Urinary Tract Infection - Kidney Atlas

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Urinary Tract InfectionAlain MeyrierThe concern of renal specialists for urinary tract infections(UTIs) had declined with the passage of time. This trend is nowbeing reversed, owing to new imaging techniques and to substantial progress in the understanding of host-parasite relationships,of mechanisms of bacterial uropathogenicity, and of the inflammatoryreaction that contributes to renal lesions and scarring.UTIs account for more than 7 million visits to physicians’ offices andwell over 1 million hospital admissions in the United States annually[1]. French epidemiologic studies evaluated its annual incidence at53,000 diagnoses per million persons per year, which represents1.05% to 2.10% of the activity of general practitioners. In the UnitedStates, the annual number of diagnoses of pyelonephritis in femaleswas estimated to be 250,000 [2].The incidence of UTI is higher among females, in whom it commonlyoccurs in an anatomically normal urinary tract. Conversely, in malesand children, UTI generally reveals a urinary tract lesion that must beidentified by imaging and must be treated to suppress the cause ofinfection and prevent recurrence. UTI can be restricted to the bladder(essentially in females) with only superficial mucosal involvement, orit can involve a solid organ (the kidneys in both genders, the prostatein males). Clinical signs and symptoms, hazards, imaging, and treatmentof various types of UTIs differ. In addition, the patient’s backgroundhelps to further categorize UTIs according to age, type of urinary tractlesion(s), and occurrence in immunocompromised patients, especiallywith diabetes or pregnancy. Such various forms of UTI explain thewide spectrum of treatment modalities, which range from ambulatory,single-dose antibiotic treatment of simple cystitis in young females, torescue nephrectomy for pyonephrosis in a diabetic with septic shock.This chapter categorizes the various forms of UTI, describes progressin diagnostic imaging and treatment, and discusses recent data onbacteriology and immunology.CHAPTER7

7.2Tubulointerstitial DiseaseDiagnosisABCFIGURE 7-1Urine test strips. Normal urine is sterile, but suprapubic aspiration of the bladder, which is by no means a routine procedure,Schematic set up ofa dip-slide containerwould be the only way of proving it. Urinary tract infection(UTI) cannot be identified simply by the presence of bacteria ina voided specimen, as micturition flushes saprophytic urethralorganisms along with the urine. Thus a certain number of colonyforming units of uropathogens are to be expected in the urinesample. Midstream collection is the most common method ofurine sampling used in adults. When urine cannot be studiedwithout delay, it must be stored at 4ºC until it is sent to thebacteriology laboratory. The urine test strip is the easiest meansof diagnosing UTI qualitatively. This test detects leukocytes andnitrites. Simultaneous detection of the two is highly suggestive ofUTI. This test is 95% sensitive and 75% specific, and its negativepredictive value is close to 96% [3]. The test does not, however,detect such bacteria as Staphyloccocus saprophyticus, a strainresponsible for some 3% to 7% of UTIs. Thus, treating UTI solely on the basis of test strip risks failure in about 15% of simplecommunity-acquired infections and a much larger proportion ofUTIs acquired in a hospital.Interpretation after 24-hour incubation at 37 CPaddle-holding NonsignificantstopperSignificantAgarMoist sponge103104105106107FIGURE 7-2Culture interpretation. Urinalysis must examine bacterial and leukocyte counts(per milliliter). An approximate way of estimating bacterial counts in the urine usesa dip-slide method: a plastic paddle covered on both sides with culture medium isimmersed in the urine, shaken, and incubated overnight.The most specific results, however, areprovided by laboratory analysis, whichallows precise counting of bacteria andleukocytes. Normal values for a midstreamspecimen are less than or equal to 105Escherichia coli organisms and 104 leukocytes per milliliter. These classical “Kass criteria,” however, are not always reliable. Insome cases of incipient cystitis the numberof E. coli per milliliter can be lower, on theorder of 102 to 104 [4]. When fecal contamination has been ruled out, growth ofbacteria that are not normally urethralsaprophytes indicates infection. This is thecase for Pseudomonas, Klebsiella,Enterobacter, Serratia, and Moraxella,among others, especially in a hospital setting or after urologic procedures.

