Antibacterial agents Flashcards
List 5 ways bacterial resistance to antibiotics
efflux pump decrease entry altered target site enzymatic degradation Bypass pathways
Selective toxicity
affects microbes > hosts
Examples of selectivity toxicity
Folate metabolisms, protein/nucleic acid synthesis (ribosomes, gyrase), Cell walls, fungal cell membrane (cell wall diff structures)
Antibiotic spectrum (3)
Narrow
Extended
Broad
Narrow antibiotic
Gram + or -
Extended antibiotic
Gram + and -
Broad antibiotic
Gram + and - and atypical
Three categories of resistance
natural/intrinsic
escape
acquired
Natural/intrinisic resistance
lack drug targets
Escape resistance
Precursor still there. Drug stopped synthesis but source is not removed - important to surgically drain/remove precursors
Acquired resistance
Mutational (requires multiple steps/generations)
Plasmid mediated: Conjugation (physical contact), transduction (virus carrying resistance), Transformation (DNA from environment)
Drugs easily enter CSF
chloramphenicol
Sulfonamides - trimethoprim
Cephalosporins (3/4)
Rifampin - Metronidazole
Enter CNS with inflammation
Penicillins
vancomycin
ciprofloxacin
tetracycline
Enter CSF poorly
aminoglycosides
cephalosporins (1/2)
Erythromycin
Lindamycin
Cholesterol is in mammalian membrane as _______ is in fungal cell membran
ergosterol
Inhibition of synthesis of stage 1 cell wall
Alanine racemase: cycloserine; enolpyruvate transferase: fosfomycin
Inhibition of synthesis of stage 2 cell wall
D-ala-D-ala pentapeptide: Vancomycin; bactoprenol lipid carrier: bacitracin
Inhibition of synthesis of stage 3 cell wall
Transpeptidase: penicillins, cephalosporins, monobactams, carbapenems
inhibition of synthesis/damage to cell membrane
daptomycin, polymixin B
Modification of synthesis or metabolism of nucleic acids
DNA gyrase: Fluoroquinolones
RNA pol: rifampin
DNA: metronidazole, nitrofurantonin
Inhibition/modification of protein synthesis
30S: aminoglycosides (irrev), tetracyclines
50S: clindamycin, macrolides, chloramphenicol, treptogramins
Isoleucyl-tRNA synthetase: mupriocin
Modification of intermediary metabolisms (ie. folate)
Dihydropteroate synthase: Sulfonamides
Dihydrofolate reductase: Trimethoprim
bactericidal mechanisms
inhibition of cell wall synthesis
disruption of cell membrane function
interference with DNA function/synthesis
Bacteriostatic mechanism
inhibition of protein synthesis (except aminoglycosides)
inhibitions of intermediary metabolic pathways
When to use bactericidal over bacteriostatics reasons (4)
- severe infection
- quickly/irreversible
- impaired host defense
- Not accessible to host immune system responses
example of altered targets
MRSA, s. pneumoniae, enterococci to b-lactam antibiotics (penicillin binding proteins)
Enteroccci (VRE), staphylococci (VRSA) –> vancomycin (peptidoglycan side chain)
S. aureus, pseudomonas to fluoroquinolones (DNA gyrase)
Strep/staph/etnerococci to macrolides, clindamycin (50S methylation)
Examples of Enzymatic destruction
S. aureus, P. aeruginosa, bacteroides, enterococci to b-lactam antibiotic (b lactamase)
Aminoglycosidesstaph/strepneisseria - chloramphenicol (acetyltransferase)
Examples of alternative resistant metabolic pathways
Streptococci to sulfonamides: over production of PABA or thymidine nucleotides
Examples of decreased entry (natural resistance)
b lactam antibiotics (pseudomonas aeruginosa)
Fluoroquinolones (P species)
Aminoglycosides (E. coli, pseudomonas)
Examples of increased efflux
Tetracyclines - strep, staph, entero
Fluoroquinolones (P species)
Macrolides
antimicrobial action outpatients vs hospitalized patients
hospital:culture sensitive within 24 hrs
outpatient
prescribed empirically based on symptoms, anatomic site, local patterns of infections, patient demographics
Selective distribution/accumulation (benefits)
Clindamycin - bone (osteomyelitis)
Macrolides - pulmonary cells (URI/pneumonia)
Tetracyclines - gingival crevicular fluids/sebum (periodontitis/acne)
Nitrofurantoin - urine (UTI)
selective distribution (toxicity)
Aminoglycosides - inner ear/renal brush border (ototoxicity, nephrotoxicity)
Tetracyclines bind Ca in developing bone/teeth (abnormal bone grwoth/tooth discoloration)
Renal excretion and formula between MD and CL
Antibiotics eliminated by renal excretions - monitored by serum creatinine and creatinine clearance (SCr and CrCl)
MD/t = CPss x CL
Hepatic metabolisms considerations
Drug drug interactions
interpatient rate difference (genetic polymorphism)
Hepatotix action - generally avoid
List narrow spectrum antibiotic drugs
Aminoglycosides Penicillinase-resistant penicillin clindamycin Vancomycin Metronidazole Penicillin G, V
List of extended spectrum antibiotics drugs
aminopenicillins (amox, amp)
Cephalosporins
fluoroquinolones (cip, levo)
Carbapenems
List of broad spectrum antibiotics drugs
Macrolides Chloramphenicol Fluorquinolones (Moxi, Gemi) Sulfonamides Tetracyclines Trimethoprim
Adverse reaction/toxicity types
DIrect to the drug
Indirect - allergies, salt effects/fillers, drug drug interactions/affect CYP
Distrubance of host microflora - superinfection - overgrowth of normal suppresed pathogenic organisms (ie. Clostridium difficile - pseudomembranous colitis)
stage 1 of bacterial cell wall synthesis
1: synthesis/assembly of cell wall subunits - in cytosol
stage 2 of bacterial cell wall synthesis
- Linear polymerization of subunits - at cell membrane
Stage 3 of bacterial cell wall synthesis
- Cross-linking of peptidoglycan polymers - at cell wall
Antibiotics that block stage 1
fosfomycin, cycloserine
Antibiotics that block stage 2
Bacitracin, vancomycin
Antibiotics that block stage 3
Penicillins, cephalosporins
