Many debilitated patients have bacteriuria associated with catheterization or aging. Whether debilitated patients have symptoms related to the urinary tract, and whether these symptoms are consistent with infection, is often difficult to evaluate as the patients may be unable to communicate discomfort.9
Symptoms such as malaise, anorexia, weakness, mental changes, and weight loss are commonly seen in debilitated patients without infection, which makes diagnosis difficult, particularly in advanced disease.10
Furthermore, debilitated patients may have difficulty mounting a response to infection; for example, fever, a common symptom of severe infection, has been noted to be present in only 50% of cancer patients with UTIs. In many cases, fever is not initially thought attributable to the UTI.11
The difficulty associated with diagnosing infections is magnified because of the substantial risk associated with either not treating an infection or treating a patient who does not have an infection. Most debilitated patients with asymptomatic bacteriuria should not be treated.
However, if there is a possibility that the patient’s symptoms, particularly fever, are associated with a UTI, then treatment should be initiated. Urine cultures must be obtained because of the possibility of multiple organisms with different antimicrobial profiles. The organisms causing UTIs most commonly are Escherichia coli, but other gram-negative organisms such as Klebsiella species and Pseudomonas are encountered frequently.
In addition, gram-positives such as enterococci, staphylococci, and even yeast may be identified, the latter presenting particularly difficult co-infections. Since catheters indwelling for any length of time may incorporate bacteria within biofilms, they should be changed, if at all possible, prior to diagnosing the infection and initiating therapy.4
Given the complexity of the microbiologic flora and the overwhelming possibility of multiple drug resistance, a severe infection should be treated aggressively with broad-spectrum antimicrobials. If time permits, culture data should be used to select agents which are most likely to be effective.
Duration of therapy is not well defined in this population, but systemic parenteral therapy should be continued until the patient’s symptoms improve. The patient can then be converted to oral therapy based on susceptibility testing. At least 7-14 days or longer therapy may be required. Cultures should be obtained during and after therapy to identify efficacy and relapse, respectively.
Complicated UTI, defined as those associated with functional or structural abnormalities in the urinary tract, are very prevalent in debilitated populations. Therefore, early imaging of the urinary tract using CT or ultrasound should be performed. If at all possible, any obstruction must be relieved by either catheter drainage or removal of the obstructing focus. Other more significant findings, such as renal or perirenal abscess, must be drained, often percutaneously.
Concomitant with initiating therapy and maximizing the status of the urinary tract, efforts must be made to improve the status of the patient and reduce comorbidities. These steps should include appropriate hydration and review and adjustment of medications to enhance management of other comorbidities such as diabetes.
Because renal function has a key role in delivering appropriate concentrations of antimicrobials to the urinary tract, serum creatinine should be monitored regularly. Dehydrated elderly patients are more susceptible to the effects of antimicrobials, particularly those with potential nephrotoxicity such as aminoglycosides.
Once-daily dosing with aminoglycosides is particularly attractive in this population for two reasons: first, because the high, initial dose takes advantage of the dose-dependent killing activity, and second, the low, sustained dose reduces toxicity.12,13 Once-daily dosing with aminoglycosides requires adherence to a simple formula; after administering the initial dose, for example, 7.5 mg/kg, a serum level should be obtained between 8-14 hours later.
A nomogram is used to determine the time for subsequent doses, for example at 24 hours, then repeated at 12-hour intervals (36 hours, 48 hours, etc). It is imperative that periodic serum aminoglycoside and creatinine be monitored to ensure effective and safe dosing. Peaks and trough levels are not appropriate for monitoring once-daily aminoglycoside therapy.14, 15
Drug-drug interactions can be particularly problematic for several reasons. Efficacy of some drugs, such as the fluoroquinolones, can be diminished by antacids, which reduce absorption from the GI tract. Other drugs may not only reduce the activity of the agent but enhance side effects. Because of these possibilities, pharmaceutical guidance should be obtained when multiple drugs are used.
