- Significant bacteriuria in presence of symptoms
- Described by location: urethritis, cystitis, or pyelonephritis
- In men <50 yr symptoms of dysuria or urinary frequency usually due to STI
- In men >50 yr incidence of UTI rises dramatically d/t prostatic obstruction
Uncomplicated UTI is defined as UTI without structural or functional abnormalities within the urinary tract or kidney parenchyma, without relevant comorbidities that place the patient at risk for more serious adverse outcome, and not associated with GU tract instrumentation ---The diagnostic standard is the isolation of 105 CFU/mL; however, in symptomatic patients, low-colony-count infections with 103 to 104 CFU/mL are clinically valid
Complicated UTI is defined as infection involving a functional or anatomically abnormal urinary tract, or infection in the presence of comorbidities that place the patient at risk for more serious adverse outcome
Risk Factor Comments Male sex In young males, dysuria is more commonly secondary to sexually transmitted disease; suspect underlying anatomic abnormality in men with culture-proven UTI. Anatomic abnormality of the urinary tract or external drainage system Indwelling urinary catheter, ureteral stent, nephrolithiasis, neurogenic bladder, polycystic renal disease, or recent urinary tract instrumentation. Recurrent UTI No universal definition exists. A pragmatic definition is three or more per year. Advanced age in men Presence of prostatic hyperplasia, recent instrumentation, recent prostatic biopsy. Nursing home residency With or without indwelling bladder catheter. Neonatal state See Chapter 126, Urinary Tract Infection in Infants and Children. Comorbidities Diabetes mellitus, sickle cell disease, others. Pregnancy See Chapter 102, Comorbid Diseases in Pregnancy. Immunosuppression Active chemotherapy, acquired immunodeficiency syndrome, immunosuppressive drugs. Advanced neurologic disease Stroke with disability, spinal cord injuries, others. Known or suspected atypical pathogens Non–Escherichia coli infections. Known or suspected resistance to typical antimicrobial agents for UTI Resistance to ciprofloxacin predicts multidrug resistance.
Relapse of UTI is recurrence of symptoms within a month, caused by the same organism, and represents treatment failure. Reinfection is the development of symptoms 1 to 6 months later, after treatment. Reinfection is usually by a different enteric organism or a different serotype of the same organism, and may represent a defect in the defense mechanisms of the host. If a patient has a cluster of infections with more than three recurrences in 1 year, a more complete evaluation may be warranted to look for the presence of structural abnormalities, tumor, renal calculi, or associated systemic illness such as diabetes mellitus.
BACTERIOLOGY The most common urinary tract pathogen remains Escherichia coli (Table 94-2). Uropathogenic organisms often have adhesins, fibrillae, or pili that allow the bacteria to adhere to the uroepithelium. Anaerobic organisms do not grow well in urine and are rarely pathogenic. Although complicated UTIs can be caused by E. coli, they are more likely to be caused by unusual pathogens, such as Pseudomonas species or enterococcus.
The infective process of UTI can progress into three patterns of renal infection not commonly considered part of the UTI spectrum: acute bacterial nephritis, renal abscess, and emphysematous pyelonephritis. These diagnoses are made based on imaging studies performed in patients who have an inadequate or atypical response to treatment for presumed acute pyelonephritis. On US or CT images, acute pyelonephritis is represented as a diffusely enlarged kidney with associated perinephric stranding but without focal renal abnormalities. Acute bacterial nephritis produces ill-defined focal areas, sometimes striated or wedge shaped, of decreased density. Renal abscesses appear as well-defined areas of decreased density. Emphysematous pyelonephritis is a rare gas-forming infection within the kidney, nearly always occurring in diabetic individuals (70% to 90% of patients).11 Patients appear toxic and septic. Nephrectomy may be needed to adequately treat emphysematous pyelonephritis.
Clinical Features -UTI requires the presence of both bacteriuria and clinical symptoms for definitive diagnosis
Common symptoms include painful urination (dysuria), hematuria, increased urinary frequency, urgency, hesitancy, suprapubic discomfort, CVA tenderness, and fever
The presence of four specific symptoms and one sign independently increase the clinical probability of UTI: dysuria, frequency, visible (gross) hematuria, fever, and CVA tenderness.
