EDITORIAL URRENT C OPINION
Urinary tract infections: a common but fascinating infection, with still many research questions Suzanne E. Geerlings
Several reviews in this issue concern urinary tract infections (UTIs), which are one of the most common bacterial infections. The self-reported annual incidence of UTI in women is 12%, and by the age of 32 years, 50% of all women report having had at least one UTI. For me, the pathogenesis always seemed to be clear: the two main steps are colonization and adherence of uropathogens in the urinary tract. Normally, bacteria can live around the urethra and colonize the urine, but are washed out during micturition. Disturbances in this process as, for example, urogenital manipulations or medical interventions, facilitate the movement of bacteria to the urethra and are therefore well known risk factors to develop a UTI. In this issue of Current Opinion Infectious Diseases, two review papers – one by the group of Catharina Svanborg [1] and one by the group of Scott Hultgren [2] – provide very interesting new insights into the pathogenesis of (recurrent) UTI. The studies presented in these papers make clear that it is not only colonization and adherence, but more complex mechanisms, which might play a role in understanding the microorganism–host interaction in the different steps of the pathogenesis of a UTI. In the first review, the authors distinguish exaggerated innate immune responses that drive pathology from attenuated responses that favor protection and highlight the genetic basis for these extremes, based on knock-out mice and patients. They describe that molecular information is now available to improve diagnosis and to assess the risk for chronic sequels like renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation. It seems that different genetic mechanisms are present in the development of lower and upper UTIs. In the second review, the investigators discuss the results of studies to understand the pathogenesis of recurrent UTIs. Animal studies show that chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodeling that sensitizes the host to a new UTI. Future studies should be directed towards understanding how the innate immune response changes as a result bladder mucosal remodeling in previously www.co-infectiousdiseases.com
infected mice, and validate these findings in human clinical specimens. This is a very interesting concept, since epidemiological studies among young healthy women with lower UTI (cystitis) have demonstrated that the infection recurs in 25% of women within 6 months after the first UTI. Although the risk of a second UTI is strongly influenced by sexual behavior, women with a first UTI caused by Escherichia coli are more likely than those with another causative microorganism of their first UTI to have a second UTI within 6 months. After reading these reviews, it is clear that the pathogenesis of such a common infection as a UTI remains fascinating, and the results of these studies are very important in unraveling all the steps in the pathogenesis, because they might be new targets for prophylactic or therapeutic interventions. Considering the clinical presentation of a UTI, we always make a differentiation between uncomplicated and complicated UTIs, because the risks for complications or treatment failure are increased in patients with a complicated UTI. This distinction has been used to guide the choice and duration of antimicrobial treatment, with broader-spectrum agents and longer courses of treatment often recommended for persons with complicated UTIs. However, this classification scheme does not account for the diversity of complicated UTIs. Of course, the clinical presentation remains the cornerstone of diagnosis of UTI, but in clinical practice, it is not always possible during the first presentation of a patient to differentiate between an acute prostatitis, pyelonephritis, or urosepsis. Since the empirical antimicrobial treatment for these diseases is the
Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands Correspondence to Suzanne E. Geerlings, Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, room F4-214, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5666130; fax: +31 20 6972286; e-mail: [email protected] Curr Opin Infect Dis 2015, 28:86–87 DOI:10.1097/QCO.0000000000000133 Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Urinary tract infections Geerlings
same, they can be summarized as febrile UTI. In this issue of Current Opinion Infectious Diseases Stalenhoef et al. [3] describe the optimal diagnostic and treatment strategies for patients with febrile UTI in the Emergency Department. They discuss that research suggests overdiagnosis, and therefore overtreatment of UTI in the ED, especially in the elderly. The data even show that blood cultures are of limited additional diagnostic value in most cases of febrile UTI and that an immediate ultrasonography of the urinary tract is only necessary in special patient groups. I hope that the readers of this review will change their practice, because the studies make clear that for some patient groups, a strategy with less diagnostics (and therefore lower costs) is safe. Another differentiation of UTIs is between community and hospital-acquired UTIs. UTIs in patients acquired within the hospital are generally complicated UTIs. More often, uropathogens other than Escherichia coli are the causative microorganisms. Furthermore, more resistant