author by eLibrary Antibiotics in septic patients in the ER ESCMID © ESCMID eLibrary by author UniversityMiquel Medical Ekkelenkamp Center Utrecht Miquel Ekkelenkamp Antibiotics in septic patients in the ER Disclosure of speaker’s interests (Potential) conflict of interest None author Potentially relevant company relationships in Noneby connection with event 1 • Sponsorship or research funding2 Polyphor AG (through European eLibraryCommision Innovative Medicines Initatiative) • Fee or other (financial) payment3 • Shareholder4 ESCMID5 • Other relationship,© ESCMID i.e. … eLibrary by author 2 Sepsis definitions • “Life-threatening organ dysfunction due to a dysregulated host response to infection.” • Acute increase in 2 or more points in SOFA scoreauthor by • Quick SOFA (for screening): 2 or 3 of: – Hypotension: SBP less than or equal to 100 mmHg – Altered mental status (any GCS less than 15) – Tachypnoea: RR greater thaneLibrary or equal to 22 • Septic shock: – “Sepsis in which underlying circulatory and cellular/metabolic abnormalitiesESCMID are profound enough to substantially increase mortality.”© ESCMID eLibrary by author author Clinical reasoningby in infectious diseases eLibrary Symptoms ESCMID © ESCMID eLibrary by author Disease (Diagnosis) Treatment author Clinical reasoningby in infectious diseases eLibrary Symptoms ESCMID © ESCMID eLibrary by authorPathogen Disease Treatment Clinical reasoning in infectious diseases Pathogen Susceptibility author by Symptoms Disease Treatment eLibrary ESCMID © ESCMID eLibrary by author Antibiotics for sepsis in ER = empiric therapy • Choice similar rationale as other infections: – Treatment usually started before culture results Severity of disease – Less room to “miss” a pathogen author by • R/ should cover the likely pathogens – Also cover likely resistant species • R/ should be “suitable” foreLibrary sepsis – Preferably (rapidly) bactericidal, intravenous • R/ should be supported by clinical evidence of efficacy – Based onESCMID infectious syndrome – Based© onESCMID activity vs pathogen eLibrary by author – If registered for “sepsis” that would also be nice author by WhicheLibrary infections are the main ESCMID © ESCMIDcauses eLibrary of bysepsis? author Main focus bloodstream infection • Community-acquired – Urinary tract – Respiratory tract 60-95% author – Abdominal / biliary tract by • Nosocomial bacteremia: Main foci HAI (all): – 1: Intravascular catheter (40%)eLibrary-Respiratory tract 23.5% – 2: Urinary tract (8%) -Surgical site infections 19.6% -Urinary tract 19% – 3: Surgical site infection (5%) -Catheter-related infections 12.2% – 4: Digestive tract (5%) -Gastro-intestinal 7.6% – 5: PulmonaryESCMID (4%) – 20% unknown © ESCMID eLibraryECDC pointby prevalence author survey hospital- acquired infections 2011-2012 Nethmap 2009, SWAB 2010; EDCD surveillance report 2011-12; Laupland e.a., Clin Microbiol Rev 2014; Søgaard e.a. Clin Microbiol Infect 2015; Cardoso e.a. Acta Med Portug 2013 author by eLibrary Which pathogens are the main ESCMID © ESCMID eLibrarycauses of bysepsis? author Community-acquired bacteremia • 1: Escherichia coli • 2: Streptococcus pneumoniae 60-70% • 3: Staphylococcus aureus • 4: Klebsiella species author by Nosocomial bacteremia eLibrary • 1. Coagulase-negative staphylococci • 2. E. coli Low • 3. S. aureus pathogenicity • 4. EnterococciESCMID • 5. Klebsiella© ESCMID spp eLibrary by author • Some institutions: Candida, P. aeruginosa, Acinetobacter, Enterobacter Refs: see previous slide Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Acinetobacter author Pseudomonas by eLibrary ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Penicillin Peni Acinetobacter Augm Amoxicillin / clavulanic acid author Pseudomonas Piptazo Piperacillin / tazobactamby 1st gen: cefazolin Metronida- 2nd gen: cefuroxime zole 3rd gen:eLibrary ceftriaxone 3rd gen: ceftazidime 4th gen: cefepime Meropenem / imipenem Mero/imi ESCMID Clinda © ESCMIDClindamycin eLibrary by authorAztreonam Vancomycin / daptomycin / linezolid Colistin Ciprofloxacin Gentamicin / tobramycin author by eLibrary ESCMID © ESCMID eLibrary by author Are we allowed drugs for sepsis? to use these author by eLibrary FDA labels ESCMID © ESCMID eLibrary by author www.accessdata.fda.gov/scripts/cder/daf / Guidelines, community-acquired sepsis (of unknown origin) • The Netherlands (SWAB-guideline): – Cefuroxime OR ceftriaxone OR amoxi-clav +/- gentamicin / tobramycin – Risk factors for ESBL: add gentamicin or tobramycinauthor – Known ESBL-positive: carbapenem by • Spain (Zaragoza University Hospital): – Ceftriaxone +/- gentamicin – Risk factors for ESBL: carbapenemeLibrary • Surviving sepsis guideline 2016 (no distinction HA-sepsis): – “empiric broad-spectrum therapy to cover all LIKELY pathogens”, if shock “at least ESCMID2 antibiotics of different antibiotic classes” • Sanford© Guide ESCMID (no distinction eLibrary HA-sepsis): by author – Vancomycin + meropenem or imipenem or piperacillin-tazobactam – Alternative: daptomycin + cefepime or piperacillin-tazobactam Basically • Preferably treat with a beta-lactam antibiotic – I.e.: penicillins, cephalosporins, carbapenems or monobactams • Bactericidal author • Usually well-known safety profile by • Usually inexpensive • If necessary: add additional antibiotic – To cover gaps in the desiredeLibrary antibiotic spectrum – Some people say “for synergy” (limited indications) • Always take into account: – Likely focus,ESCMID risk factors for certain pathogens (antibiotic use, comorbidity,© ESCMID etc) eLibrary by author – PRIOR CULTURES (positive and negative) Beta-lactams: 60% of total antibiotic use author by eLibrary Beta-lactams ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Acinetobacter author Pseudomonas Community-acquiredby sepsis: -Enterobacteriaceae: E. coli, Klebsiella -Streptococci (incl pneumococci) -S. aureus eLibrary ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Penicillin Peni Acinetobacter Augm Amoxicillin / clavulanic acidauthor Pseudomonas Piptazo Piperacillin / tazobactamby st Metronida- 1 gen: cefazolin zole 2nd gen: cefuroxime 3rd gen:eLibrary ceftriaxone 3rd gen: ceftazidime 4th gen: cefepime Meropenem / imipenem Mero/imi ESCMID Clinda © ESCMIDClindamycin eLibrary by authorAztreonam Vancomycin / daptomycin / linezolid Colistin Ciprofloxacin Gentamicin / tobramycin Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Acinetobacter author Pseudomonas by S. aureus eLibrary MRSA MSSA ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Acinetobacter author Pseudomonas by S. aureus eLibrary Enterobacteriales MRSA MSSA ESBL AMP-C Carba-R ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps H. infl Enterobacteriales Non-ferm Acinetobacter author Pseudomonas by S. aureus eLibrary Enterobacteriales MRSA MSSA ESBL AMP-C Carba-R MRSA outpatients:ESCMID ESBL outpatients: <0.1-18© / 100,000ESCMID pt years eLibrary by 2.6%author-40% E.coli Laupland CMR 2014 Talan, 2014 EARS-Net data 2015 Castillo 2015 Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps HI Enterobacteriales NF MRSA ESBL AMP-C CRE author Pseudomonas by eLibrary ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps HI Enterobacteriales NF MRSA ESBL AMP-C CRE author Pseudomonas by Amox/clav A/C AmoxicillineLibrary / clavulanate Cefuroxime Ceftriaxone Mero/imi ESCMIDM/I Meropenem / imipenem © ESCMID eLibraryGentamicin by author / tobramycin / amikacin Colistin Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps HI Enterobacteriales NF MRSA ESBL AMP-C CRE author Pseudomonas by Amox/clav A/C AmoxicillineLibrary / clavulanate Cefuroxime Ceftriaxone Mero/imi ESCMIDM/I Meropenem / imipenem © ESCMID eLibraryGentamicin by author / tobramycin / amikacin Vancomycin / linezolid / daptomycin Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps HI Enterobacteriales NF MRSA ESBL AMP-C CRE Or should we consider an intra-abdominal focus? author Pseudomonas by Metronida- zole Amox/clav A/C AmoxicillineLibrary / clavulanate Cefuroxime Ceftriaxone Mero/imi ESCMIDMeropenem / imipenem © ESCMID eLibraryGentamicin by author / tobramycin / amikacin Clinda Clindamycin Ciprofloxacin Healthcare-associated sepsis • Circulating hospital-specific pathogens – Same micro-organism but more resistant (MRSA,author ESBL, CRE) – Different micro-organism: P. aeruginosa, A. baumannii, Enterobacters, Serratia’s, etc. by • Immunocompromized population – Underlying illness, post-operativeeLibrary status, intravascular access, immunosuppressant medication – Susceptible to wider range of (opportunistic) pathogens: Pseudomonas aeruginosa and other non-fermenters, yeast and fungi ESCMID © ESCMID eLibrary by author Anaerobes Gram-positive Gram-negative Gr- Gr+ CoNS Enterococci S. aureus Streps HI Enterobacteriaceae NF MRSA ESBL AMP-C CRE Acinetobacter author Pseudomonas Amox-clv A-C Amoxicillin-clavulanate Pip-tzb P-T Piperacillin-tazobactam