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MBC
  • [lowest] that kills 99.9% of inoculum
  • Used for serious infections: endocarditis, meningitis, sepsis
MIC
  • [lowest] that prevents growth of culture
  • determined for most infections
Antibiotics that cross BBB
  • antibiotic must accumulate in CSF @ therapeutic levels
  • inflammation facilitates penetration of antibiotic
  • Penicillins: 3rd gen. Cephalosporins
Antibiotics that cross Prostatic Epithelium
  • Fluoroquinolones
Crossing the lipid barrier: lipid solubility & pKa
  • + lipophillic = + crossability
  • Uncharged= + crossability
Immune System
  • Patient factors
  • Immunosuppression in general = need for higher dose or longer tx.
Hepatic & Renal Dysfunction
  • Patient Factors
Accumulation of antibiotics --> toxicity unless dosage is modified

Kidney:
most drugs eliminated in urine, (elderly affected)

Liver
: erythromycin, tetracycline
Pregnancy & Lactation
  • Patient Factors
Placenta permeable to ALL antimicrobials, most have no effects
  • Tetracyclines: tooth dysplasia & inhibits bone growth
  • Aminoglycosides: ototoxic
  • Anthelmintics: embryotoxic/teratogenic
Poor Perfusion & Age
  • Patient Factors
  • ↓Q --> ↓ [antimicrobial]
Neonates: kidney/liver not developed     
Contraindicated in Neonates
  • Chloramphenicol: Gray baby syndrome
  • Sulfonamides: kernicterus
Contraindications in Young Kids
  • Tetracycline: inhib. bone growth
  • Fluoroquinolones: inhib. cartilage growth
Bacteriostatic Drugs
inhibit proliferation of bacteria & reduce the spread of infx. until immune system eradicates mo.
Bactericidal Agents
Kill bacteria: [] or time-dependent killing
Narrow Spectrum Antibiotic
Acts only on a single group of mo's
  • Pen G: Gm+
  • Isoniazid: Mycobacterium
Extended Spectrum Antibiotics
Effective against Gm+ & few Gm-
  • Amoxicillin
Broad Spectrum Antibiotics
Wide range of microbial species; may --> superinfection
Combination Therapy (Pros/Cons)
Pros
  1. Synergy: B-lactams/Aminoglycosides, Sulfanomides/Trimethoprim
  2. Serious, polymicrobial infx.
  3. Empiric therapy
  4. Used for mycobacterial & HIV infx.: decrease resistance
Cons
  1. antagonism: Ex. B-lactams only effective when mo's are proliferating, so using a static agent would antagonize the -cidal drug
Drug Resistance
Resistance= when bacterial growth is not inhibited by the [highest] that the patient can tolerate

