Contents:

CHAPTER 1 EXECUTIVE SUMMARY Scope of the analysis Insight into the urinary tract infections market Contributing experts Related reports Upcoming related reports CHAPTER 2 EPIDEMIOLOGY AND DISEASE BACKGROUND Etiology and symptoms Types of urinary tract infections Urethritis Cystitis Pyelonephritis Asymptomatic bacteriuria Acute urethral syndrome Complicated and uncomplicated urinary tract infections Pathogens Escherichia coli is the major UTI pathogen, although its role is less prominent in the hospital setting Data suggest that Escherichia coli is responsible for approximately half of all hospital UTI cases in the US and Canada Italian data suggest a slightly less prominent role for Escherichia coli in community-acquired disease Japanese data collected over a 20-year period suggest a less prominent role for Escherichia coli in Japan compared to Europe Risk groups General risk factors for urinary tract infection Risk factors specific to women Risk factors specific to men Recurrent UTI UTIs in children Hospital-acquired UTIs Epidemiological trends 150 million estimated cases of urinary tract infection worldwide each year US Robust data indicate over 10 million cases of UTI in the US in Differences in classification of urinary tract infection diagnoses across studies provides variation in estimated incidence UTI incidence in the US has increased by 10.7% between 1995 and Women of all ages in the US face a considerable risk of UTI, although incidence is highest in young women Study suggests over 11 million women in the US suffer from UTI each year Nosocomial UTI contributes significantly to the burden of UTI in the US Europe Nosocomial UTI represents a major problem in European hospitals UK UK data suggest a higher incidence of UTI in older women Low diagnosis rates may lead to conservative estimates of UTI incidence in the UK Nosocomial UTI represents a substantial problem in the UK Germany Each year over 150,000 UTIs are contracted in German hospitals France UTI incidence rate in France is comparable to the US and UK Italy Nosocomial UTI prevalence data in Italy is comparable with that of the UK No incidence data have been published for Japan or Spain Economic burden of urinary tract infections US expenditure on urinary tract infection up by 30% between 1994 and Inflation and population growth must be considered when considering UTI expenditure trends Expensive therapies may drive increasing expenditure for UTI in the US CHAPTER 3 PRESENTATION, DIAGNOSIS AND REFERRAL OPTIONS Overview Presentation Diagnosis Urine culture is the gold standard in the diagnosis, although most physicians rely on the presence of risk factors and/or dipstick testing Diagnosis of UTI can be challenging in the elderly and children Guidelines for the diagnosis and management of urinary tract infections are targeted at physicians across the seven major markets Physicians have different perceptions of the level of bacteriuria that is clinically significant Cost and time to results limits the use of urine culture to complicated urinary tract infection cases only Physical examination Urine samples Urine appearance Urine dipstick testing Microscopy Gram stain Urine culture Imaging techniques Ultrasound Nuclear scans Magnetic resonance imaging or computed tomography X-rays Cystoscopy Referral Primary care physicians treat most urinary tract infections, although a referral may be made in complicated or recurrent cases Suggestion of complicated urinary tract infection or an underlying urologic problem typically lead to hospitalization Nosocomial urinary tract infections are treated by the attending physician US organizations are working to educate both patients and physicians on urinary tract infections CHAPTER 4 CURRENT TREATMENT OPTIONS AND TRENDS Market overview Treatment guidelines Treatment options Penicillins Amoxicillin Co-amoxiclav Fluoroquinolones Ciprofloxacin Levofloxacin Ofloxacin Norfloxacin Gatifloxacin Trimethoprim products Trimethoprim Trimethoprim-sulfamethoxazole Carbapenems Imipenem and cilastatin Doripenem Older drugs Nitrofurantoin Fosfomycin FDA notification of tendinitis and tendon rupture risk for fluoroquinolones Resistance of bacterial pathogens to urinary tract infection therapies Growing levels of bacterial resistance have rendered a number of leading urinary tract infection drugs ineffective in many regions Increasing fluoroquinolone resistance threatens effectiveness of therapies and future treatment choices Rapidly decreasing fluoroquinolone susceptibilities threaten first-line treatment choices for UTI across the five major EU markets Resistance data suggest that aminopenicillins are an ineffective treatment option for UTIs across the five major EU markets Falling fluoroquinolone susceptibility for Escherichia coli bacteria is a significant problem across the five major EU markets Up to a quarter of Escherichia coli isolates in hospitals in some areas of the US and Canada are resistant to fluoroquinolones Japanese study suggests similar problems with Escherichia coli resistance to fluoroquinolones as identified in the US and Europe Susceptibility and