Pediatric Urinary Tract Infection Organism-Specific Therapy

Antibiotics for Pediatric UTI

Urinary tract infection is the most common bacterial infection during childhood, with a cumulative incidence of 3-7% in girls and 1-2% in boys (Habib 2012) ^[1] . The incidence decreases significantly in boys after the first year of life (Zorc et al, 2005) ^[2] . In the pre-antibiotic era, mortality rates from bacterial pediatric UTI’s reached up to 20% (Zorc et al, 2005) ^[2] . Antibiotic selection is critical to preventing potential sequela of untreated infections. Choice of antibiotic agent should be based on the specific organism isolated from a urine culture as well as the age and clinical condition of the patient and local antibiotic resistance patterns (Edlin et al, 2014) ^[3] .

Route of Administration

The AAP published guidelines for managing UTI in febrile infants and children 2 to 24 months of age. According to their recommendation, when initiating treatment for a UTI, choice of route of administration should be based on practicality, as oral or parenteral therapy is equally efficacious. Parenteral therapy should be highly considered in patients who are unable to tolerate oral intake or who appear “toxic” and should be continued parenterally until clinical improvement occurs. Additionally, if there is uncertainty regarding compliance with oral agents, consider parenteral therapy. The choice of agent should then be adjusted according to sensitivity testing of the isolated organism, and total duration of therapy should be 7-14 days (AAP, 2011) ^[4] . There is evidence that shorter courses of antibiotic therapy are inferior to a minimum 7-day course (Keren et al, 2002) ^[5] . In one 9 year retrospective observational study of currentambulatory prescribing patternsfor pediatric UTI, 10%of patients were treated with parenteral therapy and 90% with oral therapy. The majority of parenteral therapy was with 3^rd generation cephalosporins (95% ceftriaxone). Trimethoprim-sulfamethoxazole was the most commonly prescribed agent for UTI throughout the duration of study, at 49%. Amoxicillin-clavulanate was prescribed in 4-9%. Patients younger than age 2 years or those with fever were most likely to get broad spectrum antibiotic therapy (32%) (Copp et al, 2011) ^[6] .

Antibiotic Resistance

Antibiotic use is a major risk factor for development of antibiotic resistance. In fact, there is a temporal relationship between antibiotic use and resistance within a hospital (Edlin et al, 2014) ^[3] . Although antibiotic use has decreased by 17% in the US over the past decade, resistance is still a growing concern in pediatric urology (Edlin et al, 2014) ^[3] .

E. Coli is by far the most commonly isolated organism in pediatric UTI with prevalence ranging from 80-90% (Copp et al, 2011) ^[6] followed by others such as Enterococcus species, Enterobacter species, Pseudomonasaeruginosa, Kelbsiella pneumoniae,, and Proteus mirabilis, and Staphylococcus species (Dahle et al, 2012) ^[7] .

There have been increasing resistance patterns of E. Coli isolates. In fact, in male children the resistance has increased 10-fold from 2002-04 to 2009 alone. During that same time period, an overall resistance of pediatric UTIs to trimethoprim-sulfamethoxazole has been noted (Edlin et al, 2014) ^[3] . Trimethoprim-sulfamethoxazole resistance during that time period increased from 23-31% in boys and from 20-23% in girls. This was also noted in a study of outpatient pediatric UTI resistance patterns in 195 US hospitals. Resistance among E. coli isolates was highest for trimethoprim-sulfamethoxazole at 24% (Edlin et al 2013) ^[8] . This rate was even higher at 30% in the inpatient setting (Saperston et al, 2014) ^[9] . To decrease growing resistance patterns, antibiotic use should be restricted to those with documented growth on culture and subsequently tailored based onsensitivity results. Furthermore, antibiotic prophylaxis for UTI should be reservedfor those at high risk forrecurrence, and local antibiograms should be utilized in antibiotic selection (Edlin et al, 2014) ^[3] .

Antibiotic Selection

Ramlakhan et al in 2014 ^[10] provided information on potential antibiotic agents and their effectiveness against specific organisms, as follows. Ampicillin is a frequently used agent for the treatment of pediatric UTI, with bactericidal activity against gram-positive and some gram-negative organisms including Escherichia coli, Proteus species, and Staphylococcus. It is, however, ineffective against Klebsiella and penicillinase-producing organisms. Augmentin can be used to treat beta-lactamase producing coliforms, as most ESBL-producing E. coli are resistant to cephalosporins, penicillins, fluoroquinolones, and trimethoprim. Cephalosporins are effective against Staphylococcus, Klebsiella, and E. coli and are resistant to the action of most beta-lactamases. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms, but are ineffective against anaerobes. Gentamicin is effective against aerobic gram-negativerodsincluding Pseudomonas and Proteus, and is also effective against staphylococci. It, however, is not effective against anaerobic organisms. Nitrofurantoin is active against E. coli (including ESBL-producers), Staphylococcus saprophyticus, Enterobacter, and Klebsiella species. Trimethoprim-sulfamethoxazole is bactericidal against a broad spectrum of gram-positive and gram-negative aerobic bacteria with activity against some anaerobes ^[10] .

There are antibiotics which are not used as first-line treatment in children. Of note, quinolones are not frequently prescribed in the pediatric population due to potential for musculoskeletal side effects, although ciprofloxacin is FDA approved in the US for complicated UTI in children above 1 year of age. In a systematic review of 105 studies on safety of quinolones in children, musculoskeletal events were noted to be common but were found to be reversible with active treatment (Adefurin et al, 2011) ^[11] . According to the Ramlakhan et al, quinolones should not be a first choice agent in children but should be restricted to pyelonephritis caused by E. Coli. Aditionally, agents such as nitrofurantoin, which do not achieve therapeutic blood concentrations, should not be used to treat febrile UTI’s ^[10] .

The table below depicts potential antibiotic choices for each of the listed organisms, pulled from our various listed references. Common pediatric dosages are as published by Epocrates online reference ^[12] . As mentioned above, the age, renal function, and clinical condition of the patient as well as the local antibiotic resistance patterns should be taken into account when interpreting this chart for your prescribing pattern.

Table. (Open Table in a new window)

*dosing adjustment is recommended in decreased CrCl

**contraindicated in CrCl< 60

^caution in hepatic impairment