Antibiotic Guidelines in ICU

Revised and reviewed 17 December 2015

OVERVIEW

  • Antibiotic guidelines vary between ICUs
  • This variation is based on local causes of infections, resistance patterns, availability and patient factors
  • However, the principles of appropriate use of antibiotics are universal… as are the common errors!

PRINCIPLES OF APPROPRIATE USE OF ANTIBIOTICS

Adapted from Lipman:

  • Take cultures before administering antibiotics
  • Take two sets of cultures, not from a line
  • Timing of blood cultures with fever is not critical
  • Do not delay the administration of antibiotics
  • Use empirical therapy first; narrow the spectrum later
  • Ensure initial doses are sufficient – under-doing must be avoided
  • use monotherapy where possible (reduces cost and toxicity).
  • If the microbiology results suggest decreased susceptibility, consider whether the antibiotics working clinically. If there is direct bedside evidence that they are working, then continue them in spite of laboratory evidence. In vitro sensitivity does not always predict in vivo effect
  • A shorter course (e.g. 7 days) is probably as good as a standard 2-week course in most cases
  • Infectious diseases specialists should be consulted when managing serious infections
  • Know antimicrobial pharmacokinetics and pharmacodynamics; consider tissue penetration and dose adjustment to correct for altered clearance
  • Monitor antibiotic levels when available
  • Limit “prophylactic” use to appropriate situations
  • Consider non-infective causes of inflammation (sepsis mimics are surprisingly common)
  • Adhere to infection control policies
  • Have an antimicrobial stewardship program in the ICU

COMMON ERRORS IN ANTIBIOTIC USE

Adapted from Lipman:

  • Delay in antibiotic administration in severe sepsis
  • Antibiotics given before cultures taken
  • Contaminated or insufficient blood culture collection
  • Excessively long courses of antibiotics
  • Erratic changes of antibiotics in non-resolving sepsis
  • Inadequate doses
  • Poor choice of empirical antibiotics, failing to account for resident flora
  • Failure to predict toxicity or account for interactions
  • Failure to consider tissue penetration of different antibiotics
  • Inappropriate use of antibiotic polypharmacy or failure to de-escalate to monotherapy

FACTORS THAT DETERMINE INITIAL CHOICE OF ANTIBIOTICS

Table from Deranged Physiology — General principles and common errors of antimicrobial use:

12
FactorsDiscussion and examples
DISEASE
SPECIFICS
Travel history
  • Geography of endemic regions (eg. leptospirosis)
  • Known ongoing outbreaks (eg. Ebola, H1N1, MERS)
Occupational exposure
  • Abattoir workers (Coxiella burnetii)
  • Fisherman (Vibrio vulnificus)
  • Cattle farmers (Brucella sp.)
Recreational exposure
  • IV drug use (endocarditis)
  • Pets or animal exposure (eg. psittacosis or toxoplasma)
  • Bushwalking (eg. tick-borne disease)
  • Alcoholism (prognostic importance in community-acquired pneumonia)
Recent antimicrobial use
  • Was it the right antibiotic? i.e. was the course of antibiotics ineffective because of poor agent choice?
  • Did it select for a specific group of organisms?
  • Prophylaxis vs. endemic pathogens (eg, malaria)
Empiric vs. definitive
  • Are we convinced of the diagnosis?
  • Is there a need to cover broadly?
Urgency and timing
  • Septic patient (every hour delay is associated with a 1% mortality increase)
Reliability of cultures
  • Are we sure we cultured the correct pathogen?
  • Is a polymicrobial infection possible (eg. diabetic foot)?
HOST
FACTORS
Clearance
  • Decreased renal clearance (by renal failure)
  • Increased renal clearance (by dialysis, or in pregnancy)
  • Decreased hepatic clearance (eg. cirrhosis)
  • Exotically altered clearance (eg. plasma exchange, haemoperfusion, adsorption on to ECMO circuit surfaces, and so forth)
Age
  • Paediatric dosing needs to be adjusted to weight
  • Geriatric dosing needs to account for change in volume of distribution and clearance
Genetic variation
  • Genetic differences in side effects from antibiotics
  • Congenital idiosyncrasies preventing the use of certain antibiotics (eg. G6PD deficiency resulting in haemolysis when exposed to dapsone or nitrofurantoin)
  • Hepatic enzyme defects
Pregnancy and lactation
  • Early pregnancy teratogenesis (eg. nitrofurantoin, chloramphenicol, sulfonamides)
  • Late pregnancy teratogenesis (eg. tetracyclines)
Immunocompetence
  • Steroid use
  • Post-splenectomy, unvaccinated (susceptible to encapsulated organisms)
  • Chemotherapy
  • Solid organ or bone marrow transplantation
Allergies
  • Fatal hypersensitivity reaction vs. some sort of mild scaly rash with a little itching.
ORGANISM
FACTORS
Susceptibility
  • ESCAPPM, MRO, etc
  • Community prevalence of drug resistance
  • Tendency to develop resistance during treatment
Biology
  • Intracellular pathogen vs. extracellular
  • Unusual life cycle (eg. helminthes, malaria) - need to kill the eggs or dormant cocoons or whatnot
Source control
  • Success of therapy overall is largely determined by this
Duration of therapy
  • Short course, eg. in urosepsis
  • Long course, eg. osteomyelitis
Assessment of response
  • To repeat the cultures, or not?
  • Is there a point in monitoring serology?
DRUG
FACTORS
Cost
  • Fluconazole: $57.99 AUD for 28 capsules (200mg)
  • Anidulafungin: ~$ 300 AUD per single 200mg dose.
  • Cost of monitoring the drug levels
  • How much is a life worth? you amoral monsters, etc.
Toxicity
  • Risk vs benefit
  • Some drugs (eg. chloramphenicol) are uniformly  "too toxic for use", as there are less toxic alternatives in almost every situation.
Bioavailability
  • Convenience of oral dosing
  • Certainty of IV dosing
  • Altered absorption via GI tract in context of critical illness, shock states, low flow, what have you.
Site penetration
  • Basic chemistry of the drug influences this aspect. Eg:
  • Penetration to the CSF (lipophilicity)
  • Exclusive distribution into the circulating volume, (hydrophilicity, or high serum protein binding)
  • Weird organ preference (eg. the strange affinity of fluoroquinolones for the prostate)
  • Exclusion of a drug from a specific organ (eg. the inactivation of daptomycin by lung surfactant)
Bactericidal vs bacteriostatic
  • Some agents are bacteriostatic against one pathogen and bactericidal against another
  • There may not be any in-vivo difference
Synergistic combination
  • Need for multiple agent therapy (eg. in Pseudomonas)
  • Unquestioned need for synergy (eg. cocktail for TB)
  • Advantage from synergy (eg. ampicillin with gentamicin for enterococci)
  • Need for broad-spectrum coverage (in which case you use multiple agents to start with, and then narrow the spectrum of cover)
  • Need for polymicrobial coverage (eg. surgical triple therapy, or in context of bone marrow transplant)
  • Need to prevent emergence of resistance (eg. the argument offered to defend the use of selective digestive tract decontamination; also, a genuine argument for the use of  rifampicin and fusidic acid together)

