procalcitonin: Advancing Decision Making in sepsis Sean-Xavier Neath, M.D., Ph.D. Assistant Clinical Professor of Medicine Department of Emergency Medicine University of California, San Diego

Objectives Explore the scope of sepsis, its costs and effects on the healthcare system Identify the difficulties associated with the rapid diagnosis of sepsis with a focus on the differentiation of bacterial from non-bacterial causes of SIRS Utilize the performance characteristics of the biomarker procalcitonin (PCT) as a marker of sepsis or significant bacterial infection Interpret PCT levels and understand current PCT utilization in the hospital

Disclosures 1) Consultant relationships with biomedical companies working on biomarkers in acute disease states Thermo Fisher Scientific BRAHMS 2) Employed by the University of California, San Diego Medical Center as an Assistant Professor of Clinical Medicine, Department of Emergency Medicine  

What is Sepsis? Whole Body Inflammatory State plus Infection

Systemic Inflammatory Response Syndrome (SIRS) Systemic inflammatory response to a variety of severe clinical insults. Manifested by two or more of the following: Temperature >38ºC or <36ºC Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg WBC >12,000/mm3, <4000/mm3, or >10% immature (band) forms ACCP/SCCM Consensus Statement. Chest. 1992;101:1644-1655.

Sepsis: ACCP/SCCM Definitions Systemic response to infection – i.e., confirmed or suspected infection plus 2 SIRS criteria Severe Sepsis Sepsis associated with organ dysfunction, hypoperfusion, or hypotension Septic Shock Severe Sepsis that cannot be resuscitated or stabilized with IV fluids alone The American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) held a consensus conference in August 1991 to agree on a set of definitions that could be applied to patients with sepsis and organ dysfunction. The consensus panel also recommended the use of severity scoring methods to characterize the disease and develop a comprehensive model for the syndrome. This slide provides a brief definition of the various components of the sepsis syndrome. Notably, this is a non-linear process rather than a continuum, and the presence of organ dysfunction identifies a population with a significant risk of mortality. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644-1655. ACCP/SCCM Consensus Statement. Chest. 1992;101:1644.

SIRS Infection Sepsis Parasite Severe Sepsis Trauma Bacteria Burns Virus SIRS Sepsis Fungus shock Trauma Severe SIRS Bacteria BSI Burns Adapted from SCCM ACCP Consensus Guidelines

Population Adjusted Incidence of Sepsis (USA) Martin GS et al. NEJM 2003;348:1346

Cases of Sepsis by Pathogen (USA) Martin GS et al. NEJM 2003;348:1346

Infection Source in Severe Sepsis Angus DC et al. Crit Care Med. 2001; 29:1303

Determinants of Mortality Source control is most vital factor Resuscitation/re-establish perfusion in 6 hrs Appropriate antibiotic therapy within 1 hr of hypotension

Treatment of Septic Shock Source Control When Possible Based on Early Goal Directed Therapy Broad, high dose, rapid administration of antibiotics Consider Activated Protein C Minimal role for steroids Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock, 2008. Critical Care Med

Difficulties in Diagnosis and Treating Sepsis in the Emergency Department Differentiation between sepsis and non-infectious causes of SIRS is complicated The large number of patients presenting to the ER at the same time can limit the ability to obtain comprehensive histories and physical examinations

Difficulties in Diagnosis and Treating Sepsis in the Emergency Department Scoring systems and commonly available diagnostic tools provide limited value in determining which patients will have a poor outcome Initial vital signs can be incomplete, an accurate core temperature can be lacking These limitations often result in the delayed diagnosis of sepsis which in turn delays treatment, increases hospital length-of-stay, increases costs and leads to increased preventable mortality

Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock Kumar A. et al., Crit Care Med 2006, 34:1286

Failure to Intervene Quickly Can Be Fatal N=511 over 7 yrs. 2.5 years before MET and 5 yrs after MET. Before/after study design Time to shock alert = RRT activation Sebat CCM 2007; 35: 2568