pathogens are cultured compared to community-acquired UTI. Infections caused by microorganisms with extended-spectrum beta lactamase (ESBL) are also more frequently present in hospital compared to communityacquired UTI. Due to the increase in technical possibilities, renal transplant recipients are a growing group of patients, who have a complicated and also hospital-acquired UTI. They have anatomical abnormalities, use immunosuppressive drugs, and often have temporarily urinary catheters. In this issue of Current Opinion Infectious Diseases, Singh et al. [4] have written a review about this special group of patients. Studies about asymptomatic bacteriuria (ASB), which is defined as the presence of a positive urine culture collected from a patient without symptoms of a UTI and is a common but usually benign phenomenon in women, show that ASB might have other implications in renal transplant recipients. On the one hand, renal transplant recipients use immunosuppressive agents and their immune activation
is disturbed, which favor long-term bacteriuria without inflammation or pathology. On the other hand, persistent ASB has been associated with the development of acute rejection and acute allograft pyelonephritis, but the available data suggest that treatment of ASB is not very effective. These results make clear that more research in this increasing group of patients is urgently warranted. In conclusion, UTIs are a very nice example of the microorganism–host interaction to understand the development of infectious diseases. But also from a clinical point of view, they are very interesting since many different kinds of presentations exist, as, for example, in the ED and in special patient groups as renal transplant recipients. I like to thank all authors for their contributions. After reading these interesting reviews, it is clear that still much research has to be done for this common infection, because many questions remain. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES 1. 2.
3. 4.
Godaly G, Ambite I, Svanborg C. Innate immunity and genetic determinants of uninary tract infection susceptibility. Curr Opin Infect Dis 2015; 28:88–96. O’Brien VP, Hannan TJ, Schaeffer AJ, Hultgren SJ. Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection. Curr Opin Infect Dis 2015; 28:97–105. Stalenhoef JE, van Dissel JT, van Nieuwkoop C. Febrile urinary tract infection in the emergency room. Curr Opin Infect Dis 2015; 28:106–111. Singh R, Geerlings SE, Bemelman FJ. Asymptomatic bacteriuria and urinary tract infections among renal allograft recipients. Curr Opin Infect Dis 2015; 28:112–116.
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
87
Urinary tract infections: a common but fascinating infection, with still many research questions Suzanne E. Geerlings
Several reviews in this issue concern urinary tract infections (UTIs), which are one of the most common bacterial infections. The self-reported annual incidence of UTI in women is 12%, and by the age of 32 years, 50% of all women report having had at least one UTI. For me, the pathogenesis always seemed to be clear: the two main steps are colonization and adherence of uropathogens in the urinary tract. Normally, bacteria can live around the urethra and colonize the urine, but are washed out during micturition. Disturbances in this process as, for example, urogenital manipulations or medical interventions, facilitate the movement of bacteria to the urethra and are therefore well known risk factors to develop a UTI. In this issue of Current Opinion Infectious Diseases, two review papers – one by the group of Catharina Svanborg [1] and one by the group of Scott Hultgren [2] – provide very interesting new insights into the pathogenesis of (recurrent) UTI. The studies presented in these papers make clear that it is not only colonization and adherence, but more complex mechanisms, which might play a role in understanding the microorganism–host interaction in the different steps of the pathogenesis of a UTI. In the first review, the authors distinguish exaggerated innate immune responses that drive pathology from attenuated responses that favor protection and highlight the genetic basis for these extremes, based on knock-out mice and patients. They describe that molecular information is now available to improve diagnosis and to assess the risk for chronic sequels like renal malfunction, hypertension, spontaneous abortions, dialysis and transplantation. It seems that different genetic mechanisms are present in the development of lower and upper UTIs. In the second review, the investigators discuss the results of studies to understand the pathogenesis of recurrent UTIs. Animal studies show that chronic bladder inflammation during prolonged bacterial cystitis in mice causes bladder mucosal remodeling that sensitizes the host to a new UTI. Future studies should be directed towards understanding how the innate immune response changes as a result bladder mucosal remodeling in previously www.co-infectiousdiseases.com
