Biomedical Engineering Reference
In-Depth Information
OHH
3
N
CCN
H
+
N
N
O
H
3
N
S
-
SO
3
O
CH
3
C
H
3
C
COOH
Aztreonam
HH
S
CH
2
C
2
H
5
CCC
-
N H
CO
L
-Leu
D
-Glu
CH
3
NH
2
-
α
+
D
-Asp
L
-Asn
L
-His
ε
α
L
-Lys
L
-Ileu
D
-Phe
+
L
-Ileu
D
-Orn
Bacitracin A
FIGURE 25.3
Aztreonam and bacitracin A.
25.2.3 V
ANCOMYCIN
AND
R
ELATED
P
RODUCTS
Vancomycin was isolated by Williams in 1956 in the Lilly laboratories from a culture of
Streptomyces
orientalis
. Its very complex structure was studied mainly by D.H. Williams in Cambridge.
Vancomycin is active only against Gram-positive microorganisms, mainly staphylococci and
streptococci, and also against
Clostridium difi cile
. It is a quite toxic product. As intramuscular
injections cause pain and necrosis, the administration has to be intravenous. Febrile reactions,
thrombophlebitis, ototoxicity, and nephrotoxicity are the other side effects. For these reasons, its
use is limited to infections due to resistant staphylococci and streptococci, mainly in patients treated
with immunosuppressants. Oral application may be used in pseudomembranous colitis, due to
Clostridium difi cile
, which may occur after the administration of antibiotics like lincomycin and
clindamycin. Teicoplanin, also named teichomycin, was isolated in 1978 from
Actinoplanes teicho-
mycelicus
. Its structure and activity spectrum are related to that of vancomycin.
25.3
ANTIBIOTICS AFFECTING THE CYTOPLASMIC MEMBRANE
25.3.1 A
NTIBIOTICS
THAT
D
ISORGANIZE
M
EMBRANE
S
TRUCTURE
25.3.1.1 Tyrothricin
Tyrothricin was isolated from
Bacillus brevis
by R. Dubos in 1939. Because of its toxicity, e.g., lysis
of erythrocytes, its application has always been limited to external use like troches for throat infec-
tions, nose drops, etc.
It is a mixture of a neutral acetone-ether soluble part (about 20%) called gramicidin and a solvent
insoluble part, tyrocidine HCl. Tyrocidine is a cyclic peptide. Gramicidin is a mixture of neutral
linear peptides. It is neutral because the
N
-terminal amino group is formylated and because the
carboxy group is linked to ethanolamine (Figure 25.4).
