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Genital (reproductive) tract infections

 

 

Genital (reproductive) tract infections

 

Balanitis

 

Inflammation of the glans penis is rare in circumcised males and should be referred for specialist advice. In prepubertal boys, Streptococcus pyogenes is commonly cultured from skin swabs taken when the foreskin is retracted. In adults, bacterial causes are less common than Candida albicans.

 

If Streptococcus pyogenes is cultured, use

phenoxymethylpenicillin (child: 10 mg/kg up to) 500 mg orally, 6-hourly for 10 days.

 

Candidal balanitis occurs typically in a sexually active uncircumcised male, who presents with itching, red, maculopapular lesions of the glans penis, with circumferential scale and satellite lesions. Take swabs to confirm the diagnosis. The female partner may have vaginal candidiasis but usually does not.

Drying under the foreskin after showering is recommended. A combination of an anticandidal agent and hydrocortisone is usually successful. Use

1	clotrimazole 1% +hydrocortisone  1% topically, applied twice daily[Note]
	OR
1	miconazole 2% + hydrocortisone 1% topically, applied twice daily.[Note]

 

Continue treatment for 2 weeks after symptoms resolve.

Some patients respond better to ointments, which offer the added benefit of ‘waterproofing’ the area. The only anticandidal preparation available in ointment form is nystatin. Use

	hydrocortisone 1% ointment topically, twice daily
	PLUS
	nystatin 100 000 units/g ointment topically, twice daily.

 

If the female partner is a candida carrier, either symptomatic or asymptomatic, treat as for chronic vulvovaginal candidiasis.

Some patients get recurrent relapsing candidal balanitis, reflecting either a carrier state or sensitivity to their partner’s commensal levels of Candida albicans; consider circumcision in these cases.

 

Consider noninfectious balanitis when there has been no response to antibiotic or antifungal treatment, even where there was positive microbiology.

First-line treatment should include use of a soap substitute, attention to personal hygeine and use of a bland emollient. If this is unsuccessful, consider a dermatosis such as psoriasis, lichen planus, plasma cell balanitis, fixed drug eruption or squamous cell carcinoma in situ. These are difficult conditions to diagnose and treat. A skin biopsy is usually required. Referral to a dermatologist is recommended.

Epididymo-orchitis

Apart from mumps, acute epididymo-orchitis is usually either a complication of genitourinary infection with enteric Gram-negative bacteria, (especially in prepubertal boys and men older than 35 years), or a complication of a urethral infection by sexually transmitted pathogens in young sexually active patients. Rarely it occurs via a haematogenous route as a complication of other systemic infection.

 

For mild to moderate infection, use

1	trimethoprim (child: 6 mg/kg up to) 300 mg orally, daily for 14 days
	OR
2	cephalexin (child: 12.5 mg/kg up to) 500 mg orally, 12-hourly for 14 days
	OR
3	amoxycillin+clavulanate (child: 12.5+3.1 mg/kg up to) 500+125 mg orally, 12-hourly for 14 days.

 

If resistance to the above drugs is suspected or proven, use

norfloxacin 400 mg orally, 12-hourly for 14 days.

 

For severe infection, use

	amoxy/ampicillin (child: 50 mg/kg up to) 2 g IV, 6-hourly
	PLUS
	gentamicin (child <10 years: 7.5 mg/kg; >=10 years: 6 mg/kg) 4 to 6 mg/kg IV, daily (adjust dose for renal function, see Monitoring of aminoglycosides).

 

Continue therapy until there is substantial clinical improvement, then change to an appropriate oral drug based on the susceptibility of the pathogen(s) isolated, to complete a 2-week course of treatment.

 

Chlamydia trachomatis (D-K serovars) or Neisseria gonorrhoeae are usually involved although among men who are the insertive partner during anal intercourse, epididymitis can be caused by sexually transmitted enteric organisms eg Eschericia coli. Appropriate specimens (urethral exudate or swab or first void urine) should be taken prior to institution of empirical therapy.

	doxycycline 100 mg orally, 12-hourly for 10 to 14 days
	PLUS
	ceftriaxone 250 mg IM, as 1 dose.

 

For more information on alternative regimens, including for areas where penicillin-resistant Neisseria gonorrhoeae is uncommon, see Urethritis and cervicitis.

Where adherence to 2 weeks of doxycycline is unlikely there are theoretical grounds to indicate that it may be replaced by azithromycin 1 g orally on days 1 and 8, although no clinical trial has assessed this.

 

Genital itch

 

 

Genital itch is more commonly due to dermatitis and psoriasis than infection. It is recommended that appropriate diagnostic fungal specimens are taken prior to the commencement of therapy, as dermatophytes or Candida albicans are the commonest infective agents. Never assume a fungal diagnosis without microbiological confirmation. Use a topical imidazole preparation, see Tinea corporis, pedis and cruris. Ensure that the patient continues treatment until the lesions are completely healed. Refer to Genital skin diseases.

Lice

 

 

Head lice are common and not indicative of poor hygiene. The only complication is secondary infection from scratching.

Approximately one-third of cases can be cured by wet combing (applying hair conditioner or olive oil to wet hair and using a fine nit comb) every 3 to 4 days for several weeks after detection.

Alternatively, topical insecticides can be used

1	maldison 0.5 to 1% topically, according to the manufacturer’s instructions. Not to be used in children <6 months
	OR
1	permethrin 1% topically, according to the manufacturer’s instructions
	OR
1	pyrethrins 0.165% + piperonyl butoxide 1.65% to 4% topically, according to the manufacturer’s instructions.

