Antibiotics in sepsis

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1 Antibiotics in sepsis Jennifer Curello, PharmD, BCPS Antimicrobial Stewardship Program Ronald Reagan UCLA Medical Center September 13, 2013

2 Outline Sepsis definitions The sepsis bundle Timing of antimicrobials sepsis Choosing appropriate therapy Broad-spectrum antimicrobial therapy Targeting therapy towards likely pathogen(s) Community- vs. hospital-acquired Source of infection Order of drug administration

3 Definitions Systemic inflammatory response syndrome (SIRS) Temp > 38.3 C or Temp < 36 C Heart rate > 90 beats per minute Respiratory rate > 20 breaths/min or PaCO 2 < 32mmHg WBC > 12,000 cells/mm 3 or < 4,000 cells/mm 3 Sepsis Infection + 2 SIRS criteria Severe sepsis Sepsis + organ dysfunction/tissue hypoperfusion Septic shock Sepsis + hypotension refractory to adequate fluid resuscitation (initial: ~20-30mL/kg crystalloid)

4 The sepsis bundle To be completed within the first 3 hours Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics (within 1 hour of TOP) Administer ml/kg crystalloid for hypotension or lactate 36mg/dL (4 mmol/l) To be completed in the first 6 hours For patients in septic shock (fluid-refractory hypotension) Apply vasopressors to maintain MAP 65 mmhg Measure CVP* & SCVO 2 * Re-measure lactate* if initial lactate was elevated *Targets for resuscitation: CVP 8 mmhg, SCVO 2 70%, normalization of lactate

5 The sepsis checklist Diagnosis & Antibiotics Blood cultures: obtain 2 cultures Initiate antibiotics Imaging Hemodynamics Fluids: using colloid or crystalloids Vasopressors/Inotropes Miscellaneous Steroids: hydrocortisone*/dexamethasone Blood glucose control Stress ulcer prophylaxis *Preferred Dellinger RP, et al. Crit Care Med. 2013; 41(2):

6 Sepsis = STAT Timing of the first antibiotic dose matters! Kumar A, et al. Crit Care Med. 2006;34:

7 Choosing appropriate empiric antimicrobial therapy Sepsis pathogens Broad-spectrum antibiotics Order of antibiotic administration

8 Common sepsis pathogens Evolution of sepsis pathogens over time Martin GS et al. N Engl J Med 2003; 348:

9 Gram-positive pathogens Common gram-positive pathogens Staphylococcus spp. Streptococcus spp. Enterococcus spp. Clostrodium spp. (C. difficile) Associated infections Skin & skin structure infections Endocarditis/bloodstream Osteomyelitis Pneumonia Meningitis Infectious colitis accessed 9/11/2013 ± Urinary tract infections, intra-abdominal infections

10 Gram-negative pathogens Common gram-negative pathogens Enterobacteriacea (enteric gram-negatives) Haemophilous influenzae Pseudomonas aeruginosa Bacteroides fragilis Associated infections Urinary tract infections Intra-abdominal infections Pneumonia Endocarditis/bloodstream Meningitis ± Osteomyelitis a-coli2.jpg accessed 9/11/2013

11 Always consider the source Common Pathogens by Site of Infection Site of Infection Gram Positive Gram Negative Other Respiratory Streptococcus pneumoniae Staphylococcus aureus H. influenzae M. catarrhalis Enteric gram negatives (aspiration) Pseudomonas Mycoplasma pneumoniae (at) Chlamydophila pnuemoniae (at) Legionella spp. (at) Viruses Urinary Staphylococcus saprophyticus Enterococcus E. Coli Proteus Klebsiella Pseudomonas Candid spp. Gastrointestinal Staphylococcus spp. Streptococcus spp. Peptostreptococcus (a) Enterococcus E. Coli Klebsiella Proteus Enterobacter B. fragilis (a) Bacteroides/Provetella spp. (a) Candida spp. Skin/Soft Tissue Streptococcus spp. Staphylococcus spp. Corynebacterium Clostridium spp. (a) Peptostreptococcus (a) Bacteroides (a) Vibrio vulnificus Aeromonas hydrophilia Enterobacteriacea Pseudomonas aeruginosa Eikenella spp. Pasteruella spp. (a) = anaerobic bacteria, (at) = atypical bacteria

12 Broad spectrum antimicrobials Broad spectrum antimicrobials Combination of antimicrobial agents with a spectrum of activity likely to treat all potential pathogens with good penetration into presumed source Considerations for antimicrobial selection Source of infection Determine likely pathogen Tissue penetration of drug Patient-specific factors Allergies Co-morbidities/organ function Recent antibiotic exposure Local resistance patterns Dellinger RP, et al. Crit Care Med. 2013; 41(2):

13 Broad spectrum antimicrobials Ronald Reagan UCLA Medical Center: Five Most Common Gram-negative Bacteria Percent Susceptible UCLA Antimicrobial Susceptibility Summary

14 Broad-spectrum antimicrobials Ronald Reagan UCLA Medical Center: Gram-positive Cocci Percent Susceptible UCLA Antimicrobial Susceptibility Summary

15 Example empiric regimens Table adapted from: UCSF Infectious Disease Management Program:

16 Order of administration Gram-negative coverage Piperacillin/tazobactam Meropenem Aztreonam Gram-positive coverage Vancomycin Linezolid Double gram-negative coverage and/or antifungal coverage and/or misc. Tobramycin (gram-neg) Metronidazole (anaerobic) Caspofungin (antifungal) 1 st 2 nd 3 rd May infuse over 30 minutes Vancomycin is infused 1 hour

17 Questions?

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