Key Areas of Sepsis Management Initial Resuscitation Diagnosis Antibiotic therapy Source Control Fluid therapy Vasopressors Inotropic Therapy Steroids Recombinant Human Activated Protein C (rhAPC) [drotrecogin alfa (activated)] Blood Product Administration Mechanical Ventilation Sedation, Analgesia, and Neuromuscular Blockade in Sepsis Glucose Control Renal Replacement Bicarbonate Therapy Deep Vein Thrombosis Prophylaxis Stress Ulcer Prophylaxis Limitation of Support This index list also provides a means to quickly link to the specific slides related to the topic. Click on the subject when the slide is in the “show” mode and the slides automatically advances to the first slide of that specific guideline. Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Role of Procalcitonin in initial Sepsis management

Why Procalcitonin? Integrated use of PCT with other clinical and laboratory information permits: Increased accuracy of clinical diagnosis of relevant bacterial infection / sepsis Improved clinical decision making and patient management

Procalcitonin – A biomarker for the assessment of critically ill patients at risk for severe bacterial infection and sepsis Simple blood test specific for bacterial infection During severe bacterial infections and sepsis, blood levels rise rapidly (up to x100K) – no elevation from viral infections Is the Standard of Care for much of Europe in the management of infection and sepsis Morgenthaler N. et al., Clin Lab 2002, 48: 263-270

Procalcitonin – normally an intermediate product in the synthesis of Calcitonin Thyroid After P. Linscheid, Endocrinology 2003 Site of synthesis for PCT in healthy persons are the C-cells of the thyroid. Expression of CT-mRNA takes place only in the neuroendocrine cells. Release occurs in the form of the posttranslational processed hormone Calcitonin enclosed in Golgi vesicles. This hormone plays an important role in the pathway and regulation of calcium and phosphate in the bone metabolism. N-Pro Calcitonin Katacalcin N C 1 57 60 91 96 116 LOW PCT values in the blood of healthy persons: 46.7 pg/ml (97.5 percentile); median = 12.7 pg/ml* Morgenthaler N. et al., Clin Lab 2002, 48: 263-270

Procalcitonin – Presence of Bacterial Infection Stimulates PCT Production Linscheid et al. 2004 described the mechanism of the biochemical pathway and site of synthesis of PCT after bacterial infection. They investigated which factors affected the synthesis. Results show that in case of bacterial infection two mechanisms of synthesis are at work. At first cytokine-stimulated adherent monocytes release PCT in low quantities (<2h). This synthesis is limited. But it plays an important role in the initiation of PCT synthesis in storage tissues of humans. This PCT burst is initiated in all storage tissues (>18h). Parenchymal tissue is the most common type of tissue in the human organism. This explains why extreme concentrations of PCT can be generated (100.000 fold increase in contrast to physiological concentrations). The PCT burst continues as long as the stimulus for synthesis exists. In additional experiments it was clarified why PCT is only synthesized during bacterial but not in viral infections. Cells were incubated on one hand with IL-1β and on the other hand with IL-1β and INF-γ. The results showed that cells treated with both cytokines do not synthesize PCT. The conclusion was that cells infected by viruses released INF-γ. This cytokine has a direct influence on the synthesis of PCT. These findings led to the explanation of the fact that PCT is a perfect tool to differentiate between viral and bacterial infections (e.g. Gendrel et al. 1999). Alternative synthesis of PCT Bacterial toxins (gram+/-) and cytokines stimulate production of PCT in all parenchymal tissues PCT is immediately released into bloodstream This process can be blocked during viral infections Adapted from Christ-Crain et al. 2005

Highly specific induction and release of PCT due to bacterial infection Calcitonin: Sources of production in healthy people Healthy Sepsis PCT: Sources of Production in Septic Patients In bacterial infection, PCT is produced and released into circulation from the entire body Müller B. et al., JCEM 2001

PCT Level Increase = Increased Significance of Bacterial Infection In critically ill patients, PCT levels elevate in correlation to the severity of bacterial infection In healthy people, PCT concentration are found below 0.05ng/ml Concentrations exceeding 0.5ng/ml can be interpreted as abnormal