 

Apply to hair (avoiding contact with eyes and mucous membranes), leave for the time advised, then rinse thoroughly with warm water. Wash hands thoroughly after use. Two to 3 days after the treatment, comb hair with a fine comb. If pyrethrins or permethrin are used, treatment should be repeated at 7 to 10 days.

Family and other intimate contacts should be examined and treated.

After 1 or 2 treatments, persisting adult lice suggest resistance, so re-treatment with an alternative regimen may be necessary. Pyrethrins and permethrin are chemically similar, but maldison has a different mode of action. This may be important, as head lice may become resistant to each group of agents.

 

For head lice that are resistant to topical insecticides, the recommended treatment is

olive oil applied thickly to scalp and hair for 8 hours on treatment days 1, 2, 5, 9, 13, 17 and 21, to coincide with the lifecycle of the louse. Then comb out with a fine comb.

 

The basis for this treatment is that the oil suffocates the lice. If this fails, use

trimethoprim+sulfamethoxazole 80+400mg orally, twice daily for 3 days. Repeat after 10 days.

 

It is thought that the effectiveness of trimethoprim+sulfamethoxazole is due to the destruction of symbiotic bacteria in the gut of the lice.

 

Phthirus pubis colonises pubic, axillary, beard and body hair. It may also involve eyebrows and eyelashes. It is transmitted by close physical contact, often sexual. It is most often seen in adults. In children sexual abuse should be considered but is not invariable. The main symptom is itching with the louse and eggs visible on hairs. Treatment is the same as for head lice (above). Contact tracing is essential. The whole body surface should be examined, including eyelashes and eyebrows. Shaving pubic hair is also helpful. Underwear and bedclothes should be washed. Treatment failure may be due to re-infection, and family and sexual partner(s) should therefore be checked and treated as appropriate.

 

Treat as for head lice (above) applying the preparation to the whole body, but avoiding contact with eyes and mucous membranes. The parasites and eggs are found in clothing and bedclothes, which should be discarded, hot washed or sealed in plastic bags for 30 days.

 

White soft paraffin is applied thickly to the eyelashes twice a day for 8 days to suffocate the insects. The nits may then be physically removed with fine forceps. This may be difficult, requiring slit lamp control. In this situation, referral to an ophthalmologist is recommended.

 

Scabies (Sarcoptes scabiei)

 

 

Scabies is a dermatosis caused by infestation with the mite Sarcoptes scabiei var hominis. This insect is a human pathogen and is spread by close physical contact between infected persons. Human scabies is not acquired from animals. Scabies is common in school-age children and in closed communities such as nursing homes. If untreated, it will usually spread to all members of a patient’s family.

The diagnosis of scabies is often difficult, especially if it is not suspected. This is because the clinical picture is variable and signs may be subtle. An allergic reaction to the presence of the mite is responsible for signs and symptoms. The degree of this reaction is variable and may sometimes be absent. Sometimes the only complaint is itch without an obvious rash. The itch exacerbates at night and after hot showers. Typically there is an itchy, excoriated but nonspecific rash on the trunk, associated with scaly burrows on the fingers and wrists. Papular lesions are often seen around the major flexures in children, on the penis in men, or on the nipples in women. In babies and young children, there are often vesicles and pustules on the palms and soles and sometimes on the scalp. Nodules may occur in axillae, groin and sometimes other parts of the skin. Secondary bacterial infection may occur.

Confirmation of the diagnosis is made by microscopy of scrapings from a burrow. The main pitfall in using this technique is the selection of a suitable burrow, as these are few in number and difficult to identify. This procedure therefore requires some skill. Response to antiscabetic medication may therefore be used as the most practical diagnostic test. In doubtful cases, or where the patient has difficulty accepting the diagnosis, a scraping is very useful. The burrow is a superficial lesion, which involves only the epidermis, and its contents may easily be scraped from the skin surface using a scalpel blade. The material is smeared onto a drop of oil or potassium hydroxide 10%. Microscopy of this material reveals the mite, eggs or faecal material.

 

If secondary bacterial infection is present, treat as for impetigo at the same time as scabicide treatment.

1	permethrin 5% cream (child >6 months) topically, to the whole body including face and hair (avoid eyes and mucous membranes), leave overnight
	OR
2	benzyl benzoate 25% emulsion (child <2 years: dilute with 3 parts of water; child 2 to 12 years and sensitive adult: dilute with equal parts of water) topically to the whole body, including face and hair (avoid eyes and mucous membranes), leave for 24 hours.

 

Treat family and close contacts even if free of symptoms, since these can take several weeks to develop and contacts may by then have become a source of re-infection. After the recommended treatment, wash clothing and bedclothes and hang in the sun. Clothing or bedding that cannot be washed should be placed in plastic bags for 7 days.

Children under 2 months of age can be treated with sulfur 5% cream daily for 2 to 3 days or crotamiton 10% cream daily for 3 to 5 days, according to the manufacturer's instructions. These agents are less efficacious and cure may not occur. If relapse occurs, consider treatment with permethrin.

For moderate and severe infections, repeat scabicide treatment in 14 days.

 

Contact tracing, notification and treatment are essential to prevent treatment failure. All members of the patient’s family and close contacts should be treated simultaneously. In closed communities such as nursing homes, all patients and staff require treatment. If a school-age child has had scabies, the school should be notified, but treatment of clinically uninvolved children is not required.

 

The itching of scabies does not resolve immediately after treatment and may take 3 weeks to subside. Part of this itching may be irritation from the antiscabetic agent itself. Patients must be warned and instructed not to apply further antiscabetic agents. During this time, relieve the itch and dermatitis that occurs secondarily.

