Case Reports

Recurrent Multidrug Resistant Urinary Tract Infections in Geriatric Patients

Fed Pract. 2014 July;31(7):32-35

Author(s):

Four case studies are presented, which suggest the safety and efficacy of methenamine hippurate to treat complicated urinary tract infections in geriatric patients.

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References

1. Foxman B. Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. Am J Med. 2002;113(suppl 1A):5S-13S.

2. Kamel HK. Managing urinary tract infections: Guide for nursing home practitioners. Ann of Long Term Care. 2005;13(9):21-28.

3. Blix HS, Røed J, Sti MO. Large variation in antibacterial use among Norwegian nursing homes. Scand J Infect Dis. 2007;39(6-7):536-541.

4. Nicolle LE. Asymptomatic bacteruria in diabetic women. Diabetes Care. 2000;23(6):722-723.

5. Rhoads J, Clayman A, Nelson S. The relationship of urinary tract infections and falls in a nursing home. Director. 2007;15(1):22-26.

6. Rodhe N, Mølstad S, Englund L, Svärdsudd K. Asymptomatic bacteriuria in a population of elderly residents living in a community setting: Prevalence, characteristics and associated factors. Fam Pract. 2006;23(3):303-307.

7. Woodford HJ, George J. Diagnosis and management of urinary tract infection in hospitalized older people. J Am Geriatr Soc. 2009;57(1):107-114.

8. Levison ME, Kaye D. Treatment of complicated urinary tract infections with an emphasis on drug-resistant gram-negative uropathogens. Curr Infect Dis Rep. 2013;15(2):109-115.

9. Miller LG, Tang AW. Treatment of uncomplicated urinary tract infections in an era of increasing antimicrobial resistance. Mayo Clin Proc. 2004;79(8):1048-1053.

10. Nicoletti J, Kuster SP, Sulser T, et al. Risk factors for urinary tract infections due to ciprofloxacin-resistant Escherichia coli in a tertiary care urology department in Switzerland. Swiss Med Wkly. 2010;140:w13059.

11. Nicolle LE. Urinary tract infection in geriatric and institutionalized patients. Curr Opin Urol. 2002;12(1):51-55.

12. Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010;7(12):653-660.

13. Spellberg B, Guidos R, Gilbert D, et al; Infectious Diseases Society of America. The epidemic of antibiotic-resistant infections: A call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(2):155-164.

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20. Drugs.com. Methenamine (systemic). http://www.drugs.com/mmx/methenamine-hippurate.html?printable=1. Updated March 28, 2000. Accessed June 17, 2014.

21. Lee BSB, Simpson JM, Craig JC, Bhuta T. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012;10:CD003265.

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Urinary tract infections (UTIs) account for 8.3 million doctor visits, 1 million emergency department (ED) visits, and 100,000 hospitalizations annually, with an estimated cost of $1 billion annually in the U.S.¹ Urnary tract infections are the most common bacterial infections found in nursing home residents, accounting for 50% of reported infections in Norwegian nursing homes, 30% to 50% in U.S. nursing homes, and 25% of all infections in the noninstitutionalized elderly in the U.S.^2-4In the geriatric population, UTIs are often found incidentally at the time of hospitalization for other admitting diagnoses, such as mentation changes or falls.⁵Asymptomatic pyuria was found in 14.8% of community residents aged ≥ 80 years.⁶ Woodford and colleague found that 37% of geriatric patients admitted through an ED diagnosed with UTIs had no dysuria or urinary frequency.⁷

The incidence of UTIs is higher in the elderly due to genitourinary abnormalities, urolithiasis, dehydration, and diabetes, among other causes. These are considered complicated UTIs, defined as those in the presence of factors that predispose to persistent or relapsing infection, such as foreign bodies (calculi, indwelling catheters), obstruction, renal failure, and urinary retention.⁸

In elderly men, prostate enlargement causes bladder outlet obstruction predisposing them to urinary stasis and UTIs.² Urinary tract infections are prone to recur when urinary tract abnormalities persist or treatment ineffectively eradicates resistant bacteria. Urinary tract infections are considered recurrent when ≥ 3 occur within 1 year or ≥ 2 occur in a 6-month period. The anticipated recurrence rate of complicated UTIs at 4 to 6 weeks following completion of therapy is 40% to 60%.⁴

Current practice standards recommend not treating asymptomatic UTIs to avoid contributing to bacterial antibiotic resistance.⁹ The frequent use of antibiotics, such as quinolones, which are increasingly inactive against these organisms, contributes to the overgrowth of bacteria in the gastrointestinal tract and their appearance in the genitourinary tract.^10,11

As UTI-causing bacteria become more resistant to available antibiotics, the need to explore new strategies for managing UTIs is clear.¹² The spread of extended spectrum beta-lactamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE), among other emerging bacterial resistance factors, present increasing treatment cost and poor patient outcomes. This challenge is occurring at a time when the discovery and development of new anti-infective agents is slowing down.¹³

Methenamine hippurate, a drug developed 60 years ago, offers an option to the bacterial resistance challenge for select patients with recurrent, multidrug reistant (MDR) UTIs. The action of methenamine is novel—it converts to formaldehyde when it comes in contact with acidic urine. Formaldehyde destroys Gram-positive organisms by lysis of the bacterial cell wall. Gram-negative bacteria are destroyed when formaldehyde denatures enzyme proteins involved in vital metabolic processes.¹⁴ Formaldehyde in dilute solutions has the ability to inhibit cell division, and higher levels are bactericidal.¹⁵ Exposure to formaldehyde for ≥ 2 hours is necessary to achieve bacteriostatic effects.¹⁶

The European Commission Scientific Committee on Health and Environmental Risk reported that in patients receiving up to 4,000 mg/d methenamine for preventive long-term treatment of UTIs, no adverse effects (AEs) were noted (Figure).¹⁷

Complicated UTIs in the elderly are difficult to treat due to bacterial resistance. The off-label use of methenamine hippurate for treatment/prophylaxis of MDR-recurrent UTIs is a compelling option, explored further in the following case studies. Four case studies using methenamine for treatment and prevention of recurrent MDR UTIs in geriatric patients are presented.

Treating UTI Patients

Case Study 1
A man aged > 89 years, symptomatic with nocturia due to benign prostatic hypertrophy (BPH) with bladder outlet obstruction had 8 symptomatic UTIs over 15 months. His urine culture tested positive for MDR Providencia stuartia (resistant to ampicillin, chephazolin, gentamycin, tigecycline, tobramycin and sulfamethizole) and Staphylococcus haemolyticus (resistant to ciprofloxacin, levofloxacin, and nitrofurantoin). Postvoid residual urine was identified as the cause for his recurrent UTIs. Self-catheterization was recommended, but the patient declined. Due to his advanced age and preference, surgical intervention was not pursued. His renal function was within normal limits.

Treatment with methenamine hippurate 500 mg bid with 1,000 mg ascorbic acid to acidify the urine was initiated. This reduced dose of 500 mg bid (rather than 1,000 mg bid) was prescribed due to his advanced age and a choice to “err on the side of caution.” Two months later, urinalysis was negative for leukocyte esterase and nitrates, and the growth culture tested negative. Three- and 6-month urinalyses also showed no growth. The patient’s renal function remained stable. He experienced no AEs from the methenamine.

Due to his urinary retention, formaldehyde was able to collect in his bladder for longer than 2 hours, achieving bactericidal levels and effectively preventing recurrence of MDR UTIs.