Optimal management of common STIs in general practice

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1 Drug review STIs Optimal management of common STIs in general practice Nadi Gupta MRCP and George Kinghorn MD, FRCP Skyline Imaging Ltd STIs can be detrimental to both physical and psychological health and, without effective treatment, can result in serious complications. Our Drug review describes the available treatment options for the most commonly encountered STIs, followed by sources of further information. Sexually transmitted infections (STIs) are increasing in incidence and they constitute a major public health problem, not only in the UK but worldwide. A 2003 House of Commons Health Select Committee inquiry into sexual health described a sexual health crisis in the UK that amounted to a public health emergency. 1 Effective management is imperative as STIs can be detrimental to both physical and psychological health, and can result in very costly complications. The common STIs encountered in the general practice setting are Chlamydia trachomatis, Neisseria gonorrhoeae, genital warts, genital herpes and Trichomonas vaginalis. The aim of this article is to summarise the drugs available to treat these infections, their effectiveness, principal side-effects and interactions, and their place in management. Although the most common and important sideeffects and interactions will be discussed, reference to the product literature and the BNF will provide a more 16 Prescriber 5 January

2 comprehensive list. Readers are also encouraged to read the British Association of Sexual Health and HIV guidelines for more detailed information (see Resources). Drugs selected should have a high efficacy, low cost and acceptable toxicity and tolerance. Single-dose oral administration is preferred, and the treatment should not be contraindicated in pregnant or lactating women. 2 The tables outline the recommended treatment regimens. It is beyond the remit of this article to discuss the treatment of syphilis and HIV infection. Bacterial infections Chlamydia trachomatis One in ten sexually active young people aged between 16 to 24 years old have genital C. trachomatis infection. Furthermore, results from the national Chlamydia screening programme demonstrate a high level of asymptomatic infection that would have otherwise been missed, reinforcing the need for screening in community settings. 3 Women may develop pelvic inflammatory disease (see Figure 1), which can lead to ectopic pregnancy and infertility. In men, complications include urethritis and epididymitis. Chlamydia, like other acute bacterial and viral STIs, has also been associated with an increased risk of HIV transmission and acquisition. 4 The consequences of these complications represent a considerable health and economic burden. The antibiotics available to treat uncomplicated genital infection are summarised in Table 1. First-line therapy is usually with azithromycin or doxycycline. Contact tracing of sexual partners should be pursued, and patients should be advised to avoid sexual intercourse until they and their partner(s) have finished treatment. Pregnancy Erythromycin is safe for use in pregnancy but less efficacious. A test of cure should therefore be performed three weeks after completion of therapy. Azithromycin may be taken in pregnancy but the manufacturers advise that it should only be used if there is no alternative. Neisseria gonorrhoeae Gonorrhoea (see Figure 2) is the second most common bacterial STI in the UK. There are particularly higher rates in young people, men who have sex with men and black ethnic groups. Resistance to antibiotics complicates treatment of gonorrhoea: in 2007, 28 per cent of genitourinary medicine (GUM) clinic isolates were resistant to ciprofloxacin. 3 Figure 1. Chlamydia trachomatis infection in women can cause pelvic inflammatory disease. Azithromycin and doxycycline are first-line drug treatments in uncomplicated infection The complications of gonorrhoea include epididymitis, involvement of the prostate gland, pelvic inflammatory disease and disseminated gonococcal infection. Co-infection with C. trachomatis is common (up to 20 per cent of men and 40 per cent of women with gonorrhoea), and it is essential that screening for C. trachomatis is performed as a matter of routine. 5 The sites of infection are the urethra, endocervix, pharynx, conjunctiva and rectum. Table 2 summarises the main antibiotics used in the management of uncomplicated anogenital infection. Cefixime (unlicensed indication) is a good first-line choice. Quinolones are generally not recommended for use in children and growing adolescents as they may cause an arthropathy that affects weight-bearing joints. Contact tracing of sexual partners should be pursued, and patients should be advised to avoid sexual intercourse until they and their partner(s) have finished treatment. Pregnancy The cephalosporins are safe for use in pregnancy. Syphilis There has been a marked increase in the number of cases of syphilis observed since the late 1990s. There were a total of 2680 cases of primary and secondary syphilis diagnosed in 2007 alone. 3 Rates of diagnosis were highest among men who have sex with men. Syphilis is caused by the spirochaete Treponema continued on page 20 VM Prescriber 5 January

