{"id":1337,"date":"2013-10-11T06:29:32","date_gmt":"2013-10-11T06:29:32","guid":{"rendered":"http:\/\/jacobimed.org\/NS\/?page_id=1337"},"modified":"2013-10-11T06:29:32","modified_gmt":"2013-10-11T06:29:32","slug":"nejm-management-of-urinary-tract-infections-in-adults","status":"publish","type":"page","link":"https:\/\/jacobimed.org\/old\/ambulatory\/intern-ambulatory-block\/spring\/nejm-management-of-urinary-tract-infections-in-adults\/","title":{"rendered":"NEJM – Management of Urinary Tract Infections in Adults"},"content":{"rendered":"

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 <\/p>\n

Management of
\nUrinary Tract Infections in Adults<\/span><\/strong><\/p>\n

Walter E. Stamm, and Thomas M. Hooton
\n<\/em><\/span><\/p>\n\n\n\n
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Urinary
\ntract infections account for more than 7 million visitsto
\nphysicians’ offices and necessitate or complicate well over1 million
\nhospital admissions in the United States annually1<\/sup><\/a>,<\/sup>2<\/sup><\/a>.
\n<\/sup>It is helpful to categorize adult patients with urinary infection
\n<\/sup>into five groups: young women with acute uncomplicated cystitis,
\n<\/sup>young women with recurrent cystitis, young women with acute
\n<\/sup>uncomplicated pyelonephritis, all adults with complicated urinary
\n<\/sup>infection, and all adults with asymptomatic bacteriuria. This
\n<\/sup>review will highlight recent advances in the treatment of patients
\n<\/sup>in each of these categories, emphasizing cost-effective strategies
\n<\/sup>that may be particularly important in the coming era of managed
\n<\/sup>care.<\/p>\n

Acute Uncomplicated Cystitis in
\nYoung Women<\/strong><\/span><\/p>\n

A remarkably narrow spectrum of etiologic agents with highly
\n<\/sup>predictable profiles of antimicrobial susceptibility cause infections
\n<\/sup>in young women with acute uncomplicated cystitis: Escherichia
\n<\/sup>coli in 80 percent, Staphylococcus saprophyticus in 5 to 15
\n<\/sup>percent, and occasionally klebsiella species, Proteus mirabilis,
\n<\/sup>or other microorganisms3<\/sup><\/a>.
\nSeveral factors increase the riskof infection, including sexual
\nintercourse, the use of a diaphragmand a spermicide (and possibly
\nspermicide use alone), delayedpostcoital micturition, and a history
\nof a recent urinary infection4<\/sup><\/a>,<\/sup>5<\/sup><\/a>,<\/sup>6<\/sup><\/a>.
\n<\/sup>Localization studies indicate that as many as 30 percent of
\n<\/sup>patients who present clinically with a cystitis-like syndrome
\n<\/sup>may have subclinical upper urinary tract involvement7<\/sup><\/a>.
\nSincenone of the currently available localization tests are
\nbothaccurate and feasible for use in practice, however, these
\npatientsare all initially treated as though they have cystitis.
\n<\/sup><\/p>\n

A young woman presenting with acute dysuria usually has oneof
\nthree types of infection: acute cystitis; acute urethritisdue to
\nChlamydia trachomatis, Neisseria gonorrhoeae, or herpessimplex
\nvirus; or vaginitis due to candida or trichomonas3<\/sup><\/a>.
\n<\/sup>Women with cystitis, urethritis, or vaginitis can usually be
\n<\/sup>presumptively differentiated on the basis of their presenting
\n<\/sup>symptoms, signs, and findings on urinalysis (Table
\n1<\/a>). If needed,a urine culture can be used to confirm the
\npresence of acutecystitis. In symptomatic young women with suspected
\ncystitis,a urine culture demonstrating 100 or more colony-forming
\nunitsof a uropathogenic species per milliliter usually
\nindicatesinfection8<\/sup><\/a>,<\/sup>9<\/sup><\/a>.
\nNearly all such patients can also be shown tohave pyuria by an
\naccurate and reproducible method such as theuse of a counting
\nchamber to enumerate cells in unspun urine.The leukocyte esterase
\ndipstick, a widely used office test toidentify patients with pyuria,
\nhas a reported sensitivity of75 to 96 percent in detecting pyuria
\nassociated with infection9<\/sup><\/a>.
\n<\/sup>For patients with a negative test who have urinary symptoms,
\n<\/sup>microscopical evaluation for pyuria or a culture should be performed.
\n<\/sup><\/p>\n

