Urinary tract infections in childhood: An update

Urinary tract infections in childhood." An update Although controversies remain regarding the definition, diagnosis, and management o f urinary tract infections, such infections can pose a major risk to a child's well-being. Bacteriuria or recurrent urinary tract infections often pose difficult management problems. Symptomatic and asymptomatic bacteriuria during infancy are generally characterized by a benign outcome. In some children repeated episodes and, possibly, renal scarring result. The prognosis in young boys may be guarded i f neonatal bacteriuria, with or without symptoms, occurs in the presence o f anatomic defects. Although a variety o f pathogens have been identified as causing urinary tract infections, Enterobacteriaceae are usually the cause o f initial uncomplicated lower tract infections. Accepted therapy for such infections is reviewed, as are the combination therapies used for hospitalized patients with upper tract infections. An investigation o f piperacillin, a new, extended-spectrum acylaminopenicillin, raises the hope that it may provide effective monotherapy for upper tract infections. The criteria for selecting patients who require radiologic evaluation in the management o f urinary tract infections are reviewed. (J PeDIATe 106:1023, 1985)

Pearay L. Ogra, M.D., and Howard S. Faden, M.D. Buffalo, New York

INFECTION of the urinary tract has been described for nearly two centuries, yet the definition, pathogenesis, outcome, and managment of UTI continues to generate significant controversy. Notable areas of current debate include the definition of asymptomatic bacterial colonization vs disease of the urinary tract; the role of vesicoureteral reflux, lower tract obstruction, renal calculi, and catheterization in the pathogenesis of infection; the effectiveness of antireflux surgery; and the choice and duration of specific antibiotic therapy for primary or recurrent infections. It is unlikely that the following discussion will resolve any of these long-standing controversies. Nonetheless, it is hoped that a critical analysis of the available information may provide the reader with a better perspective of the problem areas and possibly contribute to the clinical management of serious UTI.

THE PROBLEM: DEFINITION AND DIAGNOSIS The urinary tract consists of the urinary conduit, which extends from the renal corticomedullary tissue to the external urethral meatus; the kidneys; and the mucosal components of the external genitalia. The kidneys and the urine in the bladder are normally sterile. On the other hand, the lower urethra in the female and, to a lesser extent, in the male has a detectable bacterial flora. The number of such organisms in the urethra diminishes I

TMP-SMZ UTI

Trimethoprim-sulfamethoxazole Urinary tract infection

toward the urinary bladder. (The proximity of the vagina and perianal region to the urethral meatus accounts for higher bacterial counts in females.)

Symptomatic bacteriuria: Acute uncomplicated UTI. From the Departments o f Pediatrics and Microbiology, School o f Medicine, State University o f New York at Buffalo. and Division o f lnfectious Diseases and Microbiology Laboratories, Children's Hospital. Reprint requests: Pearay L. Ogra, M.D., Children's Hospital, Division o f Infectious Diseases, 219 Bryant St,, Buffalo, N Y 14222.

Earlier studies have suggested that the presence of >1 • 105 organisms of a single species per milliliter of freshly voided ar~&cultured urine in patients with symptoms of dysuria, increased frequency, a n d urgency of micturition is highly (80% to 85%) indicative of active UTI. The likelihood of active UTI increases to about 96%

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Ogra and Faden

Table I. Test systems for detection of bacteriuria Bacteriologic Dip-slide inoculum transport medium. Inexpensive; highly reliable; easy to do at home. Pad culture: mixture of nitrite-tetrazoline culture. Rapid; highly reliable, with CFU >~100,000. Filter paper-agar plate. Variable reliability; requires incubation in the laboratory. Biochemical End0ioxin assay. Rapid; highly reliable. Triphenyl tetrazoline dye reduction. Simple to perform; rapid; variable reliability. Urinary glucose. Concentration 1.5 mg/dl glucose indicative of bacteriologic infection; unreliable; many variables. Catalase determination. Unreliable Nitrite (Greiss) test. Variable reliability