3 Drug Dose Mechanism Efficacy Principal Interactions of action side-effects 1st line azithromycin 1g single dose inhibits protein >95% occasional: GI pimozide synthesis intolerance, nausea, diarrhoea, abdominal pain doxycycline 100mg twice daily inhibits protein >95% occasional: digoxin, for 7 days synthesis oesophagitis, warfarin, hepatitis, GI penicillins, intolerance, bismuth salts candidosis, photosensitivity stains teeth in children <12 Alternative erythromycin 500mg 4 times daily inhibits protein 77-95% frequent: GI ergot alkaloids, for 7 days or synthesis intolerance midazolam, 500mg twice daily occasional: simvastatin, for 14 days stomatitis, fentanyl, cholestatic pimozide hepatitis, rash (higher likelihood of side-effects with 4 times daily) ofloxacin 200mg twice daily disrupts similar to occasional: GI antacids, or 400mg once bacterial DNA doxycycline intolerance, sulcralfate, daily for 7 days replication but more headache, procainamide expensive malaise, insomnia, restlessness tetracycline 500mg 4 times daily inhibits protein 94-99% frequent: GI penicillins, iron, for 7 days synthesis upset, stains calcium, teeth in bismuth, children <12 warfarin, occasional: digoxin hepatotoxicity, photosensitivity Table 1. Summary of the drugs used to treat uncomplicated Chlamydia trachomatis infection pallidum. It has a wide variety of presentations and may mimic many other diseases; clinical features of secondary syphilis can be easily misdiagnosed as glandular fever. Diagnosis is based on history, clinical features and serological confirmation. Left untreated, it can lead to serious complications and even death. Suspect and proven cases should always be referred for appropriate management. Viral infections Genital warts Genital warts are caused by infection with human papilloma virus (HPV) and are the most prevalent 20 Prescriber 5 January

4 SPL Figure 2. Treatment of gonorrhoea is complicated by resistance. First-line antibiotics include cefixime (unlicensed) and ceftriaxone viral STI diagnosed in the UK. Infection may not be clinically apparent. There are over 100 documented genotypes. Most anogenital warts are benign. However, there are certain genotypes that are associated with an increased risk of anogenital neoplasia; specifically, genotypes 16 and 18 are associated with the greatest risk. However, most visible warts (see Figure 3) are due to types 6 and 11, which are the least likely to have neoplastic potential. 6 Treatment is usually for cosmetic rather than medical purposes. All treatments have significant failure and relapse rates, 7 and no single treatment is considered to be better than another. There are multiple treatments available; Table 3 illustrates some of the most commonly used. By stimulating the immune response, imiquimod (Aldara) may have a lower relapse rate. Podophyllotoxin can be used as a 0.15 per cent cream (Warticon Cream) or a 0.5 per cent solution. The solution is an option when treating warts that are easily visible and accessible to the patient: in practice this means that it is more appropriate in males. Other treatments available in specialist settings include curettage, trichloroacetic acid, laser therapy and electrosurgery. These too have significant failure and relapse rates. Patients should be reviewed to assess progress. Different options may need to be tried if the patient is not tolerating the treatment or if there is a poor response. Pregnancy Cryotherapy is safe for use in pregnancy; podophyllotoxin, however, is contraindicated. 22 Prescriber 5 January

