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2014 Antimicrobial Resistance in N. gonorrhoeae A Review.

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1 2014 Antimicrobial Resistance in N. gonorrhoeae A Review

2 2014 INTRODUCTION Progressive antimicrobial resistance in Neisseria gonorrhoeae is an emerging public health threat The Public Health Agency of Canada (the Agency) released updated recommendations in July 2013 for the diagnosis, treatment, follow-up and reporting of gonorrhea Antimicrobial Resistance in N. gonorrhoeae – A Review

3 2014 OBJECTIVES To promote: Test-of-cure recommendations Optimal use of antibiotics Appropriate laboratory testing Proper action on detecting, reporting and re-treatment in cases of documented or suspected treatment failure To increase awareness and knowledge of the status of antimicrobial resistance of N. gonorrhoeae Antimicrobial Resistance in N. gonorrhoeae – A Review

4 2014 BACKGROUND Antimicrobial resistance occurs when bacteria, fungi, viruses, or parasites develop the ability to resist the effects of antimicrobial drugs used to kill them or slow their growth A recent report from the World Health Organization (2014) identified antimicrobial resistance as a global threat Results from this study showed a significant increase in antimicrobial resistance worldwide Warned about the possibility of a post-antibiotic era “in which common infections…can kill.” Antimicrobial Resistance in N. gonorrhoeae – A Review

5 2014 BACKGROUND Aligns with World Health Organisation’s “Global Action Plan to Control the Spread and Impact of Antimicrobial Resistance in Neisseria gonorrhoeae (2012)“ Identified antimicrobial resistant gonorrhea as the next drug resistant ‘superbug’ Antimicrobial Resistance in N. gonorrhoeae – A Review

6 2014 Reported cases of gonococcal infection in Canada have increased since 1997 Infection rates are increasing more rapidly among females than among males. A network of people with high-transmission activities may play a key role in current prevalence levels and in sustaining infections within a community. EPIDEMIOLOGY Males 20–24 years of age Females 15–19 years of age Most affected: Antimicrobial Resistance in N. gonorrhoeae – A Review

7 2014 KEY ISSUES Antimicrobial Resistance in N. gonorrhoeae – A Review Gonococcal infections have been resistant to certain antibiotics Gonococcal infections are becoming more difficult to treat. Potential increase in major sequelae due to prolonged duration of original infection The problem is worldwide, and is growing

8 2014 KEY ISSUES Progressive resistance to penicillin, tetracycline and quinolones has emerged Treatment failure with third generation oral and injectable cephalosporins has been observed To date, resistance particularly observed among MSM* Antimicrobial Resistance in N. gonorrhoeae – A Review * Men Who Have Sex With Men

9 2014 Individuals with a history of other STIs, including HIV Individuals who have had unprotected sex with a resident of an area with high gonorrhea burden and/or high risk of antimicrobial resistance Individuals with a history of previous gonococcal infection Individuals who have had sexual contact with a person with a confirmed or suspected gonococcal infection AT RISK Antimicrobial Resistance in N. gonorrhoeae – A Review

10 2014 Sex workers and their sexual partners Individuals who have had sex with multiple partners Street-involved youth and other homeless populations Sexually active youth < 25 years of age Men who have unprotected sex with men AT RISK Antimicrobial Resistance in N. gonorrhoeae – A Review

11 2014 *e.g., arthritis, dermatitis, endocarditis, meningitis Ophthalmia Neonatorum Conjunctivitis Sepsis Disseminated gonococcal infection* Urethritis Vaginitis Conjunctivitis Pharyngeal Infection Proctitis Disseminated gonococcal infection* Cervicitis Pelvic Inflammatory Disease Urethritis Perihepatitis Bartholinitis Urethritis Epididymitis Pharyngeal Infection Conjunctivitis Proctitis Disseminated gonococcal infection* Neonates and Infants ChildrenFemales Males Both MANIFESTATION S Youth (≥ 9 years) and Adults Antimicrobial Resistance in N. gonorrhoeae – A Review

12 2014 Females Males Vaginal discharge Dysuria Abnormal vaginal bleeding Lower abdominal pain Deep dyspareunia Rectal pain and discharge (with proctitis) Urethral discharge Dysuria Urethral itch Testicular pain and/or swelling or symptoms of epididymitis Rectal pain and discharge (with proctitis) SYMPTOMS Often asymptomaticOften symptomatic In both females and males, rectal and pharyngeal infections are more likely to be asymptomatic Antimicrobial Resistance in N. gonorrhoeae – A Review *

