Patrick A. Murphy
Urinary tract infection (UTI) is one of the most common disorders seen in primary care. Most of these infections respond well to therapy, but complicated urinary infections can cause significant morbidity and mortality. This chapter provides a practical approach to the diagnosis, evaluation, management, and followup of ambulatory patients with UTIs. Some sexually transmitted diseases (STDs) (Chapter 37) and vulvovaginal infections (Chapter 102) may be confused with UTIs and are discussed elsewhere in this book.
General Considerations
Gram-negative, aerobic bacteria cause 90% to 95% of UTIs in all age groups, with Escherichia coli accounting for approximately 80% of community-acquired infections in women and 30% to 50% of nosocomial UTIs in men and women. There are more than 100 serotypes of E. coli, but only 8 of these commonly cause infection. Enterobacter, Klebsiella, Proteus species, and Pseudomonas are especially important as causes of nosocomial UTIs or of infection in people with structurally abnormal urinary tracts. Gram-positive bacteria cause 5% to 10% of UTIs; Staphylococcus saprophyticus is common in young women in the ambulatory setting (1), as is the enterococcus in nosocomial UTIs in patients of either sex. Viruses, mycobacteria, fungi, and parasites rarely cause UTIs. Fungi are most often seen in urine from patients who were recently in hospital and were or still are catheterized. Diabetes mellitus (DM) fosters fungal infection of the urine, as does failure to empty the bladder completely.
In women, the major cause of UTI is invasion of the urinary tract by bacteria that have ascended the urethra from the introitus. Women who are prone to infection have colonization of the vaginal introitus with the same serotypes of E. coli found in the fecal flora. Risk factors for acute UTI in women include a history of a recent UTI, increased sexual activity, use of a diaphragm and a spermicide, and failure to void after intercourse (2). There is little evidence to support the commonly held views that the direction of wiping after bowel movements or the use of oral contraceptives or tampons plays a role in the pathogenesis of UTIs in women (3).
Infection of the bladder and kidneys in men is unlikely unless there is a structural abnormality of the urinary tract. The much lower incidence of UTI in men has been attributed to the long male urethra, the absence of colonization by bacteria near the meatus, and an antibacterial factor—prostatic antibacterial factor—that is present in the prostatic fluid and is markedly diminished in some men who have recurrent prostatic infection. UTIs occur in some male homosexuals who have no abnormalities of the urinary tract (4) and in some men who are not circum-cised (5).
The bladder has unique intrinsic defenses against infection. The washout of bacteria by periodic voiding is probably one important defense mechanism. The bladder mucosa also removes surface organisms, perhaps by phagocytosis, secretion of mucus, production of surface antibody, or all of these methods. This defense mechanism
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is severely limited if residual urine is regularly present after voiding.
Host factors play an important role in the pathogenesis of UTIs (6). UTIs occur more often and more persistently in men and women who have structural abnormalities of the urinary tract (e.g., an obstruction) or who have been catheterized or instrumented. Vesicoureteral reflux (the retrograde flow of urine from the bladder to the ureters) may be associated with ascending infection but is not necessarily causal. Infection in women occurs more often during pregnancy (4% to 6% incidence), especially in women who also have sickle cell trait (10% to 15% incidence). DM does not increase the risk for development of a UTI unless there is an associated disorder of bladder emptying or the patient has been instrumented. However, once a UTI has developed in a diabetic patient, it may be more virulent.
General Diagnostic Evaluation
The diagnosis of UTI is suggested by the history and physical examination and confirmed by examination of the urine. Sometimes, radiographs and instrumentation of the urinary tract are necessary ancillary procedures.
The Patient with Irritative Symptoms—Diagnostic Approach
In young adults, UTIs are characterized by symptoms of bladder irritation such as frequency of micturition and dysuria. There may be urgency of micturition, and if a toilet is not immediately available, there may be minor leakage of urine or even complete incontinence. The urine is commonly cloudy and smells offensive. Suprapubic pressure or pain is commonly described. In a severe infection, there may be hematuria. If so, blood is evenly mixed throughout the volume of urine.
Approximately 30% of women with no fever and no symptoms other than those just described prove to have pyelonephritis when subjected to detailed examination (7). Clinical evidence of pyelonephritis is present only in a minority of women who in fact do have pyelonephritis. Such evidence would be temperature greater than 101.3°F (38.5°C), pain in the loin, chills and rigors, and evidence of frank sepsis such as tachypnea and hypotension. It is axiomatic that any woman with a UTI and a positive blood culture has pyelonephritis.
