Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized with Pseudomonas aeruginosa: A randomized,double-blind, placebo-controlled trial

Critical Care Medicine

Volumn 40, Issue 8, 2012, Pages 2320-2326

  François, Bruno ^a   Luyt, Charles Edouard ^b   Dugard, Anthony ^a   Wolff, Michel ^c   Diehl, Jean Luc ^c   Jaber, Samir ^d   Forel, Jean Marie ^e   Garot, Denis ^f   Kipnis, Eric ^g   Mebazaa, Alexandre ^a   Misset, Benoit ^c   Andremont, Antoine ^c   Ploy, Marie Cécile ^c   Jacobs, Alan ^h   Yarranton, Geoffrey ^h   Pearce, Tillman ⁱ   Fagon, Jean Yves ^c   Chastre, Jean ^b  

^a DUPUYTREN UNIVERSITY HOSPITAL   (France)

^b SORBONNE UNIVERSITÉ   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d HÔPITAL SAINT ELOI   (France)

^e HÔPITAL SAINTE MARGUERITE   (France)

^f CHU BRETONNEAU   (France)

^g UNIV LILLE   (France)

^h LIMOGES UNIVERSITY HOSPITAL   (France)

ⁱ KaloBios Inc   (United States)

Author keywords

intensive care unit; monoclonal antibody; prevention; Pseudomonas aeruginosa; type III secretion system; ventilator associated pneumonia

Indexed keywords

KB 001; MONOCLONAL ANTIBODY; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ARTIFICIAL VENTILATION; BACTERIAL COLONIZATION; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DISTRIBUTION VOLUME; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ENDOTRACHEAL TUBE; FEMALE; HUMAN; INTENSIVE CARE UNIT; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS PNEUMONIA; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; PNEUMONIA, VENTILATOR-ASSOCIATED; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS; YOUNG ADULT;

EID: 84864289317     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0b013e31825334f6     Document Type: Article

References (51)

