Microbiology E. coli remains the most common organism (generally strains with fewer virulen ce characteristics). Recommendations The Infectious Disease Society of America has recently reviewed asymptomati c bacteriuria and made a number of recommendations. These include: \200 Natural history Antimicrobial therapy hastens the resolution of symp- toms. Most women will improve without antibiotic therapy, but at a higher risk of upper tract or complicated inf ections. Cure rates of 85 \200\22395% are achieved with antimicrobial ther- apy. It is not associated with an increased risk of chronic kidney disease. Screening and treatment is not appropriate except for pregnant women and patients about to undergo trau- matic urological procedures. Pregnant women should be screened at least once in early pregnancy and if results are positive treated with a 3 \200\2237 day course of ant imicrobial therapy. Periodic screen- ing for recurrent bacteriuria should be undertaken fol - lowing therapy. Patients about to undergo traumatic urological proce- dures should be scr eened beforehand. If positive, appro- priate antimicrobial therapy should be given shortly before the procedure. Antimicrobial therapy should not be continued unless an indwelling ca theter remains in place. The role of screening and treatment is not established in patients with a renal allograft or in severely neutropenic patients. Clinical features Acute onset of dysuria, frequency and urgency of micturi- tion, and/or su prapubic pain. Usually there are no speci \201 c physical signs. Differential diagnosis Complicated infection is suggested by other conditions as detailed i n Table 7.1.3. Fever, \202 ank pain and systemic symptoms suggest infection of the upper tract. Acute urethritis due to Chlamydia trachomatis, Neisseria gonorrhoeae or herpes simpl ex. Vaginitis due to Candida or Trichomonas. Uncomplicated lower urinary tract infection Cystitis is very common. Urinary tract infectio ns are considered complicated if there are features which suggest a higher risk of treatmen t failure. Risk factors for treatment failure are detailed in Table 7.1.3. A pragmatic appr oach is to consider cystitis in healthy young nonpregnant women as uncomplicated and in all others as complicated. Diagnosis De \201 nitive diagnosis is made by demonstration of bacteriu- ria (traditionall y this is \211 105 cfu/mL). This may miss \200\230low count cystitis \200\231 which may a ccount for up to one-third of cases of cystitis. Counts of \211 103 cfu/mL in young women with typical symp- toms achieves reasonable sensitivity and speci \201 city. Urine dipstic k positivity for leukocytes and nitrites may be a useful diagnostic adjunct. Table 7.1.3 Complicated vs uncomplicated urinary tract infection Microbiology As detailed in Table 7.1.1, E. coli and Staphylococcus sapro- phyticus are the most common causative organisms. Uncomplicated Infections considered complicated Other conditions with an increased incidence of complicated infection (male gender, pregnan cy, elderly, recent urinary tract instrumentation, children, recent antimicrobials, diabete s mellitus, immunosuppression). Obstruction or other structural abnormalities of the urinar y tract (nephrolithiasis, malignancy, strictures, bladder diverticuli, cysts, \201 stulae , ileal conduits, and other urinary diversions). Functionally abnormal urinary tract (neuro genic bladder, vesicoureteric re \202 ux). Foreign bodies (urinary catheters, ureteric ste nts, nephrostomy tubes) Multiresistant organisms. Others (e.g. renal failure, renal transpl antation, nosocomial infection, prostatitis-related infection). Young healthy non-pregnant females Other investigations No other investigations are required in most women. Pharmacological therapy Three-day courses of trimethoprim, trimethoprim-sulfam- ethxazole ( TMP-SMX) and \202 uoroquinolones are as effec- tive as longer courses of these antimicrob ials (in most cases). Fluoroquinolones may not be as effective against Staphylo- coccal sap rophyticus when administered as a 3 day course. The optimal duration of nitrofurantoin ther apy is not well established. Beta-lactam antibiotics are less effective when given for 3 da ys and longer courses of these agents are probably required. The ef \201 cacy of single do se regimens remains controver- sial. Single dose regimens of TMP-SMX, \202 ouroquinolones and other agents, while highly effective, may not be as effective as three day regimens. Adapted with permission from: Hooton T. Urinary tract infections in adults. In: Johnson RJ, Feehally J (eds) Comprehensive clinical nephrology, 2nd edn. Baltimore: Mosby; 2003. Table 53.1, p. 695. CHAPTER 7.1 Lower and upper urinary tract infection in adults 247 Empiric therapy \200 \200 \200 Epidemiology It is much less common than cystitis. Incidence 20 \200\22380 per 10 000 peopl e per year. Narrow