( Management, prognosis, and prevention of UTI -(1

Management, prognosis, and prevention of UTI
Nader Shaikh, MD
Alejandro Hoberman, MD

INTRODUCTION — Urinary tract infections (UTI) are a common and important clinical problem in childhood, and may lead to renal scarring, hypertension, and end-stage renal disease. Although children with pyelonephritis tend to present with fever, it is often difficult on clinical grounds to distinguish cystitis from pyelonephritis. Thus, we have defined UTI broadly here without attempting to distinguish cystitis from pyelonephritis, particularly in young children.

Current evidence about the management of UTI in childhood will be reviewed here. The epidemiology, risk factors, clinical features and diagnosis of UTI, asymptomatic bacteriuria (colonization of the lower urinary tract by bacteria), UTI in newborns, and urethritis are discussed separately.

MANAGEMENT

Acute management — Treatment of children with presumed UTI depends upon a number of factors, including age of the patient, degree of toxicity, presence of vomiting, duration of fever prior to presentation, and the antimicrobial resistance patterns in the community. Treatment prior to 72 hours was effective in reducing subsequent renal damage in a monkey model [ 1], underscoring the importance of early aggressive treatment.

Hospitalization — Traditionally, young children with pyelonephritis were managed as inpatients. However, in a randomized, controlled trial of 306 children 1 to 24 months of age with a febrile UTI, the rates of symptom resolution, reinfection, and renal scarring did not differ between children receiving oral or intravenous therapy [ 2]. Most infants older than 2 months with pyelonephritis may safely be managed as outpatients as long as close follow-up is possible. Mean time to defervescence is approximately 24 hours [ 2]. Children who are not responding to outpatient therapy, who are vomiting and therefore cannot tolerate oral medication, or who are not able to be adequately followed should be managed as inpatients.

Choice of antibiotics — The choice of initial antimicrobial should be guided by local resistance patterns. Gram staining of the urine, if readily available, can better guide the practitioner in the choice of initial antimicrobial therapy.

Given that E. coli is the most common pathogen causing UTI, and that approximately 50 percent of E. coli are resistant to amoxicillin or ampicillin [ 3,4], these agents cannot routinely be recommended for the empiric treatment of a young child with UTI. First-generation cephalosporins [ 5], amoxicillin-clavulanate or ampicillin-sulbactam [ 6], and trimethoprim-sulfamethoxazole (TMP-SMX) [ 3,4] should be used with caution, as increasing rates of resistance to these antibiotics have been reported in some communities [ 7].

Alternatives include second- and third-generation cephalosporins and gentamicin, although these drugs are not effective in treating enterococcal infections. Cefixime in particular has been studied in young children with UTI, and has been shown to be effective in the treatment of outpatients with UTI [ 2]. Quinolones are effective and resistance is rare, but the safety of these antimicrobials in children is still under study. Therefore, quinolones are not appropriate choices for first-line therapy [ 8]. The ultimate choice of antimicrobial therapy should be based upon the sensitivities of the patient's urine isolate(s).

· Patients receiving antibiotic prophylaxis — Whether the child has been receiving antibiotic prophylaxis (for urinary tract or other medical problems) is another factor to consider in the initial choice of antibiotic. This was illustrated in a review of antibiotic resistance patterns among 361 children hospitalized for UTI at a tertiary care children's hospital between 1997 and 2001 [ 9]. E.coli was the causative organism in 87 percent of cases overall, but was less frequent among children receiving prophylactic antibiotics (58 percent) and in children with a history of previous UTI (47 percent).

Antibiotic resistance patterns of isolated organisms differed according to whether the child was receiving prophylactic antibiotics.
Among the isolates from 26 children receiving prophylaxis (with amoxicillin, TMP-SMX, penicillin, or nitrofurantoin), the following findings were noted:

· Resistance to cefotaxime was 27 percent, compared to 4 percent overall

· Resistance to ceftazidime and cefepime were 19 and 16 percent, respectively (compared to 4 and 2 percent overall)

· Sensitivity to aminoglycosides remained high (98 and 95 percent for amikacin and gentamicin, respectively)

It is not clear whether the increased resistance to third- and fourth-generation cephalosporins among patients receiving prophylaxis is caused by altered bacterial flora, a predisposition to acquisition of resistant organisms, and/or previous exposure to third-generation cephalosporins [ 9].

