Infect Dis Obstet Gynecol 2001;9:249–255

Urinalysis and urinary tract : update for clinicians

Jennifer L. Young and David E. Soper

Medical University of South Carolina, Charleston, SC

Dysuriais a common presentingcomplaint of women andurinalysis is a valuable tool inthe initial evaluationof this presentation.Clinicians need to beaware that pyuriais the bestdeterminate of bacteriuriarequiring therapy and that valuessignificant for infection differ dependingon the method of analysis.A hemocytometer yieldsa valueof ³ 10 WBC/mm3 significantfor , while manual microscopystudies show ³ 8 WBC/high-power field reliably predictsa positiveurine culture. In cases of uncomplicatedsymptomatic urinarytract infection, a positive valuefor nitrites and leukocyte esterase by urine dipstick can be treatedwithout the needfor a urineculture. Auto- mated urinalysisused widely inlarge volume laboratoriesprovides more sensitivedetection of leukocytesand bacteria inthe urine.With automatedmicroscopy, a valueof > 2WBC/hpf issignificant pyuria indicative of inflam- mation ofthe urinarytract. In complicated casessuch as pregnancy, recurrent infection or renal involvement, further evaluation is necessary including manual microscopy and urine culture with sensitivities.

Key words: D YSURIA; PYURIA; BACTERIURIA; URINE CULTURE; AUTOMATED URINALYSIS

Asmany as oneinfour women experience anepi- bringthe clinician upto date on automated sodeof dysuriaeach year, makingthis oneof the urinalysis procedures. most commonpresenting complaints of women seen byclinicians 1.Dysuria suggests thediagnosis BACTERIURIA IN DIAGNOSIS ofcystitis butmay bepresentin other conditions suchas vaginitis, chlamydial urethritis orpyelo- While aurineculture is thegold standard in the nephritis2.Urinalysis is valued as aquickand in- diagnosis ofaUTI, thelimitations ofthis test have expensive screening methodfor the presence ofa led many physiciansto use urinalysis asaninitial lowerurinary tract infection (UTI). Oftenthis test step inthe evaluation ofdysuria. Bacteriuria is is usedin conjunction with or inplace of aurine classically definedas aurineculture with greater culturein the diagnosis ofa UTI.However, a than100 000 cfu/ mlofa single microorganism 4. recentstudy found many practicingclinicians use Thisvalue distinguishes patientswith asymptom- differentstandards to determine thepresence or atic bacteriuria fromthose with a contaminated absence ofa UTI, most notupdated on current specimen. However, Stamm andcolleagues 5 literature3.Tofurthercomplicate matters, thelevel foundthat this culturecount was insufficientto ofautomation in urinalysis is increasing and includealmost halfof patients withsymptoms of acceptedcut-off values differfor these more sensi- dysuriaand frequency. In a studyof 181women tive methods.This article will review thecompo- withsymptoms ofdysuriaand frequency, 102 had nentsof a standardurinalysis, examine the ³ 105 cfu/ml but79 had < 10 5 cfu/ml andwould usefulness ofeach in the diagnosis ofUTI, and nothave yielded apositive cultureby thestandard

Correspondenceto: David E.Soper,MD, Medical Universityof SouthCarolina, Gynecology& Obstetrics,96 JonathanLucas St. Suite 634, P.O. Box 250619, Charleston, SC 29425, USA. Email: [email protected]

