Procalcitonin and Endotoxin Sequential Levels to Optimize the Treatment of Bloodstream Infections

NCT00870623 | Completed

• 1 other identifier: 0540-08-FB
• Study Type: observational
• Target: 223
• Locations: 1 country
• Sites: 1

Brief Summary

Bloodstream infections (BSI) are a major cause of morbidity and mortality. Bloodstream infections are also costly and result in prolonged hospital stays. The duration of therapy necessary to clear blood stream infections is unknown and no study has systematically addressed this issue. However, the use of antimicrobials is not without consequence. These include financial cost, side-effects, promotion of superinfection (especially Clostridium difficile-associated diarrhea), and the promotion of microbial resistance. This study hypothesizes that a procalcitonin (host biomarker) and endotoxin (microorganism biomarker) guided treatment plan could significantly decrease unnecessary exposure to antibiotics in patients with bloodstream infections.

Conditions

Bloodstream Infection

Outcome Measures

Primary Outcomes (1)

• Optimal length of treatment

  To determine the optimal length of treatment by observing the normalization of procalcitonin (PCT) and Endotoxin levels, compared with the length of treatment by standard of care.

  30 days

Secondary Outcomes (1)

• Association of procalcitonin and endotoxin levels and outcomes

  30 days

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Hospitalized adult patients with positive blood cultures

You may qualify if:

• Hospitalized, adult patient, at least one positive blood culture reported within 24 hours of enrollment

You may not qualify if:

• Previously enrolled in the study; discharged/deceased before first positive culture; receiving antibiotic for greater than or equal to 48 hours; endocarditis or osteomyelitis; antithymocyte globulin in the last 12 months; blood cultures positive for coagulase-negative staphylococcus only.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

Unversity of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (26)

• Diekema DJ, Beekmann SE, Chapin KC, Morel KA, Munson E, Doern GV. Epidemiology and outcome of nosocomial and community-onset bloodstream infection. J Clin Microbiol. 2003 Aug;41(8):3655-60. doi: 10.1128/JCM.41.8.3655-3660.2003.

  PMID: 12904371 BACKGROUND

• Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 1;39(3):309-17. doi: 10.1086/421946. Epub 2004 Jul 15.

  PMID: 15306996 BACKGROUND

• Laupland KB, Gregson DB, Flemons WW, Hawkins D, Ross T, Church DL. Burden of community-onset bloodstream infection: a population-based assessment. Epidemiol Infect. 2007 Aug;135(6):1037-42. doi: 10.1017/S0950268806007631. Epub 2006 Dec 7.

  PMID: 17156500 BACKGROUND

• Shorr AF, Tabak YP, Killian AD, Gupta V, Liu LZ, Kollef MH. Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database. Crit Care Med. 2006 Oct;34(10):2588-95. doi: 10.1097/01.CCM.0000239121.09533.09.

  PMID: 16915117 BACKGROUND

• Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable mortality and costs of primary nosocomial bloodstream infections in the intensive care unit. Am J Respir Crit Care Med. 1999 Sep;160(3):976-81. doi: 10.1164/ajrccm.160.3.9808145.

  PMID: 10471627 BACKGROUND

• Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ. Attributable cost of catheter-associated bloodstream infections among intensive care patients in a nonteaching hospital. Crit Care Med. 2006 Aug;34(8):2084-9. doi: 10.1097/01.CCM.0000227648.15804.2D.

  PMID: 16763511 BACKGROUND

• Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality. JAMA. 1994 May 25;271(20):1598-601. doi: 10.1001/jama.271.20.1598.

  PMID: 8182812 BACKGROUND

• Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, Craven DE; Infectious Diseases Society of America; American College of Critical Care Medicine; Society for Healthcare Epidemiology of America. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis. 2001 May 1;32(9):1249-72. doi: 10.1086/320001. Epub 2001 Apr 3. No abstract available.

  PMID: 11303260 BACKGROUND

• Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; 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 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available.

  PMID: 17278083 BACKGROUND

• Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999 Oct;29(4):745-58. doi: 10.1086/520427.

