Antibiotic Effectiveness Research

Antibiotic Effectiveness Research | CPCE

The rapid emergence of antimicrobial resistance among bacteria is a major threat to the health of individuals as well as society as a whole. Antibiotic therapy is a first treatment of choice for many childhood infections and, for some conditions, it is used to prevent infection among those most susceptible to recurring infection. Continued antibiotic effectiveness requires research to improve pediatric treatment protocols.  

CPCE researchers are delving into ways to improve standard course therapies to reduce antibiotic exposure among seriously ill or chronically ill children. We hope to answer questions about when prophylactic antibiotics are an effective strategy or can be avoided; if oral antibiotics are just as effective for post-discharge therapy for children recovering from a serious bacterial infection as parent-administered Intravenous (IV) Antibiotics and; if shorter-course antibiotic therapy can be as effective as longer standard-course protocols.

Prophylactic Antibiotics for Vesicoureteral Reflux

Oral Antibiotics vs. Intravenous (IV) Antibiotics for Serious Bacterial Infections

Short Course vs Standard Course Antibiotic Therapy for Common Infections

Antibiotic Effectiveness Published Research


Prophylactic Antibiotics for Vesicoureteral Reflux

An ongoing line of research at CPCE has studied the management of urinary tract infections (UTI) in children, covering the gamut of questions including optimal duration of antibiotic therapy, risk factors for recurrent UTI, effectiveness of prophylactic antibiotics, variability in outcomes for children hospitalized with UTI, impact of prior antimicrobial exposure on development of drug-resistant UTI, and the role of Vesicoureteral reflux (VUR) in recurrent UTI and kidney scarring.

Two important studies in this area were the Careful Urinary Tract Infection Evaluation (CUTIE) study and the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study. These studies sought to identify risk factors for kidney scarring and recurrent UTI and to determine the effectiveness of prophylactic antibiotics for the prevention of recurrent UTI.

The RIVUR study was an 8-year multi-center placebo controlled randomized controlled trial, for which CPCE’s Ron Keren, MD, MPH was a site PI. The RIVUR study settled a controversy that had been ongoing for decades about prophylactic antibiotic effectiveness for preventing UTI in children with VUR. The trial showed that prophylaxis halved the risk of recurrent UTI but did not prevent renal scarring.

The CUTIE study sought to identify risk factors for recurrent UTI in children, regardless of whether they had VUR.  It found that high grade VUR (III-IV) and bladder and bowel dysfunction were the strongest predictors of UTI in children.

What’s Next: Analyses of the CUTIE and RIVUR data is ongoing.

See the Published Research

Funding: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Please contact Ron Keren, MD, MPH, CPCE Associate Director for Implementation and CHOP Vice President of Quality and Chief Quality Officer, for more information on this line of research.


Oral Antibiotics vs. Intravenous (IV) Antibiotics for Serious Bacterial Infections

This project compares the effectiveness of oral- versus- intravenous antibiotic therapy for children who have been hospitalized with one of three serious bacterial infections (perforated appendicitis, complicated pneumonia, or osteomyelitis), and assesses the comparative effectiveness of patient and caregiver reported health-related quality of life and adherence to antibiotic treatments.

Ultimately, we want to produce evidence on the comparative effectiveness of these options to help clinicians, patients, and their caregivers make an informed choice.

When clinicians want to prescribe prolonged antibiotic therapy for children who have been hospitalized with a serious bacterial infection, they have two options: (1) discontinue the intravenous antibiotics and discharge the child to receive a prolonged course of oral antibiotics at home; or (2) insert a central venous catheter (usually a peripherally inserted central catheter, or PICC), train the parents in care of the PICC and administration of intravenous antibiotics, and discharge the child to receive a prolonged course of intravenous antibiotics via the central venous catheter at home.

These two options have major implications for the overall experience of the child and their caregiver.

Three separate retrospective comparative effectiveness studies were conducted to compare the clinical effectiveness of oral antibiotics vs. intravenous (IV) antibiotics delivered via a PICC in children who require prolonged (at least 1 week) home antibiotic therapy after hospitalization for a serious bacterial infection. These were completed using detailed electronic data on diagnoses, procedures, laboratory tests, and orders for drugs and devices supplemented by limited chart review from 36 free standing children’s hospitals that are members of the Children’s Hospital Association (CHA).

