Pediatric Urinary Tract Infection Organism-Specific Therapy 

Pediatric Urinary Tract Infection Organism-Specific Therapy 

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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 3rd 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)

ORGANISM

ANTIBIOTIC REGIMEN OPTIONS

Escherichia coli

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Trimethoprim-sulfamethoxazole **

>2 mo: 8-10 mg/kg/day TMP PO/IV divided q12h

Amoxicillin/clavulanate* ^

25-45 mg/kg/day amoxicillin PO divided q12h (depending on age/wt)

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h (max 400 mg/day)

Cephalexin*

25-50 mg/kg/day PO divided q6-12h (max 4 g/day)

>15 yr: 500 mg PO q12h

Ceftazidime/avibactam

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Enterococcus species

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Vancomycin *

10-20 mg/kg IV q6-24h (depending on age/wt); Max: 1 g/dose; then adjust

based on serum levels

Gentamicin *

2.5 mg/kg IV/IM q8-24h (depending on age/wt); then adjust based on serum

levels

Enterobacter species

Trimethoprim-sulfamethoxazole **

>2 mo: 8-10 mg/kg/day TMP PO/IV divided q12h

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Ceftriaxone*

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Ceftazidime/avibactam

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Pseudomonas aeruginosa

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h (max 400 mg/day)

Ceftazidime*

< 7 days, < 1.2kg: 100 mg/kg/day IM/IV divided q12h

>7 days, >1.2 kg:150 mg/kg/day IM/IV divided q8h

>1mo: 90-150 mg/kg/day IM/IV divided q8h

(max 6 g/day)

Ceftriaxone*

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Klebsiella species

Amoxicillin/clavulanate*^

25-45 mg/kg/day amoxicillin PO divided q12h depending on age/wt

Gentamicin *

2.5 mg/kg IV/IM q8-24h (depending on age/wt); then adjust based on serum

levels

Ceftriaxone *

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Imipenem*

< 7 days, < 1.5 kg: 50 mg/kg/day IV divided q12h

1-4 wks, >1.5 kg: 75 mg/kg/day IV divided q8h

1-3 mo, >1.5 kg:100 mg/kg/day IV divided q6h

>3 mos: 60-100 mg/kg/day IV divided q6h

(max 2-4 g/day)

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Proteus mirabilis

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Amoxicillin/clavulanate*^

25-45 mg/kg/day amoxicillin PO divided q12h depending on age/wt

Cefuroxime *

3mo-12yr: 30 mg/kg/day susp PO divided q12h; (Max: 1000 mg/day)

>13yr: 250-500 mg tab PO bid

Piperacillin/tazobactam *

2-9 mos: 240 mg/kg/day IV divided q8h

>9 mos, < 40 kg: 300 mg/kg/day IV divided q8h

>9 mos, > 40 kg: 3.375 g IV q6h x7-10 days

Aztreonam *^

60-120 mg/kg/day IV divided q6-12h (depending on age/wt); (Max: 120

mg/kg/day up to 8 g/day)

Imipenem *

< 7 days, < 1.5 kg: 50 mg/kg/day IV divided q12h

1-4 wks, >1.5 kg: 75 mg/kg/day IV divided q8h

1-3 mo, >1.5 kg:100 mg/kg/day IV divided q6h

>3 mos: 60-100 mg/kg/day IV divided q6h

(max 2-4 g/day)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

*dosing adjustment is recommended in decreased CrCl

**contraindicated in CrCl< 60

^caution in hepatic impairment

Habib S. Highlights for Management of a Child with a Urinary Tract Infection. International Journal of Pediatrics. 2012. 2012:Article ID 943653.

Zore JJ, Kiddoo DA, Shaw KN. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinical Microbiology Reviews. April 2005. 417-422.

Edlin RS, Copp HL. Antibiotic resistance in pediatric urology. Therapeutic Advances in Urology. 2014. 6:54-61.

Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics. August 2011. 128:

Keren R, Chan E. A meta-analysis of randomized, controlled trials comparing short- and long-course antibiotic therapy for urinary tract infections in children. Pediatrics. 2002. 109(5):E70.

Copp HL, Shapiro D, Hersh AL. National Ambulatory Antibiotic Prescribing Patterns for Pediatric Urinary Tract Infection. Pediatrics. June 2011. 172:6:

Dahle KW, Korgenski EK, Hersh AL, Srivastava R, Gesteland PH. Clinical Value of an Ambulatory-Based Antibiogram for Uropathogens in Children. Journal of the Pediatric Infectious Diseases Society. 2012. 1(4):333-336.

Edlin RS, Shapiro DJ, Hersh AL, Copp HL. Antibiotic Resistance Patterns of Outpatient Pediatric Urinary Tract Infections. Journal of Urology. July 2013. 190(1):222-227.

Saperston KN, Shapiro DJ, Hersh AL, Copp HL. A Comparison of Inpatient Versus Outpatient Resistance Patterns of Pediatric Urinary Tract Infection. Journal of Urology. May 2014. 191 (50):1608-1613.