In women, usually (but not exclusively) between the ages of 15 and 50 years, vaginal infections and sexually transmitted diseases (STDs) may mimic UTIs (8). If a woman is treated for a UTI and she does not improve rapidly, the real cause of her problem may be one of these other infections. A pelvic examination should be performed if the history is suggestive of vulvovaginitis from candidiasis, trichomoniasis, or other infections that may account for the symptoms of bladder irritation (see Chapter 37). Chlamydial or gonococcal urethritis should also be considered in sexually active women (see Chapter 37). Both of these infections are most probable in women with many sexual partners, but both are found in 2% to 4% of married women presenting for routine antenatal care (6). Chlamydial cervicitis is characterized by mucopurulent cervical discharge with endocervical edema. Gonococcal infection typically causes a purulent discharge from the cervix. Both infections are best detected by polymerase chain reaction (PCR) tests on urine. The PCR test has completely replaced endocervical culture: the specimen is easier to get, and both sensitivity and specificity approach 100%.
In children younger than 5 years of age, UTI may present in atypical ways, such as bed-wetting, fever, vomiting, or inconsolable crying. Older children generally have the same symptoms as adults. Aged people, especially if demented or psychotic, may have very few symptoms referable to the urinary tract. They commonly experience delirium, fever, urinary incontinence, or even sepsis of unknown cause. Therefore, at the extremes of life it is unwise to rely on urinary symptoms.
UTI in pregnancy, known to older obstetricians as pyelitis of pregnancy, is a highly dangerous condition (9). The diagnosis is difficult because there may be few bladder symptoms. Instead, the patient commonly has intractable vomiting in the second or third trimester, elevated blood pressure with superimposed preeclampsia or eclampsia, renal failure, sepsis, or premature labor. UTI in pregnant women usually takes the form of pyelonephritis because the ureters are dilated and atonic and ascending infection is facilitated. Most cases of frank pyelitis of pregnancy are preceded by asymptomatic bacteriuria: treatment of the bacteriuria as soon as it is discovered leads to a much lower subsequent incidence of pyelonephritis and its serious complications.
Urine Examination
The urinalysis is the most important initial study in the evaluation of the patient suspected of having a UTI, because a negative urinalysis makes a UTI unlikely and because a urinalysis may aid in the localization of an infection within the urinary tract.
Urine Collection
Collection of a clean-catch midstream urine specimen can be difficult, especially for women. The superiority of this procedure for reducing contamination compared with routine midstream urine collection has not been demonstrated (10). Therefore, culturing a simple midstream urine specimen voided into a sterile container should be
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sufficient for most outpatients of both sexes. The midstream collecting procedure may be impossible in women who are very obese or who have other disabilities. In this instance, urine must be obtained by bladder catheterization.
Catheterization of the urinary bladder is accomplished by using a no. 14 catheter inserted through the urethra into the bladder and removed when the specimen has been obtained. This requires careful preparation and cleansing of the urethra with an aseptic solution such as povidone-iodine (Betadine). Even with this precaution, a single straight catheterization has a 1% risk of inducing a new infection in ambulatory patients.
Urinalysis
If the urine specimen cannot be processed by the laboratory within 10 to 15 minutes after collection, it must be refrigerated until it reaches the laboratory.
The uncentrifuged specimen can be examined microscopically under a coverslip with use of the oil immersion lens. The finding of bacteria by this method has a 90% correlation with the subsequent culture of more than 1 million bacteria per milliliter of urine. The number of white blood cells (WBCs) in the uncentrifuged urine can be roughly quantitated microscopically in a counting chamber by the use of the low-power lens. In women, the finding of more than seven WBCs per cubic millimeter is abnormal (although not specific for infection). The finding of seven or fewer WBCs per cubic millimeter suggests that infection is not present. In men, the finding of any number of WBCs should be considered abnormal.
Centrifuged urine in some ways is more convenient to examine than is uncentrifuged urine. WBC casts are more easily seen in centrifuged urine; they are important because they are positive proof of pyelonephritis. Red cells, WBCs, and bacteria are all concentrated and more easily detected. Small numbers of WBCs seen in centrifuged urine are unreliable, and pyuria should not be considered significant unless there are more than 10 WBCs per high-powered field (HPF).
As a practical matter, microscopic examination of the urine for bacteria is difficult or impossible in most doctors’ offices. Because in many cases there is little doubt about the diagnosis, it is reasonable either to treat the patient empirically (e.g., first or recurrent uncomplicated infections in women) or to use the urine dipstick as a rapid diagnostic aid. There may be abnormalities in tests for pH, protein, or blood, but these are nonspecific. The abnormalities specifically correlated with infection are found with the dipstick-based nitrite test and the test for leukocyte esterase. Nitrite is generated by the reductive activity of bacteria on urinary nitrate. Leukocyte esterase reflects the presence of WBCs in the urine. If both of these are positive, the specificity for UTI is greater than 90% (11,12). Not all bacteria reduce nitrate, and not all UTIs are associated with a sufficient number of WBCs in the urine to yield a positive esterase test. (For example, the sensitivity of the test is 100% for 50 WBCs per HPF or more, but it is approximately 40% for 6 to 12 WBCs per HPF.) An important cause of a false-negative nitrate test is the ingestion of large amounts of vitamin C. If the patient is symptomatic but the dipstick is negative, one should try direct demonstration of bacteriuria by microscopy or culture before deciding that infection is not present.