Use

	a moderately potent topical corticosteroid applied 2 to 3 times daily
	AND
	an emollient.

 

Postscabetic nodules may last for months despite treatment with a topical corticosteroid.

 

In this variant of scabies, the mite population on the patient is very high due to a poor host response. This is seen in physically incapacitated and immunocompromised patients, including those with HIV infection. It presents with gross, fissured thickening of the skin, particularly on the back of the neck and around the hands and feet and under the nails. Often there is secondary dermatitis but, paradoxically, itch may be absent. Diagnosis is easily made by a scraping because of the vast number of lesions.

For crusted (Norwegian) scabies, consider ivermectin (child >5 years) 200 micrograms/kg orally initially as a single dose, in association with scabicides. Topical keratolytics containing, for example, lactic acid 5% and urea 10% can be applied daily after washing, on days when scabicides are not applied. It may be necessary to repeat scabicides twice-weekly for 2 to 6 weeks, together with repeated ivermectin doses. One regimen for severe crusted scabies is ivermectin (child >5 years) 200 micrograms/kg orally on days 1, 2, 15, 16 and 29.

 

The source of a scabies outbreak in this situation is frequently a new, infested patient. If possible, this patient should be identified, as they may have Norwegian scabies. The safety of ivermectin in elderly and debilitated patients has not yet been established.

The affected ward should be quarantined and all patients, medical and nursing staff and their families should be treated. Bedding, clothes and towels should be laundered and communal sitting areas sprayed with insecticide. If staff from the affected ward have worked elsewhere, that area should also be treated.

 

The recommended treatment is permethrin 5% cream, see Background and treatment. Permethrin is classified as category B2; however, this must be balanced against the significant morbidity of untreated scabies. Patients may elect to postpone treatment if scabies is acquired in the first trimester of pregnancy.

Alternative treatment with sulfur 5 to 10% in sorbolene cream may be used if the clinician judges the risks of treatment with permethrin to outweigh the benefit.

 

Scabies in HIV-infected individuals may be resistant to repeated attempts at topical therapy. In this situation, use

ivermectin 200 micrograms/kg orally, weekly.

 

Note:

Ivermectin is available in Australia but is not specifically approved for use in scabies. It is not recommended in geriatric patients.

 

If treatment fails after the use of permethrin, consider the possibility of a wrong diagnosis, an unidentified source of reinfestation, inadequate contact tracing or noncompliance with instructions. Recommended measures are to consider other diagnoses and treat accordingly, to supervise treatment (inpatient, community nurse) or specialist referral.

If topical treatment fails, and the diagnosis of scabies is not in doubt, use

ivermectin 200 microgram/kg orally, as a single dose.

Genital lumps

 

Lymphogranuloma venereum (Chlamydia trachomatis L1-L3 serovars)

There is no known endemic focus in Australia. The infection commences as a transient, painless ulcer but presents usually with inguinal lymphadenopathy and has severe late complications including perirectal/perianal strictures and fistulae. Specialist advice should be sought.

1	doxycycline 100 mg orally, 12-hourly for 21 days
	OR
2	roxithromycin 300 mg orally, daily for 21 days
	OR
3	azithromycin 1 g orally, weekly for 3 weeks.

Molluscum contagiosum

This common poxvirus infection is seen often in young children where lesions occur anywhere on the body and in adults where it is seen most often as a sexually acquired infection of the genital area. In human immunodeficiency virus (HIV) infection, lesions may be widespread and atypical. In children, infection is usually acquired from family members or others with whom they swim or bathe. The typical lesion is a pearly papule with a central umbilication and a core that may be extracted with the tip of a needle.

The infection may be complicated by dermatitis, particularly in atopic patients, and by bacterial superinfection. Spontaneous resolution is the rule in immunocompetent patients but may take up to 2 years.

Chemical therapies are ineffective in treating these lesions. In children, conservative management is usually best, unless lesions are widespread and interfering with lifestyle and function. If treatment is required, the most effective treatment is extracting the core with a large needle or curetting the lesions if small. In children with numerous lesions, this may require a general anaesthetic. In adults, cryotherapy is effective.

Treat secondary dermatitis with topical therapy, see General treatment of dermatitis and Control of xerosis.

To avoid secondary infection following extraction, use

mupirocin 2% ointment or cream OR povidone iodine 10% alcoholic solution.

 

Avoiding heated swimming pools and showering rather than bathing reduces the spread of these lesions. It is not practicable or necessary to isolate children with molluscum contagiosum.

In patients with HIV infection, treatment may be very difficult, although where the lesions are few in number cryotherapy may be effective.

 

Genital warts (human papillomavirus infection)

 

Human papillomavirus (HPV) infection causes 4 different but related abnormalities in the human female genital tract:

·            Genital warts are most commonly caused by HPV types 6 and 11. Like all sexually active women, those with genital warts or sexual partners also infected should have regular Papanicolaou (Pap) smears.

·            Low grade cervical dysplasia is caused by both oncogenic and nononcogenic HPV types.

·            High grade dysplasia, which is the premalignant lesion, is only associated with infection by oncogenic viruses.

·            Cervical cancer is most commonly caused by HPV types 16 and 18, and strongly associated with various other oncogenic HPV types. This gives the HPV type an importance over and above the acute infective episode (which is usually transient, asymptomatic and detectable only by cellular changes seen by the Pap smear, at colposcopy or by HPV-DNA testing). The use of HPV-DNA testing in guiding management is being evaluated, but not yet routinely recommended.

