Urinary Tract Infections

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Definitions, Classification, and Clinical Presentation of Urinary Tract Infections Caroline C. Johnson, MD*

Urinary tract infections (UTIs) are one of the most common infectious diseases enc.ountered in the practice of medicine today. It is estimated that UTIs account for 5 million office visits yearly in the United States. 8 In addition, UTIs, including catheter-related bacteriuria, constitute the most common nosocomial bacterial infection, with an average infection rate of 13.1 cases/lOOO hospital discharges. 2o Clearly, on the basis of their prevalence alone, UTIs warrant careful consideration by clinicians. This article defines commonly used terminology and reviews the various clinical manifestations of urinary tract infections. DEFINITIONS OF URINARY TRACT INFECTION Urinary tract infections encompass a spectrum of clinical and pathologic conditions involving various parts of the urinary tract. The syndromes range from asymptomatic bacteriuria to perinephric abscess with sepsis. Each has its own unique epidemiology, natural history, and diagnostic considerations. Differentiating the syndromes associated with UTI has important implications for treatment and prognosis. To communicate information on the subject of UTIs effectively, terminology should be standardized and precise. Several authors have recently published recommendations for definitions and classifications of UTIs. 26. 30. 33

Microbiologic Terminology

Urinary tract infection (UTI) refers to the presence of microorganisms in the urinary tract, including the bladder, prostate, collecting system, or kidneys. Most commonly, UTIs are caused by bacteria, although occasionally fungi and viruses are involved. There is no diagnostic requirement for *Assistant Professor of Medicine, Medical College of Pennsylvania, and Veterans Administration Medical Center, Philadelphia, Pennsylvania

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organisms to be detectable in the urine because their presence may be restricted to a localized tissue abscess (e. g., a perinephric abscess). In most cases, however, UTIs are accompanied by bacteriuria. Bacteriuria refers to the presence of bacteria in the urine. Normally, bladder urine is sterile. 34 Bacteriuria may occur as a result of infection or contamination of the urine specimen at the time of collection. Contamination usually arises from inoculation of the urine sample with urethral or periurethral flora during micturition. Although specimens collected by urethral catheterization or suprapubic aspiration more accurately reflect the microbiologic status of the urine, such procedures are invasive and uncomfortable. Therefore, it is usually necessary to rely on cultures of voided urine to diagnose UTI. The term significant bacteriuria has been introduced to differentiate the bacteriuria of true infection from that due to contamination. It relies on the early observations of Kass et a}24 that contamination of the urine at the time of collection resulted in lower numbers of bacteria in the urine, whereas infection was associated with larger numbers. Thus, the probability of infection can be ascertained by means of quantitating the numbers of bacteria in voided urine. The threshold traditionally used for defining significant bacteriuria is 105 or more colony-forming units (CFU) of bacteria/ ml of voided urine. Although this number is highly specific for UTI in symptomatic women, it has low sensitivity. More recent studies suggest that a threshold of 102 CFU of coliform bacteria/ml of urine may be a more sensitive indicator of infection in acutely symptomatic women while being only slightly less specific than a value of 105 CFU/ml,5° Moreover, in symptomatic men, in whom urine contamination is less likely, a threshold of 103 CFU of bacteria/ml reliably suggests infection. 31 To establish a diagnosis of significant bacteriuria in a catheterized patient, a quantitative threshold of 102 CFUiml has been suggested. 56 This is based on the observation that organisms present in the urine at this number will invariably reach concentrations of 105 CFU/ml over succeeding days. 52 Thus, significant bacteriuria that has been traditionally designated as 105 CFUiml or greater may be defined differently depending on the clinical setting and the manner in which the specimen was collected (Table 1). Asymptomatic bacteriuria refers to significant bacteriuria in a patient without symptoms attributable to the urinary tract. It occurs most commonly in pregnant women and the elderly. 1. 5 Patients with significant bacteriuria who have symptoms referable to the urinary tract are said to have symp-

tomatic bacteriuria.