if two consecutive cultures reveal 1 • 105 organisms per milliliter of urine. 1 Others believe that, in symptomatic subjects, the presence of >1 • 104 organisms of the same species may be acceptable evidence of UTI. These patients may have lower bacterial counts because of excessive hydration, increased voiding, prior empiric antimicrobial therapy, or dysuria caused by localized urethritis. 2 In symptomatic subjects, the presence of even lower numbers of organisms (200 to 1000 bacteria per milliliter) in catheterized or aspirated suprapubic samples of urine have been considered indicative of UTI2 Asymptomatie bacteriuria. Healthy individuals or otherwise asymptomatic patients being screened for bacteriuria have been considered to be at risk of UTI if two or three consecutive cultures reveal > 105 organisms per milliliter of freshly voided urine.4 Other investigators have preferred to term such abnormalities covert bacteriuria, because many of these children have some symptoms of lower UTI. Upper tract infection: Acute complicated UTI. Upper tract infections include renal parenchymal infection (e.g., cellulitis, carbuncle), acute pyelonephritis, infections complicated by structural abnormalities of the upper collecting system or the presence of renal calculi, and other underlying renal diseases in association with other systemic illnesses (e.g., bacteremia in diabetes mellitus). Upper tract infection is often associated with bacteriuria, fever, chills, flank pain, and sometimes, severe systemic manifestations, including circulatory collapse.5 Recurrent UTI. Recurrent infection is generally defined as repeated symptomatic episodes of UTI with symptomfree intervals. Most recurrent UTIs are caused by the entry of new organisms from the perineal-fecal flora. Relapse. Recurrent UTI should be differentiated from

The Journal of Pediatrics June 1985

relapse, which is caused by the persistence of the same organism despite appropriate antibiotic therapy. Relapses often appear to be associated with underlying congenital or structural defects, renal calculi, or systemic disease. 6'v Other definitional considerations. Pyuria, hematuria, and the presence of other formed elements such as white blood cells, cell casts, epithelial cells, and red blood cells in the urine are frequently observed in patients with recurrent infection and pyelonephritis. However, it must be emphasized that these findings do not confirm the presence of underlying infection. They may not accompany acute renal parenchymal infections and they may exist in the absence of bacterial pyelonephritis. Therefore, a definitive diagnosis of UTI must rely on specific bacteriologic investigations. Unfortunately, it is not always possible to obtain appropriate clean-catch specimens from infants and young children. It is suggested that diagnosis of significant bacteriuria should be based on at least two cultures or, if necessary, a culture of catheterized or aspirated suprapubic urine. Suprapubic aspiration is safe and reliable even in young infants.8 Such an approach to diagnosis must be considered because urine cultures based on a single voided specimen may yield false positive results in as many as 25% of patients. 8 Diagnosis of hacteriuria. Many biochemical and specific bacteriologic test systems have been developed to document bacterial infections of the urinary tract (Table I). Under most circumstances, it is not necessary, and often prohibitively expensive to use agar plate cultures. It is unfortunate that in current usage the term "urinary tract infection" does not differentiate between upper and lower tract infections. The methods used to demonstrate the presence of upper tract involvement have included bladder washout, presence of antibody-coated bacteria, appearance of phase reactants in serum, ureteral catheterization, and careful assessment of clinical signs and symptoms. The success of these methods in identifying upper tract disease varies considerably, with the possible exception of ureteral catheterization. Depsite the possibility of a somewhat guarded outcome in upper tract disease, invasive, overaggressive attempts to document upper tract infection are, in general, not justified. NATURAL HISTORY AND PATHOGENESIS

Incidence of UTI. The incidence of UTI in otherwise healthy persons varies considerably with age and sex. It is estimated that about 1.5% to 2% of children ranging in age from 1 year to 5 years will develop symptomatic UTI. 9 Recent epidemiologic studies have suggested that, based on specimens of urine obtained via catheter, the prevalence of asymptomatic bacteriuria in infants younger than 23 months is 0.5% in boys and 1.8% in girls. In children 24 to