Several complicated UTIs can be particularly difficult to treat in debilitated patients. For example, infected hydronephrosis can lead to pyonephrosis and destruction of renal parenchyma. Xanthogranulomatous pyelonephritis is an acute necrotizing parenchymal and perirenal infection caused by gas forming uro-pathogens.16
It is usually associated with urinary calculi, obstruction, diabetes, and significant renal functional impairment—all characteristics of debilitated patients. The mortality rate for this condition can exceed 50%. Severe cases require prompt drainage or removal of the site of infection. Because of the risk of surgery in these patients, percutaneous or open drainage and aggressive antimicrobial therapy should be initially attempted if possible until the patient’s condition can be stabilized or improved.
UTI in the debilitated patient occurs frequently and causes significant morbidity and mortality. Diagnosis must be based on a high index of suspicion and careful interpretation of symptoms. Although severe symptoms can occur, paradoxically debilitated patients may present with symptoms that are either thought to be associated with other conditions, and/or relatively asymptomatic.
Conversely, the diagnostics of bacteriuria in asymptomatic debilitated patients can lead to false diagnosis of infection and unnecessary treatment. Diagnosis must be confirmed by urinalysis and culture. A chronic indwelling catheter should be changed before obtaining a specimen so the bacteria within the catheter’s biofilm do not contaminate the bladder.
Initially, antimicrobial therapy must be broad-spectrum to cover multiple organisms and drug resistance. Once-daily aminoglycoside therapy is effective and reduces morbidity but must be carefully monitored. Oral therapy should be instituted when clinically indicated.
Efforts should be made to maximize response by improving the overall status of the patient and the urinary tract during and after the infection. Imaging must be employed to rule out obstruction and other structural or functional abnormalities. Response to therapy is the key indicator for duration of antimicrobial therapy and decisions regarding interventions are required.
Relief of obstruction by percutaneous or by catheter drainage is imperative. Following resolution of the acute event, risk factors and comorbidities should be managed aggressively to maximize therapeutic outcomes and minimize relapse.
- Homsi J, Walsh D, Panta R, et al. Infectious complications of advanced cancer. Support Care Cancer. 2000;8:487-492.
- Williams DH, Schaeffer AJ. Current concepts in urinary tract infections. Minerva Urol Nefrol. 2004;56:15-31.
- Korzeniowski OM. Urinary tract infection in the impaired host. Med Clin North Am. 1991;75:391-404.
- de Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nat Clin Pract Nephrol. 2008 (epub ahead of print).
- Patterson JE, Andriole VT. Bacterial urinary tract infections in diabetes. Infect Dis Clin North Am. 1995;9:25-51.
- O’Donnell JA, Hofmann MT. Urinary tract infections. How to manage nursing home patients with or without chronic catheterization. Geriatrics. 2002;57:45, 49-52, 55-56 passim.
- Actis LA, Tolmasky ME, Crosa JH. Bacterial plasmids: replication of extrachromosomal genetic elements encoding resistance to antimicrobial compounds. Front Biosci. 1999;4:D43-62.
- DeNap JC, Hergenrother PJ. Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria. Org Biomol Chem. 2005;3(6):959-966.
- Juthani-Mehta M. Asymptomatic bacteriuria and urinary tract infection in older adults. Clin Geriatr Med. 2007;23:585-594, vii.
- McClure CL. Common infections in the elderly. Am Fam Physician. 1992;45(6):2691-2698.
- Bodey GP. Infection in cancer patients. A continuing association. Am J Med. 1986;81(1A):11-26.
- Bailey TC, Little JR, Littenberg B, et al. A meta-analysis of extended-interval dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis. 1997;24:786-795.
- Freeman CD, Nicolau DP, Belliveau PP, Nightingale CH. Once-daily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother. 1997;39:677-686.
- Yoshida M, Morita R, Lefor AT, Nabeshima T. Implementation and evaluation of a once-daily amikacin dosing protocol in a long-term care facility. Int J Antimicrob Agents. 2007;29:113-116.
- Bartal C, Danon A, Schlaeffer F, et al. Pharmacokinetic dosing of aminoglycosides: a controlled trial. Am J Med. 2003;114:194-198.
- Loffroy R, Guiu B, Watfa J, et al. Xanthogranulomatous pyelonephritis in adults: clinical and radiological findings in diffuse and focal forms. Clin Radiol. 2007;62:884-890.