13 2014 *e.g., arthritis, dermatitis, endocarditis, meningitis MAJOR SEQUELAE FemalesMales Pelvic inflammatory disease Infertility Ectopic pregnancy Chronic pelvic pain Reactive arthritis (oculo-urethro- synovial syndrome) Disseminated gonococcal infection* Epididymo-orchitis Reactive arthritis (oculo- urethro-synovial syndrome) Infertility (rare) Disseminated gonococcal infection * Youth (≥ 9 years) and Adults Antimicrobial Resistance in N. gonorrhoeae – A Review

14 2014 DIAGNOSIS Depending on clinical situation, consider collecting both cultures and NAAT especially in symptomatic patients Antimicrobial Resistance in N. gonorrhoeae – A Review

15 2014 However, culture is strongly recommended because it allows for testing of antimicrobial susceptibility NAAT may be the only available testing method in some jurisdictions Where NAAT is routinely used, sentinel surveillance mechanisms using culture are important to ensure continued monitoring for antimicrobial resistance Increase in the number of cases diagnosed due to higher sensitivity and specificity of test NAAT Antimicrobial Resistance in N. gonorrhoeae – A Review

16 2014 CULTURE Antimicrobial Resistance in N. gonorrhoeae – A Review Critical for improved public health monitoring of antimicrobial resistance and trends Provides clinicians with important case management information Cultures obtained less than 48 hours after exposure may give false negative results

17 2014 DIAGNOSIS Where there is an increased probability or a suspected treatment failure If the infection was acquired in a geographical area with high rates of antimicrobial resistance In symptomatic MSM Antimicrobial Resistance in N. gonorrhoeae – A Review In suspected pelvic inflammatory disease Cultures are particularly important in the following situations:

18 2014 SPECIMENS Take specimen from any exposed site Urine NAAT if urethral swab or pelvic examination is not practical Cervical or vaginal culture or NAAT Urethral culture or NAAT Rectal culture or validated NAAT and/or Pharyngeal culture or validated NAAT Asymptomatic Patients Antimicrobial Resistance in N. gonorrhoeae – A Review

19 2014 SPECIMENS Rectal culture or validated NAAT if anogenital symptoms Cervical or vaginal culture or NAAT Urine NAAT if urethral swab or pelvic exam not practical Urethral culture or NAAT if patient has urethral syndrome *Symptomatic Patients Antimicrobial Resistance in N. gonorrhoeae – A Review Take specimen from any exposed site * *

20 2014 Appropriate samples based on site of exposure and test type should be obtained prior to treatment When making treatment decisions, relevant history, physical examination and epidemiologic factors should be considered MANAGEMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Syndromic management: Mucopurulent cervicitis Non-gonococcal urethritis Epididymitis Pelvic inflammatory disease Or if patient is being treated as a contact Presumptive treatment is to be provided for:

21 2014 Combination therapy also provides effective treatment for chlamydia given high rates of concomitant infections Using medications with two different mechanisms of action may also improve treatment efficacy To help prevent the spread of antimicrobial resistant gonorrhea Monotherapy should be avoided TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review

22 2014 Cefixime treatment failures in MSM have recently been documented Ceftriaxone + azithromycin is recommended as the preferred treatment for gonococcal infections in MSM TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Cephalosporins

23 2014 Azithromycin should not be used as monotherapy. Resistance has been reported. Exception: when cephalosporins are contraindicated Cross-sensitivity between penicillin and 2 nd or 3 rd generation cephalosporins is low, but if patient has history of immediate hypersensitivity reaction to penicillin, may also react to cephalosporins Allergy to cephalosporins History of anaphylactic reaction to penicillin TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Azithromycin

24 2014 Uncomplicated anogenital infection (urethral, rectal) and pharyngeal infection ≥ 9 years of age TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Full treatment details at: Preferred treatment Ceftriaxone 250 mg IM in a single dose Azithromycin 1 g PO in a single dose +

25 2014 Preferred treatment TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Uncomplicated anogenital infection (urethral, rectal) only in adults and youth (≥ 9 years), excluding MSM is: Cefixime 800 mg PO in a single dose Azithromycin 1 g PO in a single dose + Full treatment details at:

26 2014 Due to the rapid increase in quinolone-resistant gonorrhea, quinolones are no longer recommended Quinolones should ONLY be given as an alternative treatment IF: Antimicrobial susceptibility testing is available and quinolone susceptibility is demonstrated OR Local quinolone resistance is under 5% AND a test of cure can be performed. Antimicrobial Resistance in N. gonorrhoeae – A Review TREATMENT Quinolones

