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PCT for Antimicrobial Stewardship.pptx
- 1. Fathima Paruk, PhD Professor in Critical Care Head of Department of Critical Care & Emergency Services Steve Biko Academic Hospital University of Pretoria South Africa PCT Informing Antimicrobial Stewardship
- 2. Patient AB 55 years Obese Diabetic Paraplegic (Trauma many years ago) Day 4 Hospital admission For elective repair large incisional hernia (delay) Respiratory distress Confusion Oliguria MAP 60 mmHg
- 3. Patient AB 55 years Obese Diabetic Paraplegic (Trauma many years ago) Day 4 Hospital admission For elective repair large incisional hernia (delay) Hospital acquired pneumonia Organ dysfunction Pip-Taz + Ertapenem Cureus 12(4): e7804. doi:10.7759/cureus.7804
- 4. ICU Previous day Day1 Day2 TEMP 37.20C 390C 38.10C HR 85 95-110 90-95 MAP 80 60 66 FiO2 RA 0.60 0.40 WCC 12 19 13.6 PLATELETS 155 150 160 BGL 7-9mmol/L CRP 45 150 155 PCT ng/mL 0.4 2.2 2.0 URINE >1mL/Kg/Hour SCVO2 71 70 AVCO2 5 4 Fluid Balance 1050 400
- 5. ICU Previous day Day1 Day2 TEMP 37.20C 390C 38.10C HR 85 95-110 90-95 MAP 80 60 66 FiO2 RA 0.60 0.40 WCC 12 19 13.6 PLATELETS 155 150 160 BGL 7-9mmol/L CRP 45 150 155 PCT ng/mL 0.4 2.2 2.0 URINE >1mL/Kg/Hour SCVO2 71 70 AVCO2 5 4 Fluid Balance 1050 400 H48 E. Coli ESBL De-escalate
- 6. Day1 Day2 Day3 Day4 TEMP 390C 38.10C 37.20C 37.60C HR 95-110 90-95 MAP 60 65-75 FiO2 0.60 0.40 0.4 0.35 WCC 19 13.6 13.4 11.7 PLATELETS 150 160 155 161 BGL 7-9mmol/L CRP 150 155 130 99 PCT ng/mL 2.2 2.0 1.8 1.4 URINE >1mL/Kg/Hour SCVO2 71 70 70 70 AVCO2 5 4 - - Fluid Balance 1050 400 -450 -300 >72 hours of antibiotics
- 7. ICU Day1 Day2 Day3 Day4 TEMP 390C 38.10C 37.20C 37.60C HR 95-110 90-95 MAP 75-80 FiO2 0.60 0.40 0.4 0.35 WCC 19 13.6 13.4 11.7 PLATELETS 150 160 155 161 BGL 7-9mmol/L CRP 150 155 130 99 PCT ng/mL 2.2 2.0 1.8 1.4 URINE >1mL/Kg/Hour SCVO2 71 70 70 70 AVCO2 5 4 - - Fluid Balance 1050 400 -450 -300
- 8. How long would you treat with Ertapenem? 1. Continue until Day 5 at least 2. Stop when the PCT is below 0.5 ng/mL 3. Stop when the PCT and CRP are both normal 4. Stop now as patient is clinically improved and PCT has declined significantly.
- 9. How long would you treat with Ertapenem? 1. Continue until Day 5 at least 2. Stop when the PCT is below 0.5 ng/mL 3. Stop when the PCT and CRP are both normal 4. Stop now as patient is clinically improved and PCT has declined significantly.