This report highlights the importance of consideration of antibiotic resistance patterns when choosing empiric therapy [ 10]. It also suggests that aminoglycoside therapy may be indicated pending sensitivity results for certain children who are hospitalized with UTI, particularly those who are highly febrile or clinically unstable [ 10].

Duration of therapy — The duration of antibiotic therapy for afebrile older children with presumed cystitis has been the subject of several meta-analyses [ 11,12]. Several conclusions can be drawn from reviewing these meta-analyses. A one-day course of treatment is inadequate. After excluding trials in which the short course was one day or less, children treated with antibiotics for two to four days had similar cure rates (resolution of bacteriuria and recurrence rates) as children treated with longer courses of antibiotics (seven to 14 days) [ 11]. However, a number of the primary studies included had limitations, and thus, these results should be applied with caution.

We recommend a three-day course of antibiotics in older children with their first episode of cystitis (low risk of recurrence or complications). We believe a 10- to 14-day course of an antimicrobial is more prudent for young children and for those with recurrent or febrile UTIs.

2007 UpToDate

Dr. Salim alatwane
Ped. Nephrologists.

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( Management, prognosis, and prevention of UTI -(1 Dralatwani2gif

Long-term management and follow-up

Children with recurrent UTI symptoms — Approximately 8 to 30 percent of children with UTI experience one or more symptomatic reinfections [ 2,13,14], usually within the first six months after the initial UTI. Breakthrough UTIs are most common in girls [ 15]. All children with UTI symptoms should be evaluated promptly. Prompt recognition and treatment of UTIs may perhaps be the most important factor in the prevention of renal scarring. In one study, parents were instructed to immediately seek care if their child had unexplained fever or urinary symptoms [ 2]. Eight percent of children had recurrence of UTI, but none suffered from additional renal scarring. In another study, a history of fever for more than 24 hours prior to diagnosis was associated with renal scarring [ 16].

Progression of renal scarring is associated with recurrent episodes of pyelonephritis [ 17-20], suggesting that prompt diagnosis and treatment of these infections may be of key importance in reducing renal scarring. In a retrospective study of 52 children with renal scarring, a delay in diagnosis was documented in 41 cases [ 21]. Routine surveillance of asymptomatic children with monthly urine studies has not been shown to be associated with a better prognosis and is therefore not recommended [ 22].

Children with recurrent febrile UTIs may be candidates for low-dose, long-term antimicrobial therapy. Systematic reviews concluded that the quality and size of the primary studies precluded any conclusions about the efficacy of antimicrobials for the prevention of UTIs [ 23-25]. Nonetheless, we would consider 6 to 12 months of TMP-SMX or nitrofurantoin in selected children with recurrent febrile UTIs and scarring, in whom all other treatment options have been ineffective.

Children with VUR — The goal of treating VUR is to prevent progressive renal damage. The majority of young children with VUR have low-grade (grade I to III) VUR, which will resolve spontaneously in most cases. Children with grades IV and V VUR and older children are less likely to experience spontaneous resolution. Children with VUR traditionally have been treated either medically with low-dose, long-term antimicrobials or surgically.

Surgical treatment involves reimplantation of the ureter into the bladder and the creation of a longer mucosal tunnel. Surgery has been shown to be effective in eradicating VUR in approximately 95 percent of cases [ 14]. Several large prospective randomized studies have compared medical and surgical therapy in children with persistent grade III and IV VUR [ 26-29]. Children on medical therapy experienced approximately twice as many episodes of febrile UTIs, but the incidence of scarring was similar in both groups. Thus, it has been recommended that young children with mild to moderate VUR receive treatment with low-dose, long-term antimicrobials until resolution of VUR [ 14].

Although the evidence is not conclusive, it appears the risk of scarring diminishes with age. Accordingly, some experts recommend cessation of prophylaxis after age 5 to 7 years, even if low-grade VUR persists. In one study of 51 low-risk (no voiding abnormalities or renal scarring) older children (mean age 8.6 years) with grades I to IV VUR, cessation of prophylactic antibiotics resulted in no new renal scarring on annual DMSA [ 30]. ( See "Epidemiology and risk factors for urinary tract infections in children", section on Risk factors for renal scarring).

Antimicrobial agents most appropriate for prophylaxis include TMP-SMX and nitrofurantoin in half the usual therapeutic doses given at bedtime. One out of every five patients on prophylactic nitrofurantoin doses, however, may experience GI adverse events [ 25]. Amoxicillin and cephalosporins are not recommended for prophylaxis because infection with resistant strains is likely to emerge.

