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
Declaration Advisory boards Fresenius-Kabi, Sanofi Speaker honoraria Aspen-GSK, Abbott, Adcock-Ingram, Baxter, Pfizer, MundiPharma No payment for today s talk
CAP The Unacknowledged Compulsive Prescribing Epidemic Antibiotic Results in Resistance: ESBL Klebsiella CRAB GISA CR Strep Pneumo Antibiotic era = <100 years
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
Increased Antibiotic Use
Medical Tourism International travel Spreads resistance Esp. after medical procedures NDM-1 in south Asia Soon found worldwide
Microbes and humans Very few microbes are always pathogenic Many microbes are potentially pathogenic Most microbes are never pathogenic
Effect of broad-spectrum antibiotics on microbial ecosystems
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
Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? http://emcrit.org/pulmcrit/problems-sepsis-3-definition/ 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
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)
Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? Sepsis: q-sofa http://www.qsofa.org Hypotension: SBP < 100mmHg Altered Mental Status: CAM Tachypnea: RR > 22 Severe Sepsis Persistent Hypotension after fluids Lactate > 2mmol/l
SOFA Algorithm http://jama.jamanetwork.com/article.aspx? articleid=2492881
Does THIS patient Need an Antibiotic PATIENT FACTORS 1. Does this patient have an infection? Sepsis 3: http://lifeinthefastlane.com/ccc/sepsis-definitions/ Positive Negative Simple & Quick Resp Rate NOT Automated Nearly 150k patients ONLY Germany & USA Pre-existing disease Variable endorsement
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
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
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
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) 100 90 80 70 60 50 40 30 20 10 0 2005 2006 2007 Other Serratia Acinetobacter Stenotrophomonas Enterobacter/citrobacter E. coli Klebsiella spp. P. aeruginosa
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
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. 3 5 7 14 days
Antibiotic outcome timeline
Appropriate Empiric Therapy Community Acquired Soft Tissue infection Penicillin / Cloxacillin ± Metronidazole Pneumonia Co-Amoxiclav / Cefuroxime Macrolide (Quorum sensing) Peritonitis Co-Amoxiclav / Aminoglycoside
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
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
Colistin Back to the Future Polymixin E: decapeptide from Bacillus Polymyxa 2.5-5 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
Decision @ 48 hours Clinical Condition Better Worse Culture Results +ve -ve De-Escalate Stop Stop Adjust Broaden Source control Broaden? Stop & Culture
Inappropriate Use Untreatable organisms - Colistin resistant G-ve - X-MDR TB - VRE - GISA
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
Microbivores http://www.rfreitas.com/nano/microbivores.htm