Pseudomonas aeruginosa Bacteremic Patients Exhibit Nonprotective Antibody Titers Against Therapeutic Antibody Targets PcrV and Psl Exopolysaccharide.
BACKGROUND
The type 3 secretion protein PcrV and Psl exopolysaccharide are promising therapeutic antibody targets against Pseudomonas aeruginosa. We examined P. aeruginosa bloodstream infection (BSI) isolates for the ability to express PcrV and Psl and evaluated corresponding patient serum for active titers to these targets.


METHODS
We identified 114 patients with acute P. aeruginosa BSI; 56 cases were accompanied by acute sera. Serum was evaluated for PcrV- and Psl-specific immunoglobulin G (IgG) and for cytotoxicity and opsonophagocytosis. Isolates were evaluated for susceptibility to antibiotics, expression of PcrV and Psl, and susceptibility to the anti-PcrV/Psl bispecific antibody and clinical candidate MEDI3902.


RESULTS
In-hospital mortality for patients with P. aeruginosa BSI was 39%. A total of 26% of isolates were resistant to ≥3 antibiotic classes. Although PcrV and/or Psl were detected in 99% of isolates, a majority of patients lacked active titers to PcrV (100%) and Psl (98%). In addition, MEDI3902 was active against all tested isolates.


CONCLUSIONS
A vast majority of P. aeruginosa BSI isolates express PcrV and Psl; however, patient sera most often lacked IgG and functionally active responses to these targets. These results suggest that therapies directed at PcrV and Psl could be a promising approach for combating P. aeruginosa bloodstream infections.
Division of Infectious Diseases, Duke University, Durham, North Carolina.
Joshua T
JT
Thaden
MedImmune, LLC, Gaithersburg, Maryland.
Ashley E
AE
Keller
MedImmune, LLC, Gaithersburg, Maryland.
Norah J
NJ
Shire
MedImmune, LLC, Gaithersburg, Maryland.
M Margarita
MM
Camara
Astrazeneca, Waltham, Massachusetts.
Linda
L
Otterson
Astrazeneca, Waltham, Massachusetts.
Mike
M
Huband
MedImmune, LLC, Gaithersburg, Maryland.
Caitlin M
CM
Guenther
MedImmune, LLC, Gaithersburg, Maryland.
Wei
W
Zhao
MedImmune, LLC, Gaithersburg, Maryland.
Paul
P
Warrener
MedImmune, LLC, Gaithersburg, Maryland.
C Kendall
CK
Stover
Division of Infectious Diseases, Duke University, Durham, North Carolina.
Vance G
VG
Fowler
MedImmune, LLC, Gaithersburg, Maryland.
Antonio
A
DiGiandomenico
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000097:blood*; D000920:Antibody-Dependent Cell Cytotoxicity; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D009895:Opsonin Proteins
Pseudomonas aeruginosa; Psl exopolysaccharide; bacteremia; bispecific antibody; prophylaxis; type 3 secretion