Table 1. Criteria for Defining Significant Bacteriuria CFU coliforms/ml or ~105 CFU non-coliforms/ml in a symptomatic woman ~l(J3 CFU bacteria/ml in a symptomatic man ~l(f CFU bacteria/ml in asymptomatic individuals on two consecutive specimens Any growth of bacteria on suprapubic catheterization in a symptomatic patient ~102 CFU bacteria/ml in a catheterized patient ~1()2

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Clinical Terminology Infection may involve various parts of the urinary tract, alone or in combination. Clinical syndromes are useful in distinguishing the areas of involvement. Cystitis can be defined as infection of the urinary bladder accompanied by symptoms of dysuria, frequency, and urgency; however, the same symptoms may be produced by inflammation of the bladder or urethra in the absence of infection. Also, vaginitis and urethritis caused by sexually transmitted pathogens such as herpes simplex, Chlamydia trachomatis, or Neisseria gonorrhoeae may mimic cystitis. Patients presenting with complaints of dysuria, frequency, and urgency in the absence of significant bacteriuria on a voided urine specimen are described as having the acute urethral syndrome. 16 This diagnosis is not exclusive of cystitis because many such patients are actually found to have bacterial infection of the bladder or urethra. In these patients (usually young women), the counts of bacteria in voided urine are lower than the traditional threshold used to define significant bacteriuria (105 CFU/ml). However, the presence of infection can be verified by culture of urine obtained by suprapubic aspiration. Acute pyelonephritis describes a syndrome that consists of localized flank or back pain combined with systemic symptoms such as fever, chills, and prostration. It is caused by infection of the renal parenchyma and collecting system, and is often complicated by bacteremia. Chronic pyelonephritis is a confusing term that cannot be defined in terms of a clinical syndrome. Strictly speaking, it refers to a specific pathologic appearance of the kidney. Chronic pyelonephritis is the result of progressive inflammation of the renal interstitium and tubules. Grossly, the kidneys show uneven scarring and contraction. This asymmetry is useful in differentiating chronic pyelonephritis from conditions such as chronic glomerulonephritis that show symmetric involvement. 54 On microscopic examination, interstitial and periglomerular fibrosis is distributed throughout the renal parenchyma, which is also infiltrated with various inflammatory cells. 40 Areas of tubular dilatation may contain colloid casts that produce the appearance of the thyroid gland ("thyroidization of the kidney"). The term rhronic pyelonephritis suggests that the pathologic appearance of the kidneys occurs as a result of recurrent UTIs. However, this pathology is not specific and is commonly found in association with other renal diseases, such as chronic obstruction, uric acid nephropathy, analgesic abuse, and hypokalemic nephropathy. Furthermore, there is little evidence to support the belief that chronic pyelonephritis occurs as result of infection alone. Studies have found no correlation between the occurrence of chronic pyelonephritis and preceding uncomplicated UTI. 14, 15, 35 To avoid the implication that chronic pyelonephritis indicates infection, many authors suggest that the term chronic interstitial nephritis be used to describe this pathologic condition of the kidneys. 26, 33 An uncommon manifestation of UTI is the formation of discrete renal abscesses. Iflocated within the renal parenchyma, it is termed an intrarenal abscess. An abscess located in the soft tissues surrounding the kidneys is termed perinephric. Both may develop as complications of acute pyelonephritis or from bacteremic seeding of the kidney or perinephric space.

