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Experimental Therapeutics

Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia

D. Battaglini, A. Motos, G. Li Bassi, H. Yang, F. Pagliara, M. Yang, E. Aguilera Xiol, A. Meli, J. Bobi, G. Frigola, T. Senussi, F. Idone, C. Travierso, C. Chiurazzi, L. Fernandez-Barat, M. Rigol, J. Ramirez, P. Pelosi, D. Chiumello, M. Antonelli, D. P. Nicolau, J. Bringue, A. Artigas, L. Guerrero, D. Soy, A. Torres
D. Battaglini
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
bDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
cAnesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
fUniversity of Barcelona, Barcelona, Spain
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A. Motos
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
dCentro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
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G. Li Bassi
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
dCentro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
gBITRECS, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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H. Yang
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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F. Pagliara
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
bDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
cAnesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
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M. Yang
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
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E. Aguilera Xiol
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
dCentro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
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A. Meli
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
hUniversity of Milan, Milan, Italy
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J. Bobi
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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G. Frigola
jDepartamento de Anatomía Patológica, Hospital Clínic de Barcelona, Barcelona, Spain
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T. Senussi
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
bDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
cAnesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
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F. Idone
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
kDepartment of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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C. Travierso
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
hUniversity of Milan, Milan, Italy
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C. Chiurazzi
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
iHumanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy
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L. Fernandez-Barat
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
dCentro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
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M. Rigol
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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J. Ramirez
jDepartamento de Anatomía Patológica, Hospital Clínic de Barcelona, Barcelona, Spain
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P. Pelosi
bDepartment of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
cAnesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy
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D. Chiumello
hUniversity of Milan, Milan, Italy
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M. Antonelli
kDepartment of Anesthesiology and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
lUniversità Cattolica del Sacro Cuore, Rome, Italy
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D. P. Nicolau
mCenter for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA
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  • ORCID record for D. P. Nicolau
J. Bringue
nDepartment of Intensive Care Medicine, CIBER Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain
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A. Artigas
nDepartment of Intensive Care Medicine, CIBER Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli, Autonomous University of Barcelona, Sabadell, Spain
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L. Guerrero
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
oDivision of Medicines, Pharmacy Service, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
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D. Soy
oDivision of Medicines, Pharmacy Service, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
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A. Torres
aDivision of Animal Experimentation, Department of Pulmonology, Hospital Clínic, Barcelona, Spain
dCentro de Investigación en Red de Enfermedades Respiratorias, Madrid, Spain
eInstitut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
fUniversity of Barcelona, Barcelona, Spain
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  • ORCID record for A. Torres
DOI: 10.1128/AAC.01009-20
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ABSTRACT

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

FOOTNOTES

    • Received 20 May 2020.
    • Returned for modification 19 June 2020.
    • Accepted 24 September 2020.
    • Accepted manuscript posted online 12 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia
D. Battaglini, A. Motos, G. Li Bassi, H. Yang, F. Pagliara, M. Yang, E. Aguilera Xiol, A. Meli, J. Bobi, G. Frigola, T. Senussi, F. Idone, C. Travierso, C. Chiurazzi, L. Fernandez-Barat, M. Rigol, J. Ramirez, P. Pelosi, D. Chiumello, M. Antonelli, D. P. Nicolau, J. Bringue, A. Artigas, L. Guerrero, D. Soy, A. Torres
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01009-20; DOI: 10.1128/AAC.01009-20

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Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia
D. Battaglini, A. Motos, G. Li Bassi, H. Yang, F. Pagliara, M. Yang, E. Aguilera Xiol, A. Meli, J. Bobi, G. Frigola, T. Senussi, F. Idone, C. Travierso, C. Chiurazzi, L. Fernandez-Barat, M. Rigol, J. Ramirez, P. Pelosi, D. Chiumello, M. Antonelli, D. P. Nicolau, J. Bringue, A. Artigas, L. Guerrero, D. Soy, A. Torres
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01009-20; DOI: 10.1128/AAC.01009-20
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KEYWORDS

telavancin
linezolid
MRSA
severe pneumonia
pig
animal models
mechanical ventilation
porcine model

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