Jones & Bartlett Learning Medicine Blog

    Antibiotic Stewardship with the Aid of Procalcitonin Measurements

    Posted by Joseph Esherick on Aug 23, 2011 4:37:43 PM

    Dr. Joseph Esherick Monthly Blog – August 2011

    There has been considerable interest in antibiotic stewardship programs over the past decade given the increase in drug-resistant bacteria.  The best way to combat the problem of drug-resistant bacteria is to develop systems which discourage the inappropriate initiation of antibiotics or the unnecessary prolongation of antibiotics.  The measurement of serum procalcitonin levels can aid sound clinical judgment for decisions regarding proper antibiotic use.

    Procalcitonin, the precursor peptide of calcitonin, is released in response to a body’s exposure to bacterial antigens or toxins.  Furthermore, the procalcitonin levels are suppressed by exposure to cytokines activated during viral infections, namely interferon gamma.  We know that the level of procalcitonin elevation is directly correlated with the severity of the bacterial infection.[1] In addition, procalcitonin levels rise within 6-12 hours after symptom onset of bacterial infections and decrease by about 50% per day once a bacterial infection is under control.[2]

    A number of randomized controlled trials have led to the development of procalcitonin guided clinical algorithms for various infections which have been used throughout Europe.  These protocols have led to a marked reduction in the use of antibiotics in adult patients treated in a variety of clinical settings with no increase in mortality or morbidity...

    A recent systematic review of 14 randomized clinical trials has been published and has proposed procalcitonin-guided algorithms for use in the United States in primary care, emergency department, and ICU settings.[3]

    This systematic review included over 4,400 adult patients and two RCTs in the primary care setting, six RCTs in the emergency department setting, and five RCTs in the ICU setting.  The review found no difference in mortality or morbidity between the procalcitonin-guided treatment groups and the control treatment groups despite a reduction in antibiotic use of roughly 35% across the spectrum of clinical settings.

    The two randomized controlled trials in the primary care setting examined whether procalcitonin levels can guide therapy for upper and lower respiratory tract infections.  The study participants were all adults who presented to an ambulatory clinic with signs of an acute respiratory tract infection which could include rhinosinusitis, pharyngitis, tonsillitis, tracheobronchitis, otitis media, flu-like illness, a COPD exacerbation or community-acquired pneumonia (confirmed by chest radiograph).  They recommended against the use of antibiotics if the initial procalcitonin level was <0.25 µg/L and recommended the use of antibiotics if the procalcitonin level was ≥0.25 µg/L.  The  protocols resulted in a 57% reduction in the initiation of antibiotics with no change in clinical outcome.[4,5]

    The six randomized controlled trials in the emergency department setting examined whether procalcitonin levels can guide therapy for acute exacerbations of COPD or community-acquired pneumonia.  The patients enrolled had to have clinical signs of an acute respiratory tract infection and pneumonia was defined as a new infiltrate on chest radiograph.  The protocols recommended against initiation or for discontinuation of antibiotics if the procalcitonin level was <0.25 µg/L.  The protocols recommended the use of antibiotics if the procalcitonin level was ≥0.25 µg/L.  These protocols led to an 18% reduction in the initiation of antibiotics and a 34% reduction in the duration of antibiotic use with no difference in clinical outcome.[6,7,8,9]

    Finally, the five randomized controlled trials in the ICU setting examined whether procalcitonin levels can guide therapy for severe sepsis/septic shock, postop infections, or ventilator-associated pneumonia.  The protocols were more heterogeneous in this setting, but generally recommended discontinuation of antibiotics if the procalcitonin levels fell below 0.5 µg/L or fell by at least 80% of their peak levels.  The protocols resulted in a reduction in antibiotic duration of 32% with no change in clinical outcome.[10,11,12,13]

    The recommended procalcitonin-guided algorithms for use in the United States are summarized in the tables below:

    Management of Respiratory
    Tract Infections in the Primary Care Setting
    Procalcitonin (µg/L) <0.1 <0.25 0.25-0.5 >0.5
    Abx recommendation Strongly discouraged Discouraged Encouraged Strongly encouraged
    Overruling the algorithm Recommend antibiotic use if patients are clinically unstable, have
    strong evidence of pneumonia, have advanced COPD, or need hospitalization
    Management of Moderate-Acuity
    Respiratory Infections in the Hospital or ED Settings
    Initial Procalcitonin (µg/L) <0.1 <0.25 0.25-0.5 >0.5
    Abx recommendation Strongly discouraged Discouraged Encouraged Strongly encouraged
    Follow-up Procalcitonin q2-3d (µg/L) <0.1 <0.25 0.25-0.5 >0.5
    Stopping antibiotics Strongly encouraged Encouraged Discouraged Strongly discouraged
    Overruling the algorithm Consider antibiotics if patients are clinically unstable,
    immunosuppressed, have a high Pneumonia Severity Index, or strong evidence of
    a bacterial infection
    Management of High-Acuity
    Infections in the ICU (Sepsis or Pneumonia)
    Initial Procalcitonin (µg/L) <0.25 0.25-0.49 0.5-1 >1
    Abx recommendation Strongly discouraged Discouraged Encouraged Strongly encouraged
    Follow-up Procalcitonin q1-2d (µg/L) <0.25 or drop by >90% 0.25-0.49 or drop >80% 0.5-1 >1
    Stopping antibiotics Strongly encouraged Encouraged Discouraged Strongly discouraged
    Overruling the algorithm Consider continuation of antibiotics if patient is clinically unstable

    ___________________________________________________________

    Joseph Esherick, MD, FAAFP is the Associate Director of Medicine and the Medical ICU Director at the Ventura County Medical Center in Ventura, California.  He is also an Associate Clinical Professor of Family Medicine at The David Geffen School of Medicine at UCLA. He received his medical degree from Yale University School of Medicine, New Haven, Connecticut, and completed a family practice residency at the Ventura County Medical Center, Ventura, California. He is board certified in family medicine and the author of the Tarascon Primary Care Pocketbook and the Tarascon Hospital Medicine Pocketbook. He instructs the Hospitalist Procedures course for the National Procedures Institute and is an editorial board member for Tarascon Publishing and for Elsevier’s First Consult.

    Dr. Esherick is the author of some of Tarascon Publishing’s best-selling titles including:
    The recently published Tarascon Medical Procedures Pocketbook, Tarascon Hospital Medicine Pocketbook and Tarascon Primary Care Pocketbook. Both titles are available in print and mobile (iPhone, Android and Blackberry).

    ___________________________________________________________


    [1] Gogos CA et al. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000; 181 (11): 176-180.

    [2] Linscheid P et al.  Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullinn expression in human adipose tissue. Endocrinology. 2005; 146 (6): 2699-2708.

    [3] Schuetz P et al. Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms. Arch Intern Med. 2011; 171 (15): 1322-1331.

    [4] Briel M et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008; 168 (18): 2000-2007.

    [5] Burkhardt O et al. Procalcitonin guidance and reductions of antibiotic use in acute respiratory tract infection. Eur Resp J. 2010; 36 (3): 601-607.

    [6] Schuetz P et al. ProHOSP Study Group.  Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial.  JAMA. 2009; 302 (10): 1059-1066.

    [7] Christ-Crain et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster randomized, single-blinded intervention trial. Lancet. 2004; 363: 600-607.

    [8] Christ-Cain et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Resp Crit Care Med. 2006; 174 (1): 84-93.

    [9] Stolz D et al. Antibiotic treatment of exacerbation of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy.  Chest. 2007; 131(1): 9-19.

    [10] Nobre V et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Resp Crit Care Med. 2008; 177 (5): 498-505.

    [11] Stolz et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomized study. Eur Respir J. 2009; 34 (6): 1364-1375.

    [12] Hochreiter M et al. Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care. 2009; 13 (3): R83.

    [13] Bouadma L et al. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a muticentre randomized controlled trial. Lancet. 2010; 375 (9713): 463-474.

    Topics: Dr. Joseph Esherick, Authors, Prescribing, viral infection, antibiotic, Hospital Medicine Blog, drug-resistant bacteria, hospital medicine

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