Antibacterial Agents

Methods of Resistance

 Target tissue alteration

 Active efflux
 Inactivation or degradation of antimicrobial agent
 Decreased uptake (mutation in permeases and/or porins)
 Production of decoy molecules – Competative inhibition
 Mutational resistance – Mutation on Chr gives resistance
 Plasmid resistance – Plamid conveys resistance and conjugation allows transfer of resistance to
susceptible cells.
 Repeat infections – Alternate a/b to avoid resistance backteria.

Inhibitors of Cell Wall Synthesis

Major Class Mechanism Resistance Susceptible Bacteria

Beta Lactams Bind to and inhibit ALTERATION OF Mostly G+ but some G-
enzyme which TARGET: Alter PBP (cephalosporin). Attack G- much get
bind PBP, or alter transport thru porins and periplasmic space
transpetidases, porins for G- to get to peptide.
carboxypeptidases, Inactivation of
inhibiting synthesis Microbial agent
of Peptidogycan with B-lactamace
layer by picking up the
gene for it.

Glycopeptides Inhibit cross G+

linkage of layers
preventing
incorporation of
subunits into
growing
Peptidoglycan
Bacitracin Inhibits PM and G+
blocks transport.
Interfere with
recycling of
transport proteins
Isoniazid Blocks synthesis of Reduced drug Acid Fast
Mycolic acid and uptake or
arabinoglactan alteration of
enzymes
  Augmentin – Combination drug therapy, Amoxil and Clavulanic Acit which is an inhibitor of beta
lactamase

Inhibitors of protein synthesis

Major Class Mechanism Resistance

Aminogycosides Interfere with ACTIVE EFFLUX
binding of f-met Mutation of ribosomal binding site – target
tRNA Decreased uptake of a/b via modify permeases for
G+ and porins/permeases for G-
Production of Proteins that mimic elongation factions
and act to protect the 30s ribosome.
Tetracyclines Inhibit tRNA entry
into acceptor site
therefore
prevening
elongation
Macrolides Prevent
translocation of
bact from A to p
site
Oxazolidnoes UNIQUE – Blocks
initiation of
translation by
blocking formation
of initiation
complex at the 30s
of the 70

Inhibitors of NA synthesis

Major Class Mechanism Resistance

Quinolones Inhibit DNA gyrase Changes in DNA gyrase subunit.
therefore prevent
transcription and
DNA rep
Rifampin and Inhibit DNA CHANGES IN CELL WALL PERMEABILITY AND
Rifamycin Depended Pol to DECREASED UPTAKE
inhibit
transcription
Metronidazole Destroys the NA
itself by blocking
H2 production,
bind DNA, reduced
nitro group
cytotoxic free rad
Anti – metabolites

Major Class Mechanism Resistance

Sulfonamides Compete with Permeability barriers
PABA resulting in Alteration in target - dihydrofolate reductase
decrease Folic Exogenous source of folic acid
Acid Synthesis Intrinsic resistance in organisms which use
exogenous thymidine (enterococci)
Trimethoprim Inhibit
dihydrofolate
reductace .
Therefore
decrease DNA

Inhibitors of Cytoplasmic Membrane Function

Major Class Mechanism Resistance

Polymyxins Forms pores to Mutation of the binding site (target)
increase cell Enzymatic modification of the antibiotic
permeability. Imp. Decreased transport of the antibiotic (this is primarily
For G- seen in gram negatives where the modified
phostpholipid bilayer and/or porins block transport)
Lipopeptides Trigger reapid
depolarization
resuling in loss of
membrane
potential and
decrease protein,
DNA, and RNA syn
Bacitracin Blocks transport of
cell wall
components and
damage integrity
of PM

Anti-Viral

 Attachment/Penetration

Fusion inhibitors (Enfuviritide).

 Uncoating – May require pH changes therefore neutralization helps

Neutralizing agents inhibit uncoating (Amantadine, Rimantatine)

  Nucleic Acid Synthesis

Base analogs (AZT)

Inhibition of nucleotide biosynthesis (Ribavirin)

Inhibition of DNA polymerase (Acyclovir, Ganciclovir)

Inhibition of Reverse transcriptase (Nevirapine) – HIV HBV

 Protein synthesis

Interferon

 Assembly

Protease inhibitors (Ritonavir)

 Release

Inhibit Neuraminidase or Hemagglutinin (Zanamivir)

 Antiviral Resistance

Most virus can alter a/b

Mutation of the binding site (target)

Enzymatic modification of the antibiotic

Decreased uptake of the antibiotic into host cell if step is intracellular

Anti Fungal

Major Class Mechanism

Polyenes Forms pore next to ergosterol cauing ion leak. Osmolality
changes allow easy Lysis. Targets membrane sterols
Azoles Inhibit Ergosterol production by blocking 14α demethylation
of it
Echinocandins Inhibit synthesis of glucan at the β1,3 glucan synthase
complex
Base analogs Inhibit RNA function or DNA synth.

Also Know that Dermatophyte infections are superficial cutaneous infections: Ringwork, Tenia versicolar
Anti Parasitic

The best way to control helmiths is to limit the burden of disease. Parasites are hard to treat because of
complex life cycles, parasitic cuticles and low selective toxicity because of the eukaryotic nature.
Trypanosomiais – Aftrican sleeping sickness. Suramin – Blocks glycolitic path

• DNA Replication

– Animoquinoline analogues – Chloroquine

• Interfere with DNA replication; hemoglobin digestion

– Diamidines – Pentamidine

• Bind DNA

– Nitroimidazoles – Metronidazole

• Inhibits synthesis

• Folic Acid Biosynthesis

– Pyrimethamine

– Inhibition of biosynthetic pathway

• Inhibitors of Protein Synthesis

– Paramomycin

• Bind to the ribosome

• Transport Disruption

– Benzimidazole – Mebendazole

• Multiple paths: inhibit glucose transport and fumurate reductase, disrupts

microtubles

• Inhibition of Neuromuscular Action

– Piperazines – Piperazine

• GABA antagonists; stimulate phagocytic cells

– Avermectins – Ivermectin

• Block neuromuscular action; GABA antagonists

• Resistance: Effelux, Mutations of target @ microtube, Alternative, Life cycle alter: larva to adult
or sex to asex