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1、Urinary Tract Infections,Overview of UTI,7 million office visits yearly1 million hospitalizationsAbout 2/3rds of patients are women;40%to 50%of women have UTI at some point during their livesImportant complications of pregnancy,diabetes mellitus,polycystic disease,renal transplantation,conditions th
2、at impede urine flow(structural and neurologic),Overview of UTI by age and sex,Terms,Urinary tract infectionSignificant bacteriuriaAsymptomatic bacteriuriaAcute pyelonephritisChronic pyelonephritis“Upper”versus“lower”UTIUrethral syndrome,Terms(2),UTI:the finding of microorganisms in bladder urine wi
3、th or without clinical symptoms and with or without renal diseaseSignificant bacteriuria:the finding of 105 cfu/ml of urine(but lower counts can be significant),Terms(3),Asymptomatic bacteriuria:Significant bacteriuria without clinical symptoms or other abnormal findings.Acute bacterial pyelonephrit
4、is:a clinical syndrome of fever,flank pain,and tenderness,often with constitutional symptoms,leukocyte casts in the urine,and bacteriuria;or histologic findings thereof,Terms(4),Chronic bacterial pyelonephritis:Long-standing infection associated with active bacterial growth in the kidney;or the resi
5、duum of lesions caused by such infection in the pastChronic interstitial nephritis:renal disease with histologic findings resembling chronic bacterial pyelonephritis but without evidence of infection,Terms(5),“Upper UTI”:infection above the level of the bladder“Lower UTI”:infection at or below the l
6、evel of the bladder“Urethral syndrome”:clinical manifestations of lower UTI(dysuria,frequency,urgency)without significant bacteriuria,Terms(6),Pyuria:the presence of pus(WBCs leukocytes in urine,which may or may not be caused by UTI.The preferred method for quantitation is enumeration in unspun urin
7、e using a counting chamber.The leukocyte esterase nitrite test has a sensitivity of between 70%and 90%for symptomatic UTI,Asymptomatic bacteriuria,In patients with asymptomatic bacteriuria without infection,a colony count of 105 cfu/ml defines infectionScreening has little apparent value in adults e
8、xcept during pregnancy and prior to urologic surgeryUp to 40%of elderly men and women have asymptomatic bacteriuria,Frequency of significant bacteriuria,After one bladder catheterization:2%Medical outpatients:5%Pregnancy at term:10%Hypertensive patients:14%Diabetes mellitus:20%Women with cystocoele:
9、23%,Frequency of significant bacteriuria(2),Congenital urologic disease:57%Hydronephrosis;nephrolithiasis:85%Indwelling catheter,open drainage 48 hours:98%(reference:Jackson et al,Arch Intern Med 1962;110:663),Screening for significant bacteriuria,Screening for asymptomatic bacteriuria in adults has
10、 little value except for two situations:pregnancy(because of the high risk of acute pyelonephritis with its accompanying risk of fetal complications)and prior to urologic surgery(because of the risk of postoperative sepsis).,Urinary tract bacteriology,At room temperature,the doubling time of common
11、aerobic bacteria is about 20 minutesSome contaminants in voided urine:Lactobacilli,Cornyebacterium species,Gardnerella,alpha-hemolytic streptococci,anaerobesAny bacterial growth is significant if the specimen is collected from a normally-sterile site(e.g.,direct bladder puncture),Urinary tract bacte
12、riology(2),In pyelonephritis,the“105 cfu/ml”rule breaks down;fewer colonies can be significant.Up to 20%of young women with acute uncomplicated pyelonephritis have between 103 and 104 cfu/ml.In catheterized patients in whom specimens are obtained directly from the catheter,between 102 and 104 cfu/ml
13、 should may be significant.,Urinary tract bacteriology(3),Patients with uncomplicated infection almost invariably have a single organism;this is not necessarily the case with complicated infectionsUnspun midstream urine:One bacterium/high-powered field(hpf)correlates with 105/ml(thus,high positive p
14、redictive value),Urinary tract bacteriology(4),Grams stain of spun urine:absence of visible bacteria makes 105 cfu/ml highly unlikely(that is,high negative predictive value)20%of patients with urinary tract infection do not have pyuria,Etiology of community-acquired UTI,Aerobic gram-negative rods mo
15、st oftenE.coli accounts for about 90%Staphylococcus saprophyticus has been increasingly appreciated in recent years(with seasonality,tending to occur in the summer)Rare:anaerobes;pyogenic cocci;viruses,Etiology of nosocomial UTI,E.coli is the most common pathogenHowever,also common are other Enterob
16、acteriacae(Proteus,Klebsiella,Enterobacter,Serratia,Providencia species)and Pseudomonadaceae(notably,Pseudomonas aeruginosa)Enterococci:often in obstructive uropathyYeasts:Candida albicans,others,Urease-producing microorganisms,Urease splits urea into ammonia,which has a direct toxic effect on the k
17、idney;inactivates C4,and alkalinizes the urine with production of struvite crystals(MgNH4P04.6H20)crystalsProteus mirabilis most often;also Providencia,Morganella,S.saprophyticus,Klebsiella,Corynebacterium D2;mycoplasmaEradicate if at all possible,UTI in children,Newborns:overall rate is about 1%(hi
18、gher in males than in females)Preschool children:UTI is 10 to 20 times more common in girlsSchool-aged children:about 1.2%of schoolgirls have bacteriuria on any given day,UTI in adults,Women:bacteriuria increases with age and sexual activityMen:bacteriuria is rare before age 50(and as a corollary,ca
19、lls for more aggressive evaluation than in women).Subsequently,bacteriuria increases with onset of prostatism,Role of bacterial virulence in UTI,Bacterial adherence to uroepithelial cells involves specific binding of bacterial surface receptors(adhesins)to complementary components on the epithelial
