"Honeymoon cystitis"- urinary infection and the female urinary tract

Dr Rodney Cove-Smith MD, FRCP, Consultant Physician & Nephrologist, South Tees Acute Hospitals NHS Trust

Key Words: Cystitis; sexual intercourse; urinary infection; pyelonephritis; pregnancy

Introduction
'Honeymoon cystitis' is a splendidly old-fashioned term, referring to urinary infection following a girl's first intercourse, which traditionally occurred on the wedding night. Since the advent of the oral contraceptive pill (OCP) in the 1960s, however, sexual intercourse before marriage has become the norm in Western society. It is not uncommon nowadays to be faced with a 15-year-old in the clinic, referred with recurrent urinary tract infection (UTI), who denies having had intercourse until the parent is tactfully removed from the consultation! A recent survey among young teenagers in Scotland showed that 18% of boys and 15.4% of girls had already experienced heterosexual intercourse by the age of 14. 1

Acute cystitis is commoner in females. In a Swedish study, 7.8% of girls and 1.6% of boys entering school had had a symptomatic UTI 2. The incidence rises during the sexually active years (see Fig) and at least 50% of adult women will have a UTI at some stage in their life. A study of unmarried female university students in the USA suggests that sexual intercourse three times a week increases the risk of UTI 2.6 times, while daily intercourse increases the risk 9-fold.3

The paper examines the pathogenesis, clinical features and treatment of acute cystitis in women, including the problems which may arise in pregnancy.

Pathogenesis and Microbiology
In women bacteria from the faecal flora can readily colonise the vaginal introitus and gain access to the urethra and bladder. The development of a UTI depends on several factors:

• The virulence of the host bacteria: some strains have particular virulence factors such as fimbriae and adhesins which enable them to adhere strongly to the bladder wall 
• Host factors: women who are non-secretors of histo-blood group antigens are three times more likely than other women to have recurrent UTIs 
• Chemical factors: spermicidal contraceptive creams and devices, vaginal deodorants and antiseptic lotions may all alter the vaginal environment in favour of bacterial colonisation.
• Sexual intercourse, by its mechanical effect, introduces faecal flora into the urethra.

Escherichia coli is the pathogen in 70-95% of cases of acute uncomplicated cystitis. The remainder of infections are due to Staphylococcus saprophyticus (5-11%), Klebsiella, Enterococci and Proteus. In the setting of the STD clinic, and particularly in women who have frequent casual sex with many partners, urethritis with Neisseria gonorrhoea or Chlamydia trachomatis is relatively more likely.

Symptoms
Most women with a UTI will report urinary frequency, urgency and dysuria, while some may also have suprapubic pain or haematuria. Untreated, symptoms last 5-7 days. The history should include details of previous UTI, especially in childhood, recent sexual intercourse, haematuria, urethral or vaginal discharge, enuresis, passage of stones, previous kidney disease or a family history of kidney problem.
Abdominal examination should include the suprapubic area and the renal angles, and if STD is 
suspected then the introitus, urethra and cervix should also be examined and the appropriate swabs taken.

Investigations
A dipstick urine test is a useful guide and, in the presence of bacterial infection will be positive for leucocyte esterase (pyuria) and nitrites. Enterobacteriaceae convert urinary nitrate to nitrite, but the test may not detect "low count" UTI or infection with certain bacteria. Dipstick haematuria is common in UTI, but rare with urethritis or vaginitis.
The standard investigation is the mid-stream urine (MSU), which will demonstrate white cells, red cells (if present) and bacteria. It is important to remember that the concept of "significant bacteriuria" was developed to study cohorts of women with asymptomatic bacteriuria. It depended on finding > 105 colony forming units (CFU) per ml of urine. In symptomatic UTI many women will have lower counts than this and recent studies suggest that 102 CFU/ml should be considered positive.4 Some would say that any bacterial growth in women presenting with acute cystitis should be regarded as significant.
Some women present with symptoms of cystitis, accompanied by pyuria but no bacterial growth on routine MSU. This combination, often called the urethral syndrome, requires further investigation. Suprapubic aspiration of urine in such women may reveal bacteria, and in about a third of cases infection will be due to Chlamydia trachomatis.The presence of any bacteria in a suprapubic aspirate is significant and treatment with the appropriate antibiotic may cure the infection.5

Treatment
Simple uncomplicated UTI is a benign condition and responds promptly to oral antibiotics. In patients with urinary tract abnormalities, stones, pregnancy or neurogenic bladders, eradication of infection may be more difficult and referral to a specialist is advised.
40-60% of E.coli are now resistant to ampicillin/amoxycillin. Antibiotic therapy should be guided by local resistance patterns. In Teesside 50% of coliforms are resistant to amoxycillin and 24% to trimethoprim, but only 5% to cephalexin, and 2% to nitrofurantoin. 
For uncomplicated infections 3 day courses of antibiotics are sufficient on the basis of cost, efficacy and fewer adverse reactions. Cephalexin is the drug of first choice. Nitrofurantoin is effective against most E.coli strains, as well as gram positive cocci and some gram negative bacteria, but it is inactive against Proteus and Klebsiella. It should be given for 5-7 days. Ciprofloxacin is effective against most pathogens but should be reserved for more serious infections or organisms resistant to the other antibiotics (see Table 1)
Patients should be encouraged to drink plenty of fluids, and it is not necessary to avoid intercourse while receiving antibiotics for a UTI.

Follow-up
In adults, uncomplicated cystitis which resolves with a short course of antibiotics needs no further investigation. In children any UTI should be investigated, and teenagers with more than one episode of infection, whether or not related to intercourse, should be referred for further investigation. This is to look for underlying abnormalities of the urogenital tract which may predispose to recurrent infection (see Table 2). Such abnormalities should be excluded before a woman embarks on pregnancy, since infection of the kidney - acute pyelonephritis - is associated with high risk of fetal loss, while pre-existing renal damage, such as chronic pyelonephritis, may result in hypertension and further renal damage in pregnancy (see later section).