Urinary Tract InfectionCAUSES OF ASEPTIC LEUKOCYTURIASelf-medication before urine cultureSample contamination by cleansing solutionVaginal dischargeUrinary stoneUrinary tract tumorChronic interstitial nephritis (especially due to analgesics)Fastidious microorganisms requiring special culture medium (Ureaplasma urealyticum,Chlamydia, Candida)7.3FIGURE 7-3Leukocyturia. A significant number of leukocytes (more than 10,000per milliliter) is also required for the diagnosis of urinary tract infection, as it indicates urothelial inflammation. Abundant leukocyturiacan originate from the vagina and thus does not necessarily indicateaseptic urinary leukocyturia [1]. Bacterial growth without leukocyturia indicates contamination at sampling. Significant leukocyturiawithout bacterial growth (aseptic leukocyturia) can develop fromvarious causes, among which self-medication before urinalysis is themost common.BacteriologyA. MAIN MICROBIAL STRAINS RESPONSIBLEFOR URINARY TRACT INFECTIONMicrobial StrainEscherichia coliProteus ococcus saprophyticusOther speciesPercent100First Episode orDelayed RelapseRelapse Due toEarly ��3.2%3%–7%2%–6%60%15%20%———5%FIGURE 7-4Principal pathogens of urinary tract infection (UTI). A and B, Mostpathogens responsible for UTI are enterobacteriaceae with a high predominance of Escherichia coli. This is especially true of spontaneousUTI in females (cystitis and pyelonephritis). Other strains are lesscommon, including Proteus mirabilis and more rarely gram-positivemicrobes. Among the latter, Staphylococcus saprophyticus deservesspecial mention, as this gram-positive pathogen is responsible for 5%to 15% of such primary infections, is not detected by the leukocyteesterase dipstick, and is resistant to antimicrobial agents that areactive on gram-negative rods.C, Acute simple pyelonephritis is a common form of upper UTIin females and results from the encounter of a parasite and a host.In the absence of urologic abnormality, this renal infection is mostly due to uropathogenic strains of bacteria [5,6], a majority ofcases to community-acquired E. coli. The clinical picture consistsof fever, chills, renal pain, and a general discomfort. Tissue invasion is associated with a high erythrocyte sedimentation rate andC-reactive protein level well above 2 mg/dL.MinimumMaximumE. coli60%Other5%50P. mirabilis15%Klebsiella20%0BE. coli P. mirabilis Klebsiella Enterococcus S. saprophyticus OtherEnterobacterC

7.4Tubulointerstitial DiseaseVirulence Factors of Uropathogenic StrainsEscherichia coliPFimbriaeS Type 1FlagellaHemolysinAerobactin Na NaFe3 ErythrocyteFIGURE 7-5Bacterial uropathogenicity plays a major role in host-pathogen interactions that lead to urinary tract infection (UTI). For Escherichiacoli, these factors include flagella necessary for motility, aerobactinnecessary for iron acquisition in the iron-poor environment of theurinary tract, a pore-forming hemolysin, and, above all, presence ofadhesins on the bacterial fimbriae, as well as on the bacterial cellsurface. (From Mobley et al. [7]; with permission.)Proteus mirabilisFimbriae MR/P PMF ATF NAFDeaminaseUreaseFlagellaNiUrea2 [Keto acid]3Fe3 Amino acidNH3 CO2IgA protease HemolysinNa Renal epithelial cellFIGURE 7-7Proteus mirabilis is endowed with other nonfimbrial virulence factors,including the property of secreting urease, which splits urea into NH3and CO2.FIGURE 7-6An electron microscopic view of an Escherichia coli organismshowing the fimbriae (or pili) bristling from the bacterial cell.FIGURE 7-8Staghorn calculi.Ammonium generation alkalinizes theurine, creatingconditions favorablefor build-up ofvoluminous struvitestones, which canprogressively invadethe entire pyelocalyceal system, forming staghorn calculi.These stones are anendless source ofmicrobes, and theurinary tractobstruction perpetuates infection.

Urinary Tract InfectionFimbrial adhesive structuresType 1 FimbriaeType P FimbriaeAdhesinFibrillum7.5Nonfimbrialadhesive structurePapGFimHPapFFimH, FimGPapEFimF, FimGPapKFimA 100FimARigid fiberPapAAdhesinsPapHPilinMinor subunitsAdhesinFIGURE 7-9Schematic representation of morphology and composition of type Pand type 1 adhesive structures. Bacterial adhesins are paramount infostering attachment of the bacteria to the mucous membranes of theperineum and of the urothelium. There are several molecular formsof adhesins. The most studied is the pap G adhesin, which is locatedat the tip of the bacterial fimbriae (or pili). This lectin recognizesbinding site conformations provided by oligosaccharide sequencespresent on the mucosal surface [8].FIGURE 7-10Uropathogenic strains of Escherichia coli readily adhere to epithelialcells. This figure shows two epithelial cells incubated in urine infectedwith E. coli–carrying pap adhesins. Numerous bacteria are scatteredon the epithelial cell membranes. About half of all cases of cystitis aredue to uropathogenic strains of E. coli–carrying adhesins. Femaleswith primary pyelonephritis and no urologic abnormality harbor auropathogenic strain in almost 100% of cases [5].APPROPRIATE ANTIBIOTICS FOR URINARY TRACT oroquinolonesCephalosporinsFirst generationSecond generationThird ycin trometamoleNitroturantoinGeneral IndicationsPregnancyProphylaxis † ‡ § * - ¶ ** †† - ‡ ‡ * Aminoglycosides should not be prescribed during pregnancy except for very severe infection and for the shortestpossible duration.With the exception of amoxicillin plus clavulanic acid, aminopenicillins should not be prescribed as first-line treatment,owing to the frequency of primary resistance to this class of antibiotics.‡ According to antibiotic sensitivity tests.§ Fluoroquinolones carry a risk of tendon rupture (especially Achilles tendon).¶ Oral administration only.** Single-dose treatment of cystitis.†† Simple cystitis; not pyelonephritis or prostatitis.FIGURE 7-11Appropriate antibiotics for urinary tractinfections (UTI). An appropriate antibioticfor treating UTI must be bactericidal andconform to the following general specifications: 1) its pharmacology must include, incase of oral administration, rapid absorption and attainment of peak serum concentrations; 2) its excretion must be predominantly renal; 3) it must achieve high concentrations in the renal or prostate tissue;4) it must cover the usual spectrum ofenterobacteria with reasonable chance ofbeing effective on an empirical basis.Excluding special considerations for childhood and pregnancy, several classes ofantibiotics fulfill these specifications andcan be used alone or in combination. Thechoice also depends on market availability,cost, patient tolerance, and potential forinducing emergence of resistant strains.

