Micro Flashcards
Decrease abx peak concentration
Reduced gut absorption
Increased Vd
Reduced penetration to site of action
Increase Abx peak concentration
Reduced protein binding
Reduced clearance mechanism
Increase Abx t 1/2
Decreased renal or hepatic clearance
Decreased overall metabolism eg hypothermia
Decrease Abx t1/2
RRT
INCREASED hepatic clearance
Increased glomerular filtration
Increased drug metabolism
Ways that critical illness can change pharmacokinetics and dynamics of Abx
Enhanced organ toxicity due to poor clearance and increased risk of damage to organs directly
How does shock affect pharmacokinetics and dynamics of Abx
Increased Vd
Decreased bioavailability of basic drugs (due to increase in alpha 1 glycoproteins)
Increased penetration of formerly impenetratable tissue eg meningitis
Impaired hepatic metabolism due to inhibited cyp 450
In renal failure you would..... For Beta lactams Carbapebems Aminoglycosides Fluriquinolones Glycopeptides
BL - can be dose of interval adjusted
Carb - as above
Amino - same dose, interval adjust, check levels
Fluor - same dose, interval adjust, check QT
Glycopeptides - same dose, interval adjust, check levels
Interval adjusting is most relevant for;
Concentration dependent abx which have toxicity with high levels
Examples - amino glycosides and Glycopeptides
Why do you dose adjust Abx
Relevant for time dependent abX that have toxicity associated with high concentration peaks
Eg fluroquinolones
Important to be above MIC for as long as possible - only need to load and then give small frequent doses to remain above MIC
Abx that rely on renal clearance
Beta lactams, cephalosporins and car spends Amino glycosides Fluconazole Aciclovir Vanc
Abx that do not need adjustment with renal failure
Linezolid Clindamycin Amphoteracin Azitgromyxib Ceftriaxome Voriconazole
General principles of abx dose adjusting in CRRT
Abx with time dependent killing - if rapidly cleared by CRRT need to give more frequently
Abx with concentration dependent killing - if cleared rapidly dose should be increased
If RRT is intermittent eg SLED should give at the end of each session
Drugs with large Vd, which do not rely on renal clearance
Eg - don’t need changes with RRT
Ceftriaxone Moxifloxacin Clindamycin Linezolid Voriconazole
Drugs that have large Vd and rely on renal clearance - need to have increased dosing interval as the filter can’t act the same way as the kidney with active pumps
Levofloxacin
Ciprofloxacin
Colostin
Amphiteracin
Drugs with small Vd that do rely on renal clearance - doe shouldn’t be adjusted with RRT as the filter can act as kidney in terms of glomerular filtration action
Beta lactams Carbapenems Amino glycosides Glycopeptides Fluconazole
MAY need to increase dose as filter may be more efficient esp fluconazole which must be increased at high filter rates
Time dependent Abx
Beta lactams Carbapenems Monobactams Linezolid Clindamycin Macrolides
Abx that kill bacteria most effectively when the bacteria are about to divide
Concentration dependent killing abx
Amino glycosides
Metronidazole
Daptomycin
Drugs that affect bacterial metabolism or protein synthesis; higher concentration means more enzyme molecules are inhibited
Time and concentration dependent killing
Fluroquinolones Azithromycin Tetracyclines Vanc Tigecycline
Drugs that inhibit DNA synthesis or other components of cellular division
Why are Abx not working
Wrong dose
Delayed dose
Inadequate source control
Inadequate blood levels
Inadequate penetration
Anti microbial neutralisation or antagonism
Superinfection or unsuspected secondary infection
Non bacterial infection
Non infectious source of illness
Eagle effect - paradoxical loss of effect
Factors that influence Abx choice
Disease factors - travel hx, occupation, ivdu, reliability of cultures
Host factors - age, allergies, pregnancy
Organism factors - source control, susectibility,
Drug factors - cost, toxicity, drug synergy
MIC definition
The lowest concentration of an antimicrobial that will inhibit visible growth of an organism after overnight incubation
Lower MIC = more effective
Drugs with post antibiotic effect
Those with concentration dependent kill characteristics; Amino glycosides Clindamycin Macro life's Tetracyclines Rifampicin Dalfopristin
Is when effects are seen long after concentration below MIC
Drugs with no post Abx effect
Beta lactams
Cephalosporins
Monobactams
These would benefit from continuous infusion
Polyenes
Antifungals - Amphiteracin and nystatin
They weaken cell wall
Amphiteracin
Active against fungi and yeast
Large Vd
No reliance on renal clearance
Toxicity - nephrotoxic, hypokalaemia, fever Ags chills, RTA, hypochromic normocytic anaemia
Azoles
Antifungals
Fluconazole, Voriconazole
Prevent synthesis of ergosterol
Early generations are only active against candida albicans and, most non albicans and are resistant
Fluconazole
Candida albicans Other candida resistant Active against cryptococcus No activity against aspergillus Penetrates into CSF Small Vd Relies on renal clearance, readily cleared by dialysis Toxicity - LFTS, alopecia, drug interactions (inhibits CYP 450)
Prophylaxis - use does not reduce mortality IV surgical pts
May reduce mortality if given in septic shock
Voriconazole
Covers all candida, cryptococcus, aspergillus
Highly protein bound
Vd massive
Not renally cleared, not dialysable
Inhibits CYP 450
Toxicity - long Qt, hallucinations, psychosis, drug interaction
Echinocandins
Anti fungal eg caspofungin
Inhibit cell wall synthesis by blocking synthesis of glycine 1,3 beta glucose synthase
Very active against candida, useless for cryptococcus, not very helpful for aspergillus
Highly protein bound
But dependent on renal excretion, not dialysable
Minimal toxicity
Toxicities of linezolid
Thrombocytopaenia Anaemia Neuropathy Lactic acidosis Serotonin syndrome
All due to mitochondrial toxin activity