Ramlakhan S, Singh V, Stone J, Ramtahal A. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014. 8:31-37.

Adefurin A, Sammons H, Jacqz-Aigrain E, Choonara I. Ciprofloxacin safety in paediatrics. Arc Dis Child. July 2011. 96:874-80.

ePocrates Rx online reference. Available at https://online.epocrates.com. Accessed: December 2014.

ORGANISM

ANTIBIOTIC REGIMEN OPTIONS

Escherichia coli

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Trimethoprim-sulfamethoxazole **

>2 mo: 8-10 mg/kg/day TMP PO/IV divided q12h

Amoxicillin/clavulanate* ^

25-45 mg/kg/day amoxicillin PO divided q12h (depending on age/wt)

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h (max 400 mg/day)

Cephalexin*

25-50 mg/kg/day PO divided q6-12h (max 4 g/day)

>15 yr: 500 mg PO q12h

Ceftazidime/avibactam

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Enterococcus species

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Vancomycin *

10-20 mg/kg IV q6-24h (depending on age/wt); Max: 1 g/dose; then adjust

based on serum levels

Gentamicin *

2.5 mg/kg IV/IM q8-24h (depending on age/wt); then adjust based on serum

levels

Enterobacter species

Trimethoprim-sulfamethoxazole **

>2 mo: 8-10 mg/kg/day TMP PO/IV divided q12h

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Ceftriaxone*

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Ceftazidime/avibactam

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Pseudomonas aeruginosa

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h (max 400 mg/day)

Ceftazidime*

< 7 days, < 1.2kg: 100 mg/kg/day IM/IV divided q12h

>7 days, >1.2 kg:150 mg/kg/day IM/IV divided q8h

>1mo: 90-150 mg/kg/day IM/IV divided q8h

(max 6 g/day)

Ceftriaxone*

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Klebsiella species

Amoxicillin/clavulanate*^

25-45 mg/kg/day amoxicillin PO divided q12h depending on age/wt

Gentamicin *

2.5 mg/kg IV/IM q8-24h (depending on age/wt); then adjust based on serum

levels

Ceftriaxone *

50-100 mg/kg IM/IV divided q12-24h (depending on age/wt); (Max: 4 g/24h)

Imipenem*

< 7 days, < 1.5 kg: 50 mg/kg/day IV divided q12h

1-4 wks, >1.5 kg: 75 mg/kg/day IV divided q8h

1-3 mo, >1.5 kg:100 mg/kg/day IV divided q6h

>3 mos: 60-100 mg/kg/day IV divided q6h

(max 2-4 g/day)

Nitrofurantoin **

5-7 mg/kg/day PO divided q6h  (max 400 mg/day)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Proteus mirabilis

Ampicillin *

Neonate: (depending on age/wt) 50-200 mg/kg/day IM/IV divided q6-12h

Infants/children: 100-400 mg/kg/day IM/IV divided q4-6h; (Max: 12 g/day

IM/IV, 2-3 g/day PO); Alt: 50-100 mg/kg/day PO divided q6h

Amoxicillin/clavulanate*^

25-45 mg/kg/day amoxicillin PO divided q12h depending on age/wt

Cefuroxime *

3mo-12yr: 30 mg/kg/day susp PO divided q12h; (Max: 1000 mg/day)

>13yr: 250-500 mg tab PO bid

Piperacillin/tazobactam *

2-9 mos: 240 mg/kg/day IV divided q8h

>9 mos, < 40 kg: 300 mg/kg/day IV divided q8h

>9 mos, > 40 kg: 3.375 g IV q6h x7-10 days

Aztreonam *^

60-120 mg/kg/day IV divided q6-12h (depending on age/wt); (Max: 120

mg/kg/day up to 8 g/day)

Imipenem *

< 7 days, < 1.5 kg: 50 mg/kg/day IV divided q12h

1-4 wks, >1.5 kg: 75 mg/kg/day IV divided q8h

1-3 mo, >1.5 kg:100 mg/kg/day IV divided q6h

>3 mos: 60-100 mg/kg/day IV divided q6h

(max 2-4 g/day)

Ceftazidime/avibactam*

3 months to < 2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to < 18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams)

Kristi Lynn Hebert, MD Resident Physician, Department of Urology, Ochsner Clinic Foundation, Louisiana State University School of Medicine in New Orleans

Kristi Lynn Hebert, MD is a member of the following medical societies: Alpha Omega Alpha, American Urological Association, Society of Women in Urology, Louisiana State Urological Society

Disclosure: Nothing to disclose.

Christopher C Roth, MD Associate Professor of Urology, Children’s Hospital of New Orleans, Louisiana State University School of Medicine in New Orleans

Christopher C Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Urological Association, Society for Pediatric Urology, Society for Fetal Urology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

Disclosure: Nothing to disclose.

Pediatric Urinary Tract Infection Organism-Specific Therapy 

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