Introduction

The treatment of urinary tract infection (UTI) will depend on whether the infection was acquired in the community or in hospital, due to different patterns of resistance among infective organisms.  Lower UTI acquired in the community is extremely common and is generally mild and self-limiting.  Any such infections that are the primary reason for referral to hospital are therefore usually at the difficult end of the spectrum, either because of a virulent pathogenic strain of infecting organism, an anatomical abnormality or other host factors.

Risk factors for community-acquired lower UTI

Any anatomical or physiological factor that results in incomplete emptying of the bladder allows a reservoir of residual urine within which bacteria can multiply.

Common causes of incomplete bladder emptying include:

• Pregnancy: UTIs are common in pregnancy (about 15% of pregnant women will experience a UTI)
• Prostate problems: men over the age of 50 have a greater incidence of UTIs, but below the age of 50, UTIs are rare in men
• Obstruction, bladder or uterine prolapse
• Neurogenic bladder.

Other risk factors include:

• Immunosuppression
• Diabetes mellitus.

Aetiology of community-acquired lower UTI

UTIs can be caused by a variety of organisms, most commonly Gram-negative bacteria from the gastrointestinal flora, although Gram-positive cocci cause infection in up to 20% of cases.

Common pathogens include:

• Escherichia coli (approximately 80% of community-acquired UTIs)
• Staphylococcus saprophyticus.
• Proteus spp.
• Enterococcus spp.

Less common pathogens include:

• Ureaplasma urealyticum
• Mycoplasma hominis
• Mycobacteria.

Pathogenicity of Escherichia coli

Diagnosis of community-acquired lower UTI

Clinical diagnosis

UTI may be asymptomatic, especially in the elderly.

Signs and symptoms include:

• Dysuria
• Frequency
• Cloudy urine
• Haematuria
• Loin pain or suprapubic pain.

Laboratory diagnosis

Microbiological tests are very useful for diagnosing UTI and should always be performed.

• Mid-stream urine (MSU) samples, if taken carefully, provide a good snapshot of events within the bladder.

Interpretation of urine form (Click on blue text for further information)

• If urine culture is negative then fastidious organisms or non-infectious causes are possible.
• Blood culture is useful in a pyrexial patient, as systemic infection may have occurred.

Dipstick tests

Imaging

• Imaging techniques can reveal underlying structural abnormalities in the urinary tract.

Management of community-acquired lower UTI

Antibiotic rationale

Empirical therapy should always be active against the most common pathogen of urinary tract infections, Escherichia coli. The regimen should be chosen in accordance with local resistance patterns and be active against Gram-positive species as well as other Gram-negative species.

• Trimethoprim.  
• Nitrofurantoin.
• Amoxicillin.
• Cephalosporins.
• Quinolones.

Empirical therapy

Consult your local microbiologist or local treatment recommendations for details of preferred antibiotic regimens.

Suitable empirical regimens for uncomplicated community-acquired lower UTI include:

• Trimethoprim
• Nitrofurantoin
• Oral cephalosporin (such as cephalexin)
• Co-amoxiclav
• A quinolone such as ofloxacin or ciprofloxacin.

Once culture results are known, antibiotic therapy can be adjusted if necessary.

Treatment duration:

• Uncomplicated UTI in non-pregnant women: 3-day courses
• Pregnant women: 7-day courses
• Men: 7-day courses
• Recurrent UTI.
• If anatomical or neurological abnormality is present a longer course may be required.

Complications of lower UTI include acute pyelonephritis, particularly in pregnant women.  Successful treatment of urinary tract infection in these groups is the most effective method of preventing acute pyelonephritis. 

Duration of treatment for uncomplicated UTI in non-pregnant women

Investigation for non-response to treatment

If the infection does not respond to initial treatment, or if persistent sterile pyuria is seen and the patient has clinical symptoms consistent with UTI, a further specimen should be taken and the culture repeated to check for fastidious, atypical or resistant organisms. Standard laboratory media kill many of the possible pathogens so the laboratory must be informed of the clinical suspicion of fastidious, atypical or resistant organisms.

• Atypical organisms such as Ureaplasma urealyticum or Mycoplasma hominis normally respond to doxycycline or a single dose of azithromycin 1 g.

Management of UTI in special populations

Pregnant women

UTIs and even asymptomatic bacteriuria in pregnant women lead to an increased incidence of preterm labour, premature rupture of the membranes, and pyelonephritis (up to 30%).  The use of antibiotics to eradicate asymptomatic bacteriuria in pregnant women has been proven to reduce the incidence of preterm births.

The aetiology of UTI in pregnant women is essentially the same as in non-pregnant women but the presence of Group B streptococci, while still a less common finding, has important implications for management to prevent neonatal sepsis or possibly meningitis in the newborn infant.

Asymptomatic bacteriuria should always be treated in pregnant women.

Certain agents must be avoided because of their potential for fetal harm:

• Doxycycline, streptomycin, gentamicin, and kanamycin are contraindicated in pregnancy, and sulphonamides are not safe for the fetus after the 34^th week
• Some doubts have been raised over the safety of some cephalosporins (especially when administered intravenously); however, cephalexin has a good track record for safety 
• Quinolones (produce arthropathy in animal studies) and trimethoprim (possibly teratogenic) are not recommended in pregnancy, and these agents should be used only when the benefit clearly outweighs the risk
• Co-amoxiclav should be used with caution in pregnancy unless essential, as there is little information on the safety of the clavulanic acid component in pregnancy.