Unfortunately, the correlation between symptoms and the presence of infection is inexact, because only 50% to 60% of women with dysuria have significant bacteriuria. Internal dysuria, a burning suprapubic pain during urination accompanied by bladder tenderness, is more associated with UTIs than external dysuria, a burning sensation as urine passes over inflamed perineal tissue. In females, external dysuria or a history of vaginal discharge or irritation is more often associated with vaginitis, cervicitis, or pelvic inflammatory disease than with UTI. The presence of specific symptom combinations (e.g., dysuria and frequency) along with the absence of vaginal discharge or irritation increases the probability of uncomplicated UTI in otherwise healthy, nonpregnant, sexually active young women to approximately 90%. When a patient develops one or more of the aforementioned symptoms (dysuria, frequency, gross hematuria), further history taking, physical examination, and urinalysis are unable to provide sufficient strength of evidence to lower the post-test probability of UTI to a point at which it can be safely ruled out
The only physical examination finding that increases the likelihood of a UTI is costovertebral angle tenderness.
Flank pain, CVA tenderness, or specific renal tenderness to deep palpation may be associated with cystitis because of referred pain. However, when these findings occur in association with fever, chills, nausea, vomiting, and prostration, the clinical diagnosis is acute pyelonephritis
In males, dysuria with a urethral discharge indicates urethritis.3 Gram staining of the discharge may reveal gram-negative intracellular diplococci, which suggests gonococcal urethritis. If the results of the Gram staining are inconclusive, the diagnosis is most likely nonspecific urethritis, which is caused mainly by chlamydial infection or another sexually transmitted infection
UTI is uncommon in healthy young adult males, so a urine specimen should not be obtained routinely at triage or under standing orders for males with dysuria. Withholding urination may enhance the likelihood of a positive result on urethral swab testing in the male patient with minimal discharge. Obtaining a first-void specimen rather than a midstream specimen is helpful to diagnose urethritis. If bacteriuria is present and is not clinically associated with urethritis or prostatitis, then UTI is present.
In women, Chlamydia infection should be suspected in the following settings: a new sexual partner, a partner with urethritis, examination findings of cervicitis, and low-grade pyuria with no bacteria seen on urinalysis. Concurrent gonorrhea is common with Chlamydia infections.
For patients at risk for complex UTI (Table 94-1), the clinical features and the classic presenting signs and symptoms of UTI may vary widely or be entirely absent. Fever, pain, and an inflammatory response may be absent. UTI should be suspected in more complicated cases involving patients with atypical and diverse signs and symptoms, including weakness, malaise, altered mental status, fever, and flank or abdominal pain.
Diagnosis COLLECTION OF THE URINE SPECIMEN
The midstream voiding specimen is as accurate as urine obtained by catheterization if the patient follows instructions carefully
In addition to taking special care in cleansing, using a tampon also helps women to obtain a clean-catch specimen if menstruation or profuse discharge is present.
If the sample is properly collected, it should contain no or few epithelial cells.
URINE WHITE BLOOD CELL COUNT OR PYURIA BY MICROSCOPY
WBC of >5 cells/high-power field (HPF) in a centrifuged specimen, in a patient with appropriate symptoms, is abnormal. Although the combination of pyuria and bacteriuria is likely to be found with typical coliform infection, lower degrees of pyuria with or without bacteriuria may be clinically significant, especially in the presence of UTI symptoms.
In a symptomatic patient who has <5 WBCs/HPF in a centrifuged specimen, other causes of false negative pyuria should be considered. These include ingestion of large amounts of fluids, which washes out the bladder and produces a dilute urine; systemic leukopenia; and self-medication resulting in a partially treated UTI (patients often take old or leftover medications from previous UTIs, or medications prescribed to another person). Pyuria may be intermittent or absent if the patient has an obstructed and infected kidney.
In men, more than 1 or 2 WBCs/HPF in a centrifuged specimen can be significant when bacteria are present.3 Urethritis and prostatitis are far more likely causes of pyuria in young males who are sexually active and complain of dysuria, regardless of the presence or absence of urethral discharge.