7.6Tubulointerstitial DiseaseClassification of Urinary Tract InfectionUpper versus lower urinary tract infectionFIGURE 7-12Cystitis in a female patient. In case of urinary tract infection (UTI), distinguishing betweenlower and upper tract infection is classical, but the distinction is also beside the point. The realpoint is to determine whether infection is confined to the bladder mucosa, which is the case insimple cystitis in females, or whether it involves solid organs (ie, prostatitis or pyelonephritis).The dots in this figure symbolize the presence of bacteria and leukocytes (ie, infection) in therelevant organ. Here, infection is confined to the bladder mucosa, which can be severelyinflamed and edematous. This could be reflected radiographically by mucosal wrinkling onthe cystogram. In some cases inflammation is severe enough to be accompanied by bladderpurpura, which induces macroscopic hematuria but is not a particular grave sign.FIGURE 7-13Prostatitis. Anatomically, prostatitis involvesthe lower urinary tract, but invasion ofprostate tissue affords easy passage ofpathogens to the prostatic venous system—and, usually, poor penetration by antibiotics. Presence of bacteria in the bladder isalso symbolized in this picture, but owing tofree communication between bladder urineand prostate tissue, it can be accepted thatpure cystitis does not exist in males.FIGURE 7-14Acute prostatitis can be complicated byascending infection, that is, pyelonephritis.FIGURE 7-15Pyelonephritis in females. Essentially, this isan ascending infection caused by uropathogens. From the perineum the bacteria gainaccess to the bladder, ascending to the renalpelvocalyceal system and thence to the renalmedulla, from which they spread toward thecortex. It has been shown that “pyelitis” cannot be considered a pathologic entity, as renalpelvis infection is invariably associated withnearby contamination of the renal medulla.

Urinary Tract Infection7.7CRITERIA FOR TISSUE INVASIONClinicalKidney or prostate infection is marked by fever over 38 C, chills, and pain. The patient appears acutely ill.LaboratoryTissue invasion is invariably accompanied by an erythrocyte sedimentation rate over 20 mm/h and serum C-reactive proteinlevels over 2.0 mg/dL. Blood cultures grow in 30%–50% of cases, which in an immunocompetent host indicates simply bacteremia, not septicemia. This reflects easy permeability between the urinary and the venous compartments of the kidney.ImagingWhen indicated, ultrasound imaging, tomodensitometry, and scintigraphy provide objective evidence of pyelonephritis.In case of vesicoureteral reflux, urinary tract infection necessarily involves the upper urinary tract.FIGURE 7-17Criteria for tissue invasion.FIGURE 7-16Renal abscess formation. As specified elsewhere, renal abscess due to enterobacteriaceae (as opposed to hematogenous renalabscess, often of staphylococcal origin) canbe considered a severe form of pyelonephritiswith renal tissue liquefaction, ending in awalled-off cavity.Primary versus secondary urinary tract infectionFIGURE 7-19Cystogram of a65-year-old woman.A voluminous bladder tumor (arrows)infiltrates the bladder floor and theinitial segment ofthe urethra.FIGURE 7-18An episode of urinary tract infection (UTI) should prompt consideration of whether it involves a normal urinary tract or, alternatively, ifit is a complication of an anatomic malformation. This is especiallytrue of relapsing UTI in both genders, and this hypothesis should besystematically raised in males and in children.Recurrent cystitis in females can be explained by hymeneal scarsthat pull open the urethral outlet during intercourse. Althoughrarely, other malformations that promote recurrent female cystitisare occasionally discovered, such as urethral diverticula (arrows).Finally, it should be recalled that recurrent or chronic cystitis in anolder woman can also reveal an unsuspected bladder tumor.