EXAMPLE OF AN ICU ANTIBIOTIC GUIDELINE

General rules

  • investigate first, start aggressively, and streamline quickly to reduce resistance
  • ideally 3 sets of blood cultures first from fresh sites, 10 mL each
  • empiric antibiotic choices based on syndromic approach

Pneumonia

  • ceftraixone + azithromycin (community acquired)
  • ceftriaxone + metronidazole (aspiration)

Abdominal focus

  • ampicilin + gentamicin + metronidazole

Neurosurgical infection

  • vancomycin 1g q6h + ceftazidime 2g q6h
  • no need for routine prophylaxis if EVD inserted

Necrotizing fasciitis

  • meropenem 1g q8h + benzylpenicilin 2.4g q4h + lincomycin 900mg q8h
  • if GPC on biopsy = suspect group A streptococcus -> IvIg 1g/kg on day 1, 0.5 g/kg/d on days 2 and 3

Sepsis unknown source or VAP

  • always cover prior resistant bacteria even if found much earlier (e.g. VRE if previously colonised)
  • tazocin + gentamicin
    if mild rash to penicillin then cefepime + gentamicin
    if anaphylaxis/ DRESS/ Steven-Johnson to penicillin then vancomycin + aztreonam + gentamicin
    use ciprofloxacin not gentamicin if eGFR <50, age >65y or recently on gentamicin
  • add vancomycin if:
    hospitalised >7 days or recent admission past 3 months
    prior MRSA
    pre-existing longterm lines
  • teichoplanin if VRE colonised
  • add fungal cover in severe sepsis using fluconazole if ECMO or yeast isolated
    if already on fluconazole change to caspofungin
    if already on posaconazole or voriconazle talk to ID!

When to stop antibiotics

  • Day 2
    vanc/ gent/ cipro/ flucon/ caspo
    if patient improved and no MRSA, resistant GNBs or candida
    streamline tazocin when sensitivities available
    switch gentamicin to ciprofloxacin if 2nd agent still needed
  • Day 6
    stop all antibiotics unless specific diagnosis requires longer – discuss with ID
  • Line sepsis
    Staph aureus – change lines, perform TOE -> Rx for 14d if no endocarditis or low risk
    Coag neg staph – change lines -> Rx 2-5 days

References and Links

LITFL

FOAM and web resources

Journal articles and textbooks

  • Lipman, J. Principles  of  antibiotic  use. Chapter 72  in Oh’s Intensive Care Manual
  • Leekha S, Terrell CL, Edson RS. General principles of antimicrobial therapy. Mayo Clinic proceedings. 86(2):156-67. 2011. [pubmed] [free full text]

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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