Urine Culture
Many women know perfectly well that they have a UTI and merely need a prescription for antibiotics with instructions to recontact the caregiver if symptoms persist (see Management of Symptomatic Urinary Tract Infections in Women). Culture of the urine in such patientsincreases the cost of the evaluation, is inconvenient, and rarely affects one's decision because the patient is better before the answer is known. On the other hand, a urine culture should always be obtained before therapy in patients who have recently been hospitalized or who are seriously ill and febrile. Infections in pregnant women are so serious that urine should always be cultured. Infections in young men are sufficiently unusual that a culture should also be obtained. In other patients, clinical judgment should dictate whether a culture is done.
If a urine culture is performed, the specimen should be refrigerated during transport to the laboratory. Most patients with symptomatic UTI have at least 105 bacteria per milliliter of urine. However, some people develop symptoms of cystitis in the presence of 103 or even 102organisms per milliliter of urine. If such patients are not treated, they tend to return with more severe symptoms and higher bacterial counts in the urine (13).
When urine is sent for culture, the species of bacteria isolated is also important. Multiple species suggest contamination, except in chronically catheterized patients or in special circumstances such as a vesicocolic fistula. Even small numbers of definite pathogens such asE. coli or Klebsiella should be regarded as suspicious. Conversely, large numbers of skin flora such as Staphylococcus epidermidis or diphtheroids can usually be ignored. Anaerobic bacteria virtually never cause UTI, and if they are repeatedly present, a communication with the bowel is suggested. The presence of fungi, usually Candida, is seldom correlated with symptoms or signs of UTI and in most cases is inconsequential.
Culture of urine specimens can be difficult in remote parts of the country. Commercially available kits allow one to dip a coated slide into fresh urine, drain it, and incubate it. Colonies develop directly on the slide, and the counts
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correlate well with those obtained by quantitative plate cultures (14).
Culture-Negative Urine
If the patient has not taken an antimicrobial, has symptoms of cystitis with or without pyuria, but the urine does not contain visible or cultured bacteria, the most likely explanation is that the patient has urethritis, prostatitis, or vaginitis. However, adenovirus can cause symptomatic cystitis, and chemical cystitis can be caused by several chemotherapeutic agents. In patients with culture-negative pyuria, tuberculosis of the kidney, bladder stone, bladder tumor, and interstitial cystitis should be con-sidered.
Localizing the Site of Infection
Several techniques may characterize a UTI as either confined to the bladder or involving the kidneys. However, in most cases it is unnecessary to try to decide whether the patient has cystitis, pyelonephritis, or prostatitis. Many patients with pyelonephritis respond to standard 3-day treatment regimens described later in this chapter.
The simplest indication that a patient has pyelonephritis or prostatitis that requires prolonged treatment is that the UTI relapses after a standard 3-day course of antimicrobials that would be expected to clear a simple bladder infection. Relapse means that all of the infectious episodes are caused by the same organism, as defined not only by species but also by any other available characteristics such as antimicrobial sensitivity or serotype. Relapsing episodes are not necessarily caused by pyelonephritis: They may be caused by persistent colonization of the introitus and multiple episodes of ascending infection. Most cases of recurrent UTI are managed by prolonged courses of antibiotics, as discussed in section Management of Recurrent Infection, Reinfection Type.
In pyelonephritis, the bacteria in the urine are usually coated with antibody. This can be detected with the use of fluorescent goat antihuman immunoglobulin. In cystitis, bacteria in the urine are generally free of antibody. This test is not absolutely reliable: antibody-coated bacteria may be found in prostatitis, and antibody-negative bacteria may be obtained from some cases of pyelonephritis. For this reason, the test is of limited clinical value and should rarely be performed.
Other techniques are cumbersome because they require urethral or ureteral catheterization. The standard criterion for localization of upper tract infection is bilateral ureteral catheterization with separate collection of the urine from each kidney. There is a less complicated bladder washout technique that detects pyelonephritis but gives no information about the side of the infection. Radiographic abnormalities such as renal cortical scars are not present in most cases of pyelonephritis. Localization of the UTI is so seldom needed in clinical practice that patients who require it should be referred to a urologist.
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TABLE 36.1 Indications for Evaluating Patients Who Have Urinary Tract Infections with Ultrasonography |
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Imaging
Uncomplicated UTIs that respond to treatment do not require additional workup. However, some clinical situations warrant investigation for anatomic abnormalities (Table 36.1). In office practice, an intravenous pyelogram (IVP) is no longer the most appropriate way to evaluate renal anatomy. Sonography is quicker and less dangerous to renal function. It detects kidney size, cortical scars, stones, and hydronephrosis. If sonography is normal, IVP is unlikely to add more information (15). Sonography is particularly useful for detecting and estimating the volume of residual urine in patients who cannot empty the bladder.