<\/a><\/p>\n\n\n\n
\n\n\n\n
View this
\ntable:<\/strong>
\n[in
\nthis window]<\/a>
\n[in a new window]<\/a><\/td>\n		Table 1.<\/strong> Major Infectious Causes of
\nAcute Dysuria in Women.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Since the
\ncausative organisms and their antimicrobial-susceptibilityprofiles
\nare so predictable in women with acute cystitis, weand others have
\nadvocated an abbreviated laboratory workup followedby empirical
\ntherapy, on the grounds that this approach is efficacious,safe, and
\ncost effective10<\/sup><\/a>,<\/sup>11<\/sup><\/a>.
\nThus, in patients with typicalsymptoms, the diagnosis can be
\npresumed if pyuria is presenton microscopy or leukocyte esterase
\ntesting. No urine cultureis performed, and a short course of
\nempirical antimicrobialtherapy is given. No follow-up visit or
\nculture after therapyis recommended unless symptoms persist or
\nrecur. If pyuria isabsent or there are atypical clinical features or
\nfactors thatsuggest a complicated infection (Table
\n2<\/a>), a culture shouldbe performed before therapy is started.
\n<\/sup><\/p>\n

<\/a><\/p>\n\n\n\n
\n\n\n\n
View this
\ntable:<\/strong>
\n[in
\nthis window]<\/a>
\n[in a new window]<\/a><\/td>\n		Table 2.<\/strong> Treatment Regimens for
\nBacterial Urinary Tract Infections.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

A plethora
\nof studies have been conducted in recent years todefine the optimal
\ntreatment for uncomplicated cystitis in women10<\/sup><\/a>,<\/sup>12<\/sup><\/a>,<\/sup>13<\/sup><\/a>,<\/sup>14<\/sup><\/a>,<\/sup>15<\/sup><\/a>,<\/sup>16<\/sup><\/a>,<\/sup>17<\/sup><\/a>,<\/sup>18<\/sup><\/a>,<\/sup>19<\/sup><\/a>.
\n<\/sup>With most antimicrobial agents, three-day regimens appear optimal,
\n<\/sup>with efficacy comparable to seven-day regimens but with fewer
\n<\/sup>side effects and lower cost (Table
\n2<\/a>). Single-dose therapy canalso be used, but it generally
\nresults in lower rates of cureand more frequent recurrences,
\nespecially with drugs such asamoxicillin and oral cephalosporins,
\nwhich are very rapidlyexcreted and are often ineffective in patients
\nwith occult renalinfection12<\/sup><\/a>,<\/sup>14<\/sup><\/a>,<\/sup>15<\/sup><\/a>.
\nFor single-dose therapy, the best resultshave generally been
\nachieved with trimethoprim-sulfamethoxazole.Fluoroquinolones and
\nfosfomycin-tromethamine (where approvedfor use) have also been used
\nsuccessfully14<\/sup><\/a>,<\/sup>15<\/sup><\/a>,<\/sup>17<\/sup><\/a>.
\nEven withtrimethoprim-sulfamethoxazole and fluoroquinolones,
\nhowever,therapy for three days or longer was more effective than
\nsingle-dosetherapy in most trials and in a meta-analysis12<\/sup><\/a>,<\/sup>14<\/sup><\/a>,<\/sup>15<\/sup><\/a>,<\/sup>16<\/sup><\/a>.
\nSingle-dosetherapy with a fluoroquinolone is particularly prone to
\nfailurein patients infected with S. saprophyticus15<\/sup><\/a>,<\/sup>17<\/sup><\/a>.
\nRegimens ofseven days or longer offer no additional therapeutic
\nbenefitbut cost more and cause substantially more side effects
\nthatrequire medical intervention (primarily rash and yeast
\nvaginitis).Seven-day regimens (and a pretreatment culture) can be
\nreservedfor patients with factors, including pregnancy, that may
\nresultin lower rates of cure with shorter regimens (Table
\n2<\/a>).<\/p>\n