BACTERIURIA BY MICROSCOPY
Bacteriuria is a sensitive tool for detection of UTI in the symptomatic patient. The presence of any bacteria on a Gram-stained specimen of uncentrifuged urine (>1 bacterium/oil-power field or 1000x) is significant and highly correlates with culture results of >105 CFU/mL.
NITRITE REACTION BY DIPSTICK TEST LEUKOCYTE ESTERASE REACTION BY DIPSTICK TEST
The urine nitrite reaction has a very high specificity (>90%), and a positive result is very useful in confirming the diagnosis of a UTI caused by bacteria that convert nitrates to nitrite, primarily the coliform bacteria, including E. coli.
Enterococcus, Pseudomonas species, and Acinetobacter do not convert nitrates to nitrites in the urine and therefore are not detected by the nitrite test. Unfortunately the urine nitrite reaction has a low sensitivity (about 50%), so it is not always useful as a screening examination because a negative result does not exclude the diagnosis of UTI.
In summary, a positive urinary dipstick nitrite or leukocyte esterase test result supports the diagnosis of UTI, but a negative test result does not exclude it.
URINE CULTURE For the patient with typical symptoms of cystitis or an uncomplicated UTI and "positive" findings on urinalysis—either pyuria on microscopic examination, positive leukocyte esterase test result, bacteria in a Gram-stained specimen, and/or positive urine nitrite test result—urine culture is not required.
Urine culture should be performed for the following patients: those with complicated UTI, pregnant women, children, adult males, and patients with relapse or reinfection
BLOOD CULTURE A retrospective study showed that results of blood cultures in patients admitted for clinical pyelonephritis are positive in 29% of cases, that organisms in blood culture matched those in urine culture 97% of time, and that blood culture results did not alter management.
IMAGING Male, elderly, diabetic, or severely ill patients with acute pyelonephritis should be considered for imaging, particularly if there is a renal stone or a poor initial response to antibiotic therapy.
Differential Diagnosis for Dysuria
Disorder Comments Urinary tract infection Cystitis and pyelonephritis Vaginitis/cervicitis Infections (STD), atrophy, allergy Urethritis Infections (STD), allergy Trauma Trauma involving vagina, urethra, or bladder Allergy Typically a reaction to a hygienic product or spermicide Rectal/colon disorders Diverticulitis and others Nephrolithiasis — Urethral stricture or obstruction — Uterine/bladder/vaginal prolapse — Fistulas Ileovesicular, urethral, urethrorectal, bladder Urethral foreign body Includes urethral stone disease Urethral diverticulum — Cystocele — Chemical irritation Spermicides, cleansing douches, feminine hygiene products Behavioral symptom without detectable pathology Consider previous rape, sexual abuse Chronic disorders Chronic cystitis, chronic urethritis
Treatment The discussion of treatment is divided into two sections, Acute Cystitis and Acute Pyelonephritis and Complicated Urinary Tract Infection, with the understanding that although pyelonephritis can be classified as uncomplicated if the patient has normal anatomy and is otherwise healthy, complicated UTI is managed much the same as pyelonephritis, with larger drug dosages and/or broader-spectrum antibiotics, urine culture to guide ongoing therapy, and longer duration of treatment
ACUTE CYSTITIS AND UNCOMPLICATED URINARY TRACT INFECTION
SEE TABLE 94-5 Table 94-5 contains treatment recommendations for four separate groups of patients with UTI: (1) women with uncomplicated lower tract disease, (2) women with complicated UTI or pyelonephritis, (3) men with upper or lower UTI, and (4) women with UTI symptoms in whom coexistent urethritis cannot be excluded
Specific antibiotic choice varies according to local resistance patterns.24–27 Local guidelines for antimicrobial use should be consulted. Rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) are over 30% in some areas, whereas resistance to ciprofloxacin approaches 11%.26,27 Resistance to ciprofloxacin predicts multidrug resistance
Most uncomplicated UTIs in women can be treated with a 3-day course of antibiotics. UTIs not thought to be sexually transmitted in young males should be treated with a 7- to 10-day course of antibiotics. Fourteen-day courses are indicated for more complex cases involving patients with significant comorbidities, diabetic patients, those who are immunocompromised, and the elderly
Currently, recommendations are to avoid TMP-SMX as the first-line empiric agent of choice when local resistance rate exceeds 20%, unless treating based on the results of urine culture with sensitivity testing.
