Amit Akirov, MD 

February 24, 2021

MS is the most common neurological disease in young adults with a prevalence of 1 in every 1000 people in the US.^1,2 It is associated with at an increased risk for infections, including UTIs, respiratory, skin, and opportunistic infections. Data suggest that following MS diagnosis, infections are the most frequent comorbidities, reported in 80% of patients.³  

Epidemiology

About 50% to 80% of patients with MS report urinary-related symptoms, which are associated with an increased risk for UTI, morbidity and mortality.^2-5 In a study of over 15,000 patients with MS from the US and the UK, the risk for urinary or renal infections was 2-fold higher among patients with MS, compared with patients without MS.⁶  Furthermore, patients with MS may be more likely to develop complications secondary to severe infections, as the risk for hospitalization due to infection was also found to be significantly higher in this group.

The most common bacteria responsible for UTIs among patients with MS were Escherichia coli, Group B Streptococcus, Klebsiella pneumoniae, Proteus mirabilis, and coagulase negative Staphylococcus.¹

Multiple sclerosis is associated with an increased risk for neurogenic bladder secondary to a discoordination among the brainstem centers and the sacral parts of the spinal cord.⁴ Bragadin and colleagues reported a high prevalence of lower urinary tract symptoms among patients with MS, including storage or voiding symptoms, associated with an increased risk for UTIs.⁷

Patients with MS with significant disability, especially those who are independent and require assistance for personal activities of daily living, experience greater difficulties with maintaining adequate hydration, regular bathing and perineal hygiene. Due to urinary stasis, high bladder pressures, bladder stones, and catheters, they are more prone to UTIs.⁸

Morbidity and Mortality

Immune response activation following infection was suggested to increase the risk for MS relapse during UTIs.¹ While there are no studies to explore the specific risk for relapse following UTI, the possibility of an increased risk of relapse following UTI was suspected based on studies of other types of infections. However, a recent literature search for publications in English and French, performed as part of clinical practice guidelines on UTI and MS from the French Multiple Sclerosis Society, concluded that UTIs are not associated with an increased risk for MS relapse or prolonged disability aggravation. On the other hand, febrile UTIs were found to be associated with an increased risk for transient worsening disability of patients with MS.⁹ A study by Fitzgerald and colleagues showed that UTIs at the time of a suspected MS relapse are relatively uncommon in both a hospitalized as well as ambulatory patient population.¹⁰

Urinary tract infection is a major cause for hospitalization in patients with MS, and is responsible for about 30% to 50% of hospitalizations in these patients.¹ Patients with MS who are hospitalized for UTIs are more often men, older, with progressive MS and significant disability. 

Furthermore, a history of UTI was found to be associated with decreased survival, with data suggesting UTI was the main cause of death among patients with MS, contributing to 8% of deaths in this patient group, compared with only 2% of general population deaths.  The increase in deaths due to UTI was greater for MS deaths in men than in women, although UTIs had an important impact on MS deaths in both sexes.¹¹ However, others claimed that this is most likely a reflection of MS severity rather than a causal association.³

Diagnosis

The diagnosis of UTI may be difficult in patients with MS. While the infection may be associated with clinical symptoms such as fever, urgency, increased frequency, incontinence, and hematuria, MS patients do not necessarily have the classical symptoms described in the general population.¹ Furthermore, urgency, frequency modification, and incontinence may result from MS dysfunction and be present in patients with MS who do not have an infection.

The gold standard for the UTI diagnosis is urine culture of samples collected either from a clean-catch midstream sample, an indwelling urethral catheter, or a suprapubic aspiration from a suprapubic catheter.¹ Additionally, the Acute Cystitis Symptom Score, a validated self-reported questionnaire for the diagnosis of acute cystitis in women, is a sensitive and a specific tool to differentiate UTI from other urogenital disorders.¹²

Management

• Asymptomatic bacteriuria – Studies have shown no clinical efficacy of pharmacologic treatment of asymptomatic bacteriuria inpatients with MS. Treatment of asymptomatic bacteriuria may induce resistant bacterial strains; therefore, it is considered exceptionally for patients with recurrent acute UTIs, prior to handling of the UTI, pregnancy, or immunosuppression.¹
• Symptomatic UTI – Broad-spectrum antibiotics, depending on microbial susceptibility local patterns, are recommended for patients with MS diagnosed with UTI and can later be adjusted based on the urine culture result.¹³ Corticosteroid therapy should not be discontinued in patients with MS relapse who may have UTI.¹
• Prophylaxis of UTI – Prophylactic antibiotics, bladder irrigation, and cranberry extract were not efficacious in the prevention of UTI in patients with MS.¹ Additional studies are required to provide data on the efficacy of probiotics. For patients with neurogenic bladder, catheter type choice and pharmacological treatment of neurogenic bladder with oxybutynin, tolterodine, trospium or propiverine may reduce the risk for UTIs.¹³ In refractory cases, botulinum toxin injection into the detrusor muscle may be considered.

