SPECIAL ARTICLES

THE DIAGNOSIS OF URINARY TRACT Charles V. Pryles, M.D. Department of Pediatrics, Boston University School of Medicine, and the Pediatric Service, Boston City Hospital

T HE TWO major problems in bacterial in tients with during fections facing us today are the control this age period may recover with no impair of staphylococcal , and the con ment of renal function, or they may die trol of cases of bacillary sepsis.1 Infections during the acute phase of their illness. They due to staphylococci that are resistant to may recover and have latent almost all existing chemotherapeutic and with impairment of function and a de antibiotic agents are prevalent in hospital creased renal reserve, or they may have an patients and are especially common in intermittent or recurrent or progressive in wound infections. Bacillary sepsis, on the fection with a healing or healed pyelone other hand, makes its greatest impact in phritis and renal insufficiency that fre urinary tract infections and they, too, are quently leads to , , renal common in hospital patients. Keefer1 has dwarfism, or all three.1 stated, “¿pyelonephritis,whether acute or The lack of clear understanding of the chronic, active or healed or healing, is the pathogenesis, diagnosis and treatment of number one problem in infectious infections of the urinary tract is well rec due to today, and demands con ognized. It is equally well known that the tinuing attention and intensive study . classic syndrome of , flank pain, dys it is a problem calling for a high priority uria, frequency and pyuria may be absent of investigation.― in pyelonephritis, and that such disease The morbidity from urinary tract infec may occur as a smoldering chronic infec tions generally is not well appreciated. Few tion in which diagnosis is often overlooked data are available that accurately reflect the until too late. Thus, if the serious conse prevalence of bacteriuria and true pyuria. quences of pyelonephritis are to be averted, However, such infections perhaps rank sec early and more precise recognition of the ond only to respiratory infections in fre presence of such infections is necessary. It quency among patients; they probably out is important, therefore, that criteria be rank all other bacterial disease in children established that may prove helpful to the under 2 years of age.2'3 It is well, then, to clinician in making an early diagnosis of concentrate attention on urinary tract in infection of the urinary tract. fection in infancy and childhood, for it is The development of many new antimi not only one of the most important and crobial agents has emphasized the impor most frequent bacterial infections occurring tance of studying the bacterial flora found in this age group, but it is in this age period in urinary tract infections with great care, that chronic disease begins, and that infec because the selection of therapy will de tions most frequently cause premature pend in part on the species of organisms death and protracted illness. That urinary present in the . The two commonest tract infection is frequently associated with organisms isolated from single-type infec congenital abnormalities of the urinary tract tions are Escherichia coli and Staphylococ is well known.4@ The infection may be cus aureus. The other common Gram acute or chronic, unilateral or bilateral. Pa negative organisms that cause urinary tract

ADDRESS: Boston City Hospital, 818 Harrison Avenue, Boston 18, Massachusetts. PEDIATRICS, September 1960 441

Downloaded from www.aappublications.org/news by guest on October 1, 2021 442 URINARY TRACT INFECTION infection in declining frequency are Aero diagnosis of urinary tract infection, it may bacter aerogenes, Pseudomonas aeruginosa be useful to advance the following gen and Proteus vulgaris. Aside from staphylo eralizations based on our own experience cocci, enterococci are the commonest Gram and that of others: positive organisms found in urine.1012 Gen era! experience with adult patients indicates Urine as a Culture Medium that 75 to 80% of urinary tract infections Urine is usually an excellent culture me are bacillary in origin, and 20 to 25% are dium for the common pathogens of the coccal in origin. Our own experience with urinary tract. Pasteur was the first to direct children indicates that only 6 to 8% of in attention to this important fact. Thus, if fections are coccal in origin, the remainder small numbers of these bacteria were to be bacillary. In the experience of several clin discharged into the urine from a urinary ics, including our own, roughly three-fourths tract lesion, they would multiply rapidly of acute bacillary infections were caused by to reach a concentration of many thousands a single organism in the acute phase of the of bacteria per milliliter of urine.14 disease. Once a patient, however, has been Further, it has been noted by us and treated with an antimicrobial agent or has others@@that storage of urine at room temp required an inlying catheter or an operation eratures for 2 hours or longer leads to a on the urinary tract, the infection is likely distinct increase in the number of bacteria; to become mixed. A mixed infection may on the other hand, storage of a specimen also be present in a complicated urinary of urine at usual refrigerator