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60 months of age, it is estimated to be about 0.8% in girls and negligible in boys.9 In premature neonates, the prevalence of asymptomatic bacteriuria is estimated to be about 3%20 In children 5 to 10 years of age, the prevalence is bout 1% to 1.5%. ",~2 The rate of UTI rises by approxinately 1% for each decade of life thereafter? It has been suggested that the risk of acquiring bacteriuria in girls is about 5% to 10% during the school years. ~3 In general, symptomatic UTI appears to occur less frequently than asymptomatic bacteriuria in every age group, and it is believed that as many as 50% of patients with asymptomatic bacteriuria have had previous symptomatic UTI. ~4 Several authors have suggested that asymptomatic bacteriuria may simply reflect an abnormal laboratory value, which is not necessarily related to actual disease. ~5-~7More recent observations, however, have suggested a strong relationship between asymptomatic bacteriuria. UTI, and upper tract damage. ~.9.~ Based on a careful prospective evaluation of large numbers of children with asymptomatic bacteriuria, Siegel et al? have observed the presence of upper urinary tract damage in 17% of infants aged 23 months and in 13% of children aged 24 to 60 months (Table II). It is also noteworthy that 46~ of infants younger than 23 months and as many as 9% of children 24 to 60 months of age with UTI exhibit vesicoureteral reflux. 9 However, urinary reflux by itself does not appear to cause UTl. This impression is based on the observation that 80% of UTIs that recur after appropriate antimicrobial therapy do so regardless of coexisting reflux or antireftux surgery. ~9-2~ Significantly, however, 50% to 60% of patients with reflux develop signs of systemic illness and upper tract involvement, compared with only 8% of those without reflux. 22 Outcome of infection. The urinary tract mucosa is endowed with a variety of nonspecific and immunologically specific defense mechanisms that, even in the presence of bacteriurla, may make development of overt disease an exception rather than the rule. These include (1) immunobiologic barriers (perineum, vaginal flora, bladder resistance, adherence, mucosal immunity), (2) factors that prevent reflux. (3) anatomic barrier of calyx, (4) cortical barrier, and (5) systemic antibody and cellular immune reactivity23 In the female, the bacteria in all likelihood enter the urethra and bladder via the vagina and from the perinealfecal reservoir. During the course of micturition, turbulence in the stream of urine may result in retrograde carriage of organisms into the bladder, and closure of the urethra at the end of micturition may return urine containing bacteria to the bladder. Normally, such bacteria are cleared from the bladder spontaneously within 72 to 96 hours. 24Inability to clear these organisms from the bladder

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Table II. Outcome of urinary tract infection and associated disease based on long-term prospective evaluation in children with asymptomatic bacteriuria

P~symptomatic bacteriuria* Boys ' Girls Total Upper urinary tract damage Vesicoureteral reflux

Infants 1 to 23 mo (%)

Children 24 to 60 mo (%)

0.5 (1.8) 1.8 (3.6) 2.3 (5.4) 17.0

0 0.8 (1.9) 0.8 (1.9) 13.0

46.0

9.0

Data fromSiegelSR, SiegelB, SokoloffBZ, KanterMH: Am J Dis Child 134:369, 1980.) Incidencebased on cleancatch collections. *Incidencein girls 5 to I0 years, 1%to 1.2%;rate rises by about 1% each decade thereafter.

may then result in the establishment of lower tract infection in the bladder and proximal urethra. Ascent of organisms to the ureters or transport of organisms to the susceptible renal corticomeduliary tissue may be followed by the occurrence of upper tract infection. Acute pyelonephritis usually resolves spontaneously in 8 to 10 weeks; and may heal With the formation of a nonfunctional scar extending as a wedge from the medulla to the cortex of the kidney.25 The precise reasons underlying the establishment of bacterial invasion in the urinary tract with the development of inflammation in some but not all bacteriuric subjects are not known. However, several host- and pathogen-related factors appear to contribute significantly, including the presence Of anatomic or structural defects, renal calcUli, prior sexual intercourse, possible underlying defects of host defense, the nature of specific bacterial antigens that promote adherence, colonization, and mucosal damage, and other virulence factors of the organism that result in increased microbial invasion and the subsequent development of disease. Following the development of recurrent UTI, renal parenchymal infection, acute pyelonephritis, or scarring of renal corticomedullary tissue are well-established complications. However, chronic pyelonephritis is not solely (and may not even be usually) related to repeated UTI. 4 An elegant long-term case control study based on careful longitudinal follow-up ranging from 9 to 18 years has demonstrated that bacteriuria in early childhood in girls "defines a group at greaJ;,wisk of recurrent symptomatic UTI and renal scars and ht low risk of reduced renal function. ''26 A summary of these data is presented in Table III. These observations suggest that the natural history of symptomatic or asymptomatic bacteriuria in infancy is in