resistance data suggests more prominent future roles for nitrofurantoin and fosfomycin French data highlight the problems of prescribing amoxicillin and trimethoprim-sulfamethoxazole and the potential usefulness of fosfomycin Spanish data highlight the potential efficacy of nitrofurantoin and fosfomycin in the treatment of ESBL-producing strains of Escherichia coli Emerging pathogens Extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus pose an increasingly potent risk for UTIs Treatment choice acy against pathogens is highly influential in treatment choice for urinary tract infections, although safety and cost also play a role Treatment by site of infection Cystitis Urethritis Pyelonephritis CHAPTER 5 UNMET NEEDS AND NEW DEVELOPMENTS Recently approved therapies and drugs in development for urinary tract infections New drug approvals for uncomplicated urinary tract infections have been sparse over the past 5 years as the impact of generics grows Doripenem Sitafloxacin Prulifloxacin Higher dose, short-course regimen of Levofloxacin has received FDA approval Pipeline drugs in late-stage development NXL104/ceftazidime Finafloxacin Unmet needs and future developments Treatment satisfaction Variation in resistance patterns may be highly influential in the levels of UTI treatment satisfaction expressed by physicians Unmet needs in the diagnosis of urinary tract infections Education of physicians remains an issue despite widespread guideline publication Unmet needs in the treatment of urinary tract infections Surveillance of antimicrobial resistance patterns and development of novel therapies are paramount to maintaining effective treatment options for UTIs Future developments Researchers at UCLA are developing point-of-care technology for the detection of urinary tract bacterial pathogens US researchers have recently suggested strategies for developing new virulence-targeted urinary tract infection therapies BIBLIOGRAPHY Journal papers Websites Other APPENDIX A Contributing experts APPENDIX B List of Tables Table 1: Pathogens responsible for urinary tract infections in the community and hospital setting Table 2: Pathogens isolated most frequently among community outpatients with a urinary tract infection in Brescia, Italy, 2002- Table 3: Pathogens isolated from urine of patients with a catheter-associated urinary tract infection in Brescia, Italy, 2002- Table 4: Pathogens most frequently isolated among hospital inpatients with a urinary tract infection in Brescia, Italy Table 5: Estimated number of visits to physicians for UTI in the US, Table 6: Number of physician visits for urinary tract infection (site not specified) in the US, 1995- Table 7: Number of physician visits for cystitis and other disorders of the bladder in the US, 1995- Table 8: Number of physician visits for urinary tract infection (site not specified) and cystitis and other bladder disorders in the US, 1995- Table 9: Annual incidence of urinary tract infection in the UK Table 10: US expenditure on urinary tract infection, 1994- Table 11: Expenditure on female and male urinary tract infection in the US and share of costs by site of service, Table 12: Average annual spending and use of outpatient prescription drugs for treatment of UTI (male and female), 1996- Table 13: Volume sales (standard units, 000s) for drugs used to treat urinary tract infections (UTIs) in the US and five major EU markets, Table 14: Value sales ($000s) for drugs used to treat urinary tract infections (UTIs) in the US and five major EU markets, Table 15: Aminopenicillin susceptibility results for Escherichia coli isolates in the five major EU markets, 2002- Table 16: Fluoroquinolone susceptibility results for Escherichia coli isolates in the five major EU markets, 2002- Table 17: Third generation cephalosporin susceptibility results for E. coli isolates in the five major EU markets, 2002- Table 18: Resistance rates of outpatient Escherichia coli isolates to urinary tract infection drugs in the US and Canada, April 2003-June Table 19: Antimicrobial resistance of Escherichia coli isolates from women with community and hospital acquired urinary tract infections in Rennes, France Table 20: Antimicrobial susceptibility of Escherichia coli in 15 laboratories across nine regions in Spain, March-July 2002 Table 21: Antimicrobial resistance rates of Escherichia coli isolates in 15 laboratories across nine regions in Spain, February-June 2006 List of Figures Figure 1: US expenditure on urinary tract infection (UTI), 1994- Figure 2: Volume sales (standard units, 000s) for drugs used to treat urinary tract infections (UTIs) in the US and five major EU markets, 2007 Figure 3: Value sales ($000s) for drugs used to treat urinary tract infections (UTIs) in the US and five major EU markets, Figure 4: Aminopenicillin susceptibility results for Escherichia coli isolates in the five major EU markets, 2002- Figure 5: Fluoroquinolone susceptibility results for Escherichia coli isolates in the five major EU markets, 2002- Figure 6: Third generation cephalosporin susceptibility results for E. coli isolates in the five major EU markets, 2002-