Urinary Tract Infections

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Management of Acute U ncompl icated Urinary Tract Infection in Adults Thomas M. Hooton, MD, * and Walter E. Stamm, MDt

UNCOMPLICATED URINARY TRACT INFECTION IN WOMEN Acute uncomplicated urinary tract infections (UTIs) in adults include episodes of acute cystitis and acute pyelonephritis that occur in otherwise healthy individuals who have none of the risk factors that are known to increase the risk of treatment failure. The majority of these infections occur in women, but occasional cases are seen in men without urologic abnormalities or instrumentation. It has been reported that approximately 25% to 35% of women between the ages of 20 and 40 give a history of having had an episode described by their physician as a UTI.25 The cost of evaluation and treatment of ambulatory women with dysuria, not including the many thousands who require hospitalization, has been estimated to approximate 1 billion dollars annually in the United States. 22 A large but undefined proportion of these infections and costs is related to the diagnosis and management of uncomplicated infections. What Defines an Uncomplicated Urinary Tract Infection? The distinction between uncomplicated and complicated UTIs is important mainly because of its implications regarding pre- and posttreatment evaluation, type and duration of antimicrobial regimens, and extent of evaluation of the urinary tract. A complicated infection is one that is associated with a condition that increases the risk of developing an infection or having a persistent infection. Acute cystitis results from superficial infection of the bladder mucosa, whereas acute pyelonephritis involves an invasion of the renal interstitium. Acute cystitis is uncomplicated if there is only superficial mucosal involvement, as is almost always the case, but it may be complicated, for example, if there is a coexisting bladder stone. From the University of Washington School of Medicine; and Department of Medicine, Harborview Medical Center, Seattle, Washington


Professor of Medicine and Head, Division of Infectious Diseases

t Professor of Medicine;

Medical Clinics of North America-Vo!' 75, No. 2, March 1991







Based on localization tests, it appears that approximately one third of patients who have characteristic symptoms of acute cystitis also have evidence of occult infection of the upper urinary tract. 23 Although generally uncomplicated, such infections can certainly be considered more extensive. Likewise, acute pyelonephritis, usually considered to be a complicated infection, should be considered uncomplicated in the healthy host infected with a virulent uropathogen; from the host's perspective, the infection is uncomplicated. Of course, one generally does not have complete knowledge about patients who present with acute onset of urinary tract symptoms with which to determine whether an infection is complicated. However, several factors have been identified that are markers for the presence of occult renal infection or complicated UTI (Table 1). It is generally safe to assume that a young, sexually active, nonpregnant woman with recent onset of dysuria, frequency, or urgency who has not been recently instrumented or treated with antimicrobials and who has no history of a genitourinary tract abnormality has an uncomplicated lower (cystitis) or upper (pyelonephritis) UTI. What Is the Pathogenesis of an Uncomplicated Urinary Tract Infection? A UTI develops when uropathogens, generally from the reservoir of fecal flora, colonize the vaginal introitus, enter the urethra, ascend into the bladder, and stimulate a host response manifested by symptoms and, in most cases, pyuria. It has been established that colonization of the vaginal introitus with uropathogens precedes most UTIs 52 . 54 although the colonizing strain may not always be identical to the infecting strain.4 It may be that, in some cases, the infecting strain colonizes the vaginal introitus and urethra for only a short time before the onset of urinary tract infection. Women with recurrent UTI have been shown to have an increased susceptibility to vaginal colonization with uropathogens compared with women without a history of recurrent UTI. At least in part, this appears to result from a greater propensity for uropathogenic coliforms to adhere to the uroepithelial cells of recurrently infected women as compared with cells from women without recurrent infection. 11. 48 Women with recurrent UTI also are more Table 1. Factors That Suggest the Presence of an Occult Renal Infection or a Complicated Urinary Tract Infection Male sex Presentation in an urban emergency department Hospital-acquired infection Pregnancy Indwelling urinary catheter Recent urinary tract instrumentation Functional or anatomic abnormality of the urinary tract Childhood urinary tract infection Recent antimicrobial use Symptoms for >7 days at presentation Diabetes Immunosuppression

Adllpted from Johnson JR, Stamm WE: Diagnosis and treatment of acute urinary tract infections. Infect Dis Clin North Am 1:773, 1987.