temperatures tract lesion, i.e., with some anatomic or (4-5°C) up to 1 week will not alter signifi functional anomaly.10'12 cantly the number of organisms present. The evaluation of organisms in cultures These considerations must be kept in mind of urine has received scant attention. The at all times in the examination of urine significance of any given bacterial strain specimens. has been usually determined by the de monstration of its constancy in the urine in Definition of Pyuria the absence of specific therapy. This method Pyuria is said to be the hallmark of has the obvious disadvantage of requiring pyelonephritis but it alone is not satisfac multiple cultures before therapy, each tory for making a diagnosis of urinary tract taken with meticulous care; even then, the infection. In the first place, there is no gen significance of the findings may remain in eral agreement as to what constitutes pyu doubt. It should be emphasized that the na. Wilson and Schloss15 used the term to mere presence (or absence) of any given designate “¿thepresence of sufficient pus to microorganism is not an adequate basis for cause definite cloudiness of the urine.―They ruling it in or out as a cause of clinical further restricted the term to cases in which urologic disease. It is absolutely necessary the pus cells were not only very numerous that a distinction be made between true on microscopic examination, but were pres bacteriuria, i.e., the presence of bacteria ent in definite clumps. CampbelP6 considers in the urine of the urinary tract, and con three to five cells per low-power micro tamination of the urine during the pro scopic field in an uncentrifuged catheter cedure of collection. The bacterial count specimen to be within normal limits; Helm of the urine has offered a means of resolv holz (cited by Campbell16) has stated that ing the problem.13 two to eight cells per low-power field are normal. It is of no moment if the leukocytes GENERAL CONSIDERATIONS are single or clumped, especially in girls Prior to a discussion of the validity of where vaginal mucus may be the cause of bacterial counts in urine in relation to the clumping. Stevenson17 considers more than

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two to four leukocytes per low-power field, febrile condition such as pneumonia, tonsil from an uncentnifuged specimen, as abnor litis, appendicitis, or one of the exanthe mal. mata; or b) to a specific vaginitis, which Others― have defined pyunia as the pres is frequently associated with urethritis; or ence of five or more leukocytes per high c) to contamination from the stool in acute power microscopic field in a centrifuged entenitides. Chown, in addition, reported @specimen of urine. has shown that four children with marked pyunia, but with pyunia defined in this way occurs in one no source for the pyunia detectable at care third to one-half of patients with a true ful post-mortem examination; deaths were bacteriunia (i.e., with more than 100,000 due to extra-renal infection in all cases. organisms/mi of urine), but in only 2% of While sterile pyunia may be uncommon, it those with less than 100,000 organisms/mi may occur in 1) the extreme dehydration of of urine. Even if the criteria of pyunia were pyloric obstruction, low fluid intake, or lowered to three leukocytes per high-power acute toxemia; 2) in trauma caused by in field, the incidence in those with true bac struments or calculi; 3) when infection has teniuria rose by but 10%. In the patients in disappeared but an irritating agent re whom the house staff of the Harvard Medi mains; 4) in chemical ; and 5) cal Service at the Boston City Hospital had in acute ruhnti224 We have diagnosed pyelonephritis on clinical encountered a fair degree of pyunia in sev grounds, pyuria was found in only about eral patients with the last-mentioned dis one-half; 95% of the same patients had bac order. Unless all these sources are ruled terial counts greater than 100,000 organisms out, no case can be considered one of true /ml of urine. pyunia. It is clearly evident, then, that Jackson and associates2° found that 22% pyunia may be of diagnostic value only of 41 adult patients with pyelonephnitis when it is clearly present; its absence from (as determined by histopathologic findings any single specimen cannot be taken as evi in kidneys removed at surgery) had no pus dence of the absence of bacteniunia. It is cells in their urine. Of the patients without equally clear that pyunia may frequently pyelonephnitis, 20% showed 2 to 10 leuko be found in the presence of extra-renal in cytes per high-power microscopic field and fections, and in the absence of urinary tract 33% showed more than 10. The importance infection. of extra-renal infections in causing, on being associated with, pyunia is pointed up by Technique of Gram Staining the report of Beeler and Helmholz― who It has been known for many years that found pyunia present in 9 out of 18 infants bacteria can usually be found in stained (less than 2 years of age), and in 7 out of specimens of urine if infection is present. 