Time to first antibiotic dose for community-acquired pneumonia: a challenging balance

  • Maddalena Giannella
    Correspondence
    Corresponding author. Maddalena Giannella, Infectious Diseases Unit, Policlinico Sant’Orsola Malpighi, Via Massarenti 11, 40137, Bologna, Italy.
    Affiliations
    Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant’Orsola Malpighi, University of Bologna, Italy
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  • Emilio Bouza
    Affiliations
    Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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  • Pierluigi Viale
    Affiliations
    Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant’Orsola Malpighi, University of Bologna, Italy
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Published:October 29, 2020DOI:https://doi.org/10.1016/j.cmi.2020.10.025
      Early administration of antibiotic therapy has been considered a standard of care in the management of community-acquired pneumonia (CAP) since two retrospective studies showed that receiving the first antibiotic dose within 8 or 4 hours of admission improved survival [
      • Meehan T.P.
      • Fine M.J.
      • Krumholz H.M.
      • Scinto J.D.
      • Galusha D.H.
      • Mockalis J.T.
      • et al.
      Quality of care, process, and outcomes in elderly patients with pneumonia.
      ,
      • Houck P.M.
      • Bratzler D.W.
      • Nsa W.
      • Ma A.
      • Bartlett J.G.
      Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia.
      ]. These studies prompted the use of ‘time to first antibiotic dose’ (TFAD) as a quality-of-care indicator in the management of patients evaluated for CAP. However, such studies were criticized because of their retrospective, dataset-based design, their use of discharge diagnosis instead of the real-life perspective of a patient suspected of having CAP, and their lack of adjustment for several confounding factors. Indeed, a clear association between early TFAD (4–8 hours) and improved outcome was not confirmed in further prospective studies and meta-analyses [
      • Yahav D.
      • Leibovici L.
      • Goldberg E.
      • Bishara J.
      • Paul M.
      Time to first antibiotic dose for patients hospitalised with community-acquired pneumonia.
      ]. In addition, adherence to a predefined TFAD was associated with an increased rate of CAP misdiagnosis, lowering the yield in microbiological workup and leading to antibiotic overuse [
      • Pines J.M.
      • Isserman J.A.
      • Hinfey P.B.
      The measurement of time to first antibiotic dose for pneumonia in the emergency department: a white paper and position statement prepared for the American Academy of Emergency Medicine.
      ]. A severe outbreak of Clostridioides difficile infection linked to a strict pneumonia care plan, including predefined TFAD as quality-of-care indicator, was reported. Review of medical records showed that half of patients treated for pneumonia may not have had pneumonia [
      • Polgreen P.M.
      • Chen Y.Y.
      • Cavanaugh J.E.
      • Ward M.
      • Coffman S.
      • Hornick D.B.
      • et al.
      An outbreak of severe Clostridium difficile-associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia.
      ]. Thus, the Infectious Diseases Society of America (IDSA) guidelines released in 2007 abandoned a predefined time window for delivery of the first antibiotic dose, but just recommended that it should be given in the Emergency Department (ED) [
      • Mandell L.A.
      • Wunderink R.G.
      • Anzueto A.
      • Bartlett J.G.
      • Campbell G.D.
      • Dean N.C.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      ]. Current IDSA guidelines on the management of adults with CAP, published in 2019, do not address the issue of the ‘time to first antibiotic dose’ [
      • Metlay J.P.
      • Waterer G.W.
      • Long A.C.
      • Anzueto A.
      • Brozek J.
      • Crothers K.
      • et al.
      Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American thoracic society and infectious diseases society of America.
      ]. However, the debate about TFAD in patients suspected of having CAP is far from being closed, mainly because the available evidence comes from observational low-quality studies [
      • Lee J.S.
      • Giesler D.L.
      • Gellad W.F.
      • Fine M.J.
      Antibiotic therapy for adults hospitalized with community-acquired pneumonia: a systematic review.
      ]. Another issue is the use of early (3–5 days) versus late (30 days) endpoints for assessing therapeutic strategies in patients with CAP [
      • Talbot G.H.
      • Powers J.H.
      • Fleming T.R.
      • Siuciak J.A.
      • Bradley J.
      • Boucher H.
      Progress on developing endpoints for registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections: update from the Biomarkers Consortium of the Foundation for the National Institutes of Health.
      ], which adds concerns about the interpretation of results from previous studies and the design of new ones.

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