Nitrofurantoin extended release is also an effective agent for treating UTI, although it is not effective against S. saprophyticus. The twice-a-day formulation is more expensive than ciprofloxacin. Nitrofurantoin is a favorite antibiotic among obstetricians for treatment of asymptomatic bacteriuria and otherwise uncomplicated UTI in pregnant women. A 5-day course of nitrofurantoin extended release is as effective as 3 days of TMP-SMX therapy.22 Nitrofurantoin has a favorable resistance profile in many regions, is a generally safe alternative, and concentrates well in the urine. Choosing to use nitrofurantoin avoids contributing to another problem—growing pathogen resistance to fluoroquinolones due to their frequent use to treat a wide array of infections.
Because of bacterial resistance to traditional antibiotics used for UTI, local sensitivities may be used to guide the substitution of alternative agents such as cephalosporins. Third-generation cephalosporins are highly effective against enterobacteria. First-generation cephalosporins are more effective against staphylococci. Amoxicillin-clavulanate is less effective than fluoroquinolones30 or oral cephalosporins31 for UTI due to enterobacteria. It also often leads to selection of Klebsiella. Aminopenicillins are therefore not recommended as first-line therapy in uncomplicated UTI. Another important alternative is the phosphonic acid antibiotic fosfomycin. A single 3-gram dose is highly effective, the resistance rate is only 2%,32 and the drug is the first-line choice for uncomplicated UTI as recommended by the European Association of Urology.23
In cases of treatment failure, or in the host with a structural or immunologic defect, one of the fluoroquinolones should be considered. Urine culture with sensitivity testing should be performed to guide treatment. Where TMP-SMX resistance is known to be higher than 10% to 20% and empiric short-course (3-day) therapy is indicated, fluoroquinolones may be the best choice. Unfortunately, fluoroquinolone resistance in organisms causing UTI is already becoming a problem and is expected to increase dramatically in the coming years. Fluoroquinolones are also the favored agents for treating UTI in men in most cases. UTI in men should not be treated with a 3-day course of antibiotics.
If the patient has UTI symptoms and there is also suspicion of Chlamydia infection and gonorrhea (cervicitis and/or salpingitis) antibiotic treatment is more complex. If the patient is not sufficiently ill to require admission and is not pregnant, one initial treatment approach is to use ofloxacin, 400 milligrams twice a day for 14 days. Ofloxacin effectively covers all common UTI pathogens as well as Chlamydia and Neisseria gonorrhoeae, but increasing N. gonorrhoeae resistance to fluoroquinolones has been reported. If salpingitis is clinically evident, additional therapy is required (see Chapter 144, Sexually Transmitted Diseases). When treating a young teenage patient with recurrent UTI, if the patient is sexually active, the physician should consider counseling the patient regarding contraception and prevention of STDs.
Recurrent infection is often due to a new serotype of E. coli, or it may be due to organisms that have newly developed resistance as a result of exposure to antibiotics excreted into the GI tract. If empiric therapy is considered for recurrent infections, it should probably be with fluoroquinolones unless community resistance to TMP-SMX is known to be low. However, successful management in cases of recurrent UTI depends on urine culture and sensitivity testing. Because many factors are involved in reinfection and some of these are correctable, referral to a primary care physician is needed.