13 children (over 2 years of age) with extra This has been subjected to quantitative renal infections. evaluation with one group14 finding that It is of further interest that in the early Gram-stained smears of uncentnifuged work on “¿pyelitis,―findings indicated that were positive in 80% of adults with the disease affected almost exclusively fe counts of 100,000 microorganisms or more male babies. As Chown― has indicated, it per milliliter of urine, and in 20% of speci seems that little or no attempt was made to mens with counts between 100 and 100,000. be sure that the urine, upon which the diag Sanford and his associates,25 studying meth nosis was based, was uncontaminated. The ylene blue stains of urinary sediments in, error is continued up to the present time. adults, found organisms in 6 of 34 patients There are three main sources of error here: (17%) with urinary bacterial counts between a) That pyunia may be due to catarrhal 1 and 1,000/rn!, in 5 of 18 (27%) with counts vaginitis, itself secondary to some acute between 1,000 and 10,000/mi, and in all

Downloaded from www.aappublications.org/news by guest on October 1, 2021 444 URINARY TRACT INFECTION of 91 patients with counts greater than from 0 to approximately 100,000 organ 100,000 organisms/mI of urine. Gram stains isms/mi of urine. Interestingly, he found of uncentrifuged specimens of urine in a less contamination in the non-catheter spec large group of children26 showed organisms imens than in those obtained by catheter. in 95% when the bacterial count was Linneweh,3° in an evaluation of catheter 100,000/mi or more. No organisms were specimens in children, found the zone be found when the colony count was less than tween contamination and infection to be 1,000/mi, except in one specimen (a ran approximately 1,000 organisms/mi of urine. dom voided one) in which Gram-positive Others@' reported findings in 21 adult cocci were seen in association with epi women from whom both clean-voided and thelial cells. The use of the Gram stain as catheterized specimens were taken. Five of a clinical guide to the presence of infec this group had more than 10,000 organ tion (as distinguished from contamination) isms/mi of urine in clean-voided culture, appears amply justified by these observa and in each case the catheterized specimen tions. The intrinsic error in the procedure confirmed this. The other 16 patients had varies from 5 to 27%. 900 or fewer organisms/mi of urine in both clean-voided and catheterized specimens. BACTERIAL COUNTS Jackson et al.2°compared 50 pairs of voided EarlyStudies and catheter specimens of urine from a Helmholz and Milleken27 in 1922 were group of adult women with hypertension among the first to point out the fact that attending an outpatient department, and chances for contamination during the col found that the voided specimen was com lection of specimens were so great that the parable to the catheter specimen in 96% of presence of organisms in the urine did not cases in which the growth from the cath prove, without further control, that they eter sample was greater than 100,000 col came from the urinary tract. Some two dec onies/ml of urine. Among 11 catheter spec ades later, Marple,13 studying adult women, imens that yielded a positive culture but again called attention to the necessity of less than 100,000 colonies/mi of urine, the performing quantitative bacterial counts in voided specimen produced the same re urine specimens. In 1940, Rantz and sult in 10 of the 11, or 95% of the observa Keefer,28 in a quantitative study of micro tions. organisms in the urine of patients with Kass19 studied a group of unselected pyelonephnitis, found that 1056 (100,000- women in a medical outpatient department 1 million) or more organisms per milliliter who presumably were free of clinical in of freshly voided and promptly cultured fection of the urinary tract. All specimens urine were always present during acute in of urine were obtained by catheterization. fections. He found that bacterial counts fell into two separate but overlapping population Criteria for Contamination versus Infection groups: one group with bacterial counts In the only published account in the between 0 and 10,000, and a second group English literature of a study relating to with more than 100,000 organisms/mi of children, Masters2° reported semi-quantita urine; this latter group was presumed to tive findings in five children from whom represent patients with infection of the catheter and non-catheter specimens were urinary tract. The two population groups obtained on the same day, and six others overlapped at 10,000 organisms/mi. On the for whom the intervai between the two basis of these data, Kass arbitrarily desig types of specimens were 1 or 2 days. The nated a count of 10@(100,000) or more or bacterial contamination varied from 0 to ganisms/mi of urine as the dividing line be more than 100 colonies/3-mm michrome tween true bacteriuria and contamination. loop (3 to 5 mm) of well-shaken urine, i.e., He found that 5% of patients with known