range of causative organisms. Relatively predictable antimicrobial sensitivities. Ba cterial culture and sensitivities are generally not avail- able until most patients are cur ed. Urine culture is usually unnecessary in cases with a typi- cal presentation. Presence o f leukocytes or nitrites on urine dipstick may aid clinical decision-making in this situati on (a recent study suggests, however, that treatment should be offered whatever the dipstic k result). Empiric therapy should re \202 ect local antimicrobial sensi- tivities. Antimic robial sensitivity data may overestimate resist- ance levels, due to the disproportionate q uantity of cul- tures obtained in treatment failures and more serious infections. An arbitr ary level of 20% resistance has been suggested as a cut-off for empiric antimicrobial choic e. Trimethoprim is as effective as TMP-SMX. Fluoroquinolone resistance is increasing. Natural history Acute uncomplicated pyelonephritis, when effectively treated, does not caus e chronic damage. Acute renal failure is an uncommon complication. It is usu- ally associat ed with complicated infection in an abnormal urinary tract. Clinical features Acute onset of \202 ank pain, nausea, vomiting, myalgia and fever with or without lower tract symptoms. Lower tract symptoms (when present) may occur before, afte r or at the same time as upper tract symptoms. The kidney(s) may be exquisitely tender. Differential diagnosis Complicated upper tract infection is suggested by the pres- ence of another condition as detailed in Table 7.1.3. Severe pain, insidious onset or severe sepsis suggests the presence of a complicated infection. Other causes of flank/back/abdominal pai n with fever include: \200 \200 \200 Alternative therapies \200 \200 There is no evidence supporting urinary alkalinization. There is no evidence for cranberry products in the treat- ment of cystitis (see \200\230Prevention \200\231). There is no evi dence for or against increasing \202 uid intake to increase urine volumes and micturition frequency. pneumonia/lung abscess/empyema; intra-abdominal sepsis (pancreatitis, appendicitis, chole- cystitis); pelvic in \202 ammatory disease; vertebral osteomyelitis/discitis; obstructive uropathy; other renal disease (acute glomerulonephritis, renal inf- arction, renal vein thr ombosis). \200 \200 \200 Follow-up Post-treatment urine cultures in patients whose symptoms have resolved are not in dicated. Prevention Avoid spermicidal agents. Cranberry products may prevent recurrence. Maintaining a high urine output with frequent micturition as well as voiding after intercourse are oft en recommended but are of unproven bene \201 t. Diagnosis Urine microscopy and culture is required in all suspected cases. Almost all patie nts have pyuria and a bacterial count of \211 104 cfu/mL. Blood cultures are not usually r equired (the demonstra- tion of bacteremia does not alter the management or out- come). Recommendations Healthy nonpregnant women with a typical presentation of cystitis, with no risk factors for complicated UTI, can be treated empirically, without a urine culture. Anti biotic choice should be based on local sensitivities. Trimethoprim or TMP-SMX is an appropr iate choice in most areas. Unless there is a speci \201 c reason to use a \202 uoroquino lone, the use of these agents as empiric therapy should be avoided. The optimum duration of therapy with these agents is probably 3 days. If nitrofurantoin or -lactams are used, a longer course of treatment is advisable. Microbiology As for cystitis, E. coli is by far the most common causative organism. Most ot her cases are caused by Staphylococcus saprophyti- cus or other Enterobacteriaceae. Other investigations Imaging is not usually performed but would generally dem- onstrate an enlarged kidney with decreased opacity of the affected parenchyma on CT. Indications for im aging (ultrasound or CT) of the urinary tract are: \200 \200 \200 no clinical improvement after 72 h of treatment; two recurrences of acute pyelonephritis; t he presence of any complicating factor (Table 7.13). Histology is characterized by an acute interstitial nephritis with neutrophilic in \201 ltration and oedema (Fig. 7.1.1). Uncomplicated upper urinary tract infection It is important to recognize the difference bet ween acute pyelonephritis and chronic pyelonephritis (a misnomer) associated with urinary t ract obstruction or vesicoureteric re \202 ux. The spectrum of acute pyelonephritis ranges from cystitis with mild \202 ank pain to severe sepsis with multiple organ dysfunction s yndrome. Treatment Mild \200\223moderate cases may be managed in the community with oral antimicrobials with o r without a single parental dose. J. SCHOLLUM 248 Complicated urinary tract infection UTIs are considered complicated if they occur in the set- ting of a structurally, functiona lly or