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The Journal of Pediatrics June 1985

Table IlL Outcome in schoolgirls 8 years of age with bacteriuria during follow-up of 8 to 18 years. Observations at follow-up

Bacteriuria (n = 60)

Controls (n = 38)

P

Episode Of bacteriuria (%) With clinical infection (UTI) With ~5 episodes of recurrent bacteriuria With episodes of bacteriuria during pregnancy Blood pressure Renal scarring (radiologic) (%) Serum creatinine

11.6 21.7 63.8 114,/73 26.6 0.88

0 26 26.7 115,/71 0 0.76

<0.05 <0.01 NS <0.01 <0.05

(Data from GillenwaterJY, HarrisonB, KuninCM: N Engl J Med 301:396, 1979.) general characterized by a benign outcome insofar as renal function is concerned. However, recurrent episodes of UTI as well as evidence of renal Scars must be expected in a certain proportion of these Children. On the other hand, neonatal UTI and bacteriuria associated with anatomic defects (often seen in boys) may have a worse prognosis and result more frequently in renal scarring, and sometimes in rapidly developing renal atrophy. 6. ~6 Microbiology of UTI. Because the principal reservoir of infectious agents for the urinary tract is the flora o f the external genital, perineal, and perianal regions, the organisms most frequently implicated in UTI include species of Enter0bacteriaceae, especially Escherichia coli and other gram-negative enteric organisms. In addition, organisms such as Proteus, Pseudomonas, Streptococcus viridans, StaphylOcoccus aureuS, Klebsiella, Haemophilus, coagu: lase-negative Staphylococcus, and others have been associated with the development of UTI. 27 Recently, studies carried out in a general practice setting have suggested that infection with Proteus spp is more common in boys, whereas the frequency of infection witti E: coli appears to be similar in both sexes. 27Renal parenchymal infections of hematogenous origin are predominantly caused by E. coli and S. aureus. 28"29In addition, recent reports have suggested that either nosocomially acquired UTI or an occult focus of infection in the urinary tract is the cause of baeteremia in many hospitalized patients?~ Such invasion of the bloodstream by urinary tract bacteria has been encountered at the rate of about 2 to 16 episodes per 100 UTIs. The responsible organisms include E. coli, Serratia, Proteus, and other microorganisms mentioned above: M A N A G E M E N T G U I D E L I N E S AND USE OF ANTIMICROBIAL AGENTS The clinical approach to the evaluation and treatment of UTI is extremely variable and is determined to a large extent by the physician's perception as to how such testing or treatment will influence the outcome of the infection in a given patient. Although the long-term prognosis of UTI is Still not well understood, based on the information

summarized, several specific guidelines for management have been developed. Asymptomafie bacteriuria. Based on our experience, we recommend that bacteriuria of 105 organisms per milliliter of urine observed on successive cultures in children and asymptomatic pregnant women be treated with antibiotics. Appropriate antimicrobial agents should be chosen on the basis of the in Vitro antibiotic sensitivity of the organism) However, it should be pointed out that other investigators have observed that treatment of covert bacteriuria in childhood does not prevent recurrences of infection.17

Symptomatic bacteriuria: Acute uncomplicated UTI. Symptoms such as urinary urgency, increased frequency, and dysuria associated with bacteriuria generally reflect cystitis or urethritis in women of child-bearing age and m young children. The predominant single organism associated with these infections is a member of the Enterobacteriaceae family. Therefore, in vitro sensitivity testing may not be necessary routinely when initiating antimicrobial therapy. With or without therapy, signs and symptoms usually disappear within 48 hours, and most infections resolve bacteriologically and clinically within a week. Infection is by and large self-limited, and it is estimated that in up to 80% of patients bacteriuna will resolve spontaneously? Despite these observations, it is generally considered prudent to treat such infections with antibiotics. It appears that symptomatic bacteriuria can be treated quite effectively with single-dose therapy with amoxicillin3~ or trimethoprim-sulfamethoxazole.32 Single-dose antibiotic therapy is not recommended in patients with renal parenchyma! infections and upper UTI, in males, during pregnancy, or in patients who are not available for careful follow-up?2 Other investigators prefer to treat all symptomatic and asymptomatic bacteriuria for 10 days, because recurrence may be somewhat higher in patients treated for fewer than 3 to 4 days. 32 Upper tract infection: Acute complicated UTI. In general, there is little disagreement concerning the need for