Teenagers or young adults with recurrent UTI should have their renal function checked and imaging of the urinary tract. A DMSA scan is preferred in children, but in older teenagers and adults an intravenous urogram (IVU) gives more information than an ultrasound scan about the anatomy, for example mild degrees of renal scarring, duplex collecting systems or pelvi-ureteric junction obstruction. 

In patients found to have abnormalities of the urinary tract recurrent UTIs may require more prolonged therapy, usually 5-7 days of antibiotics, and an MSU should be repeated after completion of the course. Prophylactic antibiotics, such as nocturnal trimethoprim, nitrofurantoin, cephalexin or ciprofloxacin should be reserved for those patients who have frequent proven UTIs - more than six episodes a year.

Urinary infections and pregnancy
As mentioned above, women with recurrent UTI should be investigated before they embark on pregnancy, so that any existing abnormalities of the urinary tract are known. Correctable abnormalities such as renal stones or pelvi-ureteric junction obstruction should be dealt with before pregnancy. 
Acute pyelonephritis in pregnancy is a serious condition, with an increased incidence of premature labour and intrauterine growth retardation, and a significant risk of fetal loss. It typically presents with vomiting, rigors, fever and/or loin pain, but urinary symptoms may be minimal or absent. Women with suspected acute pyelonephritis in pregnancy should be admitted to hospital and given intravenous antibiotics and fluids.
Acute cystitis occurs in 1% of healthy pregnant women, but diagnosis may not be easy, since pregnancy itself can produce frequency, nocturia, urgency and incontinence. Obvious dysuria and haematuria should suggest a UTI. Bacterial contamination of the vagina and perineum is common in pregnancy and 5-6% of woman have asymptomatic bacteriuria in the first trimester. Dilatation of the ureters and relative delay in excretion due to the gravid uterus make ascending infection more likely. Prompt treatment of acute cystitis is recommended in pregnancy with cephalexin or co-amoxiclav for 3-7 days. Symptoms usually resolve quickly but the MSU should be repeated 1-2 weeks after completing the course of antibiotics to ensure clearance of the infection.
Chronic pyelonephritis is the term given to scarring of one or both kidneys arising from childhood infections and vesico-ureteric reflux. It is often asymptomatic and only picked up because of the presence of white cells and protein in the urine, sometimes with a raised blood pressure. Nowadays it should be diagnosed when girls are screened or seen for contraceptive advice, but many cases present for the first time in pregnancy. It may be confused with pre-eclamptic toxaemia (PET) because of proteinuria and hypertension, but PET typically presents in the third trimester, whereas proteinuria in the first trimester, with elevated blood pressure, usually indicates underlying renal disease or essential hypertension.

Investigations of urinary infections in pregnancy should include MSU, blood urea and creatinine. Radioisotopes and X-rays should be avoided in pregnancy, so imaging of the kidneys is by ultrasound scanning. If proteinuria is present a 24 hour urine should be sent to measure 24-hour excretion. Women with impaired renal function or significant abnormalities of the renal tract should be referred for specialist opinion. If hypertension is present (BP > 140/90) this should be controlled with medication known to be safe in pregnancy - methyldopa, labetalol or hydralazine. Long-acting nifedipine is also widely used and appears to be safe, but is not currently licensed for use in pregnancy.

If blood pressure and infection are controlled then pregnancy and labour can be allowed to proceed normally. If renal function is impaired (creatinine > 100 mmol/L in pregnancy) and BP is difficult to control, then early delivery may be indicated.

The puerperium is another time when UTI or systemic infection is common. Blood cultures and MSU should be sent from any post-partum woman developing a fever. Examination of the urine may be misleading because of the presence of lochia and other contaminants. Suprapubic aspiration of urine may be preferred.

Summary
The incidence of UTI in women increases with sexual activity. Risks of infection can be reduced by ensuring complete emptying of the bladder after intercourse and before retiring. This may entail 'double' or 'treble' micturition. Chemical deodorants, antiseptic baths and vigorous rubbing of the vaginal area with flannels should be avoided!
Simple UTI responds rapidly to simple antibiotic regimes. Recurrent UTI or infections in women with known urinary tract abnormalities require investigation and referral to a nephrologist or urologist.

Notes

• Antibiotic choice should take into account local bacterial resistance patterns
• Do not use nitrofurantoin if significant renal impairment (serum creatinine > 300 mmol/L)
• Trimethoprim 200 mg orally twice daily is a cheaper alternative for uncomplicated UTI but over 20% of isolates are resistant. Avoid in pregnancy
• Symptomless bacteriuria in pregnancy should be treated because of the risk of ascending infection

References

1. Wight D, Henderson M, Raab G, et al Extent of regretted sexual intercourse among teenagers in Scotland: a cross sectional survey. BMJ 2000; 320: 1243
2. Hellstrom A, Hanson E, Hansson S, et al Association between urinary symptoms at 7 years old and previous urinary tract infection. Arch Dis Child 1991; 66: 232
3. Hooton TM, Scholes D, Hughes JP, et al A prospective study of risk factors for symptomatic urinary tract infection in young women N Engl J Med 1996; 335: 468
4. Stamm WE, Counts GW, Running KR, et al Diagnosis of coliform infection in acutely dysuric women. N Engl J Med 1982; 307: 463
5. Stamm WE, Wagner KF, Amsel R, et al Causes of the acute urethral syndrome in women. N Engl J Med 1980; 303: 409

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