Review article 249 Urinalysis and UTI Young and Soper criterion. Furtherstudy demonstrated that women However, some hospitals andmany clinicians in withdysuria, pyuriaand a colonycount of practiceonly perform microscopy if there are any ³ 103 cfu/ml have alowerUTI 1,5.Theadditional abnormalities foundwith dipstick analysis. Aurine problemof urinesample contaminationclouds the dipsticktests forspecific gravity andpH, as well as already muddypicture surrounding urine culture. thepresence ofurobilinogen, ketones, glucose, Several studies found29– 32% of urine cultures hemoglobin,leukocyte esterase andnitrite. The were contaminatedand concluded that the determinationof apositive result is basedon com- methodologyused in collection does not alter this parisonof color development with the standard value6,7.Because ofthese difficulties withurine strip providedby themanufacturer. The urinedip- culture,in addition to the fact that it is slowand stickis valued as aquickand inexpensive test that expensive, physicianshave turnedto urinalysis to requires little expertise toperformcorrectly. The give aquickanalysis ofelements inthe urine. Of results canprove useful in determining whether to these components,leukocytes in the urinedemon- treat empirically orto order a urineculture for strate inflammation andtissue invasion ofthe definitive determinationof bacteriuria. Themost urinarytract, distinguishinginfection from coloni- usefulanalytes forUTI diagnosis are leukocyte zationor contamination 8.Pyuriais valued asthe esterase and nitrite. single best indicatorof bacteriuria thatwill resolve Leukocyteesterase is anenzyme foundin withantimicrobial therapy.If pyuriais absent, anti- neutrophilgranules thatreacts withagents onthe biotic therapy is not indicated 9. dipstickto produce a bluecolor in 1– 2 min. Specificpositive values vary fromtrace tomany, correlatingwith a minimum numberof PYURIA IN DIAGNOSIS WBC/hpf.For the Chemstrip (Boehringer Pyuriais thereforethe most usefulanalyte fordiag- Mannheim,IN) L/Nthis minimum thresholdis nosis ofinfection and the clinician has achoice > 5 WBC/hpf 13,butthis value may vary depend- betweenmultiple laboratorytests. Thegold stan- ingon thetest strip. While trace orsmall leukocyte dardfor the definition of pyuria is theleukocyte esterase activity may beconsidereda positive result excretionrate. Aleukocyteexcretion rate of forthis analyte, this result is notvery specific fora >400000 cells/ hcorrelates well withsymptoms UTIas many otherconditions can cause pyuria. ofdysuriaand frequency as well as thepresence of White bloodcells canbe foundin the urine in a bacteriuria 10.Research demonstratedthat all variety ofconditionsranging from chlamydial ure- abacteriuricpatients had an excretion rate of thritis topyelonephritis. For this reason, theposi- <400000 cells/ hand144 of 152 bacteriuric tive predictive value ofleukocyte esterase has been patients hada rate of ³ 400000 cells/ h,yielding shownto vary between19 and 88% 14,15. The asensitivity of95% and specificity of100% 11. absence ofleukocyteesterase activity has anegative Collectionof a 24-hurine is notfeasible forthe predictive value of97– 99% indicating that the clinicsetting. Forthis reason, thechamber count urineculture will be<10 3 cfu/ml14.Thisdiscrep- methodis usedin the literature foraccurate deter- ancyis basedon the fact that if theurinary tract minationof pyuriain place of theleukocyteexcre- is infected,the significant inflammation ofthe tionrate. Avalue of> 10cell/ mm 3 of unspun mucosashould produce pyuria. In the absence of urineis always associated witha leukocyteexcre- pyuria, the diagnosis of a UTI is unlikely. tionrate >400000 cells/ h 12.Formost physicians, Nitrite is producedfrom dietary nitrate by these values are onlyimportant in determining the bacteria containingnitrate reductase. Theamine in accuracy of urinalysis in the detection of pyuria. thedipstick reacts withthe nitrite andproduces a bluecolor in 60 s. Thepresence ofnitrites is highly specific forbacteriuria (96.6–97.5%), buthas alow URINALYSIS PART 1: URINE DIPSTICK sensitivity of0– 44% for bacteriuria between10 3 Aurinalysis withmanual dipstickand manual and 105 cfu/ml13,14.False negatives may bethe microscopyis commonlyordered on all patients result ofa lackof dietary nitrate, dilutionof withthe presenting symptom of dysuria. thenitrite inthe urine (such as withdiuretics), or