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Acute prostatitis is the term used to describe acute bacterial infection of the prostate gland. The syndrome manifests with abrupt onset of fever and perineal pain associated with symptoms of irritative and obstructive voiding dysfunction. 32 Bacteriuria often accompanies acute prostatitis. In contrast, chronic prostatitis is a more subtle condition. Although it also represents bacterial infection of the prostate gland, the inflammation is persistent and low-grade. Relapsing episodes of UTI, either cystitis or pyelonephritis, are common. On occasion, patients with chronic prostatitis have voiding dysfunction and abdominal or low back discomfort. Urosepsis may be defined as symptomatic bacteremia of urinary tract origin.7 It is a rare but life-threatening complication of UTI. Communityacquired urosepsis in an otherwise healthy host typically arises from acute pyelonephritis or renal abscess. Nosocomial urosepsis most often complicates urinary tract instrumentation such as urethral catheterization. Treatment Terminology Despite treatment with antimicrobial agents, UTIs are often recurrent. Recurrence of bacteriuria with an organism different from that originally isolated is termed a reinfection. Recurrence of bacteriuria with the same organism as originally isolated is termed a relapse. Reinfection indicates acquisition of a new pathogen, whereas relapse indicates persistence of the organism within the urinary tract. Occasionally, reinfection may occur with an organism identical to the original strain. In this situation, reinfection cannot be distinguished from relapse. The term chronic urinary tract infection is sometimes used to describe patients with frequent recurrences of symptomatic UTI. True chronic infection should mean persistence of the same organism in the urine after months or years. Thus, chronic UTI best describes the situation of a patient with multiple relapses of infection, not the patient with frequent reinfections. Nevertheless, the term has been applied in both situations. It is preferable to specify chronic infections as either relapses or reinfections. CLASSIFICATION AND CLINICAL PRESENTATION OF URINARY TRACT INFECTIONS Asymptomatic Bacteriuria Asymptomatic bacteriuria is the classification for patients who are incidentally found to have bacteriuria without classical symptoms referable to the urinary tract. Two consecutive cultures should yield the same organism in counts of 105 CFU or greater/ml of urine to confirm this diagnosis. Asymptomatic bacteriuria is largely a problem for the clinician in children, pregnant women, and the elderly. The implications for prognosis and treatment depend on the population in question. Bacteriuria in children is common, occurring in up to 3.7% of boys and 2.0% of girls during the first year of life. 21 Approximately half of these patients are asymptomatic. Vesicoureteral reflux is found in 30% to 50% of bacteriuric children up to age 5, whether symptomatic or asymptomatic. 47

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Because reflux in the presence of infection may ultimately lead to permanent renal scarring, treatment for bacteriuria in all young children is advised. Mter the age of 5 years, there is much less association of renal scarring with bacteriuria. It is unclear if treatment of asymptomatic children in this age group is beneficial. Pregnant women with asymptomatic bacteriuria are at substantial risk for subsequent development of symptomatic UTI and obstetric complications. There are no overt clinical manifestations of asymptomatic bacteriuria in pregnancy. Complaints of urinary frequency and nocturia are common in pregnancy regardless of the microbiologic status of the urine. Likewise, the presence of pyuria and proteinuria cannot be equated with significant bacteriuria. I Quantitative urine culture is the only reliable means for establishing the diagnosis. Asymptomatic bacteriuria in pregnant women differs from that in nonpregnant women in a number of ways. First, the overall prevalence of bacteriuria is higher. Studies have shown a 4% to 7% prevalence of bacteriuria during pregnancy, compared to a 1% to 3% prevalence in young nonpregnant women. 25, 37 Second, the bacteriuria in pregnant women persists throughout the gestational period, whereas in nonpregnant women the episodes of bacteriuria are intermittent and selflimited. 9 Finally, there is a significant risk that pregnant women with asymptomatic bacteriuria will develop symptomatic UTI later in the course of the pregnancy. 23, 45 Routine screening and treatment of all pregnant women with bacteriuria is advised. The most common association of asymptomatic bacteriuria is with the elderly. At least 20% of women and 10% of men over the age of 65 have bacteriuria. 3 The majority of elderly individuals with bacteriuria do not have typical symptoms of cystitis (dysuria, urgency, frequency) or pyelonephritis (fever, flank pain). Nevertheless, generalized complaints of malaise, insomnia, and fatigue are common in this population. Previously, it had been of concern that these nonspecific symptoms might be related to the presence of bacteriuria. However, a recent study found no difference in symptoms and frequency of change in these symptoms when bacteriuric individuals were compared with themselves when they were not bacteriuric. 4 The conclusion was that asymptomatic bacteriuria in the elderly is indeed asymptomatic. At present, most experts believe that asymptomatic bacteriuria of the elderly is a benign condition. 3 There is no convincing evidence that treatment leads to improvement in well-being or survival. Lower Urinary Tract Infection Lower UTI resulting from infection of the bladder is termed cystitis. Typical symptoms arise from disturbances of normal voiding sensation and function caused by inflammation of the bladder and urethra. Dysuria is the cardinal complaint of patients with cystitis. Pain and burning may occur at the onset, during, or just after urination. Other symptoms include urinary urgency, suprapubic discomfort, and frequent voiding of small amounts of urine. On occasion, patients will note hematuria or turbid urine that may have an intense odor. Notably, fever and other systemic symptoms are absent if infection is limited to the lower urinary tract. Physical examination is unremarkable in most patients with lower UTI.

