, Rabe LK, Macio I, Meyn LA, Wiesenfeld HC, Hillier SL. Use of nucleic acid amplification testing for diagnosis of extragenital sexually transmitted infections. J Clin Microbiol 2017;55:2801-7. Bristow CC, McGrath MR, Cohen AC, Anderson LJ, Gordon KK, Klausner JD. Comparative evaluation of 2 nucleic acid amplification tests for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae at extragenital sites. Sex Transm Dis 2017;44:398-400. Smith DW, Tapsall JW, Lum G. Guidelines for the use and interpretation of nucleic acid detection tests for Neisseria gonorrhoeae in Australia: a position paper on behalf of the Public Health Laboratory Network. Commun Dis Intell 2005;29:358-65. Hughes G, Ison C, Field N, et al. Guidance for the detection of gonorrhoea in England. In: Public Health England, ed. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/405293/170215_Gonorrhoea_testing_guidance_REVISED__2_.pdf, 2014. Palmer H, Mallinson H, Wood RL, Herring AJ. Evaluation of the specificities of five DNA amplification methods for the detection of Neisseria gonorrhoeae. J Clin Microbiol 2003;41:835-7. Tabrizi SN, Unemo M, Limnios AE, Hogan TR, Hjelmevoll SO, Garland SM, Tapsall J. Evaluation of six commercial nucleic acid amplification tests for the detection of Neisseria gonorrhoeae and other Neisseria species. J Clin Microbiol 2011;49:3610-5. Golparian D, Borng S, Sundqvist M, Unemo M. Evaluation of the New BD Max GC Real-Time PCR assay, analytically and clinically as a supplementary test for the BD ProbeTec GC Qx Amplified DNA assay, for molecular detection of Neisseria gonorrhoeae. J Clin Microbiol 2015;53:3935-7. Ison CA, Golparian D, Saunders P, Chisholm S, Unemo M. Evolution of Neisseria gonorrhoeae is a continuing challenge for molecular detection of gonorrhoea: false negative gonococcal porA mutants are spreading internationally. Sex Transm Infect 2013;89:197-201. Golparian D, Tabrizi SN, Unemo M. Analytical specificity and sensitivity of the APTIMA Combo 2 and APTIMA GC assays for detection of commensal Neisseria species and Neisseria gonorrhoeae on the Gen-Probe Panther instrument. Sex Transm Dis 2013;40:175-8. Pope CF, Hay P, Alexander S, et al. Positive predictive value of the Becton Dickinson VIPER system and the ProbeTec GC Q x assay, in extracted mode, for detection of Neisseria gonorrhoeae. Sex Transm Infect 2010;86:465-9. Whiley DM, Lahra MM; National Neisseria Network. Review of 2005 Public Health Laboratory Network Neisseria gonorrhoeae nucleic acid amplification tests guidelines. Commun Dis Intell Q Rep 2015;39:E42-5. Field N, Clifton S, Alexander S, et al. Confirmatory assays are essential when using molecular testing for Neisseria gonorrhoeae in low-prevalence settings: insights from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Sex Transm Infect 2015;91:338-41. Guy RJ, Causer LM, Klausner JD, Unemo M, Toskin I, Azzini AM, Peeling RW. Performance and operational characteristics of point-of-care tests for the diagnosis of urogenital gonococcal infections. Sex Transm Infect 2017;93:S16-S21. Toskin I, Govender V, Blondeel K, et al. Call to action for health system integration of point-of-care tests to mitigate the transmission and burden of sexually transmitted infections. Sex Transm Infect 2020. In press van Liere GAFS, Dukers-Muijrers NHTM, Levels L, Hoebe CJPA. High proportion of anorectal Chlamydia trachomatis and Neisseria gonorrhoeae after routine universal urogenital and anorectal screening in women visiting the sexually transmitted infection clinic. Clin Infect Dis 2017;64:1705-10. van Liere GA, Hoebe CJ, Niekamp AM, et al. Standard symptom- and sexual history-based testing misses anorectal Chlamydia trachomatis and Neisseria gonorrhoeae infections in swingers and men who have sex with men. Sex Transm Dis 2013;40:285-9. van Liere GA, Hoebe CJ, Dukers-Muijrers NH. Evaluation of the anatomical site distribution of chlamydia and gonorrhoea in men who have sex with men and in high-risk women by routine testing: cross-sectional study revealing missed opportunities for treatment strategies. Sex Transm Infect 2014;90:58-60. Anschuetz GL, Paulukonis E, Powers R, Asbel LE. Extragenital screening in men who have sex with men diagnoses more chlamydia and gonorrhea cases than urine testing alone. Sex Transm Dis 2016;43:299-301. Moncada J, Shayevich C, Philip SS, Lucic D, Schachter J. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and oropharyngeal swabs and urine specimens from men who have sex with men with Abbott's M2000 RealTime. Sex Transm Dis 2015;42:650-1. den Heijer CDJ, Hoebe CJPA, van Liere GAFS, van Bergen JEAM, Cals JWL, Stals FS, Dukers-Muijrers NHTM. A comprehensive overview of urogenital, anorectal and oropharyngeal Neisseria gonorrhoeae testing and diagnoses among different STI care providers: a cross-sectional study. BMC Infect Dis 2017;17(1):290. doi: 10.1186/s12879-017-2402-0. Trebach JD, Chaulk CP, Page KR, Tuddenham S, Ghanem KG. Neisseria gonorrhoeae and Chlamydia trachomatis among women reporting extragenital exposures. Sex Transm Dis 2015;42:233-9. Dombrowski JC. Do women need screening for extragenital gonococcal and chlamydial infections?. Sex Transm Dis 2015;42:240-2. Sultan B, White JA, Fish R, et al. The "3 in 1" Study: Pooling self-taken pharyngeal, urethral, and rectal samples into a single sample for analysis for detection of Neisseria gonorrhoeae and Chlamydia trachomatis in men who have sex with men. J Clin Microbiol 2016;54:650-6. Durukan D, Read TRH, Bradshaw CS, et al. Pooling pharyngeal, anorectal and urogenital samples for screening asymptomatic men who have sex with men for Chlamydia trachomatis and Neisseria gonorrhoeae [published online ahead of print, 2020 Mar 4]. J Clin Microbiol 2020;JCM.01969-19. Badman SG, Bell SFE, Dean JA, et al. Reduced sensitivity from pooled urine, pharyngeal and rectal specimens when using a molecular assay for the detection of chlamydia and gonorrhoea near the point of care. Sex Health 2020;17:15-21. Romanowski B, Robinson J, Wong T. Gonococcal infections chapter. In: Canadian guidelines on sexually transmitted infections. Ottawa, ON: Public Health Agency of Canada; 2013.  HYPERLINK "http://www.phac" www.phac-aspc.gc.ca/std-mts/sti-its/cgsti-ldcits/assets/pdf/section-5-6-eng.pdf Australasian Sexual Health Alliance (ASHA). Gonorrhoea. In: Australian STI management guidelines for use in primary care [website]. ASHA; 2018. www.sti.guidelines.org.au/sexually-transmissible-infections/gonorrhoea#management World Health Organization (WHO). WHO guidelines for the treatment of Neisseria gonorrhoeae. Geneva: WHO; 2016. http://www.who.int/reproductivehealth/publications/rtis/gonorrhoea-treatment-guidelines/en/ Unemo M, Workowski K. Dual antimicrobial therapy for gonorrhoea: what is the role of azithromycin?. Lancet Infect Dis 2018;18:486-8. Bignell C, Garley J. Azithromycin in the treatment of infection with Neisseria gonorrhoeae. Sex Transm Infect 2010;86:422-6. Handsfield HH, Dalu ZA, Martin DH, Douglas JM Jr, McCarty JM, Schlossberg D. Multicenter trial of single-dose azithromycin vs ceftriaxone in the treatment of uncomplicated gonorrhoea. Sex Trans Dis 1994;21:107-11. Mensforth S, Ross JDC. Should we still use azithromycin for gonorrhoea treatment?. Sex Health 2019;16:442-8. Moran JS, Levine WC. Drugs of choice in the treatment of uncomplicated gonococcal infection. Clin Infect Dis 1995;20(Suppl 1):S47-65. Newman LM, Moran JS, Workowski KA. Update on the management of gonorrhoea in adults in the United States. Clin Infect Dis 2007;44:S84-101. Ito S, Yasuda M, Hatazaki K, et al. Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis. J Antimicrob Chemother 2016;71:2559-62. Muratani T, Inatomi H, Ando Y, Kawai S, Akasaka S, Matsumoto T. Single dose 1 g ceftriaxone for urogenital and pharyngeal infection caused by Neisseria gonorrhoeae. Int J Urol 2008;15:837-42. Japanese Society of Sexually Transmitted Infections. Gonococcal infection. Sexually transmitted infections, diagnosis and treatment guidelines 2011. Jpn J Sex Transm Dis 2011;22(suppl 1):52-9. In Japanese Boiko I, Golparian D, Krynytska I, et al. Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018. APMIS 2019;127:503-9. Unemo M, Shipitsyna E, Domeika M; Eastern European Sexual and Reproductive Health (EE SRH) Network Antimicrobial Resistance Group. Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial. Sex Transm Infect 2010;86:442-4. Tapsall JW. Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci. Sex Transm Infect 2009;85:256-8. Moran JS. Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important? Sex Trans Dis 1995;22:39-47. Hananta IPY, De Vries HJC, van Dam AP, et al. Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012-2015: a retrospective cohort study. Sex Transm Infect 2017;93:467-71. Sathia L, Ellis B, Phillip S, Winston A, Smith A. Pharyngeal gonorrhoea is dual therapy the way forward? Int J STD AIDS 2007;18:647-8. Unemo M, Shafer WM. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin Microbiol Rev 2014;27:587-613. Golparian D, Harris SR, Snchez-Bus L, et al. Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (19282013): antimicrobial use/misuse selects for resistance and drives evolution. BMC Genomics 2020;21:116. https://doi.org/10.1186/s12864-020-6511-6. Unemo M, Nicholas RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol 2012;7:1401-22. Unemo M. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect Dis 2015;15:364. doi:10.1186/s12879-015-1029-2 Barbee LA, Soge OO, Holmes KK, et al. In vitro synergy testing of novel antimicrobial combination therapies against Neisseria gonorrhoeae. J Antimicrob Chemother 2014;69:1572-8. Pereira R, Cole MJ, Ison CA. Combination therapy for gonorrhoea: in vitro synergy testing. J Antimicrob Chemother 2013;68:640-3. Wind CM, de Vries HJ, van Dam AP. Determination of in vitro synergy for dual antimicrobial therapy against resistant Neisseria gonorrhoeae using Etest and agar dilution. Int J Antimicrob Agents 2015;45:305-8. Furuya R, Nakayama H, Kanayama A, et al. In vitro synergistic effects of double combinations of beta-lactams and azithromycin against clinical isolates of Neisseria gonorrhoeae. J Infect Chemother 2006;12:172-6. Singh V, Bala M, Bhargava A, et al. In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era. PLoS One 2018;13:e0193678. doi: 10.1371/journal.pone.0193678 Kong FYS, Horner P, Unemo M, Hocking JS. Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review. J Antimicrob Chemother 2019;74:1157-66. Harris SR, Cole MJ, Spiteri G, et al. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. Lancet Infect Dis 2018;18:758-68. Barbee LA, Kerani RP, Dombrowski JC, Soge OO, Golden MR. A retrospective comparative study of 2-drug oral and intramuscular cephalosporin treatment regimens for pharyngeal gonorrhea. Clin Infect Dis 2013;56:1539-45. Cole MJ, Spiteri G, Jacobsson S, Pitt R, Grigorjev V, Unemo M; Euro-GASP Network. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. BMC Infect Dis 2015;15:321. doi: 10.1186/s12879-015-1013-x. Cole MJ, Spiteri G, Jacobsson S, Woodford N, Tripodo F, Amato-Gauci AJ, Unemo M; Euro-GASP network. Overall low extended-spectrum cephalosporin resistance but high azithromycin resistance in Neisseria gonorrhoeae in 24 European countries, 2015. BMC Infect Dis 2017;17:617. doi: 10.1186/s12879-017-2707-z. Day MJ, Spiteri G, Jacobsson S, et al. Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016. BMC Infect Dis 2018;18:609. doi:10.1186/s12879-018-3528-4 Horner PJ. Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy. Sex Transm Infect 2012;88:154-6. Unemo M, Clarke E, Boiko I, Patel C, Patel R; ECCG Core Group. Adherence to the 2012 European gonorrhoea guideline in the WHO European Region according to the 2018-19 International Union against Sexually Transmitted Infections European Collaborative Clinical Group gonorrhoea survey. Int J STD AIDS 2020;31:69-76. Fifer H, Cole M, Hughes G, et al. Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study. Lancet Infect Dis 2018;18:573-81. Ross JDC, Brittain C, Cole M, et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial. Lancet 2019;393:2511-20. Tapsall JW, Schultz TR, Limnios EA, Donovan B, Lum G, Mulhall BP. Failure of azithromycin therapy in gonorrhoea and discorrelation with laboratory parameters. Sex Trans Dis 1998;25:505-8. Cole MJ, Tan W, Fifer H, et al. Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea: the relationship between antibiotic MIC and clinical outcome. J Antimicrob Chemother 2020;75:449-57. Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium. Nat Rev Urol 2017;14:139-52. Crokaert F, Hubloux A, Cauchie P. A Phase I determination of azithromycin in plasma during a 6-week period in normal volunteers after a standard dose of 500mg once daily for 3 days. Clin Drug Investig 1998;16:1616. Zheng S, Matzneller P, Zeitlinger M, et al. Development of a population pharmacokinetic model characterizing the tissue distribution of azithromycin in healthy subjects. Antimicrob Agents Chemother 2014;58:6675-84. Matzneller P, Krasniqi S, Kinzig M, et al. Blood, tissue, and intracellular concentrations of azithromycin during and after end of therapy. Antimicrob Agents Chemother 2013;57:1736-42. Clifton S, Town K, Furegato M, et al. Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England. Sex Transm Infect 2018;94:421-6. Kenyon C, Buyze J, Spiteri G, Cole MJ, Unemo M. Population-level antimicrobial consumption is associated with decreased antimicrobial susceptibility in Neisseria gonorrhoeae in 24 European countries: An ecological analysis. J Infect Dis 2020;221:1107-16. KirkcaldyRD, BartocesMG, SogeOO, etal. Antimicrobial drug prescription and Neisseria gonorrhoeae susceptibility, United States, 20052013. Emerg Infect Dis 2017;23:1657-63. Olesen SW, Torrone EA, Papp JR, Kirkcaldy RD, Lipsitch M, Grad YH. Azithromycin susceptibility among Neisseria gonorrhoeae isolates and seasonal macrolide use. J Infect Dis. 2019;219:619-23. Wind CM, de Vries E, Schim van der Loeff MF, et al. Decreased azithromycin susceptibility of Neisseria gonorrhoeae isolates in patients recently treated with azithromycin. Clin Infect Dis 2017;65:37-45. Unemo M, Lahra MM, Cole M, et al. World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts. Sex Health 2019;16:412-25. Nakayama S, Shimuta K, Furubayashi K, et al. New ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain with a novel mosaic penA gene isolated in Japan. Antimicrob Agents Chemother 2016;60:4339-41. Lahra MM, Martin I, Demczuk W, et al. Cooperative recognition of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain. Emerg Infect Dis 2018;24(4). doi: 10.3201/eid2404.171873. Lefebvre B, Martin I, Demczuk W, et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Canada, 2017. Emerg Infect Dis 2018;24:735-40. Terkelsen D, Tolstrup J, Johnsen CH, et al. Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017. Euro Surveill 2017;22(42). doi: 10.2807/1560-7917.ES.2017.22.42.17-00659. Poncin T, Fouere S, Braille A, et al. Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017. Euro Surveill 2018;23(21). doi: 10.2807/1560-7917.ES.2018.23.21.1800264. Golparian D, Rose L, Lynam A, et al. Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018. Euro Surveill 2018;23(47). doi: 10.2807/1560-7917.ES.2018.23.47.1800617. Ko KKK, Chio MTW, Goh SS, et al. First case of ceftriaxone-resistant multidrug-resistant Neisseria gonorrhoeae in Singapore. Antimicrob Agents Chemother 2019;63:e02624-18. doi: 10.1128/AAC.02624-18.. Eyre DW, Town K, Street T, et al. Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018. Euro Surveill 2019;24(10). doi: 10.2807/1560-7917.ES.2019.24.10.1900147. Lee K, Nakayama SI, Osawa K, et al. Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates. J Antimicrob Chemother 2019;74:1812-9. Chen SC, Han Y, Yuan LF, Zhu XY, Yin YP. Identification of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, China. Emerg Infect Dis 2019;25:1427-9. Eyre DW, Sanderson ND, Lord E, et al. Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Euro Surveill 2018;23(27). doi: 10.2807/1560-7917.ES.2018.23.27.1800323. Jennison AV, Whiley D, Lahra MM, et al. Genetic relatedness of ceftriaxone-resistant and high-level azithromycin resistant Neisseria gonorrhoeae cases, United Kingdom and Australia, February to April 2018. Euro Surveill 2019;24(8):1900118. doi:10.2807/1560-7917.ES.2019.24.8.1900118 Hernando Rovirola C, Spiteri G, Sabid M, et al. Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme [published online ahead of print, 2020 Feb 4]. Sex Transm Infect 2020;sextrans-2018-053912. doi:10.1136/sextrans-2018-053912 Chisholm S, Mouton J, Lewis D, Nichols T, Ison C, Livermore D. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J Antimicrob Chemother 2010;65:2141-8. Rob F, Klubalov B, Ny ov E, Hercogov J, Unemo M. Gentamicin 240 mg plus azithromycin 2 g vs. ceftriaxone 500 mg plus azithromycin 2 g for treatment of rectal and pharyngeal gonorrhoea: a randomized controlled trial. Clin Microbiol Infect 2020;26:207-12. Kirkcaldy RD, Weinstock HS, Moore PC, et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis 2014;59:1083-91. Girard D, Finegan SM, Dunne MW, Lame ME. Enhanced efficacy of single-dose versus multi-dose azithromycin regimens in preclinical infection models. J Antimicrob Chemother 2005;56:365-71. Pfizer Canada. Zithromax Product Information. Quebec, Canada: Pfizer 2013. Di Paolo A, Barbara C, Chella A, Angeletti CA, Del Tacca M. Pharmacokinetics of azithromycin in lung tissue, bronchial washing, and plasma in patients given multiple oral doses of 500 and 1000 mg daily. Pharmacol Res 2002;46:545-50. Amsden GW, Nafziger AN, Foulds G. Pharmacokinetics in serum and leukocyte exposures of oral azithromycin, 1,500 milligrams, given over a 3- or 5-day period in healthy subjects. Antimicrob Agents Chemother 1999;43:163-5. Kong F. Is the current treatment of urogenital and anorectal chlamydia infection appropriate? In., vol. Chapter 5; 2017. Foulds G, Johnson RB. Selection of dose regimens of azithromycin. J Antimicrob Chemother 1993;31(suppl E):39-50. Read TRH, Fairley CK, Murray GL, et al. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: A prospective evaluation. Clin Infect Dis 2019;68:554-60. Hook EW III, Martin DH, Stephens J, Smith BS, Smith K. A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis 2002;29:486-90. Takahashi S, Kiyota H, Ito S, et al. Clinical efcacy of a single two gram dose of azithromycin extended release for male patients with urethritis. Antibiotics (Basel) 2014;3:109-20. Unemo M, Bradshaw CS, Hocking JS, et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis 2017;17:e235-79. Alirol E, Wi TE, Bala M, et al. Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines. PLoS Med 2017;14(7):e1002366. doi: 10.1371/journal.pmed.1002366. Tapsall JW, Ndowa F, Lewis DA, Unemo M. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther 2009;7:821-34. Pichichero ME, Casey JR. Safe use of selected cephalosporins in penicillin-allergic patients: A meta-analysis. Otolaryngol Head Neck Surg 2007;136:340-7. Yates AB. Management of patients with a history of allergy to beta-lactam antibiotics. Am J Med 2008;121:572-6. Zagursky RJ, Pichichero ME. Cross-reactivity in beta-lactam allergy. J Allergy Clin Immunol Pract 2018;6:72-81.e1. Novalbos A, Sastre J, Cuesta J, et al. Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins. Clin Exp Allergy 2001;31:438-43. Romano A, Gaeta F, Valluzzi RL, et al. IgE-mediated hypersensitivity to cephalosporins: cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J Allergy Clin Immunol 2010;126:994-9. Moran JS. Ciprofloxacin for gonorrhea 250 mg or 500 mg? Sex Trans Dis 1996;23:165-7. Pond MJ, Hall CL, Miari VF, et al. Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy. J Antimicrob Chemother 2016;71:897-902. Allan-Blitz LT, Wang X, Klausner JD. Wild-type Gyrase A genotype of Neisseria gonorrhoeae predicts in vitro susceptibility to ciprofloxacin: A systematic review of the literature and meta-analysis. Sex Transm Dis 2017;44:261-5. Allan-Blitz LT, Humphries RM, Hemarajata P, et al. Implementation of a rapid genotypic assay to promote targeted ciprofloxacin therapy of Neisseria gonorrhoeae in a large health system. Clin Infect Dis 2017;64:1268-70. Hadad R, Cole MJ, Ebeyan S, et al. Evaluation of the SpeeDx ResistancePlus GC and SpeeDx GC 23S 2611 (beta) molecular assays for prediction of antimicrobial resistance/susceptibility to ciprofloxacin and azithromycin in Neisseria gonorrhoeae. Submitted European Medicines Agency. Review of Quinolone- and fluoroquinolone- containing medicinal products. https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containingmedicinal-products2018 Gratrix J, Bergman J, Egan C, Drews SJ, Read R, Singh AE.  HYPERLINK "https://www.ncbi.nlm.nih.gov/pubmed/24113412" Retrospective review of pharyngeal gonorrhea treatment failures in Alberta, Canada. Sex Transm Dis 2013;40:877-9. Allen VG, Mitterni L, Seah C, et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA 2013;309:163-70. Barbee LA, Nayak SU, Blumer JL, et al. A Phase 1 pharmacokinetic and safety study of extended-duration, high-dose cefixime for cephalosporin-resistant Neisseria gonorrhoeae in the pharynx. Sex Transm Dis 2018;45:677-83. Lewis DA. Will targeting oropharyngeal gonorrhoea delay the further emergence of drug-resistant Neisseria gonorrhoeae strains? Sex Transm Infect 2015;91:234-7. Taylor SN, Marrazzo J, Batteiger BE, et al. Single-dose zoliflodacin (ETX0914) for treatment of urogenital gonorrhea. N Engl J Med 2018;379:1835-45. Ota KV, Fisman DN, Tamari IE, et al. Incidence and treatment outcomes of pharyngeal Neisseria gonorrhoeae and Chlamydia trachomatis infections in men who have sex with men: a 13-year retrospective cohort study. Clin Infect Dis 2009;48:1237-43. Fifer H, Natarajan U, Jones L, et al. Failure of dual antimicrobial therapy in treatment of gonorrhea. N Engl J Med 2016;374:2504-6. Ohnishi M, Golparian D, Shimuta K, et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 2011;55:3538-45. Taylor SN, Morris DH, Avery AK, et al. Gepotidacin for the treatment of uncomplicated urogenital gonorrhea: A phase 2, randomized, dose-ranging, single-oral dose evaluation. Clin Infect Dis 2018;67:504-12. Barbee LA, Soge OO, Morgan J, et al. Gentamicin alone inadequate to eradicate Neisseria gonorrhoeae from the pharynx [published online ahead of print, 2019 Nov 12]. Clin Infect Dis 2019;ciz1109. doi:10.1093/cid/ciz1109 Ohnishi M, Watanabe Y, Ono E, et al. Spread of a chromosomal cefixime-resistant penA gene among different Neisseria gonorrhoeae lineages. Antimicrob Agents Chemother 2010;54:1060-7. Igawa G, Yamagishi Y, Lee KI, et al. Neisseria cinerea with high ceftriaxone MIC is a source of ceftriaxone and cefixime resistance-mediating penA sequences in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2018;62:e02069-17. Blandizzi C, Malizia T, Lupetti A, et al. Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases. J Periodontol 1999;70:960-6. Foulds G, Shepard RM, Johnson RB. The pharmacokinetics of azithromycin in human serum and tissues. J Antimicrob Chemother 1990;25(Suppl A):73-82. Chisholm SA, Quaye N, Cole MJ, et al. An evaluation of gentamicin susceptibility of Neisseria gonorrhoeae isolates in Europe. J Antimicrob Chemother 2011;66:592-5. Mann LM, Kirkcaldy RD, Papp JR, Torrone EA. Susceptibility of Neisseria gonorrhoeae to gentamicin-gonococcal isolate surveillance project, 2015-2016. Sex Transm Dis 2018;45:96-8. Bala M, Singh V, Philipova I, Bhargava A, Chandra Joshi N, Unemo M. Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae. J Antimicrob Chemother 2016;71:1856-9. Liu JW, Xu WQ, Zhu XY, et al. Gentamicin susceptibility of Neisseria gonorrhoeae isolates from 7 provinces in China. Infect Drug Resist 2019;12:2471-6. Unemo M, Golparian D, Limnios A, Whiley D, Ohnishi M, Lahra MM, Tapsall JW. In vitro activity of ertapenem versus ceftriaxone against Neisseria gonorrhoeae isolates with highly diverse ceftriaxone MIC values and effects of ceftriaxone resistance determinants: ertapenem for treatment of gonorrhea? Antimicrob Agents Chemother 2012;56:3603-9. Yang F, Yan J, Zhang J, van der Veen S. Evaluation of alternative antibiotics for susceptibility of gonococcal isolates from China. Int J Antimicrob Agents 2020;55:105846. doi:10.1016/j.ijantimicag.2019.11.003 Quaye N, Cole MJ, Ison CA. Evaluation of the activity of ertapenem against gonococcal isolates exhibiting a range of susceptibilities to cefixime. J Antimicrob Chemother 2014;69:1568-71. Lagac-Wiens PRS, Adam HJ, Laing NM, et al. Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to alternative antimicrobials with therapeutic potential. J Antimicrob Chemother 2017;72:2273-7. Ramus RM, Sheffield JS, Mayfield JA, Wendel GD. A randomised trial that compared oral cefixime and intramuscular ceftriaxone for the treatment of gonorrhoea in pregnancy. Am J Obstet Gynecol 2001;185:629-32. Brocklehurst P. Antibiotics for gonorrhoea in pregnancy. Cochrane Database Syst Rev 2002;(2):CD000098. doi:10.1002/14651858.CD000098 Cavenee MR, Farris JR, Spalding TR, Barnes DL, Castaneda YS, Wendel GD Jr. Treatment of gonorrhea in pregnancy. Obstet Gynecol 1993;81:33-8. Sandoz Limited. SPC on Azithromycin 28/09/2010. See http://www.medicines.org.uk/EMC/medicine/21720/SPC/Azithromycin+500mg+Tablets/#PREGNANCY Wise CM, Morris CR, Wasilauskas BL, Salzer WL. Gonococcal arthritis in an era of increasing penicillin resistance. Presentations and outcomes in 41 recent cases (1985-1991). Arch Intern Med 1994;154:2690-5. Thompson SE. Treatment of disseminated gonococcal infections. Sex Transm Dis 1979;6(Suppl 1):181-4. Haimovici R, Roussel TJ.Treatment of gonococcal conjunctivitis with single-dose intramuscular ceftriaxone. Am J Ophthalmol 1989;107:511-4. European Centre for Disease Prevention and Control (ECDC). Response plan to control and manage the threat of multi- and extensively drug-resistant gonorrhoea in Europe. https://www.ecdc.europa.eu/en/publications-data/response-plan-control-and-manage-threat-multi-and-extensively-drug-resistant Tiplica GS, Radcliffe K, Evans C, et al. 2015 European guidelines for the management of partners of persons with sexually transmitted infections. J Eur Acad Dermatol Venereol 2015;29:1251-7. Sadiq ST, Mazzaferri F, Unemo M. Rapid accurate point-of-care tests combining diagnostics and antimicrobial resistance prediction for Neisseria gonorrhoeae and Mycoplasma genitalium. Sex Transm Infect 2017;93:S65-8. Low N, Unemo M. Molecular    %)-.;<HIVW\]_afgijlqxl^SlJlhT5mH sH hd"hmH sH hd"h5H*mH sH hd"hq~5mH sH hd"h5mH sH hd"hgB5mH sH hah5}5mH sH hahF+5mH sH hah5mH sH hahgB5mH sH hah25mH sH hah>5mH sH hah5mH sH hah56mH sH hahp56mH sH    ]^_ p lmw $]gdx $7$8$H$a$gdH0 7$8$H$gdH0]gdx]gdT]gdYgdxqrt}~ S r Ź薋nd[RIR@hd"h=<PJhd"h5}PJhd"hPJhd"h>PJhd"hq~H*PJ hd"h5B*mH phsH hd"hgBH*mH sH hd"hmH sH hd"h5mH sH hd"hq~5mH sH hd"h2mH sH hd"hoH*mH sH hd"h25mH sH hd"hD?mH sH hd"hD?5mH sH hd"hq~mH sH hd"h|wH*mH sH r F H J n p r    غ~~m\QIhhJwnHtHhehhJwnHtH hd"h<5B*PJRHph# hd"hq~5B*PJRHph# hd"hoB*phhd"hoB*H*phhd"hB*phhd"hB*ph hd"ho hd"h=<hd"h|wB*phhd"hTB*phhTB*phhd"h|wB*H*phhd"hPJhd"h>PJhd"h00JPJ Q { #$^_`l ̶̫̫ti̫^itSthth%nHtHhd"h_nHtHhd"henHtHhd"hh2nHtHhd"h~xnHtHhd"h<>nHtHhd"h~ nHtHhd"haonHtHhd"h6nHtHhd"hnHtHhd"h2nHtHhd"hCRnHtHh,1hhJwnHtHhhJwnHtHhehhJwnHtHhYhhJwnHtH -LYZ]^5@ABDO[v'5g꫶궫thahH0nHtHhd"hS+nHtHhd"h[nHtHhd"h&+nHtHhd"h)nHtHhd"hRmnHtHhd"hh2nHtHhd"hnHtHhd"h=<nHtHhd"h2nHtHhnHtHhd"hCRnHtHhd"henHtH, DcilmnouvwλΨyyrdXdXLhd"h+5PJRHkhd"hhlI5PJRHkhd"hhlI5@PJRHk hd"hgBhd"hPJhd"h`;PJhd"h`;6PJ$hd"h<5@B*PJRHph# $hd"h5@B*PJRHph# $hd"h5@B*PJRHph# hd"h5B*PJRHph# hd"h\}nHtHhahH0nHtHhd"hH0nHtH  !ɾ}tl`UL@Uhd"h\}H*nHtHhqgH*nHtHhd"h\}nHtHhd"hgB5mH sH hd"hgB5hd"hPJ hd"hHG!hd"h>PJhd"hq~@ PJhd"hUD@ PJhd"hhlIPJhd"hs{PJhd"h+PJhd"h+@PJhd"hUD@PJhd"hhlI@PJhd"h+@PJhd"hhlI@PJhd"hhlI5PJ *ST]7Ve f v $ & F a$gda $7$8$H$a$gdY$a$gdY$ & F a$gdagdYgdx]gdxgdY'()*ĹĮģāxmbbWLLhd"h3mmH sH hd"h2mH sH hd"hs{mH sH hd"h>mH sH hqgH*mH sH hd"hgB6mH sH hd"hHG!mH sH hd"h+mH sH hd"h SmH sH hd"h0mH sH hd"h$mH sH hd"hgBmH sH hd"hgB5mH sH hd"h2G5mH sH hd"hhlI5mH sH hd"h\}5mH sH .VWz01Ƚߵ߽꽟|pibibib hd"hhlI hd"hKheehw1H*mH sH heehkH*mH sH heeh H*mH sH hd"hemH sH hd"h75mH sH hd"h2mH sH hTmH sH hd"hgBmH sH hd"h>mH sH hd"h H*mH sH hd"hHG!mH sH hd"hs{mH sH hd"h3mmH sH  123KRgty  ü|qf]Qhd"hHG!H*mH sH heeH*mH sH hd"hz/xmH sH hd"hBxmH sH  hd"ho hd"htG hd"hrnh hd"hv# heeH* hd"hKx j~hd"he hd"hPF hd"h hd"he hd"h3 hd"hKhd"hdu6 hd"hdu hd"h[ hd"hHG!!hd"hHG!@B*EHRHph#  Pisz  /U_bԾԨ|q|f||f[Phd"hzrmH sH hd"h3>mH sH hd"hdumH sH hd"h=mH sH hd"h5>*mH sH hee5H*mH sH hd"hk5H*mH sH hd"h+5mH sH hd"hhlI5mH sH hd"hPF5mH sH hd"h>mH sH hd"hnmH sH hd"h H*mH sH hd"hIH*mH sH heeH*mH sH hd"hHG!mH sH hd"hgBmH sH hd"h9mH sH hd"hv#mH sH #;AQRST\]v!"özzododoYNYNYhd"h mH sH hd"hdmH sH hd"h&mH sH hd"h3>mH sH hd"h-[mH sH hd"hfrmH sH hd"hgB56mH sH hd"hhlI56mH sH hd"h+56hd"h>PJnHtHhd"h2wPJnHtHhd"hhRPJnHtHhd"hPJnHtHhd"hmH sH hd"hgBmH sH "#567klmv{~LZ\lnpx,HJRTVbdlrɾɾɫɫɠti^hd"hs{mH sH hd"hhRmH sH hd"h%ZfmH sH hd"h-[mH sH hd"hdumH sH hd"hymH sH hd"h(`FmH sH hd"hb/6mH sH hTmH sH hd"he$dmH sH hd"hgBmH sH hd"h>mH sH hd"h3>mH sH hd"hdmH sH hd"hnN-mH sH $5 6 c d e f u v !!!!Ƚߧtiߧ^Sߧhd"h;mH sH hd"h_mH sH hd"h3>mH sH hd"hCmH sH hd"h>56mH sH hd"hhlI56mH sH hd"h>5mH sH hd"h>mH sH hd"hmH sH hd"he$dmH sH hd"hhRH*mH sH hd"hkmH sH hd"hgBmH sH hd"h mH sH hd"hhRmH sH v !!!o"###$$$$%a%%%&&U&&&K'L'b' & F gdagdY$a$gdY$ & F a$gda!!!!!!! "<"m"o""""""""""""""" #"###+#~vkd\W\WdPdIdW\d hd"h[| hd"h> heeH*hd"hFlH* hd"hFlhd"h7mH sH h}ymH sH hd"hnN-mH sH hd"h+mH sH hd"hhRmH sH hd"h1XmH sH hd"hA+mH sH hd"hgBmH sH hd"hLmH sH hd"hs{mH sH hd"h>56mH sH hd"hhlI56mH sH hd"hA+56mH sH +#3#>#q#r###################s$v$$$ɾɾ굩{slelT hd"hv%XB*]mH phsH  hd"hD hd"hv%Xhd"h>#5hd"he5hd"hv%X5hd"h>mH sH  hd"hFlhd"hFlH*mH sH hd"hOlH*mH sH heeH*mH sH hd"hmH sH hd"hK/mH sH hd"h?mH sH hd"hnN-mH sH hd"h3>mH sH hd"hgBmH sH $$$%%%%%%%%&&&&&&&''D'E'F'G'I'J'L'Y'a'b'd'k'o'׻״׻׬ד{ocXhd"hgBmH sH hd"hgB5mH sH hd"hs{5mH sH hd"h>5mH sH hd"hv%X5mH sH hd"h` ;5mH sH hd"h(H* heeH*hd"hH* hd"hhR hd"hk hd"hn hd"hI> hd"hD hd"hv%X hd"hv%XB*]mH phsH  hd"heIB*]mH phsH  o'}'''''''''''''''''''' ( (%(*(>(F(w(y(z(걨҅yncncn[Phd"hhJwmH sH hhJwmH sH hd"hIDmH sH hd"h8mH sH hd"h?6mH sH hd"h86mH sH hd"h>mH sH hd"hOlH*mH sH h<9H*mH sH hd"h?mH sH hd"hs{mH sH hd"h!!mH sH hd"hL6mH sH hd"hgB6mH sH hd"hgBmH sH hd"h&mH sH b''(Y,023\468':!;J<K<b<<gdf $ & F 7$8$H$a$gdnD$ & F 7$8$H$a$gdF$7$8$H$^`a$gda$ & F 7$8$H$a$gda$ & F a$gdaz((((((((((((()/)>)L){))))))))))****ɾzoodYdMhd"hOlH*mH sH hd"hemH sH hd"hb/6mH sH hd"hVrmH sH hd"hWRmH sH hd"hl7mH sH hd"hgBmH sH hd"hmH sH hd"h5mH sH hd"hgB5mH sH hd"h>mH sH hd"h?mH sH hd"hmmH sH hd"h?mH sH hd"hQ8umH sH hd"hyYmH sH ******* *<*H*`**********++++4+++++++++++++++ȽȲȧȲȧȜȑȑ{oooochd"h?H*mH sH hd"h8\H*mH sH hd"hemH sH hd"hb/6mH sH hd"hWmH sH hd"h imH sH hd"hVrmH sH hd"hnDmH sH hd"hNrmH sH hd"hgBmH sH hd"hmH sH hd"h?H*mH sH hd"hOlH*mH sH h~$yH*mH sH &+++ ,,,,&,0,8,;,I,K,X,Y,`,,,,,,,,,,-------'.).8.ɾxqldldl]] hd"hAhd"hGH* h~$yH* hd"hG hd"hN< hd"hQ8u hd"h d hd"h^T hd"hgBhd"h dmH sH hd"hgB5mH sH hd"h>\mH sH hd"himH sH hd"h'omH sH hd"hs{mH sH hd"hWmH sH hd"h^TmH sH hd"h imH sH "8.:.;.=.>.?.I.L.V............