7.8Tubulointerstitial DiseaseFIGURE 7-20Urethrocystogram of a man following acute prostatitis. In males,acute prostatitis may reveal urethral stenosis. Urethral stenosis is agood explanation for acute prostatitis. The beaded appearance of thestenosis (arrow) suggests an earlier episode of gonorrheal urethritis.IIIIIIIVVFIGURE 7-21The severity of vesicoureteral reflux (VUR) as graded in 1981 bythe International Reflux Study Committee. When children haveAFIGURE 7-22Cystogram demonstrating left ureteral reflux (A). The consequences on the left kidney (B) consist of calyceal distension and aclubbed appearance due to the destruction of the papillae and ofpyelonephritis, the possibility of VUR should always be considered.Childhood vesicoureteral reflux is five times more common in girlsthan in boys. It has a genetic background: several cases occasionallyoccur in the same family. Unless detected and corrected early, especially the most severe forms of this class and when urine is infected(one episode of pyelonephritis suffices), childhood VUR is a majorcause of cortical scarring, renal atrophy, and in bilateral cases chronicrenal insufficiency. The International Reflux Study classifies refluxgrades as follows: I) ureter only; II) ureter, pelvis, and calyces, nodilation, and normal calyceal fornices; III) mild or moderate dilationor tortuosity of ureter and mild or moderate dilation of renal pelvisbut no or slight blunting of fornices; IV) moderate dilation or tortuosity of ureter and moderate dilation of renal pelvis and calyces,complete obliteration of sharp angle of fornices but maintenance ofpapillary impressions in majority of calyces; V) gross dilation andtortuosity of ureter, gross dilation of renal pelvis and calyces. Papillaryimpressions are no longer visible in the majority of calyces. (FromInternational Reflux Study Committee [9]; with permission.)Bthe adjacent renal tissue. The calyceal cavities are very close to therenal capsule, indicating complete cortical atrophy. This picture istypical of chronic pyelonephritis secondary to vesicoureteral reflux.

Urinary Tract InfectionFIGURE 7-23In case of bilateral, neglected vesicoureteral reflux, chronic pyelonephritis is bilateral and asymmetric. Here, the right kidney is globallyatrophic. A typical cortical scar is seen on the outer aspect of the leftkidney. The lower pole, however, is fairly well-preserved with nearlynormal parenchymal thickness.FIGURE 7-25(see Color Plate)In children, isotopiccystography allowsa diagnosis of vesicoureteral refluxwith much less radiation than if cystography were carriedout with iodinatedcontrast medium.7.9FIGURE 7-24When intravenous pyelography discloses two ureters, the one drainingthe lower pyelocalyceal system crosses the upper ureter and opensinto the bladder less obliquely than normally, allowing reflux of urineand explaining repeated attacks of pyelonephritis followed by atrophyof the lower pole of the kidney. Retrograde cystography is indicatedfor repeated episodes of pyelonephritis and when intravenous pyelography or computed tomography renal examination discovers corticalscars. In adults, retrograde cystography is obtained by direct catheterization of the bladder.FIGURE 7-26In the paraplegic,and more generallyin patients withspinal disease,neurogenic bladderis responsible forstasis, bladderdistension, anddiverticula. Thesefunctional andanatomic factorsexplain the frequencyof chronic urinarytract infectioncomplicated withbladder and upperurinary tractinfectious stones.

7.10Tubulointerstitial DiseaseImagingFIGURE 7-27When acute pyelonephritis occurs in a sound, immunocompetentfemale with no history of urologic disease, imaging can be limitedto a plain abdominal film (to rule out renal and ureteral stones) andrenal ultrasonography. Ultrasonography typically discloses a swollenkidney with loss of corticomedullary differentiation, denoting renalinflammatory edema. Images corresponding to the infected zonesare more dense than normal renal tissue (arrows).AFIGURE 7-29Computed tomodensitometry. Simple pyelonephritis does notrequire much imaging; however, it should be remembered that thereis no correlation between the severity of the clinical picture and therenal lesions. Therefore, a diagnosis of “simple” pyelonephritis atfirst contact can be questioned when response to treatment is notclear after 3 or 4 days. This is an indication for uroradiologic imaging, such as renal tomodensitometry followed by radiography of theurinary tract while it is still opacified by the contrast medium.The typical picture of acute pyelonep

Urinary Tract Infection T he concern of renal specialists for urinary tract infections . This test is 95% sensitive and 75% specific, and its negative predictive value is close to 96% [3]. The test does not, however, . There are several molecular forms of adhesins. Th

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