Background

Most urinary infections occur in women who are otherwise healthy. Escherichia coli is the cause of 70% or more of such uncomplicated urinary infections presenting in general practice.2 Most of the rest are caused by Proteus mirabilis, Klebsiella pneumoniae, and, especially in young women, Staphylococcus saprophyticus. The key risk factors for uncomplicated infections include sexual intercourse, a personal or family history of urinary infection and the use of a contraceptive diaphragm plus spermicide (which may alter the vaginal flora). Complicated urinary infections are those in which colonisation is associated with an anatomical or functional defect of the urinary tract, recent urinary tract instrumentation or catheterisation. The causative organisms include those that cause uncomplicated infection and also Staphylococcus aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa and other organisms.

Clinical presentation

Infection generally presents as either cystitis or acute pyelonephritis. Typical symptoms of cystitis include dysuria, frequency and urgency of urination. Suprapubic pain, cloudy or foul-smelling urine, haematuria, or in elderly patients, confusion, may also occur. Acute pyelonephritis typically causes flank pain and fever, often with nausea, vomiting, malaise or symptoms of cystitis.

Asymptomatic bacteriuria (significant bacteriuria without symptoms of urinary infection) is found in 15-20% of women aged 65-70 years3 and does not seem to impair renal function or shorten life.4^,5 Asymptomatic bacteriuria also occurs in 4-7% of pregnant women but is then associated with premature delivery and low birthweight.6

Diagnosis

In women with uncomplicated cystitis, diagnosis can be based on the history and clinical signs, together with results of urine dipstick testing for nitrites and/or leucocyte esterase. With this information, an antibiotic can be given empirically. Culture of urine is not usually necessary although microscopic examination may provide helpful clues.

The nitrite test relies on bacteria converting nitrates in the urine to nitrites which takes several hours. Therefore, the test is best done on the first sample of urine passed in the morning. In a general practice study, urine culture proved positive (>=10 bacteria/mL) in 89% of samples yielding positive nitrite results and negative (<0/mL) in 79% of negative nitrite results.7 The leucocyte esterase dipstick test which detects pyuria, gave true positive and negative values in 66% and 90% of samples. If the nitrite test is positive, it is reasonable to start empirical therapy without accompanying culture of the urine. However, if both tests are negative, urine should be sent for culture.

Urine culture is essential in the management of women with complicated infection, in those who are pregnant, where empirical antibiotic treatment fails and in those who have pyelonephritis. In these circumstances, treatment can be started with the 'best guess' antibiotic before results are available, but it may need to be modified in the light of culture findings.

Urine culture

When a sample is required for culture it should be collected mid-stream with the labia held apart; cleaning the perineum is unnecessary.8 When an indwelling catheter is in place, the sample should be taken by syringe aspiration via a port in the drainage tube. It should not be taken from the base drain of the catheter bag or by disconnecting the catheter from the drainage system, as these approaches risk introducing new organisms. Ideally, the sample should be cultured within 4 hours of collection; otherwise it should be refrigerated at 4C or preserved in borate, or a dip-slide used. Uncomplicated urinary tract infections are usually caused by single organisms. When there is mixed bacterial growth, this suggests that there has been a delay in transport or the sample has been contaminated. The threshold for distinguishing infection from bacterial contamination for most of the more common bacteria is taken as 10 bacteria/mL (10/L). However, lower bacterial counts can sometimes indicate clinically significant infection,9 e.g. 10-10mL for symptomatic infections caused by gram-positive (e.g. S. saprophyticus), or atypical, organisms (e.g. Proteus).

If all symptoms have cleared following treatment, a follow-up culture is unnecessary. However, one should be done 1-2 weeks after an antibiotic course has been completed in pregnant women, if the infection is complicated, or in those in whom there have been repeated recurrences.

Radiology

Any woman who has recurrent, symptomatic and unexplained urinary infections should be referred for investigation using radiological imaging, such as intravenous urography and ultrasonography, to exclude anatomical abnormalities.

Treatment

General measures to treat urinary infection include drinking more to increase urinary output, and an analgesic or antipyretic for pain or fever. Oral treatments that alkalinise the urine may alleviate symptoms of cystitis.