///L//////////////////ݹݲzszhhd"h^TB*ph hd"hhd"hgBB*phhd"hOlH*hd"h8\H* hd"he hd"h,X2hd"hemH* hd"h d hd"hgB hd"ht hd"hb hd"hs{hT hd"hQ8uhhJw hd"h7* hd"hW hd"hA h~$yH*hd"hAH*(//0000&0001060K0L0M0P0Q0S0U0V0i0r000000000000111ȽӲȲӽ~v~og`X~hd"hX[H* hd"hLnhd"hLn5 hd"hc,hd"hPH* h~$yH*hd"h8\H* hd"h? hd"h hd"h[ hd"hgBhd"hQB*phhd"hPB*phhd"htSB*phhd"h^TB*phhd"hB*phhd"hs{B*phhd"h[B*phhd"hgBB*ph!1111 1 1 1 1<1C1D1I1L11111112222V2W2X222222222222222222Ӻvo hah hd"h nHtHhd"h,tH* hd"h? hd"h2 hd"hla hd"hg1 hd"h+ hd"h$ hd"ha hd"hgBhT hd"h]/ hd"hy hd"hLnhd"hLnH*hd"hX[H* h~$yH*hd"h8\H*hd"h9!H**222-3;3F3G3P3W3a3h3q3r3t3u3w3x3y3{3|3~3333333333333344@4A4B4D4E4F4ʻ״xqxj hd"hL hd"he hd"hy hd"hUzh hd"h hd"h[ hd"hQ_ hd"h:*[ hd"h9 hd"hc, hd"hu hd"hahd"h,tH* h~$yH*hd"h8\H* hd"h hGT hd"h Z hd"hc/ hd"hihd"h 5)F4H4I4K4L4M4N4O4P4Q4R4S4U4W4X4Y4Z4[4\4a4444444444444444444444&5T5c5d5Ǽxq h=h% h- h^T h- h%h;`h%H*hah%H*h =h;`H*h- h;`H* h =h% h;`h%hah%5h=h>nHtHh- hE6?nHtH h- hJP hd"hgB h;`H*hd"hH* hH* h~$yH*hd"h H*,d5f5g5i5j5l5m5n5o5p5q5r5s55556&6(6)6+6,6.6/616263686966666666677.787P7T7⻳{tmt hd"hu hd"hA>hd"h*.6 hd"h-9 hd"h*.hd"h-95hah%nHtHh=h%H* h- h%h- h%6 h =h% h =H*h;` h;`h%h;`h%H*hah_j0H*h =h%H*h =h;`H* h;`H*hah;`H**T7_7q7x77777777777777777888888"8%8,848?8R8V8Y8Z8b8t8w888888888888888 hd"he hd"hs{ hd"hOGS hd"h$a hd"h$ hd"h4 hd"h+ hd"h@ hd"h^T hd"h*w= hd"h(lhd"h H* h =H*hd"htH* hd"h$ hd"h7g hd"hA> hd"h-9388888888888889;9M9W9i9p999:::::: :":#:':.:/:3:wphhah5 hd"hhd"h5hd"h3WH*hd"h[H*hd"hH* hd"hP hd"h&le hd"h]K hd"h* hd"hTbX hd"hb< hd"hhG hd"hU, hd"h'hd"h'5 hd"h>hd"hvH* hH*hd"htH* h =H*!3:=:@:K:T:U:n:q:r:|::::::::::;;;;˺veTDh =B*H*PJnHphtH!hd"h B*PJnHphtH!hd"hfm7B*PJnHphtH!hd"h5cB*PJnHphtH!hd"hB*PJnHphtH!hd"hAB*PJnHphtH!hd"hB*PJnHphtH!hd"h` ;B*PJnHphtH hd"h+hah+5$hahs{5B*PJnHphtH$hah` ;5B*PJnHphtH;;;;;;; ;!;2;3;<;=;>;A;^;_;`;c;r;s;t;{;ʺyncnXnMnBMnhd"h_B*phhd"h8cB*phhd"he^B*phhd"hB*phhd"h PB*ph hd"h+hah+5hah P5B*phhah$w5B*ph hd"h8c!hd"hfm7B*PJnHphtHhB*H*PJnHphtH$hd"h[B*H*PJnHphtHh =B*H*PJnHphtH$hd"h`B*H*PJnHphtH{;;;;;;;;;;;;;;;;;;<(<+<,<H<I<J<K<L<a<b<ȾȂȂwwpe]UMhd"hgB5hd"h]5hd"hhlI5hd"hgBmH sH  hd"hgBhd"h)B*phhd"h~B*phhd"h +B*H*phhB*H*phhd"hB*H*phhd"h[B*H*phh =B*H*phhd"h^IB*phhd"h PB*phhd"hFCB*phhd"h$wB*phhd"hm=B*phb<<<<<<<<<<<<<%=&='=+=-=Z=^=`=a=h=w=~=============)>:>;><>E>S>о巜оyrkr hd"h> hd"hMP hd"h,t hd"h#I hd"hF8 hd"he hd"h$ hd"h hd"h+Chd"h3P(H* htH* hd"h` hd"h9! hd"hkK*h X hd"h{w@ hd"h~4 hd"h] hd"hgBhd"hgB56hd"hhlI56*<<>>?:@;@Q@?AqILLLM9NYOPPmQoQgdx$a$gd"T$ & F a$gdagd"T $`a$gdO $`a$gdagdkgdf $ & F a$gdaS>V>a>q>}>>>>>>>>>>>>)?E?K?L???????????@@@ @!@+@Ⱥ֨ևևth]hd"h9!nHtHhd"h]6nHtHhd"hnHtHhpnHtHhd"h]nHtHhd"hb/6B*phhd"hwB*phhd"h%ZfB*ph hd"h> hd"hb/6 hd"he hd"hFtB hd"h5? hd"h] hd"h#I hd"h{w@ hd"hgB hd"hMP hd"h+C#+@/@2@4@5@6@8@9@:@;@B@I@J@L@O@P@Q@@@@0A7A:A;A>A?AIAƿ{ri`W`IEh hahk5H*mH sH h- H*nHtHhH*nHtHhFH*nHtHh[6nHtHh[nHtHhd"hknHtHhahgB5H* hO5H* h5H*hd"hjI)5H* ht5H*hd"hhlI5 hd"hgB hd"h> hd"h{w@hd"h"TnHtHhd"henHtHhd"h]nHtHhd"hJPnHtHIATAYAfAsAAAABBBB!B5B6B7BwBxBzB{B|BBCCCCCCC*C-C8C;CECGCJCaCsC}CCCCCCDDʸѰѸ~v~hd"h]hd"hb]hd"hgT] h]hd"hw]hd"h{] hk]hd"hZH*hd"h +H*hd"h] h};H* hBcYH* hd"hQ hd"hh}yh hvh h hd"h. hd"hjI) hd"hb-DD D D DDDDDDDDDD*D/D;DRDSDTDaDjDkDlDnDoDpDqDrDsDzDDĽyqid]V hd"hY hd"hS* h};H*hd"hZH*hah'H*h=hBcYH* hBcYH*h; hd"h6hd"h.6hd"h(w6 hd"h(w hd"h. hd"hH hd"hjI) hd"h{hd"hZH*] hBcYH*] h H*]hd"h[H*] h};H*]hd"h +H*]hd"hS*]DDDDDDDDDDDDEE*E+E,E-E/E0E1E:EbEnE{EEEEEEEEEEEEBFûóëëÑÑÁunjfnh*Rrh(Q hah hd"hd"H*mH sH h(QmH sH h;mH sH h*RrmH sH h};H*mH sH hBcYH*mH sH h mH sH hd"mH sH h.mH sH hd"hd"mH sH  h};H*hd"hoH* hd"h= hd"hZ hd"hw; hd"hYhd"hY6$BFCFDFEFFFIFNFOFSFjFzFFFFFFFFFFFFFFFFGGGGGGGGGGGGGGGGGGGGG4H5H7H8H:HH?HbHHHHHHHHHHHHHHHHHH I'I)I8I9I:IFIdIfIgIiIkImIoIpIqIrIyIIIIIIII Jžгx hd"hR hd"h@ hd"hi hd"hIhWKhiH* hd"hlhd"h \&H*hd"hWH*h hd"hA hd"hG hd"h&POh:\h- hd"h#i hFH*hd"h;H* hd"h;h*Rr hd"h0 h dH*. JJJJJJ.J9J?JBJLJYJ_JyJJJJJJJJJJJJJJJJJJJJJJJJJJJJJKչΤΜΊ|Ճtm hd"hf hd"hyRH* hd"hM hd"h6hd"h66 hNmPH* hFH*hd"h4BH* hd"hcC hd"h hd"h5O hd"hx hd"hV hd"h X hd"hR< hd"h@ hd"h)0 hd"hihd"hi6 hd"hx hd"h~*KKKKKKKKK&K0K2K9K>KIKPKnKqKuKKKKKKKKQLRLZL]LhLiLjLtLLLLLLLLLLLLLLҲҹҤҝxhd"hE.NH*hd"hWH* hd"h6 hd"hd; hd"h% hd"h;lZ hd"hK hd"hgB hd"hw( hd"hTHh- hd"h_V hd"hq7 hd"hFU hd"hi hd"h)0hd"h4BH* hFH* hNmPH* hd"hx.LLLLLLMM,MPM\MaMcMfMrMsMwMMMMMMMMMMMMMMMMMMMMMĽIJ||ungg]ghd"h)Q6] hd"h)Q hd"h> hd"h6 hd"h hd"h|" hd"hwC8 hd"h5Oh- hd"h^ hd"hJh-mH sH hd"h|"mH sH  hd"h- hd"hgBhd"hgB56hd"h"T56hd"hhlI56hd"hwB*phhd"hgBB*ph$MMMNNN)N.N2N3N6N7N8N9NaNpNtN}NNNNNNNNNN)O,O/OKOYOOOCPMPWPeP򺳬}vookd hd"h_[h7p hd"hwC8 hd"hx4 hd"hy hd"h*hd"hOB*mH phsH hd"h"TH* hNmPH* hFH* hd"h] hd"hJ hd"h7* hd"h#+ hd"h> hd"h6 hd"h5O hd"hR hd"hU hd"h)Q hd"hgB hd"h^%ePsPtPPPPPP*Q9QUQVQXQYQZQ\Q]Q_Q`QbQcQfQgQhQiQjQlQmQoQ{Q|Q}QQQQQQͻxqjc\j\j\j hd"hR< hd"hih hd"h)Q hah)Qhd"h>56h``:56H*hk856H*hd"hm56H*h 56H*hd"ha56H*hd"h956H*h 56H*hd"h7*56hd"hhlI56 hd"hJ hd"h>h7p hd"hgB hd"h.hd"h.6$QQQQQQQQQQQQQQQQRRR&R2R6R7RkRyR}RRRRRRRRRRRR}u}nfhd"hN*5 hd"h3`chd"hmH* hcH* h``:H* hd"hR[b hd"hwhd"h@{5 hd"h w~ hd"h@{ hd"h hd"h!r hd"h hd"hm hd"h5 hd"hb hd"hFtB hd"hO hd"hw hd"h#hd"hL $5 hd"hR<$oQQRRSSSSTTGTTT%UUUWW?XXX$a$gd#9gdx$a$gd3iN $S^Sa$gda$a$gd"T$ & F `a$gda$ & F a$gdaRRRS/S1S4SX?X^XtXXXXXXXXXXXXXXY*YYYYYYY Z ZZZĽ{s{l{l{s{g_ghd"hcH* hcH* hd"hThd"hH5 hd"hHhd"hH6hBch3-6hd"h$6 hd"h{ h H*hd"haH*hd"h.H* hd"h)9l hd"h3-hd"hv6H*hd"h56H*hd"hX^56H*h``:56H*hd"h3-56hd"hv56%XXWYZZZZZ\\\4]]]e`f` $7$8$H$a$gdw($ ^a$gda$ & F a$gda $7$8$H$a$gd#9 $^a$gd#9 $^a$gdcgda$ & F `a$gda$ & F a$gdHgdxZZZZTZcZZZZZZZZZ[[[ [%['[([)[*[5[9[B[Y[][`[[[[[[[ǿ||u|ung`nY hd"hm hd"h@+ hd"h}B hd"hK hd"h? hd"h)9l hd"h3hd"h>aH*hd"hc"H* h H* hd"h>ah7p hd"h] hd"hN hd"hX.hd"h3-6hd"h 6hd"hc6PJnHtHhd"hcPJnHtHhd"hc5 hd"hc hd"hH"[[[[[\ \\e\n\\\\\\\\\\\\\\\\\\\\\\\\]3]f]p]q]t]u]v]]㞗zslslsls hd"hK hd"h'hd"h5 hd"h hd"h~ hd"hN hd"h#9 hd"h? hd"h3-hd"h>aH* h H*hd"hHH* hP, H*hah)6 hd"h) hd"hH hd"h}B hd"h@+hd"h@+6 hd"hm hd"h;$)]]]]]]]]]]^%^/^h^i^^^^^^^^^^ _!_D_K_Y_Z_qfYYYLhd"h%PJnHtHhd"h3-PJnHtHh H*PJnHtHhd"h>aH*PJnHtHhd"hc"H*PJnHtHhd"hnPJnHtHhd"h'PJnHtHhd"hvPJnHtHhd"hfm7PJnHtHhd"hNPJnHtHhd"hN5PJnHtH hd"hN*hd"hcH* hcH* hd"h'hd"h'5Z__________(`7`d`e`f`p````````̿ٲ٘xnd]V]NF>hd"h%]hd"h3-]hd"h@] hd"hL hd"h3-hd"hL56hd"hm56hd"hD756hd"hmH*hd"hj)6PJnHtHhd"hj)PJnHtHhd"h_`3PJnHtHhd"hnPJnHtHhd"h@PJnHtHhd"hmPJnHtHhd"h3-PJnHtHhd"h]PJnHtHhd"hfm7PJnHtHf`` b b#bb@cAccccd ee{f|fgd8$a$gd#9$ & F^`a$gda $7$8$H$a$gdO $^a$gdj) $h^ha$gda$ & F `a$gda$ & F^`a$gda$a$gdr sgdx```aaa aa&akapaxaaaaaaaaaaaaaaaaabbbbb b b b b b#b%bKbXbbbb߾緰|t||hd"hZ*(5 hd"hZ*( hd"h'hd"he6 hd"hehd"h3-B*]phhd"h>aH*] h H*] hP, H*] hd"h%hd"h]hd"hZ']hah%6]hd"h%]hd"h3-]hd"hcC]hd"hL],bbbbbbbbbbbbb8c;c=c?c@cAcGcccccccc0d2dzddddddddyrrkf h H* hd"hX$ hd"htGw hd"h$W hd"hO hd"hqqchd"hO6hd"hj)6 hd"hj)hd"hj)6PJnHtHhd"hj)PJnHtHhd"hj)5 hd"hZ*(hd"hcH* hcH*hd"h'5 hd"hn hd"hK hd"h' hd"hm$ddddddd e eeee&e4eeeeeeeeeeeeefff-f.fsftfvfwfyfzf{f|f}füvlhd"hem56 *hd"h56 hd"hO hd"h.hd"h.6 hd"hS= hd"hfm7hd"h\H* hP, H*hd"h6] hd"h hd"hZ*(hd"hZ*(5hd"hN*5hd"hO56 hd"h  hd"hO h H*hd"h H*'}fffffg g'g*g5gIgogpgrgsgugvgwgyg{g|g}ggggggggggggggggggggggggggghd"h8H*hd"h*.H*]hd"h(gH*]hd"h]FH*] hJH*] hQH*] hJH*hd"h*.H* hQH* hd"h hd"hW+ hd"h@ W hd"h8 *hd"h856hd"h856hd"hm56/|ffggghhhPiQifiiijj:j$a$gd#Ne$ & F^`a$gda $^a$gdj)$a$gd/*]$ & F `a$gdX$ & F ^`a$gdagd|$a$gd8gd8ggggggihmhhhhhhhhi"iOiPiQifihiiiiiiiijjj jzskcs\T *hd"h#Ne hd"h zhd"h/*]5hd"hN*5 hd"h/*] hd"h(2 hd"hN*hd"h86 hd"hS hd"hj)hd"hj)6PJnHtHhd"hj)PJnHtHhd"hj)5hd"hj)6hd"hcH* hcH*hd"hX5 hd"hXhd"h|6 hd"h8hd"h8B*ph j4j9j:j;j@jAjBjEjFjMjNjPjQjVjdjejtjjjjk kk k3kPkRkSk^k_kbkckdkkkkkkkkԷ밫뜒~tjthd"h[)v56hd"hhlI56hd"h56hd"h$g056hd"hem56 hd"hShd"h H* h H* hd"hX$hd"h#Ne6 hd"htGw hd"he hd"h hd"hu,Vhd"h#Ne5hd"hN*5 hd"h#Ne hd"h#9 hd"h8(:j;jckdkkmmnnZo\oooppoq $^a$gdj) $7$8$H$a$gda $^a$gda$ & F ^`a$gd $^a$gda$ & F ^`a$gda$a$gd'$a$gd#9gd#9 $7$8$H$a$gd#9kkkkkkkkkkk l0lLlVl\l}l~llllllmm!mĺveTe!hd"hc|B*PJnHphtH!hd"hF8B*PJnHphtH!hd"hB*PJnHphtH!hd"h#9B*PJnHphtH!hd"h'B*PJnHphtH!hd"hB*PJnHphtHhd"h>56hd"hhlI56hd"hc|56H*hd"h#b56H*hJ56H*hd"h<56H*hQ56H*!m/mTmmmmmmmmnnnn1n5n7n9n:nAnFn]n^n_nangnsnvnwnxnyn|n~nnn˺{tmfm__X__X_t_XX_ hd"h=h hd"h[)v hd"h:-\ hd"hId hd"h#9 hd"hOhd"h}5 hd"h} hd"hhd"h_56 hd"h_!hd"hB*PJnHphtH!hd"hKB*PJnHphtH!hd"h'B*PJnHphtH!hd"h7B*PJnHphtH$hd"h'6B*PJnHphtH"nnnnnnnnnnn o-oYoZo\o^ovoxoooooooooooooooooooooooooppǸǪǣǜև뀇yr hd"h hd"h] hd"h hd"h? hd"h *hd"h> hd"hj)hd"hj)PJnHtH%oqpqqqWrXrrrssssKt$ & F ^`a$gdz3$a$gd$ & F `a$gd$ & F ^`a$gdgd$wgdxgd#9$a$gdwE$ & F ^`a$gda $7$8$H$a$gda rrrrrrrrrrrrnsrsssssssstt~tttttttuuuu uIu~~wobhd"hj)PJnHtHhd"hj)5 hd"hj) hd"h.Thd"hz35 hd"hz3hd"hO6hd"hi6hd"hcH* hcH*hd"h5 hd"hhd"hgB6hd"h&b6hd"hgBH*hd"h|56H*hJ56H*hd"hin556H*hd"hhlI56#KtuuuuuuwwwwwOxPx{$ & F ^`a$gda `gdagd_`3 $^a$gd_`3$a$gd_`3^gd$w$ & F^`a$gda $ a$gda $^a$gda$ & F `a$gdkK* IuXuuuuuuuu[vjvuvvvzvvvvvvvvvvwww&w/w7wEwHwPwSwuwwww֖zssssldhd"hin5H* hd"hz hd"hF hd"h hd"h7 hd"hx hd"h7p hd"h hd"h@3 hd"h  hd"h) hd"h &4 hd"hhd"h &45 hd"hgB hd"h( hd"hz3 hd"hj)hd"hj)PJnHtHhd"hj)6PJnHtH$wwwwwwwwwwwwwwwwwwxxLxMxNxOxPxQxlxɿɤsfYfOEhd"hH456hd"hHD56hd"hvB*\phhd"h5RB*\phhd"hH40JB*\phhd"hH4B*\ph hd"h5R hd"hH4 hd"heg3 hd"hgBhd"h'v56hd"heg356hd"h9&56hd"hhlI56hd"hem56 hd"h> hd"hO hd"h  hJH*hd"hH*PxmxyyCyzzz {2{Y{Z{||.