metabolically abnormal urinary tract or in association with a condition which is ass ociated with risk of treatment failure (Table 7.1.3). At initial presentation it may be dif \201 cult to identify a com- plicated infection. Longer-lasting symptoms, more promi- nen t systemic features and known abnormalities of the urinary tract suggest complicated infect ion. Complicated infections are associated with a wider range of causative organisms, with a higher rate of antimicrobial resistance. All patients with a suspected complicated infec- tion must have their urine cultured. Due to the wide range of organisms it is dif \201 cu lt to make speci \201 c treatment recommendations beyond this: that most complicated infec tions require a longer course of therapy ( \211 7 days), based on microbial culture and sen sitivity. Infections related to conditions such as an obstructing stone are unlikely to imp rove without correction of the underlying pathology. Similarly, if the underlying structura l or functional abnormality is not corrected, there is a high chance (50%) of recurrent inf ection in the subsequent 6 weeks. Fig. 7.1.1 Acute pyelonephritis. High power view of renal medulla with prominent neutrophil ic in \201 ltrate and visible bacteria (arrow). (Courtesy of Dr Alex Dempster, Southern Co mmunity Laboratories, Dunedin, New Zealand.) Indications for admission to hospital are: \200 \200 \200 \200 inability to take oral medications or maintain hydration; compliance concerns; diagnostic u ncertainty; severe illness. Urinary tract infections in males UTIs are much less common in men than in women. Urethriti s is the main differential diagnosis in sexually active men. Prostatitis must be considered in those with recurrent infection. Lower UTI in healthy young men, with no features of a c omplicated infection, may be treated with a 3 day course of antimicrobials. In others, empi ric therapy should be broad spectrum (e.g. a fluoroquinolone), for \211 7 days and rationa lized according to culture and sensitivity testing. If there is no clinical response at 48 \200\22372 h, consider repeat cultures and urinary tract imaging. If there is no obvious ca use for the infection, urological evaluation should be considered. Young healthy males, wit h a single episode of cystitis, do not need urological evaluation. Urine should be cultured 2 weeks after treatment is com- pleted. Persistent bacteriuria suggests the presence of pr ostatitis or another underlying abnormality of the urinary tract. Empiric antimicrobial choice should be guided by local antimicrobial sensitivity. Certain a ntimicrobials, such as some \202 uoroquinolones (cipro \202 oxacin) and aminoglycosides, achieve high concen- trations in the renal medulla. Fluoroquinolones such as cipro \202 o xacin or levo \202 oxacin are the oral agents of choice. Aminoglycosides or third-generati on cephalosporins such as ceftriaxone are effective parental agents. Oral agents should be substituted when the patient is improving and can tolerate oral medications and hydra- tion . If there is suspicion of Enterococci, amoxicillin should be added until culture results a re available. Two weeks of therapy is as effective as 6 weeks. Shorter treatment regimens ( 5 \200\2237 days) are often effective in patients with mild disease who respond rapidly, bu t these regimens have not been evaluated in well-controlled trials. Alternative therapy As for cystitis, no alternative therapies have been proven to be effect ive. Pregnant women Asymptomatic bacteriuria and UTI in pregnancy are associ- ated with an incre ased incidence of premature delivery and reduced infant birth weight. About 1% of pregnant women will have cystitis. There is an increased risk of acute pyelonephritis in preg- nancy associated with asymptomatic bacteriuria. The clinical presentation is as for nonpregnant women. Treatment of cystitis is with a 3 \200\2237 day course with an agent that is safe in pregnancy. Acute pyelonephritis is associated with a higher complica- tion rate and is tra ditionally managed as an inpatient. Acute pyelonephritis has a recurrence rate of 6 \200 \2238% and antimicrobial prophylaxis should be considered. Follow-up Post-treatment urine cultures are not cost-effective in patients whose symptoms h ave resolved. Recommendations Parental therapy with an aminoglycoside, \202 uoroquinolone or an extende d spectrum cephalosporin. Amoxicillin if infection with Enterococci is suspected. Oral ther apy with \202 uoroquinolones. Shorter courses of therapy (5 \200\2237 days) for mild case s with a rapid response to therapy. CHAPTER 7.1 Lower and upper urinary tract infection in adults 249 Following treatment, urine should be screened intermit- tently for the remainder of the pre gnancy. Urinary tract infection in renal transplant recipients UTIs are the most common infection i n renal allograft