5 Genital herpes Herpes simplex virus (HSV) types 1 and 2 can both cause genital herpes. Genital herpes is the commonest ulcerative STI in the UK and its prevalence is increasing. The presence of genital ulcers also increases the likelihood of HIV transmission. 9 Disease episodes may be initial (primary) or recurrent, and symptomatic or asymptomatic. Primary genital herpes (see Figure 4) can be very painful and distressing. Most clinicians would make a clinical diagnosis and prescribe treatment after taking swabs for HSV; full STI screening is important but is usually deferred until lesions have healed. General advice includes saline bathing, analgesia and lidocaine gel. Oral antiviral drugs reduce the severity and duration of the episode, 10,11 and are indicated within five days of the start of the episode and while new lesions are still forming. Topical agents are not as effective as oral. The three antiviral drugs all have similar efficacy but differ in cost. It is the authors preference to use valaciclovir (Valtrex) for primary genital herpes as it achieves a high plasma drug concentration more rapidly, and aciclovir for recurrent infection. Treatment of recurrent genital herpes could be episodic or suppressive. Episodic treatment should ideally be patient initiated. Patients experiencing more than six episodes a year may be considered for suppressive treatment with aciclovir 400mg twice daily, usually for a maximum of one year. Referral to a GUM clinic is recommended for management during pregnancy and for those considering suppression therapy. Table 4 summarises the main options. Human immunodeficiency virus The prevalence of HIV infection is increasing. In 2006 there were an estimated people living with HIV infection in the UK, about a third of whom were unaware of their infection. 3 Transmission rates in men who have sex with men remain high but heterosexual transmission is rising. Heterosexual acquisition now predominates among diagnosed cases worldwide. HIV is a multisystem disorder. However, many people with early infection are essentially asymptomatic and unaware of their infection. Treatment involves complex antiretroviral regimens aimed at viral suppression. The prognosis has improved dramatically since the advent of highly active antiretroviral therapy (HAART). Drug Dose Mechanism Efficacy Principal Interactions of action side-effects 1st line cefixime 400mg disrupts synthesis 96% occasional: allergic probenecid single dose of bacterial cell reaction, diarrhoea, wall eosinophilia ceftriaxone 250mg im disrupts synthesis 98.9% occasional: allergic probenecid single dose of bacterial cell reaction, diarrhoea, wall eosinophilia If organism ciprofloxacin 500mg disrupts bacterial >98% occasional: GI sucralfate, known to be single dose DNA replication intolerance, antacids, sensitive or headache, malaise, theophylline, regional insomnia, warfarin resistance <5% restlessness ofloxacin 400mg disrupts bacterial >98% occasional: GI antacids, single dose DNA replication intolerance, sulcralfate, headache, malaise, procainamide insomnia, restlessness Table 2. Summary of the drugs used to treat uncomplicated anogenital gonorrhoea Prescriber 5 January

6 Dose Mechanism Side-effects Clearance at Recurrence of action end of treatment rates Cryotherapy with apply until a halo cytolysis at local irritation/ 63-88% 0-39% liquid nitrogen forms a few millimetres dermoepidermal occasional around the lesion, junction scarring every 1-2 weeks Podophyllotoxin apply twice daily for 3 days antimitotic agent localised 42-88% 10-91% (0.15% cream) a week, repeat up to reaction 4 months Imiquimod 5% 3 times a week, wash induces a cytokine localised 50-62% 13-19% cream off 10 hours later response response irritation repeat up to 4 months to treatment may be delayed for some weeks Surgical - excision infection, bleeding 89-93% 36% Table 3. Summary of the treatments used in genital warts SPL Figure 3. A variety of treatments are available for genital warts; imiquimod has a lower recurrence rate Protozoal infection Trichomonas vaginalis T. vaginalis (TV) is a flagellate protozoan and is one of the commonest STIs worldwide. The only prevalence study in the UK within the last 10 years detected a prevalence of 0.1 per cent among women requesting cervical smears; 12 however, there is a high false-positive rate of trichomoniasis detected on cervical cytology. The prevalence in GUM clinics is much higher. TV is associated with premature labour, low birth weight, prostatitis and HIV transmission. 12 Metronidazole is the drug of choice (see Table 5). A single dose has the advantage of improved compliance and being cheaper, although there is some evidence to suggest that the failure rate is higher, though not significantly, especially if the partners are not treated concurrently. 13 There are various drugs that have been administered in the form of topical preparations but these are largely ineffective; eradication requires systemic treatment. Patients should be advised to avoid sexual intercourse until they and their partner(s) have finished treatment. Partners should have a full STI screen and be treated for trichomoniasis irrespective of the results of investigations. In the event of persistent treatment failure with metronidazole, there are other treatments available such as tinidazole (Fasigyn). Referral is advised. Pregnancy Course of metronidazole for one week; the manufacturers advise that single high-dose metronidazole should be avoided in pregnancy. Conclusion The involvement of primary-care physicians in the diagnosis and management of STIs is encouraged within the National Sexual Health and HIV strategy. 14 It should be emphasised that optimal management of any diagnosed STIs should include screening for other STIs, partner notification and follow-up where appropriate. Patients should be given a detailed explanation of their condition with particular emphasis on the long-term health implications for themselves and their partners. Early diagnosis and treatment of STIs not only alleviates symptoms and reduces complications, but 24 Prescriber 5 January

