Beruflich Dokumente
Kultur Dokumente
Antimicrobial Agents
Dr. Salman
Khan
Chemotherapeutic Agents OR
Anti-microbials
Some Definitions:
Anti-Biotics: These are chemical substances
produced by various species of micro-
organisms ( bacteria, fungi, actenomycetes)
that suppress the growth of other micro-
organisms and may eventually destroy them.(
antibacterials, antivirals, anti-fungals)
Chemotherapeutic Agents OR
Anti-microbials
Important consideration: Common
usage often extends the term
antibiotics to include synthetic
antibacterial agents, such as
sulfonamides, quinolones, that are not
products of microbes (Goodman & Gillman)
BUT: we will call them anti-bacterials OR
antimicrobials OR Chemotherapeutic
agents derived from non-living things
OR synthetically produced.
Some Important Definitions:
Bactericidal: An antimicrobial drug that
can eradicate an infection in the absence of
host defense mechanisms; kills bacteria
Bacteriostatic: An antimicrobial drug that
inhibits microbial growth but requires host
defense mechanism to eradicate the infection;
does not kill bacteria.
Beta-lactam antibiotics: drugs with
structures containing a beta-lactam ring;
include penicillins and cephalosporins. The
ring must be intact for antimicrobial action.
Beta-lactamases: Bacterial enzymes
( penicillinase, cephalosporinase) that
hydrolyze the beta lactam ring of certain
penicillins and cephalosporins.
Minimal Inhibitory concentration: lowest
concentration of antimicrobial drug capable of
inhibiting growth of an organism in a defined
growth medium. (MIC)
Penicillin binding Proteins: Bacterial
cytoplasmic membrane proteins that act as
the initial receptors for penicillins and other
beta-lactam antibiotics. (PBPs)
Peptidoglycan, murein: Chains of
polysaccharides and polypeptides that are
cross linked to form bacterial cell wall.
Selective toxicity: More toxic to the invader
than to the host; a property of useful
antimicrobials.
Transpeptidases: bacterial enzymes
involved in the cross-linking of linear
Peptidoglycan chains, the final step in cell wall
synthesis.
Targets for Antimicrobial
∀• Bacterial Cell Wall ∀• Drugs that Bind to the
Synthesis Inhibitors 30S bacterial ribosomal
subunit, leading to cell
death
• Protein Synthesis
Inhibitors: interfere with
30S or 50S bacterial ∀• Agents that interfere
Membrane Permeability
∀• Antimetabolites
Bacterial cell wall synthesis Protein synthesis inhibitors: interfere
inhibitors: with 30S or 50S bacterial ribosome
penicillins
function.
Bacteriostatic
cephalosporins
chloramphenicol (Chloromycetin)
cycloserine
tetracyclines
vancomycin (Vancocin)
erythromycin
bacitracin
clindamycin
Drugs that bind to the 30S Agents that interfere with nucleic
bacterial ribosomal subunit, acid synthesis:
leading to cell death. rifamycins (rifampin (Rimactane)):
Biological
Toxic
Allergic Reactions to Antimicrobials
Beta-lactams
more likely with parenteral than oral
administration
shift to different family of drugs
Biological Adverse Effects of
Antimicrobials
More likely
Broad spectrum drugs
Alteration of normal flora
Skin
Mucous membranes
Gastrointestinal tract
Reproductive tract
Likely pathogens
yeasts
Clostridium difficile
Superinfection / Suprainfection
Antibiotic Associated Enterocolitis
ACCESS!!
ampicillin, tetracyclines, LINCOMYCIN, and
other broad spectrum antibacterials
spectrum -- broad, effective against anaerobes
Antibiotic Associated Pseudomembranous
Enterocolitis
Associated with overgrowth of Clostridium
difficile
Direct Toxic Effects of
Antibacterials
Life threatening
o Liver failure -- isoniazid
o Respiratory paralysis -- neuromuscular paralysis --
aminoglycosides
Severe
o Hearing loss (ototoxicity)-- aminoglycosides
o Nephrotoxicosis -- proximal tubular cells --
aminoglycosides
o Nephrotoxicosis -- tubular crystal formation --
Sulfonamides
o Decreased immune function -- many
antibiotics
o Bone / tooth malformation due to binding to
calcium -- tetracyclines
o Antibody production inhibited by --
amphotericin B, cefoxitin, doxycycline,
rifampin, cefotaxime, chloramphenicol,
moxalactam, and trimethoprim-
sulfamethoxazole.
o Microbiocidal activity impaired by -- amikacin,
cephalothin, gentamicin, sulfonamides,
tetracycline, and tobramycin
Unpleasant
o Mild abdominal discomfort / pain --
erythromycin
o Dizziness -- minocycline
o Mild vomiting
o Loose stools to mild diarrhea
o Tooth discoloration -- tetracyclines
Appropriate and Inappropriate
Uses of Chemotherapy
Appropriate Use
Before the organism is identified: either
combination therapy or a single broad
spectrum agent may be used.
After the organism is identified, a low-toxicity
regimen with a narrow-spectrum drug is
indicated.
Selection of the drug should be governed by
its selectivity for the most likely involved
bacteria and its toxicity.
First decide if an antibiotic is indicated since
antibiotics may be toxic. Inappropriate use
may hinder diagnosis, and can result in
Some Clinical Issues