recipients. Infections are associated with graft dysfunction and an incre ased risk of rejection. Prophylactic TMP-SMX given for other reasons effectively reduces th e incidence of UTI. Diabetes mellitus, emphysematous pyelonephritis and papillary necrosis Most forms of urinar y tract infection are more common in diabetics. In general, all diabetics with infective ur inary tract symp- toms require urine culture and empiric broad spectrum antimicrobials. Indwelling urinary catheter Bacteriuria occurs in 3 \200\22310% of patients with an indwell ing urinary catheter (IDUC) per day. The best prevention for bacteriuria associated with an IDUC is to avoid catheterization and to remove catheters as soon as possible. A sterile in sertion technique, good catheter care, and use of a closed system reduce the rate of infect ion. Intermittent self-catheterization may reduce the risk of infection when long-term cath eterization is required. All other strategies are either unproven or have con \202 icting evidence. Urine samples are preferably taken following exchange of the catheter and are tak en directly from the catheter (not from the urine drainage bag). Signs and symptoms of IDUC -associated infection may be subtle. Pyuria is not a reliable marker of infection. Initial treatment should be broad spectrum and rational- ized according to culture and sensitivity testing. Optimal duration of therapy is unknown but a minimum of 7 days is usually appropri ate. Bio \201 lm on urinary catheters represents a reservoir of infection which antimicrob ial therapy may not penetrate, therefore an IDUC associated with infection should be change d. There is no role for screening or treatment of asympto- matic patients. Emphysematous pyelonephritis \200 \200 \200 \200 \200 \200 \200 This occurs most commonly in diabetic patients (90%). It is caused by gas-producing Enterob acteriaceae. It presents as fulminant pyelonephritis. Urine culture is usually positive. Ga s is seen on plain X-ray and CT (Figure 7.1.2). CT is required to con \201 rm the diagnosi s. Treatment is with emergency nephrectomy and broad spectrum antimicrobials (mortality 60% without and 20% with nephrectomy). Papillary necrosis \200 This occurs most commonly in diabetics, almost always in association with infection, and is due to a combination of infection and ischemia. Presentation is as for upper UTI, with pos sible obstruc- tive symptoms in addition (if a sloughed papilla lodges in the urinary tract ). Renal calculi Infection plays an important role in the formation of renal stones and is als o an important complication of renal stones. Prostatitis Acute bacterial prostatitis This is likely due to the re \202 ux of infected u rine into the prostatic ducts. Presentation is with symptoms of lower tract infection, asso ciated with fever, myalgia and occasionally urethral obstruction. On rectal examination the prostate is tender and swollen. Urine testing demonstrates pyuria and bacteriuria. Prostat ic massage may precipitate bacteremia and should be avoided. Treatment of \211 4 weeks dur ation is required. Fluoroquinolones are the best choice for empiric oral therapy. Prostatic abscess is uncommon and is suggested by failure to respond to therapy. Fig. 7.1.2 Emphysematous pyelonephritis with gas visible in the left kidney on plain \201 lm and abdominal CT scan (arrows). (Courtesy of Gabriel Lau, Dunedin Hospital, Dunedin, Ne w Zealand.) Chronic prostatitis This is characterized by recurrent single pathogen UTIs with intervenin g asymptomatic periods. J. SCHOLLUM 250 Diagnosis is based on the presence of in \202 ammatory cells on split urines before and af ter prostatic massage. Treatment is with a 1 \200\2233 month course of an antimicrobial (us ually a \202 uoroquinolone). Renal malacoplakia This is an uncommon chronic granulomatous disorder of unknown etiology. It involves the genitourinary, gastrointestinal, skin and pul- monary systems. Genitourinar y disease is secondary to urinary tract infec- tion. It presents with recurrent UTI or obst ructive symptoms. Intravesical plaques on cystoscopy with submucosal aggre- gates of macrop hages containing bacterial debris (Michaelis \200\223Gutman bodies) are characteristic. It may involve the kidneys and present as \202 ank pain and fever with lower urinary tract s ymptoms. Renal insuf \201 ciency may occur if both kidneys are involved. It is probably du e to a monocyte \200\223macrophage bactericidal defect. Treatment is with prolonged courses of appropriate anti- microbials. Renal and perinephric abscesses These are uncommon. The majority are secondary to ascending infection with pyelonephritis followed by liquefaction and walling off. They usually occur in the setting of an abnormal urinary tract. They are usually caused by Gram-negative Ente robacte- riaceae. The medulla is characteristically involved. Hematogenous