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Approximately 10% of patients will have pain on suprapubic palpation. 57 Although examination is not usually helpful in confirming a diagnosis of lower UTI, it may aid in excluding other conditions. In particular, careful pelvic examination may detect findings of vaginitis, cervicitis, or vulvar infection. Lower UTI must be differentiated from several other infectious and noninfectious causes of dysuria and frequency (Table 2). In addition to cystitis, the differential diagnosis of the dysuria-frequency syndrome includes mechanical or chemical irritation, allergy, vulvovaginitis, and urethritis due to a sexually transmitted pathogen. Clinical information may be helpful in distinguishing these disorders. A history of trauma or exposure to a new drug or topical agent suggests a noninfectious cause of dysuria, whereas contact with a new sexual partner suggests the presence of a sexually transmitted disease. Cystitis should be suspected in patients with a history of previous UTI or diaphragm use. 12 Some authors advise that the site of a patient's dysuria be distinguished as either internal or external in origin.22 Internal dysuria arises from within the body and begins with the initiation of voiding. With external dysuria, the discomfort localizes to the perineum and occurs during or upon completion of voiding. The latter is more typical of patients with vulvovaginitis, such as that caused by yeast, Trichomonas, or herpes simplex. Internal dysuria suggests cystitis or urethritis. Acute Urethral Syndrome In the absence of significant bacteriuria, patients presenting with complaints of dysuria without obvious etiology are said to have the acute urethral syndrome. Approximately half of all women evaluated for acute dysuria and frequency do not have significant bacteriuria (defined as 105 CFU or more of bacteria/m I of urine). As many as 30% of such women actually have sterile urine. 6, 16 To better define the causes of acute urethral syndrome, Stamm et al 51 performed careful microbiologic evaluation of 59 dysuric women who did not have significant bacteriuria. By suprapubic aspiration or catheterization, 27 of 59 women (44%) were actually found to have bacteria in the bladder urine, all at counts less than 3.4 X 104 CFU/ ml. Of the 32 women with sterile bladder urine, 11 were infected with Chlamydia trachomatis. Pyuria, defined as 8 or more leukocytes/mm3 of uncentrifuged urine, was found in almost all women with documented Table 2. Causes of Dysuria and Frequency Acute cystitis Acute pyelonephritis with cystitis Genitourinary trauma Urethral irritants Allergic reaction Vulvovaginitis with or without urethritis Trichomoniasis Candidiasis Herpes simplex Chlamydia trachomatis Neisseria gonorrhoeae