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Table IV. Outcome of treatment with piperacillin in patients with complicated urinary tract infections

Age Patient 1

(yr)

Sex

Pathogen

5~2

F

P_ aeruginosa Klebsiella P. aeruginora Acinetobacter E. coli P. aeruginosa E. coli E. coli P. aeruginosa P. aeruginosa P. aeruginosa

2

16 16

M M

3 4 6 8 9

1

M

16)~z 2 5 3 %2 Vt2 2

F F F F F F F

10 11 12

Duration of treatment (day)

Piperacillin MIC (~g/ml)

16 6

4 --

12

32

5

8

8

0.5

6

--

6

32

6 6 6 6

4 4 2 4

Outcome

Cure Cure Cure Cure Cure Cure Cure Cure; relapse* Cure Cure; relapse* Cure

*Insufficientduration of therapy; iO0 to 500 mg/kg/day in four to six doses. effective antimicrobial therapy in patients with renal parenchymal infection, acute pyelonephritis, or upper t r a c t infections complicated by structural anomalies, obstruction, or renal calculi, and in. infected subjects who have surgically induced urinary tract alterations because of underlying defects in the uririary conduit, These patients should receive treatment for 2 to 3 weeks o r a l l y or parenterally, depending on the clinical severity of illness. Moderatley ill patient s often require hospitalization and intensive parenteral therapy. Therapy can be initiated l'ntravenously with a combination of an aminoglycoside and ampicillin, a cephalosporin, or TMP-SMZ. Subsequent therapy can be tailored to the specific identity of the Organism and its in vitro antibiotic sensitivity. The introduction of new extended-spectrum acylaminopenicillins such as piperacillin, azlociilin, and mezlociliin has raised the possibility that a single antibiotic may be used quite effectively as the initial and subsequent mode of therapy for complicated UTIs. For example, piperacillin is active in vitro against a broad spectrum of bacteria, including the gram-negative and gram-positive organisms associated with UTI. The drug appears to be more active in vitro than carbenicillin, ticarcillin, and ampicillin against E. coli, Klebsiella, and Serratia spp. Moreover, piperacillin is extremely active against Pseudomonas aeruginosa. 33,34 Studies carried out in our program with the use of piperacillin to treat acute complicated UTI have shown this drug to be safe and effective (Table IV). Twelve patients were studied (one, twice). The majority of subjects had complications of the urinary tract. For example, patient 2, evaluated once for a Pseudornonas infection and once for a Klebsiella infection, had an ileal loop because of severe bladder dysfunction. Three of the children (patients 9, 10, and 12) previously had received ureteral reimplantations because of recurrent urinary tract infections with moderate to severe reflux. Another child (patient 6), who had a neurogenic bladder, required daily self-catheteriza-

tion. In one child (patient 1 1), a congenital bladder exotrophy had been repaired several years previously. One child (patient 3) had acute severe pyelonephritis with bilateral hydronephrosis, which necessitated bilateral ureteral reimplantation. The remaining patients had acute infections without prior history of urinary tract abnormalities. Treatment with piperacillin in a dose of 100 to 150 mg/kg/day, administered intravenoUsly in 4 tO 6 divided doses, resulted in prompt clinical and bacteriologic cure in 9 of 11 (82%) UTIs caused by different gram-negative organisms, after 1 to 2 weeks of therapy (Table IV). Two children (patients 9 and 1 1) who became bacteriologically sterile after initial therapy had recurrence of baeteriuria with the same organism. The organisms were susceptible to piperacillin in vitro, and it Was thought that the relapses were probably caused by insufficient duration of therapy. It is encouraging that the newer penicillins used alone are quite effective in the treatment of Severe and often complicated UTIs: However, at the present time, most infectious disease experts rarely use Such penicillins alone for initial treatment of serious infections. Although the extended-spectrum igenicillins are relatively safe and have been used successfully to treat patients with serious bacterial infections, comparative data are not available to establish their superiority over other conventional therapeutic approaches. It should be pointed out, however, that piperacillin is a highly effective therapy for serious UTIs caused by many gram-negative orgeanisms. We recommend the Use of piperacillin alone in patients in whom further aminoglycoside therapy may be undesirable because of prior e;~J~ensive impairment of renal function. Recurrent infection.'Recent observations have suggested that recurrent episodes of symptomatic oF asymptomatic bacteriuria often can be prevented by the prophylactic use of such antibiotics as T M P - S M Z or nitrofurantoin? 5,36