7 also reduces the period of infectivity and onward transmission. VM References 1. House of Commons Health Committee. Sexual health. Third report of session , vol World Health Organization. Reproductive tract infections and sexually transmitted infections including HIV/AIDS. Factsheet Health Protection Agency (HPA) data, 4. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to the sexual transmission of HIV infection. Sex Transm Infect 1999;75: Centers for Disease Control and Prevention. Sexually transmitted disease treatment guidelines MMWR 2002;51(No. RR-6): Kazzi A, Ghadishah D. Genital warts. com/emerg/topic640.htm. 7. Beutner KR, Wiley DJ. Recurrent external genital warts: a literature review. Papilloma Virus Rep 1997;8: Department of Health. Immunisation against infectious disease - the Green Book Keet IPM, Lee FK, Van Griensven GJP, et al. Herpes simplex virus type 2 and other genital ulcerative infections as a risk factor for HIV-1 acquisition. Genitourin Med 1990; 66: Corey L, Benedetti J, Critchlow C, et al. Treatment of primary first-episode genital herpes virus infections with aciclovir: results of topical, intravenous and oral therapy. J Antimicrob Chemother 1983;12(Suppl B): Fife KH, Barbarash RA, Rudolph T, et al. Valaciclovir versus aciclovir in the treatment of first-episode genital herpes Figure 4. Oral antiviral drugs are recommended for primary and recurrent genital herpes infection infection. Results of an international, multicentre, doubleblind randomised clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis 1997;24: Bowden FJ, Garnett GP. Trichomonas vaginalis epidemiology: parameterising and analysing a model of treatment interventions. Sex Transm Infect 2000;76: Drug Dose Mechanism Efficacy Principal Interactions of action side-effects 1st line aciclovir 200mg 5 times a converted by viral significant usually none probenecid, day for 5 days or thymidine kinase reduction in occasional: rash, theophylline 400mg 3 times and cellular duration of nausea, diarrhoea, daily for 3-5 days catalase into active lesions and renal and hepatic form inhibits viral viral dysfunction DNA polymerase shedding 1st line famciclovir 250mg 3 times converted into as above usually none probenecid daily for 5 days penciclovir, then occasional: active form headache, inhibits viral DNA dizziness, polymerase nausea, diarrhoea 1st line valaciclovir 500mg twice daily cleaved into as above as for famciclovir probenecid for 5 days aciclovir Table 4. Summary of the drugs used to treat genital herpes Prescriber 5 January

8 Drug Dose Mechanism Efficacy Principal Interactions of action side-effects 1st line metronidazole 2g single dose exact mechanism 95% GI intolerance, ethanol, not fully approx. metallic taste, disulfiram, understood headache, dark phenytoin, urine, disulfiram- warfarin, like reaction with barbiturates alcohol metronidazole mg as above similar to as above as above twice daily above for 5-7 days Alternative tinidazole 2g single dose as above as above as above as above Table 5. Summary of the drugs used to treat trichomoniasis 13. Hager WD, Brown ST, Kraus SJ. Metronidazole for vaginal trichomoniasis. Seven-day vs single-dose regimens. JAMA 1980;244(11): Sexual health and HIV strategy. Department of Health, June Resources Associations The British Association for Sexual Health and HIV (BASHH), RSM, 1 Wimpole Street, London W1G 0AE. Tel: , website: The Royal College of Obstetricians and Gynaecologists (RCOG), 27 Sussex Place, Regent s Park, London NW1 4RG. Tel: , website: Guidelines Chlamydia uncomplicated, genital (women) management. NHS Clinical Knowledge Summaries. cks.library.nhs.uk/chlamydia_uncomplicated_ genital. Herpes simplex genital management. NHS Clinical Knowledge Summaries. herpes_simplex_genital. Management of genital herpes in pregnancy. RCOG, National guideline on the management of anogenital warts. BASHH, Dr Gupta is a specialist registrar in the Department of Genitourinary Medicine, and Professor Kinghorn is clinical director for communicable diseases and honorary professor in genitourinary medicine, Royal Hallamshire Hospital, Sheffield National guideline for the management of genital tract infection with Chlamydia trachomatis. BASHH, National guideline for the management of genital herpes. BASHH, National guideline on the diagnosis and treatment of gonorrhoea in adults. BASHH, documents/116/116.pdf. National guideline on the management of Trichomonas vaginalis. BASHH, Sexually transmitted infections in primary care. BASHH and RCGP, Patient support The Family Planning Association. The fpa provides a national service in the UK providing information, training, research and publications. Further reading ABC of sexually transmitted infections. Adler M. London: BMJ Press, Prescriber 5 January

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