Highly specific induction and release of PCT due to bacterial infection Linscheid et al. 2004 described the mechanism of the biochemical pathway and site of synthesis of PCT after bacterial infection. They investigated which factors affected the synthesis. Results show that in case of bacterial infection two mechanisms of synthesis are at work. At first cytokine-stimulated adherent monocytes release PCT in low quantities (<2h). This synthesis is limited. But it plays an important role in the initiation of PCT synthesis in storage tissues of humans. This PCT burst is initiated in all storage tissues (>18h). Parenchymal tissue is the most common type of tissue in the human organism. This explains why extreme concentrations of PCT can be generated (100.000 fold increase in contrast to physiological concentrations). The PCT burst continues as long as the stimulus for synthesis exists. In additional experiments it was clarified why PCT is only synthesized during bacterial but not in viral infections. Cells were incubated on one hand with IL-1β and on the other hand with IL-1β and INF-γ. The results showed that cells treated with both cytokines do not synthesize PCT. The conclusion was that cells infected by viruses released INF-γ. This cytokine has a direct influence on the synthesis of PCT. These findings led to the explanation of the fact that PCT is a perfect tool to differentiate between viral and bacterial infections (e.g. Gendrel et al. 1999). IFN- released in viral infection, blocks the activation of PCT production, therefore in viral infection PCT levels remain normally low Adapted from Christ-Crain et al. 2005

Benefits and limitations of other Sepsis diagnostic tools Microbiology (Blood Culture) Standard of care, time to result, ?Sens., ? Spec. Availability, costs, variability of source detection Imaging (X-Ray, Hr-CT) Molecular Biological Testing Availability, costs, time to results Biopsy Invasive, relatively expensive Easy to measure, not invasive, relatively inexpensive Biomarker Testing (PCT) Slow kinetics , high impact of inflammation (specificity), suppressed by corticosteroids, relatively inexpensive C-Reactive Protein (CRP)

Diagnostic accuracy of PCT compared to other biomarkers used in sepsis Sensitivity: 89% Specificity: 94% NPV: 90% / PPV: 94% PCT levels accurately differentiate sepsis from noninfectious inflammation* PCT has been demonstrated to be the best marker for differentiating patients with sepsis from those with systemic inflammatory reaction not related to infectious cause Simon L. et al. Clin Infect Dis. 2004; 39:206-217.

Adding PCT results to clinical assessment improves the accuracy of the early clinical diagnosis of sepsis AUC with PCT: 0.94 AUC without PCT: 0.74 When PCT is used as a reference, the sensitivity and specificity of sepsis diagnosis can be significantly increased compared with conventional clinical parameters. Harbarth S et.al. AM J Resp Crit Care Med. 2001; 164:396-402

PCT levels increase according to severity of sepsis PCT can aid in the diagnosis and severity stratification in patients suspected of sepsis, severe sepsis, and septic shock. In multiple studies, PCT has demonstrated a high sensitivity and specificity for the differentiation of sepsis from SIRS (Systemic Inflammatory Response Syndrome) PCT levels can be useful for the management of patients after surgery or transplant and in peritonitis Harbarth S et al. Am J Respir Crit Care Med 2001, 164: 396-402 ; Meisner M et al., Critical Care 1999, 3(1): 45-50 ; Krüger S. et al., Eur Respir J 2008; 31: 349–355

Adding PCT results to clinical assessment improves the accuracy of the early clinical diagnosis of infection post organ transplant PCT plasma concentrations in 16 patients without postoperative complications after Liver-Transplantation, Tx: day of transplantation. PCT plasma concentrations in infection and rejection (n = 11), day 0: day of diagnosis PCT used in early detection of infection after liver transplantation – differentiation from rejection Kuse ER et al., Crit Care Med 2000; 28: 555-559

PCT kinetics provide important information on prognosis of sepsis patients Clinical symptoms alone are often insufficient for early and accurate diagnosis PCT levels, can be observed within 3-6 hours after an infectious challenge with a peak - up to 1000 ng/ml - after 6-12 hrs. Half-life: ~24hrs Specific to bacterial origin of infection and reflects the severity of the infection Brunkhorst FM et al., Intens. Care Med (1998) 24: 888-892

Interpreting Procalcitonin values

PCT release in the absence of infection Newborn < 48hr - increased PCT values (physiological peak) On 3rd day after birth, normal adult reference ranges apply Primary inflammation syndrome following trauma: multiple trauma, extensive burns, major surgery (cardiac, transplant, abdominal) Rapid decrease (half-life 24hr) in the absence of bacterial infection Medullary C-cell cancers of the thyroid, pulmonary small-cell carcinoma and bronchial carcinoma Prolonged circulatory failure (e.g.. cardiogenic shock, hemorrhagic shock, thermal shock) Treatments that can cause a cytokine storm e.g. OKT3, anti-lymphocyte globulins, etc.