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Ogra and Faden

Use of low doses of T M P - S M Z every other day appears to prevent recurrences for long periods; the development of secondary infections with resistant organisms seems to be rare during such antibiotic prophylaxis? 2 The use of nitrofurantoin has also been found to be quite effective; however, it may be associated with somewhat more severe side effects. Antibiotic prophylaxis may be continued for from 6 months to 2 years, and under certain circumstances, longer if necessary. It is Our recommendation that before long-term antibiotic prophylaxis is considered to prevent recurrent infections, additional evaluation may be necessary in certain patient groups, including girls younger than 6 years with first episodes of symptomatic or asymptomatic bacteriuria, girls of any age with a history of recurrent UTI, and boys of any age. These patients should be evaluated radiologiearly to rule out any underlying Structural defects and prior renal scarring and to identify the presence and degree of vesicoureteral reflux~ if any. Evaluation by a urologist must be considered in patients with moderate to severe reflux. The severity of reflux decreases Considerably with increasing age, especially if urine remains sterile, 2z and in many children, reflux may disappear completely by puberty: However, there is strong evidence that Severe (grade 3) reflux that persists despite sterile urine may be harmful, leading to clubbing and renal scarring (sterile reflux nephropattiy). Such patients may require corrective surgical intervention. REFERENCES 1. Kass EH: How and why to treat urinary infections. Hosp Med, May 1968, p 73. 2. Kass EH: Infections of the urinary tract. In Kass EH, Platt R, editors: Current therapy in infectious disease, 1983-84. Philadelphia, 1983, B.C. Decker, p 161. 3. Stickler GB: Urinary tract infection in children. Postgrad Med 66:159, 1979. 4. Rifkin RH: Urinary tract infection in childhood. Pediatrics 60:508, 1977. 5. Turck M: Urinary tract infections. Hosp Prac, January 15:49, 1980. 6. Cohen M: The first urinary tract infection in male children. Am J Dis Child 130:810, 1976. 7. Siegel SR, Sokoloff B, siegel B: Asymptomatic and symptomatic urinary tract infection in infancy. Am J Dis Child 125:45, 1973. 8. Aronson AS, Gustafson B, Svenningsen NW: Combined Suprapubic aspiration and clean voided urine examination in infants and children. Acta Pediatr Scand 62:396, 1973. 9. Siegel SR, Siegel B, Sokoloff BZ, Kanter MH: Urinary infection in infants and preschool children. Am J Dis Child 134:369, 1980. 10. Edelmann CM, Ogwo JE, Fine BP, et al: Prevalence of bacteriuria in full-term and premature infants. J PEDIATR 82:125, 1973.