About one third of the bacterial strains causing uncomplicated
\n<\/sup>cystitis in the United States now demonstrate in vitro resistance
\n<\/sup>to amoxicillin and sulfonamides, and 15 to 20 percent are resistant
\n<\/sup>to nitrofurantoin12<\/sup><\/a>,<\/sup>13<\/sup><\/a>,<\/sup>14<\/sup><\/a>,<\/sup>15<\/sup><\/a>,<\/sup>17<\/sup><\/a>.
\nResistance to trimethoprimand trimethoprim-sulfamethoxazole is 5 to
\n15 percent, variesgeographically, and appears to be increasing
\nnationwide, whereasresistance to the fluoroquinolones remains below
\n5 percent inmost places8<\/sup><\/a>,<\/sup>12<\/sup><\/a>,<\/sup>13<\/sup><\/a>,<\/sup>14<\/sup><\/a>,<\/sup>15<\/sup><\/a>,<\/sup>16<\/sup><\/a>,<\/sup>17<\/sup><\/a>,<\/sup>18<\/sup><\/a>.
\nThe effects of an antimicrobialagent on the vaginal flora are also
\nimportant in the lastingeradication of bacteriuria12<\/sup><\/a>.
\nThe concentrations of trimethoprimand the fluoroquinolones that have
\nbeen studied in vaginal secretionsare high, eradicating E. coli but
\nminimally altering normalanaerobic and microaerophilic vaginal
\nflora10<\/sup><\/a>.
\nSingle-dose regimensusing these drugs are less effective than
\nmultiple-day regimensin this regard,12<\/sup><\/a>
\nwhich probably explains why there are moreearly recurrent infections
\nafter single-dose therapy with thesedrugs. Nitrofurantoin and
\nbeta-lactam drugs are generally noteffective in eliminating E. coli
\nfrom the vagina.<\/p>\n

Considering all factors, including current patterns of resistance
\n<\/sup>among uropathogens, the duration of urinary excretion of drug,
\n<\/sup>antimicrobial effects on the vaginal flora, safety, and cost,
\n<\/sup>trimethoprim-sulfamethoxazole and trimethoprim are the optimal
\n<\/sup>choices for empirical three-day therapy for uncomplicated cystitis
\n<\/sup>(Table
\n2<\/a>). The fluoroquinolones are also highly effective andwell
\ntolerated in three-day regimens but are more expensive.In women with
\nuncomplicated cystitis, we use a fluoroquinoloneprimarily for
\nrecurrent infections, treatment failures, infectionsin patients with
\nallergies to other drugs, and infections causedby strains resistant
\nto other antimicrobial agents. Only inareas where trimethoprim
\nresistance is common among the pathogenscausing uncomplicated
\ncystitis should fluoroquinolones be usedfor empirical therapy. We
\nand others have had less satisfactoryresults with three-day courses
\nof amoxicillin, cefadroxil, ornitrofurantoin in the management of
\nacute cystitis,15<\/sup><\/a>,<\/sup>20<\/sup><\/a>
\nevenwith susceptible microorganisms, but these regimens may be
\nusefulin selected patients or settings.<\/p>\n

Recurrent Infections in
\nWomen<\/strong><\/span><\/p>\n

About 20 percent of young women with an initial episode of cystitis
\n<\/sup>have recurrent infections. Occasionally, such recurrences are
\n<\/sup>due to a persistent focus of infection, but well over 90 percent
\n<\/sup>of recurrences in young women are episodes of exogenous reinfection,
\n<\/sup>typically months apart21<\/sup><\/a>,<\/sup>22<\/sup><\/a>.
\nOnly rarely do such patients haveanatomical or functional
\nabnormalities of the urinary tract,and excretory urography,
\ncystography, and cystoscopy are thereforeof little use23<\/sup><\/a>.
\nThe use of diaphragms and spermicides has beenassociated with
\nrecurrence in some patients, probably becausethe spermicide induces
\ncolonization of the vagina by E. coli24<\/sup><\/a>.
\n<\/sup>Alternatively, susceptibility may be genetic, since women who
\n<\/sup>do not secrete blood-group antigens (nonsecretors) are
\noverrepresentedamong those with recurrent infections and
\nuroepithelial cellsfrom such women have specific E. coli-binding
\nglycolipids thatare absent in women who secrete blood-group
\nantigens25<\/sup><\/a>,<\/sup>26<\/sup><\/a>.
\n<\/sup><\/p>\n

