Cystitis in Females Differential Diagnoses
- Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD more...
Occult pyelonephritis occurs in 15-50% (or more) of all urinary tract infections (UTIs), based on several studies on localization of organisms within the urinary tract. This usually occurs in older women. It appears that these patients are unable to mount a fever or develop an elevated white count or costovertebral angle (CVA) tenderness. These patients may present with an unexplained fall or a change in mental status.
Postmenopausal women may also experience senile urethritis. In addition to urinary burning, frequency, and urgency, these patients may complain of vaginal and vulvar itching and discharge. Physical examination reveals a dry, pale vaginal epithelium and eversion of the urethral mucosa. Senile urethritis responds to topical estrogen therapy.
The differential diagnosis for infectious causes of sterile pyuria includes perinephric abscess, urethral syndrome, renal tuberculosis, and fungal infections of the urinary tract system. Noninfectious causes of pyuria include the following:
Uric acid and hypercalcemic nephropathy
Lithium and heavy metal toxicity
Sarcoidosis and other granulomatous diseases (eg, tuberculosis)
Polycystic kidney disease
Renal transplant rejection
Any periurethral process
Consider UTI in any condition involving pain the flank and back or pain in the abdomen and pelvis. Also consider cervicitis and Chlamydia infection. Do not assume that a sexually active female with dysuria has a UTI without first excluding the possibility of sexually transmitted disease–related cervicitis, vaginitis, or pelvic inflammatory disease.
UTIs in pregnancy have potentially adverse outcomes for both the mother and the fetus. Obtain a urine culture in all pregnant patients with suspected UTI, as the results may provide the physician or the follow-up physician with valuable information if the patient does not respond as expected to treatment. Pyuria and bacteriuria are always treated during pregnancy, regardless of whether symptoms are present.
Patients with diabetes mellitus are at increased risk for complicated UTIs. Diagnostic considerations include the following:
Renal and perirenal abscess
Older patients who appear toxic are more likely to have obstruction complicating their UTI. Obtain a structural study to rule out this possibility.
[Guideline] Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar. 52(5):e103-20. [Medline]. [Full Text].
[Guideline] Wagenlehner FM, Schmiemann G, Hoyme U, Fünfstück R, Hummers-Pradier E, Kaase M, et al. [National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients]. Urologe A. 2011 Feb. 50(2):153-69. [Medline]. [Full Text].
Abrahamian FM, Moran GJ, Talan DA. Urinary tract infections in the emergency department. Infect Dis Clin North Am. 2008 Mar. 22(1):73-87, vi. [Medline].
Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, et al. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technol Assess. 2009 Mar. 13(19):iii-iv, ix-xi, 1-73. [Medline].
Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. 2011 Aug. 29(3):539-52. [Medline].
Czaja CA, Stamm WE, Stapleton AE, et al. Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women. J Infect Dis. 2009 Aug 15. 200(4):528-36. [Medline].
Adeghate J, Juhász E, Pongrácz J, Rimanóczy É, Kristóf K. Does Staphylococcus Saprophyticus Cause Acute Cystitis only in Young Females, or is there more to the Story? A One-Year Comprehensive Study Done in Budapest, Hungary. Acta Microbiol Immunol Hung. 2016 Mar. 63 (1):57-67. [Medline].
Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc. 2011 Mar. 86(3):250-9. [Medline]. [Full Text].
[Guideline] Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1. 50(5):625-63. [Medline]. [Full Text].
Tiemstra JD, Chico PD, Pela E. Genitourinary infections after a routine pelvic exam. J Am Board Fam Med. 2011 May-Jun. 24(3):296-303. [Medline].
Hsiao CJ, Cherry DK, Beatty PC, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2007 summary. Natl Health Stat Report. 2010 Nov 3. 1-32. [Medline].
Naber KG, Schito G, Botto H, Palou J, Mazzei T. Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy. Eur Urol. 2008 Nov. 54(5):1164-75. [Medline].
Little P, Merriman R, Turner S, Rumsby K, Warner G, Lowes JA, et al. Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study. BMJ. 2010 Feb 5. 340:b5633. [Medline]. [Full Text].
Molander U, Arvidsson L, Milsom I, Sandberg T. A longitudinal cohort study of elderly women with urinary tract infections. Maturitas. 2000 Feb 15. 34(2):127-31. [Medline].
Johnson L, Sabel A, Burman WJ, Everhart RM, Rome M, MacKenzie TD, et al. Emergence of fluoroquinolone resistance in outpatient urinary Escherichia coli isolates. Am J Med. 2008 Oct. 121(10):876-84. [Medline].
[Guideline] American College of Obstetricians and Gynecologists (ACOG). 2008. Treatment of urinary tract infections in nonpregnant women. Available at http://guideline.gov/content.aspx?id=12628. Accessed: September 22, 2010.
Barclay L. Urinary Tract Infection: 3 Questions Aid Diagnosis in Women. Medscape Medical News. Available at http://www.medscape.com/viewarticle/810667. Accessed: September 16, 2013.
Knottnerus BJ, Geerlings SE, Moll van Charante EP, Ter Riet G. Toward a simple diagnostic index for acute uncomplicated urinary tract infections. Ann Fam Med. 2013 Sep-Oct. 11(5):442-51. [Medline]. [Full Text].
Schaeffer AJ, Schaeffer EM. Infections of the Urinary Tract. In: McDougal WS, Wein AJ, Kavoussi LR, et al, eds. Campbell-Walsh Urology. 10th Ed. Philadelphia, PA: Elsevier Saunders; 2012. 46-55.
Lifshitz E, Kramer L. Outpatient urine culture: does collection technique matter?. Arch Intern Med. 2000 Sep 11. 160(16):2537-40. [Medline].