Adding PCT results to clinical assessment improves the accuracy of the early clinical diagnosis of sepsis in Neonates UNINFECTED INFECTED PCT (ng/ml) PCT (ng/ml) Time (hours) Time (hours) In early onset neonatal sepsis PCT provides a clear differentiation of infected from uninfected neonates in the first 2 days of life In neonates the PCT values are physiologically and in relation to their age increased. A peak is reached at 24 h with Median at 2 ng/ml and 95%-Percentile at 20 ng/ml. After 3 days the normal values for children and adults apply. C Chiesa et al. CID 1997

Low PCT levels in the presence of bacterial infection may occur: Conditions of bacterial infection where PCT may be low in the presence of bacterial infection Low PCT levels in the presence of bacterial infection may occur: Early course of infection: Re-measure in 6-12hrs Subacute Endocarditis Localized infections

Interpretation of PCT levels PCT values must always be interpreted within the clinical context of each individual patient Serial measurement is preferred to assess the situation in real-time Always pay attention to conditions that may influence the PCT level Always consider the dynamics of the disease process (which affect onset of PCT production)

PCT kinetics after an infectious challenge Brunkhorst FM et al., Intens. Care Med (1998) 24: 888-892 What is so special about PCT? Highly specific induction due to bacterial infection Rapid increase (more rapid compared to CRP) Correlation to severity of disease Enormeous magnitude of elevation that can be reached (up to 105 compared to healthy; other parameters: magnitude 10-100fold ) Half life of ~24 h Can be used also in patients with renal insufficiency Easy to measure Rapid kinetics: detectable 3 hours after infection has begun, with a peak after 6-12 hrs. Peak values up to 1000 ng/ml Half-life: ~ to 24 hrs Non or minor dependence on renal function Brunkhorst FM et al., Intens. Care Med (1998) 24: 888-892

PCT reflects the response of the organism to the bacterial challenge Elevated / rising PCT levels Systemic response to the infection - indicates that infection is developing or is outside the control of the immune system Risk for further progression Low PCT levels despite clinical signs and symptoms Self-limiting bacterial infection Non-infectious cause Early phase of infection

Procalcitonin utilization to improve patient care in the hospital

No PCT increase in bacterial contamination, only in real bacterial infection In addition to clinical and microbiological parameters, PCT may help discriminate blood stream infections from blood culture contamination due to coagulase-negative staphylococci At a cut-off of 0.1ng/ml sensitivities and specificities were Day –1 of BC: 86% and 60% Day 0 of BC: 100% and 86% CRP could discriminate only on day +1, but not as clear-cut as PCT Schuetz P. et al., Infection 2007;35 (5): 352-5

PCT levels predict bacteremia in patients with community acquire pneumonia (CAP) Current guidelines recommend blood culture sampling from hospitalized patients with suspected CAP. Is there a way to reduce the patient harm, costs and errors associated with these recommendations? Prospective cohort study with derivation and validation set including 925 patients with CAP who underwent blood culture sampling on hospital admission. Muller et al. CHEST July 2010

PCT predicts bacteremia in patients with CAP: patient flow in derivation and validation cohorts Muller et al. CHEST July 2010

PCT cutoff of 0. 1 enables reduction of blood cultures by 12 PCT cutoff of 0.1 enables reduction of blood cultures by 12.6% and identifies 99% of Positive Blood Cultures Muller et al. CHEST July 2010

PCT levels predict bacteremia in patients with community acquire pneumonia PCT levels accurately predicted blood culture positivity in patients with CAP. PCT measurement demonstrated the potential to reduce the number of blood cultures drawn in the ED to better implement resources The use of PCT in targeting rational blood culture utilization allows for more directing allocation of limited health-care resources. Muller et al. CHEST July 2010

Procalcitonin correlates to the severity of the infection/sepsis Organ Dysfunction Pneumonia Harbarth S et al. Am J Respir Crit Care Med 2001, 164: 396-402 Meisner M et al., Critical Care 1999, 3(1): 45-50 Krüger S. et al., Eur Respir J 2008; 31: 349–355

PCT results provide important information on prognosis of CAP patients in emergency room PCT can be used for Risk stratification of patients with CAP Low PCT levels identify patients presenting in the ED with Pneumonia that have a low risk for mortality (N=1,651). Huang, et.al., Annals of Emergency Medicine, Vol 51, March 2008