likely to be nonsecretors of blood group antigens. 50 Data from a recent prospective study that we have done shows that women with a history of recurrent UTI are, in fact, more likely to be colonized with uropathogens as compared with women without such a history, but the difference in colonization was not nearly so dramatic as the difference in UTI incidence during prospective observation. It is likely that introital or urethral colonization merely facilitates entry of bacteria into the bladder but is not itself the main predisposing factor leading to UTI. Bacterial virulence factors may influence whether or not a specific colonizing strain eventually causes symptomatic infection, 59 but virulence factors unique to strains causing cystitis have not as yet been identified. Data from both retrospective and prospective studies suggest that sexual intercourse, presumably through a mechanical effect of introducing uropathogens into the bladder, is one of the most important risk factors for developing uncomplicated UTIs in women. 30, 42, 58 Retrospective studies have demonstrated a dose-response relationship between intercourse and risk of UTI, with the most sexually active women having a 40-fold greater infection risk than women who were not sexually active. 42 In one prospective study, 15 (79%) of 19 UTIs developed within 12 hours of intercourse. 3D On the other hand, in another prospective study, the frequency of sexual activity was no greater in women with a history of recurrent UTI than in women without such a history.26 Use of the diaphragm has also been found in several retrospective studies to be associated with an increased risk of UTI in women,8, 42, 58 and it was estimated in one such study that, among diaphragm users, 66% of UTIs were caused by use of the diaphragm. 42 In a recent prospective study, we, too, demonstrated a strong association between UTI and sexual intercourse but only when a spermicide or diaphragm-spermicide was used during intercourse. 18 Our data suggest that spermicides increase vaginal colonization of the vagina with uropathogens and, thus, facilitate entry of the pathogens into the bladder at the time of intercourse. Local changes in the vagina, such as pH, and both urine and bladder defense mechanisms may play an as yet unidentified role in predisposing women to uncomplicated UTI. 51 Although early postintercourse micturition appears to have a protective effect against UTI,12 no other behavioral factors, including masturbation, oral sex, type of clothing, volume of fluid ingested, or hygienic measures, have been identified as risk factors for UTI. However, none of these factors have yet been evaluated in prospective studies. It is not known why, in the apparently normal host, uropathogens occasionally ascend to the upper urinary tract and cause symptomatic infection. It is likely that, at least in some women, there are subtle functional or anatomic conditions, not detectable by currently available tests, that facilitate this process. Further, women who possess the PI blood group have a greater risk of developing recurrent pyelonephritis than women who are negative for P I . 28 On the other hand, in otherwise healthy hosts, pathogen virulence factors may play a relatively more important role in pathogenicity than host factors. For example, it has been established that the Escherichia coli strains causing pyelonephritis in otherwise normal





hosts belong to a small number of clones as defined by 0, H, and K serotyping. 35 These strains are far more likely to have P fimbriae than strains infecting hosts with known upper tract abnormalities or strains causing cystitis,55 and such strains also generally produce aerobactin and hemolysin. When Is a Pretreatment Culture Indicated? A pretreatment urine culture is indicated in anyone who has a presumptive upper UTI or who has one of the complicating factors listed in Table 1. Cultures are often not performed in women with uncomplicated cystitis because results generally become available only after the patient's symptoms have resolved or considerably improved. Further, a recent study showed that routine use of pretreatment urine cultures in such patients increases the cost of their care by 39% but decreases the duration of symptoms by only 10%.5 Therefore, it is reasonable not to obtain pretreatment cultures in patients with presumptive uncomplicated cystitis if the presence of pyuria, hematuria, or bacteriuria can be documented. However, such cultures probably should be performed even in the setting of presumptive acute uncomplicated cystitis if none of these findings are present or if the symptoms are not characteristic of UTI. Cultures should be performed routinely in women with acute uncomplicated pyelonephritis because there is a potential for serious sequelae if an inappropriate antimicrobial regimen is used. What Pathogens Are Most Likely in Acute Uncomplicated Urinary Tract Infection? The spectrum of etiologic agents is similar in uncomplicated upper and lower UTI, with Escherichia coli the causative pathogen in approximately 80% to 95% and Staphylococcus saprophyticus in 5% to 10%. Occasionally, other Enterobacteriaciae, such as Proteus mirabilis and Klebsiella sp. or enterococci, are isolated from such patients. In as many as 10% to 15% of symptomatic patients, bacteriuria cannot be detected with routine methods. 45 Using selective media, fastidious organisms such as Lactobacillus sp. and CO 2-dependent streptococci can be isolated in some of these patients, but their role in causing infection is debatable. 45 Ureaplasma urealyticum and Mycoplasma hominis may cause occasional episodes of pyelonephritis, but it is not clear whether they are seen in uncomplicated infections. We do not advocate the routine culture for fastidious pathogens because the yield is low and interpretation of positive cultures is often difficult. Escherichia coli strains isolated from patients with uncomplicated UTI are almost always susceptible to one or more of the commonly used oral agents, although as many as 25% to 35% of isolates demonstrate in vitro resistance to ampicillin and sulfonamides. 9 . 14 Antimicrobial susceptibility data from strains causing community-acquired cystitis and pyelonephritis are shown in Table 2. Factors to Consider in the Selection of Antimicrobials for Treatment of Urinary Tract Infection As summarized in Table 3, a variety of characteristics must be considered in selecting drugs for the treatment of uncomplicated UTI. Among