Computed tomography (CT) scanning is most useful for the detection of perinephric abscess and as a prelude to operations on the kidneys.Voiding cystourethrography is another test that should be delegated to the urologist.
Management of Symptomatic Urinary Tract Infections in Women
First Infection, Occasional Infection, or Uncomplicated Infection
Most women with UTIs experience only one or an occasional uncomplicated infection. The diagnosis of a UTI can be confirmed by urinalysis and urine culture; however, as discussed earlier, a therapeutic trial is usually sufficient and is more convenient and far less costly for the patient. Although an uncomplicated infection may clear spontaneously in time, treatment with antimicrobials dramatically shortens the symptomatic period and should be given. Forcing fluids, historically a common practice, is discouraged once antimicrobial therapy has been initiated because it may actually dilute significantly the concentration of antimicrobial in the urine.
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TABLE 36.2 Antimicrobial Agents for Uncomplicated Urinary Tract Infections (3-Day Therapy) |
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Antimicrobial Treatment
Uncomplicated UTIs should usually be treated with an antimicrobial for 3 days (Table 36.2). Three days of treatment gives the same cure rate as the traditional 7- to 10-day courses, and there is little superinfection with Candida, a common occurrence with the longer course. One-dose therapy was popular a number of years ago, but the cure rate is less than that attainable with 3 days of therapy.
There is a randomized controlled trial showing that UTI in presumably healthy young women can be managed effectively over the telephone (16). There is also a controlled trial showing that patients who are given antibiotics in advance can diagnose and treat their own UTIs (17).
For patients who are not pregnant, a wide range of drugs can be used. Probably the best available therapy is trimethoprim–sulfamethoxazole (TMP-SMX). This produces little in the way of allergy, kills most gram-negative rods, tends to sterilize the vaginal introitus, and is inexpensive. Overall, the cure rate is 90% to 95% (18). Patients who are allergic to sulfonamides can be treated with a quinolone, a tetracycline, or nitrofurantoin. Because TMP-SMX has been extensively used in the last 20 years, the incidence of resistance is rising all over the country. Surveys show that resistance to TMP-SMX varies from a minimum of 7% in Pennsylvania to a maximum of 33% in Iowa (19). Resistance reported in the laboratory is not necessarily correlated with clinical failure because of the very high concentrations of antibiotics in the urine. However, at some point TMP-SMX is going to lose its effective-ness (20).
β-Lactams such as ampicillin and cephalosporins are less effective than the four drugs mentioned earlier. However, in pregnant women there is no reasonable alternative to β-lactams because of the risk of harm to the fetus. Therefore, a somewhat increased risk of recurrent UTI must be accepted. In the rare pregnant woman with a serious penicillin allergy, aztreonam should not cause anaphylaxis, and will be effective against most gram-negative rods. One could consider an aminoglycoside, but there is a risk of fetal deafness.
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TABLE 36.3 Points to Consider in Educating Women Who Have Had an Uncomplicated Infection |
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Any of the above treatments usually sterilizes the urine and produces total relief of symptoms in 24 hours or less. In very symptomatic patients, one could add the bladder analgesic phenazopyridine (Pyridium), 200 mg three times a day for 1 day or longer. This drug, which requires a prescription, usually alleviates annoying symptoms, especially dysuria and urgency, within hours after the first dose. The patient should be told that phenazopyridine will cause the urine to become dark orange.
If the patient remains asymptomatic after treatment, she may be regarded as cured without the need for any additional followup.
Table 36.3 summarizes the points to stress to women after a UTI episode. The behaviors that most often help prevent recurrent UTI are emptying the bladder after sexual intercourse and avoiding a full bladder. If a woman is using a diaphragm for contraception, a change in contraceptive method should be considered (see Chapter 100).
Management of Recurrent Infection, Reinfection Type
Most women with recurrent UTIs have reinfection (rather than relapse, which is discussed below). Although the
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infections are symptomatic and occasionally may be associated with pyelonephritis, recurrent reinfections in women with structurally normal urinary tracts rarely, if ever, lead to chronic renal failure.
The approach to women with anatomically normal urinary tracts and the syndrome of reinfection has been vastly improved by the understanding of the pathogenesis of UTI in women. In the past, women often were treated with a variety of painful manipulations such as urethral dilation, urethral incision, transurethral resection of the bladder neck, installation of a variety of intravesical agents, and other inappropriate and ineffective maneuvers. Instead, each episode of bacterial infection should be treated as outlined previously in the section on first infections. If there are three or more recurrences in a year, the urinary tract should be evaluated for anatomic abnormalities (seeGeneral Diagnostic Evaluation). Patients with structural problems should be referred to the appropriate specialist (urologist or gynecologist). If the urinary tract is normal, prophylactic antimicrobials should be considered.
Prophylactic Antimicrobial Therapy
A number of studies have confirmed the efficacy of prophylaxis in reducing the frequency of UTI in women, and prophylactic therapy has dramatically improved the lives of many women with multiple UTIs. The agents that have been used are effective when given as a single small dose at bedtime. A dose taken only after sexual intercourse is also effective in patients whose recurrent UTIs are clearly associated with sexual activity. Patient acceptance is good, and side effects are uncommon.