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infection, whereas few women without pyuria had demonstrable infection. The pathogenesis of the acute urethral syndrome in patients in whom all cultures were negative is unknown. Causes such as Ureaplasma urealyticum and noninfectious factors have been suggested. 47 Patients with either Chlamydia infection or cystitis due to low counts of bacteria have been shown to benefit from antimicrobial therapy. Upper Urinary Tract Infection Patients with upper UTI classically present with signs and symptoms of acute pyelonephritis. Characteristic features include both systemic complaints, such as fever and chills, and localized features, such as flank or back pain. These manifestations result from inflammation of the renal pelvis and parenchyma. Some of these patients have accompanying bacteremia. Suppurative necrosis is the hallmark histologic feature of acute pyelonephritis. 40 The distribution of the lesions is unpredictable, sometimes involving one or both kidneys in a haphazard fashion. Thus, clinical manifestations may be either uni- or bilateral. The signs and symptoms of acute pyelonephritis develop rapidly over a period of hours to days. According to some experts, fever is the most reliable clinical finding in upper UTI.lO It readily reaches heights of 39.5°C to 40.5°C (103°F to 105°F). Associated rigors suggest that the infection is complicated by bacteremia. Other systemic complaints include chills, headache, nausea, vomiting, and prostration. Localized symptoms take the form of aching pain in the flank or lumbar region adjacent to the involved kidney(s). Sometimes, pain is referred to the abdomen or epigastrium. Examination may detect tenderness of the costovertebral angle or of the flank area; however, these physical findings are quite nonspecific. Frequently, lower tract symptoms of dysuria, urgency, and frequency may accompany presentation with acute pyelonephritis. These symptoms may antedate upper UTI by a few days, or they may develop concomitantly. At times, the clinical manifestations of upper UTI are protean. In children, gastrointestinal symptoms of nausea, vomiting, and abdominal pain may predominate. Patients with indwelling catheters may present only with fever. Gleckman et aps have reported bacteremia and shock to be common manifestations of pyelonephritis in the elderly. IS The differential diagnosis of patients presenting with flank or costovertebral angle pain should include urinary tract obstruction, acute renal infarction, and papillary necrosis. Severe pain or radiation into the groin suggests the presence of a renal calculus (which mayor may not be complicated by infection). When signs and symptoms of pyelonephritis involve the abdomen, intra-abdominal pathology such as appendicitis or cholecystitis may be suggested. Asymptomatic Upper Urinary Tract Infection (Subclinical Pyelonephritis) A surprising proportion of women who have dysuria, but no symptoms of pyelonephritis, nevertheless have upper UTI. 46 This entity has been termed subclinical pyelonephritis. 27. 28 Its existence has been demonstrated in studies using ureteral catheterization and the Fairley bladder washout technique for urine cultures, as well as those using assays for antibody-

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coated bacteria. 10, 41, 42, 48 Subclinical pyelonephritis may be associated with minimal symptoms, may smolder for long periods, and may be difficult to eradicate. It is likely that asymptomatic upper UTIs account for many cases of "cystitis" treatment failures when short courses of therapy are employed. Subclinical infection of the kidneys also appears to be associated with asymptomatic bacteriuria in certain populations. Recent studies report that the majority (67%) of elderly, institutionalized women with asymptomatic bacteriuria have infection localizing to the upper urinary tract. 36, 53 In the same type of population, upper tract localization correlated well with persistence of bacteriuria over time (:::d year)," Also, in diabetic women, approximately half of the cases of asymptomatic bacteriuria seem to arise from the kidney. 13, 38 Patients with subclinical pyelonephritis are indistinguishable from patients with bacteriuria solely of lower tract origin. Several clinical risk factors increase the likelihood that asymptomatic upper UTI may complicate lower UTI (Table 3). It is reasonable to consider the diagnosis in patients with underlying urinary tract abnormality, diabetes mellitus, immunocompromise, history of childhood UTIs, lengthy duration of cystitis symptoms, and relapsing infections. However, it is important to note that subclinical pyelonephritis can also occur in otherwise healthy young women presenting with dysuria only. Localization of infection on the basis of clinical suspicion is not very reliable. Laboratory tests such as the Fairley bladder washout technique and antibody coating of bacteria are helpful, but they also will misclassify a substantial number of patients. 49 Recognition of subclinical pyelonephritis in a patient with cystitis has important therapeutic implications. Longer courses of therapy are required because patients with upper UTI do not respond to single-dose regimens. 11 Some patients with occult pyelonephritis may actually require 6 weeks of treatment for cure. The prognosis in patients treated for subclinical pyelonephritis is good. Although recurrences of infection are common, there is no evidence of serious long-term sequelae on either renal function or structure in the absence of other predisposing conditions. It is not yet known if asymptomatic bacteriuria of upper tract origin has clinical significance. Although some patients will undoubtedly develop symptomatic UTI in the future, benefits of therapy to eradicate asymptomatic bacteriuria must be weighed against the possible costs and toxicities of treatment.