20、cells(receptors).The ability of E.coli to adhere to uroepithelial cells is associated with the presence of pili or fimbriae.,The role of bacterial virulence(2),Specificity has been associated with the Gal-alpha-4-Gal specific adhesion localized at the fimbrial polymer.However,virulence of E.coli str
21、ains does not seem to depend upon a single virulence factor.There may well be an additive effect among multiple virulence factors(including adhesins,hemolysin,capsular polysaccharide,aerobactin),Host defenses:antibacterial properties of urine,Osmolality(extremes of high or low osmolalities inhibit b
22、acterial growth)High urea concentrationHigh organic acid concentrationpH,Host defenses:anti-adherence mechanisms,Bacterial interference(naturally endogenous bacteria in the urethra,vagina,and periurethral region)Urinary oligosaccharides(have the potential to detach epithelial-bound E.coliTamm-Horsfa
23、ll protein(uromucoid):coating of E.coli by this protein might prevent attachment,Host defenses:miscellaneous,Mucopolysaccharide lining of the bladderUrinary immunoglobulinsSpontaneous exfoliation of uroepithelial cells with bacterial detachmentMechanical flushing of micturition,Routes of urinary tra
24、ct infection,Ascending infection is thought to be the common route of nearly all forms of urinary tract infection(bacteria initially colonize periurethral tissues)Descending(hematogenous)infection can be important for a few organisms such as S.aureus and Candida albicans,but in general the kidney re
25、sists“metastatic infection.”,Mechanisms of lower UTI,Experimentally,99.9%of a bladder inoculum of bacteria is promptly excreted by voiding.Possible biologic explanations for the frequency of UTI in some women include:deficient antibodies in vaginal secretions;and biochemical differences in receptors
26、 on uroepithelial cells.,Mechanisms of upper UTI,Ascent of bacteria from the bladder to the kidneys is promoted by obstruction and by reflux.In addition,motile bacteria can ascend against the flow of a column of urine.Gram-negative bacteria(or endotoxin derived from them)can inhibit ureteral perista
27、lsis.,Mechanisms of upper UTI(2),The renal medulla is an“immunologic desert.”Its low pH(5.5)and high osmolality(which may reach 1300 mOsm/LK with a sodium of 425 mM and urea of 850 mM)drastically interfere not only with all aspects of leukocyte function but also with antibody and complement function
28、.,Localization of upper versus lower UTI,Indirect:pattern of recurrence(i.e.,same organism?);maximum urinary concentration;water loading test;serum antibodies;cellular excretion;urinary proteinsDirect:renal biopsy;ureteral catheterization;Fairleys bladder washout test;antibody-coated bacteria test,L
29、ocalization of upper versus lower UTI(2):in practice,Frequency,dysuria,and urgency(lower UTI symptoms)can occur with upper UTI as well.Fever and flank pain indicate acute upper urinary tract infection.Scarring of the kidney by imaging procedures suggests chronic UTI.The distinction is sometimes diff
30、icult.,Acute uncomplicated cystitis in young women,Acute dysuria in young women usually indicates:acute bacterial cystitis;the urethral syndrome;or vaginitisAcute bacterial cystitis is usually characterized by sudden onset,multiple urinary symptoms,pyuria,and sometimes hematuria,Acute uncomplicated
31、cystitis in young women(2),Although most patients have lower urinary symptoms only,30%to 50%may have subclinical renal involvementCauses:E.coli(80%),S.saprophyticus(10%to 15%),and occasionally Klebsiella,Proteus mirabilis,and other microorganisms,Acute uncomplicated cystitis in young women(3),A shor
32、t course of antibiotics(e.g.,three days)usually sufficesAbbreviated work-ups(e.g.,leukocyte-esterase nitrite test)without culture or routine follow-up is now acceptable for typical encounters.,Acute uncomplicated pyelonephritis in young women,Largely a clinical diagnosisPyuria is usually present;abo
33、ut 20%have positive blood cultures;causative organisms the same as with cystitisPredisposing factors:structural abnormalities;strains of E.coli with unique markers;genetically-determined carbohydrate receptors on uroepithelial cells,White blood cell casts,Highly significant!Presence suggests pyelone
34、phritis,Recurrent UTIs in women,Between 20%and 25%of young women with acute uncomplicated cystitis have 2 or more infections per year,usually due to reinfection with a different E.coli strainPredisposing factors:genetically-determined receptors on uroepithelial cells;diaphragm-spermicide use,Complic
35、ated UTIs,Definition:UTI in patients with predisposing anatomic,functional,or metabolic abnormalitiesSpectrum of organisms is skewed toward difficult-to-treat pathogens(e.g.,Pseudomonas sp.,yeasts,enterococci,Enterobacteriaceae other than E.coli),Catheter-associated UTI,Over 1 million catheter-assoc
36、iated UTIs occur in the United States each yearRisk factors:female sex;duration of catheterization;disconnecting the junction between the catheter and the collecting tube,Long-term bladder catheterization,Incidence of significant bacteriuria in patients who are not receiving antibiotics is 8%to 10%p
37、er dayMore than 85%of patients have at least two strains of bacteria and 10%have more than five strainsSome species(notably,enterococci,Pseudomonas,and Proteus)notoriously tend to persist,Prostatitis,Relapsing acute urinary tract infection in men caused by the same bacterial species often suggests chronic prostatitis with periodic spill-over into the bladderSymptoms:pelvic“heaviness,”rectal or perineal pain,urinary hesitancy,dribbling,and burningA risk of catheterization,