Treatment regimens

Suitable regimens for pregnant women, if supported by culture results after screening, include:

• Amoxycillin
• Nitrofurantoin (to be avoided approaching term)
• Oral cephalexin.
• Treatment should be given for seven days
• There is no evidence yet to support the use of single dose courses in pregnant women.

The elderly

In general, the elderly may have:

• A higher risk of adverse drug reactions to antibiotics
• Decreased rates of antibiotic metabolism and excretion
• Compromised defences as a result of physiological or anatomical changes
• Multiple concomitant diseases.

Asymptomatic bacteriurias are very common in the elderly but are not associated with an increased risk of renal damage or death in this age group. Treatment brings no benefit to the patient, exposes them to the adverse effects of antimicrobials, and increases the probability of resistance developing, and therefore asymptomatic bacteriurias are not generally treated in the elderly. 

Pyuria alone is also not an indication for treatment in the elderly; pain or new lower urinary tract symptoms are more reliable indicators of a need for treatment. 

UTI in the elderly is frequently considered complicated in women, and always considered as complicated in men.  Complicating factors include the presence of an indwelling catheter or intermittent catheterisation, >100 mL residual urine, obstructive uropathy, vesico-ureteric reflux/other urological abnormality, or raised blood levels of urea and reduced creatinine clearance.

In addition, UTIs may have an altered presentation in the elderly:

• Presentation may be with non-specific symptoms, in particular confusion, recent bladder incontinence, fever, apathy, and decreased ability to cope.

Therapy decision points

There are five key decision points in deciding upon therapy for UTI in the elderly:

1. Is urine culture required?
   
2. How reliable is urinalysis in confirming the presence of UTI?
3. If a UTI is present, what antibiotic should be used? 
4. What duration of therapy is appropriate? 
5. Should parenteral or oral therapy be used?

Recurrent lower UTI in women

Recurrent UTIs are common in otherwise healthy young women: 20–50% of women have recurrent episodes of UTI.  Recurrences tend to cluster over a few months, and most are uncomplicated.  Recurrent UTI may result from:

• Relapse (generally taken to be a recurrence occurring within two weeks of the original infection with an organism identical to that causing the original infection)
• Re-infection (occurs more than two weeks after the original infection and need not be caused by the original pathogen). 

Most recurrent UTIs are re-infections, but the original strain is often involved.

Several factors contribute to the pathophysiology of recurrent UTI. 

Management of recurrent UTI in women

Refer to local guidelines for management of recurrent UTI in women.

Management of recurrent UTI in women is controversial as there is no consensus on which of several treatment options is the most effective. Such options include:

• Increased duration of therapy
• Prophylaxis
• Patient-initiated therapy
• Oestrogen-replacement therapy.

In cases of recurrent UTI, consult your local microbiologist.

Controversial issues in the control of recurrent UTI in women

Men

The diagnosis of a confirmed urinary tract infection in men between the ages of 3 and 50 demands further investigation.  Diabetes, immunosuppression and previous surgery are risk factors for UTI in men.  Infection of the upper urinary tract is more likely to occur in males than females with a UTI.  UTI in men can be complicated by the involvement of the prostate. The antibiotics used to treat UTI in men should be capable of penetration into prostatic tissue, which is why the preferred antibiotics are different from those chosen for UTI in women.

Treatment should be for a minimum of seven days.

Asymptomatic bacteriuria

Asymptomatic bacteriuria has been observed in both sexes, in a wide range of populations from juveniles to the elderly, and is often only transient.

The presence of asymptomatic bacteriuria provides the potential for symptomatic UTI, acute pyelonephritis or other sequelae.  However, despite the fact that asymptomatic bacteriuria responds readily to antibiotic treatment, there is no evidence for benefit from treatment in most patients, including the elderly, and most guidelines on screening do not support screening for asymptomatic bacteriuria.

The exceptions are:

• Pregnant women
• Men or women about to undergo an invasive genitourinary procedure
• Anyone (especially the elderly) colonised by an organism with a high potential for bacteraemia, eg. Serratia marcescens in institution-based patients.

Asymptomatic bacteriuria in renal transplant patients

There are few studies that show any problems from asymptomatic bacteriuria in renal transplant patients but the consequences of any infection can be severe and many units have a policy of post-transplant antibiotic prophylaxis. The need to treat asymptomatic bacteriuria in renal transplant patients, neutropenic patients or patients with diabetes remains controversial and hence should be decided on an individual patient basis after discussion with the microbiologist.

Treatment is mandatory in pregnant women, in whom asymptomatic bacteriuria has a high risk of serious sequelae.

Sterile pyuria

The finding of pyuria without bacteriuria can be a diagnostic challenge and warrants further investigation. A careful history and physical examination can help determine the cause of sterile pyuria. Sterile pyuria is associated with a number of infectious and non-infectious causes, including:

Sterile pyuria is more common in the elderly.

Before further investigation, it is important to ensure that repeat specimens are collected appropriately. A mid-stream clean catch sample can help avoid contamination with WBCs from vaginal or prostatic secretions.

Culture-negative results can be seen in a single sample if the patient has taken antibiotics immediately before giving the sample. But if persistent sterile pyuria is seen and the patient has clinical symptoms consistent with UTI, a further specimen should be taken and the culture repeated to check for fastidious, atypical or resistant organisms. Standard laboratory media kill many of the possible pathogens so the laboratory must be informed of the clinical suspicion of atypical or fastidious organisms.