|\| & F^`gda$ & F^`a$gda$a$gdx$a$gda^gd & F^`gdagd$a$gd_`3$ & F ^`a$gdeg3`gdalxmxoxyxxxxxxxxxyyy56hd"hhlI56hd"hem56hd"hH456 hd"h> hd"hH4hd"hvB*\phhd"h5RB*\phhd"hH40JB*\phhd"hH4B*\ph hd"h5R hd"heg3hd"h9&56yyyyy z z6zjzkzlzmzpztzuzwzxzyz|z}zzzzzzzzzzzzzz { { { {{/{1{2{4{5{C{D{X{Y{{{{{{||||||ļ򮧮򮠮򮵧hah5 hd"h hd"hz hd"hq  hd"hgB hd"h>hd"hH* htH*hd"h@H* h-H* hd"hK/ hd"h  hd"h9& hd"h7* hd"h hd"h')9|||%|*|+|-|.|0|A|B|E|N|O|Z|[|\|]|c|||}}"}2}E}b}d}e}p}q}t}u}v}}}{m_hd"hhlI56B*phhd"hem56B*phh 56B*phhd"h H* h H* hd"hG>hd"hx6 hd"hu hd"hxhd"hx5hd"hq 5 hd"h> hd"hn hd"hq  hd"hhah5 hd"hK/ hd"hup hd"hz hd"hgB#\|]|u}v}}N~O~~ghDgd_`3  ]^ gd_`3 $^a$gdj)$ & F `a$gdA $ & F ^`a$gdA $7$8$H$a$gd_`3 7$8$H$gd_`3 $^a$gd $7$8$H$a$gda }}}}}}}}} ~%~0~5~M~N~O~s~~_bdfghƸrkckck^V^kIhd"hA 6B*phhd"hcH* hcH*hd"hA 5 hd"hA hd"hO6B*phhd"h>PJnHtHhd"hB*phhd"h}$B*phhd"h5B*phhd"h TB*phhd"h>56B*phht56B*H*phhd"h%_q56B*H*phhd"hb56B*H*phh-56B*H*phhn <=?@ACȺtdVJ;J;Jhd"h956H*PJRHoh-56H*PJRHohd"hO56PJRHohd"hO56@PJRHihd"hO56PJRHihd"hO56@PJRHmhd"hO56PJRHmhd"hO56@)PJhd"hO56PJhd"hem56B*phhd"hj)6B*ph hd"hj)hd"hj)6PJnHtHhd"hj)PJnHtHhd"hj)5CDVkpźů䦝wne\Shd"hS@)hd"hS@#hd"hS@,hd"hS@hd"hS@hd"hSRHnhd"hSRHhd"hS@RHnhd"hSRHphd"hS@hd"hS@RHjhd"hS@!RHjhd"hSRHjhd"hS@RHjhd"hA@RHj hd"hS hd"hOhd"hO56H*PJ€ŀƀˀ̀πЀҀӀԀ LN]_z|}𪣕xxmfbfbfXQ hd"hv&&hd"hv&&56hN&` hd"hm hd"hm 56H*hd"hb56H*h-56H*hd"hm 56hd"hem56B*ph hd"h p hd"hd/phd"hS@hd"hS@,hd"hS@hd"hSRHnhd"hS@ hd"hS@hd"hS@ hd"hShd"hS@%ӀԀ|}܁pqkՄ"H؍ٍ$a$gdO $ & F a$gd#M" $ & Fa$gd#M"$a$gdemgdO$a$gdv&&gd$w & F B]B^`gda}ԁՁہ܁݁ 57FHIblnpq1dfhjkʿ籏ti^itiW hd"h5Rhd"h`nHtHhd"h5RnHtHhd"hOnHtHhd"hgB5hd"hhlI5hd"h5R5 hd"h8Lr hd"h/hN&`hd"h!6 hd"hem hd"h!hd"hem56H*ht56H*hd"h #56H*hd"h!56hd"hem56hd"hem56B*phknz܃#2Ą΄ЄӄԄՄք܄ 5<GSTUWXYZ\]_`acdefmҼ򼵮 htH*hd"hrH* h-H* hd"h hd"hA hd"h> hd"h& hd"hO hd"hK/hd"h6 hd"hs hd"h hd"h5x hd"hCTZhp hd"h` hd"h5R hd"hgB5mnЅӅ!",Wqˆ -BCEGHJMQ]jćž䰩䰢䔩yt h@sH*hd"hrH* h-H* hd"h;$ hd"h3H hd"h` hd"h=h hd"h& hd"h* hd"h$?# hd"h;{ hd"hZ$hd"hgB5hd"h3H5hd"hhlI5 hd"h> hd"hgB hd"hD+ hd"h hd"h5R-ćŇƇԇ:=>EFKRUd.<IR_g|޻쟴ɘ||wohd"h{AQH* h-H* hd"h$g0 hd"h?! hd"h{%c hd"hBw hd"hmn hd"hRQ hd"h& hd"ht7 hd"hM hd"hUK hd"h7* hd"hT hd"hT hd"h* hd"hq! hd"hF hd"hF hd"h` h@sH*(‰ÉΉщOP@TWcklyz|}~Ǹꬤxqqjqx hd"hv hd"h} hd"hUK hd"h h-H*hd"hSuH* hd"hia5 hd"h& hd"h` hd"hT hd"h?! hd"hF h@sH*hd"h{AQH*hd"hrH*( 34;JKO[su$4567FMWepܻܰܥܰ}rg_hN&`B*phhd"hUKB*phhd"hAB*phhd"h!B*ph hd"h+hd"h2RB*phhd"h5hd"hp 5hd"hhlI5 hd"h1P&hd"h}5B*ph hd"hihd"hdB*H*phh@sB*H*phh-B*H*ph hd"h+hd"h2B*phhd"h @B*phhN&`B*phhd"hN&`B*phhd"hdB*phhd"h5AB*phٍَ#=ΐ\]eӑԑ 7$8$H$gdFV 7$8$H$`gda $7$8$H$a$gda 7$8$H$gdLO$a$gdFVgdLO 7$8$H$gdp $@&a$gdpgdpgdO$a$gdOntz؎َ#=@noΐҐؐ[]eӑԑʾԯ{{p{pdpXhd"hFV5nHtHhd"hLO5nHtHhd"hLOnHtHhd"h=lnHtHhd"h3iNnHtH *hd"hFVhd"hFVhx( h-H* hd"hFVhd"hLO5 hd"hphd"hp0J0PJ\hd"hp0J0\hd"hp5hd"h45 hd"h> hd"h2 hd"h1P& hd"hK g̓ϓ@ENYcd&'23xѕߕ˹{tttlhd"hN:26 hd"h"thd"hp 6 hd"h4_e hd"hN:2 h-H* hd"hF+ hd"h2 hd"hz-J hd"h} hd"h@s hd"hp hd"h}nHtHhd"hF+nHtHhd"h4_e5hd"hp 5hd"hFV5 hd"hFVhd"hFVnHtH*̖͖șəQښ & F gd#M" & F -DM gdIRgdFVgdx 7$8$H$gdO 7$8$H$gdx 7$8$H$`gdO $7$8$H$a$gdOgdO 7$8$H$gdFV1P_˖̖fə2@FHQಧzjzZzOhd"h B*ph!!!hd"hIR5mH nHsH tHhd"hIR6mH nHsH tHhd"hIRmH nHsH tHhd"hgB5>*hd"hhlI5>*hd"h4i5>*hd"hFVnHtHhd"hFV5nHtHhd"h nHtHhd"hx(nHtHhd"hp 5nHtHhd"hp nHtH hd"h4 hd"h4_e hd"hp Țٚښ5:C`'k|JX^`gǼǩǩǩǟNJǃypǩNJh]hd"h mH sH hd"h 5hd"hI0J4hd"hI0J45 hd"hIhd"h 0J6hd"h 6\]hd"h 6]hd"h 6hd"h mHsHhd"h mH sH  hd"h hd"h 5B*ph!!!hd"h B*ph!!!hah 6B*]ph!!!hah B*ph!!! g4ĞRɡ1 w=&d  & F gd>z & F -DM gdGV1 & F gdGV1 & F gd#M"3 & F [$\$gd#M" & F [$\$gd#M"#)+4;[_žĞPQR ƿƿ}vnvg`X`X`P`hd"hgB5hd"hhlI6 hd"hgB hd"hA<hd"hk6 hd"hkhd"hBhmH sH  hd"hBhhd"hBhmHnHuhd"hI0J4hd"hI0J45 hd"hIhd"h 0J6 hd"h hd"h \hd"h 5mH sH hd"h 0J6mH sH hd"h mH sH hd"h 6mH sH Z]x{ɡ!').01 agmnuvwBCcrxzͽͶͪ̀yrrͽ hd"hxG hd"hhd"h5hd"hmHsHhd"hgB5mHsHhd"hgBmHsHhd"hhlI6mHsH hd"h?hd"hgB5hd"hhlI6 hd"hgBhd"hF6hd"h c6 hd"hF hd"h c hd"h{AQ hd"h>(ʤפؤ"7apuw#+13=D^cef&ȸȥ{{hXhd"hGV15mH nHsH tH%jhd"hGV1UmH nHsH tHjhd"hGV1Uhd"hGV16mH nHsH tHhd"hGV1mH nHsH tH%hd"hGV1B*mH nHphsH tHhd"hGV15hd"hGV16 hd"hGV1hd"h(`F5hd"hhlI6hd"h(`F6 hd"h hd"h(`Fhd"hemHsH!&çԧڧݧVW`acd֨ר[\hiklک۩Z[hijkDZDZDZDZDZy hd"hxGhd"h75hd"hhlI6 hd"h hd"h7%jhd"h0J>*B*Uphhd"h70J>*B*ph hd"hjhd"hU hd"hGV1hd"hGV15B*ph!!!hd"hGV16B*]ph!!!hd"hGV1B*ph!!!+)>r~FSY[ >DKƭȭ )*./67=>MNֵּhd"hhlI6 hd"h hd"h" hd"h| hd"h,hd"h|6hd"h>z6 hd"h>zhd"h(6]hd"h(5hd"h(6 hd"h(hd"h(5mH sH hd"h(6mH sH hd"h(mH sH 2>LRT\] !#'(,0MR}ֺ㳫|tmtmbTbhd"h%D0J6mH sH hd"h%DmH sH  hd"h%Dhd"h%D\hd"hX[5hd"hX[6] hd"hX[ hd"h> hd"h/hd"hgB5hd"hhlI6 hd"hgBhd"h:b5PJnHtHhd"h:b6PJnHtHhd"h:bPJnHtH hd"h:b hd"hhd"h"5 hd"h" ],(ϲc B{S[?;&$ & F 1$G$a$gd#M"m$ $ & F a$gd#M"m$3 & F [$\$gd#M" & F 7$8$H$gd#M" & F gd#M"(ñ ~òƲβϲ0EGTZ[cسһ~v~v~n~cUchd"hXi6B*]ph!!!hd"hXiB*ph!!!hd"h6J5hd"h6J6 hd"h6Jhd"h6J6mHsHhd"h6JmHsHhd"hgB5hd"hhlI6hd"hgB6 hd"hgB hd"h>hd"hO5hd"hO6 hd"hOhd"h;$k6 hd"h;$khd"h%DmH sH hd"h%D5mH sH ! *^nsu},24=>AB)>|ҬyrkdZdPhd"hhlI6]hd"h;$k6] hd"h;$k hd"h hd"h6Jhd"hVS5B*ph!!!hd"hVS6B*]ph!!!hd"hVS6B*ph!!!hd"hVSB*ph!!!hd"h|%i5\hd"h|%i6] hd"h|%ihd"h|%imHsH hd"hXihd"hXi5B*ph!!!hd"hXiB*ph!!!hd"hXi6B*]ph!!!߶Zjprz{ #eu{}1FK`bouw~2BHǿǿǷǬ֎~֎֎hd"h85hd"h86 hd"h8hd"hhlI6mHsHhd"h>mHsHhd"h8mHsHhd"h5hd"h6 hd"hhd"hgB5hd"hhlI6 hd"hgB hd"h>hd"h;$k5\]hd"h;$k]1HJRSxy~Һ׺>KQSZ[ƻ 39FJYaouw!˼hd"h5PJnHtHhd"hPJnHtHhd"hVS6PJnHtHhd"hVSPJnHtH hd"hhd"h"5 hd"h"hd"h86hd"hhlI6 hd"h hd"h> hd"h8hd"h851!/57>?afƽ˽$*02:;H־۾%&οɴɴɴɴɨzmzhd"h6B*ph!!!hd"hB*ph!!!hd"h5mHnHuhd"h6mHnHu hd"hhd"hmHnHuhd"hVS6PJnHtH hd"hVShd"hVSPJnHtHhd"h5PJnHtHhd"hPJnHtHhd"h6PJnHtH%ο޿ _z̿tmemVhd"h0J6B*phhd"h6 hd"h hd"h5B*mH phsH $hd"h0J6B*mH phsH hd"hB*mH phsH hd"h6B*phhd"hB*phhd"hB*\phhd"hPJnHtHhd"h5B*ph!!!hd"hB*ph!!!hd"h6B*]ph!!!&s?-" ! & F gd#M" & F gd#M"$ & F 1$G$a$gdJm$ & F gdJ & F [$\$gdJ & F [$\$gd#M"3 & F [$\$gd#M" & F 7$8$H$gd#M"^agjw'<@Uwۿۮ裖{shhah=B*phh=B*ph!!!h$wh=5B*ph!!!h$wh=6B*]ph!!!h$wh=6B*ph!!!h$wh=B*ph!!! hd"hPJmHnHsHtHhd"h5PJnHtHhd"h6PJnHtHhd"hPJnHtHhd"hB*phhd"h5B*ph#Tcikrs /57?z"$-JOQ^sx"ƿtththd"hJ6mHsHhd"hJmHsHhd"hJ]mH sH hd"hJ6]mH sH hd"hJmH sH hd"hJB*phhd"hJ5hd"hJ6 hd"hJhd"hJmHsHhd"hB*ph hd"hPJmHnHsHtH#hd"h5PJmHnHsHtH'".CDIK78?@GHLMZ[f P\qv /ʼʮʧ hd"hJhd"hJPJnH tH hyuUhJ5hyuUhJ6hJ hBghJhd"hJ5mHnHuhd"hJ6mHnHuhd"hJmHnHuhd"hJ6mHnHsHuhd"hJmHsHhd"hJmHnHsHu0/D]^Shjz.C`aqijČ|sisZJhd"hJ<0J6aJmH sH hd"hJ<0JaJmH sH hd"hJ<6aJhd"hJ<aJhd"hJ<5hd"hJ<6 hd"hJ<hd"hJPJnHtH$hd"hJ6B*PJnHphtH!hd"hJB*PJnHphtHhd"hJB*phhd"hJ5PJnH tH  hd"hJhd"hJPJnH tH hd"hJ6PJnH tH qwy"BcxzPT{|EZEmnsٷ||k hd"h<[PJmHnHsHtHhd"hJ<6PJnHtHhd"hJ<PJnHtHhyuUh&5mH sH hyuUh&6mH sH h&mH sH hBgh&mH sH hd"hJ<5hd"hJ<6 hd"hh hd"hJ<hd"hJ<aJmH sH hd"hJ<5aJhd"hJ<aJ*}I_G!D7f29@ & F gd*f & F 7$8$H$gd#M" & F ^`gdb  & F [$\$gd#M" & F gd& & F gd#M"su|}!8=>@Ijo=NTVZ[^_#4:<Giʻʨunfn^nShd"hb B*phhd"h)5hd"h)6 hd"h)hd"h<[B*ph!!!hd"hJ<5B*ph!!!hd"hJ<6B*]ph!!!hd"hJ<6B*ph!!!hd"hJ<B*ph!!!hd"h<[5 hd"h<[hd"hJ<6 hd"hJ<hd"hJ<B*ph hd"hJ<PJmHnHsHtH#hd"h<[5PJmHnHsHtHiop !Ccpqz"179DhmԽ԰hd"hCN6PJnHtHhd"hCNPJnHtHhd"hG_6PJnHtHhd"hG_PJnHtHhd"hG_5hd"hG_6 hd"hCN hd"hG_hd"hb NH hd"hb hd"hb 6hd"hb 6B*ph5'-/67EV\^abef %'2ɾ䑊zhd"hG_5hd"hG_6 hd"hCN hd"hG_hd"hCNB*ph!!!hd"hG_5B*ph!!!hd"hG_6B*]ph!!!hd"hG_B*ph!!!hd"h)PJnHtHhd"hG_5PJnHtHhd"hG_PJnHtHhd"hG_6PJnHtH.2x)/1568M[ac"068<=?@hd"hG_PJnHtHhd"h3 B*ph!!!hd"hG_5hd"hG_6 hd"hG_hd"h T5B*ph!!!hd"h T6B*]ph!!!hd"h dYB*ph!!!hd"h T6B*ph!!!hd"h TB*ph!!!7cx}h} 觚}l}_Thd"hrmH sH hd"h*f5B*ph!!! hd"h*f6B*mHph!!!sHhd"h*fB*mHph!!!sHhd"h*f6B*]ph!!!hd"h*f6B*ph!!!hd"h*fB*ph!!!hd"h T5B*phhd"h T0J6B*phhd"h TB*\phhd"h T6B*phhd"h TB*phhd"h TPJnHtH !1 '(m]jpr{ETZ\nԽzhd"hrmHsHhd"hr5hd"hr6hd"hrPJnHtHhd"hr5B*ph!!!hd"hr6B*]ph!!!hd"hrB*ph!!!hd"hr6mH sH hd"hrmH sH hd"hrhIxEmH sH  hd"hrjhd"hrU0({nR4~ % $ & F a$gd#M"m$ & F 7$8$H$gdr5 & F gdr & F gdr & F gdr$ & F 7$8$H$[$\$a$gdr$ & F [$\$a$gdrQfhrxz-35Ruz|#)⣗|k|`S`E`hd"hr6B*]ph!!!hd"hr6B*ph!!!hd"hrB*ph!!! hd"hr6B*mHph!!!sHhd"hrB*mHph!!!sHhd"hr5OJQJhd"hr6OJQJhd"hrOJQJ hd"hr5B*OJQJph!!!