Older children with persistent severe VUR (grades IV and V), and those with lesser degrees of VUR but with progressive scarring while on prophylaxis, are recommended to undergo ureteral reimplantation. The efficacy of endoscopic therapy, a newer, less-invasive treatment modality that uses an endoscope introduced via the urethra to implant dextranomer/ hyaluronic acid copolymer (Dx/HA, DEFLUX) underneath the refluxing ureter, is under study. ( See "Management of vesicoureteral reflux", section on Endoscopic correction).

The routine use of long-term antimicrobial use in children with mild and moderate VUR has been questioned. Recommendations regarding either the use of antimicrobial prophylaxis or the duration of prophylaxis in children with VUR are based on limited data. A significant proportion of children on antimicrobial prophylaxis continue to have breakthrough febrile UTIs (30 percent) and scarring (6 to 32 percent by IVP) [ 31,32]. One study has examined the adverse events of long-term antimicrobial use in children. Approximately 10 percent of children on long-term antimicrobials experience adverse reactions, mostly GI and dermatologic, and most adverse events occur in the first six months of therapy [ 33].

No experimental trial to date has satisfactorily compared long-term antimicrobial prophylaxis to placebo in children with VUR. Perhaps prompt treatment of intercurrent episodes of UTI and treatment of underlying dysfunctional elimination, if present, will prove to be as effective as antimicrobial prophylaxis in the care of children with UTI and VUR. Until more research occurs in this area, we recommend antimicrobial prophylaxis for children with VUR until a repeat VCUG demonstrates resolution of VUR.

Recommendations

· Most children with UTI can be managed as outpatients.

· Empiric antibiotic therapy should be directed at E. coli, taking into account local antibiotic resistance patterns. Second- and third-generation cephalosporins or gentamicin generally are effective.

· UTI in older children can be treated with a short course of antibiotics (eg, three days). The duration of therapy for young children and for those with fever or recurrent UTI should be 10 to 14 days.

· It is reasonable to consider long-term antibiotic suppression with TMP-SMX or nitrofurantoin in patients with recurrent febrile UTIs.

· Until more data are available, children with VUR should be treated with antibiotic prophylaxis until VCUG documents disappearance of VUR.

· Older children with persistent VUR of grades IV or V and those with progressive scarring on antibiotic prophylaxis should undergo surgical ureteral reimplantation.

· Children with dysfunctional elimination should have this condition addressed with laxatives, timed voiding, and consultation with a urologist if these modalities are unsuccessful.

PROGNOSIS — Predicting which children with UTI will develop sequelae remains difficult. The large majority of children with UTIs have no long-term sequelae. In one study of 111 high-risk girls with childhood UTI followed for 6 to 32 years, seven had decreased glomerular filtration rate (GFR) [ 39].

In another study of 68 children with history of urographic renal scarring followed 16 to 26 years after their index UTI, median GFR [ 40] and mean 24-hour ambulatory blood pressure [ 41] were no different in children with and without urographic renal scarring. However, in seven patients with a history of bilateral urographic scarring, GFR decreased over time and was significantly less than children with a history of unilateral scarring. The long-term significance of scarring, as identified by DMSA, remains to be determined.

PREVENTION — To prevent renal scarring, risk factors for subsequent infection have to be addressed. Treatment of dysfunctional elimination is effective at reducing further UTIs. Management of VUR with surgery and/or prophylactic antibiotics may be warranted in children with VUR, although the evidence for the latter is scant.

Post-coital prophylaxis should be considered in adolescents with recurrent UTI. One small, randomized, double-blind trial examined the efficacy of one dose of post-coital antibiotic in the prevention of recurrent UTI [ 42]. Post-coital antibiotic use was associated with few side effects and reduced UTI recurrence significantly.

An open, randomized trial found cranberry-lingonberry juice concentrate effective in preventing symptomatic UTI recurrence in healthy women after their first UTI [ 43]. However, this finding needs to be confirmed by other studies and in children [ 44]. Although not known to be beneficial, it seems unlikely that cranberry juice in moderation is harmful. Thus, its use may be reasonable in children with recurrent UTIs.

2007 UpToDate

Dr. Salim alatwane
Ped. Nephrologists.

_________________
( Management, prognosis, and prevention of UTI -(1 Dralatwani2gif

Thanks dear Dr.Salim for your nice issue

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<p> ( Management, prognosis, and prevention of UTI -(1 HaveANicedayRose

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