 

HPV infection of the male genitalia, in addition to causing genital warts, is uncommonly associated with intraepithelial neoplasia of the penis.

Genital warts are often a recurring problem. In most cases they are trivial, but they can be very extensive and disabling. Patients often complain of some degree of discomfort from the lesions, but it may simply be their appearance and connotations that concern the patient. The concept that the presence of the wart virus infection can cause vulvitis or vulval pain is erroneous. Most condylomatous lesions eventually resolve spontaneously. The exact infectivity and period of latency of HPV have not been determined. Most HPV infections are transient, although it may be that the virus can be reactivated after years of dormancy.

Prior to undertaking therapy for genital warts, it is important to counsel the patient, explaining how the virus is acquired, the long-term prognosis and the association with neoplasia. Because of the possible latency of the virus and the fact that viral DNA may remain long term in the nucleus of human cells, the wearing of condoms will not necessarily protect the patient from re-infection, and if the patient is in a stable relationship it is likely that the partner has been exposed and will also not benefit from this measure. Also, the latency of the virus often makes it impossible to say from which sexual partner the virus was acquired. Needless blame in the patient’s present relationship may result, and this needs to be explained. Patients with HPV often experience feelings of shame and guilt that need to be addressed.

Patients with genital warts may have been exposed to other sexually transmissible infections (STIs) and the need for an STI screen should be discussed with the patient. Concomitant infection(s) should be treated. Specialist advice or referral may be needed.

External genital warts may be removed by chemical or physical means (including cryocautery or electrocautery), or by patient-applied preparations (imiquimod 5% or podophyllotoxin 0.5%). The preparations described below should be applied with care, as erythema or ulceration can follow contact with normal skin.

For small numbers of readily accessible lesions, use

1	periodic cryotherapy until resolved
	AND/OR
2	podophyllotoxin 0.15% cream or 0.5% paint topically applied by the patient to each wart, twice daily for 3 days followed by a 4-day break (repeat weekly for 4 to 6 cycles until the warts disappear)
	OR
3	imiquimod 5% cream topically applied by the patient to each wart, 3 times per week at bedtime (wash off after 6 to 10 hours) until warts are cleared (usually 12 to 24 weeks)
	OR
4	podophyllum 25% solution in compound benzoin tincture topically applied by the clinician to each wart, wash off after 6 hours (repeat once weekly until the warts disappear).

 

Do not use podophyllotoxin or podophyllum in pregnant or breastfeeding women. Imiquimod is category B1 in pregnancy but there is insufficient data on safety in breastfeeding.

Irritation, if present, is managed with

hydrocortisone 1% cream applied 3 times daily.

 

Treatment of coincident dermatitis or vaginitis will make the warts less liable to become irritable. Female patients should have a two-yearly Pap smear because of the association of genital warts with oncogenic HPVs causing carcinoma of the cervix.

 Genital ulcers

 

Chancroid (Haemophilus ducreyi)

 

Chancroid (soft chancre) presents as a painful nonindurated ulcer. It is not endemic in Australia. Specialist advice on diagnosis and management should be sought.

1	azithromycin 1 g orally, as 1 dose
	OR
1	ceftriaxone 250 mg IM, as 1 dose
	OR
1	ciprofloxacin 500 mg orally, 12-hourly for 3 days.

Donovanosis (granuloma inguinale) (Klebsiella granulomatis)

 

Donovanosis is a chronic, progressively destructive infection, presenting initially as raised, beefy nodules or sores. It occurs in northern Australia and overseas (Papua New Guinea, India, southern Africa). Microscopy of scrapings, snip or punch biopsy confirms the diagnosis.

azithromycin 500 mg orally, daily for 7 days or 1 g once weekly for 4 doses or until healing occurs.

 

Treat also for syphilis and gonorrhoea if unable to exclude these infections. Follow-up is important as resolution may be slow and recurrence may occur. Admission to hospital for supervised therapy may be necessary.

Genital herpes simplex virus infection

 

 

Herpes simplex is the commonest cause of genital ulceration in Australia. It presents as recurrent painful blisters on the genital area that rapidly erode to leave ulcers that heal spontaneously over a 2-week period. Lesions may be unilateral or bilateral and may occur elsewhere on the surrounding skin, as well as on the buttocks and legs. Genital herpes is sexually-acquired. The initial attack is the most severe. Recurrences may be infrequent, but frequent attacks become disabling in some patients. Genital herpes only causes chronic genital lesions, such as persistent ulceration, in immunosuppressed patients.

Patients should have a full STI screen including HIV serology on their first presentation. Current therapy is not curative but specific antivirals may shorten the episode if commenced in the first 72 hours of symptoms.

After taking a swab for culture, direct immunofluorescence or polymerase chain reaction (PCR), use

1	valaciclovir 500 mg orally, 12-hourly for 5 days
	OR
2	aciclovir 400 mg orally, 8-hourly for 5 days (preferred in pregnancy, seek expert advice)
	OR
3	famciclovir 125 mg orally, 12-hourly for 5 days.[Note 1]

 

Longer treatment may be needed in severe disease.

 

Infrequent but severe recurrences can be treated with episodic therapy, commencing at the onset of prodromal symptoms.

1	valaciclovir 500 mg orally, 12-hourly for 3 days
	OR
2	famciclovir 125 mg orally, 12-hourly for 5 days
	OR
3	aciclovir 400 mg orally, 8-hourly for 5 days (preferred in pregnancy, seek expert advice).