Renal Abscess Another manifestation of upper UTI is the development of renal abscesses. Gross suppuration within the renal parenchyma is termed an intrarenal abscess, whereas an abscess located in the perirenal fascia is Table 3. Risk Factors for Subclinical (Occult) Pyelonephritis in Patients with Bacteriuria Underlying urinary tract abnormality Diabetes mellitus Immunocompromised condition History of childhood UTIs

Symptoms of cystitis for 7-10 days Acute pyelonephritis within prior year Relapse of infection (same organism) Elderly, institutionalized women

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called perinephric. These processes may coexist and are often difficult to diagnose. Historically, one third of cases of renal abscess have been discovered only at autopsy. 44 With newer radiologic modalities, such as eT and MRI scans, premorbid diagnosis has probably been improved. Anatomically, intrarenal abscesses may be categorized as either cortical or corticomedullary. Most cortical abscesses (renal carbuncles) arise from hematogenous seeding of the kidneys; thus, the majority are caused by Staphylococcus aureus (90%). The source of the bacteremia is usually skin, oral cavity, lung, or bone. Hemodialysis, diabetes mellitus, and intravenous drug use predispose to staphylococcal bacteremia and abscess development. In contrast, corticomedullary abscesses usually complicate a urinary tract abnormality such as reflux or obstruction. 39 Enteric gram-negative bacilli are the most common cause of this type of abscess. Perinephric abscess typically results from rupture of an intrarenal suppurative focus into the perinephric space. 55 Predisposing conditions are urinary tract obstruction, trauma, diabetes mellitus, and steroid use. Occasionally, the perinephric space is infected hematogenously or by direct extension from adjacent infected structures, such as vertebral osteomyelitis, appendicitis, or diverticulitis. The clinical manifestations of intrarenal and perinephric abscess are similar. The onset of illness is insidious, lasting 1 to 3 weeks. Fever and chills are noted in almost all cases, whereas flank pain and tenderness are found in approximately three quarters of cases. 55 Less frequent complaints include nausea, vomiting, abdominal pain, and hematuria. Symptoms of cystitis (dysuria, frequency, and urgency) are described by fewer than 40% of patients, but may be present if the abscess communicates with the renal collecting system. On physical examination, most patients will have either unilateral flank tenderness or diffuse abdominal tenderness. Flank or abdominal masses may be palpable in 47% and 35% of cases, respectively.43 The urinalysis in patients with renal abscess is often abnormal, revealing pyuria, bacteriuria, or both. However, a normal urinalysis does not exclude the diagnosis because the infection may not communicate with the renal collecting system. Blood cultures have been reported to be positive in 64% of cases of intrarenal abscess, and in 40% of those with perinephric abscess. l9 ,55 Leukocytosis is present in most patients. Radiographic investigation is critical in the evaluation of suspected renal abscesses. Ultrasonography and eT scan permit earlier and more accurate diagnosis of renal masses. l ? In addition, these modalities allow guided needle aspiration of abscesses to obtain specimens for culture and histopathology. The differential diagnosis of renal abscess includes several renal and nonrenal disorders. Primarily, it must be distinguished from acute pyelonephritis, which also presents with fever, flank pain, and urine abnormalities. The presence of a mass may help distinguish abscess, but the finding is not present often enough to be reliable. The distinction is commonly based on the absence or slow response to appropriate antibiotics in patients with abscess. Fever, defervescence, and diminution of symptoms generally occur within 72 hours of initiating treatment in patients with pyelonephritis. Renal cell carcinoma is another important entity to be distinguished from abscess. Radiologic procedures such as arteriography and eT aid in differ-

