MISCELLANEOUS

ANTIMICROBIALS

VMED5223
Veterinary Pharmacology
10-2007
Masami Yoshimura
myoshimura@vetmed.lsu.edu
Room2423
 New Class Of Antibiotics
Discovered In Fungi 10/12/2005
A peptide identified in a fungus found in northern
European pine forests possesses as much power
as penicillin. Reporting in the October 13 issue of
Nature, an international team of researchers say
they have isolated "plectasin," the first defensin
ever found in fungi. Defensins are peptides that
are produced by a wide range of animals to protect
themselves against infection. it is believed that this
new fungal defensin, plectasin, is more potent and
targets certain bacteria more specifically.
 Crocodile blood antibiotics
8/19/2005
hope
n Scientists at McNeese State University in Louisiana are
catching crocodiles and sampling their blood in the hope
of finding powerful new drugs to fight human infections.

No crocodile in Louisiana

Even horrific fighting wounds on the animal heal quickly

Newly Discovered Protein Kills Anthrax
Bacteria By Exploding Their Cell Walls
4/23/2006

Not all biological weapons are created equal. They are

separated into categories A through C, category A biological
agents being the scariest: One of these worrisome
organisms is anthrax. But work in Vince Fischetti’s
laboratory at Rockefeller University suggests that a newly
discovered protein could be used to fight anthrax infections
and even decontaminate areas in which anthrax spores have
been released.
Sites of action of different antimicrobial agents

http://www.life.umd.edu/classroom/bsci424/Lectures/LecturePP7&8Antibiotics.ppt #17
Miscellaneous Antimicrobials
n Nucleic Acid Metabolism
n Nitroimidazoles, Nitrofurans, Rifampin
n Cell Membrane
n Polymyxins
n Cell Wall
n Bacitracin, Vancomycin
n Urinary Antiseptic
n Methenamine
n Feed additive
n Virginiamycin, Carbadox
Nitroimidazoles
Imidazole
n Prodrug - need reductive activation of
nitro group (-NO2)
n Against anaerobic bacteria and protozoa
n Generate a highly reactive nitro radical
anion - damage DNA - bactericidal
n Selective toxicity derived from anaerobic
pathogen specific energy metabolism
n Mutagenic - not approved for food animals
Nitrofurans
Furan

n Prodrug - reduced to highly-reactive, short-lived

intermediates - DNA damage
n Selective toxicity - higher concentrations of
drugs and higher nitrofuran reductase activity in
microbial cells
n Broad spectrum - bacteria, protozoa, fungi,
mycoplasma
n Topical applications
n Carcinogenic - banned from food animals
Rifampin
Rifampin

n Bind to RNA polymerase -

inhibition of transcription - bactericidal
n Eukaryotic nuclear RNA polymerase does not
bind to rifampin (mitochondria)
n Against many G+, some G- bacteria
n Potent inducer of hepatic microsomal enzymes
involved in oxidative drug metabolism
n orange-red color to body secretions
n Excreted in bile
Polymyxins
n Cationic detergent from B. polymyxa
n Penetrate, disrupt membrane
n Bactericidal, resting & growing cells
Polymyxin B
n Rare resistance development 1

DAB
n Against G-negative bacteria
,-diaminobutylic acid
n No absorption from GI tract
n Nephrotoxic
n Topical application
Bacitracin
Bacitracin A

n Isolated from Bacillus subtilis (G+),

(Margaret Tracy, an American child in
whose blood it was first isolated)
n Block peptidoglycan monomer transport
n Serious nephrotoxicity
n No absorption from GI tract
n Topical applications, feed additive
n Against G-positive bacteria - bactericidal
From http://dustman.net/wendy/mibo3500/mibo3500ch10.pdf
 Vancomycin
Vancomycin

n Isolated from Streptomyces orientalis (G+)

n Block peptidoglycan monomer incorporation
n Against G-positive bacteria - bactericidal
n histamine release, ototoxicity, nephrotoxicity
n IV never IM (painful, irritating)
n No off-label use in food animals
Methenamine
Methenamine

n Urinary antiseptic
n Prodrug - produce formaldehyde at low pH
N4(CH2)6 + 6H2O + 4H+
4NH4+ + 6HCHO
n (most effective when pH<6)

n 10-30% decomposes in the gastric juice unless

the drug is protected by an enteric coating
n Against nearly all bacteria
n Not with sulfonamides - form precipitates
 Feed Additive
n Virginiamycin, Carbadox

n 70% of all antibiotics used in the US are given

to farm animals.
n 25 million pounds of antibiotics and related
drugs are administered to animals for non-
therapeutic purposes. This is more than 8 times
the amount used to treat disease in humans.
n 25-75% of all antibiotics administered to
animals could be passed unchanged directly
into the environment.
http://www.sustainabletable.org/issues/antibiotics/
US halts Chinese seafood imports
6/28/2007

The US has said it will halt imports of five types of farmed

Chinese seafood (catfish, basa, shrimp, dace and eel),
claiming they contain antibiotics that are not allowed in
North America. The FDA said it had found that Chinese
seafood tested between October 2006 and May 2007 was
repeatedly contaminated with antimicrobial agents.

Some of the substances included nitrofuran and

fluoroquinolone, which, according to the FDA, may help
build up a resistance to antibiotics when used in food
animals.
Less Antibiotic Use In Food Animals
Leads To Less Drug Resistance In
People, Study Shows
4/17/2006

Source: Infectious Diseases Society of America

Australia's policy of restricting antibiotic use

(fluoroquinolones) in food-producing animals may
be linked with lower levels of drug-resistant
bacteria found in its citizens, according to an
article in the May 15 issue of Clinical Infectious
Diseases.
 Phage Therapy
n Bacteriophages or "phage" are viruses that
invade bacterial cells and, in the case of lytic
phages, disrupt bacterial metabolism and cause
the bacterium to lyse. Phage Therapy is the
therapeutic use of lytic bacteriophages to treat
pathogenic bacterial infections.

n In August 2006, the United States Food and

Drug Administration approved spraying meat
with phages.
New Approach Could Lower Antibiotic
Requirements By 50 Times
1/28/2007

Antibiotic doses could be reduced by up to 50 times

using a new approach based on bacteriophages. It is the
phages' ability to channel through bacterial cell
membranes that boosts antibiotic effectiveness.
Experiments in mice revealed that 75% of those infected
with a lethal dose of Pseudomonas survived if the
antibiotic gentamicin was administered in the presence of
bacteriophages. None survived without the phages
(Microb. Drug Resist., 2006, 12 (3), 164).