Recurrent urinary tract infections (UTIs) present a significant health issue for women, with uncomplicated UTI occurring in at least 50% of women, and about 30% experiencing recurrent UTI (rUTI).1–3
Although there are multiple definitions for rUTI, the American Urogynecological Society published a best-practice statement for rUTI this year (2018) with rUTI defined as “at least 2 culture-proven episodes in 6 months, or at least 3 in 1 year.”4 Of those women suffering rUTI, nearly 62% experienced between 4 and 10 UTIs per year.1
E. coli is known to cause the majority (70% – 95%) of community acquired UTIs, and rUTI often involves the same bacterial strain as the initial UTI. In 68% – 77% of cases, the bacterial strains identified in rUTI are indistinguishable from those in previous infections. However, resistant organisms and pathogens other than E. coli are very likely to be involved in rUTI.3,4
Identification of bacteria in rUTI can furnish valuable insight into the mode of recurrence. If the strains in rUTI are the same as in the initial infection, it suggests either pathogen persistence or reinfection from the gut, from the vagina, or from reservoirs that may exist within the bladder. A persistent infection implies incomplete treatment of the initial infection, which can occur through failure of patient compliance or through presence of resistant pathogens.5
There are at least two possible explanations for detection of different bacterial strains in rUTI. One is a new infection with another bacterial strain from the external environment. Another is for reinfection from the gut to cause rUTI with a different strain. De novo resistance, albeit from the same bacterial strain, has been shown to arise within an individual patient.5,6 Although prophylaxis can reduce the incidence of rUTI, it also increases the probability of antibiotic resistant pathogens.7
As a practical matter, relapses can be difficult to distinguish from recurrences. Pathogens may exist in sterile urine at levels too low to detect by culture, but at sufficient levels to sustain UTI.1 Although culture can detect pathogens other than E. coli (such as Klebsiella, Staphylococcus saprophyticus, Enterococcus faecalis, and Streptococcus agalactiae), standard urine culture has been optimized for detection of E. coli. Molecular methods, including PCR and DNA sequencing, have demonstrated that standard urine culture techniques do not detect all pathogens involved in UTI.4
Accurate and sensitive identification of uropathogens, along with antimicrobial sensitivity testing by genotyping and phenotyping, can be used to guide treatment of both UTI and rUTI. Treatment compliance and clearance of the initial infection can be tested using more sensitive detection and identification methods, such as PCR. Antibiotic resistance testing, by both genotyping and phenotyping, provides information on selection of the most effective antibiotics. Use of both genotyping and phenotyping for antibiotic resistance testing offers more complete information, especially for polymicrobial infections in which one pathogen can confer resistance on another.
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1. Wagenlehner, F., Wullt, B., Ballarini, S., Zingg, D. & Naber, K. G. Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT). Expert Rev Pharmacoecon Outcomes Res 18, 107–117 (2018).
2. Hooton, T. M., Roberts, P. L., Cox, M. E. & Stapleton, A. E. Voided Midstream Urine Culture and Acute Cystitis in Premenopausal Women. N Engl J Med 369, 1883–1891 (2013).
3. Gupta, K. & Trautner, B. W. Diagnosis and management of recurrent urinary tract infections in non-pregnant women. BMJ 346, (2013).
4. Brubaker, L., Carberry, C., Nardos, R., Carter-Brooks, C. & Lowder, J. L. American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Medicine & Reconstructive Surgery Publish Ahead of Print, (2018).
5. Silverman, J. A., Schreiber, H. L., Hooton, T. M. & Hultgren, S. J. From Physiology to Pharmacy: Developments in the Pathogenesis and Treatment of Recurrent Urinary Tract Infections. Curr Urol Rep 14, 448–456 (2013).
6. Kao, C.-Y., Chen, J.-W., Liu, T.-L., Yan, J.-J. & Wu, J.-J. Comparative Genomics of Escherichia coli Sequence Type 219 Clones From the Same Patient: Evolution of the IncI1 blaCMY-Carrying Plasmid in Vivo. Front Microbiol 9, (2018).
7. Fisher, H. et al. Continuous low-dose antibiotic prophylaxis for adults with repeated urinary tract infections (AnTIC): a randomised, open-label trial. Lancet Infect Dis (2018). doi:10.1016/S1473-3099(18)30279-2