Downloaded from www.aappublications.org/news by guest on October 1, 2021 SPECIAL ARTICLES 445 infection of the urinary tract had colony specimen of urine. However, all of these counts less than 100,000/mi of urine. In patients showed colony counts greater than over half (55%) of the group of patients with 100,000/mi of urine in subsequent speci more than 100,000 organisms/mi of urine, mens. Conversely, only 2 of 100 clean there was a history of past urinary tract voided specimens from patients without infections, instrumentation, or inlying ca clinical urinary tract infection showed col thetenization. These patients were repeat ony counts of more than 1,000/mi. Subse edly found to have bacterial counts greater quent specimens from these two patients, than 100,000/mi of urine, and the organ however, had lower counts. isms found were almost always the com Thus, it can be seen that colony counts mon pathogens of the urinary tract. These provide a valid means of differentiating patients were therefore considered to have infection from contamination in a given true bacteniunia and infection. If the pa specimen of urine. The data in children tients have fever, flank pain, dysunia, and suggest that unines containing less than pyunia, then more than 100,000 organisms/ 1,000 colonies/mi are indicative of contami ml of urine and a Gram stain positive for nation; urmnes containing between 1,000 bacteria are almost always found. In fact, and 100,000 colonies/mi are to be suspected the failure to find large numbers of bacteria of infection and studies repeated, and in the presence of the classic syndrome of unines containing more than 100,000 col urinary tract infection should raise the onies/rnl are indicative of infection. question of ureteral obstruction. Catheterization has not eliminated the possibility of contamination during collec Validity of Clean Voided Specimens tion. In addition, the procedure is un It has been long-standing medical, pedi pleasant for the child, may be difficult to atric and urologic teaching that in girls cath perform in young children, and is incon eterized urine specimens alone can be venient in outpatient clinics and in gen relied upon for the diagnosis of urinary era! practice. The demonstrated validity of tract infection. We recently completed an properly collected clean voided specimens investigation26 designed to determine the in relation to the diagnosis of urinary tract validity of a clean-voided specimen in a infection is important in view of the con group of 170 young girls (all but 17 were siderable concern expressed recently re free of clinical urinary tract infection), garding the possibility of initiation of urin ranging in age from 3 to 12 years. From 58 ary tract infection during catheterization, of the girls, paired (catheter and clean especially repeated catheterization. Mar voided) specimens of urine were obtained; pie13 reported that 4 out of 100 women de the time interval between these two collec veloped a urinary tract infection following tions of urine specimens was less than 1 a single catheterization. Kass14 has reported hour. There was a 96.5% positive correlation a 2% incidence of urinary tract infection between catheter and clean voided speci following a single catheterization in a mens. group of 200 adults seen in rnedicai outpa Of the group of 17 children with clinical tient clinics. Guze and Beeson32 studied a evidence of infection of the urinary tract, group of 12 women free from urinary tract three had colony counts less than 100,000, infection, from each of whom they obtained but more than 1,000/mi of urine in a clean a specimen of urine by direct needle aspira voided specimen; the remaining 14 children tion of the bladder at laparotomy, and by had colony counts greater than 100,000 or urethral catheterization. All 12 aspiration ganisms/mi of urine. Thus, 17% of this specimens were sterile, but four of the small group of patients with clinical infec catheter specimens showed organisms on tion of the urinary tract had colony counts culture. One of the patients developed signs less than 100,000/mi of urine in the initial and symptoms of infection 36 hours after

Downloaded from www.aappublications.org/news by guest on October 1, 2021 446 URINARY TRACT INFECTION the single catheterization. Monzon et a!.― of 4 to 6 months following catheterization. carried out a similar study; in their results, Thus, while organisms were introduced into 27 of 34 collected by catheter were sterile. the urine of the children during catheteri One of the 34 patients developed an acute zation and in apparently significant quanti 1 day following the procedure. ties, infection was not a complication. It A comparative quantitative bacteriologic is our belief that while properly collected study of urine obtained by catheter and clean voided specimens may be used in by percutaneous suprapubic aspiration was most instances for making the diagnosis of carried out recently in our clinic34 in a true bacteniunia in children, catheterization, group of 42 children who were presumed when properly done, should not be with free from clinical urinary tract infection, held in the fear of producing urinary tract and who were undergoing elective surgery infection. While in some quarters it is for conditions that did not involve urinary thought that the best way to correct abuses tract manipulation. All but two of the of a procedure is to do away with the pro aspiration specimens were sterile, and in cedure entirely, our experience with Prohi these the bacterial count was well below bition would show this not to be a solu the critical figure of 10' (1,000) colonies/ tion. In our view, while all physicians ml of urine; therefore, on the basis of these should be alert to the importance