 

This may be indicated for frequent, severe recurrences. Suppression reduces recurrences by 70% to 80% but transmission may still occur.

1	valaciclovir 500 mg orally, daily for up to 6 months
	OR
2	aciclovir 200 mg orally, 12-hourly for up to 6 months (preferred in pregnancy, seek expert advice)
	OR
3	famciclovir 250 mg orally, 12-hourly, for up to 6 months.

 

If there is breakthrough during prophylaxis higher doses may be successful.

Treatment should be interrupted every 6 months to determine the natural history of the disease in any given patient, but may be restarted in the event of recurrence.

Syphilis (Treponema pallidum)

 

The necessity for long-term follow-up with repeat serology and the frequent presence of complicating factors makes it desirable to seek specialist advice. This is particularly important for patients who are pregnant or hypersensitive to penicillin or who have HIV infection.

Penicillin remains the drug of choice. Treatment regimens with drugs other than penicillins have not been extensively studied, especially in patients with syphilis of longer than 2 years duration. Penicillin desensitisation should be performed whenever practicable, see Desensitisation protocols. Where drugs other than penicillin are used, careful follow-up is recommended.

Note that other sexually transmissible infections may be present in addition to syphilis.

 

Early syphilis is defined as primary (chancre), secondary (rash or condylomata lata) or latent (asymptomatic) syphilis confirmed to be of less than 2 years duration, based on serology results.

1	benzathine penicillin 1.8 g IM, as 1 dose
	OR
1	procaine penicillin 1 g IM, daily for 10 days.

 

For nonpregnant patients hypersensitive to penicillin in whom desensitisation is not feasible, use

doxycycline 100 mg orally, 12-hourly for 14 days.

 

Seek advice in pregnancy.

Advise the patient to avoid sexual activity until lesions are healed. Sexual contacts within the last 3 months should have the same treatment even if their serology is negative.

There is insufficient data to recommend ceftriaxone.

 

Late latent syphilis is defined as latent syphilis of more than 2 years or of indeterminate duration, in the absence of tertiary syphilis. Specialist advice should be sought regarding the need for and interpretation of lumbar puncture. This is particularly important for situations with treatment failure or HIV infection. For treatment use

1	benzathine penicillin 1.8 g IM, once weekly for 3 doses
	OR
1	procaine penicillin 1 g IM, daily for 15 days.

 

 

Tertiary syphilis includes cardiovascular syphilis and neurosyphilis. Specialist advice should be sought. Use

benzylpenicillin 1.8 g IV, 4-hourly for 15 days.

 

In cardiovascular or neurosyphilis, concomitant treatment with prednisolone 20 mg orally 12-hourly for 3 doses may be administered initially with penicillin, to reduce the likelihood of a Jarisch-Herxheimer reaction.

 

Pregnant patients should be treated with penicillin in the dosage schedule recommended for nonpregnant patients at a similar stage of the disease. Patients hypersensitive to penicillin should be desensitised, see Desensitisation protocols, or specialist advice sought. Tetracyclines should not be used in pregnancy or in the newborn, and erythromycin does not reliably treat an infected fetus.

If a mother with positive serology or active syphilis received adequate penicillin treatment before 28 weeks gestation and has not re-infected, the risk of congenital syphilis is low, but the baby should still be investigated at birth and followed thereafter and expert advice sought. The placenta should be examined by direct immunofluorescence and silver stains.

All newborns of mothers with syphilis should be investigated and treated in consultation with a specialist. For the treatment of congenital syphilis, use

1	benzylpenicillin 50 mg/kg IM or IV, 12-hourly for 10 days
	OR
1	procaine penicillin 50 mg/kg IM, daily for 10 days.

 

Pelvic inflammatory disease

 

This includes endometritis (including postpartum), chorioamnionitis, intra-amniotic syndrome, salpingitis, tubo-ovarian abscess, and/or pelvic cellulitis and/or pelvic peritonitis.

Pelvic infection in females may be sexually-acquired or may result from ascending infection with endogenous vaginal flora particularly following mechanical disruption of the normal cervical barrier, eg due to postabortal, postpartum or postoperative infection, or associated with an intrauterine contraceptive device (IUCD), for which the risk is highest at time of insertion. Even with sexually transmitted infections (STIs), the resultant upper tract infection is usually polymicrobial with mixed STI pathogens and endogenous flora, and hence empiric treatment needs to be broad-spectrum and include anaerobic pathogens. It is vital that any IUCD or retained products of conception be removed as soon as possible.

Non–sexually acquired pelvic inflammatory disease

 

Non–sexually acquired infection is usually caused by mixed pathogens originating from vaginal flora, including anaerobes, facultative bacteria and genital Mycoplasma species and often occurs postpartum or following instrumentation or surgery. It is vital that any intra-uterine contraceptive device (IUCD) or retained products of conception be removed as soon as possible.

For mild to moderate infection, use

	amoxycillin+clavulanate 875+125 mg orally, 12-hourly for 14 days
	PLUS
	doxycycline 100 mg orally, 12-hourly for 14 days.

 

Azithromycin is a possible alternative to doxycycline but less well-established.

If the patient is pregnant or breastfeeding, substitute for doxycycline

roxithromycin 300 mg orally, daily for 14 days (category B1).

 

For severe infection use the regimen for severe sexually acquired pelvic inflammatory disease.

 

Sexually acquired pelvic inflammatory disease

 

Early empirical treatment is important because it reduces complications such as infertility. Infection is usually initiated by Chlamydia trachomatis and/or Neisseria gonorrhoeae, although other organisms from the endogenous vaginal flora may subsequently be involved. Sexual partner(s) should be examined, investigated and treated empirically.