Serial measurement of PCT provides a clearer picture of the patient’s response to antibiotic treatment. Decreasing PCT levels in patients with sepsis indicate effective treatment of the underlying infection Persistently elevated PCT levels indicate a possible treatment failure When integrated into the management of septic patients, PCT can help clinicians to manage septic patients more efficiently Stueber, F. University of Bonn, Lecture at ISICEM, Brussels 2001

PCT guidance in antibiotic usage Effects on length of stay Effect of PCT-guided management in patients with sepsis on ICU length of stay Nobre V. et alAM Resp Crit Care Med 2008: 177:498-505

Pct Guidance on effect on length of icu stay Effect of PCT-guided management in patients with sepsis on ICU length of stay Nobre V. et alAM Resp Crit Care Med 2008: 177:498-505

PCT guidance in antibiotic usage has been shown to significantly shorten the time patients need to be on antibiotics KEY TAKEAWAY: Tailoring of AB treatment using PCT to the individual patient needs safely led to a reduction of average treatment duration from 12 to 5 days with same outcome Nobre V. et al AM Resp Crit Care Med 2008: 177:498-505

Schuetz P et al. J Am Med Assoc. 2009;302:1059-66. Effect of PCT testing on Antibiotic use – a multicenter, randomized control trial The ProHOSP Trial Lower respiratory tract infections (LRTI) Most frequent indication for antibiotic prescriptions in the Northwestern hemisphere 75% of patients are treated with antibiotics Predominantly viral origin of infection Procalcitonin (PCT) algorithm Reduced antibiotic use in patients with LRTIs Effect of Procalcitonin-Based Guidelines vs. Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections: The ProHOSP Randomized Controlled Trial Schuetz P et al. J Am Med Assoc. 2009;302:1059-66.

Schuetz P et al. J Am Med Assoc. 2009;302:1059-66. Study Design Multicenter, noninferiority, randomized controlled trial Patients Randomized to administration of antibiotics based on PCT algorithm Cutoff ranges for initiating or stopping antibiotics (PCT group) or standard guidelines (control) Serum PCT was measured locally Main Outcome Measures Composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection within 30 days Antibiotic exposure and adverse effects from antibiotics Schuetz P et al. J Am Med Assoc. 2009;302:1059-66.

PCT Control Risk Difference, % Group Group Group (95% CI) Rates of Combined Adverse Outcomes and Mortality by Randomization Group No. (%) of Patients PCT Control Risk Difference, % Group Group Group (95% CI) All patients (intention-to-treat) (n = 671) (n = 688) Overall adverse outcome 103 (15.4) 130 (18.9) −3.5 (−7.6 to 0.4) Death 34 (5.1) 33 (4.8) 0.3 (−2.1 to 2.5) ICU admission 43 (6.4) 60 (8.7) −2.3 (−5.2 to 0.4) Recurrence/rehospitalization 25 (3.7) 45 (6.5) −2.8 (−5.1 to −0.4) Per-protocol population (n = 633) (n = 650) Overall adverse outcome 95 (15.0) 123 (18.9) −3.9 (−8.2 to 0.03) Death 29 (4.6) 31 (4.8) −0.2 (−2.6 to 2.0) Community-acquired pneumonia (n = 460) (n = 465) Overall adverse outcome 74 (16.1) 94 (20.2) −4.1 (−9.1 to 0.9) Death 24 (5.2) 26 (5.6) −0.4 (−3.3 to 2.6) Schuetz P et al. J Am Med Assoc. 2009;302(10):1059-66.

Antibiotic Exposure in Patients Receiving Antibiotic Therapy PCT Control All Patients (n = 1359) Community-acquired Pneumonia (n = 925) 100 80 Patients Receiving Antibiotic Therapy, % 60 40 20 0 1 2 5 7 9 11 >13 0 1 2 5 7 9 11 >13 Time After Study Inclusion, d Time After Study Inclusion, d No. of Patients PCT 506 484 410 306 207 138 72 46 Control 603 589 562 516 420 324 157 100 417 410 359 272 161 126 64 41 461 453 444 428 361 292 146 91 Schuetz P et al. J Am Med Assoc. 2009;302(10):1059-66.

