Levels of evidence (I-IV) and grades of recommendation (A-C) are defined at the end of the "Major Recommendations" field.
Diagnosis
The diagnosis is established by the identification of Neisseria gonorrhoea at an infected site.
Culture offers a readily available, specific, sensitive, and cheap diagnostic test that readily allows confirmatory identification and antimicrobial sensitivity testing. It is currently the method of first choice for use in genitourinary medicine clinics in the United Kingdom (UK). Selective culture media containing antimicrobials are recommended to reduce contamination. (Jephcott, 1997) (Grade B recommendation).
Alternative tests include nucleic amplification tests (NAATs) and nucleic acid hybridization tests. NAATs are more sensitive than culture and can also be used as diagnostic/screening tests on non-invasively collected specimens (urine and self-taken vaginal swabs). Comparisons between NAATs and culture suggest the sensitivity of NAATs exceeds 90% for genital sites, whilst the sensitivity of culture may be less than 75% for endocervical swabs (Van Dyck et al., 2001). This probably indicates that NAATs are less affected than culture by inadequacies in collection and transport of specimens. The transcription mediated DNA amplification assay (TMA) (APTIMA Combo 2) and strand displacement amplification (SDA) assay (BD ProbeTec-SDA) are more sensitive in women than the polymerase chain reaction (PCR) assay (Cook et al., 2005). There are currently no NAATs which are licensed for use with rectal or pharyngeal samples, although studies suggest that the sensitivity of NAATs at non-genital sites exceeds 90% (Young, Manavi, & McMillan, 2003) whereas the sensitivity of culture can be less than 60% for rectal swabs (Young, Manavi, & McMillan, 2003) and less than 50% for pharyngeal swabs (Young, Manavi, & McMillan, 2003; Page-Shafer et al., 2002). Caution is required in interpretation of positive results, as the specificity of NAATs is not 100% (Palmer et al., 2003; Katz et al., 2004). Confirmation of a NAAT positive result by culture is advisable (Grade C recommendation).
Rapid diagnostic tests can be performed to facilitate immediate diagnosis and treatment. Microscopy (x 1000) of gram stained genital specimens allows direct visualization of N. gonorrhoea as monomorphic gram negative diplococci within polymorphonuclear leucocytes. In men, microscopy of urethral smears is more sensitive in symptomatic (90 to 95%) than in asymptomatic (50 to 75%) patients (Sherrard & Barlow, 1996). In women, microscopy of gram stained endocervical smears is more sensitive than urethral smears (37-50% vs 20%) (Barlow & Phillips, 1978). Microscopy is not appropriate for pharyngeal specimens.
Specimen Collection
Men: routinely from the urethra; rectal and/or oropharyngeal tests when symptomatic at these sites and as indicated by sexual activity. A first-pass urine provides an alternative urethral specimen for testing with a NAAT.
Women: routinely from endocervix if speculum examination performed and from the urethra; rectal and oropharyngeal tests when symptomatic at these sites, when a sexual partner has gonorrhoea, and when indicated by the sexual history. Urine or a self-taken vaginal swab provides suitable alternative specimens as screening tests using a NAAT (note: the PCR assay has poor sensitivity on female urine [Cook et al., 2005]).
- Direct plating of genital samples and use of transport media with prompt laboratory plating both give acceptable results (Jephcott, 1997; FitzGerald & Bedford, 1996) (Evidence level IV).
- The use of endocervical samples alone will identify 90-95% of women with gonococcal infection (Barlow & Phillips, 1978; Ghanem, Radcliffe, & Allan, 2004).
- Data is lacking on the sensitivity of a single set of tests from anogenital sites to identify infection with N. gonorrhoeae. To confidently exclude infection in patients who attend within three days of sexual contact with a confirmed case of gonorrhoea, a second set of tests should be considered if epidemiological treatment with effective antimicrobial therapy is not given (FitzGerald & Bedford, 1996) (Evidence level IV, Grade C recommendation).
Management
General Advice
- Referral to a Genitourinary (GU) Medicine Department for management is strongly encouraged.
- Patients should be given a detailed explanation of their condition with particular emphasis on the long-term implications for the health of themselves and their partner(s). This should be reinforced with clear and accurate written information.
- Patients should be advised to avoid unprotected sexual intercourse until they and their partner(s) have completed treatment.
Further Investigation
- Screening for coincident sexually transmitted infections should routinely be performed in patients with or at risk of gonorrhoea (Evidence level III, Grade C recommendation).
Treatment
Indications for Therapy
- A positive rapid diagnostic test
- A positive culture for N. gonorrhoea
- A positive nucleic acid test - confirmation of the diagnosis by culture is recommended prior to or at the time of treatment (Katz et al., 2004) (Grade C recommendation)
- On epidemiological grounds, if a recent sexual partner has confirmed gonococcal infection.
Recommended Treatments (Sexually Transmitted Diseases [STD], 1997; "Sexually transmitted disease treatment," 2002; Bignell, 1996; Echols et al., 1994; Korting & Kollman, 1994; Moran & Zenilman, 1990; Moran & Levine, 1995; Moran, 1996)
Uncomplicated anogenital infection in adults:
*There may be problems with availability of this drug.