Many agents have been shown to be effective prophylactically, but nitrofurantoin (Furadantin), a 50-mg tablet at bedtime; TMP-SMX, 40/200 mg (half a tablet of regular strength Bactrim, Septra, or generic) at bedtime; and cephalexin (Keflex or generic), a 250-mg capsule at bedtime, are used most commonly and are recommended. In some patients, the antibiotic may be effective when given on 3 days of the week. Prophylactic therapy should be continued for 6 months. If there are still frequent recurrences after the cessation of prophylaxis, prophylaxis for a longer period (e.g., 1 year) should be tried.
Estrogens
In elderly women, the vaginal cells lose glycogen, lactobacilli vanish from the vaginal flora, and the introitus becomes colonized with gram-negative rods. A controlled trial demonstrated that the frequency of recurrent UTIs in elderly women can be greatly reduced (from an average incidence of 5.9 to 0.5 episodes per year) by the use of intravaginal estrogen creams (21). Treated patients used intravaginal cream containing 0.5 mg of estriol on the following schedule: nightly for 2 weeks, then twice weekly for 8 months. Presumably, systemic estrogens would have the same effect.
Clinical Syndromes That Mimic Urinary Tract Infections in Women
There are two syndromes in women that mimic classic UTI: the urethral syndrome, which is common, and interstitial cystitis, which is rare.
Urethral Syndrome (Dysuria–Pyuria Syndrome)
The urethral syndrome is characterized by bladder irritation, frequency, urgency, and dysuria without significant (greater than 105) bacterial colonies per milliliter on culture. Dysuria–pyuria syndrome may be the better term, because dysuria is invariable and most patients have pyuria (more than eight WBCs per cubic millimeter of clean uncentrifuged urine). Studies show that many women with the syndrome have bacterial infection with a low bacterial colony count (22). These infections respond to the standard therapy for uncomplicated UTI described earlier.
The urethral syndrome can also be caused by any of several sexually transmitted infections. Chlamydia, gonorrhea, and herpes simplex are the most common causes. Other agents such as Mycoplasma hominis and Ureaplasma urealyticum may be found, but their significance is uncertain. Any woman who has acute onset of dysuria and has urine that is apparently sterile may have one of these infections. The patient should have a pelvic examination to check for the signs of common STDs, and the appropriate specimens should be obtained for culture and other examinations (see Chapter 37).
If the patient has never been sexually active, or has not been sexually active for years, then the dysuria–pyuria syndrome is occasionally caused by a viral infection. Adenovirus is the most common cause.
Of women who have the urethral syndrome, 5% to 10% do not have a demonstrable infectious agent even when special culture methods are used; most often these patients do not have pyuria. The cause of the syndrome in these instances is unknown. In this group, treatment with reassurance, sitz baths, and the urinary tract analgesic phenazo-pyridine (Pyridium), 200 mg three times a day for 5 to 10 days, will provide some relief. The patient should be informed that this medication causes the urine to appear orange. If symptoms persist, referral to a urologist is indicated for cystoscopic evaluation.
Measures to be recommended to patients with this syndrome should be identical to those outlined for UTI (Table 36.3) or, if there is vaginitis or an STD present, as outlined in Chapter 37.
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Interstitial Cystitis
Interstitial cystitis is an occasionally seen disorder affecting middle-aged women that, early in its course, may be confused with the urethral syndrome. Interstitial cystitis causes symptoms of suprapubic discomfort, especially when the bladder is full, and symptoms are relieved by voiding. The patient may experience progressive loss of bladder volume and increasing urinary frequency, and eventually may have to void four to six times per hour throughout the night. The urinalysis is often normal, but hematuria may be present. The urine is sterile. This disease is difficult to diagnose. If it is suspected on the basis of the history, referral to a urologist is indicated. The urologist performs cystoscopy and often a biopsy of the bladder to establish the diagnosis (usually a normal-appearing mucosa with a very small vesical capacity is identified; tissue histology may show changes consistent with the diagnosis; mucosal hemorrhage may appear with bladder filling). Also, a cystoscopic evaluation permits the urologist to exclude other causes of the symptoms (e.g., bladder tumor). No definitive therapy has yet been developed for treatment of this condition.
Vaginitis and Cervicitis
For detailed discussion of these conditions, see Chapter 37.
Symptomatic Urinary Tract Infections in Men
Bacterial Cystitis
Bacterial cystitis in men is similar in presentation to that in female patients and is diagnosed by the same method, but a urine culture should always be obtained. A UTI in a man suggests the presence of an underlying structural problem or the presence of bacterial prostatitis. In the past, it was felt that the initial evaluation should always include a prostate examination. However, because young men who are either homosexual or uncircumcised can develop UTIs in the absence of a structural abnormality, some easing of this standard is reasonable in men from either of these groups (4,5). If a workup is initiated, sonography is preferable to IVP as a screening tool.