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entiation. Other considerations in the differential diagnosis of renal abscess include hematoma and suppurative foci such as pelvic or intra-abdominal abscess. Urosepsis The urinary tract is a frequent site of origin of bacteremia, particularly gram-negative bacteremia. 29 Although bacteremia may be transient and self-limited, it may also be symptomatic, ultimately leading to shock and death. Symptomatic bacteremia originating from the urinary tract is termed urosepsis. It is not an entity distinct from other syndromes of UTI. Rather, urosepsis is a complication of UTI. Various species of enteric gram-negative bacilli are equally capable of producing symptomatic bacteremia or shock. 7 Therefore, it is probably not the virulence of the organism but the condition of the host's defenses and the site of urinary tract involvement that determines the bacteremic potential of a uropathogen. Generally, urosepsis is seen as a complication in several clinical situations: (1) instrumentation of the genitourinary tract, (2) renal abscess, (3) acute pyelonephritis, (4) UTI in the face of urinary tract obstruction or diminished host defenses, and (5) catheter-associated bacteriuria with obstruction or impaired host defenses. 2 Often, in urosepsis, the clinical manifestations of bacteremia overshadow those relating to the urinary tract. Fever is the most common finding, but it may be absent in debilitated patients or in those receiving corticosteroids. Paradoxically, hypothermia also occurs and is associated with a poor outcome. 58 Other early manifestations of sepsis are chills, rigors, changes in mental status, and hyperventilation with primary respiratory alkalosis. As the course of sepsis progresses, hypotension results from a variety of hemodynamic events, including changes in peripheral vascular resistance and cardiac output. Metabolic acidosis ensues from the accumulation oflactate. At this point, the patient is said to be in shock. Subsequent complications such as disseminated intravascular coagulation, acute renal failure, and adult respiratory distress syndrome are common. The source of bacteremia is suspected to be the urinary tract if signs and symptoms of sepsis are accompanied by those of cystitis or pyelonephritis. In the absence of clinical manifestations of UTI, an abnormal urinalysis with pyuria and bacteriuria may suggest the source. Ultimately, recovery of the same organism from cultures of blood and urine confirms the diagnosis of urosepsis. REFERENCES 1. Andriole VT: Urinary tract infections in pregnancy. Urol Clin North Am 2:485, 1975 2. Bahnson RR: Urosepsis. Urol Clin North Am 13:627, 1986 3. Boscia JA, Kaye D: Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am 1:893, 1987 4. Boscia JA, Kobasa WD, Abrutyn E, et al: Lack of association between bacteriuria and symptoms in the elderly. Am J Med 81:979, 1986 5. Boscia JA, Kobasa WD, Knight RA, et aI: Epidemiology of bacteriuria in an elderly ambulatory population. Am J Med 80:208, 1986

