MACROLIDE BEFORE A BETA-LACTAM DECREASES DISEASE SEVERITY IN A MURINE PNEUMOCOCCAL PNEUMONIA MODEL

Abstract

SESSION TITLE: Chest Infections 1 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia (CAP) and an important cause of morbidity and mortality. Clinical practice guidelines recommend against the use of macrolide monotherapy among hospitalized patients with CAP. We evaluated the hypothesis that combination therapy with Mac plus a beta-lactam (Mac/BL) compared to Mac monotherapy improves survival, decrease bacterial burden and lower disease severity in a murine pneumococcal pneumonia model. METHODS: Mice were infected intratracheally with 10ˆ5 CFU of S. pneumoniae and challenged intraperitoneally with one or two antibiotics: Ampicillin (BL) at a dose of 80mg/kg and/or Azithromycin (Mac) at 50mg/kg, respectively. After 30 hours, mice were randomized in 2 groups (Mac/BL [n=6] vs. Mac alone [n=6]). Three sets of outcomes were assessed: 1) Survival study: all groups were followed 7 days post infection; 2) Disease severity was tested by the validated lung pathology score (scored 0-5 based on peribronchial and perivascular inflammation, neutrophil infiltration and alveolar consolidation); 3) Bacterial burden: measured by daily bacteremia using colony forming units/ml. RESULTS: The 7-day survival for the Mac/BL group was 50% compared to 17% for the Mac group. After 18 hours of treatment bacteremia in the Mac/BL group had cleared (median= 0 log CFU/ml) compared to the Mac group (median=6.3 log CFU/ml). The lung pathology score was lowest among the Mac/BL group (median of 2) vs. Mac (median of 3.5). CONCLUSIONS: Our results suggest that the combination of a macrolide with a BL compared to Mac monotherapy may lower disease severity, bacterial load and survival. Translation of these findings in humans may potentially impact the use of antibiotics in pneumococcal pneumonia. CLINICAL IMPLICATIONS: This pre-clinical data supports the clinical practice guidelines regarding the use of Mac/BL combination therapy for patients with pneumococcal pneumonia. DISCLOSURES: No relevant relationships by Antonio Anzueto, source=Web Response No relevant relationships by Bettina Babu, source=Web Response No relevant relationships by Cecilia Hinojosa, source=Web Response I own stock relationship with nektar Please note: $20001 - $100000 Added 03/04/2018 by Mark Metersky, source=Web Response, value=Nothing was received No relevant relationships by Jay Peters, source=Web Response No relevant relationships by Marcos Restrepo, source=Web Response No relevant relationships by Alexander Shaffer, source=Web Response No relevant relationships by Grant Waterer, source=Web Response