Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia

• Published in: European journal of clinical microbiology & infectious diseases Vol. 33; no. 10; pp. 1861 - 1867
• Main Authors: Que, Y.-A., Lazar, H., Wolff, M., François, B., Laterre, P.-F., Mercier, E., Garbino, J., Pagani, J.-L., Revelly, J.-P., Mus, E., Perez, A., Tamm, M., Rouby, J.-J., Lu, Q., Chastre, J., Eggimann, P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-10-2014; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antibodies, Bacterial - administration & dosage; Antibodies, Bacterial - adverse effects; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cross Infection - microbiology; Cross Infection - therapy; Drug dosages; Female; General aspects; Gram-negative bacteria; Human infectious diseases. Experimental studies and models; Humans; Immunoglobulin M - administration & dosage; Immunoglobulin M - adverse effects; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - pharmacokinetics; Immunotherapy; Immunotherapy - methods; Infectious diseases; Internal Medicine; Male; Medical Microbiology; Medical sciences; Middle Aged; Monoclonal antibodies; Mortality; Nosocomial infection; Nosocomial infections; Pharmacokinetics; Physiology; Pneumology; Pneumonia; Pneumonia, Bacterial - microbiology; Pneumonia, Bacterial - therapy; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas aeruginosa - classification; Pseudomonas aeruginosa - immunology; Respiratory system : syndromes and miscellaneous diseases; Sepsis; Serogroup; Treatment Outcome; Virulence; France; Switzerland; Paris France; Human Monoclonal Antibody; Clinical Resolution; Nosocomial Pneumonia; Rabies; Sequential Organ Failure Assessment; Pseudomonadales; Lung disease; Nosocomial infection; Pneumonia; Treatment; Microbiology; Respiratory disease; Immunotherapy; Bacteria; Pseudomonadaceae; Pseudomonas aeruginosa
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-014-2156-1

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype
Pseudomonas aeruginosa
infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (
n
 = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64–79] versus an average of 50 years old (IQR: 30–73) (
p
 = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16–22) versus 15 (IQR: 10–19) (
p
 = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (
p
 = 0.048). The Kaplan–Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0–11.5] versus 18.5 [IQR: 8–30] days in those who did not receive the antibody;
p
 = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11
P. aeruginosa
pneumonia.