Link To The Antibiotics Chapter Of The Internet Book Of Critical Care With Excerpts

This post is a link to The Antibiotics Chapter from The Internet Book of Critical Care [Link is to the print chapter] by critical care specialist Dr. Josh Farkas, January 24, 2019.

Here is the direct link to the podcast for the Antibiotics chapter.

Be sure to see and review all of the excellent References Dr. Farkas includes in his Chapter. Each of his references has a link to the PubMed Abstract. And  Dr. Farkas recommends we consider two resources:

Special Acknowledgement: Pharmacokinetics and doses listed above were largely drawn from the Hopkins Antibiotic Guide and Antibiotic Essentials 15th Ed. by Cunha & Cunha. This chapter isn’t intended to replace these resources, which I would fully recommend obtaining and consulting.

The podcast that accompanies this chapter [direct link to the podcast] is 59 minutes long and worth listening to as often as possible. Before or after each listen you want to review the awesome chapter itself.

There are so many pearls in this resource.

For example, what should you do when the patient hasn’t gotten better after two or three days [I like a person to be clearly better after two days] of your antibiotic treatment. Dr. Farkas emphasizes that we should not just assume that we picked the wrong antibiotic. There are other possibilities that it is critical to think of: See Causes of antibiotic treatment failure*.

*This link that Dr. Farkas included in his chapter is from the awesome Deranged Physiology [This site is definitely worth exploring]:

A free online resource for Intensive Care Medicine.
An unofficial Fellowship Exam (CICM Part 2) preparation resource.

In his chapter Dr. Farkas referenced DRESS Syndrome which can be caused by the Carbapenem, ertapenem. Here is a link to two articles on DRESS Syndrome* which can be caused by a number of different medications, can occur after the medicine has been discontinued, and may have a mortality rate of 10%.

*(1) DRESS syndrome: remember to look under the skin, Prescriber Update 32(2): 12-13, June 2011 from the New Zealand Medicines and Medical Devices Safety Authority.

*(2) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome [PubMed Abstract] [Full Text HTML] [Full Text PDF]. J Clin Aesthet Dermatol. 2013 Jun; 6(6): 31–37. J Clin Aesthet Dermatol. 2013 Jun; 6(6): 31–37.

The above article has been cited by 20 articles in PubMed Central.

This post is a link to The Antibiotics Chapter from The Internet Book of Critical Care by critical care specialist Dr. Josh Farkas, January 24, 2019:

CONTENTS

Here are some excerpts from this awesome chapter:

*The clinical significance of enterococcus in the context of polymicrobial abdominal/pelvic infection is unclear. It is possible that they are just along for the ride.

First-line agents for common gram-positive pathogens3
  • MSSA – Cefazolin or nafcillin.  Nafcillin required for CNS penetration.
  • MRSA – Vancomycin, linezolid (not preferred for bacteremia), or daptomycin (ineffective in pneumonia)
  • Staphylococcus lugdenensis (“slug”) – Vancomycin empirically, narrow to oxacillin if sensitive.
  • Enterococcus faecalis – Ampicillin preferred (99% sensitive), may be superior to vancomycin.
  • Enterococcus faecium (VRE) – Linezolid is first-line, daptomycin 2nd line.
  • Enterococcus faecium (non-VRE) – Vancomycin or linezolid
  • Streptococcus anginosus – Penicillin G is 1st line, ceftriaxone is 2nd line
  • Streptococcus pyogenes (Group A strep) or Streptococcus agalactiae (Group B strep) – Penicillin G is 1st line, cefazolin is 2nd line
  • Streptococcus pneumoniae (not meningitis) – Ceftriaxone is 1st line, Vancomycin is 2nd line in severe allergy.
  • Listeria spp. – Ampicillin is 1st line, trimethoprim/sulfamethoxazole is 2nd line.
Commonly used agents for common gram-negative pathogens
  • E. coli, Klebsiella pneumoniae, Klebsiella oxytoca
    • No risk factors for ESBL species:  Ceftriaxone or cefepime
    • Risk factors for ESBL species:  Carbapenem
  • Proteus species:  Piperacillin-tazobactam or cefepime
  • Enterobacter or Citrobacter:  Cefepime or carbapenem
  • Pseudomonas:  Piperacillin-tazobactam, cefepime, or meropenem

aminoglycosides

agents
  • Gentamycin:  Best gram-positive coverage
  • Tobramycin:  Workhorse aminoglycoside, good gram-negative coverage
  • Amikacin:  Best gram-negative coverage (often reserved for resistant pseudomonas)
spectrum
  • Gram-positives:  Covers MSSA and Enterococcus faecalis
  • Gram-negatives:  Excellent coverage (tobramycin and amikacin cover pseudomonas)
use
  • Gentamycin is used for synergy against Enterococcus faecalis endocarditis, with other agents (at reduced dose of 1 mg/kg q8hr)
  • Gram negative bacteremia with refractory shock
  • Urinary tract infection
Medscape monographs:  GentamycinTobramycinAmikacin