Propp DA, Weber D, Ciesla ML. Reliability of a urine dipstick in emergency department patients. Ann Emerg Med. 1989 May. 18(5):560-3. [Medline].
Mehnert-Kay SA. Diagnosis and Management of Uncomplicated Urinary Tract Infections. American Family Physician. August 1, 2005. 27/No.3:1-9. [Full Text].
[Guideline] Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues DA. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010 Apr. 31(4):319-26. [Medline]. [Full Text].
Kauffman CA, Fisher JF, Sobel JD, Newman CA. Candida urinary tract infections--diagnosis. Clin Infect Dis. 2011 May. 52 Suppl 6:S452-6. [Medline].
Falagas ME, Kotsantis IK, Vouloumanou EK, Rafailidis PI. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect. 2009 Feb. 58(2):91-102. [Medline].
Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010 Dec. 7(12):653-60. [Medline].
Little P, Moore MV, Turner S, Rumsby K, Warner G, Lowes JA, et al. Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ. 2010 Feb 5. 340:c199. [Medline]. [Full Text].
Lavigne JP, Bruyère F, Bernard L, Combescure C, Ronco E, Lanotte P, et al. Resistance and virulence potential of uropathogenic Escherichia coli strains isolated from patients hospitalized in urology departments: a French prospective multicentre study. J Med Microbiol. 2016 Jun. 65 (6):530-7. [Medline].
Christiaens TC, De Meyere M, Verschraegen G, Peersman W, Heytens S, De Maeseneer JM. Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. Br J Gen Pract. 2002 Sep. 52(482):729-34. [Medline]. [Full Text].
Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?--results of a randomized controlled pilot trial. BMC Med. 2010 May 26. 8:30. [Medline]. [Full Text].
Grigoryan L, Zoorob R, Wang H, Trautner BW. Low Concordance With Guidelines for Treatment of Acute Cystitis in Primary Care. Open Forum Infect Dis. 2015 Dec. 2 (4):ofv159. [Medline].
Sigler M, Leal JE, Bliven K, Cogdill B, Thompson A. Assessment of appropriate antibiotic prescribing for urinary tract infections in an internal medicine clinic. South Med J. 2015 May. 108 (5):300-4. [Medline].
Olson RP, Harrell LJ, Kaye KS. Antibiotic resistance in urinary isolates of Escherichia coli from college women with urinary tract infections. Antimicrob Agents Chemother. 2009 Mar. 53(3):1285-6. [Medline]. [Full Text].
McKinnell JA, Stollenwerk NS, Jung CW, Miller LG. Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis. Mayo Clin Proc. 2011 Jun. 86(6):480-8. [Medline]. [Full Text].
Falagas ME, Vouloumanou EK, Togias AG, Karadima M, Kapaskelis AM, Rafailidis PI, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010 Sep. 65(9):1862-77. [Medline]. [Full Text].
[Guideline] Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005 Mar 1. 40(5):643-54. [Medline]. [Full Text].
Dalal S, Nicolle L, Marrs CF, Zhang L, Harding G, Foxman B. Long-term Escherichia coli asymptomatic bacteriuria among women with diabetes mellitus. Clin Infect Dis. 2009 Aug 15. 49(4):491-7. [Medline]. [Full Text].
Beerepoot MA, ter Riet G, Nys S, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med. 2011 Jul 25. 171(14):1270-8. [Medline].
Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008 Jan 23. CD001321. [Medline].
Tempera G, Corsello S, Genovese C, Caruso FE, Nicolosi D. Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study. Int J Immunopathol Pharmacol. 2010 Apr-Jun. 23(2):611-8. [Medline].
De Vita D, Giordano S. Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent bacterial cystitis: a randomized study. Int Urogynecol J. 2012 Dec. 23(12):1707-13. [Medline].
van der Starre WE, van Nieuwkoop C, Paltansing S, et al. Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection. J Antimicrob Chemother. 2011 Mar. 66(3):650-6. [Medline].
Cunha BA. Prophylaxis for recurrent urinary tract infections: nitrofurantoin, not trimethoprim-sulfamethoxazole or cranberry juice. Arch Intern Med. 2012 Jan 9. 172(1):82; author reply 82-3. [Medline].
Cunha BA, Schoch PE, Hage JR. Nitrofurantoin: preferred empiric therapy for community-acquired lower urinary tract infections. Mayo Clin Proc. 2011 Dec. 86(12):1243-4; author reply 1244. [Medline]. [Full Text].
Fischer HD, Juurlink DN, Mamdani MM, Kopp A, Laupacis A. Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: a population-based study. Arch Intern Med. 2010 Apr 12. 170(7):617-21. [Medline].
Hand L. Urinary Infections: Report Offers Long-Needed Clarity. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814305. Accessed: November 18, 2013.
Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013 Nov 14. 369(20):1883-91. [Medline].
Leydon GM, Turner S, Smith H, Little P. Women's views about management and cause of urinary tract infection: qualitative interview study. BMJ. 2010 Feb 5. 340:c279. [Medline]. [Full Text].
Pinson AG, Philbrick JT, Lindbeck GH, Schorling JB. ED management of acute pyelonephritis in women: a cohort study. Am J Emerg Med. 1994 May. 12(3):271-8. [Medline].
Turner D, Little P, Raftery J, Turner S, Smith H, Rumsby K, et al. Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial. BMJ. 2010 Feb 5. 340:c346. [Medline]. [Full Text].
Patients with complicated cystitis who can tolerate oral therapy may be treated with the following options:
Patients who cannot tolerate oral therapy as outlined above or patients with infection that is suspected to be due to resistant organisms should be treated with parenteral therapy, as follows:
Parenteral therapy can be switched to oral therapy once clinical improvement is observed.
Parenteral therapy can be switched to oral therapy once clinical improvement is observed.