#hd"hr6B*OJQJ]ph!!! hd"hr6B*OJQJph!!!hd"hrB*OJQJph!!!hd"hr5 hd"hr),42H]ntv 29 0kᴠᑄynanVVhd"hrnH tH hd"hr5B*phhd"hrB*phhd"hrB*ph hd"hr6B*ph hd"hr0J#5B*ph 'hd"hr0J#56B*mHph sH$hd"hr0J#5B*mHph sHhd"hr5hd"hr6]hd"hr6 hd"hrhd"hrB*ph!!!hd"hr5B*ph!!! ky%KLMRi~3̸̱}peXhd"h TPJnHtHhd"h?B*ph!!!hd"h5B*ph!!!hd"h6B*]ph!!!hd"hB*ph!!!hd"h5\hd"h6] hd"h? hd"hhd"hwl5\hd"hwl6] hd"hwl hd"hrhd"hr5\nH tH hd"hrnH tH hd"hr6nH tH  %35[f8 $ & F a$gd#M" & F gd#M"$ & F 7$8$H$[$\$a$gd#M"$ & F [$\$a$gd#M" & F 7$8$H$gd#M" $ & F a$gd#M"m$0IW]_e $*,45+@`w}赧}pb}hd"h k5PJnHtHhd"h kPJnHtH hd"hPJmHnHsHtHhd"hmH sH hd"h5PJnHtHhd"h6PJnHtHhd"hPJnHtHhd"h9PB*ph!!!hd"h5B*ph!!!hd"h6B*]ph!!!hd"hB*ph!!!hd"h6B*ph!!!!"79KQSZ[x})1279ef&,.3478W\ϳϨܖϋ}peϋXX}hd"h6B*ph!!!hd"h,WB*ph!!!hd"h5B*ph!!!hd"h6B*]ph!!!hd"hB*ph!!!#hd"h5PJmHnHsHtHhd"hmH sH hd"h5PJnHtHhd"h6PJnHtHhd"hPJnHtH hd"hPJmHnHsHtH#hd"h6PJmHnHsHtH"Sh*`m.33HлАhd"hT l5hd"hT l6 hd"hT lhd"h6B*ph!!! hd"h,Whd"h5hd"h6 hd"hhd"h6B*]ph!!!hd"hPJnHtHhd"h,WB*ph!!!hd"hB*ph!!!hd"h5B*ph!!!1 G\|:@FISvgZhd"hT l5B*phhd"hT l0J6B*phhd"hT l6B*phhd"hT lB*phhd"hT lB*\phhd"hT l5hd"hb6 hd"hbhd"hT l6 hd"hT lhd"hPJnHtHhd"h[jB*ph!!!hd"hT l5B*ph!!!hd"hT l6B*]ph!!!hd"hT lB*ph!!! SmEx7 !  & F gd [ & F 7$8$H$gd~Q & F gd+ & F gdPZ & F 7$8$H$gdPZ & F 7$8$H$gd $ & F 7$8$H$[$\$a$gd#M" & F gdFi & F gdb & F [$\$gd#M"(-9NP\bdlm#5;=DEjoq岥}vng_vgRDRhd"h 6PJmHsHhd"h PJmHsHhd"h 5 hd"hPZhd"h 6 hd"h hd"hPZPJnHtHhd"hPZ5B*ph!!!hd"hPZ6B*]ph!!!hd"hPZ6B*ph!!!hd"hPZB*ph!!!hd"hFi5B*ph!!!hd"hFi6B*]ph!!!hd"hFi6B*ph!!!hd"hFiB*ph!!! hd"hbhd"hb5q AFHJ_`uuhuZuhd"h+6B*]ph!!!hd"h+6B*ph!!!hd"h+B*ph!!! hd"hPhd"hP5B*ph!!!hd"hP6B*]ph!!!hd"hP6B*ph!!!hd"hPB*ph!!! hd"h hd"h 6PJmHsHhd"h PJmHsH hd"hPZhd"h 5PJhd"h 6PJhd"h PJ+Vflnx$+.67dik"ᜐwofhd"h~QPJhd"h~Q5hd"h~Q6]hd"h~Q6 hd"h~Qhd"h~Q6mHsHhd"h~QmHsHhd"h+6B*]ph!!!hd"h+6B*ph!!!hd"h+B*mHph!!!sHhd"h+5hd"h+6 hd"h+hd"h+B*ph!!!hd"h+5B*ph!!!'"#$)TiD Y b r x z } ~             ! D E F K M a v     @ A B H ] r     % & ӺӯӺӤӺ hd"hhd"hmHsHhd"h [ mHsHhd"h 6]mHsHhd"hPZmHsHhd"h mHsHhd"h 5\hd"h 6] hd"hPZ hd"h >! #  J +pys-5 & F gd+ & F [$\$gd & F gd0 & F gdhv & F gd & F 7$8$H$gd [  & F gd [ & ' - B W     b c d i       ,-.4\q+HMO  *JY|˿ˤ˖hd"h 6]mHsHhd"hmHsHhd"h6hd"h 5hd"h 6mHsHhd"h mHsHhd"h 6hd"h 5\ hd"hhd"h 6] hd"h ;,Rg!?TpӸӸӫ蠓~v~n~Ӹӫahd"hB*\phhd"h05hd"h06 hd"h0hd"hhv6B*]ph!!!hd"hhv6B*ph!!!hd"hhvB*ph!!!hd"h5B*ph!!!hd"h6B*]ph!!!hd"h6B*ph!!!hd"hB*ph!!!hd"h 5\ hd"h hd"h hd"h 6]#5?Rinp^zD[`bs "$,-uha hd"h+hd"h+5B*ph!!!hd"h+6B*]ph!!!hd"h+6B*ph!!!hd"h+B*ph!!!hd"h+5OJQJhd"h+6OJQJhd"h+OJQJhd"h5B*phhd"h0J6B*phhd"hB*\phhd"h6B*phhd"hB*ph&-0:BNPXZ`b  $ & 1 J O Q      !!!!!!"3"9"<"D"ʾ|thd"h] 45hd"h] 40J6 hd"h] 4hd"h:B*phhd"h05B*ph!!!hd"h06B*]ph!!!hd"h0B*ph!!!hd"hv96mHsHhd"hv9mHsH hd"hhd"hv9PJhsihd"hv95hd"hv96 hd"hv9,-b1  !D""'#s##$$%&'() & F gd| & F gd8^} & F gdX 7$8$H$^gd} & F 7$8$H$gd} & F gd] 4 & F [$\$gd: & F gdv9 & F 7$8$H$gdv9D""""""""####&#'#G#L#########s$$$$$$$$$Ƹzpzpzfz]zpzpzfz]zV hd"hXhd"hPS<PJhd"h}5PJhd"h}6PJhd"h}PJ#hd"h] 45PJmHnHsHtH hd"h] 4PJmHnHsHtH#hd"h] 46PJmHnHsHtHhd"h] 46PJnHtHhd"h] 4PJnHtH hd"h] 4hd"h] 45B*phhd"h] 46B*phhd"h] 4B*ph $$$$$ %%*%?%%%%%%%&&&%&&&1&F&G&H&P&Q&S&T&Y&Z&k&l&|&}&&&&&&&&&&&&&&&ݵݮ}hd"h8^}B*mHph!!!sHhd"h] 45hd"h] 46 hd"h] 4hd"h] 4mHsH hd"h8^}hd"h8^}5B*ph!!!hd"h8^}6B*]ph!!!hd"h8^}6B*ph!!!hd"h8^}B*ph!!!hd"hX5 hd"hXhd"hX6/&'']'r'''''''''''''''( (((())պխզykaYH!hd"h8^}B*PJnHphtHhah|6hah|hQZhah|6H*mH sH hah|6mH sH hah|mH sH  hah|hd"h|6 hd"h| hd"h8^}hd"h8^}5B*ph!!!hd"h8^}6B*]ph!!!hd"h8^}6B*ph!!!hd"h8^}B*ph!!!hd"h8^}B*mHph!!!sH hd"h8^}6B*mHph!!!sH))m*++,- ../Y04112344 & F gdF $ & F a$gd8^} & F gd~ $ & F a$gdi & F gdi & F 7$8$H$gd8^} & F gd*2 & F gd8^} & F -DM gd8^} 7$8$H$^gd8^}))))))L*M*N*\*]*b*d*l*m********peYeMBMBhd"h8^}mH sH hd"h8^}6mH sH hd"h8^}6mHsHhd"h8^}mHsH hd"h8^}5B*nHphtHhd"h8^}B*nHphtHhd"hB*nHphtH hd"h8^}6B*nHphtH.jhd"h8^}B*UmH nHphsH tH hd"h8^}!jhd"h8^}PJUmHsH%hd"h8^}B*mH nHphsH tHhd"h8^}PJnHtH**+$+)+++++++++++@,U,_,q,v,x,,,,,--ٽuui^Q^C^hd"hi6B*]ph!!!hd"hi6B*ph!!!hd"hiB*ph!!!hd"h8^}5nHtHhd"h8^}6]nHtHhd"h8^}nHtH hd"h*2hd"h*25B*ph!!!hd"h*26B*]ph!!!hd"h*26B*ph!!!hd"h*2B*ph!!! hd"h*26B*mHph!!!sHhd"h*2B*mHph!!!sHhd"h8^}mH sH hd"h8^}5mH sH - ---3-8-:-j-------. .)...0.q.}.........^/y////ҿwl__whd"hi6B*ph!!!hd"hinHtHhd"hi6B*]ph!!! hd"hi6B*mHph!!!sHhd"hiB*mHph!!!sHhd"hi5hd"hi6hd"hi6] hd"hihd"hi6mHsHhd"himHsHhd"h8^}nHtHhd"hiB*ph!!!hd"hi5B*ph!!!!///90H0N0P0Y0w0|0~0000 141R1W1111111111112 22 2$2'2+2,2;2xk```hd"hiB*ph!!!hd"h8^}5B*ph!!!hd"hi6B*]ph!!!hd"h8^}6B*]ph!!!hd"h8^}6B*ph!!!hd"h8^}B*ph!!! hd"h~6B*mHph!!!sHhd"h~B*mHph!!!sHhd"h~5B*ph!!!hd"h~6B*]ph!!!hd"h~6B*ph!!!hd"h~B*ph!!!%;2<2@2A2J2K2Z2o2x2|2~2222222222222l3z33333344 4 4444444騝vgvhd"himHnHsHtHhd"h8^}mHnHsHtHhd"h8^}5nHtHhd"h8^}6nHtHhd"hinHtHhd"h8^}nHtHhd"h8^}5B*ph!!!hd"hi6B*]ph!!!hd"h8^}6B*ph!!!hd"h8^}6B*]ph!!!hd"h8^}B*ph!!!hd"hiB*ph!!!'44(4:4?4@4A4o4444444444455 5U5c5i5k5r5S6ϽϵϦ}paTIhd"hy B*ph!!!hd"hy 5B*phhd"hy 0J6B*phhd"hy B*\phhd"hy 6B*phhd"hy B*ph hd"hy B*\mHphsHhd"hy B*mHphsHhd"hF5hd"hF6hd"hF6] hd"hFhd"hF6mHsHhd"hFmHsHhd"hF\mHsH hd"h8^}4r56)78R9::;;<<U=$>>?9@@A & F ^`gd%* & F [$\$gd%* & F gdJ & F gd@ & F gd| & F gdy  & F gd~ & F [$\$gdy S6h6j6666666666777 7)777S8n8t8v88999!9#9Q9R999:::·xxl^hd"h96B*]ph!!!hd"hy 5mH sH hd"hy 6mH sH hd"hy mH sH hd"h~5B*ph!!!hd"h~6B*]ph!!!hd"h~6B*ph!!!hd"h~B*ph!!!hd"hy B*phhd"hy 5B*ph!!!hd"hy 6B*]ph!!!hd"hy B*ph!!!hd"hy 6B*ph!!!#: : ::3:8:::o:::::::::::;;;;;;;Ͼϳ}rg`X`P`Ehd"h|B*ph!!!hd"h|5hd"h|6 hd"h|hd"h|mHsHhd"hv9mH sH hd"hF5B*ph!!!hd"h96B*]ph!!!hd"hF6B*]ph!!!hd"hF6B*ph!!!hd"hFB*ph!!! hd"hF6B*mHph!!!sHhd"hFB*mHph!!!sHhd"hy mH sH hd"hy B*ph!!!hd"h9B*ph!!!; <<<:<;<<<<<<<<T=U=>>>>`>p>v>w>>>>>>?? ???N?έxk`Y hd"h%*hd"hrB*phhd"hJ5B*phhd"hJ6B*phhd"hJB*phhd"hJ0JB*ph333hd"h@5hd"h@6 hd"h@hd"h@PJnHtHhd"h|PJnHtHhd"h|mH sH hd"h|5B*ph!!!hd"h|B*ph!!!hd"h|6B*]ph!!!!N??8@9@@@[@`@@@@@@@@@~AAAAAAAAA3Hg{+-AGISx}᠙|p|i hd"hJhd"hJ6mH sH hd"hJmH sH Uhd"h%*5hd"h%*6 hd"h%*hSeh%*B*phhd"h%*5B*phhd"h%*0J6B*phhd"h%*6B*phhd"h%*B*\phhd"h%*B*phhd"h%*PJ\hd"h%*6\)tests for the detection of antimicrobial resistant Neisseria gonorrhoeae: when, where, and how to use? Curr Opin Infect Dis 2016;29:45-51. Don V, Low N, Golparian D, Unemo M. Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae. Expert Rev Mol Diagn 2017;17:845-59. Bazan JA, Peterson AS, Kirkcaldy RD, et al. Notes from the field: Increase in Neisseria meningitidis-associated urethritis among men at two sentinel clinics - Columbus, Ohio, and Oakland County, Michigan, 2015. MMWR Morb Mortal Wkly Rep 2016;65:550-2. Bazan JA, Turner AN, Kirkcaldy RD, et al. Large cluster of Neisseria meningitidis urethritis in Columbus, Ohio, 2015. Clin Infect Dis 2017;65:92-9. Retchless AC, Kretz CB, Chang HY, et al. Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles. BMC Genomics 2018;19(1):176. doi:10.1186/s12864-018-4560-x Hjelmevoll SO, Olsen ME, Sollid JU, et al. Appropriate time for test-of-cure when diagnosing gonorrhoea with a nucleic acid amplification test. Acta Derm Venereol 2012;92:316-9. Bachmann LH, Desmond RA, Stephens J, Hughes A, Hook EW 3rd. Duration of persistence of gonococcal DNA detected by ligase chain reaction in men and women following recommended therapy for uncomplicated gonorrhea. J Clin Microbiol 2002;40:3596601. Buckley C, Beatson SA, Limnios A, Lahra MM, Whiley DM, Forde BM. Whole-genome sequencing as an improved means of investigating Neisseria gonorrhoeae treatment failures. Sex Health 2019;16:500-7.      PAGE \* MERGEFORMAT4 SP׏CDEHJKMNPQSTnopq''$a$gd}gd3? 7$8$H$gdSu & F gdd & F gda & F gdJ & F gd%*Íč΍ύԍՍۍ܍ߍ&?EGOPsxzƎՎێݎ 3I֏׏׵hd"hJB*phhd"hJ5B*ph!!!hd"hJ6B*]ph!!!hd"hJ6B*ph!!!hd"hJB*ph!!!hd"hJ6mHsHhd"hJmHsHhd"hrB*phhd"hJ5hd"hJ6 hd"hJ hd"hr1׏gy]msu)39;BCDEFG˿˳𨛨ulcVIjhC9\h+|<UjhC9\h+|<Uhd"hSuPJhd"h%*PJhd"hdmHsHhd"hd5B*ph!!!hd"hd6B*]ph!!!hd"hd6B*ph!!!hd"hdB*ph!!!hd"h5mH sH hd"h6mH sH hd"hmH sH hd"h5hd"h0J6hd"h6 hd"hhd"h\GHIKLNOQRTUjklmopqrʺضhjhUmHnHsHuh}yh}ymHnHsHuhjhUh+|jh+|Uhd"hqB*mHph!!!sHqrgd3?21h:pG/ =!"#$% Dd >  # ?"@@Dd >  # ?"