Antibiotic Exposure in Patients Receiving Antibiotic Therapy PCT Control Exacerbation of COPD (n = 228) Acute Bronchitis (n = 151) 100 80 Patients Receiving Antibiotic Therapy, % 60 40 20 0 1 2 5 7 9 11 >13 0 1 2 5 7 9 11 >13 Time After Study Inclusion, d Time After Study Inclusion, d No. of Patients PCT 56 47 30 23 16 6 4 2 Control 79 78 67 56 40 20 5 4 16 11 9 3 3 1 1 1 41 38 35 19 8 3 0 0 PCT: Procalcitoin COPD: Chronic Obstructive Pulmonary Disease Schuetz P et al. J Am Med Assoc. 2009;302(10):1059-66.

Adverse Outcomes PCT Control All Patients (n = 1359) CAP (n = 925) 0.2 Proportion with Combined Adverse Outcome 0.1 Proportion with Combined Adverse Outcome 0.1 0.0 0.0 10 20 30 10 20 30 Days Since Randomization Days Since Randomization No. at Risk No. at Risk PCT 671 605 579 568 PCT 460 408 394 386 Control 688 598 576 558 Control 465 396 383 371 Schuetz P et al. J Am Med Assoc. 2009;302(10):1059-66.

Schuetz P et al. J Am Med Assoc. 2009;302:1059-66. Conclusions An algorithm with PCT cutoff ranges was noninferior to clinical guidelines in terms of adverse outcomes in CAP: Reduced antibiotic exposure Reduced associated adverse effects In countries with higher antibiotic prescription rates, PCT guidance may have clinical and public health implications Schuetz P et al. J Am Med Assoc. 2009;302:1059-66.

Procalcitonin: Case studies from the emergency department

Case Study- H.C. 31 year old female w/ multiple sclerosis on weekly plasmapheresis Hospitalized in early July for possible catheter infection Catheter removed, only 1 blood culture growing coagulase negative staph. Transitioned from vancomycin to ofloxacin then to doxycycline

Case Study- H.C. Seen in ER June 8 the night of hospital discharge. Patient still concerned about redness and itchiness near former line site Given empiric dose of vancomycin after drawing blood cultures, CBC, PCT. Discharged home to be followed by PCP and dermatology next day to determine if broad spectrum antibiotics needed to be continued. June 9 dermatology clinic visit suggests patient w/ contact dermatitis; continues previous course of doxy

Case Study H.C. Procalcitonin 0.11 PCT level provides reassurance that: recurrence of systemic infection unlikely, present narrow-spectrum antibiotic choice likely effective providing better antimicrobial stewardship

Case Study E.P. “classic” PCT benefit case 72 yo male w/ valvular heart disease, sick sinus syndrome s/p pacemaker* to ED w/ acute SOB on July 8th middle of night shift. Not known to our system, his primary hospital ER was on bypass, no old records or previous imaging available O2, bronchodilators, empiric broad spectrum antibiotics after blood cultures, labs including PCT Admitted to intermediate care unit for high flow O2, antibiotics, monitoring, bronchodilators, trial of diuretics. *increasing prevalence of elderly patients with pacemakers or on betablockers reduces clinical vital sign effectiveness in diagnosis SIRS and Sepsis since heart rate may be artificially blunted

Case Study E.P. Within 24 hours he required transfer to the ICU and intubation for respiratory distress and sepsis PCT was 3.45 from ED draw but due to his nighttime arrival was not available until after admitted to floor.

Case Study E.C. 63 yo male w/ fever, chills, atrial fibrillation with RVR (HR 140s) Treated with diltiazem and broad spectrum antibiotics Symptoms resolved within two days and patient discharged home on azithromycin Emergency department PCT was 0.12 Record review show patient's previous admission for afib with RVR was attributed to documented influenza A No virology studies during this admission, only "positive" microbiological finding was a coag negative staph blood culture on hospital day 2. Should patient have had virology screening done even though it was not flu season?

Information from PCT adds to the quality of the clinical decision making Understand the kinetics and limitations of any test in order to optimize its utilization! Guidance of therapy Decision on antibiotic initiation Guidance of duration of therapy Risk stratification of patients Admission to hospital Admission to ICU Escalation of therapy Guidance of diagnosis More appropriate selection of who might need invasive diagnostic tests Rational utilization of advance imaging modalities Improved direction in choice of microbiology and virology studies

Thank you! Questions? Comments?