of cath findings, the suprapubic specimens showed etenization in occasionally initiating in complete correlation with our clinical im fection, catheterization must remain a nec pression of the patients. The first portion essary procedure in the diagnosis and man of the catheter samples (C1) were sterile agement of urinary tract infections in cer in 25 (59.5%) of the cases; if the 14 ad tain cases, notably the following: 1) where ditional patients showing counts of non there is ; 2) where re pathogenic organisms below the critical peated study of clean voided specimens figure of 10@and assumed to represent con yields borderline or doubtful results; 3) tamination, are added to the 25 sterile where the patient is so acutely ill that cases, there is a 92.8% diagnostic correla there is a need for immediate antimicrobial tion between the suprapubic and C1 speci therapy, and no time for multiple speci mens. There was a 97.5% diagnostic correla mens to be obtained; and 4) where the pa tion between the second few milliliters of tient is unable or unwilling to co-operate. catheter urine (C2) and the suprapubic spe It is imperative, however, that if a proper cimens. Three of the patients in our series specimen for a valid bacterial count is to be had significant bacterial counts in the spe obtained, it must be collected by the physi cimens obtained by catheter, but the C2 cian in charge or under his direct super specimens showed a significant count in vision; the collection cannot be entrusted to only one of these three patients, pointing a clinical clerk or student nurse. up the well-known importance of discard ing the initial few milliliters of urine ob Bacteriuria and Pyelonephritis tained by catheterization. In this one pa While it appears clear from all studies tient the suprapubic specimen was sterile, to date that bacteniuria is associated with and a subsequent clean voided specimen urinary tract infection, bacteriunia is not did not exhibit significant growth. synonymous with pyelonephritis. That bac In view of the reported danger of intro teniuria is indeed frequently associated with ducing infection during the process of ob pyeionephritis has been shown by the in taining urine specimens by catheter, the vestigation of MacDonald et al.@5who stud course of this group of children subsequent ied bacterial counts of the bladder urine to their catheterization was followed obtained by needle aspiration in 100 un closely. All patients in the study were free selected necropsies and correlated the from urinary tract infection within a period counts with histopathologic findings. Fifty

Downloaded from www.aappublications.org/news by guest on October 1, 2021 SPECIAL ARTICLES 447 three per cent of the urines obtained at thnitis the leukocytes do not show such necropsy by needle aspiration of the blad staining characteristics. This deserves fur den contained no bacteria, 7% contained be then study. tween 10 and 10,000 bacteria/mi of urine, Under certain conditions,26 the bacterial and 40% of the urines contained more than count in a given sample of urine from a pa 100,000 organisms/mI. Active pyelonephni tient with clinical evidence of urinary tract tis was found in 14 of the 40 patients with infection may be low; this may happen 100,000 or more bacteria/mi of urine ( who when 1) the rate of urine flow is rapid and were considered to have true bacteniuria) the number of bacteria discharged into the and occurred in but 3 of 60 patients with no urine is small; 2) the pH of the urine is be or relatively few bacteria; two of these lat low 5.0, and the specific gravity is less than ter patients had received antibiotics prior 1.003; 3) a bacteniostatic agent is in the to death, and the third patient was ad urine; and 4) there is complete obstruction mitted in a terminal state from out of town of the preventing the entrance of or and her history was not available. Three ganisms into the urine. Rarely, fastidious additionai patients with counts greater than organisms that grow poorly in urine may 100,000 organisms/mi of urine had evi be present in but small numbers during dence of acute cystitis without pyelone active infection. Should such an organism phnitis. It is of great interest that a clinical be isolated from cultures of urine in a pa diagnosis of active infection of the urinary tient thought to have active infection on tract was not made in 70% of the cases in clinical grounds, the organism can be inoc which active pyelonephritis was found at ulated into a specimen of sterile urine and necropsy. Reliable clinical means for de its growth characteristic studied. Should termining which of the patients with true the microorganism grow poorly in such a bacteriuria have renal involvement are not urine, one would be justified in incniminat presently available, but, as MacDonald ing it as a possible pathogen in the patient rightfully states,― it would appear prudent under observation.'2 in the meantime, in view of the associa Special consideration must be given to tion of bacteniunia with pyelonephnitis, to those patients with chronic or recurrent regard each case of bacteniunia as being urinary tract infection who frequently, in associated with or likely to become asso the presence or absence of symptoms, may ciated with active pyelonephnitis and