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Urinary Tract Infection, Females: Differential Diagnoses & Workup

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Coauthor(s): Jeffrey M Tessier, MD, Assistant Professor, Department of Medicine, Uniformed Services University of the Health Sciences; Mary F Bavaro, MD, Chief, Division of Infectious Disease, Navy Medical Center, San Diego
Contributor Information and Disclosures

Updated: Oct 19, 2009

Differential Diagnoses

Appendicitis
Renal Cell Carcinoma
Behcet Disease
Renal Corticomedullary Abscess
Bladder Cancer
Renal Transplantation (Medical)
Bladder Stones
Renal Transplantation (Urology)
Bladder Trauma
Schistosomiasis
Chlamydial Genitourinary Infections
Sepsis, Bacterial
Cholangitis
Septic Shock
Cholecystitis
Serratia
Colovesical Fistula
Shock and Pregnancy
Common Pregnancy Complaints and Questions
Shock, Distributive
Cystitis, Nonbacterial
Subacute Thyroiditis
Diverticulitis
Trichomoniasis
Emphysema
Tuberculosis
Emphysematous Pyelonephritis
Tuberculosis of the Genitourinary System
Enterobacter Infections
Ureaplasma Infection
Enterococcal Infections
Ureteral Injury During Gynecologic Surgery
Escherichia Coli Infections
Ureteral Stricture
Gardnerella
Ureteral Trauma
Gastroenteritis, Bacterial
Ureterocele
Glomerulonephritis, Acute
Ureterolithotomy
Gonococcal Infections
Ureteropelvic Junction Obstruction
Herpes Simplex
Ureteroscopy
Interstitial Cystitis
Urethral Prolapse
Klebsiella Infections
Urethral Syndrome
Mycoplasma Infections
Urethritis
Nephrolithiasis
Urinary Diversions and Neobladders
Nephrolithiasis: Acute Renal Colic
Urinary Tract Infection, Females
Pancreatitis, Acute
Urinary Tract Infections in Pregnancy
Pneumonia, Bacterial
Urinary Tract Obstruction
Pneumonia, Community-Acquired
Urologic Imaging Without X-rays: Ultrasound, MRI, and Nuclear Medicine
Proteus Infections
Urothelial Tumors of the Renal Pelvis and Ureters
Providencia Infections
Vaginitis
Pseudomonas Aeruginosa Infections
Vesicoureteral Reflux
Pyelolithotomy
Vesicovaginal and Ureterovaginal Fistula
Pyelonephritis, Acute
Vesicovaginal Fistula
Pyelonephritis, Chronic
Xanthogranulomatous Pyelonephritis
Pyonephrosis

Other Problems to Be Considered

Consider any condition involving flank/back pain or abdominal/pelvic pain.

The differential diagnosis for infectious causes of sterile pyuria includes perinephric abscess, urethral syndrome, renal TB, and fungal infections of the urinary tract system.

Noninfectious causes of pyuria include uric acid and hypercalcemic nephropathy, lithium and heavy metal toxicity, sarcoidosis, interstitial cystitis, polycystic kidney disease, genitourinary malignancy, and renal transplant rejection.

