Abstract
Introduction
In the UK, diagnoses rates for gonorrhoea in 2005 were 196/100,000 for 20-24 year old men, and 133/100,000 for 16-19 year old women. Co-infection with Chlamydia trachomatis is reported in 10-40% of people with gonorrhoea in the USA and UK.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for uncomplicated infections in men and non-pregnant women; and in pregnant women? What are the effects of treatments for disseminated gonococcal infection? What are the effects of dual treatment for gonorrhoea and chlamydia infection? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotic regimens (dual treatment, multiple dose, single dose).
Key Points
Gonorrhoea is caused by infection with Neisseria gonorrhoeae. In men, uncomplicated urethritis is the most common manifestation while in women only about half of cases produce symptoms (such as vaginal discharge and dyspareunia).
In the UK, diagnoses rates for gonorrhoea were 196/100 000 for 20-24 year old men and 133/100 000 for 16-19 year old women in 2005.
Co-infection with Chlamydia trachomatis is reported in 10-40% of people with gonorrhoea in the USA and UK.
Single dose antibiotic regimens have achieved cure rates of 95% or higher in men and non-pregnant women with urogenital or rectal gonorrhoea. However, resistance to many widely available antibiotics (e.g. penicillins, tetracylines, fluoroquinolones) continues to spread, making it necessary to consider local N gonorrhoeae susceptibility patterns when choosing a treatment regimen.
Single dose antibiotics are also effective for curing gonorrhoea in pregnant women.
In people with disseminated gonococcal infection, there is consensus that multidose regimens using injectable cephalosporins or fluoroquinolones (when the infecting organism is known to be susceptible) are the most effective treatments, although evidence supporting this is somewhat sparse.
We did not find any sufficient evidence to judge the best treatment for people with both gonorrhoea and chlamydia, although theory, expert opinion, and clinical experience suggest a combination of antimicrobials active against both N gonorrhoeae and C trachomatis are effective.
About this condition
Definition
Gonorrhoea is caused by infection with Neisseria gonorrhoeae. In men, uncomplicated urethritis is the most common manifestation, with dysuria and urethral discharge. Less typically, signs and symptoms are mild and indistinguishable from those of chlamydial urethritis. In women, the most common site of infection is the uterine cervix where infection results in symptoms such as vaginal discharge, lower abdominal discomfort, and dyspareunia in only half of cases. People with gonorrhoea may also have co-infection with C trachomatis.
Incidence/ Prevalence
Between 1975 and 1997, the reported incidence of gonorrhoea in the USA fell by 74%, reaching a low point of 120/100 000 people. After a small increase in 1998, the rate of new gonorrhoeal infection declined steadily to an incidence of 112/100 000 people in 2004, then increased slightly to 116/100 000 in 2005. Rates are highest in younger people. In 2005, incidence was highest in women aged 15-19 years (625/100 000) and men aged 20-24 years (437/100 000). In UK genitourinary medicine clinics, diagnoses figures for 2002 were 269/100 000 for 20-24 year old men, and 195/100 000 for 16-19 year old women. By 2005, diagnoses of gonorrhoea had fallen to 196/100 000 for 20-24 year old men and 133/100 000 for 16-19 year old women. Recent studies in the USA and UK found concurrent Chlamydia trachomatis in 7-14% of homosexual men with gonorrhoea, in 20-30% of heterosexual men, and in 40-50% of women. Overall, co-infection with C trachomatis is reported in 10-40% of people with gonorrhoea.
Aetiology/ Risk factors
Most gonococcal infections result from penile-vaginal, penile-rectal, or penile-pharyngeal contact. An important minority of infections are transmitted from mother to child during birth, which can cause a sight threatening purulent conjunctivitis (ophthalmia neonatorum). Less common are ocular infections in older children and adults as a result of sexual exposure, poor hygiene, or the medicinal use of urine.