man show counts well below the range con aged accordingly. sidered to be significant (i.e., less than 1,000 Sternheimer and Malbin'° in 1951 re microorganisms/rn! of urine). They are less newed interest in certain characteristics of likely to show low counts in the presence the leukocytes excreted in pyelonephritis. of symptoms. Reiman38 reported that 14 out Through the use of the stain recommended of 23 adult patients with chronic active by these authors, Poiier and Jackson37 have pyeionephritis, as shown by histopathologic found a good correlation between pyeione studies (at nephrectomy or necropsy), re phritis and the presence of pale-staining peatedly showed bacterial counts in urine leukocytes in the urine. When the urine has samples of less than 1,000 bacteria/mi. a low specific gravity, these cells also show Others have reported similar findings. We Brownian movement of the cytoplasmic have frequenfly encountered children with granules. Poinier believes the staining char persisting low bacterial counts in the urine acteristics of the cells are the important after treatment, and have, perhaps errone feature and granular motion incidental. The ously, considered these to represent con supravitai staining technique is especially tamination, rather than evidence of a con helpful among patients with low degrees tinning infection. Suprapubic aspiration of of pyunia and chronic pyelonephritis. Ap bladder urine33 may be one means of re parently, in patients with cystitis or ure solving this problem of low bacterial counts

Downloaded from www.aappublications.org/news by guest on October 1, 2021 448 URINARY TRACT INFECTION in patients with chronic urinary tract infec been that tissue obtained is not adequate tion, but this and other means remain to or reliably representative for interpretation be explored. in view of the local nature of pyeione phritis. In the report by Kipnis et at.,43 the BIOPSY OF THE correlation between the kidney morphol Twenty years ago Iversen and Rohoim39 ogy, as seen in the biopsy, and kidney func introduced a safe technique for percutane tion was relatively good, although the de ous needle biopsy of the liver. Since then, gree and type of functional impairment of the clinical and histologic spectrum of the the kidney could not be judged reliably most important of the liver have from the microscopic examination of the been defined. In 1951, Iversen and Brun4° biopsy specimen. Kipnis cites unpublished published a technique for aspiration biopsy data from Pironi and Dallenbach regarding of the kidney and subsequently reported the general reliability of the biopsy in re their experience in the use of biopsies to flecting the diffuse morphology of the kid study certain diseases involving the kid ney when five or more glomeruii are ex ney. The value of percutaneous renal bi amined. Open biopsy technique, permitting opsies has been shown to be no less than visualization of most of the kidney and se that for the liver, and its potentialities have lection of sites for biopsy, may be more re been investigated by several groups.41'42 In warding than the blind needle technique, discussing the clinical value of renal bi but adequate comparative data are lacking. opsy, Kark et al.42 state: “¿Renalbiopsyap With only indirect (leukocytes, casts, pears to be a more accurate method than erythrocytes) and direct (bacteria) evidence culture of the urine in determining exactly of inflammation and infection, one cannot the organism responsible for infection with of course, localize the inflammation. Only in the kidney.― General experience, includ if there are signs of functional renal dam ing our own limited one, has failed to live age due to the spread of inflammation to up to this optimistic appraisal. renal interstitial tissue, and to damage and Other workers43 found that bacteriologic destruction of the surrounding structures, cultures of a fragment of renal tissue ob can one be reasonably certain about the tained from needle biopsy, in contrast to diagnosis of pyelonephritis, i.e., of renal the urine obtained nearly simultaneously, involvement.45 Roentgenographic studies were negative in 11 out of 13 cases. In the may also be helpful in showing renal in two biopsy specimens, the organism from volvement, but the absence of roentgeno the kidney was the same species as that graphic findings does not, of course, rule out recovered from the urine. Iversen and such involvement. The performance of Brun44 performed kidney biopsies upon renal biopsy by needle is not a technically eight patients with infected urine and a difficult procedure, and with adequate pre clinical diagnosis of pyelonephritis and the cautions little morbidity will be observed. biopsy supported the diagnosis in only one However, until further experience and the of the eight patients. In the six patients in contributions of the procedure are estab whom we have carried out needle biopsies lished, we believe that its use should be during an acute urinary tract infection, all restricted. cultures were negative, and histopatho logic studies supported the diagnosis in CONCLUSIONS AND SUMMARY only one. The mere presence (or absence) of any While culture of renal tissue obtained by given microorganism is not adequate for needle biopsy has not been rewarding, his ruling it in or out as a cause of clinical topathologic examination of such tissue has urologic infection. A distinction between been somewhat more fruitful. A criticism true bacteriuria and contamination of the of the renal biopsy technique by needle has urine during the procedure of collection