- 10. If the pathogen was a MDR Pseudomonas the duration of therapy needs to be a minimum of 11-14 days ? 1. True 2. False
- 11. If the pathogen was a MDR Pseudomonas the duration of therapy needs to be a minimum of 11-14 days ? 1. True 2. False
- 12. Day1 Day2 Day 3 Day4 Day 5 HC Day 6 HC TEMP 390C 38.10C 37.20C 37.60C 37.20C 37.80C HR 100 90-95 88 MAP 70-80 mmHg FiO2 0.60 0.40 0.4 0.35 0.3 0.3 WCC 16 12 13 11 12 24 PLATELETS 150 160 155 161 180 188 BGL 8-10 mmol/L CRP 150 155 130 99 55 40 PCT 2.2 2.0 1.8 1.4 1.2 0.7 URINE >1mL/Kg/Hour High Care Discharged to HC
- 13. Day1 Day2 Day 3 Day4 Day 5 HC Day 6 HC D7 HC TEMP 390C 38.10C 37.20C 37.60C 37.20C 37.80C 39.80C HR 100 90-95 95 120⬇︎⬇︎⬇︎ MAP 75-80 mmHg 59 FiO2 0.60 0.40 0.4 0.35 0.3 0.3 Intubate WCC 19 13.6 13.4 11.7 13.7 11.9 13.1 PLATELETS 150 160 155 161 180 188 145 BGL 8-10 mmol/L 12 CRP 150 155 130 99 55 40 180 PCT 2.2 2.0 1.8 1.4 1.2 0.7 0.35 URINE >1mL/Kg/Hour⬇︎⬇︎⬇︎ ↓⬇︎⬇︎⬇︎ Clinical course- Shock in HC on Day 7 Readmitted ICU Central line – still in Situ
- 14. Is there an infection? 1. This is not an infection 2. Most likely a bacterial infection. 3. Most likely a viral infection 4. Most likely a fungal infection
- 15. Is there an infection? 1. This is not an infection 2. Most likely a bacterial infection. 3. Most likely a viral infection 4. Most likely a fungal infection
- 17. S P Host response Source (infection) HR,RR Temperature WCC Investigations CXR CT scan Pathogen: Blood culture Microbiology (MCCS) 48-72 hours culture Infection Recognition 14 Sepsis Sep c Shock with - Hypotension requiring vasopressors to keep MAP > 65mmHg - Lactate >2mmoL/L with adequate volume resuscita on INFECTION + SOFA Score é by ≥ 2 points INFECTION + SOFA Score é by ≥ 2 points Diagnostic stewardship
- 18. Early Diagnosis Biomarkers Rapid Diagnostics Pro Adenomedullin Presepsin Combination panels Rapid pathogen detection PCR technology Next generation sequencing Mass spectrometry Molecular diagnosis Protein microarrays Coagulation Biomarkers PCT CRP
- 20. • T PAMPS DAMPS Adapted from : 2015_Zsolt Becze_Can PCT levels indicate the need for adjunctive therapy in sepsis_Int J Antimicrob Agents Inflammatory response Endothelial dysfunction Capillary leak Vasodilation Hypovolemia Vasopressor refractoriness Prothrombotic Microcirculatory flow Mitochondrial dysfunction
- 21. - + CRP
- 22. Biomarker response to an infection-Depends… Meisner,2000 Vijayan et al, J Int Care,2017
- 23. Out patient *
- 24. Diagnosis value PCT IL PCT CRP IL PCT: Highest Sensitivity and Specificity Better than with IL-6 or CRP Harbarth S. Am J Respir Crit Care Med (2001); Müller B, et al. Crit Care Med (2000) Carr J. J INT Care,2015
- 25. “Eprok” 88% Change in PCT in 24 hours Absolute PCT
- 26. Charles at al.: BMC Infectious Disease 20098 2nd 1st Peak PCT: Repeat infections LOWER PCT peak value with subsequent infections 6.4ng/ml [9] PCT PCT 58 ng/ml[99] n=179 Similar SOFA ICU Infection
- 27. CRP and PCT post surgery CRP peaks D3-4 post op PCT peaks 24 hours postop Then falls progressively
- 28. PCT post surgery PCT Response - Detect ongoing sepsis - Detect new sepsis - Detect post op complications Post surgery Concern if: - PCT >10ng/mL - From 48 hours PCT stagnant or increasing Kinetics and Clearance
- 29. Post surgery patients • C
- 30. 0.65 [0.08-5.46 ng/mL] PCT PCT: Candidaemia 9.75 [1-259 ng/mL] p < 0.001 n=50 blood cultures MICU Non-neutropenic
- 31. Special situations Neutropenia HIV infection Solid Organ Transplant Autoimmune Disease Loculated infections RRT Malaria Small cell lung Ca Medullary thyroid Ca Immunomodulating agents Liver Failure INFLAMMATORY RESPONSE Immunosupression