Cystitis

Trimethoprim, a commonly used first-line therapy, is effective against around 70% of urinary pathogens.10 Nitrofurantoin and oral cephalosporins are alternative first-line drugs. Resistance of urinary pathogens to nitrofurantoin is around 15%,10 and to oral cephalosporins generally less than 10%.10 However, treatment-failure rates of around 30% have been reported for cephalexin.11–13 Amoxycillin is unsuitable for empirical therapy as around 50% of urinary pathogens are amoxycillin-resistant.10 Up to 90% of urinary pathogens are sensitive to co-amoxiclav,10 an alternative for infections caused by bacteria resistant to trimethoprim.14

The 4-quinolones ciprofloxacin, norfloxacin and ofloxacin are effective in cystitis15 because only around 5% of pathogens are resistant.10 The resistance rate is likely to increase the more these drugs are used in the community. To preserve their efficacy, the 4-quinolones should not be used as first-line therapy unless the urinary infection is complicated or caused by organisms known to be resistant to other antibiotics.

A 3-day course of an oral antibiotic will usually suffice for treating uncomplicated cystitis and appears as effective as 5-day or 7-day regimens.16^,17 However, 3-day courses are not recommended in the product licences of many antibiotics. Single-dose antibiotic therapy has been tried, but generally results in lower cure rates and more recurrences than do longer courses.17–19 If symptoms do not respond to empirical antibiotics within 2-3 days, urine should be taken for culture and sensitivity testing.

Recurrent infections - These occur either as the result of a relapse of a previously treated infection or because of reinfection. In a woman who has recurrent infection with a proven microbial cause and in whom imaging investigation has proved negative, prophylactic trimethoprim, nitrofurantoin or norfloxacin therapy can reduce the likelihood of further attacks.20 Prophylaxis should be started after successful treatment of infection and continued for 3-6 months.

Acute pyelonephritis

The patient should be admitted to hospital if she is vomiting, or needs intravenous antibiotic therapy or rehydration. Treatment should be started blind with trimethoprim, cefotaxime, a 4-quinolone or an aminoglycoside while waiting for culture results and should be changed, if necessary, depending on the persistence of symptoms and on the culture and sensitivity results. Treatment should continue for 10-14 days. A patient who is severely ill with a urinary infection is more likely to have an underlying complication, and should be referred for further investigation.

Asymptomatic bacteriuria

In women over 65 years old, treatment of asymptomatic bacteriuria is probably unnecessary.4^,5 Around 30% of pregnant women with untreated asymptomatic bacteriuria will develop acute pyelonephritis during the pregnancy.6 All pregnant women should be screened for bacteriuria at the first antenatal visit and then treated if infection is found. Whether antibiotic treatment of the bacteriuria can prevent premature birth and low birth weight is still not clear.21 Data sheets advise caution in prescribing antibiotics during pregnancy. Amoxycillin, an oral cephalosporin or nitrofurantoin is the preferred antibiotic if the causative organism is known to be susceptible. Other antibiotics are seldom needed. Treatment should continue for at least 7 days.22 Urine should be cultured 1-2 weeks after stopping treatment and a repeat 2-week course given if infection persists. Subsequent urine samples should be checked monthly to exclude relapse. Further relapse might justify more prolonged antibiotic treatment.

Catheter-associated urinary infection

Around 90% of patients with a long-term indwelling catheter develop bacteriuria within 17 days of its introduction.23 Applying antibacterials to the urethral meatus, adding one to the lubricant, taking prophylactic antibiotics, or using antiseptic irrigations do not help prevent infection.24 Culture and treatment are needed if features of systemic or urogenital infection develop. Where there have been previous infections, 4-quinolones may be particularly useful because bacterial resistance is less common and because they are active against Pseudomonas. If the patient's clinical condition permits the catheter should be removed. After catheter removal, a freshly voided urine sample should be sent for culture. An antibiotic will be needed if the culture is positive; infection may take longer to clear in older (women over 65 years) than in younger women.25 Intermittent self-catheterisation leads to fewer symptomatic infections than does use of a long-term indwelling catheter.26

Conclusion

The treatment of a woman with a urinary tract infection depends on the likely site of infection, whether it is secondary to some predisposing factor, whether it is recurrent and whether she is pregnant. Urinary culture is not necessarily required, with nitrite and leucocyte tests being adequate in a woman with uncomplicated cystitis. Urine culture and sensitivity testing is, however, required in patients with suspected pyelonephritis, recurrent or complicated infections, and during pregnancy. Uncomplicated cystitis can be managed empirically with trimethoprim or, where resistance of urinary pathogens is common, an oral cephalosporin or nitrofurantoin, taken for 3 days. Treatment failures should probably be treated with a 4-quinolone. Recurrent cystitis may be preventable with a low dose of trimethoprim, nitrofurantoin or norfloxacin taken for 3-6 months. Pyelonephritis and asymptomatic bacteriuria of pregnancy require more prolonged treatment than acute cystitis. Catheter-associated bacteriuria is difficult to avoid but only requires treatment if it is associated with symptoms or if bacteriuria persists after catheter removal.