The project used conventional and propensity-score based methods, including matching, to estimate and compare the effect of the two treatment options on patient outcomes.

Analyses comparing IV versus oral therapy for post discharge treatment of acute osteomyelitis in children revealed that those treated with oral antibiotics did not experience more treatment failures than those treated via IV administration.

Of note, children who received IV antibiotics had a much higher risk of requiring a return visit to the emergency room or for hospitalization for an adverse outcome in across-hospital and within-hospital matched analyses, due to complications related to the PICC.

What’s Next:  Analyses are on going to answer research questions about perforated appendicitis and complicated pneumonia.

See the Published Research

Funding:  Patient-Centered Outcomes Research Institute

Please contact Ron Keren, MD, MPH, CPCE Associate Director for Implementation and CHOP Vice President of Quality and Chief Quality Officer, for more information on this line of research.


Short Course vs. Standard Course Antibiotic Therapy for Common UTI

Urinary tract infections (UTI) are among the most common bacterial infections encountered by primary care physicians. Although antibiotics are the first treatment choice for UTI, antibiotic-resistant strains of E. coli, the most common cause of UTI, are increasing worldwide. The rapid emergence of antimicrobial resistance among bacteria is a major threat to the health of individuals as well as society as a whole. Prior research has shown infections with resistant bacteria increase morbidity and mortality, and greatly increase the financial burden of medical care.

While the number of resistant bacteria and the diversity of molecular mechanisms of resistance have increased sharply in recent years, the introduction of newer, effective antimicrobials has slowed significantly. The large number of children with UTI and the duration of therapy in current standard practice make UTI an important target for reducing antibiotic exposure.

The Short Course Therapy for Urinary Tract Infections in Children (SCOUT) study is a Phase 2, multi-center, centrally randomized, double-blind, placebo-controlled non-inferiority clinical trial that is investigating whether halting antimicrobial therapy in subjects who have exhibited clinical improvement five days after starting antibiotic therapy (short course therapy) have the same failure rate through test of cure (TOC) (visit Day 11-14) as subjects who continue to take antibiotics for an additional five days (standard course therapy).

Initial findings from SCOUT were published by CHOP’s Infectious Diseases research group. In a large cohort study of patients with UTI in 27 primary care pediatric practices, they found that greater than 95 percent of UTI were treated with a 10- to 14-day course of antibiotics, the standard course therapy.

What’s Next: We are comparing the effect of the short course versus standard course therapy.

Funding: National Institute of Allergy and Infectious Diseases

Please contact Theoklis Zaoutis, MD, MSCE, CPCE Director and CHOP Division Chief, Division of Infectious Diseases, for more information about this line of research.


Antibiotic Effectiveness Published Research

Prophylactic Antibiotics for VUR

RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA. Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux. The New England Journal of Medicine, 2014. 370(25):2367-76.

Keren R, Shaikh N, Pohl H, Gravens-Mueller L, Ivanova A, Zaoutis L, Patel M, deBerardinis R, Parker A, Bhatnagar S, Haralam MA, Pope M, Kearney D, Sprague B, Barrera R, Viteri B, Egigueron M, Shah N, Hoberman A. Risk Factors or Recurrent Urinary Tract Infection and Renal Scarring. Pediatrics, 2015. 136(1):e13-21.

Oral Antibiotics vs. Intravenous (IV) Antibiotics for Serious Bacterial Infections

Keren R, Shah SS, Srivastava R, Rangel S, Bendel-Stenzel M, Harik N, Hartley J, Lopez M, Seguias L, Tieder J, Bryan M, Gong W, Hall M, Localio R, Luan X, deBerardinis R, Parker A.  Pediatric Research in Inpatient Settings Network: Comparative Effectiveness of Intravenous vs Oral Antibiotics for Post-discharge Treatment of Acute Osteomyelitis in Children. JAMA Pediatrics, 2015. 169(2); 120-8.