A small number of young boys develop UTI in the apparent absence of a structural abnormality. Most turn out to have a congenital abnormality such as urethral valves. Young men with UTIs most often have stones or hydronephrosis. Older men usually have prostatic enlargement or stones.
Bacterial cystitis in men should always be treated for a minimum of 7 to 10 days (see daily dosages and schedules for antibiotics, Table 36.2). Structural problems are so common that short courses are ineffective. Even if no structural anomaly is found, men should be carefully followed up, because many of the infections relapse. Many men with relapse-type recurrences have bacterial prostatitis; therefore, a followup visit 4 to 6 weeks after the initial infection should be arranged to reculture the urine and, if it is positive, to consider treatment for chronic prostatitis.
Prostatitis
Prostatitis is classified as bacterial prostatitis (acute or chronic), nonbacterial prostatitis (prostatosis), or the much less common prostatic infections caused by a virus, a parasite, tuberculosis, a fungus, or nonspecific granulomatous changes.
Acute Bacterial Prostatitis
Acute bacterial prostatitis is characterized often by the abrupt onset of fever, chills, low back pain, and perineal pain with irritative urinary tract symptoms, although on some occasions, systemic symptoms are not pronounced. Perineal discomfort may be worsened by defecation. In addition, the patient may have initial, terminal, or occasionally total hematuria (see Chapter 49). Rectal examination usually discloses a tender, swollen, and boggy prostate. The urine and the expressed prostatic secretions contain leukocytes, and culture often grows the responsible bacterial pathogen, which most commonly is E. coli in older men and Chlamydia or Neisseria gonorrhoeae in younger men.
When the diagnosis is made, the patient may require hospitalization, although if systemic symptoms are minimal, ambulatory therapy is appropriate. Most antibiotics do not achieve high concentrations in prostatic fluid. The best initial choice for younger patients is levofloxacin(500 mg once or twice daily), which penetrates the prostate well and covers the common etiologic organisms. If quinolones cannot be used, a number of other antimicrobials may be tried.TMP-SMX does penetrate prostatic epithelium and is an alternative for treating E. coli.Penicillins and cephalosporins do not achieve effective concentrations in the prostate and are not useful. Because of the overriding effects of local antimicrobial concentration, antibiotics such as erythromycin, which would not normally be used to treat E. coli, may also prove effective. Therapy with antimicrobials for acute prostatitis should be continued for 2 weeks. Table 36.2 lists dosages and schedules.
Bed rest and sitz baths for 20 to 30 minutes two or three times a day may provide comfort. Occasionally, prostatitis results in acute urinary retention, which requires hospitalization and urgent urologic consultation. The palpable
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irregularity of the prostate gland after acute infection may persist for several months. The acute infection is readily controlled, but recurrences may occur, especially in older patients.
Chronic Bacterial Prostatitis
The organisms that cause chronic bacterial prostatitis most often are gram-negative bacilli, E. coli being the most common organism, followed by Enterococcus, Proteus, and Klebsiella. Most patients with chronic bacterial prostatitis have mild irritative symptoms (frequency, urgency, and dysuria), and occasionally there is a urethral discharge. Fever is absent. Patients may also have painless hematuria or painful ejaculation with hematospermia. On rectal examination, the prostate gland feels somewhat irregular and may be mildly tender, although the examination is often unremarkable.
Obstructive symptoms are rare. Most often the patients have intermittent symptomatic episodes that have been controlled with short courses of antibiotics. However, recurrent infection is common because of persistence of bacteria within the urinary tract. Chronic prostatitis may also be a reservoir for acute symptomatic cystitis, pyelonephritis, or epididymitis. Therefore, a prolonged course of therapy is indicated when chronic prostatitis is diagnosed clinically. If the infectious organism is sensitive, ciprofloxacin, 250 mg twice daily for 2 weeks, has been shown to be effective in eradicating infection in more than 60% of patients with chronic prostatitis (23).
If all efforts to eradicate infection fail, symptoms usually can be controlled with suppressive therapy using a low dose of TMP–SMX, one-half tablet of regular strength (Bactrim, Septra, or generic) nightly, indefinitely. The only way to effect a cure is by radical prostatectomy, but the morbidity of this procedure precludes its use for benign disease. Repeated prostatic massage has not been shown to be effective. Patients with refractory chronic bacterial prostatitis should be evaluated by an urologist.
