AMINOGLYCOSIDES

Broad spectrum
Gentamicin
Amikacin
Tobramycin
Netilmicin
Limited clinical
application
Streptomycin
Neomycin
Kanamycin
Synergy
Do not work alone on serious infections by enterococci or
streptococci but can increase antimicrobial activity of other
drus when used in combination for these infections
Broad spectrum
Gentamicin
Amikacin
Tobramycin
Netilmicin
Limited clinical
application
Streptomycin
Neomycin
Kanamycin
Synergy
Do not work alone on serious infections by enterococci or
streptococci but can increase antimicrobial activity of other
drus when used in combination for these infections
2009 Mark Tuttle
Synergy: Do not work alone on serious infections by enterococci or
streptococci but can increase antimicrobial activity of other drugs
when used in combination
NOT effective against anaerobes b/c aminoglycosides need O2 for
uptake
Target Organis Me!"anis Si#e e$$e!ts A%s&r'ti&n E(!reti&n )esistan!e
-Intrabdominal
infections with
massive bacterial
numbers
- Novel
sage!
Treat disease with
premature stop
codon "#$ since some
activity in human
ribosomes
"% instead of & at
r'N&$
-(inds at *0S ri%&s&al
where aa-t'N& binds
-&ction independent of
bacterial concentration
"Different from most )-
lactams$
-%et *ost-antibiotic effect#
-(acteriocidal+ ,ost other
protein-synthesis inhibitors
are -ust bacteriostatic
-To.icity is related to the TI,/ drug is
above to.ic concentration
-Neuromuscular blockade 0 curare-like
"binds 1a
22
at presynaptic terminal$
'eversible with 1a
22
gluconate
-Nephroto.icity 0 Intereferes with tubular
function including e.cess loss of ,g
22
and
1a
22
Increased to.icity with 3anc4 &mph (4
cephalosporins4 and diuretics
-Ototo.icity
&uditory &ND vestibular#
-N&t a%s&r%e# +ell &rally &r
t&'i!ally
-Does not penetrate human cell well
-Nee# I, &r IM
-5ighly water soluble
-6ittle binding by pp
-*eak conc in 78 min
--&&r 'enetrati&n int& CS.
-On!e a #ay #&sing is more
effective than same amount split and
less nephroto.ic+ *robably due to
post-antibiotic effect+
-'enal e.cretion
but some
reabsorbed in
pro.imal tubules
-Impaired uptake of
drug
-Drug modification
"&denlyation4
acetylation4
phosphorylation$
S-ECTINOMYCIN "&minoglycoside-like4 a )-6actam substitute$
-*enicillin-resistant
Neisseria
-Target *0S ri%&s&al
subunit
-9imilar structure as
&minoglycosides
-6ow to.icity
-Nausea4 chills4 fever4 di::iness
-I, in-ection - -*enicillin-resistant
Neisseria
Ot"er /0La!tas
Nae Target Organis Si#e e$$e!ts -"ara!&kineti!s
CA)1A-ENEMS -(road spectrum 0 useful in emergency treatment
-No cross-resistance with other )-lactams+ Not well
recogni:ed by )-lactamases
- -
Ii'ene0
!ilistatin
- -1ilastatin 're2ents ki#ney t&(i!ity of imipenem by blocking
active uptake by renal tubule cells4 5O;/3/'!
-CNS t&(i!ity! decreased consciousness and myoclonic -erking+
,ay be result of inhibited imipenem transport out of 19< by
cillistatin
-1ilistatin inhibits renal
dehydropeptidase-=4 en:yme which
inactivates imipenem
Mar&'ene -6ess active vs+ %ram 2
-,ore active vs+ %ram -
-6ess 1N9 to.icity than imipenem/cilastatin because no
cillastatin#
-*ossibly increased renal to.icity
-NOT hydroly:ed by
dehydropeptidase-=
/0La!ta Su%stitutes
Nae Target Organis Me!"anis Si#e e$$e!ts A%s&r'ti&
n
)esistan!e
,an!&y!in -,ethicillin-resistant Staph. aureus ",'9&$
"I3$
-(ackup drug vs+ Clostridium difficile "oral$
*seudomembranous colitis
-6ittle activity vs+ %ram 0 rods
-(locks D-ala-D-ala
transpeptidation of
peptidoglycan cell wall
=+Ototo.ic ! deafness "can be irreversible$
2+Nephroto.ic ! blood 2 protein in urine
>+Thrombophlebitis "clots in blood$ =?@ of
patients
4. 5ypotension A Bred manC syndrome because it
releases histamine
%ive antihistamines 2 hrs before giving drug
-I3
-Oral
-;ill not block D-ala-D-
lac transpeptidation
Ne+ Agents $&r resistant Gra 3
Da't&y!in
& cyclic lipopeptide
-Indicated for skin infections caused
by!
-Staph. aureus "including ,'9&$4
Strep. pyogenes, Strep. agalactiae,
Strep. Dysgalactiae subspecies!
/Duisimilis4 E. faecalis "3anc-
sensitive
-1a!teri&CIDAL
-Inserts in cell membrane
via lipid-like portion and
causes rapid depolari:ation
via pore portion
-Disrupts membrane
potential needed for
bacteria to make &T*
-'habdomyolosys! ,onitor patients for muscle
pain/weakness4 discontinue if blood 1*EF=???
u/6
1onsider temporary discontinuation of 9tatins
"5,%-1o& 'eductase Inhibitors$
-*aresthesias at high doses
-I3 -