S Hraiech1, J Bordes2, J L Mège3, X de Lamballerie4, R Charrel4, Y Bechah3, B Pastorino4, C Guervilly5, J M Forel5, M Adda5, J M Rolain3, H Lepidi3, D Raoult3, S Lehingue5, L Papazian6. 1. Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France; IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France. Electronic address: sami.hraiech@ap-hm.fr. 2. IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France; Fédération d'Anesthésie-Réanimation-Urgences, Hôpital d'Instruction des Armées Sainte-Anne Toulon, France. 3. IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France. 4. UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Universite - IRD 190 - Inserm 1207 - EHESP), Marseille, France; Institut hospitalo-universitaire Méditerranée infection, APHM Public Hospitals of Marseille, Marseille, France. 5. Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France. 6. Aix-Marseille Univ, APHM, URMITE UMR CNRS 7278, Hôpital Nord, Réanimation des Détresses Respiratoires et Infections Sévères, Marseille, France; IHU Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France.
Abstract
OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia. RESULTS: After MSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMV mice 2 days (5×103 (103 to 3×105) versus 102 (0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104 (1.6×104 to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice. CONCLUSIONS: MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.
OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia. RESULTS: After MSSA pneumonia, MCMVmice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMVmice 2 days (5×103 (103 to 3×105) versus 102 (0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104 (1.6×104 to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMVmice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMVmice. CONCLUSIONS:MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.
Authors: Sami Hraiech; Eline Bonnardel; Christophe Guervilly; Cyprien Fabre; Anderson Loundou; Jean-Marie Forel; Mélanie Adda; Gabriel Parzy; Guilhem Cavaille; Benjamin Coiffard; Antoine Roch; Laurent Papazian Journal: Ann Intensive Care Date: 2019-12-23 Impact factor: 6.925