Recurrent cystitis should be documented by culture at leastonce
\nand then managed by one of three strategies: continuousprophylaxis,
\npostcoital prophylaxis, or therapy initiated bythe patient (Figure
\n1<\/a>)27<\/sup><\/a>,<\/sup>28<\/sup><\/a>,<\/sup>29<\/sup><\/a>.
\nIn some women, prophylacticregimens have been successfully used for
\nyears without the emergenceof antibiotic resistance30<\/sup><\/a>,<\/sup>31<\/sup><\/a>.
\nIn women with recurrent episodesof cystitis who comply with
\ntreatment, patient-initiated therapyundertaken when symptoms arise
\nprovides a convenient, safe,inexpensive, and effective management
\nstrategy29<\/sup><\/a>.
\n<\/sup><\/p>\n

<\/a><\/p>\n\n\n\n
\n\n\n\n
\"<\/a>
\nView larger version<\/strong>
\n(51K):
\n[in
\nthis window]<\/a>
\n[in a new window]<\/a><\/td>\n		Figure 1.<\/strong> Strategies for Managing
\nRecurrent Cystitis in Women.Relapse refers to recurrent infection caused by the original
\ninfecting pathogen, usually within two weeks after the completion of
\ntherapy. Reinfection refers to recurrent infection with a different
\nspecies or strain, usually more than two weeks after the completion
\nof therapy. Patient-initiated therapy should also be considered for
\nwomen with more frequent infections if continuous or postcoital
\nregimens are not acceptable. UTI denotes urinary tract infections.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Postmenopausal
\nwomen may also have frequent reinfections21<\/sup><\/a>,<\/sup>32<\/sup><\/a>.
\n<\/sup>These infections are sometimes attributable to residual urine
\n<\/sup>after voiding, which is often associated with bladder or uterine
\n<\/sup>prolapse. In addition, the lack of estrogen causes marked changes
\n<\/sup>in the vaginal microflora, including loss of lactobacilli and
\n<\/sup>increased colonization by E. coli32<\/sup><\/a>.
\nAntimicrobial prophylaxisor topically applied estradiol cream are
\nalternative preventivemeasures in such women28<\/sup><\/a>,<\/sup>32<\/sup><\/a>.
\n<\/sup><\/p>\n

Acute Uncomplicated
\nPyelonephritis in Young Women<\/strong><\/span><\/p>\n

The clinical spectrum of acute uncomplicated pyelonephritisin
\nyoung women ranges from gram-negative septicemia to a cystitis-like
\n<\/sup>illness with mild flank pain33<\/sup><\/a>.
\nE. coli accounts for more than80 percent of cases, and most of the
\nstrains are a unique subgroupof E. coli (called uropathogenic
\nstrains) that possess specificdeterminants of virulence that enable
\nthem to infect the upperurinary tract of normal, healthy persons34<\/sup><\/a>.
\nThese uropathogenicE. coli belong to a small number of O:K:H
\nserotypic groups,usually produce both hemolysin and aerobactin, and
\ngenerallyhave specific pyelonephritis-associated pili that mediate
\ntheirattachment to uroepithelial cells.<\/p>\n

Microscopical examination of unspun urine establishes the presumptive
\n<\/sup>diagnosis. Pyuria is nearly always present, and gram-negative
\n<\/sup>bacteria are usually seen. About 20 percent of patients have
\n<\/sup>urine cultures with <105<\/sup> colony-forming units per
\nmilliliter,however, and hence negative results on Gram’s staining of
\ntheurine35<\/sup><\/a>.
\nUrine cultures should be obtained in all women withsuspected
\npyelonephritis, and a blood culture should be obtainedin patients
\nwho are hospitalized, since 15 to 20 percent arepositive33<\/sup><\/a>,<\/sup>35<\/sup><\/a>.
\n<\/sup><\/p>\n