aztreonam

spectrum
  • Covers gram-negatives well (including pseudomonas), but nothing else.
  • May fail in species that have inducible AmpC beta-lactamases (citrobacter, enterobacter, morganella, proteus, providentia, and serratia).
use
  • Excellent gram-negative coverage, safe for use in patient with anaphylaxis to penicillin (but might cross-react with ceftazidime).4
  • Can be used for many gram-negative infections (e.g. pneumonia, soft tissue, urinary tract, bacteremia).
  • Logical choice for patient found to have gram-negative bacteremia.
Medscape monograph:  Aztreonam

carbapenems (meropenem, ertapenem)

spectrum: meropenem
  • Gram-positives:  Generally very good, but does miss MRSA and Enterococcus faecium.
  • Gram-negative coverage:
    • Overall excellent (including pseudomonas, ESBL and Amp-C multi-drug resistant species).
    • Some carbapenem resistance is starting to emerge among enterobacteriaceae (especially among Klebsiella pneumoniae); this varies widely depending on geography.
  • Anaerobic coverage:  Excellent (but doesn’t cover Clostridium difficile).
spectrum:  ertapenem
  • Main differences compared to meropenem:
    • 1) Lacks coverage of pseudomonas and acinetobacter.
    • 2) Limited activity against enterococci.
  • May be superior for non-pseudomonal gram-negatives (due to broad use of meropenem and development of meropenem resistance)
use
  • Broad-spectrum beta-lactam antibiotics with a range of potential applications (e.g. pneumonia, intra-abdominal infections, urinary tract infections, bacteremia, soft tissue infections).  Unlike most beta-lactams, carbapenems decrease lipopolysaccharide release from gram-negative bacteria, which could give them an advantage in the treatment of gram-negative septic shock.
  • Front-line choice for multi-drug resistant gram-negative bacteria (e.g. bacteria with inducible AmpC beta-lactamases, ESBL bacteria).
  • Great for patient with history of anaphylaxis following penicillin exposure who requires broad-spectrum coverage.  Carbapenems (especially meropenem) have an extremely low risk of allergic reaction.  Using a carbapenem may be safer than a multi-drug regimen (e.g. vancomycin/aztreonam/metronidazole) and faster to administer in septic shock.  Meropenem can actually be given as a bolus.
  • Meropenem has better tissue penetration (e.g. allowing it to be used in meningitis), whereas ertapenem has a longer half-life (allowing once-daily dosing).
Medscape monographs:  ErtapenemMeropenem

cephalosporin G1: cefazolin

spectrum
  • Gram-positives:
    • MSSA, Staph saprophiticus, coagulase-negative staph which are sensitive to oxacillin.
    • All non-enterococcal streptococci (e.g. streptococcus groups A, B, C, G).
  • Gram-negatives
    • Hits some, but not adequate for empiric therapy against gram-negative infections.  May be used as step-down therapy once sensitivities available.
use
  • Empiric coverage before culture known:
    • Cellulitis (often treatment of choice for cellulitis without evidence of abscess/purulence).
  • After culture/sensitivity known:
    • Bacteremia, including MSSA (Increasing evidence that cefazolin is first-line therapy in MSSA bacteremia, superior to nafcillin).6  Note however that nafcillin has superior CNS penetration, so nafcillin might be better for endocarditis with brain emboli.
    • Pneumonia (e.g. due to MSSA or Group A streptococcus)
    • Urinary tract infection (e.g. due to sensitive E. coli or Proteus mirabilis)
  • Synergistic en vitro with vancomycin against MRSA, with some supportive clinical evidence as well.7
toxicity/contraindications
  • PCN allergy is not a contraindication.  Cefazolin has a unique side-chain, which isn’t cross-allergic with any other beta-lactam.8  It can also be used in patients with hypersensitivity reactions to nafcillin.8
  • Drug rash, drug fever
  • Transaminitis
  • Neutropenia, thrombocytopenia
  • Seizures, delirium

Medscape monograph: Cefazolin

No one uses second generation cephalosporins in the ICU.

cephalosporin G3: ceftriaxone

spectrum
  • Gram-positives
    • MSSA:  Does seem to cover, but inferior to cefazolin and suboptimal for MSSA bacteremia.9
    • All non-enterococcal streptococci.
    • Streptococcus pneumoniae (resistant strains will usually still be cured clinically, with the exception of meningitis).
  • Haemophilus influenzae, Moraxella catarrhalis
  • Neisseria meningitidis
  •  Gram-negatives
    • Generally good coverage.
    • Misses:  Pseudomonas, extended-spectrum beta lactamase organisms
    • Should be avoided in species that may have inducible AmpC beta-lactamases (citrobacter, enterobacter, morganella, proteus, providentia, and serratia).
use
  • Pneumonia
  • Meningitis (covers nearly everything; will miss listeria and resistant streptococcus pneumoniae)
  • Urinary tract infection without septic shock
  • Bacteremia, endocarditis
  • Peritonitis, prophylaxis in cirrhotic patients with GI hemorrhage.
Medscape monograph:  Ceftriaxone

cephalosporin G3: ceftazidime

start here

 

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