Antibiotics Flashcards
Main principle of antibiotic chemotherapy
Steady state concentration must be achieved at the side of infection for long enough or high enough concentrations to clear the infection without adversely affecting the patient or contributing unnecessarily to the development of antibiotic resistance
Chemotherapy
Use of drugs to kill or suppress growth of invasive microbial cells
Antibiotic
Natural substance produced by microbes that has the ability to harm or inhibit growth of other microbes
Selective toxicity
Ability of a drug to injure target cells without injury to the host
Minimum inhibitory concentration
Lowest concentration of an agent that prevents visible bacterial growth
Minimum bacteriocidal concentration
Lowest concentration that reduces the number of vaiable bacteria
How do we achieve selective toxicity
Exploit differences between pathogen and host cells
Target unique cellular processes to the pathogen
Target similar processes using differences in drug affinity

Bacteriostatic
Suppressing cell proliferation but not causing cell death
ultimately depends on the host immune system to clear the infection
Bacteriocidal
Property of causing cell death
Dependent on active bacterial proliferation
Time dependent antibiotics (T>MIC)
Benefits from continuous drug exposure rather than high concentrations
Ex. Cell wall inhibitors 
Peak concentration dependent antibiotics (Peak>MIC)
Permits less frequent dosing schedules
Ex. Aminoglycosides, flouraquinolones
AUC dependent antibiotics (correlates with time c concentration)
Total cumulative dose overtime is the factor determining infection clearance
Ex. Glycopeptides 
Innate antibiotic resistance
Antibiotic was never active
Ex. Anaerobes are resistant to oxygen dependent processes
Arrows are resistant to drugs are requiring enzymatic reduction and low oxygen environments
Gram-negative bacteria are resistant to lipophilic and high molecular weight hydrophilic drugs due to the lack of penetration through the outer membrane poring
A typical bacteria lack cell walls and are therefore resistant to cell wall synthesis inhibitors
Aquired resistance
Loss of formerly active antibiotic by vertical or horizontal transfer 
Ex. Inactivation by bacterial drug metabolizing enzymes
Decreased uptake and or increased efflux transporters
Reduced binding affinity due to mutations in amino acid sequence of target site proteins
Bypass blockade of target metabolic processes or pathway
Consequences of resistance
Failure to clear primary infections
Increased risk of secondary infections due to antibiotic activity against her mental flora
Antibiotics are_ and thus have poor _
Hydrophilic, oral bioavailability
You should consider direct administration when treating infection in
Bone, eye, pulmonary epithelium, abscesses tissue, or biofilms due to their difficult to penetrate nature
What route of antibiotic administration is preferred for critically ill patients or those with meningitis or endocarditis?
IV
Duration of antibiotic use
Minimum duration required for maximum efficacy
Biomarkers of infection such as procalcitonin are used to optimize treatment duration
Antibiotic distribution needs to exceed _ at site of infection
MIC breakpoint
CNS infection; hydrophilic agents cross intact blood brain barrier _
Poorly
Obese patients should be dosed based on _ rather than _
Ideal
Actual
Antibiotic doses must be adjusted based on
Liver and kidney (check CrCL) function
Combination therapy indications
Mixed infections
Empiric therapy
Drug synergy
Prevention of resistance
Disadvantages of combination therapy
Drug antagonism
Toxicity
Superinfections
Prophylactic therapy and its indications
Treat an infection before it’s an issue
Before surgery
Bacterial endocarditis
Opportunistic infections in immunocompromised patients
After exposure to sexually transmitted infections
Aminoglycoside toxicity
Ototoxicity and nephrotoxicity
Tetracycline toxicity
Bone growth suppression
 tooth staining
Sulfonamide toxicity
Kernicterus in nursing infants
Folate Antagonist toxicity
Maternal folic acid deficiency causing neural tube defects
Fluoroquinolones
Toxic to developing Cartlidge
Targets in Gram + bacteria
Thick peptidoglycan cell wall- antibiotics readily diffuse
Plasma membrane- hydrophilic antibiotics cross poorly 
Targets in Gram - bacteria
Thin cell wall (lipid membrane) hinders transport of many antibiotics
Small hydrophilic drugs across the outer membrane via passive transport through Porins
Periplasmic space concentrates inactive enzymes 
Atypical bacteria (chlamydia, mycoplasma, rickettsia, legionella)
Lack peptidoglycan layer
Resistant to cell wall inhibitors
Reside within host cells so drugs must be lipophilic to cross host cell membrane