Twenty to 30 percent of organisms that cause pyelonephritisare
\nresistant to amoxicillin and first-generation cephalosporinsin
\nvitro, and thus these compounds should no longer be usedalone for
\nempirical treatment (Table
\n2<\/a>)33<\/sup><\/a>,<\/sup>35<\/sup><\/a>,<\/sup>36<\/sup><\/a>.
\nIn the absenceof nausea and vomiting and if the patient’s overall
\ndegree ofillness is mild, therapy can safely be given orally in an
\noutpatientsetting (Table
\n2<\/a>)36<\/sup><\/a>,<\/sup>37<\/sup><\/a>.
\nPatients with nausea, vomiting, or moderate-to-severeillness and
\nthose who are pregnant require hospitalization forinitial parenteral
\ntherapy with one of the regimens shown inTable
\n2<\/a>. Typically, symptoms and signs improve or resolve after48 to
\n72 hours, and the remaining treatment can be given orally.In
\nselected patients, parenterally administered ceftriaxonecan be used
\nas outpatient therapy. Ampicillin and gentamicinshould be given
\nempirically if enterococcus species are suspectedon the basis of
\nGram’s staining of the urine that reveals gram-positivecocci.
\nTreatment for longer than two weeks has no apparent benefit,even in
\npatients with positive blood cultures3<\/sup><\/a>,<\/sup>36<\/sup><\/a>.
\nShorter regimens(e.g., five to seven days) are often effective in
\npatients whosefever abates rapidly, but they have not been evaluated
\nin well-controlledtrials.<\/p>\n

If fever and flank pain persist after 72 hours of therapy, cultures
\n<\/sup>should be repeated and ultrasonography or computed tomography
\n<\/sup>should be considered to seek perinephric or intrarenal abscesses,
\n<\/sup>unrecognized urologic abnormalities, or obstruction. The routine
\n<\/sup>use of imaging procedures for all young women who present with
\n<\/sup>acute pyelonephritis is generally unrevealing and unnecessarily
\n<\/sup>expensive38<\/sup><\/a>;
\nimaging should be limited to patients with slowresolution of
\ninfection, more than one episode, or other atypicalfeatures
\n(persistent hematuria, colicky pain, or childhood urinary
\n<\/sup>infections). It is useful to obtain a follow-up culture two
\n<\/sup>weeks after the completion of therapy.<\/p>\n

Complicated Urinary Tract
\nInfections<\/strong><\/span><\/p>\n

Complicated urinary tract infections are those that occur ina
\npatient who has a functionally, metabolically, or anatomically
\n<\/sup>abnormal urinary tract or that are caused by pathogens thatare
\nresistant to antibiotics10<\/sup><\/a>,<\/sup>39<\/sup><\/a>.
\nThese complicating factorsmay not be obvious at first, however. The
\nclinical spectrumranges from mild cystitis to life-threatening
\nurosepsis. Inaddition, there may be long periods of asymptomatic
\nbacteriuria.Unlike the narrow and predictable spectrum of causative
\nagentsin uncomplicated infection, a broad range of bacteria can
\ncausecomplicated infections (Table
\n2<\/a>), and many are resistant tomultiple antimicrobial agents.
\nUrine cultures must thereforebe obtained in patients suspected of
\nhaving complicated infectionin order to identify the infecting
\npathogen and perform susceptibilitytesting.<\/p>\n

The wide variety of underlying conditions, diverse spectrumof
\npossible etiologic agents, and paucity of controlled clinicaltrials
\nwith stratification according to specific complicatingfactors make
\ngeneralizing about antimicrobial therapy difficult14<\/sup><\/a>,<\/sup>17<\/sup><\/a>.
\n<\/sup>For empirical therapy in patients with mild-to-moderate illness
\n<\/sup>who can be treated with oral medication as outpatients, the
\n<\/sup>fluoroquinolones provide a broad spectrum of antimicrobial activity
\n<\/sup>covering most expected pathogens and achieve high levels inthe
\nurine and urinary tract tissue (Table
\n2<\/a>). If the infectingpathogen is known to be susceptible,
\ntrimethoprim-sulfamethoxazoleis also a reasonable and less costly
\ntherapeutic choice. Forinitial empirical therapy in more seriously
\nill, hospitalizedpatients, ampicillin plus gentamicin or imipenem
\nplus cilastatinprovides coverage against most expected pathogens,
\nincludingPseudomonas aeruginosa and most enterococci. A number of
\notherparenteral antimicrobial agents can also be used (Table
\n2<\/a>)14<\/sup><\/a>,<\/sup>17<\/sup><\/a>.
\n<\/sup>Therapy can be modified when the infecting strain has been identified
\n<\/sup>and antimicrobial susceptibilities are known. At least 10 to14
\ndays of therapy is usually necessary; many patients initiallygiven
\nparenteral therapy can be switched to oral treatment afterclinical
\nimprovement. Pseudomonas and enterococcal infectionsare especially
\ndifficult to treat and may warrant more prolongedtherapy. Without
\ncorrection of the underlying anatomical, functional,or metabolic
\ndefect, infection often recurs. For this reason,a urine culture
\nshould be repeated one to two weeks after thecompletion of
\ntherapy.<\/p>\n