- 32. PCT guidance to stop antibiotics? Clinically improving and - PCT threshold (<0.5ng/mL) OR - 80% ↓ in PCT (kinetics) • Robust evidence • General approach Bouadma L et al, Lancet; 2010 Matthaiou DK et al, ICM, June 2012 Schuetz P et al , Coch Collab,2012 Soni NJ et al, J Hosp Med, Sept 2013 Limit antibiotic duration in an infection which is deemed to be adequately treated SAPS Trial De Jong et al, Lancet Infect Dis, 2016 • Netherlands ICUs • Antibiotic stewardship • 15 Centers • n=1546 Clinically improving AND - PCT threshold (≤0.5μg/L) OR - 80% ↓ in PCT (kinetics)
- 33. De Jong et al, Lancet Infect Dis, 2016 SAPS Trial
- 34. Evidence Sridharan P et al, Surgical Infect, 2013 Uzzan B et al Crit Care Med,2006 Tang B et al, Lancet Infec Dis,2006 Wacker C et al, Lancet Infect Dis, May 2013 Loonen et al,2014 Chengfen Y et al,2015 • Primary care • Emergency department • General ward • Critically ill
- 35. Covid -19 Timeline Therapy Pathophysiology December 2019 Impact May 2022 Excessive inappropriate antibiotics Secondary bacterial Infections (0-45%) RTIs and BSIs Bacterial Co-infections on admission MA-3.5% (Langford et al) -7% Immunomodulatory therapy Zhou AL et al,Lancet,2020 Hyperinflammatory response
- 36. Reports: Bacterial Infections Zhou AL et al,Lancet,2020 Langford BJ et al, Clin Micro Infect,2020 Feng Y et al, AJRCC,2020 • Higher incidence with disease severity - Critically ill: 8-34% • Non-survivors- high prevalence of bacterial infections - 11 to >50% of NS have a SBI • Tend to occur late [Staph,Hemophillus,Enterococcus, Klebsiella, E coli, Pseudomonas, Acinetobacter, CRE]
- 37. CRP and PCT in SARS-CoV2 66 ICU patients No secondary infection PCT: declined over time, mean PCT 0.64 ng/ml CRP: declined over time, mean CRP 192 mg/l
- 38. CRP and PCT in SARS-CoV2 33/66 - infection
- 39. n=65 (March to June 2020) 33% secondary infections (BSI, VAP,VAT)
- 40. Immunomodulation Anti inflammatory- independent risk factor (BSI) • Tocilizumab 1.8 • Methylprednisolone 4.5 • Tocilizumab + MP 10.2 Own experience doi: 10.1111/ECI.13319 N Italy 78 ICU patients 47 BSI in 31 patients Risk 25%(15 days) >50%(30days Risk factors • DM • Devices • Antibiotic • Length of stay • Immunomodulatory therapy Rawson TM et al, Clin Infect Dis,2020 Chen et al, 2020 doi: 10.1111/ECI.13319 Conventional risk MDR XDR infection risk factors Poor functional status High APACHE II Antibiotic exposure(recent) Previous history of CPE Medical devices/Hemodialysis Exposure to known carrier Hospital/ICU stay >1 week • Italy • 731 patients • 9.3% secondary infection (BSI > RTI) • BSI- gram positive mainly • RTI: gram negative (A. Baumanii, E coli)
- 41. No Dexa No TOCI Dexa Dexa and TOCI Stopping immunomodulators n=190
- 42. No Dexa No TOCI Dexa Dexa and TOCI Stopping immunomodulators n=190
- 43. 20Infection: Dexa(27%) Dexa and TOCI(33%)
- 44. No Dexa No TOCI Dexa Dexa and TOCI Stopping immunomodulators n=190 Small study (133 infection) CRP DEXA: Rebound - 4 days(false +) DEXA+TOCI: CRP no change DEXA: 20 infection : CRP increase delayed PCT Suspect 20 infection - Kinetics - PCT increase (after D1 esp in DEXA+TOCI) - Timing:Late infections –larger magnitude
- 45. Prognosis • Severe sepsis and septic shock – Higher clearance in survivors (p=0.002) – Admission PCT >32.5μg/L independent predictor of mortality(p<0.0001) • PCT clearance – First 72 hours – Hospital mortality (OR [95%CI], 2.76[1.1-6.9],p=0.03) – Day90 mortality Sehabi Y et al, AJRCC,2014 Huang MY et al, Biomed Red Int,2016 Peschanski N Et al, Ann Int Care, Dec 2016 • Kinetics Jensen J et al, Crit Care Med,2006 PCT: Prognostic value
- 46. Impact: LOS, ICU cost, Pharmacy cost, antibiotic exposure 33 569 PCT guided vs 98 543 non-PCT guided Reduced antibiotic exposure 985 (control) vs 1167 (PCT guided) Significant reduction • Antibiotic exposure • Adverse events PCT Group Antibiotic exposure reduced ICU LOS reduced C diff reduced Cost-<25 000 USD(sepsis) Cost <3 630USD(RTI) • C
- 47. S P Comorbidities Clinical Condition + PCT PCT kinetics - Uncertainty - Coexisting Inflammatory response - Duration of therapy Therapy Disease or injury