Community-acquired pneumonia (CAP) in children is usually treated with 10 days of antibiotics. Shorter antibiotic courses may be beneficial if proven effective, with potentially fewer antibiotic adverse effects and decreased antibiotic exposure.
Methods: This randomized, double-blind, placebo-controlled superiority trial (NCT02891915) compared a strategy of short vs standard course ß-lactam therapy for outpatient CAP in children ages 6-71 months. Children demonstrating clinical improvement by day 3-5 of initial therapy were considered for enrollment. Enrolled children were randomized 1:1 to receive either 5 additional days of the originally prescribed antibiotic (standard) or matching placebo (short). The Desirability of Outcome Ranking (DOOR; PMID: 26113652) was the primary outcome, and was defined by classifying the global experience of children into an ordinal clinical response (OCR) that combined the response to CAP treatment and antibiotic adverse effects 11-15 days after the start of therapy. For those subjects with equivalent OCR, documented days of antibiotic administration was used to further rank the desirability of the outcome with the a priori assumption that shorter antibiotic exposure was more desirable. The OCR was a secondary outcome. The intention to treat population was used to estimate the probability of a more desirable outcome for the strategy of short vs. standard course therapy for both outcomes.
Results: 385 children were enrolled; 380 had complete data for analysis. Baseline characteristics were similar between the two strategies. In both strategies, > 90% of children had an adequate response to CAP treatment and most antibiotic adverse effects were minor (Table). In the OCR analysis, short course therapy had a 48% probability (95% CI: 42%-53%) of a more desirable outcome. In the DOOR analysis, short course therapy was superior to standard therapy with a 69% probability (95% CI: 63%-72%; p< 0.001) of a more desirable outcome.Ordinal Clinical Response (OCR) by Treatment Group.png)
Conclusion: Among children with CAP demonstrating initial clinical improvement with outpatient therapy, both strategies had a similar response to CAP treatment and antibiotic adverse effects, but short course therapy was superior in our a priori defined outcome that incorporated decreased antibiotic exposure.
Derek Williams, MD, MPH
Associate Professor
Vanderbilt University Medical Center
Nashville, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
C. Buddy Creech, MD, MPH
Associate Professor
Vanderbilt University Medical Center
Nashville, Tennessee
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Emmanuel B. Walter, MD, MPH
Professor
Duke University School of Medicine
Durham, North Carolina
Disclosure: Moderna (Grant/Research Support)Pfizer (Grant/Research Support)
Judith Martin, MD
Professor
University of Pittsburgh
Pittsburgh, Pennsylvania
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Jeffrey Gerber, MD, PhD
Associate Professor of Pediatrics
Children's Hospital of Philadelphia
Philadelphia, PA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Jason Newland, MD, MEd, FPIDS
Professor of Pediatrics
Washington University
St. Louis, Missouri
Disclosure: Merck : Grant/Research Support; Pfizer : Industry funded clinical trial, Other Financial or Material Support
Lee Howard, RN, CCRC
RN, CCRC
Arkansas Children's
Little Rock, Arkansas
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Meghan E. Hofto, MD, MPH
Assistant Professor
University of Alabama at Birmingham
Birmingham, Alabama
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Mary A. Staat, MD, MPH
Professor
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Randolph Oler, MS
Clinical Data Manager
Emmes Company, LLC
Rockville, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Thomas Conrad, PhD
Biostatistician Manager
Emmes Company, LLC
Rockville, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Bonifride Tuyishimire, PhD
Biostatistician
Emmes Company, LLC
Rockville, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Melinda M. Pettigrew, PhD
Professor of Epidemiology
Yale School of Public Health
New Haven, Connecticut
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Vance G. Fowler, Jr., MD, MHS
Professor of Medicine
Duke University
Durham, North Carolina
Disclosure: Abbvie : Grant/Research Support (Status: Ongoing); Actavis : Grant/Research Support; Advanced Liquid Logics : Grant/Research Support; Affinergy : Consultant, Research Grant or Support; Affinium : Consultant; Allergan : Grant/Research Support; Ampliphi Biosciences : Consultant; Armata : Consultant (Status: Ongoing); Basilea : Consultant, Research Grant or Support; Bayer : Consultant, Consultant; C3J : Consultant; CARB-X : Consultant (Status: Ongoing); Cerexa : Consultant, Research Grant or Support; Contrafect : Consultant, Research Grant or Support; Cubist : Grant/Research Support; Debiopharm : Consultant; Destiny : Consultant; Durata : Consultant; Forest : Grant/Research Support; Genentech : Consultant, Research Grant or Support; ICBiome : Consultant (Status: Ongoing); Integrated Biotherapeutics : Consultant; Janssen : Consultant, Research Grant or Support; Karius : Grant/Research Support; Locus : Grant/Research Support; Medical Biosurfaces : Grant/Research Support; Medicines Co. : Consultant; Medimmune : Consultant, Research Grant or Support; Merck : Consultant, Research Grant or Support; NIH : Grant/Research Support; Novadigm : Consultant; Novartis : Consultant, Research Grant or Support; Pfizer : Grant/Research Support; Regeneron : Consultant, Research Grant or Support; Tetraphase : Consultant; Theravance : Consultant, Research Grant or Support; Valanbio : Board Member (Status: Ongoing), Other Financial or Material Support (Status: Ongoing), Stock options (Status: Ongoing); xBiotech : Consultant
Henry Chambers, B.A., MD
Professor of Medicine, Emeritus
UC San Francisco School of Medicine
San Francisco, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Theoklis Zaoutis, MD, MSCE
Professor of Pediatrics, Attending Physician
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Scott R. Evans, PhD
Professor and Director of the Biostatistics Center
The George Washington University
Rockville, Maryland
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
W. Charles Huskins, MD, MSc
Professor of Pediatrics
Mayo Clinic College of Medicine and Science
Rochester, MN
Disclosure: ADMA Biologics (Consultant)Pfizer, Inc (Consultant)
