Treating urinary tract infections

Magnus Grabe, MD, PhD

Associate Professor of Urology, Skåne University Hospital, Malmö, Sweden

On behalf of the European Section of Infection in Urology (ESIU), a section of the European Association of Urology (EAU). (ESIU members: Truls E Bjerklund-Johansen (N) (chair), Henry Botto (F)(vice-chair), Magnus Grabe (S) (chair, guidelines working group), Richard Pickard (UK), Peter Tenke (HU), Florian Wagenlehner (D), Björn Wullt (S).)

The European Association of Urology (EAU) publishes an update of Guidelines on Urology every year.1 These guidelines describe most areas of urology, including a section on Urological Infections.2 This latter chapter covers the large field of infections of the urinary and male genital tracts, special fields such as paediatric urological infections, urinary tract infections in association with renal transplant and immunosuppression and specific infection, such as tuberculosis and bilharzia. The section gives also recommendations on antibiotic prophylaxis in urological surgery.

The guidelines are the result of a systematic review of the literature in combination with the analysis and opinion of experts expressed for instance in textbooks3 and reflects evidence-based facts as far as possible. This present short review does not include male genital infections such as prostatitis, epididymitis and orchitis, nor inflammation of the urethra (urethritis).

Urinary tract infections (UTI) are among the most frequent infections encountered in the community. The cumulative probability of UTI in women for instance is about 50% at 50 years of age. UTI treatment takes approximately 10%–15% of all antibiotics prescribed in the primary health sector.4

Catheter-associated UTI is the most frequent healthcare associated infection (HAI), representing some 40%.5,6 Recent global prevalence studies on infections in urological departments (GPIU, performed by the ESIU/EAU) have shown that approximately 10%–12% of the patients hospitalised in European urology departments have a HAI, that a large number of patients are treated for established infections such as complicated UTI and sepsis, and that a majority of patients undergoing urological surgery will receive antibiotic prophylaxis.7

In recent years, bacterial resistance to antibiotics has dramatically increased worldwide. At the same time, there are almost no new antibiotic undergoing clinical trials leading to registration within the forthcoming decade.8

Bearing these two observations in mind, it becomes especially important to use the existing antibiotics in a rational way both for treatment and prophylaxis.

The aim of the section on urological infections2 is precisely to offer to the urologist and the practitioner, on the primary level as in the hospital setting, a tool for an evidence-based use of antibiotics with the ultimate goals of avoiding both overuse and underuse of antimicrobial agents and thus to limit the risk of escalating antibiotic resistance.

Classification of UTI
The present classification is as follow:

• 
Bacteriuria or colonisation of the urine without symptoms (asymptomatic bacteriuria)
• 
Uncomplicated UTI (uUTI)
  
  • 
Cystitis (infection of the urinary bladder)
  • 
Uncomplicated pyelonephritis (infection of the kidney)
• 
Complicated UTI (cUTI)
  
  • Complicated pyelonephritis
  • Febrile, upper UTI
• 
Urosepsis (bloodstream-carried infection with the urinary tract as source).

It is understood that there are no anatomical or functional abnormalities in uncomplicated UTI, while one or several of these or any other risk factor are present in a complicated infection (Table 1 and 2). Clinical symptoms and signs of infection should be confirmed by a urine culture and/or laboratory results.

Escherichia coli is still the most frequently encountered microbe, present in as many as 75%–85% of all community acquired uUTI and approximately 35%–50% of the cUTI.4,7 Other main gram negative bacterial species are klebsiella and proteus, pseudomonas and gram positive strains such as Enterococcus faecalis and some staphylococci species.

In recent years, there has been a noticeable increase of in multiresistant bacterial strains such as MRSA, vancomycin-resistant enterococcus (VRE), Extended Spectrum Beta-Lactamase (ESBL), both in the community and the hospital settings.8

Uncomplicated UTI
Uncomplicated UTI are of two categories. The first, and most common, is cystitis or the infection of the urinary bladder (lower urinary tract), mainly observed in women. These infections, caused usually by Escherichia coli, are self-curing in a substantial number of cases, but the general recommendation is to treat with a 3 to 5 days antibiotic course with standard antibiotics. The treatment is nowadays consistent in most guidelines and it is strongly recommended to avoid broad-spectrum antibiotics such as quinolones and cephalosporins.