Workup

Laboratory Studies

  • In the 1980s, many experts felt that urine cultures were unnecessary in young women with cystitis complaints because almost all of these were caused by pan-susceptible isolates of E coli. However, since 1998, resistant isolates of E coli have emerged (in numbers as high as 20% in some communities). Trimethoprim-sulfamethoxazole (TMP-SMZ) resistance has been associated with concomitant resistance to other antibiotics. Consider obtaining urine cultures in the new millennium.
  • Urine specimens may be obtained by suprapubic aspiration, catheterization, or midstream clean catch. Bacteriuria, especially with many squamous cells without pyuria suggests contamination or colonization; some women may need to be catheterized to obtain a clean specimen. Although midstream urine specimens have been advocated, one randomized trial showed that the rate of contamination was not excessive in young women who urinated into a container without cleansing the perineum or discarding the first urine output.
  • Dipstick testing should include glucose, protein, blood, nitrite, and leukocyte esterase. A microscopic evaluation of the urine sample for WBC counts, red blood cell (RBC) counts, and cellular or hyaline casts should be performed. In the office, a combination of clinical symptoms with dipstick and microscopic analysis showing pyuria and/or positive nitrite/leukocyte esterase tests can be used as presumptive evidence of urinary tract infection (UTI).
  • The most accurate method to measure pyuria is counting leukocytes in unspun fresh urine using a hemocytometer chamber; greater than 10 WBC/mL is considered abnormal. Counts determined from a wet mount of centrifuged urine are not reliable measures of pyuria. A noncontaminated specimen is suggested by a lack of squamous epithelial cells. Pyuria is a sensitive (80-95%) but nonspecific (50-76%) method of diagnosing UTI.
  • White cell casts may be observed in conditions other than infection, and they may not be observed in all cases of pyelonephritis. If the patient has evidence of acute infection and white cell casts are present, the infection likely represents pyelonephritis. A spun sample (5 mL at 2000 revolutions per min [rpm] for 5 min) is best used for evaluation of cellular casts.
  • Leukocyte esterase is a dipstick test that can rapidly screen for pyuria; it is 57-96% sensitive and 94-98% specific for identifying pyuria.
  • Nitrite tests detect the products of nitrate reductase, an enzyme produced by many bacterial species. These products are not present normally unless a UTI exists. This test has a sensitivity and specificity of 22% and 94-100%, respectively. The low sensitivity has been attributed to enzyme-deficient bacteria causing infection or low-grade bacteriuria.
  • Microscopic hematuria is found in about half of cystitis cases; when found without symptoms or pyuria, it should prompt a search for malignancy. Other things to be considered in the differential include calculi, vasculitis, renal TB, or glomerulonephritis. In a developing country, hematuria is suggestive of schistosomiasis, which can be associated with salmonellosis and squamous cell malignancies of the bladder. For more information on this interesting topic, the reader is referred to the article on Schistosomiasis.
  • Proteinuria commonly is observed in infections of the urinary tract, but the proteinuria usually is low grade. More than 2 g of protein per 24 hours suggests glomerular disease.
  • Urine culture remains the criterion standard for the diagnosis of UTI. Collected urine should be sent for culture immediately; if not, it should be refrigerated at 4°C. Two culture techniques (dip slide, agar) are widely used and accurate. The 1999 Infectious Disease Society of America (IDSA) consensus limits for cystitis and pyelonephritis in women are more than 1000 CFU/mL and more than 10,000 CFU/mL, respectively, for clean-catch midstream urine specimens. Note that any amount of uropathogen grown in culture from a suprapubic aspirate should be considered evidence of a UTI. Approximately 40% of patients with perinephric abscesses have sterile urine cultures.
  • If a Gram stain of an uncentrifuged, clean-catch, midstream urine specimen reveals the presence of 1 bacterium per oil-immersion field, it represents 10,000 bacteria/mL of urine. A specimen (5 mL) that has been centrifuged for 5 minutes at 2000 rpm and examined under high power after Gram staining will identify lower numbers. In general, a Gram stain has a sensitivity of 90% and a specificity of 88%.
  • Patients with spinal cord injury  
    • Diagnosing a UTI in a patient with an SCI is difficult. In these patients, suprapubic aspiration of the bladder is the criterion standard for diagnosing a UTI, although it is not performed often in clinical practice.
    • All of these patients have some degree of bacteruria, but not all are actively infected. The diagnosis of significant bacteriuria, per the 1992 consensus statement of the National Institute on Disability and Rehabilitation Research (NIDRR), is any detectable concentration of a uropathogen collected from a patient with SCI and with an indwelling catheter. For patients utilizing intermittent catheterization, the definition of significant bacteriuria is 100 CFU/mL or more.
    • The optimal method to diagnose pyuria in a patient with SCI has not been determined. More than 50 WBC per high-power field (hpf) is a reasonable indicator of high-level pyuria and has been associated with increased morbidity.
  • Approximately 70% of patients with corticomedullary abscesses have abnormal urinalysis findings, whereas those with renal cortical abscesses usually have normal findings. Two thirds of patients with perinephric abscesses have an abnormal urinalysis.
  • Other lab tests  
    • The WBC count usually is elevated in patients with complicated UTI. The WBC count may or may not be elevated in patients with uncomplicated UTI. Patients with complicated UTIs may have anemia, which is observed in 40% of patients with perinephric abscesses.
    • Some patients have findings of electrolyte abnormalities, and 25% of patients with perinephric abscesses have azotemia.
    • Bacteremia is associated with pyelonephritis, corticomedullary abscesses, and perinephric abscesses. Approximately 10-40% of patients with pyelonephritis or perinephric abscesses have positive results on blood culture. Bacteremia is not necessarily associated with a higher morbidity or mortality in women with uncomplicated UTI.
    • Cervical swabs may be indicated.

