PROTEIN SYNTHESIS INHIBITORS (In order of broadness of spectrum, most broad to most narrow spectrum)

2009 Mark Tuttle

Name Target Organism Mechanism Sie e!!ects "#s$r%ti$n E&creti$n Resistance
TETR"'Y'(IN
ES
(4 rings)
-Gram + and Gram including
anaerobes
-Especially Rickettsiae,
Chlamydiae, Mycoplasmae
-Pseudomonas and Proteus
are resistant b/c teir efflu!
pumps bind all tetracyclines
-Inibits )0S
ri#$s$mal,
-"loc#s aa-t$%&
access to receptor site
-"acteria a'e passi'e
diffusion &%( acti'e
update of drug
-Bacteri$ST"TI'
-)elation wit calcium
causes binding to growing
bones/teet
-Irritation of GI (diarrea,
'omiting)
-)ange GI flora
-*inor li'er to!icity
e!acerbated during
pregnancy, li'er disease
-*i++iness ,-esti#ular.
-+ypersensiti'ity uncommon
-,otosensiti'ity after I-
-)ontraindicated during
pregnancy
-.sually gi'en orally,
absorbed in sm/ Intestine
-&bsorption 'aries
-(i'alent/tri'alent cations,
dairy products, anacids
interfere wit absorption
-401 bound to plasma pp
-Enter all body fluids
e&ce%t 'S/ ,$nl0 102
203.
-&cti'ely e!creted
in bile
(Enteroepatic
cycling)
-M$st e&crete in
urine
-.pregulation of efflu!
pump
-,roduction of proteins
interfering wit ribosomal
binding
-Inacti'ation of acti'e
upta#e
*$&0c0cline -Staph. aureaus
-Entamoeba, Plasmodium
falciparum
- - -2001 absorption -%ot e!creted in
urine/ Onl0 in
#ile4
-Staph. aureus efflu!
pump doesn3t bind4
Tigec0cline
(Glycylglycyl
tetracycline)
--ery broad spectrum
-Gram + rods
-&naerobes (+ and -)
-*$5&, -$5&, -I5&, oter
Staph
-,enicillin-resistant Strep
--$E ('anc-resist enterococci)
-Enterobacteraciae
-&ceinobacter (multidrug
resist)
-Chlamydiae, Rickettsiae,
Legionella
-6ast growing mycobacteria
- -701 de'elop nausea --ery poor oral
absorption/ %eeds I-
administration
-%ot e!creted in
urine/ Onl0 in
#ile4
-
'hl$ram%henic
$l
-&erobic/&naerobic Gram +
and Gram
-&cti'e against Rickettsiae
.sed in serious infections
-.sed in (5$$ 'NS
istri#uti$n.
Meningiococcal/Pneumococc
al infections wen "-lactams
can3t be used (e!/ ,enicillin
allergy)
-%ot acti'e against
Chlamydiae
-Inibits 60S ri#$s$me
-"loc#s peptidyl
transfer
-(ifferent site tan
macrolides
-Bacteri$ST"TI'
-&plastic anemia (rare)
-*ay antagoni8e concurrent
use of "-lactams since tese
re9uire bacterial growt and
)lorampenicol is
bacteriostatic
-Inibits li'er metabolism of
se'eral drugs (warfarin,
penytoin)
-Gray baby syndrome due to
poor glucuronic acid con:
ability
-&bsorbed well orally
,ro'ided as a salt
ydroly8ed in 'i'o
-(istributes to all body
tissues IN'(*IN5 'NS
-Inacti'ated in li'er
-*ainly e!creted in
urine 'ia li'er
glycuronic acid
con:ugation
li'er function
important
-,lasma-encoded
clorampenicol
acetyltransferase
7ETO(I*ES -6or macrolide-resistant
strains were efflu! pumps
gi'e resistance
-%ot effecti'e against
metylation
-)ommunity-ac9uired
pneuminias; Strep.