Nonbacterial Prostatitis (Prostatosis)
Some patients have all of the symptoms and signs of chronic bacterial infection of the prostate, but no organism can be demonstrated. They have nonbacterial prostatitis (prostatosis), which is the most common form of prostatic inflammation. These patients have mild perineal pain and irritative symptoms on urination with WBCs in the urine sediment, but negative urine cultures. Culture of the secretions and urine by special techniques occasionally reveals infectious agents such as Mycoplasma, Gardnerella vaginalis, U. urealyticum, or Chlamydia species; however, the significance of these findings is unknown. Most patients with this condition cannot be cured; nevertheless, treatment with an antimicrobial such as ciprofloxacin or levofloxacin at the dosage and schedule described for acute prostatitis may control symptoms. An antispasmodic agent such as oxybutynin (Ditropan), 5 mg two to three times a day, may be tried. Therapeutic prostatic massage has not been shown to be of value.
If there is no response to therapy, the patient should be referred to a urologist to exclude conditions such as interstitial cystitis and in situbladder cancer. Both conditions require cystoscopic examination for confirmation.
Prostatodynia
Patients with a syndrome called prostatodynia have symptoms suggesting prostatic inflammation but have no evidence of inflammation on physical examination, have no WBCs in the urine or in expressed prostatic secretions, and have sterile urine cultures. There is some evidence that the syndrome may be caused by a neurologic disorder and that muscle relaxants or α-sympathetic blocking agents such as phenoxybenzamine (Dibenzyline) are effective in treating it. If this syndrome is suspected, urologic consultation is suggested to confirm the diagnosis, to rule out interstitial cystitis and bladder cancer, and to initiate therapy.
Epididymitis
In young men, this infection is usually caused by sexually transmitted pathogens. Chapter 37 describes the manifestations, management, and course of sexually transmitted pathogens.
The older patient with acute epididymitis should always have a urine culture and should be evaluated for obstruction at the bladder outlet (see Chapter 53) as soon as the acute symptoms are controlled. On rare occasions, continued pain from chronic epididymitis may occur; if it does, a urologist should be consulted, because an epididymectomy may be required.
With great rarity, chronic epididymitis may turn out to be caused by tuberculous or fungal infection of the urinary tract. There is commonly involvement of the kidneys and/or the prostate in such cases, and the urine is generally positive on culture for tubercle bacilli or one of the fungi capable of causing invasive disease.
Urethritis
Urethritis is an acute inflammation of the urethra that may be classified as gonococcal or nongonococcal. All forms of urethritis are assumed to be sexually transmitted. Chapter 37 discusses this topic in detail.
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Persistent Urinary Tract Infection in Men and Women
As noted earlier, treatment in the male or female patient of infection in a normal urinary tract with an appropriate antimicrobial should result in the sterilization of the urine within 72 hours. By this time, symptoms should have abated or at least markedly diminished. If symptoms continue, a persistent infection may be present, and the urine culture should be repeated. If the urine culture is still positive despite antimicrobial therapy, further investigation is required. Modern antimicrobials are so effective and the concentrations achieved in urine are so high that persistent infection is unusual.
The possibilities to be considered are that the patient is not taking the antimicrobial or has taken it but vomited subsequently; the organism is totally resistant (unusual but seen with certain pseudomonads and enterococci); the patient's renal function is so poor (e.g., creatinine greater than 3 mg/dL) that little antimicrobial reaches the urine; the antimicrobial does not work at the current urinary pH; there is a gross structural anomaly such as bladder carcinoma, a vesicocolic fistula, or a leaking pyonephrosis; there is a nidus of sequestered bacteria such as a staghorn calculus; or the organism is not a bacterium at all, but a fungus. Once one has decided which of the above applies, the indicated treatment is usually obvious.
Recurrent Infection, Relapse Type, in Men and Women
Recurrent infection with the same organism is called relapse infection and implies the persistence of bacteria in tissue within the urinary tract. Relapse infection is similar to persistent infection except that in relapse the urine was shown to be sterile while the patient was taking or had completed antimicrobial therapy, whereas sterility is never demonstrated with persistent infection. Relapse occurs most often within 6 weeks after completion of a course of antimicrobial therapy. An underlying structural problem is often present in both men and women with this condition. In women, relapse is much less common than reinfection but is difficult to document because most infections are caused by E. coli, which has many serotypes that cannot be differentiated by routine bacteriologic laboratory techniques. Therefore, recurrent UTI caused by E. coli may be either relapse (same serotype) or reinfection (different serotype). On the other hand, relapse of infection with organisms other than E. coli may be diagnosed by routine bacteriologic culture. In women, if recurrent infection with E. coli occurs four times in a 12-month period or if relapse infection with other species occurs, evaluation as described previously (see Persistent Urinary Tract Infection in Men and Women) to exclude the possibility of structural abnormality is appropriate. If a structural abnormality is identified, it should be corrected if possible.
