Procalcitonin-Guided Duration of Antimicrobial Therapy in Healthcare-Associated Pneumonia

1
Procalcitonin-Guided Duration of Antimicrobial
Therapy in Healthcare-Associated Pneumonia
Fatima Ali, Pharm.D.1, Jill Cwik, Pharm.D. 1,
Sarah M. Wieczorkiewicz, Pharm.D., BCPS1, and
Robert Citronberg, MD, FIDSA2 (1)Department of
Pharmacy, (2) Department of Infectious Diseases
Advocate Lutheran General Hospital
INTRODUCTION
RESULTS
BASELINE CHARACTERISTICS
Inclusion Criteria Exclusion Criteria
Age gt 18 years Suspected healthcare associated pneumonia (HCAP) Managed by participating physician Documented Pseudomonas aeruginosa infection Pregnancy Neutropenia Severe burns, mechanical or surgical trauma Rejection after transplantation Actively receiving TNF-alpha infusions

• Hospitalized patients are at increased risk for
  developing infections throughout their hospital
  stay. In particular, lower respiratory tract
  infections (LRTI) such as healthcare-associated
  pneumonia (HCAP) can result in significant
  morbidity and mortality. When there is omission
  or delay in antimicrobial therapy for bacterial
  infections, particularly pneumonia, the infection
  may progress to sepsis or septic shock, resulting
  in increased mortality. Approximately 75 of
  antimicrobials are prescribed for acute
  respiratory tract infections, despite the fact
  that the majority of these infections are viral
  in nature. As a result of antibiotic overuse,
  multidrug resistance to antimicrobials has become
  a rising concern. Due to the rising rates of
  antimicrobial resistance it is important to
  determine optimal duration of antimicrobial
  therapy to achieve clinical response.
• Antimicrobials are often initiated empirically,
  but de-escalation may be delayed because it takes
  an average of 48 to 72 hours for culture data to
  become finalized. As a result, biomarkers, such
  as white blood cell counts and C-reactive
  protein, are often utilized earlier in the course
  of an infection to indicate the presence of an
  infectious process. However, these biomarkers
  have poor specificity and sensitivity for
  detecting an infection in comparison to
  procalcitonin. In addition, currently, there are
  limited objective tools to help providers
  determine duration of therapy. Studies
  performed in patients with lower respiratory
  tract infections have shown that
  procalcitonin-guided antimicrobial therapy can
  significantly reduce duration of antimicrobial
  therapy by at least 2 days. PCT-guided therapy
  also has the potential to decrease resistance
  associated with antimicrobial overuse.
• Procalcitonin
• Precursor peptide of calcitonin hormone
• Specific for bacterial infection
• Correlates with severity of infection
• Assesses appropriateness of empiric antimicrobial
  therapy
• FDA approved for use in conjunction with other
  laboratory markers and clinical assessments for
  assessing the risk of patients for progression to
  severe sepsis and/or septic shock 

Prospective Group Subsequent PCT
Baseline Demographics Retrospective Group (n 48) Prospective Group (n 7)
Age (mean /- SD) 77 14 83 9
Male Gender, No. () 29 (60.4 ) 3 (42.9 )
Smoker, No. () 4 (8.3 ) 1(14.3 )
Signs/Symptoms, No. () Signs/Symptoms, No. () Signs/Symptoms, No. ()
Dyspnea 33 (68.8 ) 6 (85.7 )
Cough 34 (70.8 ) 4 (57.1 )
Productive sputum 15 (31.3 ) 1 (14.3 )
Past Medical History, No. () Past Medical History, No. () Past Medical History, No. ()
Hypertension 37 (77.1 ) 6 (85.7 )
Coronary artery disease 18 (37.5 ) 5 (71.4 )
Hyperlipidemia 18 (37.5 ) 3 (42.9 )
Congestive heart failure 17 (35.4) 2 (28.6 )
Diabetes Mellitus 22 (45.8 ) 2 (28.6 )
Chronic obstructive pulmonary disease 14 (29.2 ) 1 (14.3 )
Asthma 4 (8.3 ) 1 (14.3 )
Lutheran General Hospital PCT Guideline
Procalcitonin Level (mcg/L) Interpretation DISCONTINUATION of Antimicrobial Therapy
lt 0.1 Absence of an infection Strongly recommended
gt 0.1 and lt 0.25 Infection is unlikely Strongly recommended
0.25 and lt 0.5 Possible bacterial infection Recommended
gt 0.5 Suggestive of infection Discouraged
Endpoints Retrospective Group (n 48) Prospective Group (n 7) p-value
Primary Endpoints Primary Endpoints Primary Endpoints Primary Endpoints
Duration of antimicrobial therapy (days SD) 10 3.5 3.8 2.6 lt 0.001
Secondary Endpoints   Secondary Endpoints   Secondary Endpoints   Secondary Endpoints  
Hospital length of stay (days SD) 6.2 2.7 6.3 2.3 0.814
ICU length of stay (days SD) 0.8 2 2.5 1 lt 0.001
Mortality, No. () 4 (8.3 ) ------ ------
Respiratory Tract Infection Algorithm
Baseline Data Retrospective Group (n 48), Mean (range) Prospective Group (n 7), Mean (range)
WBC 12.1 x 103 cells/µL (3.8 27.2) 16.3 x 103 cells/µL (5.4 37.9)
BUN 28 (7 65) 35 (25 72)
SCr 1.65 mg/dL (0.54 8.75) 1.34 mg/dL (0.92 1.91)
BP 125/64 mmHg (90/40 186/89) 127/62 mmHg (105/45 160/79)
HR 89 bpm (54 137) 75 bpm (60 97)
RR 21 (16 33) 20 (15 27)
Tmax 37.4 0C (35.9 39.6) 37 0C (36 39.2)
Final decision to discontinue therapy at
discretion of treating physician and this
guideline does not supersede physicians clinical
judgment
Discontinuation may also be considered if PCT
level decreases gt 90 of peak PCT
LIMITATIONS
STUDY PATIENT POPULATION
CONFLICTING RECOMMENDATIONS

• Limited physician participation
• Overall adherence to PCT guideline 50

CONCLUSIONS
RESULTS

• PCT-guided group with decreased duration of
  antimicrobial therapy
• Early discontinuation of antimicrobials in
  non-infectious etiology based on low baseline PCT
  levels
• Evaluating baseline PCT should be considered in
  patients with an unclear, possible respiratory
  infectious etiology

METHODS
Prospective Group Baseline PCT

• The primary endpoint includes an evaluation of
  the difference in HCAP-related duration of
  antimicrobial therapy.
• The secondary endpoints include evaluating the
  effects of PCT-guided antimicrobial therapy on
  hospital length of stay (LOS), ICU LOS, and
  mortality.
• This study included two arms
• Retrospective arm
• Identified utilizing ICD-9 codes associated with
  HCAP
• Admitted between January 1, 2008 - October 31,
  2010
• Randomly selected utilizing an online
  randomization program
• Prospective arm
• Subjects identified between November 1, 2010
  -November 1, 2011
• Reviewing daily antimicrobial use report
• Pharmacists identified nursing home patients
  initiated on antimicrobial therapy in ED
• Eligible HCAP patients were enrolled if being
  treated by a participating physician
• Physicians of eligible patients were contacted to
  order PCT levels at baseline and on days 3, 5 and
  7 after initiation of antimicrobial therapy
• Recommendation for discontinuation of
  antimicrobial therapy based on PCT-guideline was
  relayed to the treating physicians

FUTURE DIRECTIONS

• Continue to enroll eligible HCAP patients
• Provide further education hospital-wide to
  increase physician participation

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