spread (Staphylo coccus aureus) is less com- mon and typically causes a renal cortical abscess (renal carbun cle). The presentation is as for acute pyelonephritis, but the response to antimicrobial th erapy is either slow or absent. Systemic features are usually prominent. Urine culture is u sually positive unless there is no commu- nication with the urinary tract (more common with hema- togenous spread). Ultrasound or CT demonstrates a \202 uid- \201 lled cavity. Asp iration may be required to distinguish an abscess from other mass lesions. Antimicrobial th erapy, guided by culture and sensitivity testing, is required for 1 \200\2232 months. Corti cal abscesses usually respond to antimicrobials and may not require drainage. If the underl ying abnormality is corrected, ascending infec- tion may also respond to antimicrobials. Dr ainage may hasten recovery and is required for large or nonresponding collections. Perineph ric collections typically occur with obstruction or other complicating factors. They can oc cur secondary to an ascending infection with rupture of the renal capsule or due to hematog enous spread. The symptom onset may be insidious. Antimicrobials are administered according to culture and sensitivity results. Drainage of the collection is usually required. Xanthogranulomatous pyelonephritis This is an uncommon chronic infection associated with ob struction. The renal parenchyma is replaced by lipid-laden macro- phages. It is usually see n in women and causes \202 ank pain and fever. It is usually diagnosed on imaging studies . Antimicrobials are used but nephrectomy is usually required. Recurrent uncomplicated urinary tract infection Around a fourth of healthy women with an ep isode of cystitis will have a second con \201 rmed episode within 6 months. Fewer than 5% will have a third episode. Most episodes are reinfection with a different organism or with the same organism which has persisted in the gas- trointestinal tract. Risk factors are the same as for other uncomplicated UTIs. Recurrence needs to be con \201 rmed on carefully c ollected urine samples. Prevention strategies (not well validated) include: \200 \200 \200 avoidance of spermicidal agents; postcoital voiding; liberal \202 uid intake to maintain frequent micturition. Infected cysts These most commonly occur in patients with adult poly- cystic kidney disease . They may result from ascending infection or hematogenous spread. Cyst infection may be di f \201 cult to distinguish from cyst hemorrhage. Ultrasound may demonstrate the appearance s of a \200\230com- plicated \200\231 cyst. Urine culture is positive if secondary to asce nding infec- tion. Antimicrobials are administered according to urine culture and sensitivi ty results. The optimal duration of therapy has not been established, but \211 4 weeks of treatment is usually required. Large infected cysts may need external drainage. Cranberry products may reduce recurrence, but further trials are required. Prophylactic ant imicrobials, both continuous and postcoi- tal (when UTIs can be shown to be temporally rela ted to coitus) are effective at reducing recurrence. Prophylaxis should be considered in wo men with two or more infections in a 6 month period. The optimal antimi- crobial regimen ha s not been established. Intermittent self-treatment, with pre-prescribed antimicro- bials, is effective in rapidly improving symptoms. There is con \202 icting evidence regarding th e bene \201 t of topi- cal vaginal estrogen in postmenopausal women. It does not appear to be as effective as antimicrobial prophylaxis. Routine urological investigation seldom \201 nds underlying abnormalities and is usually unnecessary. CHAPTER 7.1 Lower and upper urinary tract infection in adults 251 Further reading Baerheim A. Empirical treatment of uncomplicated cystitis. Br Med J Internet resources Patient information: www.patients.uptodate.com Patient information from NHS Direct in the UK: 2001; 323: 1197 \200\2231198. Hooton TM, Scholes D, Hughes JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. New Engl J Med 1996; 335: 468 \200\223474. http://www.nhsdirect.nhs.uk/articles/article.a spx?articleId=384&sectionId=1 Patient inform ation from the National Institute of Diabetes and Digestive and Kidney Diseases in the USA: Hooton T. Urinary tract infections in adults. In: Johnson RJ, Feehally J (eds) Comprehensiv e clinical nephrology, 2nd edn. St Louis, MO: Mosby; 2003. Table 53.3 p. 697 (permission pe nding). Nicolle LE. A practical guide to the management of complicated urinary tract infection. Drugs 1997; 53: 583 \200\223592. http://kidney.niddk.nih.gov/Kudiseases/pubs/ utiadult/ Nicolle LE. A practical guide to antimicrobial management of complicated urinary tract infe ction. Drugs and Ageing 2001; 14: 243 \200\223254. See also Nicolle LE, Bradley S, Colgan, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asympto- matic bacteriuria in adults. Clin Infect Dis 2005; 40: 643 \200\223654. Urinary tract infections in infancy and childhood, p. 252 Urinalysis and microscopy, p. 8 I maging in renal disease, p. 20 Scottish Intercollegiate Guidelines Network. Management of sus- pected bacterial urinary tract infections in adults. 