250 INFECTIOUSDISEASES IN OBSTETRICS AND GYNECOLOGY Urinalysis and UTI Young and Soper non-nitrate-reducingbacteria including Staphylo- suggesting centrifuging10– 20 ml urineat varying coccus, Enterococcus , or Pseudomonas 16.VanNostrand speeds forapproximately5 min, thenresuspending andcolleagues 17 foundthat 78.9% of samples thesediment ina dropup to 0.2 ml super- containingnitrate-reducing bacteria were actually natant16,24,25.Thetechnician places thesediment negative fornitrite onthe urine dipstick. There- onthe slide andviews between5 and15 fields forethe presence ofnitrite has ahighpositive pre- beforereporting an average value ofWBC/ hpf. dictive value of94% 18,butin the absence of Visualization oftheformed elements inthe urineis urinary nitrite a UTI cannot be ruled out. thegreatest benefitof microscopy. Microscopic Takingthe leukocyte esterase andnitrite evaluation ofleukocyteshas apositive predictive togetherproves muchmore useful. Ifboth tests are value of100%for the presence ofpyuria(defined as positive, thespecificity increases to98– 99.5%, > 8 WBC/mm3)butdoes not correlate as clearly indicatinga highlikelihood of aUTI 14,19. Several withthe presence ofbacteriuria. However, as the studies concludethat from this informationalone a numberof cells/hpfincreases, thepositive predic- diagnosis ofa UTIcanbe made andtreatment tive value forbacteriuria increases 26.Microscopy initiated2,18,20,21.Thisclinical conclusionhas canalso beused to visualize bacteria inthe recentlybeen called intoquestion by a study urine. Using acountingchamber, Hiraoka and demonstratinga lowsensitivity forboth leukocyte colleagues27 foundthat the presence ofboth esterase andnitrite butdid not take into account bacteriuria andpyuria had a positive predictive theclinical presentationof the patients in the value of100% compared with the urine culture study17.Ina lowprevalence population,such as in while theabsence ofbothhada negative predictive screening asymptomatic patients, thesensitivity of value of100%. Microscopy is also valued for these tests canbe as lowas 56% 22.From this data, visualization ofcasts orcrystals thatmay indicate Lachs andcolleagues 22 concludedthat in all future renal involvement or a complicated UTI. studies concerningthe diagnosis ofUTI, clinical However, there are many drawbacksto this use- informationincluding symptomatology must be fultest. Studiesshow that cells are lost inthe included.Therefore, if bothanalytes are positive handlingof the sample andthe transfer ontothe andthe patient is asymptomatic female, thepreva- slide28,29.Manualmicroscopy is theleast standard- lence inthis populationis sufficientlyhigh that the izedand most time-consuming portionof positive predictive value is drastically increased. If urinalysis30.Because ofthis, many hospitals have bothanalytes are negative, thechances of infection resortedto examining theurine under microscope fall to 0–5%14,23.Ofnote, the colors of theurine onlyif theurine dipstick is negative. Unfortu- dipstickwill spontaneouslychange if allowedto nately, this negates thevalue ofmicroscopy as a developin air forgreater than15 min 13. Urine toolboth to increase thesensitivity ofurinalysis dipstickmust beperformed in a timely manner andto directly visualize theelements inthe urine. to ensure accurate results. Thesolution to this dilemma may beinnew tech- niquesfor automation of microscopy and urine dipstickthat allow more standardizationand URINALYSIS PART 2: MICROSCOPY decrease thenumber of samples thatmust be Microscopyis avaluable additionto the urine dip- reviewed by manual microscopy. stickin diagnosing a UTIandshould be performed whenusing urinalysis tomake atreatment deci- sion. Manualmicroscopy is still widelyused to determine pyuriadespite knowledgethat the AUTOMATED URINALYSIS results are highlyvariable dependingon the labora- Automatedinstruments forurinalysis have entered tory,technician and urine sample 24.Whenprepar- hospitaland reference laboratories andmay soon inga slide, theurine specimen is centrifuged,the findtheir wayto clinics. Dueto discrepancies supernatantdecanted, and the sediment is amongtechnicians, laboratories andhospitals, resuspended.This is typicallythe least standardized automatedtechniques have beenintroduced in the portionof the procedure with several studies past25 years toupdate urinalysis tothe level of

