title: The anti-Pseudomonas aeruginosa antibody Panobacumab is efficacious on acute pneumonia in neutropenic mice and has additive effects with meropenem.
abstract: Pseudomonas aeruginosa (P. aeruginosa) infections are associated with considerable morbidity and mortality in immunocompromised patients due to antibiotic resistance. Therefore, we investigated the efficacy of the anti-P. aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a clinically relevant murine model of neutropenia induced by cyclophosphamide and in combination with meropenem in susceptible and meropenem resistant P. aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia was dramatically increased in neutropenic mice compared to immunocompetent mice. First, Panobacumab significantly reduced lung inflammation and enhanced bacterial clearance from the lung of neutropenic host. Secondly, combination of Panobacumab and meropenem had an additive effect. Third, Panobacumab retained activity on a meropenem resistant P. aeruginosa strain. In conclusion, the present data established that Panobacumab contributes to the clearance of P. aeruginosa in neutropenic hosts as well as in combination with antibiotics in immunocompetent hosts. This suggests beneficial effects of co-treatment even in immunocompromised individuals, suffering most of the morbidity and mortality of P. aeruginosa infections.
authors.affiliation: Université d'Orléans and Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Orléans, France ; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Thomas
authors.initials: T
authors.lastname: Secher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Fas
authors.forename: Louis
authors.initials: L
authors.lastname: Fauconnier
authors.forename: Marieke
authors.initials: M
authors.lastname: Mathieu
authors.forename: Oliver
authors.initials: O
authors.lastname: Rutschi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Michael
authors.initials: M
authors.lastname: Rudolf
mesh_terms: D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D000077731:Meropenem; D051379:Mice; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000150:complications*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D013845:Thienamycins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D013845:Thienamycins; D000077731:Meropenem
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