2006. Warren JW, Abrutyn E, Hebel JR, et al. Infectious Disease Society of America guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Clin Infect Dis 1999; 29: 745 \200\223758. A. WATSON 252 Urinary tract infection in children This is an important problem because a urinary tract infec- tion (UTI) not only causes morb idity (and rarely mortality from septicemia) but it may also be the clue to an underly- ing abnormality of the urinary tract that requires urological attention, or be associated with re \202 ux-associated damage leading to hypertension and chronic renal impairment. Howeve r, the vast majority of children presenting with UTI have normal urinary tracts. Hence ther e is a need to avoid over-investigation with tests which can be traumatic to children, such as cystograms and radionuclide scans. Therefore one of the biggest problems is that the diagnosis is not thought of, especially i n the prime target groups, i.e. infants. UTI should be excluded in any febrile child with u nex- plained fever. Neonatal jaundice is the classical association of bacteriuria in the ne wborn, but a high index of suspicion is required in any baby that is nonspeci \201 cally d eteriorating. Infants may present with vomiting, diarrhea, poor feeding, failure to thrive or fever. Suprapubic aspiration should be attempted as part of the septic work-up. When inf ection occurs in an abnormal urinary tract, infants may present with AKI and also electroly te abnor- malities. Cystitis-like symptoms such as frequency and dysuria are common in the older child. Pyelonephritis with high fever, abdominal/loin pain, and rig- ors are uncommon presentations in children with upper urinary tract involvement. De \201 nition UTI is de \201 ned as symptoms plus the detection of a signi \201 - cant growth of organisms in the urine. \200 Any growth on culture of a suprapubic aspirate (this technique is usually con \201 ned to children <1 year of age and is ideally undertaken with ultrasound guidance). >105 organisms /mL in pure growth from a carefully col- lected urine sample (midstream urine from a contin ent child, or clean-catch or bag/pad urine from other chil- dren). Ideally two consecutive growths of the same organism with identical sensitivities should be obtained, but this is n ot always possible in practice. Bacteriuria in the absence of symptoms does not neces- sari ly need treatment but needs to be considered in the clinical context, e.g. predisposing uri nary tract abnor- malities or previous UTI. History and examination Always enquire about any abnormality on antenatal ultra- sound or a family history of urinary tract problems (vesi- coureteric re \202 ux (VUR) has a 30% fam ilial incidence). Try to distinguish upper tract (fever and pyelonephritis) from lower trac t (cystitis-like) symptoms. Enquire about urinary stream in boys (posterior urethral valves ) or incontinence. Palpate for abdominal masses and fecal loading as there is a strong asso ciation between UTI and constipation. A palpable bladder combined with poor urinary stream suggests obstructive uropathy or posterior urethral valves in the male infant, or a neuroge nic bladder. Examine the spine and lower limb re \202 exes especially in children with inc ontinence. The genital area should be examined for foreskin problems in boys and local irri tation and infection in females (sexual abuse is a rare cause of UTI). Measure blood pressu re using a cuff of the appropriate size. Plot the growth centiles. Epidemiology It is estimated that at least 1% of boys and 3% of girls expe- rience a UTI du ring their \201 rst decade of life. The prevalence is uncertain since children may be tre ated for febrile episodes without urine being collected in both primary and secondary care settings. During \201 rst 12 months of life both symptomatic UTI and asymptomatic bacteri uria affect males more than females. Thereafter UTI is more common in females. Nosocomial U TIs, associated mainly with urinary catheters, are an important cause of hospital morbidity in children undergoing catheterization that is not covered with pro- phylactic antibiotics . Circumcision is associated with a decreased risk of symp- tomatic UTIs and may be justi \201 ed in male infants with major abnormalities of the urinary tract when combined with ot her procedures. Breastfeeding reduces the risk of UTI. Handling of urine specimens Inappropriate handling and culture of the urine can cause dif \201 culties for the management of UTI. An enquiry must be made as to how the