For mild to moderate infection, use

	azithromycin 1 g orally, as 1 dose
	PLUS (for gonorrhoea)
	ceftriaxone 250 mg IM or IV, as 1 dose
	PLUS (in all patients)
	doxycycline 100 mg orally, 12-hourly for 14 days
	PLUS EITHER
1	metronidazole 400 mg orally, 12-hourly for 14 days
	OR
1	tinidazole 500 mg orally, daily for 14 days.

 

If the patient is pregnant or breastfeeding, substitute for doxycycline

roxithromycin 300 mg orally, daily for 14 days (category B1).

 

Where adherence to 2 weeks of doxycycline is unlikely there are theoretical grounds to indicate that doxycycline may be replaced by azithromycin 1g orally on days 1 and 8, although no satisfactory clinical trial data are available.

For severe infection, use

	doxycycline 100 mg orally or IV, 12-hourly
	PLUS
	cefotetan 2 g IV, 12-hourly.

 

Alternatively use

	doxycycline 100 mg orally or IV, 12-hourly
	PLUS
	metronidazole 500 mg IV, 12-hourly
	PLUS EITHER
1	cefotaxime 1 g IV, 8-hourly
	OR
1	ceftriaxone 1 g IV, daily.

 

Alternatively, especially for patients hypersensitive to penicillin, use

	gentamicin 4 to 6 mg/kg IV, daily (adjust dose for renal function, see Monitoring of aminoglycosides).
	PLUS EITHER
1	clindamycin 600 mg IV, 8-hourly
	OR
1	lincomycin 600 mg IV, 8-hourly.

 

If the patient is pregnant or breastfeeding, substitute for doxycycline

roxithromycin 300 mg orally, daily for at least 14 days (category B1).

 

Continue until there is substantial clinical improvement, then use oral doxycycline plus metronidazole (as above) or doxycycline plus amoxycillin+clavulanate (see Non-sexually acquired pelvic inflammatory disease) to complete at least 2 weeks of treatment.

Azithromycin (eg 1 g orally on days 1 and 8) is a possible alternative to doxycycline in the above regimens, but less well established.

Pelvic actinomycosis

 

This rare cause of pelvic inflammatory disease may mimic pelvic malignancy. It is often associated with prolonged intra-uterine contraceptive device (IUCD) use and is often a polymicrobial infection. Specialist advice should be sought. Management with a prolonged course of antibiotics (which should be broad-spectrum and needs to continue for at least 6 months to treat coexisting pathogens) and removal of any IUCD can lead to complete resolution. Surgical intervention, (particularly where abcesses are evident) may be necessary in some cases.

It is common for cervical cytology screening to report the presence of Actinomyces-like organisms when an IUCD is in situ. If this occurs, cultures for Actinomyces should be taken and if positive, the IUCD should be removed. Symptomatic patients should be investigated further and a pelvic ultrasound considered. Antibiotics should be considered if ongoing infection is demonstrated.

Prostatitis

 

Prostatitis comprises two distinct clinical syndromes:

 

Acute prostatitis presents with lower urinary tract symptoms associated with fever, systemic symptoms, perineal pain and exquisite tenderness of the prostate. Urinary tract pathogens are usually involved, although sexually transmitted pathogens may occasionally cause the condition. Most antibiotics penetrate well into the inflamed prostate and initial treatment should cover a broad range of pathogens and seek to prevent bacteraemia.

For mild to moderate infection, give oral treatment utilising one of the regimens for acute cystitis in men.

For severe infection, use

	amoxy/ampicillin 2 g IV, 6-hourly
	PLUS
	gentamicin 4 to 6 mg/kg IV, daily (adjust dose for renal function, see Monitoring of aminoglycosides).

 

Continue therapy until there is substantial clinical improvement, when therapy may be changed to an appropriate oral drug, based on the susceptibility of the pathogen(s) isolated, to complete a 2-week course of treatment.

 

Chronic prostatitis is notoriously difficult to diagnose, as there is little inflammation present and the gland is normal on clinical examination. It should be suspected in patients with recurrent lower urinary tract infection with the same organism or persistent symptoms after treatment of sexually-acquired urethritis.

Few antibiotics penetrate into the noninflamed prostate. Long-term treatment is required, but is only effective in curing about one-third of cases. Treatment of this condition is difficult and over-treatment with antibiotics should be avoided.

1	norfloxacin 400 mg orally, 12-hourly for 4 weeks
	OR
2	ciprofloxacin 500 mg orally, 12-hourly for 4 weeks
	OR
3	trimethoprim 300 mg orally, daily for 4 weeks
	OR
4	doxycycline 100 mg orally, 12-hourly for 2 to 4 weeks.

 

Urethritis and cervicitis

 

 

Chlamydia trachomatis (D-K serovars) is now the commonest identifiable cause of urethritis and cervicitis, and Neisseria gonorrhoeae is the other identified important cause. However, depending on the prevalence of these infections in the community, more than 50% of cases have no identifiable pathogen isolated. Treatment of symptomatic patients should be based where possible on the results of Gram stain, bacterial culture of an urethral/endocervical swab, and polymerase chain or ligase chain reaction tests of first-void urine/genital swab for chlamydia and gonorrhoea.

Particularly in urethritis, empiric treatment for both gonorrhoea and chlamydia should be routine practice, although some practitioners may wait for the results of investigations before commencing treatment if adherence is guaranteed.

