Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients: A Randomized Trial

The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibio...

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Published in:	American journal of respiratory and critical care medicine Vol. 177; no. 5; pp. 498 - 505
Main Authors:	Nobre, Vandack, Harbarth, Stephan, Graf, Jean-Daniel, Rohner, Peter, Pugin, Jerome
Format:	Journal Article
Language:	English
Published:	New York, NY Am Thoracic Soc 01.03.2008 American Lung Association American Thoracic Society
Subjects:	Aged Aged, 80 and over Algorithms Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anti-Bacterial Agents - administration & dosage Antibacterial agents Antibiotics Antibiotics. Antiinfectious agents. Antiparasitic agents Antimicrobial agents Bacterial infections Biological and medical sciences Biomarkers Calcitonin - blood Calcitonin Gene-Related Peptide Clinical Protocols Critical Illness Female Glycoproteins - blood Humans Infections Intensive care Intensive care medicine Kaplan-Meier Estimate Length of Stay Male Medical sciences Middle Aged Patients Pharmacology. Drug treatments Pneumonia Protein Precursors - blood Recurrence Sepsis Sepsis - blood Sepsis - drug therapy Sepsis - mortality Shock, Septic - blood Shock, Septic - drug therapy Shock, Septic - mortality Human Infection Sepsis syndrome Antibiotic Intensive care Treatment controlled trial Procalcitonin antibiotics Resuscitation sepsis
ISSN:	1073-449X, 1535-4970, 1535-4970
Online Access:	Get full text
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Abstract	The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.
AbstractList	Rationale: The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. Objectives: To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes Methods: In patients with severe sepsis and septic shock. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 mu g/L) or Day 5 (if baseline PCT levels were greater than or equal to 1 mu g/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Measurements and Main Results: Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). Conclusions: Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm. The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm. The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.RATIONALEThe duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.OBJECTIVESTo test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.METHODSIn patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).MEASUREMENTS AND MAIN RESULTSPatients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.CONCLUSIONSOur results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm. The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03). Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.
Author	Rohner, Peter Nobre, Vandack Harbarth, Stephan Graf, Jean-Daniel Pugin, Jerome
Author_xml	– sequence: 1 fullname: Nobre, Vandack – sequence: 2 fullname: Harbarth, Stephan – sequence: 3 fullname: Graf, Jean-Daniel – sequence: 4 fullname: Rohner, Peter – sequence: 5 fullname: Pugin, Jerome
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SubjectTerms	Aged Aged, 80 and over Algorithms Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Anti-Bacterial Agents - administration & dosage Antibacterial agents Antibiotics Antibiotics. Antiinfectious agents. Antiparasitic agents Antimicrobial agents Bacterial infections Biological and medical sciences Biomarkers Calcitonin - blood Calcitonin Gene-Related Peptide Clinical Protocols Critical Illness Female Glycoproteins - blood Humans Infections Intensive care Intensive care medicine Kaplan-Meier Estimate Length of Stay Male Medical sciences Middle Aged Patients Pharmacology. Drug treatments Pneumonia Protein Precursors - blood Recurrence Sepsis Sepsis - blood Sepsis - drug therapy Sepsis - mortality Shock, Septic - blood Shock, Septic - drug therapy Shock, Septic - mortality
Title	Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients: A Randomized Trial
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