INFECTIOUSDISEASES IN OBSTETRICS AND GYNECOLOGY 251 Urinalysis and UTI Young and Soper otherstandardized laboratory procedures. Auto- laboratoryand hospital benefit from the technol- mationexists onseveral levels. Ina survey oflocal ogyin a decrease inturn-around time, laborand hospitals, wefoundthat most hospitals employan cost. automatedmethod for dipstick analysis butstill performa manual microscopicevaluation. The instrumenttypically reads thechemistries con- COST ANALYSIS tainedon the dipstick by spectroscopy,reporting Indiscussing theusefulness ofurinalysis, onemust these values toa computerinterface. Atthehighest discuss theissue ofcost. UTIs promptover 5.2 level ofautomation,the instrument performs the million doctors’office visits peryear yieldinga dipstickanalysis as well as acountof the formed totalUS health-care costof over 1billiondollars 2. elements inthe urine. Ittakes upunspun, stained Cuttingthe costs inthe diagnosis ofa UTIcan urinein a thinlayer andanalyzes it byflowmicros- result insignificant savings inmedical care. As copy.Stop motion pictures are takenof eachfield previously mentioned,urinalysis is valued because andthe computerprocesses theimages, sorts parti- it is aninexpensive alternative toordering a urine cles basedon size, andcounts them. Theoperator cultureon every patientwith urinary complaints. thenidentifies theparticles presentand the instru- Currently,a urineculture costs $35 while simple ment reportsthe number of cells perhigh power urinalysis costs as little as $4. Automatedurinalysis field. at ourinstitution costs thepatient $13. Using Comparisons ofboth automated dipstick and urinalysis toguide which urine samples toculture automatedmicroscopy with manual methods canmean significantsavings. Automatedurinalysis showgood correlation between the two. Auto- has also beenproposed to cut down on the cost mated analysis oftheurine dipstick has beenshown associated withthe diagnosis ofa UTI.While the tohave comparableresults witha manual dipstick initial expense oftheequipment must beconsid- exceptfor specific gravity, whichwas better ered, this is balancedagainst adrastic decrease in measured manually 31.Automatedmicroscopy also laborcost. Automation reduces the turn-around correlates well withmanual microscopyfor most time foreach urinalysis, predominantlyby decreas- urineelements withthe exception of casts. Signifi- ingthe number of urine samples thatmust be cantlymore urinecasts were foundusing manual viewed undermanual microscopy 32.Bartlett and microscopicevaluation 29,31,32.Onereport indi- colleagues36 performeda costanalysis comparing cateda sensitivity of26–69% in automated detec- theYellow IRIS(IRIS, Chatsworth,CA) as a tionof casts andrecommended use ofmanual screening test toobtaining a urineculture on all microscopywhen renal damage is suspected 33. samples submitted 36.Theinvestigators assumed a Studieshave shownthat automated instruments $16.32/hlaborcost and found that to screen each are more sensitive inthe detection of both red urinesample wouldcost 24¢ , using0.3 min for bloodcells andwhite blood cells 34–36. Leukocyte accession, 0.5 min foranalysis, and0.1 min for countscorrelated well withmanual microscopyin reportingresults. Thisstudy demonstrated that most studies andalso predictedbacteriuria at approximately50% of the samples wouldrequire a avalue of> 2cells/hpf 36.Theautomated urineculture and still foundsignificant savings by urinalysis system is especially usefulat alower screening withautomated urinalysis 36. In deter- rangeof cell countswhere the dipstick is insensitive mining thesavings toour institution and our andthe manual microscopiccount is imprecise 32. patients, we useda urineculture cost and urinalysis Theadditionalsensitivity may bedueinpart to the costgiven above. Itwould cost a laboratoryreceiv- factthat the specimen is notcentrifuged before ing25 000urine samples/ year $875 000to screen analysis. Onestudy found an additional 50% of via urineculture and only $325 000to performa abnormalurine elements withautomated urin- urinalysis oneachsample. Ifthe urinalysis is posi- alysis over manual microscopy 34.However, aposi- tive forboth significant leukocytesand bacteria in tive result ina lowincidence population such as theurine, nofurthertesting is warrantedand the asymptomatic patients wouldrequire furthertest- urinalysis results canbe considereddiagnostic for a ing. Inaddition to increased sensitivity, the UTI.Shouldthe urinalysis reportbacteriuria