Sexual partners should be examined, investigated and treated empirically. There are many regional differences in susceptibility of organisms and recommended treatments, and as relapse may occur, post-treatment follow-up of the patient is recommended. Culture and susceptibility testing is important to ensure that changing antibiotic susceptibility patterns are closely monitored, particularly in infections acquired overseas. Specialist consultation should be sought for complicated or disseminated infections.

 

1	azithromycin 1 g orally, as 1 dose
	OR
2	doxycycline 100 mg orally, 12-hourly for 7 days.

 

If symptoms persist or recur, a second course of antibiotics, further investigation of the aetiology, and assessment of risk of re-infection are required.

Sexual partner(s) of individuals with chlamydial infection should be examined and investigated and then treated empirically to prevent re-infection and chlamydial salpingitis.

 

Antimicrobial regimens should cover the potential coexisting infection with chlamydia.

Sexual partners should be examined, investigated and then treated empirically to prevent re-infection and complications.

As penicillin-resistant Neisseria gonorrhoeae is frequent and eradication of unsuspected pharyngeal or anorectal infection is important, use

	ceftriaxone 250 mg IM, as 1 dose
	PLUS EITHER
1	azithromycin 1 g orally, as 1 dose
	OR
2	doxycycline 100 mg orally, 12-hourly for 10 days.

 

Because of the emergence of resistance, ciprofloxacin 500 mg orally as a single dose (as an alternative to ceftriaxone) is no longer recommended unless a sensitive strain has been identified.

Where penicillin-resistant Neisseria gonorrhoeae prevalence is low, eg in remote areas of Australia, use

	amoxycillin 3 g orally, as 1 dose
	PLUS
	probenecid 1 g orally, as 1 dose
	PLUS
	azithromycin 1 g orally, as 1 dose.

 

In patients subsequently proven to have pharyngeal or anorectal infection, give ceftriaxone 250 mg IM as a single dose.

Cultures should be taken for resistance testing on any gonococcal infection that relapses or fails treatment.

Where molecular testing is used exclusively within populations, cultures should be performed with sensitivity testing from time to time as a random point prevalence survey to evaluate and gauge any change in local resistance patterns.

 

Use

1	cefotaxime 1 g IV, 8-hourly
	OR
1	ceftriaxone 1 g IV, daily.

 

Continue for 48 hours after defervescence then switch to oral regimens, based on culture and susceptibility results.

Vulvovaginitis

 

The management of vulvovaginitis in prepubertal girls and postmenopausal women is substantially different from the approach used in women of reproductive age. A vaginal swab for Gram stain and culture should be taken to guide therapy. In addition, in women of reproductive age, a wet preparation of a high vaginal swab should be examined.

In prepubertal girls Streptococcus species are common, and Staphylococcus, Haemophilus and Shigella species are rare causes of vulvovaginitis. Sexually transmitted pathogens may be involved in cases of sexual assault. In postmenopausal women, atrophic vaginitis or dermatoses are more common than bacterial infection. In both prepubertal girls and postmenopausal women, a foreign body in the vagina should be excluded. In preschool children, pinworms, if present, should be eradicated, see Worms (helminths).

 

 

Bacterial vaginosis

 

 

This condition is associated with malodorous vaginal discharge, usually without redness or soreness. The discharge has a pH >4.5, few or absent lactobacilli, and there is abundant Gardnerella vaginalis and/or Mobiluncus species, other mixed anaerobes and Mycoplasma hominis. Culture adds little to microscopy where 'clue cells' are seen. Treatment of male partner(s) is not indicated.

For symptomatic patients, use

1	metronidazole 400 mg orally, 12-hourly for 5 days
	OR
2	clindamycin 2% vaginal cream, 1 applicatorful intravaginally, for 7 nights.

 

A single dose of metronidazole or tinidazole 2 g may be used, but the cure rate is lower and retreatment may be necessary.

If the patient is pregnant, use

1	clindamycin 300 mg orally, 12-hourly for 7 days (category A)
	OR
2	metronidazole 400 mg orally, 12-hourly for 5 days (category B2).

 

 

 

Vulvovaginal candidiasis

 

Many effective topical preparations are available (imidazoles [eg clotrimazole, econazole, miconazole], nystatin). The following have been shown to be effective in at least 80% of women. Occasionally topical therapy may itself cause irritation. Nystatin, although less effective, is generally better tolerated than the imidazoles.

1	clotrimazole 1% vaginal cream (1 applicatorful) OR 100 mg pessary intravaginally, for 6 nights
	OR
1	clotrimazole 2% vaginal cream (1 applicatorful) intravaginally, for 3 nights
	OR
1	clotrimazole 10% vaginal cream (1 applicatorful) intravaginally, as 1 dose at night
	OR
1	clotrimazole 500 mg pessary intravaginally, as 1 dose at night, with or without use of clotrimazole 1% cream topically, 8- to 12-hourly to vulvovaginal and perianal areas
	OR
2	nystatin 100 000 units/5 g vaginal cream (1 applicatorful) OR 100 000 units pessary intravaginally, 12-hourly for 7 days.

 

If the patient is intolerant of topical therapy or would prefer to use oral therapy, and infection is microbiologically proven and the patient is not pregnant, use

fluconazole 150 mg orally, as 1 dose.

 

If initial treatment fails, review the diagnosis and seek specialist advice.

Symptomatic sexual partners (usually balanitis in the uncircumcised male) should be swabbed and only treated if infection is present (see Balanitis). Many men describe discomfort soon after intercourse, but this is usually an irritant effect that is rapidly relieved by use of 1% hydrocortisone cream.

