Tweet
Infect Immun. 2019 Aug 5. pii: IAI.00538-19. doi: 10.1128/IAI.00538-19. [Epub ahead of print]
Linezolid Attenuates Lethal Lung Damage during Post-Influenza Methicillin-Resistant Staphylococcus Aureus Pneumonia.
Verma AK1, Bauer C1, Yajjala VK1, Bansal S1, Sun K2.
Author information
1 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900. 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900 Keer.sun@unmc.edu.
Abstract
Post-influenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus α-toxin in a lethal model of influenza and MRSA coinfection. We demonstrate that antibiotics primarily attenuate α-toxin-induced acute lethality, even though both α-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on α-toxin-induced lung damage as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine Leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from post-influenza MRSA pneumonia as compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with significantly attenuated pro-inflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of α-toxin in the extreme mortality of secondary MRSA pneumonia after influenza, but also provide support that linezolid could be a more effective treatment to improve disease outcome.
Copyright ? 2019 American Society for Microbiology.
PMID: 31383747 DOI: 10.1128/IAI.00538-19
Linezolid Attenuates Lethal Lung Damage during Post-Influenza Methicillin-Resistant Staphylococcus Aureus Pneumonia.
Verma AK1, Bauer C1, Yajjala VK1, Bansal S1, Sun K2.
Author information
1 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900. 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900 Keer.sun@unmc.edu.
Abstract
Post-influenza methicillin-resistant Staphylococcus aureus (MRSA) infection can quickly develop into severe, necrotizing pneumonia, causing over 50% mortality despite antibiotic treatments. In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus α-toxin in a lethal model of influenza and MRSA coinfection. We demonstrate that antibiotics primarily attenuate α-toxin-induced acute lethality, even though both α-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on α-toxin-induced lung damage as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine Leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from post-influenza MRSA pneumonia as compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with significantly attenuated pro-inflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of α-toxin in the extreme mortality of secondary MRSA pneumonia after influenza, but also provide support that linezolid could be a more effective treatment to improve disease outcome.
Copyright ? 2019 American Society for Microbiology.
PMID: 31383747 DOI: 10.1128/IAI.00538-19