Downloaded from www.aappublications.org/news by guest on October 1, 2021 SPECIAL ARTICLES 449 must always he made in the evaluation is reliable for the diagnosis of urinary of a positive urine culture. The bacterial tract infection, recent studies refute this. count in a given urine sample has offered a While there is always a risk of introducing means of defining this distinction. The infection during the procedure of catheteni limited data in children, supported by more zation, this is minimal if proper precautions extensive data in adults, suggest that unines are exercised, and such fear should not in containing less than 1,000 colonies/mi are terdict catheterization under certain cm indicative of contamination; unines contain cumstances which have been mentioned. ing between 1,000 and 100,000 colonies/mI While bacteniunia is not to be considered are to be suspected of infection and studies synonymous with pyelonephnitis, several repeated, and urines containing more than histologic studies (at necropsy, at nephrec 100,000 colonies/mI are indicative of in tomy, and after renal biopsy) show that fection. The proper collection and handling bacteniuria is frequently associated with of specimens after collection is mandatory, involvement of the renal parenchyma. and should not be entrusted to untrained While reliable clinical means of determin personnel. ing which of the patients with true bac Conditions under which low bacterial teniunia have renal involvement are not counts may be encountered in the presence presently available, prudence dictates that of active infection are discussed. Special each case of bacteriuria be regarded as be consideration must be given to those pa ing associated with active renal disease, or tients with chronic or recurrent urinary very likely to become so. The staining char tract infection who frequently, in the pres actenistics of leukocytes excreted in pye ence or absence of symptoms, may show lonephritis may be helpful in determining bacterial counts in the urine below the the presence of renal involvement; the range considered to be significant. Reliable leukocytes of patients with cystitis or ure clinical means for resolving this problem thritis apparently do not show the staining remain to be explored. Suprapubic aspira characteristics of those excreted in pyelo tion of bladder urine for culture and bac nephnitis. A wider use of this supravital terial counts may prove helpful in given staining technique is needed to elucidate cases. Pyuria, said to be the hallmark of pye further its usefulness. In addition, renal lonephritis, is riot of itself satisfactory for function studies and roentgenographic ex making a diagnosis of urinary tract infection. aminations may be helpful. In the first place, there is a lack of general Bacteriologic culture of renal tissue ob agreement as to what constitutes pyunia; tained by needle biopsy has not proved secondly, pyunia may be seen with many fruitful, in general. Histopathologic study extra-renal infections; and finally, pyunia of such tissue has proved more rewarding. may be absent with infection of the urinary The limitations of the renal biopsy tech tract. A Gram stain of an uncentrifuged nique by needle are in large measure due specimen of urine will usually reveal bac to the focal nature of pyeionephnitis. While teria if infection is present. This has been the open biopsy technique, permitting di subjected to quantitative evaluation, with rect visualization of the kidney and selec almost all urine specimens with bacterial tion of site(s) for biopsy, may provide more counts of 100,000 or more/mi showing or adequate tissue for examination than the ganisms when stained by Gram's method. blind needle technique, satisfactory com Thus, the Gram stain of a smear of urine parative data are lacking. provides a useful screening technique for detecting patients with urinary tract infec REFERENCES tion. 1. Keefer, C. S.: Pyelonephritis—its natural While it has been taught, generally, that history and course. Bull. Johns Hopkins only the study of catheter specimens in girls Hosp., 100:107, 1957.

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2. Jackson, G. C., Dailenbach, F. D., and 19. Kass, E. H. : Asymptomatic infections of Kipnis, G. P. : Pyelonephritis: correla the urinary tract. Tr. A. Am. Physicians, tion of clinical and pathologic observa 69:56, 1956. lions in the antibiotic era. M. Clin. 20. Jackson, C. C., Grieble, H. C., and Knud North America, 39:297, 1955. sen, K. B. : Urinary findings diagnostic 3. Campbell, M. F. : Clinical Pediatric Urol of pyelonephritis. J.A.M.A., 166: 14, ogy. Philadelphia, Saunders, 1951, p. 1958. 355. 21. Beeler, C., and Helmholz, H. F. : The 4. Bugbee, H. G., and Wollstein, M.: Surgi bacteriology of the urine in healthy cal pathology of urinary tract in infants children and those suffering from extra based on a review of 4903 necropsies. urinary infections. Am. J. Dis. Child., J.A.M.A., 83:1887, 1924. 12:345, 1916. 