urine was col - lected as previously mentioned. Urine should be stored at 40 C in the refrigerator durin g any delay in transferring to the lab. Urine microscopy is no longer routinely requested s ince the urine needs to be fresh and up to 50% of patients with signi \201 cant bacteriuri a demonstrate an insigni \201 cant number of white cells (<5 white cells per high power \201 eld in a cen- trifuged urine specimen) and pyuria may occur in 9% of febrile infants w ithout a UTI. If available, phase contrast microscopy may demonstrate bacteria and white ce lls in the acute situation. Etiology Escherichia coli is responsible for \211 80% of UTIs. Other organisms include Pro teus, Enterococcus, Pseudomonas and Klebsiella spp. Staphylococcus aureus and Staph. epider midis can be urinary pathogens in small children. In \202 ammation of the urinary tract ma y be related to viru- lence factors, particularly P- \201 mbriae in E. coli. Clinical presentation In general, the younger the child the more nonspeci \201 c the sympt oms tend to be. CHAPTER 7.2 Urinary tract infection in children 253 Urine dipstick testing Strips which detect leukocyte esterase and nitrite are usu- ally fav ored for the diagnosis of UTI. Nitrite may on occasion be falsely negative since nitrate mi ght not be reduced to nitrite with frequent bladder emptying, production of a dilute urine, inadequate dietary nitrate, or infection with enzyme-de \201 cient bacteria. A positive n itrite and leukocyte result (usually with positiv- ity for blood and protein) is a strong i ndicator of UTI in the symptomatic child and justi \201 es empirical treatment with antibi otics while the urine culture result is awaited. Outpatient follow-up of the asymptomatic c hild with a negative dipstick does not require urine to be sent for laboratory culture. Table 7.2.1 Antibiotics used to treat UTI in childhood Antibiotic Treatment (mg/kg/day) Prophylaxis (mg/kg/ day) Not recommended Coamoxiclav Check BNF as depends upon age and drug concentration Trimethoprim 4 mg/kg orally 12- hourly 2 mg/kg 24-hourly (at night) Cefuroxime 20 mg IV (max 750 mg) 8-hourly NR Cefradine 12.5 \200\22325 mg/kg orally 12-hourly 3 mg/kg 24-hourly (at night) Nitrofurantoin 0.75 mg/kg orally 6-hourly 1 mg/kg 24-hourly (at night) Management Acute infection If the child is not unwell enough to require hospitalization, or al therapy with an antibacterial drug chosen from Table 7.2.1 can be used. The best choice of empiric antibiotic should be based upon information available from the local microbiolog y labora- tory. Antibiotic resistance is high for ampicillin alone and increasing for trime thoprim. A cephalosporin is probably best \201 rst choice at present. Parenteral antibiot ic therapy is recommended in the unwell child with vomiting but oral therapy has recently b een shown to be as effective. Therapy in neonates is usually IV ampicillin and gentamicin b ut in the older child cepha- losporins such as cefotaxime are used. There is no \201 rm e vidence for the optimal duration of treat- ment but usually 10 days of oral or IV/oral anti biotics in those with vomiting appears equally effective in children with suspected pyelone phritis. A 2 \200\2234 day course of oral antibiotics for the child with lower tract sympto ms who is systemically well is adequate and supported by meta-analysis data. For children w ho have had an abnormal early ultrasound, prophylactic therapy should be continued until in vestiga- tions are completed. In all groups, a urine culture should be taken to ensure reso lution of infection. Treatment and investigation of UTI in children go hand-in- hand. Child ren who are hospitalized with severe illness and recurrent or atypical UTI should have an u ltrasound per- formed during the acute admission to rule out underlying obstructive uropath y such as posterior urethral valves or other congenital abnormalities. Such patients should be managed in centers where there is both urology and neph- rology expertise. Cipro \202 oxacin Not licensed but refer to BNF Not recommended demonstrated to have Grades 3 \200\2235 VUR (re \202 ux distending the pelvis and calyces) . Prophylaxis is usually maintained for \211 2 years in this situation. There are no forma l trials comparing prophylactic antibiot- ics vs urine culture when symptoms develop (a poi nt which needs to be stressed to parents/carers even if the child is on antibiotics). Howev er, some recent evidence indicates that prophylaxis may not signi \201 cantly decrease the risk of recurrent UTI and may increase the risk of antibiotic resist- ance. Shorter course s of prophylactic antibiotics (6 months) may be employed in children (usually girls) with r ecurrent UTIs and normal urinary tracts along with continued emphasis on general preventati ve measures. Dysfunctional voiding can be assessed by monitoring bladder emptying