Trea%ng Sepsis in 2016 Are the Big Guns Losing the War?

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1 Trea%ng Sepsis in 2016 Are the Big Guns Losing the War? ERIC HODGSON FCA (Crit Care) Inkosi Albert Luthuli Central Hospital & NELSON R MANDELA SCHOOL OF MEDICINE DURBAN, KZN

2 Declaration Advisory boards Fresenius-Kabi, Sanofi Speaker honoraria Aspen-GSK, Abbott, Adcock-Ingram, Baxter, Pfizer, MundiPharma No payment for today s talk

3 CAP The Unacknowledged Compulsive Prescribing Epidemic Antibiotic Results in Resistance: ESBL Klebsiella CRAB GISA CR Strep Pneumo Antibiotic era = <100 years

4 The Unacknowledged Consequences: Epidemic Vanco / Ceftriaxone for CVS proph What kills MRSA kills everything Levofloxacin for Uro Because Cipro cures UTI Meropenem for ICU fever Sick patients deserve the best

5 Increased Antibiotic Use

6 Medical Tourism International travel Spreads resistance Esp. after medical procedures NDM-1 in south Asia Soon found worldwide

7 Microbes and humans Very few microbes are always pathogenic Many microbes are potentially pathogenic Most microbes are never pathogenic

8 Effect of broad-spectrum antibiotics on microbial ecosystems

9 Resistance Carbapenems last new class Broad Spectrum: G+ve: Enterococci MSSA G-ve: Enterobacteriaceae Non-Fermenters Anaerobes Active against ESBL producing G-ves Over- & Misuse: Resistance

10 Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? Sepsis 2: SIRS Criteria Sepsis = SIRS + infection Severe Sepsis = SIRS + infection + OSF Sepsis 3: q-sofa Sepsis = q-sofa + infection Severe Sepsis = q-sofa+ infection+! Lactate

11 SIRS Criteria Sepsis 2: SIRS Criteria 1. T >38 C or <36 C 2. P >90/min 3. RR >20/min or PaCO2 <32 mmhg 4. WCC >12 or >10% immature band forms Sensitive but non-specific + Infection: often non-septic Severe: +OSF (Shock = Hypotension)

12 Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? Sepsis: q-sofa Hypotension: SBP < 100mmHg Altered Mental Status: CAM Tachypnea: RR > 22 Severe Sepsis Persistent Hypotension after fluids Lactate > 2mmol/l

13 SOFA Algorithm articleid=

14 Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? Sepsis 3: Positive Negative Simple & Quick Resp Rate NOT Automated Nearly 150k patients ONLY Germany & USA Pre-existing disease Variable endorsement

15 Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? 2. What is the site of the infection? 3. Can a specimen be obtained? 4. Where was the infection acquired? Community / Healthcare Associated / Nosocomial 5. Has the patient received antibiotics? >6weeks / 2-6 weeks / <2 weeks 6. Underlying diseases

16 Empiric Therapy Patient Factors Prior antibiotic exposure >6weeks / 2-6 weeks / <2 weeks Exposure to healthcare Community / Care Facility / Hospital Chronic Disease = ASA Score None / Well Controlled / Uncontrolled

17 Empiric Therapy Environmental Factors Time since onset Length of Stay / Delay 1 st dose = STAT within 1 hour AFTER appropriate cultures Surgical Procedure Iatrogenic / Missed injuries Hospital Ward Specialist Unit

18 Does THIS patient Need an Antibiotic ORGANISM FACTORS CLINICAL MICROBIOLOGIST 1.What are the likely organisms? 2.Unit Antibiogram What is the sensitivity of organisms in the patient s ward? Number of isolates (one per patient) Other Serratia Acinetobacter Stenotrophomonas Enterobacter/citrobacter E. coli Klebsiella spp. P. aeruginosa

19 A Positive Blood Culture Antibiotic overuse: New mutations Resistant Bacteria Resistance Gene Transfer Mutations Infection Control deficiency: Same Bug Susceptible Bacteria XX New Resistant Bacteria

20 Does THIS patient Need an Antibiotic DRUG FACTORS CLINICAL PHARMACIST 1. Any Contraindications? a. Esp. Allergy 2. Mono- vs. Combination therapy? a. Is more than one antibiotic needed? 3. What route & dose are indicated? a. Appropriate PharmacoKinetics/Dynamics b. Does the antibiotic penetrate the site? 4. Duration a days

21 Antibiotic outcome timeline

22 Appropriate Empiric Therapy Community Acquired Soft Tissue infection Penicillin / Cloxacillin ± Metronidazole Pneumonia Co-Amoxiclav / Cefuroxime Macrolide (Quorum sensing) Peritonitis Co-Amoxiclav / Aminoglycoside

23 Appropriate Empiric Therapy ESBL Producing bacteria Encoded by plasmids Highly mobile - Multiple drugs Selected by previous Rx 3 rd Gen Cephalosporin - Quinolone Covered by Amoxycillin-Clavulanate Dose / Interval Ertapenem Low risk of ESBL induction

24 Appropriate Empiric Therapy Nosocomial (NOT HCF/Community) G ves (non-fermenters) Pseudomonas / Acinetobacter Covered by 4 th Gen Cephalosporin Quinolone Piperacillin + Tazobactam Class 2 Carbapenems Imi/Mero/Dori penem Colistin MRSA: Glycopeptide / Linezolid Fungus: Flu- / Voriconazole / Caspofungin

25 Colistin Back to the Future Polymixin E: decapeptide from Bacillus Polymyxa mg/75-150iu/kg/day, in 2-3 doses 9-12miU load 3-4.5miU 12hrly Ineffective vs. Serratia Proteus Morganella Organ toxicity Nephrotoxicity ~20-30% Neurotoxicity (NMB) ~10% Effective in combination with Carbapenems IV Nebulised for pneumonia

26 48 hours Clinical Condition Better Worse Culture Results +ve -ve De-Escalate Stop Stop Adjust Broaden Source control Broaden? Stop & Culture

27 Inappropriate Use Untreatable organisms - Colistin resistant G-ve - X-MDR TB - VRE - GISA

28 Antibiotics Powerful medicines ONE Role: To treat bacterial infection NOT to compensate for deficiencies in: Patient: Condition, Comobidities HCW: Anxiety, Technique, CAP Appropriate use saves lives Inappropriate use COSTS lives

29 Microbivores

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