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6. Brooks D, Mauder A: Pathogenesis of the urethral syndrome in women and its diagnosis in general practice. Lancet 2:893, 1972 7. Cunha BA, Rosenbaum GS: Management of the patient with urosepsis. Clin Challenge Infect Dis 11 (1):1989 8. Cypress BK: Patients' reasons for visiting physicians: National Ambulatory Medical Care Survey. United States, 1977-1978. In Vital and Health Statistics. Data from the National Health Survey, Series 13 (56) (DHHS Publication No. 82-1717). Hyattsville, MD, National Center for Health Statistics, 1981 9. Elder EH, Santamarina BAG, Smith S, et al: The natural history of asymptomatic bacteriuria during pregnancy: The effect of tetracycline on the clinical course and the outcome of pregnancy. Am J Obstet Gynecol111:441, 1971 10. Fairley KF, Bond AG, Brown RB, et al: Simple test to determine the site of urinary tract infections. Lancet 2:427, 1967 11. Fang LST, Tolkoff-Rubin NE, Rubin RH: Efficacy of single-dose and conventional amoxycillin therapy in urinary tract infection localized by the antibody-coated bacteria technic. N Engl J Med 298:413, 1978 12. Fihn SD, Latham RH, Roberts P, et al: Association between diaphragm use and urinary tract infection. JAMA 254:240, 1985 13. Forland M, Thomas V, Shelokov A: Urinary tract infections in patients with diabetes mellitus: Studies on antibody coating of bacteria. JAM A 238:1924, 1977 14. Freedman L: Chronic pyelonephritis at autopsy. Ann Intern Med 66:697, 1967 15. Freedman LR: Natural history of urinary tract infection in adults. Kidney Int 8:(S96), 1975 16. Gallagher DJ, Montgomerie JZ, North JD: Acute infections of the urinary tract and the urethral syndrome in general practice. Br Med J 5413:622, 1965 17. Gerzof SG, Gale ME: Computed tomography and ultrasonography for diagnosis and treatment of renal and retroperitoneal abscesses. Urol Clin North Am 9:185, 1982 18. Gleckman R, Blagg N, Hibert D, et al: Acute pyelonephritis in the elderly. South Med J 75:551, 1982 19. Hoverman IV, Gentry LO, Jones DW, et al: Intrarenal abscess: Report of 14 cases. Arch Intern Med 140:914, 1980 20. Jarvis WR, White JW, Munn VP, et al: Nosocomial infection surveillance, 1983. MMWR 33(2SS):9SS, 1983 21. Jodal U: The natural history of bacteriuria in childhood. Infect Dis Clin North Am 1:713, 1987 22. Johnson JR, Stamm WE: Diagnosis and treatment of acute urinary tract infections. Med Clin North Am 1:773, 1987 23. Kass EH: Bacteriuria and pyelonephritis of pregnancy. Arch Intern Med 105:194, 1960 24. Kass EH, Finland M: Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 69:56, 1956 25. Kass EH, Savage W, Santamarina BAG: The significance of bacteriuria in preventive medicine. In Kass EH (ed): Progress in Pyelonephritis. Philadelphia, FA Davis, 1965, pp 3-10 26. Kaye D: Important definitions and classification of urinary tract infection. In Kaye D (ed): Urinary Tract Infection and Its Management. St Louis, CV Mosby, 1972, p 1 27. Komaroff AL: Acute dysuria in women. N Engl J Med 310:368, 1984 28. Komaroff AL: Urinalysis and urine culture in women with dysuria. Ann Intern Med 104:212, 1986 29. Kreger BE, Craven DE, Carling PC, et al: Gram-negative bacteremia: Ill. Reassessment of etiology, epidemiology, and ecology in 612 patients. Am J Med 68:332, 1980 30. Kunin CM: Detection, Prevention, and Management of Urinary Tract Infections, ed 4. Philadelphia, Lea & Febiger, 1987, p 1 31. Lipsky BA: Urinary tract infections in men: Epidemiology, pathophysiology, diagnosis, and treatment. Ann Intern Med 110:138, 1989 32. Meares EM Jr: Acute and chronic prostatitis: Diagnosis and treatment. Infect Dis Clin North Am 1:855, 1987 33. Medical Research Council Bacteriuria Committee: Recommended terminology of urinarytract infection. Br Med J ii:717, 1979 34. Monzon OT, Ory EM, Dobson HL, et al: A comparison of bacterial counts of the urine

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