Principles of antibiotic therapy in the critically ill

Today we are lucky to have Dr. Manjari Joshi, Associate Professor of Medicine, Division of Infectious Diseases at both the University of Maryland SOM and the R Adams Cowley Shock Trauma Center. For today’s lecture, Dr. Joshi will take us through the chaotic world of antibiotic use in critical care patients. She will show us how those rushed decisions made in when we first meet our patients REALLY can determine whether a patient even survives to go home. This talk has so tips, tricks, and pearls, one viewing might not be enough!

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PEARLS

TIP #1: Before choosing antibiotics take 3 factors into consideration:

1. Who is the patient you are treating (transplant, HIV, heart failure, etc..)
2. What environment is the patient coming from (hospital, nursing home, home…)
3. What organisms are possible based on local factors (exposures, recent outbreaks…)

TIP #2: Always consult an antibiogram in order to choose appropriate antibiotics based on your hospital and community susceptibilities

TIP #3: Leading cause of inadequate therapy is failing to consider multidrug resistant organisms (MDRO): 
Tip #4: Always consider the environment you are treating:

• Lung: acidic pH that can denature molecules (Aminoglycosides); surfactant that can inhibit Daptomycin
• CNS, Ocular, Cardiac: low penetration, will need HIGH concentrations of antibiotics
• Biofilms (heart tissue, devices): can decrease penetration, but can also decrease metabolic activity and bacterial multiplication which is vital for some abx to work

Drug Factors: 

1. Combination therapy is for a multitude of reasons:
   • Initial therapy broad coverage
   • Synergy– when 2 drugs “augment” each other
     • ex: Gentamicin can be used to lower the MIC of Ampicillin in order to treat gram neg rods (GNRs)
   • Polymicrobial infections
   • Resistance prevention (ex: Tb treatment)
2. Bioavailbility– only 5 drugs have equal PO and IV bioavailabilities:
   • Linezolid, Metroniadazole, Fluoroquinolones, Trimethoprim/Sulfamethoxazole, Rifampin
3. PK/PD parameters– its all about the Minimal Inhibitory Concentration (MIC)
   • Time dependent antibiotics (β-lactams)- only effective during the time above the MIC
     • Want 4-5 x the MIC constantly, achieved with repeated dosing OR continuous infusions
   • Concentration dependent antibiotics (Aminoglycosides): the peak of the drug determines efficacy
     • Can do once daily dosing as even when the drug is < the MIC it is still effective (post-antibiotic activity)
   • Area under the curve (AUC) antibiotics (Fluoroquinolones): the size of the area under the curve determines efficacy
     
4. Clearance: renal clearance can be increased with burns, drug abuse, leukemia, need to adjust dosing!
5. Resistance: Increased with: 3rd generation cephalosporins, Fluoroquinolones, Carbepenems
6. Empiric therapy: every hour delay to initiation of abx = ↑ 8% to mortality!
7. Deescalation: day 3 is the time to determine if there is a need to add, subtract, or change antibiotics based on the patients recovery
8. Duration of therapy: newer data shows large dose of antibiotics over a shorter period of time can be better and lead to less resistance:
   • CAP: 3-5 days, pyelonephritis: 5-7 days, intra-abdominal infections: 4-7 days
9. Inflammatory markers: CRP, Procalcitonin, etc are NOT ready for mainstream use….