Urinary Tract Infections in
\nYounger Men<\/strong><\/span><\/p>\n

Urinary tract infections are rare in men less than 50 yearsold.
\nThey have generally been considered indicative of an underlying
\n<\/sup>urologic abnormality and thus to be complicated infections40<\/sup><\/a>.
\n<\/sup>Recent studies, however, suggest that the uropathogenic strains
\n<\/sup>of E. coli that cause pyelonephritis in young women can also
\n<\/sup>cause uncomplicated infection (usually cystitis) in young men41<\/sup><\/a>,<\/sup>42<\/sup><\/a>.
\n<\/sup>Clinically, these infections often present with symptoms of
\n<\/sup>cystitis, but in some patients they mimic urethritis, causing
\n<\/sup>urethral discharge and urethral leukocytosis. Risk factors include
\n<\/sup>homosexuality (associated with exposure to E. coli through anal
\n<\/sup>intercourse), lack of circumcision (associated with enhanced
\n<\/sup>colonization of the glans and prepuce by E. coli), and havinga
\nsexual partner with vaginal colonization by uropathogens41<\/sup><\/a>,<\/sup>42<\/sup><\/a>,<\/sup>43<\/sup><\/a>.
\n<\/sup>Men with human immunodeficiency virus infection who have CD4
\n<\/sup>lymphocyte counts of less than 200 per cubic millimeter may
\n<\/sup>also be at increased risk for urinary infection, presumably
\n<\/sup>because of immunosuppression44<\/sup><\/a>.
\n<\/sup><\/p>\n

Young healthy men who present with the cystitis syndrome andhave
\nno discernible complicating factors can be treated witha seven-day
\nregimen of trimethoprim-sulfamethoxazole, trimethoprim,or a
\nfluoroquinolone. Shorter regimens should be avoided. Pretreatment
\n<\/sup>urine culture is recommended. A urologic evaluation is usually
\n<\/sup>unrewarding in young men who respond to therapy40<\/sup><\/a>.
\n<\/sup><\/p>\n

Catheter-Associated Urinary
\nTract Infection<\/strong><\/span><\/p>\n

There are more than 1 million catheter-associated urinary infections
\n<\/sup>a year in the United States,45<\/sup><\/a>
\nand catheter-associated bacteriuriaremains the most common source of
\ngram-negative bacteremia inhospitalized patients46<\/sup><\/a>.
\nRecent studies have demonstrated thatbacteria adhere to the surface
\nof urinary catheters and initiatethe growth of biofilms composed of
\nbacteria, bacterial glycocalices,Tamm-Horsfall protein, and urinary
\nsalts such as apatite andstruvite47<\/sup><\/a>.
\nOf clinical importance, biofilms appear to protectembedded bacteria
\nfrom antibiotics, causing treatment to fail48<\/sup><\/a>.
\n<\/sup>For this reason, one should consider replacing a catheter that
\n<\/sup>has been in place for more than two weeks when one is treating
\n<\/sup>a patient with a catheter-associated infection.<\/p>\n

Prevention remains the best way to reduce the morbidity, mortality,
\n<\/sup>and costs of catheter-associated infection49<\/sup><\/a>,<\/sup>50<\/sup><\/a>.
\nEffective strategiesinclude sterile insertion and care of the
\ncatheter, prompt removal,and the use of a closed collecting system45<\/sup><\/a>,<\/sup>49<\/sup><\/a>.
\nOther approachesthat have been effective in some studies but not
\nothers includethe use of preconnected catheter-collecting-tube
\nunits, theuse of disinfectants in collecting bags, the use of
\nsilver-ion-coatedcatheters, and the regular periurethral application
\nof antimicrobialcreams45<\/sup><\/a>,<\/sup>49<\/sup><\/a>.
\nAlthough systemic antimicrobial agents preventor delay the onset of
\nbacteriuria, they are not routinely usedfor this purpose in patients
\nwith catheters, because of costand the potential for the development
\nof antimicrobial resistance.Prophylactic systemic antimicrobial
\nagents may be useful, however,in selected patients at high risk who
\nare undergoing short-termcatheterization (e.g., patients undergoing
\nrenal transplantation,urologic or gynecologic surgery, or surgery
\ninvolving a foreignbody).<\/p>\n