27 2014 TREATMENT Antimicrobial Resistance in N. gonorrhoeae – A Review Full treatment recommendations, including alternative treatments available The Public Health Agency of Canada’s Canadian STI Guidelines:

28 2014 Local public health authorities may assist with partner notification and with appropriate referral for clinical evaluation, testing, treatment and health education Gonococcal infections are reportable in all provinces and territories; positive test results should be reported to local public health authorities Case finding and partner notification are critical in controlling infection CONTROL Antimicrobial Resistance in N. gonorrhoeae – A Review

29 2014 The length of time for the trace-back period should be extended in the following circumstances: If the index case states that there were no partners during the recommended trace-back period, the most recent partner should be notified If partners are exposed between testing and treatment, additional time between the date of testing and date of treatment could be included If all partners traced test negative, the last partner prior to the trace-back period should be notified PARTNER NOTIFICATION All sexual partners within 60 days prior to symptom onset or date of specimen collections (if asymptomatic) should be notified, tested and empirically treated without waiting for test results Antimicrobial Resistance in N. gonorrhoeae – A Review

30 2014 TEST OF CURE Antimicrobial Resistance in N. gonorrhoeae – A Review 2 – 3 Weeks later  NAAT Test of Cure Post-Treatment 3 – 7 days later → Culture

31 2014 Test of cure should be completed in all cases; particularly important when: Pharyngeal infections Cases treated with a regimen other than the preferred treatment Case is linked to a drug resistant/treatment failure case and was treated with the same antibiotic Case has persistent symptoms or signs post-therapy TEST OF CURE Antimicrobial Resistance in N. gonorrhoeae – A Review

32 2014 Compliance is uncertain Disseminated gonococcal infection is diagnosed Cultures from all positive sites should also be done in the following situations: Antimicrobial Resistance in N. gonorrhoeae – A Review TEST OF CURE Case is a child There is re-exposure to an untreated partner Infection occurs during pregnancy Women undergoing therapeutic abortion who tests positive gonococcal infection

33 2014 TREATMENT FAILURE TREATMENT FAILURE is defined as one of the following in the absence of reported sexual contact during post-treatment period: Positive N. gonorrhoeae on culture taken at least 72 hours after treatment Positive NAAT taken at least 2 – 3 weeks after treatment Presence of intracellular Gram-negative diplococci on microscopy taken at least 72 hours after treatment Antimicrobial Resistance in N. gonorrhoeae – A Review

34 2014 Allows provincial and territorial STI programs to quickly identify emerging patterns of antimicrobial resistance within their jurisdictions Enables provincial and territorial to collaborate with the Public Health Agency of Canada to issue timely electronic alerts Local public health should be promptly notified of treatment failures REPORTING Antimicrobial Resistance in N. gonorrhoeae – A Review

35 2014 Repeat screening for individuals with a gonococcal infection is recommended 6 months post- treatment Antimicrobial Resistance in N. gonorrhoeae – A Review REPEAT SCREENING

36 2014 Important to rapidly identify changes in antimicrobial susceptibility and assess risk factors associated with the development of resistance Enables early identification and prevention of the spread of drug-resistant gonorrhea and assists in identifying appropriate treatment regimens National enhanced surveillance protocol to integrate epidemiologic and treatment failure data into existing laboratory-based monitoring of antimicrobial resistant gonorrhea SURVEILLANCE Antimicrobial Resistance in N. gonorrhoeae – A Review

37 2014 Provide information to encourage consistent safe sex practices Counsel on sequelae and on potential impacts on reproductive system Explain the need to abstain from unprotected sex until at least 3 days after completion of treatment and no more symptoms Discuss the risk of re-infection PREVENTION Antimicrobial Resistance in N. gonorrhoeae – A Review

38 2014 CONCLUSION To successfully address the public health risk of antimicrobial resistant gonorrhea, primary care and public health professionals need to work together. Antimicrobial Resistance in N. gonorrhoeae – A Review

39 2014 RESOURCES The above based on Public Health Agency of Canada’s Canadian STI Guidelines To access the chapter and additional resources: This document is intended to provide information to public health and clinical professionals and does not supersede any provincial/territorial legislative, regulatory, policy and practice requirements or professional guidelines that govern the practice of health professionals in their respective jurisdictions, whose recommendations may differ due to local epidemiology or context. Antimicrobial Resistance in N. gonorrhoeae – A Review


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