1. Niederman MS, Craven DE, Bonten MJ, et al: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388-416.
2. Chastre J, Fagon JY: Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:867-903. (Pubitemid 34774654)
3. Fujitani S, Sun HY, Yu VL, et al: Pneumonia due to Pseudomonas aeruginosa: Part I: Epidemiology, clinical diagnosis, and source. Chest 2011; 139:909-919.
4. Combes A, Luyt CE, Fagon JY, et al: Early predictors for infection recurrence and death in patients with ventilator-associated pneumonia. Crit Care Med 2007; 35:146-154. (Pubitemid 46035690)
5. Crouch Brewer S, Wunderink RG, Jones CB, et al: Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest 1996; 109:1019-1029. (Pubitemid 26113647)
6. Nicasio AM, Kuti JL, Nicolau DP: The current state of multidrug-resistant gram-negative bacilli in North America. Pharmacotherapy 2008; 28:235-249.
7. Zavascki AP, Carvalhaes CG, Picäo RC, et al: Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: Resistance mechanisms and implications for therapy. Expert Rev Anti Infect Ther 2010; 8:71-93.
8. Sun HY, Fujitani S, Quintiliani R, et al: Pneumonia due to Pseudomonas aeruginosa: Part II: Antimicrobial resistance, pharmacodynamic concepts, and antibiotic therapy. Chest 2011; 139:1172-1185.
9. Lautenbach E, Synnestvedt M, Weiner MG, et al: Imipenem resistance in Pseudomonas aeruginosa: Emergence, epidemiology, and impact on clinical and economic outcomes. Infect Control Hosp Epidemiol 2010; 31:47-53.
10. Jones RN: Microbial etiologies of hospitalacquired bacterial pneumonia and ventilatorassociated bacterial pneumonia. Clin Infect Dis 2010; 51 Suppl 1:S81-S87.
11. Clatworthy AE, Pierson E, Hung DT: Targeting virulence: A new paradigm for antimicrobial therapy. Nat Chem Biol 2007; 3: 541-548. (Pubitemid 47294400)
12. Veesenmeyer JL, Hauser AR, Lisboa T, et al: Pseudomonas aeruginosa virulence and therapy: Evolving translational strategies. Crit Care Med 2009; 37:1777-1786.
13. Vance RE, Rietsch A, Mekalanos JJ: Role of the type III secreted exoenzymes S, T, and Y in systemic spread of Pseudomonas aeruginosa PAO1 in vivo. Infect Immun 2005; 73:1706-1713. (Pubitemid 40470759)
14. Coburn B, Sekirov I, Finlay BB: Type III secretion systems and disease. Clin Microbiol Rev 2007; 20:535-549. (Pubitemid 47623767)
15. Cornelis GR, Van Gijsegem F: Assembly and function of type III secretory systems. Annu Rev Microbiol 2000; 54:735-774.
16. Galán JE, Collmer A: Type III secretion machines: Bacterial devices for protein delivery into host cells. Science 1999; 284:1322-1328. (Pubitemid 29289652)
17. Hueck CJ: Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 1998; 62:379-433. (Pubitemid 28270280)
18. Roy-Burman A, Savel RH, Racine S, et al: Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis 2001; 183:1767-1774. (Pubitemid 32523239)
19. Hauser AR, Cobb E, Bodi M, et al: Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 2002; 30:521-528. (Pubitemid 34214611)
20. Sawa T, Ohara M, Kurahashi K, et al: In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung infections. Infect Immun 1998; 66:3242-3249. (Pubitemid 28303122)
21. Le Berre R, Nguyen S, Nowak E, et al: Pyopneumagen Group: Relative contribution of three main virulence factors in Pseudomonas aeruginosa pneumonia. Crit Care Med 2011; 39:2113-2120.
22. Finck-Barbançon V, Goranson J, Zhu L, et al: ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol Microbiol 1997; 25:547-557. (Pubitemid 27373583)
23. Yahr TL, Mende-Mueller LM, Friese MB, et al: Identification of type III secreted products of the Pseudomonas aeruginosa exoenzyme S regulon. J Bacteriol 1997; 179:7165-7168. (Pubitemid 27492504)
24. Yahr TL, Vallis AJ, Hancock MK, et al: ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginosa type III system. Proc Natl Acad Sci USA 1998; 95:13899-13904. (Pubitemid 28523070)
25. Diaz MH, Hauser AR: Pseudomonas aeruginosa cytotoxin ExoU is injected into phagocytic cells during acute pneumonia. Infect Immun 2010; 78:1447-1456.
26. Schulert GS, Feltman H, Rabin SD, et al: Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas aeruginosa isolates obtained from patients with hospital-acquired pneumonia. J Infect Dis 2003; 188:1695-1706. (Pubitemid 38010681)
27. Dacheux D, Goure J, Chabert J, et al: Poreforming activity of type III system-secreted proteins leads to oncosis of Pseudomonas aeruginosa-infected macrophages. Mol Microbiol 2001; 40:76-85. (Pubitemid 32322863)
28. Dacheux D, Toussaint B, Richard M, et al: Pseudomonas aeruginosa cystic fibrosis isolates induce rapid, type III secretiondependent, but ExoU-independent, oncosis of macrophages and polymorphonuclear neutrophils. Infect Immun 2000; 68:2916-2924. (Pubitemid 30253872)
29. Lynch SV, Flanagan JL, Sawa T, et al: Polymorphisms in the Pseudomonas aeruginosa type III secretion protein, PcrV -implications for anti-PcrV immunotherapy. Microb Pathog 2010; 48:197-204.
30. Faure K, Fujimoto J, Shimabukuro DW, et al: Effects of monoclonal anti-PcrV antibody on Pseudomonas aeruginosa-induced acute lung injury in a rat model. J Immune Based Ther Vaccines 2003; 1:2.
31. Frank DW, Vallis A, Wiener-Kronish JP, et al: Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV. J Infect Dis 2002; 186:64-73. (Pubitemid 34666915)
32. Neely AN, Holder IA, Wiener-Kronish JP, et al: Passive anti-PcrV treatment protects burned mice against Pseudomonas aeruginosa challenge. Burns 2005; 31:153-158. (Pubitemid 40430869)
33. Sawa T, Yahr TL, Ohara M, et al: Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nat Med 1999; 5:392-398. (Pubitemid 29180576)
34. Baer M, Sawa T, Flynn P, et al: An engineered human antibody fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent antibacterial activity. Infect Immun 2009; 77:1083-1090.
35. Shime N, Sawa T, Fujimoto J, et al: Therapeutic administration of anti-PcrV F(ab')(2) in sepsis associated with Pseudomonas aeruginosa. J Immunol 2001; 167:5880-5886. (Pubitemid 33062782)
36. Mandell LA, Wunderink RG, Anzueto A, et al: Infectious Diseases Society of America/ American Thoracic Society: Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(Suppl 2):S27-S72. (Pubitemid 46290553)
37. Masterton RG, Galloway A, French G, et al: Guidelines for the management of hospitalacquired pneumonia in the UK: Report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2008; 62:5-34. (Pubitemid 351865870)
38. Rello J, Lode H, Cornaglia G, et al: VAP Care Bundle Contributors: A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med 2010; 36:773-780.
39. Le Gall JR, Lemeshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993; 270:2957-2963. (Pubitemid 24000804)
40. Pugin J, Auckenthaler R, Mili N, et al: Diagnosis of ventilator- associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143(5 Pt 1):1121-1129.
41. Vincent JL, Moreno R, Takala J, et al: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/ failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22:707-710.
42. Jourdain B, Novara A, Joly-Guillou ML, et al: Role of quantitative cultures of endotracheal aspirates in the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med 1995; 152:241-246.
43. Chastre J, Trouillet JL, Combes A, et al: Diagnostic techniques and procedures for establishing the microbial etiology of ventilator-associated pneumonia for clinical trials: The pros for quantitative cultures. Clin Infect Dis 2010; 51(Suppl 1):S88-S92.
44. Meduri GU, Chastre J: The standardization of bronchoscopic techniques for ventilator-associated pneumonia. Chest 1992; 102:557S-564S.
45. Su YC, Chen BM, Chuang KH, et al: Sensitive quantification of PEGylated compounds by second-generation anti-poly(ethylene glycol) monoclonal antibodies. Bioconjug Chem 2010; 21:1264-1270.
46. Chastre J, Wolff M, Fagon JY, et al: PneumA Trial Group: Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: A randomized trial. JAMA 2003; 290:2588-2598. (Pubitemid 37443289)
47. Chapman AP: PEGylated antibodies and antibody fragments for improved therapy: A review. Adv Drug Deliv Rev 2002; 54:531-545. (Pubitemid 34615547)
48. Imamura Y, Yanagihara K, Fukuda Y, et al: Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model. Eur Respir J 2007; 29:965-968. (Pubitemid 46711902)
49. Moriyama K, Wiener-Kronish JP, Sawa T: Protective effects of affinity-purified antibody and truncated vaccines against Pseudomonas aeruginosa V-antigen in neutropenic mice. Microbiol Immunol 2009; 53:587-594.
50. Valcke Y, Pauwels R, Van der Straeten M: Pharmacokinetics of antibiotics in the lungs. Eur Respir J 1990; 3:715-722. (Pubitemid 20228711)
51. Cook D, Mandell L: Endotracheal aspiration in the diagnosis of ventilator-associated pneumonia. Chest 2000; 117(4 Suppl 2):195S-197S. (Pubitemid 30230858)