  PMID: 10589881 BACKGROUND

• Corona A, Bertolini G, Ricotta AM, Wilson A, Singer M. Variability of treatment duration for bacteraemia in the critically ill: a multinational survey. J Antimicrob Chemother. 2003 Nov;52(5):849-52. doi: 10.1093/jac/dkg447. Epub 2003 Sep 30.

  PMID: 14519681 BACKGROUND

• Corona A, Wilson AP, Grassi M, Singer M. Prospective audit of bacteraemia management in a university hospital ICU using a general strategy of short-course monotherapy. J Antimicrob Chemother. 2004 Oct;54(4):809-17. doi: 10.1093/jac/dkh416. Epub 2004 Sep 16.

  PMID: 15375106 BACKGROUND

• Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis. 2008 Feb 15;46(4):491-6. doi: 10.1086/526535.

  PMID: 18194098 BACKGROUND

• Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21;363(9409):600-7. doi: 10.1016/S0140-6736(04)15591-8.

  PMID: 14987884 BACKGROUND

• Christ-Crain M, Stolz D, Bingisser R, Muller C, Miedinger D, Huber PR, Zimmerli W, Harbarth S, Tamm M, Muller B. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1;174(1):84-93. doi: 10.1164/rccm.200512-1922OC. Epub 2006 Apr 7.

  PMID: 16603606 BACKGROUND

• Stolz D, Christ-Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007 Jan;131(1):9-19. doi: 10.1378/chest.06-1500.

  PMID: 17218551 BACKGROUND

• Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008 Mar 1;177(5):498-505. doi: 10.1164/rccm.200708-1238OC. Epub 2007 Dec 20.

  PMID: 18096708 BACKGROUND

• Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007 Mar;7(3):210-7. doi: 10.1016/S1473-3099(07)70052-X.

  PMID: 17317602 BACKGROUND

• Giamarellos-Bourboulis EJ, Grecka P, Poulakou G, Anargyrou K, Katsilambros N, Giamarellou H. Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia. Clin Infect Dis. 2001 Jun 15;32(12):1718-25. doi: 10.1086/320744. Epub 2001 May 21.

  PMID: 11360214 BACKGROUND

• Jensen JU, Heslet L, Jensen TH, Espersen K, Steffensen P, Tvede M. Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med. 2006 Oct;34(10):2596-602. doi: 10.1097/01.CCM.0000239116.01855.61.

  PMID: 16915118 BACKGROUND

• Romaschin AD, Harris DM, Ribeiro MB, Paice J, Foster DM, Walker PM, Marshall JC. A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence. J Immunol Methods. 1998 Mar 15;212(2):169-85. doi: 10.1016/s0022-1759(98)00003-9.

  PMID: 9672205 BACKGROUND

• Marshall JC, Walker PM, Foster DM, Harris D, Ribeiro M, Paice J, Romaschin AD, Derzko AN. Measurement of endotoxin activity in critically ill patients using whole blood neutrophil dependent chemiluminescence. Crit Care. 2002 Aug;6(4):342-8. doi: 10.1186/cc1522. Epub 2002 May 2.

  PMID: 12225611 BACKGROUND

• Marshall JC, Foster D, Vincent JL, Cook DJ, Cohen J, Dellinger RP, Opal S, Abraham E, Brett SJ, Smith T, Mehta S, Derzko A, Romaschin A; MEDIC study. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis. 2004 Aug 1;190(3):527-34. doi: 10.1086/422254. Epub 2004 Jul 2.

  PMID: 15243928 BACKGROUND

• Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA. 1995 Jul 5;274(1):29-34.

  PMID: 7791255 BACKGROUND

• McFarland LV, Clarridge JE, Beneda HW, Raugi GJ. Fluoroquinolone use and risk factors for Clostridium difficile-associated disease within a Veterans Administration health care system. Clin Infect Dis. 2007 Nov 1;45(9):1141-51. doi: 10.1086/522187. Epub 2007 Sep 26.

  PMID: 17918075 BACKGROUND

• Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588.

  PMID: 14625336 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood (maximum 40mL) will be collected for future use or for purposes that are not integral to the current research.

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andre Kalil, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2009
• First Posted: March 27, 2009
• Study Start: June 1, 2009
• Primary Completion: January 13, 2016
• Study Completion: January 13, 2016
• Last Updated: September 15, 2023

Record last verified: 2023-09

Locations

US (1)