- - -Interacts wit
)ytocrome ,4<0 7&4
li#e erytromycin
- -
Telithr$m0cin
(5mall
macrocyclic)
pneumonia, Mycoplasma,
Legionella, Chlamydophila
pneumonia
PROTEIN SYNTHESIS INHIBITORS continued
2009 Mark Tuttle
Name Target Organism Mechanism Sie e!!ects "#s$r%ti$n E&creti$n Resistance
M"'RO(I*ES
(*acrocyclic
lactone ring wit
deo!y sugars)
-Gram + and
-eisseria
-5ome Mycobacteria
-Intracellular bacteria,
5pirocetes, Mycoplasma,
Legionella, Listeria,
!elicobacter
-Inibits 60S
ri#$s$mal
-=75 r$%&
-"loc#s
transpeptidation
-Bacteri$ST"TI'8 #ut
can #e
#acteri$'I*"( at
high c$ncentrati$n
- -(estroyed by stomac acid
-Esters and salts can elp
wit acid resistance
-6ood interferes wit upta#e
-)an be I-
-Ma9$rit0
e&crete in #ile
-*etylation of <05
(5ometimes induced by
presence of macrolide)
-Efflu! pumps
Er0thr$m0cin -Corynebacteria (erythrasma,
diphtheria)
-Chlamydia
-)ommunity-ac9uired
pneuminias; Strep.
pneumonia, Mycoplasma,
Legionella
-.sed for Staph/Strep in
,enecillin-resistent fol#s
- 2/ %ausea, anore!ia,
diarrea (rare); 'ia
increased gut motility
2. >i'er to!icity
epatitis (interaction
wit ,4<0)
7/ &llergy
-*etabolites inibit
)ytocrome , 4<0
-Increased teopylline, oral
anticoags, cyclosporine, oral
digo!in
- -.sually plasmid-
encoded
-$educe cell permeability
-Increase acti'e efflu!
-H0r$l0sis #0 5ram :
R$s
-
'larithr$m0cin -?or#s better tan
erytromycin on
Mycobacterium a"ium
-&lso effecti'e on M. leprae,
#o$oplasma gondii
- - - - -
"+ithr$m0cin --ery acti'e against
Chlamydia
- - -(oes %@A interact wit
)ytocrome , 4<0
-7 day alf life/ @nce a wee#
dosing possible -er0
use!ul !$r ST*s
- -
(IN'OS"MI*ES -*ost anaerobes (Gram + and
-)
-Inibits 60S
ri#$s$mal
-"loc#s
transpeptidation
-(5ame target as
erytromycin)
-Bacteri$ST"TI'
-+ig ris# of inducing C.
difficile
pseudomembranous
colitis
-*ainly used for acne as a lotion and in combination
wit anoter drug
- E!/ &bdominal wounds, endocarditis
propyla!is in dental, pel'ic abscess, septic
abortion (6A>)
-
'linam0cin
Ne; agents !$r Resistant 5ram <
STREPTO5RMI
NS
-Areatment of -$5& and
*$5&
-Areat -ancomycin-resistant
Enterococcus faecium %@A
E. faecalis
-&ct on 60S ri#$s$mal
(& B " act at diff sites)
-$apidly
#acteri$'I*"(
-*uscle and :oint pain
-
-Inibition of )ytocrome ,4<0
7&4 ()yclosprin, warfarin,
%%$AIs, etc)
- -Enterococcus faecalis is
resistant
=uinu%ristin2
al!$%ristin
(a mi! of & B ")
O>"?O(I*ONE
S
-&cti'e against gram +
including anaerobes
-"inds at uni@ue site
$n 60S ri#$s$me
-*ild trombocytopenia
and bone marrow
-Arombocytopenia possible
-Inibits *&@; a'oid food ric
-I- and @ral -NO cr$ss reacti-it0 $!
resistance ;ith $ther
-*$5&, -$5&, Enterococci
"@A+ faecium, faecalis
(=75 r$%&) before
assembly of ribosome/
suppression in tyramine or drugs
metaboli8ed by *&@
(epineprine)
anti#i$tics
(ine+$li
Chloramphenicol Macrolides Lincosamides
Tetracyclines Ketolides Streptogramins
Linezolid
Broad spectrum Intermediate spectrum Narrow spectrum
Chloramphenicol Macrolides Lincosamides
Tetracyclines Ketolides Streptogramins
Linezolid
Broad spectrum Intermediate spectrum Narrow spectrum
Tetracyclines Bind 30S subunit + renal clearance except tigecycline and doxycycline
Bind to growing bones and teeth
Tigecycline MRSA, RSA, !"# $seudo%onas&$roteus
Quinupristin-dalfopristin Rapidly bactericidal MRSA, RSA !"# '. (aecalis
Linezolid MRSA, RSA, R'
Erythromycin )o%%unity*ac+uired pneu%onia, Corynebacteria
Clindamycin ,- toxicity including C. difficile colitis
Azithromycin .ong hal( li(e. Many S#/s 0chla%ydia1, treated using one dose
Chloramphenicol ,ray baby syndro%e