@@^7 0000hH02 0@P`p28 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p8XV~_HmHnHsHtH@`@ yNormalCJ_HaJmH sH tH >@> yRubrik 1$dh@&6]6@6 yRubrik 2$@&>*T@T JRubrik 3$<@&5CJOJQJ\^JaJJA`J StandardstycketeckensnittTiT 0 Normal tabell4 l4a 0k 0 0 Ingen lista JOJ y Balloon Text1CJOJQJ^JaJ6U`6 y0 Hyperlnk >*B*ph&& yheader1e@" JHTML - frformaterad72( Px 4 #\'*.25@9CJOJ QJ ^J _HaaJtH$fo1f JHTML - frformaterad CharOJ QJ ^J _HamH sH tH$F@BF J BallongtextCJOJQJ^JaJD'`QD >0KommentarsreferensCJaJN@bN >0 Kommentarer 1$CJOJPJQJaJToqT >0Kommentarer CharOJPJQJ^JmH sH tH Rj@abR c{Kommentarsmne 1$5OJPJQJ\`o` c{Kommentarsmne Char"5OJPJQJ\^JmH sH tH 4@4 xG0 Liststycke^ O <{jrnl*O* .H[ highlightD`DR<0RevisionCJ_HaJmH sH tH 88 jRubrik1dd[$\$2O2 jdescdd[$\$88 jdetails dd[$\$FOF Ss Rubrik 2* !<aJmH sH tHTo!T i`0EC-Caption-GreenB*CJH*OJQJY(phi#(W`1( i``Stark5\2oA2 ]b0A8B*CJ ^J aJ ph8R8 &}Sidhuvud %p#FoaF %} Sidhuvud CharCJaJmH sH tH 4 @r4 (}0Sidfot 'p#BoB '}0 Sidfot CharCJaJmH sH tH \Z@\ *\30Oformaterad text) CJOJPJQJ^JaJmHsHfof )\30Oformaterad text Char$CJOJPJQJ^JaJmHsHtH .X`. b@Betoning6](( btp-label4o4 bdate1B* CJaJphQ@O@ d/p0Pa36.d7$8$H$ OJ QJ tH VoV Default /7$8$H$!B*CJ_HaJmHphsHtH o None@o@  Hyperlink.2>*B*phwhBV`!B wAnvndHyperlnk >*B*ph@O2@ PMvtitle3dd[$\$ mHsHtH<oA< Ivolume-issue-pageslORl6 q EndNote Bibliography 5 & FOJPJQJmHnHsH tH uroar5 q EndNote Bibliography Char'CJOJPJQJaJmHnHsH tH uPK![Content_Types].xmlN0EH-J@%ǎǢ|ș$زULTB l,3;rØJB+$G]7O٭V`1P(|&Z2q6lpP9]&!fmhH+1,L14Lޫ߿z?xvh9qw?xG_Te@h9/|۳'/U7Cn#cpDŵv #L;6Pk-{*r7eq7wGc E+4DuŽU pŤJw'N~{x3/KnD3NIB!ݥԉ.|]:VdHGN56m2fpV9tU?$ us$-,dPB$h2Jr E\)[aWԗ]5 1ƪ\hsE+ZY\Ʉo:1͐pY\!kXDDyZ5\v0#QLp@isT7Ike-}q<%j%m-- %IeuI e lG%M8m{c'8K=Gb»&_ [6Y6[cnՇB-,#[QV,њME9PFgbe _視WdVt׌JD1#4b!TJxaAws:KYӕ߈],pFENpCH [OJ3ÛaDž8PQ/`p0w16 r=geKڧ!# BL"]V$*+Sk6vEPM20~:h!ogz Np+/0(Kv@ 'hIF'I{"ڲ.3WӋ,NPCfO(,IK݃Doo)&J`Fu/PK! ѐ'theme/theme/_rels/themeManager.xml.relsM 0wooӺ&݈Э5 6?$Q ,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{P8g/]QAsم(#L[PK-![Content_Types].xmlPK-!֧6 0_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-!6?theme/theme/theme1.xmlPK-! ѐ' theme/theme/_rels/themeManager.xml.relsPK] 9 (((+qr 1 b"!+#$o'z(*+8./12F4d5T783:;{;b<S>+@IADDBF?@BCDEKLMv b'<oQXf`|f:joqKtPx\|ٍ&%! -)4qr#',16:AJN Dz ~ (FOa9XXXXXXXX "$+!L# @0(  B S  ? _Hlt16189631 _Hlt16189632_PictureBulletsˉˉ89@@̉̉897099?*urn:schemas-microsoft-com:office:smarttags stockticker  ;DFO`gnvU X s}AM!Zg".=G7ACO'v6@ !!""p"|"""""#$$ $$$&&.(3(P)])k*x**+-%-..//11559999:,:::u;;&>0>-?NXX`eoALNRSV !%&-'kuv[a15dj'.EJ#'+io ;DKR      ! !!!!!b"l"t"}"""""E#O#W#`#t#}#####$$-$3$$$$$$$?%I%J%S%%%%&4&<&'''$'='?''' ((.(7(((((() ))D)H)))))/*8*******e+o+p+y+++++:,@,A,H,Z,f,,,,,-"-O-U-V-]- ...#. ///!/,/5/9/@/A/M///00q1t1u1y1z111111W2]2222233333333444444U5Y5t5}555f6p6666666777777778!8&8-88888888888889   A"I"%%("(@0H0124455nAvA,C0CE F7H;HHHIIIIKKUU__een$nNqXqsstt^{i{?AY^~ %,̑ԑ\dʕѕ!ԙۙŚ}NV'/BIJQģˣǤfnըب6=&25:Aذ߰ӱڱAD8@ OW.5:| ع߹ź̺»ZbZaQX#*"3;mr6=7>),@BV]jqnt>EoqYaDK")ZaOV '^fX_adszHO;Bu| mu`g]f)-fn#&vy`hDGMP[^  V ^ JP~_bpsCILT%cj2:jqEM x &/" *   !!""e#o#"$)$$$X%_% &&)'1'''))))**~++++M,U,,,b-h-..////11i2p2333344i5o5<6?6 778 88888888888888893333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333333 T]7 Jf^{C\yAAHHLLUUF[\[\ ]?aaObbJfafzggfk{kklcntnǂFVm֍5~ 52 ؑFhDmՕ&#Ǚʚg\5W0M7VУ̤Ss( B +#֭$C%Ű߱ʲr4SF-E\:ĹѺƻoEgGh;].'? D$C! 0CaUuk_y(Ir|>g (.O"-Ef'4Z+ qJkv`2So%GZMzJlLkFt@}dkKl2{Ihj  B c   K h 3 Q  -    ~2UR#N?XNo>xiWw1RFQe$3 /   !!b""E#t#$-$$$=%c%%&'5'''($)))**c++5,Z,,,*-l-l../,///o11S2u2233344U5t5+6f6677888888888888889-7;;446688888888888889Hz.J5@bc`%-k,z.x6z.w?8VBy29Hz-:h':z. eAz64DJ@RflUz.OoVV"bf2f4 CA;p[C6~Da #/Dx4 "+H Xv C@V ] s D 2 W_ fz W?s } <0\  C\O,dgeM Iw?tA(  VRfgFD>4$\6cprivcH77LPc]q += b'fLFN~i$>;Dw@':Q],;M`?m)I.} nF'fgFDwQ2 e C@V "D\0"lc ~"  z#"na #%37#$u?pi$Zkb'X']BtR+W+.zZP.pr)I."D6x/35gXvT/}A\/XvT/X70pH Q17Wg 3h2(z u)2>*'3X70)N3S]%3)N3Dx4_TgzY5CE[C6/(  '6+z7iM :Ry3E:n;u?pi};$>A;~D=q>$>S> 8cKdd E@],?tAY/Cz }A5tDPBprECC*}"D66zfgFD[;Ds Dz KCE GZ >pH*'3<0\H7D\z7S]XDq{^& _W_``aoa{^ cfLivc] lc? 8cUczdC}35gc=IKdd _Tg'6,dgzY5 g~"7Wgi8+ru?pi[{FN~izdXjD\ bjZk!nNm!n"nS>XDqqwQ2 ]q8+r W?s]Bt<<<covXv)xRyC66z`Y/Cz[{$\6C}$*};YZ-N*l ?pGLZ 1KAEHgsm{|e *.l89;7=_w{!k^bL _X^wzw5R}y(4>"TTXx3<[[A/2o  Sw y    7 < Q8 hF ;Z Ss  - 3 J oZ [ Iw ( * : A a g q u w  P, c F 3;yTb5cg`o(w 0;JP?Y>@AWY $(,w.z33>J-?KC!N\c=hx Fx a},-4A Bbdi=l6npw6/RScx${,A5PtS4m]vy}nq!#9ALMIdwmt1  C% OPQ[cYls x}Q,-_7FTq  w})D7MP\^upx["8,_ $+ :NM_a gh $ * 6 f ~ 1$!<&!*!5!?!HG!%l!"Z1"5"B"#M"QW"c"# # ##u#>#$?#fO#U#n#b$L $$X$<$3$;$@$Z$%%%!%*%u%&&v&&?;&1P& \&a&'''k)'2'd'w(2'(Z*(<(C(]D(3P(s(x( {(,))):)jI)&X)d)i)j)**%*F*kK*S*[*z_*N*&++#+:+@+L+O+P+W+n+Qw+e, ,,",/,>;,T,U,Y,/j,<-E-nN-.*.C.[.r{.K//]/c/Xi/~/I 0)0w#0H0W0`0$g0_j0Zz0{01GV1g1t1222(2*2N:2>2F2L2,X2e2h2t2z2303<3>3@3@3_`3eg3h3l3"q3y3] 44 &4 *4H42I4kQ4x4?|45-575ia5in5|t566b/6Z^6kv6G7D7D7V7d7fm7q7e8wC8b8k88s8-9F9jK9W9v9sz9:0:=:``:s:` ;. ;mh;l;_m; q;<<=<A<F<J<PS<p`<]h<w<x<= = ====?'=9:=kG=S=e=*w=)>G>^>?,?"?E6?_?p? @f@@h@@%@ ,@]F@E[@{w@A5A?AgAiA'B*B15BgBFtB}B,1C96C>CFCRCTC_CrC!~CDnD%D-,D3Da;Oagahala9b b^bb&b',b:b PbR[bib c=c{%c8cBcLc3`cocqqc d de$d,d[6dDdyde)e^Ke#Ne4_ezaeee&lefd$f5f'5fa6f%Zf(g7g9g>ghgjgqgf;hBhkYhdhrnhi)ii|%i7&i4iN(CKx? Qp i]bmp;"0?ktllVrb*ff/wzy1 -\3IrvQ]i(lxkJ )>D8\di z!!,28KrLETY#baoL38I>DPQ*Cc7p7"6<AC Stg*06q:jS3(QyRnt<{A $d*182w)P+3Wgec|?GQOVS3mwx:OYtpA- $.45gE u}y\Z')F+8"BWRLn7&EaK tj5J_V#is| H6Jnx|,#'*~49H#I^a MTco}/ >KQgTYj^ke>zX.1pGx)`,jntuu]xGb)!1@&?PIUs,0%6@AC~9'.9zO\UW Xm| P6UDH3Qs_s?$R<A>@A[|>e^eeiw#&I.F^bh$MT[j p}r++U#-6AJSXiskU(JCNemr b2FPySsy$DTg)wk{v 9!7?nL'UkhdbBeIJWX[_ck"vv +8FJKsit;{ \'SUSu?vp$b'N<Pg iS ( 9]_nb(+6BxyH{ 0b<s>Akx i m eny|}Dc$%>8s=CZy-2KZ2};5?dqLru $0.;M`d">$'d;&1Iaefiun\:py'.5=Muh{R$F8R[1x)3-6??GyF69Mg_x|b,<FPc8S(+K.96=IDX`g%u%A+9<QU$f&+3+54BCGNEStqZ8H`S[bfr|ab 7 :',nFJQ~Q8rv{0FPrFx yy :3Z/bub[gno }+2<9?CViuy8A1DF9`w}4KS` uz.7c?=n{|')Q./0v<3?@bm pQ*6Cj}T)4Sw0%6`;Pev(')w+Qi``);?S^TXesm=tGY+gk03?`MCRm| '}$3,37V<<>Rci{} K:Vqq!eus7:;IZ-]rc"%,:>h?A.T cs#}=@HG_,appRV $ /w1L7bckr7*I,WWUO<:*\=UihAopru~ v#\~=%,(Fk5|G{MzO!kKPqnqz""=$9cCx ;E[UY[~!&3m8L]`bnqzx L])c,s5Jeg3mzT Y5=h} 3GUKY k VDNXW].-t7D?Niwn'482HCRWXFluz~88@7777 JK 29@ @@@*X@V@0@@@@UnknownG* Times New Roman5Symbol3. * ArialWCalibri-LightMS Gothice  AdvTT1dfd66bbArial Unicode MSeAGaramondPro-RegularMS Gothic7.*{$ Calibri; Batang5. .[`)Tahoma?= .Cx Courier NewsAdobe Garamond ProAdobe Garamond Prok Myriad Pro LightMyriad Pro Light;WingdingsA$BCambria Math"1':G 'Y1/11/108888 CQHP  ?8$ 2! xx YDraft IUSTI/WHO European Guideline on the Diagnosis and Treatment of Gonorrhoea in AdultsBIGNELL#Unemo Magnus, US Labmed lnsklinikd                 Oh+'0$8 dp    \Draft IUSTI/WHO European Guideline on the Diagnosis and Treatment of Gonorrhoea in AdultsBIGNELL Normal.dotm$Unemo Magnus, US Labmed lnsklinik22Microsoft Office Word@Vn @q~@@lb@ʮ 1/՜.+,D՜.+,0 hp  PRIVATE188 ZDraft IUSTI/WHO European Guideline on the Diagnosis and Treatment of Gonorrhoea in AdultsZDraft IUSTI/WHO European Guideline on the Diagnosis and Treatment of Gonorrhoea in Adults6A list of contributing organisations can be found at: REFERENCESQTreatment of gonococcal conjunctivitis with single-dose intramuscular ceftriaxonZDraft IUSTI/WHO European Guideline on the Diagnosis and Treatment of Gonorrhoea in Adults RubrikTitel OverskrifterTitle 8@ _PID_HLINKSAp0Z -https://www.ncbi.nlm.nih.gov/pubmed/24113412[http://www.phac/t^fhttp://www.ncbi.nlm.nih.gov/pubmed?term=Cunningham%20FG%5BAuthor%5D&cauthor=true&cauthor_uid=22353959a ahttp://www.ncbi.nlm.nih.gov/pubmed?term=Sigman%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22353959* ghttp://www.ncbi.nlm.nih.gov/pubmed?term=Wendel%20GD%20Jr%5BAuthor%5D&cauthor=true&cauthor_uid=22353959V5ehttp://www.ncbi.nlm.nih.gov/pubmed?term=Sheffield%20JS%5BAuthor%5D&cauthor=true&cauthor_uid=22353959aDbhttp://www.ncbi.nlm.nih.gov/pubmed?term=Bleich%20AT%5BAuthor%5D&cauthor=true&cauthor_uid=22353959Y -https://www.ncbi.nlm.nih.gov/pubmed/23920397  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOQRSTUVWYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~Root Entry F Cv Data P1TableX WordDocument 4SummaryInformation(DocumentSummaryInformation8MsoDataStoreP9 P < 4540I555Q==2P9 P < Item  PropertiesUCompObj r   F Microsoft Word 97-2003-dokument MSWordDocWord.Document.89q