In patients with catheters whose culture specimens are obtained
\n<\/sup>directly from the catheter, a level of 100 or more colony-forming
\n<\/sup>units per milliliter is evidence of infection, since these counts
\n<\/sup>usually persist or increase within 48 hours51<\/sup><\/a>.
\nSymptomatic episodesof infection should be treated with
\nantimicrobial agents, asrecommended for complicated urinary tract
\ninfections. Treatmentof asymptomatic bacteriuria has little apparent
\nbenefit in patientswith catheters. One study suggested, however,
\nthat in women,asymptomatic bacteriuria after catheterization may
\nalso warranttherapy52<\/sup><\/a>.
\nFurther studies are needed to confirm these resultsand establish the
\ncost effectiveness of screening asymptomaticwomen with catheters for
\nbacteriuria.<\/p>\n

When catheterization is long-term (more than 30 days), bacteriuria
\n<\/sup>eventually occurs in almost all patients53<\/sup><\/a>.
\nPeriods of bacteriuriamay alternate with periods of sterile urine,
\nor bacteriuriamay become chronic; in both instances the infecting
\nstrainsoften change. Bacteriuria is frequently polymicrobial49<\/sup><\/a>,<\/sup>53<\/sup><\/a>.
\n<\/sup>A recurrent problem is catheter encrustation and eventual
\nobstruction.Periodic catheter changes may prevent these
\ncomplications.<\/p>\n

The prevention of bacteriuria and associated complications in
\n<\/sup>patients undergoing long-term catheterization has been largely
\n<\/sup>unsuccessful. In contrast, intermittent catheterization has
\n<\/sup>resulted in lower rates of bacteriuria than long-term indwelling
\n<\/sup>catheterization in studies with historical controls49<\/sup><\/a>,<\/sup>54<\/sup><\/a>.
\nInpatients undergoing intermittent catheterization, bacteriuria
\n<\/sup>may be reduced by bladder irrigation with a solution of neomycin
\n<\/sup>and polymyxin or by oral methenamine, nitrofurantoin, or
\ntrimethoprim-sulfamethoxazoleprophylaxis49<\/sup><\/a>,<\/sup>55<\/sup><\/a>.
\nProphylactic regimens are not effective inpatients with long-term
\nindwelling catheters. Likewise, treatingepisodes of asymptomatic
\nbacteriuria does not reduce the complicationsof bacteriuria in
\npatients undergoing long-term catheterization56<\/sup><\/a>.
\n<\/sup><\/p>\n

Asymptomatic Bacteriuria in
\nPatients without Catheters<\/strong><\/span><\/p>\n

In patients with asymptomatic bacteriuria, a level of \">=\"
\n105<\/sup> colony-formingunits per milliliter (preferably on two
\nsuccessive cultures)should be the diagnostic criterion for
\ninfection9<\/sup><\/a>.
\nScreeningfor asymptomatic bacteriuria has little apparent value in
\nadults,with two exceptions: before urologic surgery and during
\npregnancy.Postoperative complications, including bacteremia, are
\nreducedby recognizing and treating asymptomatic bacteriuria
\nbeforeurologic surgery57<\/sup><\/a>.
\nAll pregnant women should be screened forbacteriuria in the first
\ntrimester and should be treated ifbacteriuria is present, to reduce
\ntheir markedly increased riskof acute pyelonephritis and the
\naccompanying risks of prematurityand low birth weight in their
\ninfants58<\/sup><\/a>.
\nThe results of susceptibilitytesting should be available to direct
\ntherapy. We recommendthree-day courses of amoxicillin,
\nnitrofurantoin, an oral cephalosporin,or
\ntrimethoprim-sulfamethoxazole. After successful treatment,monthly
\nurine cultures should be performed to detect recurrentbacteriuria58<\/sup><\/a>.
\n<\/sup><\/p>\n

