Antibiotics

• beta lactam
• cell wall synthesis inhibitor
• binds PBPs transpeptidase which are regulatory enzymes for cross linking of peptidoglycan layers

• Natural Penicillins: G / V: G+
• Amino Penicillins: Amoxicillin / Ampicillin: Broad
• Anti-Staph Penicillins (resistant to beta lactamase): Methicillin: not G-
• Anti-pseudomonal Penicillins: Piperacillin: Broad (including G-)

• Resistance
• G-: beta lactamase
• G+: modified PBP + inducible beta lactamase

• beta lactam
• cell wall synthesis inhibitor
• binds PBPs D alanyl Carboxy Peptidase

• 1st Gen: Cephalexin / Cephradine: G+
• 2nd Gen: Cefoxitin / Cefotetan: Anaerobes (G+ / G-)
• 3rd Gen: Cefepime: G- (G+) : Risk of forming extended spectrum beta lactamases
• 4th Gen: Cefclidine: Pseudomonas (Broad)
• 5th Gen: Ceftobiprole: MRSA (G+ / G-)

• Resistance
• G-: beta lactamase
• G+: modified PBP + inducible beta lactamase

• immipenem / meropenem
• beta lactam
• cell wall synthesis inhibitor
• binds PBPs and enzymes responsible for peptidoglycan synthesis

• Everything except: MRSA / VRE / Pseudomonas / Mycoplasma
• Reserve antibiotic (IV only)

very stable against beta lactamases

• binds to ß-lactamases of bacs and prevent enzymatic inactivation of ß-lactam
• used in combination with normal beta lactam antibiotic

• Vancomycin
• cell wall synthesis inhibitor
• inhibits cross-linkage of peptidoglycan layers (D-ala - D-ala)

inactive against G- (molecule can't pass outer membrane)

• Intrinsic Resistence Enterococci: D-ala - D-ser instead of D-ala - D-ala
• Plasmid mediated acquired resistance of Staph

causes depolarization of cytoplasmic membrane --> resulting in disruption of ioni concentration gradients

• Cell membrane inhibitor
• inserted into bacterial membrane and causes increased cell permeability

• G- bacili
• G+ dont have outer membrane so not as effective
• Topical usually

• cell wall synthesis inhibitor
• inhibit myocolic acid synthesis
• bactericidal

Mycobacetria  (antituberculotic!!)

inhibits arabinogalactan synthesis

• actively replicating bacteria
• antituberculotic!!

inhibits cross-linkage of petidoglycan layers

• protein synthesis inhibitor
• produce premature release of aberrant peptide chains from 30S ribosomes
• Bactericidal
• IV only

• G- bacilli
• Used only in serious infection, long term therapy and patients with renal failure
• high toxicity

• Resistance:
• Decreased uptake via cell wall (need oxygen to pass cell membranes so anaerobes are resistant)
• enzymatic modification of peptides of antibiotic
• mutation of ribosomal binding site (Enterococci)

• protein synthesis inhibitor
• Binds to peptidyl Transferase on 50S ribosomal subunit

• Broad Spectrum but only used for Typhoid fever
• Crosses blood brain barrier
• Toxicity: Irreversible aplastic anemia (affects human protein synthesis too)

• Resistance:
• acetyltransferase enzyme modifies chloramphenicol (plasmid)
• mutation fo outer membrane porin protein (G-)

• protein synthesis inhibitor
• prevent binding of tRNA at 30S ribosome
• bacetreiostatic

Broad Spectrum

• Resistance: very common
• decreased penetration into cell by mutation in outer membrane porin (G-)
• active efflux - most common
• altered target site
• Chelates with mmilk etc. in diet so could pass through GIT without absorption
• enzymatic modification of the antibiotic

• Protein synthesis inhibitor
• Linezolid
• prevents initiation of protein synthesis at 50S ribosome

Reserved for multidrug resistant strains

• Resistance:
• no cross resistance because it is a unique mechanism

• Protein synthesis inhibitor
• prevent polypeptide elongation at 50S ribosomal subunit
• Bacteriostatic

Absorbed better in G+

• Resistance:
• Methylation of 50S ribosomal subunit
• erythromycin esterase

• protein synthesis inhibitor
• Clindamycin
• prevents polypeptide elongation at 50S ribosomal subunit

• Anaerobic G- bacilli
• G+ cocci (staph)

• Resistance:
• Inducible methylation of 50S ribosomal subunit (cross resistance)

• Nucleic acid synthesis inhibitor
• Binds alpha subunit of DNA gyrase
• Bactericidal

• 1st Gen: G-
• 2nd Gen: Broad
• 3rd Gen: G+ and Anaerobes
• Popular because it si cheap, has high tissue distribution and can be taken orally

• Resistance:
• changes in porin proteins (G-)
• efflux pumps (unable to affect intracellular bacteria)
• inhibiting proteins

• nucleic acid synthesis inhibitor
• prevent transcription by binding DNA-dep. RNA polymerase

• Antituberculotic!!
• G+ cocci
• Hepatotoxic

• Resistance: develops fast
• mutation of beta subunit of RNA polymerase (G+)
• unable to be taken up by G-

• nucleic acid synthesis inhibitor
• disrupts DNA of bacs (is a cytotoxic compound)

• anti-metabolite
• Sulfonamide
• inhibits dihydropteroate synthase and disrupts folic acid synthesis (B9)

Broad

• Resistance:
• decreased affinity
• natural resistance if use thymidine as external source of B0 (enterococci)

• Anti-metabolite
• inhibits dihydrofolate reductase and disrupts folic acid synthesis