Antimicrobial resistant gonorrhoea

The emergence of multi-drug resistant gonorrhoea and how management methods are being adapted to combat this. By Michelle Cole, Professor Jonathan Ross and Professor Catherine Ison

 N gonorrhoeae has become resistant to a succession of therapeutic agents
N gonorrhoeae has become resistant to a succession of therapeutic agents

Gonorrhoea is a common bacterial STI, second only to chlamydia in the UK. There has been a 21% increase in the number of gonorrhoea cases reported in England, from 21,024 in 2011 to 25,525 in 2012.1

The increase has been attributed to advances in detection methods, more widespread testing and increased rates of transmission.

This trend is of particular concern, because the causative agent, Neisseria gonorrhoeae, has become resistant to a succession of therapeutic agents, together with the emergence of multi-drug resistant gonorrhoea and the lack of new alternative drugs.2

Drug-resistant gonorrhoea

Effective treatment of infected patients is an essential component of public health control in gonorrhoea, but is often given before the results of laboratory tests are known, so the choice is dependent on data from surveillance programmes.

In England and Wales, the Gonoccocal Resistance to Antimicrobials Surveillance Programme (GRASP) monitors antimicrobial susceptibility of gonococcal isolates through GUM clinics and laboratories.

GRASP detected a rise in the prevalence of decreased susceptibility to cefixime (from 1.5% to 17.1%), the treatment of choice at that time, between 2007 and 2010.

These gonococci were multi- resistant, showing high-level ciprofloxacin resistance, and were clonal and mainly in men who have sex with men.3

In 2011 the recommended treatment was changed, owing to this drift towards resistance and the reports of cefixime treatment failures, to the more active injectable drug ceftriaxone.

There has been a subsequent decline in resistance (17.1% in 2010 to 10.8% in 2011) and although this decrease cannot be fully attributed to the treatment guideline changes, it has bought some time to take further action to combat the threat of multi-drug resistant gonorrhoea.

GRASP has produced an action plan for England and Wales,4 which was launched in response to the emerging resistance, with the aim of enhancing public health control of gonorrhoea.

The action plan provides guidance on collection of robust and timely data, rapid detection and reporting of treatment failures, provision of confirmed and probable treatment failure case definitions, and adherence to management guidelines. It also offers laboratories technical advice for susceptibility testing.

Health promotion programmes to encourage safer sex, as well as the availability of widely accessible STI screening and sexual health services to help reduce gonorrhoea transmission, are discussed, with recommendations to maintain resources for isolation of N gonorrhoeae.

The GRASP action plan runs parallel to documents produced by the WHO5 and the European Centre for Disease Prevention and Control,6 which describe the public health response at a global and a European level.

Presenting symptoms

Rapid detection and effective therapy are essential to reduce the burden of infection in the population.

Most infection is diagnosed in specialised clinics, but it is paramount that cases presenting to general practice and other primary care settings are diagnosed and given appropriate therapy.

Most men with gonorrhoea present with symptoms of dysuria and penile discharge, which is usually profuse and purulent. These symptoms typically develop fairly rapidly (two to five days) after sexual contact with an infected partner.

Women can also have symptoms of discharge, but most infections in females remain asymptomatic and are only diagnosed when microbiology testing is carried out.

Infection can occur in the throat or rectum and these sites should be screened in both men and women if the sexual history indicates they have been at potential risk of infection, even in the absence of symptoms. Auto-inoculation of the eye from the genital area via finger contact can lead to purulent conjunctivitis.

Detection and diagnosis

The diagnosis of gonorrhoea has, until recent years, been achieved by examination of a smear to detect the presence of intracellular Gram- negative diplococci or by isolation of N gonorrhoeae. This presented logistical problems for diagnosis in general practice. However, advances in molecular methods have improved the detection of gonorrhoea because these methods are more tolerant to delays in transport to the laboratory and can be used with specimens, such as urine or self-taken vaginal swabs, allowing more patients to be screened both in primary care settings and specialised clinics.

In addition, nucleic acid amplification tests have an increased sensitivity, allowing detection of more positive cases, particularly at extra-genital sites (rectum and pharynx), and a high specificity, limiting the number of false positives.

Nevertheless, there remains a need to isolate N gonorrhoeae using culture because molecular tests do not detect antimicrobial resistance and this information is needed to guide patient management and inform treatment guidelines.

It is also essential that a viable organism is available from treatment failures, to enable detection of new mechanisms of resistance. These patients may benefit from referral to specialist services.

Consequences of infection

If left untreated, gonorrhoea can spread locally and, rarely, develop systemically.

Men may develop epididymo-orchitis, with swelling and tenderness in the scrotum developing over a period of 12-24 hours. More uncommonly, a para-urethral abscess or sinus can develop.

The main concern in women is salpingitis, with subsequent tubal damage leading to infertility, chronic pain or future ectopic pregnancy. The risk of tubal damage is, however, lower with gonorrhoea than with chlamydia, probably because gonococcal infections are more likely to be symptomatic and women therefore present earlier for treatment.

Current treatment

Current treatment for gonorrhoea is with a single IM injection of ceftriaxone (500mg) combined with a single dose of oral azithromycin (1g).7

Oral cefixime (single dose 400mg) is not recommended as first-line treatment, owing to the lower tissue levels achieved with oral dosing. It should only be used if no alternative treatment is available and referral to a sexual health clinic is not possible. A repeat test is recommended two weeks after treatment to ensure eradication of the infection.

The patient should be advised to avoid sex until 48 hours after both they and their partner have been treated, and tracing, screening and empirical treatment of their partner is therefore recommended.

If the index patient is symptomatic, all partners from within the past two weeks should be seen (or their last partner if this was longer ago).

For asymptomatic patients, all partners within the past three months should be sought. The local sexual health clinic can help with arranging treatment, finding and managing sexual partners, and providing appropriate advice to patients. Many clinics offer the option of a walk-in or appointment-based service, and patients can also self-refer if they prefer.

Patients who have gonorrhoea are at an increased risk of acquiring it again in future and their initial presentation offers an opportunity to provide advice on safer sex.

This should be tailored to the individual patient, but might include the use of negotiating skills when using a condom with their partner, using a condom throughout sexual contact and putting it on correctly, the risks of infection from oral and anal sex, and the asymptomatic nature of many STIs.

Advice that is presented in an acceptable format, repeated and supported through their peer group is most likely to result in behavioural change in these patients.

  • Professor Ison is head of the Sexually Transmitted Bacteria Reference Unit, Public Health England, Professor Ross is professor of sexual health and HIV, Whittall Street Clinic, Birmingham, and Ms Cole is a healthcare scientist at Public Health England.

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Resources

References

1. Sexually transmitted infections and chlamydia screening in England, 2012. HPR 2013; 7(23).

2. Unemo M, Nicholas RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol 2012; 7: 1401-22.

3. Ison CA, Town K, Obi C et al. Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis 2013. Epub ahead of print.

4. Health Protection Agency. Gonoccocal Resistance to Antimicrobials Surveillance Programme (GRASP) action plan for England and Wales: informing the public health response. 2013.

5. Ndowa F, Lusti-Narasimhan M, Unemo M. The serious threat of multidrug-resistant and untreatable gonorrhoea: the pressing need for global action to control the spread of antimicrobial resistance, and mitigate the impact on sexual and reproductive health. Sex Transm Infect 2012; 88: 317-18.

6. European Centre for Disease Prevention and Control. Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe. 2012.

7. Bignell C, Fitzgerald M. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS 2011; 22: 541-7.

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