Table 2. Susceptibility of Pathogens Causing Community-Acquired Urinary Tract Infections to Commonly Used Antimicrohials. PERCENT OF STRAINS SUSCEPTIBLE

Acute Pyelonephritis


Ampicillin First-generation cephalosporin Nitrofurantoin Sulfonamide Trimethoprim Trimethoprimsulfamethoxazole Gentamicin Third -generation cephalosporin

Seattle 1983 to 1984 (n = 384)

United Kingdom 1982 (n = 655)

Seattle 1985 to 1987 (n = 43)

65 87

66 82

72 81

86 73 93 95

84 75

90 93

71 97

100 100 96

Adapted from Johnson JR, Stamm WE: Diagnosis and treatment of acute urinary tract infections. Infect Dis Clin North Am 1:773, 1987

these factors are the antimicrobial spectrum of the agent, the duration of adequate urinary levels achieved, the effect of the antimicrobial on the fecal and vaginal flora, the potential for undesirable side effects, and the cost of the treatment regimen. Relatively frequent resistance to sulfonamides and amoxicillin has lessened the desirability of these agents, whereas E. coli resistant to trimethoprim, trimethoprim-sulfamethoxazole, nitrofurantoin, and the fluoroquinolones is uncommon in patients with uncomplicated UTI. The duration of drug concentration above the infecting organism's minimum inhibitory concentration (MIC) in the urine is of importance because rapidly excreted agents may provide less therapeutic activity than those that are present at significant urinary levels for longer periods of time. Additionally, drugs that achieve high concentrations in the urine for long periods can be given on a twice-daily basis, enhancing patient convenience. Studies in animal models of pyelonephritis suggest that the intramedullary concentration of drug may be of considerable importance in treating upper UTI. In general, high intramedullary drug levels are thought to be more closely correlated with cure in upper UTI than either serum or urinary levels; thus, there may be a rationale for selecting agents that provide high kidney tissue levels for treatment of presumptive uncomplicated pyelonephritis. The effect of an antimicrobial on the fecal and vaginal flora has not received adequate attention as a property that influences long-term cure. Agents that have little effect on the anaerobic flora but eradicate aerobic gram-negative rods from the fecal and vaginal flora are probably best suited for providing long-term cure of uncomplicated UTIs. Examples include trimethoprim-sulfamethoxazole and fluoroquinolones. These agents have little impact on the anaerobic and microaerophilic normal vaginal flora such as lactobacillus and therefore do not alter what may be colonization resistance attributable to the normal vaginal flora. Additionally, they



Table 3. Characteristics of Antimicrobial Agents Used for Treatment of Uncomplicated Urinary Tract Infection SULFA~ETHOXAZOLE

Uropathogen resistance Urine concentration Half-life in urine Intestinal/vaginal effect anaerobes coliforms Side effects Cost
















+ ++

++ + ++


+++ + +++

+++ ++

+++ ++







Key: - = no apparent effect; + = short half-life or minimal antimicrobial effect; ++ = long half-life, strong antimicrobial effect, or frequent side effects.




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Management of acute uncomplicated urinary tract infection in adults.

Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity an...
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