252 INFECTIOUSDISEASES IN OBSTETRICS AND GYNECOLOGY Urinalysis and UTI Young and Soper withoutpyuria or the reverse thena urineculture Table 1 Signsand symptoms ofurinary tract infection. shouldbe obtained to rule outa UTI. Even if Comparison of symptoms to a positive urine culture 37 50%of these samples require furthercharacteriza- Positive predictive value Specificity tionwith a urineculture (based onthe results of theurinalysis andthe prevalence ofUTI inthat Frequency 58% 6% patientpopulation) the total savings wouldexceed Lower abdominal pain 59% 36% $110 000per year. Thisfigure justifies theexpense Loin pain 60% 68% Dysuria 65% 28% ofautomatedurinalysis workstationsand advocates Hematuria 72% 87% theuse ofthese machines notonlyto reduce cost in Fever 78% 85% diagnosinga UTIbutalso toenhancethe reliability ofurinalysis as botha screening anddiagnostic tool.

Table 2 Correlation of pyuria with bacteriuria USING URINALYSIS TO DIAGNOSE A UTI Cut-off Bacteriuria Mostphysicians order a urinalysis forany patient value (cfu/ml) withthe presenting symptom of dysuriaand may Leukocyte excretion onlyorder a urineculture on thosewith a positive rate10 400 000 cells/h 95% (³ 104) urinalysis. Thehistory may suggest aparticular Hemocytometer 8 ³ 10 cells/mm 3 > 96% (³ 105) diagnosis andthis pretest probabilitymust betaken Leukocyte esterase intoaccount in evaluation oftheurinalysis results activity41 small 84% (³ 103) 37 (Table 1 ).Ithas beensuggested inthe literature Manual microscopy 26 ³ 8 cells/hpf 82% (³ 103) thata positive urinalysis forboth nitrites andleuko- Automated cyteesterase activity fora symptomatic patient microscopy36 ³ 2 cells/hpf 93% (³ 104) doesnot require furthertesting. Aurineculture is notwarrantedin these cases forseveral reasons: the findingof pyuriaand bacteriuria is 99.5%specific population,such as inscreening forasymptomatic fora UTI, most urinarypathogens are susceptible bacteriuria ofpregnancy,a urinalysis is notsensi- tocommon antimicrobial therapy,and the possi- tive enoughto rule outinfection and a urinecul- bility ofincreased morbidity(associated withlower tureis necessary todetermine thepresence or sensitivity) is lowfor uncomplicated cases 20. absence ofa UTI 38–40.Inthis populationonly Manualmicroscopy should not be overlooked, 4–7% of patients may actuallyhave aUTIbutthe even inthe setting ofautomatedurinalysis, if renal associated significant morbidityto both mother damage is suspected.In this instance, visualization andfetus warrants the expense ofscreening each oftheurine would be necessary tolook for specific patient with a urine culture 39. casts orcrystals thatmay pointto particular renal Whethermanual orautomated, urinalysis will pathology. helpdetermination of thepresence orabsence of Thereare specific circumstances inwhich leukocytesand bacteriuria inthe urine. Withthis urinalysis is insufficientand urine culture must be knowledge,combined with the clinical presenta- usedin making treatment decisions. Physicians tionof thepatient and the pretest probabilityof a shouldorder a urineculture on all patients with UTI, theclinician can decide whether to ordera symptoms suggestive ofpyelonephritis or symp- urineculture or treat onthe basis ofthese data. toms persisting 3days after theinitiation of Pyuriais thebest indicatorof thosepatients with therapy.Further, a urineculture should be per- bacteriuria correspondingwith active infectionof formedin all cases ofrecurrentinfection to deter- theurinary tract. Practicingclinicians needto be mine theorganism andits antibioticsensitivities 1. aware ofthemethod of urinalysis beingperformed Itmay bethat the original infectioninvolved an andthe values ofpyuriathat correlate withinfec- unusualor resistant organism. Ina lowprevalence tion (Table 2).

INFECTIOUSDISEASES IN OBSTETRICS AND GYNECOLOGY 253 Urinalysis and UTI Young and Soper

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