ß-Lactams

                                      - Penicillin

                                      - Cephalosporin

                                      - Carbapenem

                                      - ß-Lactamase Inhibitors

Vancomycin

Bacitracin

Cycloserine

Isonziad

Ethionamide

Ethambutol

ß-Lactams

MOA

Interfere w/ Cell Wall Synthesis by inhibiting Penicillin Binding Proteins: Transpeptidase, Transglycosylase and Carboxypeptidase. Peptidoglycan Monomers will build up and trigger Autolytic Enzymes to kill the bacteria

EXCEPT: B-Lactamase Inhibitors

ß-Lactam + Thiazolidine

Bacteriocidal

Active against: Gram(+) Cocci and Bacilli

                                   Gram(-) Cocci and Spirochetes

Inactive against: Gram(-) Rods                

Penicillin G = Acid Labile, Narrow Spectrum

Penicillin V = Acid Stable, Narrow Spectrum

Semi-Synthetic Penicillins

ß-Lactam + Thiazolidine

Bacteriocidal 

Methicillin             Ampicillin

  Nafcillin                Amoxicillin

Oxacillin  

Similar to Natural Penicillin except it has better activity against Gram(-) Rods

Resistant to ß-Lactamase

Increased Stability in Stomach Acid

ß-Lactam + Dihydrothiazine

Bacteriocidal

1st Gen: Cefazolin= Gram(+), Narrow Spectrum

2nd Gen: Cefuoxime= Expanded Spectrum w/  Gram(-)

3rd Gen: Cefriaxone= Broader Spectrum w/ more Gram(-)

4th Gen: Piperocillin= Extended Spectrum against Pseudomonas Aeroginosa

Pharmacology: Bacteriocidal

Broadest Spectrum in comparison to other ß-Lactams

Active against: Gram(-), Gram(+), Strict Anaerobes and most ß-Lactamases

Resistance: occurs by enzymatic inactivation by Carbapenemase

Resitant Gram(-) rods are increasing

MOA: Bind strongly to ß-Lactamase to protect ß-Lactams

Has very little antibacterial properties but it is used in combo w/ other ß-Lactams to protect it from degradation

Augmentin= Clavulenic Acid+Amoxycillin

Unasym= Sulbactam+Ampicillin

Zosyn= Tazobactam+Piperacillin

ß-Lactam

Drug Resistance Mechanisms

Intrinsic Resistance = Bacteria lacking a cell wall

(Chlamydia, Ureaplasma, Mycoplasma, Anaplasma)

Mutation of Porins = decreased permeability against Gram(-)

Inactivating Enzymes on Plasmids = inactivates components of the drug (ß-Lactamase)

Mutation of PBPs = MRSA

Vancomyocin

MOA: Inhibits Peptidoglycan cross-linking by binding to the terminal D-Alanine

Pharmacology: Bacteriocidal, Narrow Spectrum

Active against: Gram(+)

Resistance: VanA and VanB replace the terminal D-Alanine with Lactic Acid via MDR on Plasmids or Transposons

MOA: Binds to Bacteroprenol and inhibits transfer of Peptidoglycan monomers

Pharmacology: Bacteriocidal, Narrow Spectrum, Topical

Active Against: Gram(+)

Resitance: occurs by decreasing penetrance of the drug

MOA: Analog to D-Alanine leading inhibition of cross-linking

Active against: Mycobacterial Infections (Acid Fast)

Isonziad

(INH)

MOA: Inhibits Mycolic Acid

Active against: Mycobacterial Infections (Acid Fast)

MOA: Inhibits Mycolic Acid (derivative of INH)

Active against: Mycobacterial Infections (Acid Fast)

MOA: Inhibits Arabagalactan synthesis which is part of the cell wall in Acid Fast bacteria

Active against: Mycobacterial Infections (Acid Fast)

Cell Membrane Dysfunction

Polymyxin B and Polymyxin E (Colistin)

MOA: Cationic Detergent that disrupts the cell membrane

Pharmacology: Bacteriocidal, Narrow Spectrum

Active against: Gram(-)

30S: Aminoglycosides and Tetracyclines

50S: Macrolides, Chloramphenicol, Oxazolidinone, Streptogramin and Lincosamides

Aminoglycosides

(30S)