 

Candida glabrata is the commonest of the nonalbicans species of Candida, which show reduced susceptibility to azoles. Candida glabrata accounts for 5% to 10% of recurrent vulvovaginal candidiasis. In clinically resistant infection, boric acid 600 mg (extemporaneously prepared in a gelatin capsule) intravaginally, daily for 10 to 14 days is effective. Do not use in pregnancy. This condition is recurrent and may need repeated treatment or long-term maintenance therapy.

 

Recurrent vulvovaginal candidiasis (RVVC) is defined as four or more attacks of symptomatic candida vaginitis in a 12-month period.

Chronic candidiasis refers to continuous symptoms due to Candida albicans infection; however, the definition and treatment of this common condition remains an area of controversy. The problem presents with a history, often dating back to teenage years, of vulval itching and burning with premenstrual exacerbation. Typically, it is worsened by courses of systemic antibiotics, and the male partner may become hypersensitive to C. albicans in his partner’s vagina and therefore experience postcoital itching. The appearance is of a nonspecific vulvitis and there is usually no discharge. Diagnosis is based on typical history and repeated positive vaginal swabs (the exact number has not been defined). The presence of diabetes mellitus and iron deficiency anaemia may predispose to candidal infection and these conditions should be ruled out prior to commencing therapy.

Treatment of either chronic or recurrent candidiasis is difficult and often has to be aimed at control rather than cure. It may be effected with either topical or oral antifungal medication, but the latter is easier to use, less likely to produce irritancy and has better patient acceptance. Because there is still no consensus on managing this condition, the following broad principles relating to a 2-stage management plan are recommended.

Induce symptom remission with continuous antifungal treatment. Use

1	a vaginal imidazole (eg clotrimazole) or nystatin (see recommendations above) intravaginally, at night
	OR
2	fluconazole 50 mg orally, daily
	OR
2	itraconazole 100 mg orally, daily
	OR
3	ketoconazole 100 mg orally, daily.

 

The time to achieve remission of symptoms varies from 2 weeks to 6 months.

Relieve itching with

hydrocortisone 1% cream topically, 2 to 3 times daily.

 

Hydrocortisone may be used for itching at any stage. Do not use stronger topical corticosteroids.

Maintain remission with interval therapy; the treatment interval varies from weekly to once a month (eg premenstrually) depending on response. A suitable weekly regimen is

1	fluconazole 150 to 300 mg orally, weekly
	OR
1	itraconazole 100 to 200 mg orally, weekly
	OR
2	clotrimazole 500 mg pessary intravaginally, weekly
	OR
2	nystatin 100 000 units/5 g vaginal cream (1 applicatorful) OR 100 000 units pessary intravaginally, weekly.

 

If oral antibiotics are required for intercurrent infection, the patient may have to return to continuous antifungal therapy after the course is completed to treat an antibiotic-induced flare of their condition.

There is generally no need to treat the male partner or stop a low-dose oral contraceptive pill. However, in postmenopausal women, hormone replacement therapy may predispose to candidiasis and may have to be suspended (see postmenopausal chronic vulvovaginal candidiasis).

 

Group B streptococcus (Streptococcus agalactiae)

 

Group B streptococcus (GBS) is a commensal in the gastrointestinal and genital tracts of up to 30% of healthy women of childbearing age.

 

The use of intrapartum antibiotics has been shown to reduce the incidence of early onset neonatal infections with GBS and other penicillin-sensitive organisms and of maternal postpartum infections. Intrapartum antibiotics should be started on the basis of screening pregnant women either for GBS carriage (low vaginal and anal swab for culture between 35 and 37 weeks) or maternal risk factors:

·            spontaneous preterm onset of labour (<37 weeks gestation)

·            prolonged rupture of the membranes (>18 hours)

·            maternal fever (>38°C)

·            previous neonate that developed GBS disease

·            GBS bacteriuria (of any count/L).

Use

benzylpenicillin 1.2 g IV, stat, THEN 600 mg IV 4-hourly until delivery (category A).

 

For patients hypersensitive to penicillin, use

1	clindamycin 450 mg IV, 8-hourly until delivery (category A)
	OR
1	lincomycin 600 mg IV, 8-hourly until delivery (category A).

 

For maternal fever (>38°C—potential chorioamnionitis), the spectrum needs to be broadened. For prolonged rupture of the membranes and maternal fever, see Severe sepsis, female genital tract source.

 

Treatment of GBS in the nonpregnant female is not indicated for asymptomatic carriage but only for clinically evident acute vaginitis with a Gram stain suggestive of an active pyogenic infection, ie the presence of numerous pus cells (polymorphs) and a predominance of Gram-positive cocci of characteristic morphology without other pathogens. This is rare. Use

phenoxymethylpenicillin (child: 10 mg/kg up to) 500 mg orally, 6-hourly for 7 days.

Trichomoniasis (Trichomonas vaginalis)

 

 

This infection often presents as vaginal discharge which may be yellow-green and frothy (pH >4.5), associated with a fishy smell, and inflamed vagina and cervix. However, it may be asymptomatic. Empirical treatment of partners is indicated. Investigation for other sexually transmitted infections should be considered.

1	metronidazole 2 g orally, as 1 dose
	OR
1	tinidazole 2 g orally, as 1 dose.

 

For cases that relapse after this treatment, a longer course of metronidazole may be necessary.

metronidazole 400 mg orally, 12-hourly for 5 days.

 

If the patient is pregnant and symptomatic, give single dose treatment as above as trichomoniasis in pregnancy is associated with adverse pregnancy outcomes.

 

 

 

 

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