If a woman or man has a structural or functional abnormality of the urinary tract that cannot be corrected, sterilization of the urinary tract usually is not possible. In a patient who has had recurrent infections because of urine stasis caused by an atonic bladder, intermittent straight catheterization by the patient or a trained member of the family may help to prevent recurrent infections (see Urinary Incontinence in Chapter 54). In patients with other abnormalities, suppressive therapy (see regimens for prophylaxis of recurrent cystitis, discussed previously) may decrease the frequency of symptomatic exacerbations or episodes of sepsis. Relapsing infection may occur in patients with no evidence of a structural abnormality. In women, that usually means that the patient has chronic pyelonephritis. In men, the most common cause is chronic bacterial prostatitis. Chronic pyelonephritis is generally treated with a 6-week course of an appropriate antimicrobial, on several occasions if necessary. Some patients may eventually respond to prolonged antimicrobial courses of 6 months or more. These prolonged courses are generally indicated only in young patients where there is some hope of cure.
If the patient has chronic bacteriuria that cannot be eradicated, there is some evidence that the ingestion of large quantities of cranberry juice will reduce the number of symptomatic episodes (24).
Infection in Catheterized Patients
In the ambulatory setting, one often sees patients who were catheterized while acutely ill in the hospital, developed infection, and now have bacteriuria, even though the catheter has been removed. In general, these patients should be treated based on bacterial sensitivities, because otherwise they will probably develop symptomatic episodes of cystitis or pyelonephritis. The usual course of treatment is 10 days, and because recurrence is common, a “cure” urine culture should be done.
Acute Pyelonephritis in Men and Women
Pyelonephritis is a bacterial infection of the kidney that most often results from ascending infection. It is suggested by flank pain, fever, and often, abdominal pain in addition to symptoms of bladder irritation. Bacterial infection of the kidney may also be present without any of these signs or symptoms or with only bladder irritation. The urinalysis will show changes as outlined previously, but only
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the presence of WBC casts is diagnostic of pyelonephritis.
Clinically apparent acute pyelonephritis in men suggests the presence of a structural problem predisposing to infection and is an indication for immediate hospitalization, parenteral antimicrobial therapy, a sonogram, and possibly other urologic investigations. If an abscess is seen or suspected, a CT scan is indicated, because abscesses usually need surgical drainage.
In women, an underlying structural problem is much less likely to be present. Therefore, the decision for hospitalization and evaluation requires careful consideration. The patient can be treated at home if she does not have complicating medical illnesses, is not severely ill, does not exhibit sepsis, is reliable, and can take antimicrobials by mouth, and if access to the physician is guaranteed should symptoms worsen. If a patient is treated at home, followup in 24 to 48 hours by telephone is necessary. If there has not been significant improvement during that time, the possibility of an undrained infection (caused, for example, by an obstruction or abscess) should be considered and prompt hospitalization should be arranged for parenteral antimicrobials, sonography, and emergency urologic consultation.
The initial treatment for the patient treated at home can be a 10- to 14-day course of any of the antimicrobial agents listed in Table 36.2, with an appropriate adjustment based on the results of the urine culture and on sensitivity testing. Forcing fluids (once antimicrobial therapy has been started) is unnecessary and may theoretically be detrimental because the concentration of antimicrobials in the urine and in the renal tissue may be diluted. However, intake should be adequate to replace fluid losses, including the additional fluid lost by fever or by vomiting.
If the acute episode of pyelonephritis promptly resolves, followup in 3 to 4 weeks is appropriate. At that time, the urine culture should be sterile. If the urine is not sterile and if the organism is the same one that caused the clinical attack of pyelonephritis, the patient is a candidate for a prolonged course of antibiotic therapy (6 weeks).
Asymptomatic Bacteriuria
Asymptomatic Bacteriuria Not Associated with Pregnancy
Asymptomatic bacteriuria is more common in women and increases in both sexes with advancing age. Among people age 20 to 50 years, bacteriuria is present in 0.5% of men and fewer than 5% of women. In contrast, 3% of men and 20% of women 65 to 70 years of age have positive urine cultures. After age 80, 22% of men and 23% to 50% of women have bacteriuria (25).
In addition to advancing age, asymptomatic bacteriuria is also associated with indwelling urinary catheters, urinary incontinence, multiple medical illnesses, impairment of functional status, and impairment of mental status.
Several population studies report an unexplained increase in mortality among elderly patients with asymptomatic bacteriuria. This increase appears to be secondary to concomitant illnesses rather than a direct consequence of the bacteriuria, and treatment of the bacteria does not affect mortality (26). It is not known how often non-pregnant patients with asymptomatic bacteriuria develop symptomatic infections. Treatment with antimicrobial therapy is often unsuccessful in eradicating infection and may be associated with the development of more resistant infections (27). Therefore, screening for or treatment of asymptomatic bacteriuria in nonpregnant adult women or men of any age is not recommended.
Asymptomatic Bacteriuria Associated with Pregnancy
Asymptomatic bacteriuria in pregnancy is common, affecting up to 6% of women in the first trimester. Recognition of this fact is important, because eradication of bacteriuria reduces the high incidence of symptomatic UTI that subsequently occurs during pregnancy and may increase the risk of premature birth (9). The drugs used are β-lactams, which are known to be associated with a higher rate of recurrent infection than are quinolones or TMP–SMX. Good followup is therefore essential.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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