Imaging Studies

  • No imaging studies are indicated in the routine evaluation of cystitis or pyelonephritis. Women with acute pyelonephritis should be considered for imaging if they continue to have symptoms or clinical progression despite standard antimicrobial therapy for their infection. Complicated UTIs may require imaging. Options include simple kidneys, ureter, and bladder (KUB) radiography; renal ultrasonography; computed tomography (CT) scanning; MRI; nuclear imaging; and angiography. Urologic intervention may be required, including intravenous pyelography (IVP) and ureterography (ie, retrograde and percutaneous).
  • Renal ultrasonography is a useful imaging modality in patients with complicated UTIs, and it may be performed at the bedside in a patient who is hemodynamically unstable. It is relatively inexpensive, does not involve radiation, and iodinated contrast is not needed. A renal abscess may appear as a fluid-filled mass with a thick wall. Acute focal bacterial nephritis appears as a poorly defined mass with low-amplitude echoes and disruption of the corticomedullary junction. Xanthogranulomatous pyelonephritis images reveal stones in approximately 70% of patients. Ultrasonographic findings may be falsely negative in 36% of perinephric abscesses. A drawback to ultrasonography is the difficulty in differentiating renal abscess from tumor; it also is difficult to interpret in a patient who is obese.
  • Renal angiography may help differentiate renal abscess from renal tumor because an abscess often has increased peripheral vascularization (the remainder of the mass is avascular).
  • Nuclear studies  
    • Gallium (Ga) scans also may be used in the workup of a complicated UTI. The patient is injected with a transiently radioactive substance and returns 1-3 days later. The emitted radiation provides an image, which, although it lacks precise anatomic detail, does provide functional information. A subtraction technique using Ga citrate and technetium (Tc) glucoheptonate needs to be performed to differentiate intrarenal abscess from tumor, obstruction, and severe pyelonephritis.
    • An indium-111–labeled WBC scan can help to diagnose infection in persons with autosomal-dominant polycystic kidney disease.
  • For complicated UTIs, CT scans provide the best definition, and the information is available quickly. Drawbacks to CT scans include some exposure to irradiation and the need for iodinated contrast. Abscesses should appear as low-density masses with contrast enhancement of the wall from inflamed/dilated blood vessels. Acute focal bacterial nephritis has a lobar distribution of inflammation, wedge-shaped hypodense lesions (postcontrast), and masslike hypodense lesions in severe infections. Xanthogranulomatous pyelonephritis may appear as large renal calculi, nonfunctioning kidneys, contrast enhancement around low attenuation areas, thickening of Gerota fascia, and spherical areas of low attenuation.
  • Patients with spinal cord injuries with more than 2 symptomatic UTIs within 6 months should be evaluated to rule out high-pressure voiding, vesicoureteral reflux, and the presence of stones. Evaluations often include urodynamic studies, nuclear scanning, renal ultrasonography, voiding cystourethrography, abdominal CT scans, IVP, and/or cystoscopy.

Procedures

  • The consulting urologist may wish to perform IVP, cystoscopy, or ureterography (either retrograde or percutaneous).

More on Urinary Tract Infection, Females

Overview: Urinary Tract Infection, Females
Differential Diagnoses & Workup: Urinary Tract Infection, Females
Treatment & Medication: Urinary Tract Infection, Females
Follow-up: Urinary Tract Infection, Females
Multimedia: Urinary Tract Infection, Females
References
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Further Reading

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Keywords

urinary tract infection, UTI, urinary infection, cystitis, pyelonephritis, bacteriuria, candiduria, urosepsis, sexually transmitted disease, STD, Escherichia coli, E coli, Pseudomonas aeruginosa, P aeruginosa, Klebsiella pneumoniae, K pneumoniae, candidal species, enterococcal species, enterococci, pelvic inflammatory disease, PID, yeast infection, uropathogens, hematuria, indwelling urethral catheter, indwelling urethral catheterization

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Contributor Information and Disclosures

Author

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey M Tessier, MD, Assistant Professor, Department of Medicine, Uniformed Services University of the Health Sciences
Jeffrey M Tessier, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine
Disclosure: Nothing to disclose.

Mary F Bavaro, MD, Chief, Division of Infectious Disease, Navy Medical Center, San Diego
Mary F Bavaro, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Mark Jeffrey Noble, MD, Consulting Staff, Urologic Institute, Cleveland Clinic Foundation
Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, and Southwest Oncology Group
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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