895. Macrolide Immunomodulation and Clinical Outcomes in Hospitalized Patients with Community-Acquired Pneumonia
Session: Poster Abstract Session: Respiratory Infections
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • RL_IDSA_2013_CAPISG_Arnold.pdf (240.0 kB)
  • Background:

    Community-acquired pneumonia (CAP) may be treated with a macrolide plus a third generation cephalosporin or with a fluoroquinolone alone per the IDSA guidelines for CAP.  Distinguishing whether immunomodulatory effects due to a macrolide is beneficial is difficult.  The objective of this study was, in hospitalized patients for community-acquired pneumonia with and without a macrolide in their antimicrobial regimen, to measure neutrophil function, cytokine levels and clinical outcomes. 

    Methods:

    Subjects had serum analyzed for neutrophil function (secretory vesicles CD35 and specific granule release CD66b with and without fMLF stimulation, phagocytosis – respiratory burst (H2O2) and Staphylococcus aureus stimulated) and cytokine levels.  Neutrophil function in healthy volunteers was measured for reference.  Early and late clinical outcomes were also evaluated. 

    Results:

    A total of 40 subjects were in the study; 14 received a macrolide, and 26 did not.  Neutrophil function (mcf) in the macrolide group, the non-macrolide group, and healthy volunteers was, respectively: CD35 (118, 146, 82), CD35 with fMLF (396, 361, 181), CD66b (61, 62, 54), CD66b with fMLF (168, 144, 89), respiratory burst (817, 638, 390), and S. aureus stimulated (604, 1031, 769).  The cytokines (pg/mL) were the following in the macrolide versus the non-macrolide group, respectively: IL-1β (0.6, 3.2), IL-6 (9.5, 12), IL-8 (8.7, 25.6), IP-12p40 (3.2, 6.4), TNF-a (8.2, 12.5), IFN-g (3.2, 6.5), IP-10 (978, 1137), IL-1ra (3.8, 6.4), IL-10 (7.9, 15.5) and IL-17 (28.4, 10.1).  Clinical outcomes for the macrolide versus the non-macrolide group were, respectively: time to clinical stability (2, 2.5 days, length of stay (3.5, 5.5 days), 30-day mortality (0, 2) and 30-day rehospitalization (1, 2).  No differences were statistically significant.

    Conclusion:

    Neutrophil function was elevated in patients with CAP compared to healthy volunteers, but differences were not noted based on macrolide administration.  Alternatively, all but two cytokines trended higher in the non-macrolide group than the macrolide group, and all clinical outcomes trended worse in the non-macrolide group.  This study indicates that further evaluation is warranted.

    Forest W. Arnold, DO, MSc1, Julio A. Ramirez, MD1, Rafael Fernandez-Botran, PhD2, Madhavi Rane, PhD3, Silvia Uriarte, PhD1, Robert Kelley, PhD1, Timothy L. Wiemken, PhD, MPH, CIC1, Paula Peyrani, MD1 and Jose Bordon, MD, PhD4, (1)Division of Infectious Diseases, University of Louisville, Louisville, KY, (2)Pathology and Laboratory Medicine, University of Louisville, Louisville, KY, (3)Division of Nephrology, University of Louisville, Louisville, KY, (4)Section of Infectious Diseases, Providence Hospital, Washington, DC

    Disclosures:

    F. W. Arnold, None

    J. A. Ramirez, Pfizer, Inc.: Consultant and Investigator, Consulting fee and Research support

    R. Fernandez-Botran, None

    M. Rane, None

    S. Uriarte, None

    R. Kelley, None

    T. L. Wiemken, None

    P. Peyrani, None

    J. Bordon, None

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.