infected mice, and validate these findings in human clinical specimens. This is a very interesting concept, since epidemiological studies among young healthy women with lower UTI (cystitis) have demonstrated that the infection recurs in 25% of women within 6 months after the first UTI. Although the risk of a second UTI is strongly influenced by sexual behavior, women with a first UTI caused by Escherichia coli are more likely than those with another causative microorganism of their first UTI to have a second UTI within 6 months. After reading these reviews, it is clear that the pathogenesis of such a common infection as a UTI remains fascinating, and the results of these studies are very important in unraveling all the steps in the pathogenesis, because they might be new targets for prophylactic or therapeutic interventions. Considering the clinical presentation of a UTI, we always make a differentiation between uncomplicated and complicated UTIs, because the risks for complications or treatment failure are increased in patients with a complicated UTI. This distinction has been used to guide the choice and duration of antimicrobial treatment, with broader-spectrum agents and longer courses of treatment often recommended for persons with complicated UTIs. However, this classification scheme does not account for the diversity of complicated UTIs. Of course, the clinical presentation remains the cornerstone of diagnosis of UTI, but in clinical practice, it is not always possible during the first presentation of a patient to differentiate between an acute prostatitis, pyelonephritis, or urosepsis. Since the empirical antimicrobial treatment for these diseases is the
Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands Correspondence to Suzanne E. Geerlings, Department of Internal Medicine, Division of Infectious Diseases, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, room F4-214, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5666130; fax: +31 20 6972286; e-mail: [email protected] Curr Opin Infect Dis 2015, 28:86–87 DOI:10.1097/QCO.0000000000000133 Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Urinary tract infections Geerlings
same, they can be summarized as febrile UTI. In this issue of Current Opinion Infectious Diseases Stalenhoef et al. [3] describe the optimal diagnostic and treatment strategies for patients with febrile UTI in the Emergency Department. They discuss that research suggests overdiagnosis, and therefore overtreatment of UTI in the ED, especially in the elderly. The data even show that blood cultures are of limited additional diagnostic value in most cases of febrile UTI and that an immediate ultrasonography of the urinary tract is only necessary in special patient groups. I hope that the readers of this review will change their practice, because the studies make clear that for some patient groups, a strategy with less diagnostics (and therefore lower costs) is safe. Another differentiation of UTIs is between community and hospital-acquired UTIs. UTIs in patients acquired within the hospital are generally complicated UTIs. More often, uropathogens other than Escherichia coli are the causative microorganisms. Furthermore, more resistant pathogens are cultured compared to community-acquired UTI. Infections caused by microorganisms with extended-spectrum beta lactamase (ESBL) are also more frequently present in hospital compared to communityacquired UTI. Due to the increase in technical possibilities, renal transplant recipients are a growing group of patients, who have a complicated and also hospital-acquired UTI. They have anatomical abnormalities, use immunosuppressive drugs, and often have temporarily urinary catheters. In this issue of Current Opinion Infectious Diseases, Singh et al. [4] have written a review about this special group of patients. Studies about asymptomatic bacteriuria (ASB), which is defined as the presence of a positive urine culture collected from a patient without symptoms of a UTI and is a common but usually benign phenomenon in women, show that ASB might have other implications in renal transplant recipients. On the one hand, renal transplant recipients use immunosuppressive agents and their immune activation
is disturbed, which favor long-term bacteriuria without inflammation or pathology. On the other hand, persistent ASB has been associated with the development of acute rejection and acute allograft pyelonephritis, but the available data suggest that treatment of ASB is not very effective. These results make clear that more research in this increasing group of patients is urgently warranted. In conclusion, UTIs are a very nice example of the microorganism–host interaction to understand the development of infectious diseases. But also from a clinical point of view, they are very interesting since many different kinds of presentations exist, as, for example, in the ED and in special patient groups as renal transplant recipients. I like to thank all authors for their contributions. After reading these interesting reviews, it is clear that still much research has to be done for this common infection, because many questions remain. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES 1. 2.
3. 4.
Godaly G, Ambite I, Svanborg C. Innate immunity and genetic determinants of uninary tract infection susceptibility. Curr Opin Infect Dis 2015; 28:88–96. O’Brien VP, Hannan TJ, Schaeffer AJ, Hultgren SJ. Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection. Curr Opin Infect Dis 2015; 28:97–105. Stalenhoef JE, van Dissel JT, van Nieuwkoop C. Febrile urinary tract infection in the emergency room. Curr Opin Infect Dis 2015; 28:106–111. Singh R, Geerlings SE, Bemelman FJ. Asymptomatic bacteriuria and urinary tract infections among renal allograft recipients. Curr Opin Infect Dis 2015; 28:112–116.
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
87