Asymptomatic bacteriuria occurs in as many as 40 percent of
\n<\/sup>elderly men and women, especially in nursing homes. Although
\n<\/sup>symptomatic infection (even pyelonephritis or sepsis) develops
\n<\/sup>in a few of these patients, such complications are rare anddo
\nnot appear to justify either screening or the routine useof
\nantimicrobial agents for the prevention or treatment of asymptomatic
\n<\/sup>bacteriuria in this setting59<\/sup><\/a>.
\nAlthough asymptomatic bacteriuriahas been associated with an
\nincreased risk of death in the elderlyin some studies, a causal link
\nhas not been demonstrated60<\/sup><\/a>.
\n<\/sup><\/p>\n

Conclusions<\/strong><\/span><\/p>\n

Management strategies designed for specific groups of patients
\n<\/sup>with urinary infection can maximize therapeutic benefits while
\n<\/sup>reducing costs and the incidence of adverse reactions. In women
\n<\/sup>with uncomplicated cystitis, the predictable nature of the etiologic
\n<\/sup>agents and their antimicrobial susceptibilities obviates the
\n<\/sup>need to identify the specific microbial agent routinely. In
\n<\/sup>such patients, three-day empirical therapy is highly effective,
\n<\/sup>inexpensive, and well tolerated. Recurrent cystitis in women
\n<\/sup>can be effectively managed by continuous antimicrobial prophylaxis,
\n<\/sup>postcoital prophylaxis, or patient-administered therapy at home.
\n<\/sup>Uncomplicated pyelonephritis in women results from infection
\n<\/sup>with specific uropathogenic strains of E. coli in patients with
\n<\/sup>anatomically normal urinary tracts. In such patients, antimicrobial
\n<\/sup>therapy for 10 to 14 days appears optimal, given entirely by
\n<\/sup>mouth in an outpatient setting for patients with mild illness
\n<\/sup>and initiated parenterally in sicker patients who require
\nhospitalization.Complicated infections encompass a broad spectrum of
\nclinicalconditions for which it is difficult to make all-inclusive
\nrecommendationsfor empirical treatment. Controlled clinical trials
\nin whichpatients are stratified according to the type of
\ncomplicatingfactor are needed to define optimal treatment
\nstrategies. Ingeneral, empirical regimens for such infections should
\nbe broad-spectrum,since antibiotic-resistant strains are often
\npresent, and therapyshould be given for at least 10 to 14 days.
\nWidespread resistanceto ampicillin, amoxicillin, sulfonamides, and
\nfirst-generationcephalosporins makes these drugs less attractive for
\nempiricaltherapy of most types of urinary infection. Given their
\noralbioavailability and broad spectrum of activity against
\nurinarypathogens, the fluoroquinolones are especially useful in
\ntheoutpatient management of complicated infections. There has
\nbeendecreased emphasis on urologic evaluations in women with
\nacutepyelonephritis or recurrent infections. Except in selected
\ncircumstances,screening for asymptomatic bacteriuria is unnecessary
\nin adults.<\/p>\n

 <\/p>\n

 <\/p>\n

Supported in part by a grant (DK 40045) from the National
\nInstitutesof Health.
\n<\/span><\/p>\n

Source Information<\/strong><\/span><\/p>\n

 <\/p>\n

From the Division of Infectious Diseases, Department of
\nMedicine, University of Washington and Harborview Medical Center, 325 9th Ave.,
\nSeattle, WA 98104, where reprint requests should be addressed to Dr.
\nStamm.<\/span><\/p>\n

References<\/strong><\/span><\/p>\n

 <\/p>\n

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    <\/a><\/p>\n

    Related Letters:<\/strong><\/span><\/p>\n

    Management of Urinary Tract
    \nInfections<\/a><\/strong>
    \nMiddendorf D. F., Hebert L. A., Hutt D. M., Spital
    \nA., Stamm W. E., Hooton T. M.
    \n    Extract<\/a>
    \n|     Full
    \nText<\/a>
    \nN Engl J Med 1994; 330:792, Mar 17, 1994.
    \nCorrespondence<\/strong> <\/span><\/p>\n

    Collection of Urine for
    \nCulture<\/a><\/strong>
    \nJaffe J. S., Stamm W. E., Hooton T. M.
    \n    Extract<\/a>
    \n|     Full
    \nText<\/a>
    \nN Engl J Med 1994; 331:617-618, Sep 1, 1994.
    \nCorrespondence<\/strong> <\/span><\/p>\n

    <\/a><\/p>\n

    This article has been cited by other
    \narticles:<\/strong><\/span><\/p>\n

     <\/p>\n