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11. Savage DCL, Wilson MI, McHardy M, et al: Covert bacteriuria of childhood. Arch Dis Child 48:8, 1973. 12. McLachlan MSF, Meller ST, Verrier-Jones ER: Urinary tract in schoolgirls with covert bacteriuria. Arch Dis Child 5;0:253, 1975. 13. Kunin CM: A ten-year study of bacteriuria in schoolgirls. J Infect Dis 122:382, 1970. 14. Freeman JW, Sindhu SS: A survey for bacteriuria in schoolgirls. Med J Aiast i:135, 1974. 15. Asscher AW: UTI. Lancet 2:1365, 1974. 16. Randolph MF, Morris KE; Gould EB: The first UTI in the female infant. J PEDiATR86:342, 1975. 17. Savage DCL, Howie G, Adler K, Wilson MI: Controlled trial of therapy in covert bacteriuria of childhood. Lancet 1:358, 1975. 18. Sidor TA, Resnick MI: Urinary tract infection in children. Pediatr Clin Nortfi Am 30:323, 1983. 19. Kun~n CM: The natural history Of recurrent bacteriuria in schoolgirls. N Engl J Med 282:1443, 1970. 20. Kunin CM: The natural history of recurrent bacteriuria in schoolgfiqs. In Kincaid Smith P, Fairley KR, editors: Renal infection and renal scarring. Melbourne, Australia, Mercedes Publishing Service, 1970, p 3. 21. Friedland GW: Recurrent urinary tract infections in infants and children. Radiol Clin North Am 15:19, 1977. 22. Govan DE, Fair WR, Friedland GW, et al: Management of children with urinary tract infections: The Stanford experience. Urology 6:273, 1975. 23. Ogra PL, Yamanaka Y, Losonsky GA: Local immunologic defenses in the genital tract. Reproductive immunology, New York, 1981, Alan R. Liss, p 381. 24. Bran JL, Lewison M, Kaye D: Entrance of bacteria into the female urinary bladder. N Engl J Med 286:626, 1972. 25. Braude AI: Current concepts in pyelonephritis. Medicine 52:257, 1973. 26. Gillenwater JY, Harrison B, Kunin CM: Natural history of bacteriuria in schoolgirls. N Engl J Med 301:396, 1979. 27. Naylor GRE: A 16-month analysis of urinary tract infection in children: J Med Microbiol 17:31, 1984. 28. Lebowitz RL, Fellows KE, Colodny AH: Renal parenchymal infections in children. Radiol Clin North Am 15:37, 1977. 29. Schiff M, Glickman M, Weiss RM, Ahern M J, et at: Antibiotic treatment of renal carbuncle. Ann Intern Med 87:305, 1977. 30. Krieger JN, Kaiser DL, Wenzel RP: Ur!nary tract etiology of bloodstream infections in hospitalized patients. J Infect Dis 148:57, 1983. 3i. Shapiro ED, Wald ER: single-dose amoxiciltin treatment of urinary tract infections. J PED1ATR99:989, 1981. 32. Treatment of urinary tract infections. Med Lett 23:689, 1981. 33. Eliopoulos GM, Moellering RC: Aziocillin, mezlocillin and piperacillin: New broad-spectrum penicillins. Ann Intern Med 97:755, 1982. 34. Winston D J, Murphy W, Young LS, Hewitt WL: Piperacillin therapy for serious bacterial infection. Am J Med 96:255, 1980. 35. Hard!rig GKM, Ronald AR: A controlled study of antimicrobial prophylaxis of recurrent urinary infection in women. N Engl J Med 291:597, 1974. 36. Stamey TA, Condy M, Mihara G: Prophylactic efficacy of nitrofurantoin macrocrystats and trimethoprim-sulfamethoxazole in urinary infections. N Engl J Med 296:780, 1972.

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COMMENTS DR. NELSON: Among the patients in your series, Dr. Ogra, one had an infection with an Pseudornonas strain that had an MIC of 8 /zg/ml to piperacillin. In general, Acinetobacter species are resistant to the newer antibiotics. Is this case an exception, or are a large number of Acinetobacter strains susceptible to piperacillin? DR. OGRA:Although we have not had a large number of Acinetobacter isolates, the MICs of most of those we have observed have fallen into the same range that was observed for this patient. DR. BROWN:We have used piperacillin in the treatment of Acinetobacter infections related to Broviac or Hiekman catheters. The combination of piperacillin and an aminoglycoside has permitted us to retain the catheter in a good number of these instances. DR. KLEIN: What would be the initial therapy, while

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awaiting culture results, for the child who has recently undergone eystoscopy or other manipulative procedures, has high temperature spikes, and has a presumed tissueinvasive infection of the urinary tract. DR. O6RA: I think that Pseudomonas is a problem in patients with underlying disease. Thus, I would think that, if combination therapy is to be administered, the use of piperacillin with an aminoglycoside would be more appropriate. DR. KLEIN: Our experience is that Pseudomonas does occur with sufficient frequency in these patients to be a source of concern. DR. NELSON: Many of the children with Pseudomonas urinary tract infection are not, however, very sick. DR. O~RA: Nonetheless, some do go on to develop bacteremia.