In uncomplicated UTIs, the urine should be bacteria free in 24 to 48 hours with substantial relief of symptoms within the same time period. Three-day regimens are the standard of care for uncomplicated infections in nonpregnant women
Nevertheless, in 20% to 30% of patients given short-duration therapy, treatment fails or there is rapid relapse. A longer treatment course (Table 94-6) is indicated for patients with complicated UTIs, including those with symptoms lasting longer than a week, patients with diabetes, individuals who had a UTI in the previous 4 weeks, men, those who are >65 years of age, and women who use spermicides or a diaphragm.1,3,5,7–10,13 Those patients who experience relapse need 14 days of subsequent therapy
-Empiric Initial Treatment for Inpatient Management of Pyelonephritis and Complicated Urinary Tract Infection- - Ciprofloxacin, 400 milligrams IV every 12 h Ceftriaxone, 1 gram IV once daily Cefotaxime, 1 or 2 grams IV every 8 h Gentamicin, or tobramycin, 3.0 milligrams/kg/d divided every 8 h ± ampicillin 1–2 grams every 4 h Trimethoprim-sulfamethoxazole, 160/800 milligrams IV twice a day Piperacillin-tazobactam, 3.375 grams IV every 6 h Cefepime, 2 grams IV every 8 h Imipenem, 500 milligrams IV every 8 h Meropenem, 1 gram IV every 8 h
ACUTE PYELONEPHRITIS AND COMPLICATED URINARY TRACT INFECTION See 94-5 for outpt, see table 94-6 for inpt
Duration of Therapy for Pyelonephritis and Complicated Urinary Tract Infection Although treatment courses as short as 5 days have been studied in patients with pyelonephritis,36 guidelines recommend a total of 14 days of therapy for the majority, regardless of whether or not parenteral therapy is used.9 For patients with sepsis syndrome, a total of 21 days of treatment may be required to eradicate bacteriuria
Disposition and Follow-Up DISPOSITION FOR PATIENTS WITH UNCOMPLICATED URINARY TRACT INFECTION OR CYSTITIS Patients who are unable to retain fluids and medication should be admitted and antibiotics chosen as listed in Table 94-6. Adjunctive therapies for patients in stable enough condition for discharge include ingestion of plenty of fluids to enhance diuresis and fruit juices containing vitamin C to acidify the urine, consumption of a proper diet, and frequent voiding (at least every 2 hours) to diminish tissue contact with bacteria. The offer of 1 to 2 days of treatment with an oral bladder analgesic, such as phenazopyridine, is considerate when urination is painful for the patient. Cranberry juice appears to be mildly effective in reducing the incidence of recurrent infection.37 There is no conclusive evidence that postcoital voiding prevents cystitis.38
DISPOSITION FOR PATIENTS WITH PYELONEPHRITIS Young, otherwise healthy females with uncomplicated acute pyelonephritis are candidates for outpatient management provided they are able to tolerate fluids and medication.28,29 Urine culture with sensitivity testing should be performed. Patients should be instructed to return if they experience increasing pain, fever, or vomiting. Prescriptions for systemic analgesics (e.g., hydrocodone plus acetaminophen) and antiemetics (i.e., promethazine) should be considered. Overall, 80% to 90% of selected patients with acute pyelonephritis respond well to outpatient oral therapy.
The decision to admit a patient with UTI is based on age, host factors, and response to initial ED interventions. Overall, approximately 1% to 3% of patients with acute pyelonephritis die from the infection, with younger patients experiencing the fewest complications. Factors associated with an unfavorable prognosis are advanced age and general debility, renal calculi or obstruction, a history of recent hospitalization or instrumentation, diabetes mellitus, evidence of chronic nephropathy, sickle cell anemia, underlying carcinoma, and immunocompromised state [e.g., chemotherapy, human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS)].
Dangerous complications of acute pyelonephritis include acute papillary necrosis with possible ureter obstruction, septic shock, perinephric abscesses, and emphysematous pyelonephritis (see Imaging above).
PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION/ACQUIRED IMMUNODEFICIENCY SYNDROME In HIV/AIDS patients, resistance to TMP-SMX is increased due largely to its use in Pneumocystis jiroveci prophylaxis. Fluoroquinolones should be the initial antibiotic used for UTI in these patients unless urine culture and sensitivity test results are available to guide therapy. Most UTIs in HIV/AIDS patients are caused by typical pathogens or common STD organisms. Mycobacterium tuberculosis is an infrequent cause of UTI in the HIV/AIDS population. Close outpatient follow-up (recheck in 1 week) and possible infectious disease consultation is warranted when treating UTI in this population
Special Populations PREGNANT WOMEN See Chapter 102, Comorbid Diseases in Pregnancy, for a detailed discussion.