The second category of uncomplicated infection is pyelonephritis, an ascending infection of the kidney (upper urinary tract) without demonstrated risk factor. The treatment requires antibiotics penetrating the kidney parenchyma. In severe infections, the patient has to be hospitalised for intravenous antibiotic treatment and monitoring.

In a few number, there will even be a urosepsis (bloodstream infection), that could be life-threatening. These infections will be cured with the use of powerful antibiotics such as quinolones and cephalosporins. The treatment duration is usually 10 to 14 days.

Complicated UTI
Complicated urinary tract infections require a prompt management both in terms of surgical intervention (i.e. drainage) and a medical treatment with antibiotics. The patients with such infections have to be cared for in urological wards. The treatment is usually empiric and initiated with two antibiotics. Most of these patients will also require hospitalisation for several days, including support by critically ill patient unit in case of sepsis.

Sepsis is a life-threatening bloodstream carried infection often necessitating intensive care for antibiotic and supportive treatment in addition to surgical treatment. The urinary tract is one of the major sources of sepsis, especially in an elderly population.

Recent prevalence studies have shown an increase in severe complicated UTI and sepsis. Antibiotic treatment must be administrated promptly in order to reduce the risk of multiple organ failure leading to death.  

Catheter-associated infections are very common. After a few days of treatment with an indwelling catheter, the patient will be colonised by bacteria. Instrumentation of the colonised urinary tract is a risk factor for complicated UTI and sepsis.

All hospitals and health institutions must have guidelines on the management of patients with indwelling catheters. The EAU guidelines give clear recommendations resulting from a European and Asian consensus on the issue.5

Table 1 shows some of the main factors increasing the susceptibility of individuals to a UTI. These factors are either inherent to the patient (host), or related to secondary urological conditions and/or instrumentation, as defined by 
Table 2.

Table 3 gives a summary of the treatment recommendation of standard urinary tract infections.

Antibiotic prophylaxis
Antibiotic prophylaxis is one of several essential measures used to reduce the risk of infectious complication associated with urological surgery. The guidelines give a review of evidence-based knowledge and suggest a classification of the different procedures in relation to the level of expected peri-operative contamination level.

Procedures are grouped in clean, clean-contaminated, contaminated and dirty categories. The basic principle is that no antibiotics should be given in instances of clean operations and a single dose given in association with clean-contaminated operations, where the urinary tract or the bowel is open (i.e. urine deviation or use of bowel to divert urine through a urostomy or neo-bladder), and in contaminated procedures. There are evidently deviations from these basic principles. Combining these data, the EAU guidelines give recommendations as for the type of antibiotic, regimen and dose for each type of intervention.2

Future
There is a need for both clinical and basic science (molecular, genetic) research regarding UTI. For the forthcoming years, focus should be directed, among others, towards:

1. 
The development of a new classification of UTI and male genital infections for consistency in clinical classification and reporting and interpretation of clinical research. The ESIU is presently working on this issue3
2. 
The use of antibiotics and its relation to development of resistance microbes
3. 
The role of antibiotic prophylaxis in different types of urological interventions
4. 
The social and economic impacts of healthcare-associated infections
5. 
The development of new antimicrobial agents and alternative treatment approaches
6. 
Host-pathogen interaction and bacterial expre§§§§§ssion of aggressively
7. 
Genetic factors and the cause of susceptibility to infections in individuals.

Health authorities and research foundations have a crucial role in providing funds for research in this field as well as the development of new antibiotics and new treatment approaches. Innovating thinking is of utmost importance.

References

1. 
EAU Guidelines, edition presented at the 25th EAU Annual Congress, Barcelona 2010.www.uroweb.org/professional-resources/guidelines/online/
2. 
Grabe M et al. Guidelines on Urological Infections. In EAU Guidelines, edition presented at the 25th EAU Annual Congress, Barcelona 2010. www.uroweb.org/professional-resources/guidelines/online/
3. 
Naber KG et al (eds). Urogenital infections. International Consultations on Urological Diseases and European Association of Urology.
4. 
Foxman B. Am J Med 2002;113:5S-13S
5. 
Tenke P et al. Internat J of Antimicrob Agents 2008;31S:S68-S78
6. 
Marcel J-P et al. Clin Microbiol Infect 2008; 14:895-907
7. 
Bjerklund-Johansen T et al. Eur Urol 2007;51:1100-1112
8. 
ECDC-EMEA. Joint technical report; Sept 2009 (www.ecdc.europe.eu)