Alternative Regimens
May be used when an infection is known to be sensitive to these antimicrobials or where the regional prevalence of resistance to them is less than 5%:
- Ciprofloxacin 500 mg orally as a single dose (Grade A recommendation)
or
- Ofloxacin 400 mg orally as a single dose (Grade A recommendation)
or
- Ampicillin 2 g or 3 g plus probenecid* 1 g orally as a single dose (Grade B recommendation)
- Other single dose cephalosporin regimes, notably Cefotaxime 500mg IM as a single dose. (grade A recommendation) or Cefoxitin 2g IM as a single dose plus probenecid* 1g oral
- Cefpodoxime is an alternative oral third generation cephalosporin that as a single dose of 200 mg is licensed for the treatment of uncomplicated gonorrhoea (Novak et al., 1992). Published trial data is limited, but in view of its short half-life, less favourable pharmokinetics than cefixime and suboptimal efficacy against pharyngeal infection, it cannot be recommended (Grade C recommendation).
- Clinicians using alternative regimens are recommended to regularly review local antimicrobial sensitivity testing with microbiology colleagues.
- The alternative treatment regimens listed do not comprise all effective treatment regimens, but reflect clinical practice in the UK.
- High-dose azithromycin (2.0 g as a single dose) has shown acceptable efficacy in clinical trials but is associated with a high gastrointestinal intolerance (Handsfield et al., 1994). The emergence of azithromycin-resistant N. gonorrhoea has been reported and clinical efficacy does not always correlate with in-vitro sensitivity testing (Young, Moyes, & McMillan, 1997; Tapsall et al., 1998). Azithromycin is not a recommended treatment for gonorrhoea.
Beta-Lactam Allergy
- Spectinomycin* 2 g IM as a single dose
or
- Ciprofloxacin 500 mg orally as a single dose when the infection is known or anticipated to be quinolone sensitive
Pregnancy and Breastfeeding
Pharyngeal Infection
Recommended treatments: (Bignell, 1996; Moran, 1995)
- Ceftriaxone 250 mg IM as a single dose (Grade B recommendation)
or
- Ciprofloxacin 500 mg orally as a single dose if N. gonorrhoea known to be quinolone sensitive (Grade B recommendation)
or
- Ofloxacin 400 mg orally as a single dose if N. gonorrhoea known to be quinolone sensitive (Grade B recommendation)
Single dose treatments using ampicillin or spectinomycin* have a poor efficacy in eradicating gonococcal infection of the pharynx (Bignell, 1996) (Evidence level II).
*There may be problems with availability of these drugs in the UK.
Co-infection with Chlamydia trachomatis
Genital infection with C. trachomatis commonly accompanies genital gonococcal infection (up to 20% of men and 40% of women with gonorrhoea). Screening for C. trachomatis should routinely be performed on adults with gonorrhoea or treatment given to eradicate possible co-infection (STD, 1997; FitzGerald & Bedford, 1996; "Sexually transmitted disease treatment," 2002). Combining effective antimicrobial therapy against C. trachomatis with single dose therapy for gonococcal infection is particularly appropriate when there is doubt that a patient will return for follow up evaluation.
Sexual Partners
Partner notification should be pursued in all patients identified with gonococcal infection, preferably by a trained health advisor in genitourinary medicine. Action and outcomes should be documented (FitzGerald et al., 1996). Male patients with symptomatic urethral infection should notify all partners with whom they had sexual contact within the preceding 2 weeks or their last partner if longer ago. Patients with infection at other sites or asymptomatic infection should notify all partners within the preceding 3 months. Sexual partners should be treated for gonorrhoea preferably after evaluation for sexually acquired infection (Grade C recommendation).
Follow-up
Patients should be assessed after treatment (Grade C recommendation):
- To confirm compliance with treatment
- To ensure resolution of symptoms
- To enquire about adverse reactions
- To re-take the sexual history to explore the possibility of re-infection
- To pursue partner notification and health promotion
A microbiological test of cure is not routinely necessary when the infection has been treated with a recommended directly observed therapy, the infection is fully sensitive to the antimicrobial administered, symptoms have resolved, and there is no risk of re-infection (Evidence level III, Grade C recommendation) (Holland et al., 2003; Komolafe, Sugunendran, & Corkill, 2004). If a patient is symptomatic after treatment, has received a suboptimal treatment, a resistant strain is identified, or there is a possibility of re-infection, test of cure with culture is recommended (Grade C recommendation). Pregnancy does not diminish treatment efficacy. All treatments are less effective at eradicating pharyngeal infection (Moran, 1995) and test of cure is recommended following treatment of infection at this site (recommendation C). If a test of cure is performed, culture tests should be performed at least 72 hours after completion of antimicrobial therapy (Jephcott, 1997) and NAATs tests two weeks after therapy (Bachmann et al., 2002). Infection identified after treatment more commonly indicates re-infection rather than treatment failure (Lewis et al., 1999; Komolafe, Sugunendran, & Corkill, 2004).
Definitions:
Levels of Evidence:
Ia
- Evidence obtained from meta-analysis of randomised controlled trials
Ib
- Evidence obtained from at least one randomised controlled trial
IIa
- Evidence obtained from at least one well designed controlled study without randomisation
IIb
- Evidence obtained from at least one other type of well designed quasi-experimental study
III
- Evidence obtained from well designed non-experimental descriptive studies such as comparative studies, correlation studies, and case control studies
IV
- Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grading of Recommendations:
A (Evidence Levels Ia, Ib)
- Requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation.
B (Evidence Levels IIa, IIb, III)
- Requires availability of well conducted clinical studies but no randomised clinical trials on the topic of recommendation.
C (Evidence Level IV)
- Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities.
- Indicates absence of directly applicable studies of good quality.