While the risk of contracting a UTI during treatment of MS has not been specifically studied, there are several studies to suggest a potential impact of the medications used to treat MS on the risk for UTIs. A 2016 study by Wilkenmann and colleagues reported that long-term treatment with interferons or glatiramer acetate present a low risk of infections, while natalizumab, dimethyl fumarate, and fingolimod were associated with an increased risk for opportunistic infections, including UTIs.¹⁴ Data indicated that the risk for serious infections among patients with MS who were treated with rituximab was higher, compared with natalizumab and fingolimod, and this remained significant in comparisons with patients treated with interferon beta and glatiramer acetate.¹⁵

Awareness of UTI among patients with MS is vital in early diagnosis, management, and infection prophylaxis in this population. “UTI represents a great risk and concern in MS patients. The high prevalence, hospitalization rate, and mortality rate of UTI in MS is worrying, such as the cause-consequence relationship between UTIs and the use of corticosteroids in outbreaks,” according to Medeiros Junior and colleagues.¹ “Thus, further studies are needed to thoroughly analyze each nuance of this important comorbidity for [patients with] MS.”¹

References

1. Medeiros Junior WLG, Demore CC, Mazaro LP, et al. Urinary tract infection in patients with multiple sclerosis: An overview. Mult Scler Relat Disord. 2020;46:102462. doi:10.1016/j.msard.2020.102462

2. Nicholas R, Young C, Friede T. Bladder symptoms in multiple sclerosis: a review of pathophysiology and management. Expert Opin Drug Saf. 2010;9(6):905-915. doi:10.1517/14740338.2010.501793

3. Jick SS, Li L, Falcone GJ, Vassilev ZP, Wallander MA. Epidemiology of multiple sclerosis: results from a large observational study in the UK. J Neurol. 2015;262(9):2033-2041. doi:10.1007/s00415-015-7796-2

4. Fowler CJ, Panicker JN, Drake M, et al. A UK consensus on the management of the bladder in multiple sclerosis. Postgrad Med J. 2009;85(1008):470-477. doi:10.1136/jnnp.2008.159178

5. Nikseresht A, Salehi H, Foroughi AA, Nazeri M. Association between urinary symptoms and urinary tract infection in patients with multiple sclerosis. Glob J Health Sci. 2016;8(4):253-259. doi:10.5539/gjhs.v8n4p253

6. Persson R, Lee S, Yood MU, et al. Infections in patients diagnosed with multiple sclerosis: A multi-database study. Mult Scler Relat Disord. 2020;41:101982. doi:10.1016/j.msard.2020.101982

7. Bragadin MM, Motta R, Uccelli MM, et al. Lower urinary tract dysfunction in patients with multiple sclerosis: A post-void residual analysis of 501 cases. Mult Scler Relat Disord. 2020;45:102378. doi:10.1016/j.msard.2020.102378

8. Li V, Barker N, Curtis C, et al. The prevention and management of hospital admissions for urinary tract infection in patients with multiple sclerosis. Mult Scler Relat Disord. 2020;45:102432. doi:10.1016/j.msard.2020.102432

9. Donzé C, Papeix C, Lebrun-Frenay C.  Urinary tract infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society. Rev Neurol (Paris). 2020;176(10):804-822. doi:10.1016/j.neurol.2020.02.011

10. Fitzgerald KC, Cassard LA, Fox SR, Probasco JC, Cassard SD, Mowry EM. The prevalence and utility of screening for urinary tract infection at the time of presumed multiple sclerosis relapse. Mult Scler Relat Disord. 2019;35:61-66. doi:10.1016/j.msard.2019.06.038

11. Harding K, Zhu F, Alotaibi M, Duggan T, Tremlett H, Kingwell E. Multiple cause of death analysis in multiple sclerosis: A population-based study. Neurology. 202094(8):e820-e829. doi:10.1212/WNL.0000000000008907

12. Alidjanov JF, Naber KG, Abdufattaev UA, Pilatz A, Wagenlehner FME. Reevaluation of the Acute Cystitis Symptom Score, a self-reporting questionnaire. Part I. Development, diagnosis and differential diagnosis. Antibiotics. 2018;7(1):6. doi:10.3390/antibiotics7010006

13. European Association of Urology. Urological infections. https://uroweb.org/guideline/urological-infections/. Accessed February 20, 2020.

14. Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016;12(4):217-233. doi:10.1038/nrneurol.2016.21

15. Luna G, Alping P, Burman J, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol. 2020;77(2):184-191. doi:10.1001/jamaneurol.2019.3365

Urinary Tract Infection in Multiple Sclerosis: Risk, Diagnosis, and Management – Neurology Advisor