MOA: Inhibits the initiation complex at 30S resulting in misreading mRNA. Its uptake depends on oxygen

Pharmacology: Bacteriocidal, Narrow Spectrum, Poor GI absorption. Neurotoxic to CN 8

Active against: Aerobic, Gram (-)

Inactive against: Anaerobic, Gram (+)

Natural Derivatives: Tobramyocin, Neomyocin, Kanamyocin, Gentamyocin, Amikacin and Streptomycin (for Mycobacterium)

Synthetic Derivatives: Netilmycin and Amikacin

Resistance: 

Enzymatic Modification

Transport Interference

Mutation of binding sites

Accelerated Export of Drug

Tetracycline

(30S)

MOA: Binds to 30S to prevent binding of tRNA to mRNA

Pharmacology: Bacteriostatic, Broad Spectrum 

(w/ Chlamydia, Mycoplasma, Rickettsia)

Derivatives: Minocycline, Doxycyclin, Tetracycline

Side Effects: Photosensitivity, Calcium and Iron Chelator, Discoloration of Teeth

Resistance: Decreased Permeability, Active Efflux, Acetylation and Altered Binding Sites

Macrolides

(50S)

MOA: Binds to 50S and prevents tRNA release AFTER peptide bond formation

Pharmacology: Bacteriostatic, Used when theres Penicillin Allergy,  Broad Spectrum

(w/ Gram(+), Gram(-), Chlamydia and Mycoplasma)

Derivatives: Azithromycin, Erythromycin and Clarithromycin

Resistance: Alteration of 50S and Enzymatic Modification

Chloramphenicol

(50S)

MOA: Binds to 50S and inhibits the elongation phase by inhibiting Peptidyl Transferase (mitochondrial)

Pharmacology: Bacteriostatic, Broad Spectrum including Anaerobes

Lincosamides

(50S)

MOA: Prevents peptide bond formation

Pharmacology: Bacteriostatic

Active against: Gram(+) and Anaerobes

Inactive against: Gram(-)

Derivatives: Clindamycin and Lincomycin

Resistance: Methylation of 23S rRNA

Streptogramins

(50S)

Derivative and MOA: 

Quinupristin - Prematurely releases Peptides

Dalfopristin - Binds to 50S and prevents Elongation

Pharmacology: Bacteriocidal, Good for Vanco resistance with Staph and Enterococcus

Active against: Gram(+) 

Oxazolidinones/Linezolid

(50S)

MOA: Binds to 50S and interferes with the formation of an Initiation Complex

Pharmacology: Bacteriostatic, Gram(+), Reserved for VREF and MRSA

Sulfanomides and Trimethoprim

Para-aminosalicyclic Acid and Dapsone

MOA: 

Sulfonamides - Inhibits Dihydropteroate Synthase

Trimethoprim - Inhibits DHF Reductase

These enzymes are utilized in DNA synthesis in bacteria

Pharmacology: Bacteriostatic, Broad Spectrum, Usually used together

Active against: UTIs, GIT Infections and Respiratory Infections

Resistance: Overproduction of PABA or DHF, Folic Acid Dependency

SIMILAR TO SULFONAMIDES AND TRIMETHOPRIM

EXCEPT:

Narrow Spectrum --> Mycobacterium

Metronidazole/Flagyl

Quinolones/Fluroquinolones

Rifamycin

MOA: Reduced to its active form in vivo and disrupts DNA under Anaerobic conditions

Pharmacology: Bacteriocidal, Narrow Spectrum, active form of the drug disrupts DNA under anaerobic conditions

Active against: Anaerobic Bacteria, Anti-Protozoa

MOA: Inhibits DNA Topoisomeriase II/Gyrase and DNA Topoisomerase IV which is needed for DNA Replication, Recombination and Repair

Pharmacology: Bacteriocidal, Broad Spectrum, Affects bone and cartilage

Derivatives: Ciprofloxacin, Ofloxacin and Norfloxacin

MOA: Inhibits DNA-dependent RNA Polymerase needed for Transcription

Pharmacology: Bacteriocidal, Broad Spectrum

Active against:  Mycobacterium Tub. Gram(+)

Inactive Against:  Gram(-)