Prognosis
The natural history of untreated gonococcal infection is spontaneous resolution and microbiological clearance after weeks or months of unpleasant symptoms. During this time, there is a substantial likelihood of transmission to others and of complications developing in the infected individual. In many women, the lack of readily discernible signs or symptoms of cervicitis means that infections go unrecognised and untreated. An unknown proportion of untreated infections causes local complications, including lymphangitis, periurethral abscess, bartholinitis, and urethral stricture; epididymitis in men; and in women involvement of the uterus, fallopian tubes, or ovaries causing pelvic inflammatory disease (see pelvic inflammatory disease). One review found N gonorrhoeae was cultured from 8-32% of women with acute pelvic inflammatory disease in 11 European studies and from 27-80% of women in eight US studies. The proportion of N gonorrhoeae infections in women that lead to pelvic inflammatory disease has not been well studied. However, one study of 26 women exposed to men with gonorrhoea found that 19 women were culture positive and, of these, five women had pelvic inflammatory disease and another four had uterine adnexal tenderness. Pelvic inflammatory disease may lead to infertility (see pelvic inflammatory disease). In some people, localised gonococcal infection may disseminate. A US study estimated the risk of dissemination to be 0.6-1.1% among women, whereas a European study estimated it to be 2.3-3.0%. The same European study found a lower risk in men, estimated to be 0.4-0.7%. When gonococci disseminate, they cause petechial or pustular skin lesions; asymmetrical arthropathies, tenosynovitis, or septic arthritis; and rarely, meningitis or endocarditis.
Aims of intervention
To relieve symptoms; avoid complications; and prevent further transmission, with minimal adverse effects of treatment.
Outcomes
Microbiological cure rates (number of infected people or infected sites culture negative 1-14 days after treatment, divided by number of infected people or infected sites cultured 1-14 days after treatment), quality of life, and adverse effects of treatment.
Methods
BMJ Clinical Evidence search and appraisal July 2006. The following databases were used to identify studies for this review: Medline (1966 to July 2006), Embase (1980 to July 2006), and The Cochrane Library, Issue 2, 2006. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE) clinical guidelines. Abstracts of the studies retrieved were assessed independently by two information specialists using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this chapter were: published systematic reviews, RCTs, and cohorts in any language, and containing any number of individuals. There was no minimum length of follow up required to include studies. We evaluated all studies described as "blinded" and also included "open", "open label", or not blinded. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are continually added to the chapter as required. The contributor did an additional search of Pubmed in December 2006, using the keywords gonorrhoea and N gonorrhoeae infections, plus a hand search of references of key articles and books. Non-randomised comparative studies and observational studies from these results were included; in these studies, participant selections were not biased, diagnoses were reliably established, and treatment outcomes were well described. Studies were excluded if they defined possible treatment failures as "reinfections", if they did not use end points based on microbiological cure, or if they were based on drug regimens unlikely to be of general use (e.g. those using antibiotic regimens that are toxic or to which resistance is now widespread). The contributor did not search for, or include, studies published before 1981 as the susceptibility of N gonorrhoea changes over time. The results of particularly old clinical trials may be misleading because of intervening changes in susceptibility. The contributor updated his own systematic review using the original methods. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
GRADE evaluation of interventions for gonorrhoea
| Important outcomes | Cure rates, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for uncomplicated infections in men and non-pregnant women? | |||||||||
| At least 28383 people | Cure rates | Single-dose regimens compared with each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for inclusion of CCTs. Directness point deducted for no direct comparison of different antibiotics |
| What are the effects of treatments for uncomplicated infections in pregnant women? | |||||||||
| 2 (362) | Cure rates | Different single-dose regimens compared with each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for small number of comparisons |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion.Consistency: similarity of results across studies. Directness: generalisability of population or outcomes.Effect size: based on relative risk or odds ratio.
Glossary
- Dual treatment
The routine treatment of people with gonorrhoea with an antimicrobial regimen effective against genital Chlamydia trachomatis infection in addition to a regimen effective against gonorrhoea (sometimes called dual therapy or co-treatment).
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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