on ultra- sound or occasionally urodynamics if symptoms are severe. Investigation This is a surprisingly controversial area previously with a lot of focus on d etecting VUR because of its known asso- ciation with scarring (reflux nephropathy), CKD, an d hypertension. There is increasing recognition from antenatal studies that VUR without inf ection may be associated with abnormal renal development giving rise to \200\230global sca rring \200\231 without UTI (dysplasia). A signi \201 cant dissociation between the presenc e of scars on DMSA and the presence of VUR has been recognized. In younger children VUR can only be de \201 ned by micturat- ing cystourethrography (MCUG) which is a potentially tra umatic examination in children. For continent children aged >4 years, one can assess re \202 ux by using MAG3 scans with indirect micturating cystograms (see below). Algorithms fo r the investigation of UTI have not distin- guished between those who have upper tract symp toms from those with lower tract (dysuria and frequency) symptoms. Until recently, the cons ensus was that all chil- dren (both boys and girls) should undergo appropriate investigatio n after the \201 rst proven UTI. However, there is often dif \201 culty interpreting uri ne cultures, particularly in young children where the risk of renal damage is probably grea test. Prevention of UTI recurrences Recurrence of UTI is common with 30% of girls having another UTI within 1 year (mainly lower urinary tract in nature). A good \202 uid intake needs t o be encouraged with regular voiding (school toilets are often a problem!). Enquire about c onstipation which has a strong association with voiding dysfunction and recurrent UTI. Ensu re that personal hygiene is stressed with proper wiping, and avoidance of bubble bath and t ight- \201 tting underwear. Antibiotic prophylaxis with trimethoprim or nitrofu- rantoin ( Table 7.2.1) is usually only employed in patients A. WATSON 254 Ultrasound scan (USS) is the primary investigation and will reveal anatomical information e ven in nonfunctioning kid- neys. Kidney size should be recorded and interpreted with refere nce to centile charts based on the child \200\231s height. USS will also reveal problems wi th bladder obstruction and other abnormalities such as stones (plain AXR is no longer routi nely performed). USS is operator dependent and can demonstrate scarring of kidneys in exper ienced hands. One important caveat is that significant VUR may be present with a normal USS , particularly in the newborn period. Recent NICE guidance suggests restricting MCUG to tho se aged <6 months who have severe, atypical, or recurrent UTI (Table 7.2.2(a)). MCUG is onl y required in older children if operative inter- vention is being considered. MCUG is the m ost traumatic of the imaging investiga- tions for a UTI and children require prophylactic a ntibiot- ics for 48 h to cover the procedure. In addition infor- mation for the family and play preparation for the child is required. A DMSA scan is the best technique for detection of scars and determination of differential renal function. This should be delayed for 6 mo nths after the UTI if permanent renal damage following an episode of pyelonephritis is bein g sought. Isotope renography (MAG3) is used to determine the presence of obstruction as wel l as for calculating differen- tial kidney function. In the co-operative child aged >4 year s the scanning can be continued until the child empties his or her bladder (indirect mictur ating cystography). Direct nuclear cystography has less radiation burden but still requires catheterization. IVU, CT or MRI should be used after consultation at the nephrouroradiolog y meeting. The majority of children with UTI have lower tract cystitis-like symptoms and no demonstrable abnormality on imaging. However, it can be difficult to distinguish between u pper and lower tract symptoms and there is always the concern regarding the presence of rare abnormalities of the urinary tract. NICE guidelines (2007) suggest that in children with UTI who are systemi- cally well it is only those who are aged <6 months who need a routine ultrasound. In older children it should onl y be done in those with atypical or recurrent UTI (Table 7.2.2(b,c)). Vesicoureteric re \202 ux This is classi \201 ed grades 1 \200\2235; grade 1 into ureter only and grade 5 gross dilatation of pelvis and calyces involving tor- tuosity of the urete r. Although 30% of children investigated for symptomatic UTI have VUR, in most it is of mi nor grade. Table 7.2.2(b) Atypical UTI Recurrent UTI Responds well to treatment within 48 h without any features for atypical and/or recurrent U TI Children aged \211 6 months but <3 years Yesa USS during the acute infection No No USS within 6 weeks No No Yes Yesb Yesb No DMSA 4 \200\2236 weeks follow- ing the acute infection Noc Noc MCUG No