Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia | Pediatrics | JAMA Pediatrics | JAMA Network
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1.
AHRQ. National estimates on use of hospitals by children from the hcup kids' inpatient database (KID). 2012; http://hcupnet.ahrq.gov/. Accessed January 12, 2014.
2.
Gerber  JS, Kronman  MP, Ross  RK,  et al.  Identifying targets for antimicrobial stewardship in children’s hospitals.  Infect Control Hosp Epidemiol. 2013;34(12):1252-1258.PubMedGoogle ScholarCrossref
3.
Bradley  JS, Byington  CL, Shah  SS,  et al; Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.  The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.  Clin Infect Dis. 2011;53(7):e25-e76.PubMedGoogle ScholarCrossref
4.
Jain  S, Williams  DJ, Arnold  SR,  et al; CDC EPIC Study Team.  Community-acquired pneumonia requiring hospitalization among U.S. children.  N Engl J Med. 2015;372(9):835-845.PubMedGoogle ScholarCrossref
5.
Jain  S, Self  WH, Wunderink  RG,  et al; CDC EPIC Study Team.  Community-acquired pneumonia requiring hospitalization among U.S. adults.  N Engl J Med. 2015;373(5):415-427.PubMedGoogle ScholarCrossref
6.
Gardiner  SJ, Gavranich  JB, Chang  AB.  Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.  Cochrane Database Syst Rev. 2015;1:CD004875.PubMedGoogle Scholar
7.
Biondi  E, McCulloh  R, Alverson  B, Klein  A, Dixon  A, Ralston  S.  Treatment of mycoplasma pneumonia: a systematic review.  Pediatrics. 2014;133(6):1081-1090.PubMedGoogle ScholarCrossref
8.
Eliakim-Raz  N, Robenshtok  E, Shefet  D,  et al.  Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults.  Cochrane Database Syst Rev. 2012;(9):CD004418.PubMedGoogle Scholar
9.
Min  JY, Jang  YJ.  Macrolide therapy in respiratory viral infections.  Mediators Inflamm. 2012;2012:649570.Google Scholar
10.
Kronman  MP, Hersh  AL, Feng  R, Huang  YS, Lee  GE, Shah  SS.  Ambulatory visit rates and antibiotic prescribing for children with pneumonia, 1994-2007.  Pediatrics. 2011;127(3):411-418.PubMedGoogle ScholarCrossref
11.
Hersh  AL, Shapiro  DJ, Pavia  AT, Shah  SS.  Antibiotic prescribing in ambulatory pediatrics in the United States.  Pediatrics. 2011;128(6):1053-1061.PubMedGoogle ScholarCrossref
12.
Brogan  TV, Hall  M, Williams  DJ,  et al.  Variability in processes of care and outcomes among children hospitalized with community-acquired pneumonia.  Pediatr Infect Dis J. 2012;31(10):1036-1041.PubMedGoogle Scholar
13.
Rice  TW, Wheeler  AP, Bernard  GR, Hayden  DL, Schoenfeld  DA, Ware  LB; National Institutes of Health, National Heart, Lung, and Blood Institute ARDS Network.  Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS.  Chest. 2007;132(2):410-417.PubMedGoogle ScholarCrossref
14.
Rosenbaum  PR, Rubin  DB.  Constructing a control-group using multivariate matched sampling methods that incorporate the propensity score.  Am Stat. 1985;39(1):33-38.Google Scholar
15.
Austin  PC, Stuart  EA.  Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies.  Stat Med. 2015;34(28):3661-3679.PubMedGoogle ScholarCrossref
16.
Lunt  M.  Selecting an appropriate caliper can be essential for achieving good balance with propensity score matching.  Am J Epidemiol. 2014;179(2):226-235.PubMedGoogle ScholarCrossref
17.
Ambroggio  L, Taylor  JA, Tabb  LP, Newschaffer  CJ, Evans  AA, Shah  SS.  Comparative effectiveness of empiric β-lactam monotherapy and β-lactam-macrolide combination therapy in children hospitalized with community-acquired pneumonia.  J Pediatr. 2012;161(6):1097-1103.PubMedGoogle ScholarCrossref
18.
Leyenaar  JK, Shieh  MS, Lagu  T, Pekow  PS, Lindenauer  PK.  Comparative effectiveness of ceftriaxone in combination with a macrolide compared with ceftriaxone alone for pediatric patients hospitalized with community-acquired pneumonia.  Pediatr Infect Dis J. 2014;33(4):387-392.PubMedGoogle ScholarCrossref
19.
Bacharier  LB, Guilbert  TW, Mauger  DT,  et al.  Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial.  JAMA. 2015;314(19):2034-2044.PubMedGoogle ScholarCrossref
20.
Garin  N, Genné  D, Carballo  S,  et al.  β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial.  JAMA Intern Med. 2014;174(12):1894-1901.PubMedGoogle ScholarCrossref
21.
Hicks  LA, Harrison  LH, Flannery  B,  et al.  Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004.  J Infect Dis. 2007;196(9):1346-1354.PubMedGoogle ScholarCrossref
22.
Link-Gelles  R, Thomas  A, Lynfield  R,  et al.  Geographic and temporal trends in antimicrobial nonsusceptibility in Streptococcus pneumoniae in the post-vaccine era in the United States.  J Infect Dis. 2013;208(8):1266-1273.PubMedGoogle ScholarCrossref
23.
Bergman  M, Huikko  S, Huovinen  P, Paakkari  P, Seppälä  H; Finnish Study Group for Antimicrobial Resistance (FiRe Network).  Macrolide and azithromycin use are linked to increased macrolide resistance in Streptococcus pneumoniae.  Antimicrob Agents Chemother. 2006;50(11):3646-3650.PubMedGoogle ScholarCrossref
24.
Lee  GC, Reveles  KR, Attridge  RT,  et al.  Outpatient antibiotic prescribing in the United States: 2000 to 2010.  BMC Med. 2014;12:96.PubMedGoogle ScholarCrossref
25.
Neuman  MI, Shah  SS, Shapiro  DJ, Hersh  AL.  Emergency department management of childhood pneumonia in the United States prior to publication of national guidelines.  Acad Emerg Med. 2013;20(3):240-246.PubMedGoogle ScholarCrossref
26.
Ross  RK, Hersh  AL, Kronman  MP,  et al.  Impact of Infectious Diseases Society of America/Pediatric Infectious Diseases Society guidelines on treatment of community-acquired pneumonia in hospitalized children.  Clin Infect Dis. 2014;58(6):834-838.PubMedGoogle ScholarCrossref
27.
Williams  DJ, Edwards  KM, Self  WH,  et al.  Antibiotic choice for children hospitalized with pneumonia and adherence to national guidelines.  Pediatrics. 2015;136(1):44-52.PubMedGoogle ScholarCrossref
28.
Hicks  LA, Chien  YW, Taylor  TH  Jr, Haber  M, Klugman  KP, Active Bacterial Core Surveillance (ABCs) Team.  Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996-2003.  Clin Infect Dis. 2011;53(7):631-639.PubMedGoogle ScholarCrossref
Original Investigation
December 2017

Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia

Author Affiliations
  • 1Division of Hospital Medicine, Monroe Carell Jr. Children’s Hospital, Vanderbilt University Medical Center, Nashville, Tennessee
  • 2Division of Infectious Diseases, Monroe Carell Jr. Children’s Hospital, Vanderbilt University Medical Center, Nashville, Tennessee
  • 3The Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center, Nashville
  • 4Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
  • 5Division of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
  • 6Division of Infectious Diseases, Le Bonheur Children’s Hospital, Memphis, Tennessee
  • 7Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis
  • 8Division of Infectious Diseases, Primary Children’s Medical Center, Salt Lake City, Utah
  • 9Department of Pediatrics, University of Utah School of Medicine, Salt Lake City
  • 10Division of Infectious Diseases, Departments of Medicine and Pediatrics, Emory University School of Medicine, Atlanta, Georgia
  • 11Centers for Disease Control and Prevention, Atlanta, Georgia
  • 12Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee
JAMA Pediatr. 2017;171(12):1184-1191. doi:10.1001/jamapediatrics.2017.3225
Key Points

Question  Is treatment with a β-lactam antibiotic in combination with a macrolide more effective than β-lactam monotherapy among children hospitalized with pneumonia?

Findings  In this prospective cohort of more than 1400 children hospitalized with pneumonia, there were no significant differences in length of stay, intensive care admission, rehospitalizations, or recovery at follow-up among children receiving β-lactam plus macrolide combination therapy compared with β-lactam monotherapy.

Meaning  The results of this study question the routine empirical use of macrolide combination therapy in this population.

Abstract

Importance  β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches.

Objective  To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia.

Design, Setting, and Participants  We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children’s hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017.

Main Outcomes and Measures  We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients’ length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up.

Results  Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the Etiology of Pneumonia in the Community Study with radiographically confirmed pneumonia in the study period; 1019 (71.9%) received β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes.

Conclusions and Relevance  Empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population.

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