title: Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.
abstract: OBJECTIVE
  Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients.
  
  
  METHODS
  This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia.
  
  
  RESULTS
  Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ± 8.0 μg/mL, total area under the serum concentration-time curve was 5397 ± 1993 μg h/mL and elimination half-life was 102.3 ± 47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ± 2.7 days. Two patients suffered a recurrence at days 17 and 20.
  
  
  CONCLUSIONS
  These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trials.
authors.affiliation: Multidisciplinary Intensive Care Unit, Department of Anesthesiology, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, UPMC Paris 6, France.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Rouby
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Philippe
authors.initials: P
authors.lastname: Eggimann
authors.forename: Anthony
authors.initials: A
authors.lastname: Dugard
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Mercier
authors.forename: Jorge
authors.initials: J
authors.lastname: Garbino
authors.forename: Charles-Edouard
authors.initials: CE
authors.lastname: Luyt
authors.forename: Jean
authors.initials: J
authors.lastname: Chastre
authors.forename: Violetta
authors.initials: V
authors.lastname: Georgescu-Kyburz
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rudolf
authors.forename: Verena
authors.initials: V
authors.lastname: Gafner
authors.forename: Hedvika
authors.initials: H
authors.lastname: Lazar
authors.forename: Holger
authors.initials: H
authors.lastname: Koch
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000009:adverse effects*; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D016756:Immunoglobulins, Intravenous