  1. Innate resistance
  2. Resistant Strains: spontan. mutation, acquired & selection (alteration in protein expression in resistant mo)
Genetic Alterations
  • Drug resistance
  1. Spontaneous mutation: chromosomal bc of nt changes. Ex. Rifampin-resistant-M. tuberculosis
  2. DNA transfer of plasmids: plasmids passed between cells (result of overuse) Ex. pts. w/ Vanc-R-SA have obtained the R plasmid from Vanc-R-enterococcus
Altered Protein Expression
  • Drug Resistance
  1. Alteration in target proteins: Δ PBP in MRSA, modification of 50S ribosome in Azithro-R-Gm+ mos
  2. Reduced accumulation: mos produce LPS layer or use an efflux pump to ↓ [Ab], Tetracyclines
  3. Enzymatic inactivation: mos produce Ab-inactivating enzymes, Ex. B-lactamases
CTI (Chemotherapeutic Index)
CTI = Toxicitypt/toxicitypathogen
=LD50pt/LD(orED)50pathogen
HIGH CTI = selective toxicity
Ampho"terrible" B: CTI=2 (bad!)
Complications with Antimicrobial Therapy
  1. Hypersensitivity: Ex. Penicillins & Sulfonamides (sx. urticaria --> shock)
  2. Direct Toxicity: Elevated [serum] --> direct actions on cellular fx. Ex. Aminoglycosides-->directly damage Organ of Corti
  3. Superinfections: bc of broad spec, or combination therapy
Superinfections
Caused by use of broad spectrum Ab that destroys normal flora of upper resp. & GI/GU tracts
  • C.difficile --> pseudomembraneous collitis
  • Staph Aureus--> staph. enterocolitis
  • Candida--> intestinal candidiasis
Classification of Antimicrobials
  • Chemical Structure (11)
  • Mechanism of Action (5)
  • Activity against specific kids of mos (6)
Inhibition of Cell Wall Synthesis: Bactericidal
  • Mechanism of action
  • B-lactams (Penicillins, Cephalosporins, Monobactams, Carbapenems)
  • Bacitracin
  • Vancomycin: inhibits synthesis of phospholipids & peptidoglycan X-linking
  • Fosfomycin
  • Cycloserine: antimycobacterial
Inhibition of Metabolism
  • Mechanism of action
  • Sulfonamides: inhibit folic acid synthesis of mo
Inhibition of protein synthesis
  • Mechanism of Action
  • Tetracyclines: bind to 30S bacterial ribosome & block tRNA binding to mRNA ribosome complex
  • Aminoglycosides: irreversible inhib, diffuse through channels formed by proteins of Gm- bacteria-->30S:misreading of the DNA
  • Macrolides: bind 50S & block translocation of the ribosome
-mycin: think protein synthesis inhibitor, EXCEPT for 1. Vancomycin 2. Fosfomycin 3. Daptomycin
Inhibition of DNA/RNA fx. or synthesis
  • Mechanism of action
Inhibition of cell membrane function
  • Mechanism of action
  • Daptomycin (unique: depolarizes membrane potential)
  • Polymyxins: bind to & disrupt cell membranes
B-lactam Abs
  • Penicillins
Peptide Ab
Sulfonamides
Tetracyclines
Aminoglycosides
Lincosamides
  • Lincomycin
  • Clindamycin
Macrolides: 14-16 mem. lactone ring
  • Erythromycin
  • Clarithromycin
Ketolide: (macrolide + ketone @C3 +carbanamine)
  • Telithromycin
Fluoroquinolones
Oxazolidinone
  • Linezolid
Streptogramins
Common (& safe) for Peds. (& Preggos)
  1. Penicillins: Amoxicillin, Augmentin, Pen. V
  2. Cephalosporins: Cephalexin, Cefprozil, Cefurox
  3. Macrolides: Erythromycin, Azithromycin, Clarithromycin
  4. Co-trimoxazole (SMX-TMP)
Common Antibiotics (List)
  1. Amoxicillin
  2. Augmentin (Amox/Clavulanate)
  3. Azithromycin
  4. Cephalexin
  5. Levaquin
  6. SMX-TMP
  7. Valtrex
  8. Fluconazole: (crosses BBB & antifungal)
  9. Doxycycline
  10. Penicillin V (oral of Pen G)
  11. Ciprofloxacin
  12. Omnicef: 3rd gen, broadest oral cephalosporin
  13. Avelox
  14. Clindamycin
  15. Mupirocin
  • B-lactam Antibiotics
Cell wall synthesis (must be actively proliferating) inhibitors: inhibit transpeptid. & X-linking
4-mem B-lactam ring essential to activity
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactam: Aztreonam (Azactam)
Penicillins (Classes)
  • B-lactam antibiotics
  1. Standard Penicillins: G (Pfizerpen) & V               Depot Penicillins: Benzathine pen G (Biciliin L-A), Benzathine pen G/Procaine pen G, Procaine pen G
  2. Antistaphylococcal Penicillins: Naficillin, Oxacillin, Dicloxacillin
  3. Extended Spectrum Penicillins: Amoxicillin, Amoxicillin/K+Clavulanate (Augmentin), Ampicillin, Ampicillin/sulbactamNa (Unasyn)
  4. Antipseudomonal Penicillins: Ticarcillin/K+Clavulanate (Timentin), Piperacillin, Piperacillin/tazobactamNa (Unasyn)
  5. Penicillin & Aminoglycides = synergy
B-lactamase inhibitors (can use with mos that produce B-lactamases)
  • B-lactam antibiotics
  1. Augmentin: amox/clavulanate
  2. Unasyn: amp/sulbactam
  3. Timentin: ticarcillin/clavulanate
  4. Zosyn: piperacillin/tazobactam
Cephalosporin Antibiotics
  • B-lactam antibiotics
Generations
  1. Cephalexin (Keflex, Panixine), Cefazolin, Cefadroxil
  2. Cefzil, Ceftin, Zinacef, Cefaclor, (Cefoxitin, Cefotan)
  3. Rocephin, Claforan, Fortaz (Tazicef), Cefizox, Omnicef, Suprax, Cedax, Vantin, Spectracef
  4. Cefepime (Maxipime)
Carbanapenems
  • B-lactam antibiotics
  1. Iminipenum (Primaxin IM/IV): broadest B-lactam on market, UTIs (Entero, Proteus) Resp. tract (Strept. pneum & Klebsiella) & Nosocomial (Serratia & Acinetobacter)
  2. Meropenem (Merrem IV): like Primaxin but >Gm- & <Gm+
  3. Doripenem (Doribax): same as Merrem but +Pseudomonas
  4. Ertapenem (Invanz): like Primaxin but INACTIVE against Pseudomonas & Acinetobacter
PharmacoKINETICS
what the body does to the drug
PharmacoDYNAMICS
what the drug does to the body
Size & MW
  • nature of drugs
MW: 100-1000
too small = no selectivity
too large = poor absorption

large & hydrophillic: need endocytosis
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