5. Helmholz, H. F.: Congenital abnormalities 22. Chown, B. : Pyelitis in infancy; a path of the urinary tract in childhood. ological study. Arch. Dis. Childhood, J.A.M.A., 89:1932, 1927. 2:97, 1927. 6. Campbell, M. F.: Chronic urinary tract in 23. Campbell, M. F.: Reference 3, p. 3. fections in infancy and childhood. 24. Riley, C. M.: Pediatric Conference: The J.A.M.A., 99:2231, 1932. Roosevelt Hospital, New York. Arch. 7. Butler, A. M., and Lanman, T. H.: Ex Pediat., 76:364, 1959. amination of the child with chronic 25. Sanford, J. P., Favour, C. B., Mao, F. B., pyelonephritis. New England J. Med., and Harrison, J. H.: Evaluation of the 217:725, 1937. positive urine culture. Am. J. Med., 8. Erb, I. H., and Summerfeldt,P.:Con 20:88, 1956. genitai anomalies of the urinary tract 26. Pryles, C. V., and Steg, N.: Specimens of in children and infants and their rela tion to chronic pyuria. Canad. M.A.J., urine obtained from young girls by catheter versus voiding: a comparative 44:14, 1941. study of bacterial cultures, Gram strains 9. Campbell, M. F.: Symposium on pedi and bacterial counts in paired speci atric : indications for urologic mens. PEDIATRICS,23:441, 1959. examination in children. Pediat. Clin. North America, August, 1955, p. 653. 27. Helmhoiz, H. F., and Milleken, F.: The 10. Coleman, P. N., and Taylor, S.: Coiiform bacteriology of normal infants' urine. infections of the urinary tract. J. Clin. Am. J. Dis. Child., 23:309, 1922. Path., 2:134, 1949. 28. Rantz, L. A., and Keefer, C. S.: Sulfanil 11. Erlanson, P., and Jonsson, G.: Bacterial amide in the treatment of infections of aspects of chemotherapy of surgical the urinary tract due to bacillus coli. urinary infections. Acta chir. scandinav., Arch. mt. Med., 64:933, 1940. 106:399, 1953. 29. Masters, P. L.: Urinary changes in infec 12. Kass, E. H.: Management of infections of tions of the urinary tract in childhood. the urinary tract. Am. J. Med., 18:764, Guy's Hosp. Rep., 102:76, 1953. 1955. 30. Linneweh, F.: Zur Klinik der Harnweg 13. Marpie, C. D.: The frequency and char sinfektion. II. Neuere Kriterien zur acter of urinary tract infection in an Diagnostik der Hamwegsentztindungen. unselected group of women. Ann. mt. Deutsche med. Wchnschr., 82:438, Med., 14:2220, 1941. 1957. 14. Kass, E. H.: Bacteriuria and diagnosis of 31. Boshell, B. R., and Sanford, J. P.: A infections of the urinary tract. Arch. screening method for the evaluation of mt. Med.,100:709,1957. urinary tract infections in female pa 15. Wilson, J. R., and Schloss, 0. M.: Path tients without catheterization. Ann. ology of so-called “¿acutepyelitis― in Tnt. Med., 48:1040, 1958. infants. Am. J. Dis. Child., 38:227, 32. Guze, L. B., and Beeson, P. B.: Observa 1929. tion on the reliability and safety of 16. Campbell, M. F.: Reference 3, p. 37. bladder catheterization for bacteriologic 17. Stevenson, S. S.: Urinary tract infection in study of the urine. New England J. childhood. J. Louisiana M. Soc., 110:219, Med., 225:474, 1956. 1958. 33. Monzon, 0. T., Ory, E. M., Dobsen, H. D., 18. Anderson, A. S.: Urinary tract infections Carter, E., and Yow, E. M.: A compari in children: diagnosis and management. son of bacterial counts of the urine Bull. St. Louis Park M. Center, 1:240, obtained by needle aspiration of the 1957. bladder, catheterization and mid-stream

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voided methods. New England J. Med., 39. Iversen, P., and Roholm, K.: An aspira 259:764, 1958. tion biopsy of the liven, with remarks 34. Pryles, C. V., Atkin, M. D., Morse, T. S., on its diagnostic significance. Acta med. and Welch, K. J.:A comparativebac scandinav., 102:1, 1939. teriologic study of urine obtained by 40. Iversen, P., and Brun, C.: Aspiration percutaneous suprapubic aspiration of biopsy of the kidney. Am. J. Med., the bladder and by catheter in children. 11:324, 1951. PEDIATRICS, 24:983, 1959. 41. Parrish, A. E., and Howe, J. S.: Needle 35. MacDonald, R. A., Levitin, H., Mallory, biopsy as an aid in diagnosis of renal C. K., and Kass, E. H.: Relation be disease. J. Lab. & Clin. Med., 42:152, tween pyelonephnitis and bacterial 1953. counts in the urine: an autopsy study. 42. Kank, R. M., Muehrcke, R. C., Pollak, New England J. Med., 258:915, 1957. V. E., Pirani, C. L., and Kiefen, J. H.; 36. Sternheimer, R., and Malbin, C.: Clinical An analysis of five hundred percutane recognition of pyelonephritis, with a ous renal biopsies. Arch. Int. Med., new stain for urinary sediments. Am. J. 101:439, 1958. Med., 11:312, 1951. 43. Kipnis,C. P., Jackson, C. G., Dalien 37. Poirier, K. P., and Jackson, G. G.: Char bach, F. D., and Schoenberger,J.A.: acteristics of leucocytes in urine sedi Renal biopsy in pyeionephritis. Arch. ment in pyelonephritis: correlation with mt. Med., 95:445, 1955. renal biopsies. Am. J. Med., 23:579, 44. Brun, C., and Raaschow, F.: Recognition of 1957. pyelonephritis in renal biopsies, in Inter 38. Relman, A. S.: Some clinicalaspectsof nationalSymposium on the Biology of chronic pyelonephritis, in International Pyelonephritis, Henry Ford Hospital. Symposium on the Biology of Pyeloneph Boston, Little Brown, to be published. ntis, Henry Ford Hospital. Boston, Little 45. Brod, J.: Chronic pyelonephnitis. Lancet, Brown, to be published. 1:973, 1956.

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