INHIBITORSOFPROTEINSYNTHESIS

*All inhibit translation and transcription, leading to cessation of protein synthesis

*All bind components of either 30S or 50S subunits of ribosomes, either before or after formation of 70S initiation complex
* Most are bacteriostatic [Note: Aminoglycosides are bacteriocidal. Prefer bacteriocidal if 1) immunocompromised, notably neutropenia; 2) meningitis; 3) endocarditis]
INHIBIT 50S SUBUNIT
Oxazolidinones
Chloramphenicol
Lincosamides
Macrolides
Streptogramins

CLASS

INHIBIT 30 S SUBUNIT
Aminoglycosides
Tetracyclines
Spectinomycin

DRUGS

MECHANISM OF ACTION
16S rRNA of the
30S ribosomal

AMINOGLYCOSIDES

Tobramycin
Amikacin
Neomycin
Gentamicin
Streptomycin

10, trough <2 for gm infxns

Gm + infxns peak ~4, trough ~1

Clindamycin

Amikacin
Aim for levels 3-4x higher than

USES/COMMENTS
Main uses: Gm neg
nosocomial infxns,
mycobacterial infxns
(streptomycin, amikacin),
pseudomonal infxns, Gm pos
synergy in endocarditis
Dosing of gentamicin and
tobramycin (normal renal fxn)
- Var. by indication & renal
fxn

gent/tobra

LINCOSAMIDES

Bactericidal

PHARMACOKINETICS
[ ]- dependent
Very low BA
Renal elimination
Sub-optimal penetration
Pharmacokinetic monitoring
Gentamicin, Tobramycin
Traditional (q8h) dosing- peak 8-

50S subunit
of bacterial
ribosomes (inhibits
peptidyl
transferase)

Not used in gm + infxns

Extended internal (q24h)
dosing- monitor infreq. via
nomogram
Benefits of extended interval
dosing: higher peak, lower trough
(~0), less monitoring, not for gram
+ synergy
Metabolized by liver
Minimal CNS penetration

Main use: aspiration

pneumonia (not MRSA),
anaerobic infxns,
SSTIs,
acne (topical)

SPECTRUM
Excellent activity vs.
Enterobacteriaciae,
Acinetobacter spp, P.
aeruginosa, other GNR
Resistance in P.
aeruginosa
Resistance due to:
enzymatic inactivation
(enterobacteriaciae),
altered membrane
permeability
(pseudomonas) and/or
target site mutation
(many organisms)

Staphylococci,
streptococci
Anaerobes
Not active vs. atypicals
Resistance due to
alteration in target site
(in gm +, often cross
resistant w/ macrolides,
streptogramins)

ADVERSE EFFECTS
Nephrotoxicity
Ototoxicity
Neuromuscular
blockade
Onset: variable:
can occur w/first
dose (rarely), but
usually takes
several days

Pseudomembranou
s colitis **

- Diarrhea
- Abdominal pain
- Nausea
- Rash

CLASS

DRUGS

MECHANISM OF ACTION
23 rRNA of 50S
exit tunnel for new
peptides

Erythromycin
MACROLIDES

KETOLIDES

Clarithromycin

PHARMACOKINETICS
Excellent lung penetration, poor
CNS penetration
Azithromycin- long terminal half life
Elimination: hepatic metabolism
or biliary excretion

USES/COMMENTS
Main use: CAP, URTIs
Mycobacterium aviumintracelulare (MAI/MAC), ,
STDs, infxns, PUD
(clarithromycin), promotility
(erythromycin)

PO only

CAP (outpatient)

Macrolide analogue w/
increased activity vs. S.
pneumoniae

Azithromycin

Telithromycin

TETRACYCLINES

16S rRNA of 30S

tRNA from binding
the ribosome
mRNA complex
Bacteriostatic

[ ] independent
Highly BA
Poor CNS penetration
Minocycline, doxycycline are
hepatically eliminated, others are
mostly renal

Main use: Peptic ulcer

disease, acne, cap, tickborne, stds, siadh
Drug interactions
o Multivalent cations
o Cell-wall synthesis
o inhibitors- cidal activity
TICK BUGS
TEETH
TETRACYCLINE

ADVERSE EFFECTS
GI disturbances
N/VD (esp @ high
dose)

Atypicals

Tooth
discoloration
Borborygmous
Photosensitivity
Kelation
GI- (NV)

Some GNR and GPC,

limited by resistance
(especially tetracycline)
Bacillus anthracis, B.
burgdorferi, Y. pestis, T.
pallidum, H. pylori
Minocycline- some
MRSA
Resistance d/t efflux
pump

Minocycline
Tetracycline
Doxycycline

Tigecycline

SPECTRUM
- S. pneumoniae
- Atypicals
- Some GNR (including
H. flu & M.
catarrhalis)
- Clarithromycin- H.
pylori

Modified tetracycline that

expands spectrum
Uses: SSTIs, intraabdominal infxn (not
adequate empiric coverage

Coverage includes many

GNRs and GPC,
including MRSA and
VRE

Rash
Especially
erythromycin
Azithromycinmuch lower
interaction
potential
Macrolides plus
Hepatotoxicity

eat
divalen
t
cations
,
discolo
r teeth
and get
photos
ensitivt
y
Significant N/V
(~30%)

for HAP)

CLASS

DRUGS

CHLORAMPHENICOL

MECHANISM OF
ACTION
Binds to 23S
rRNA of 50S
subunit,
inhibiting
protein
synthesis by
blocking tRNA
Inhibits
peptidyl
transferase

Quinupristin/
Dalfopristin
STREPTOGRAMINS

(marketed
rogether as
Synercid)

Bind to
different parts
of 23S rRNA of
50S ribosome,
halting protein
synthesis
Bactericidal
in combo with
MSSA, MRSA

PHARMACOKINETICS

Good CNS penetration

Hepatically metabolized by conjugation

USES/COMMENTS

Drug interactions: increase

levels of phenytoin,
phenobarbital, warfarin

SPECTRUM

ADVERSE EFFECTS

Streptococci,
Staphylococci (not
MRSA),
Enterococci including
VRE

Gray baby
syndrome- due to
inability of newborns
to conjugate
chloram. (vomiting,
flaccidity, gray color,
resp distress, met
acidosis)

Anaerobes
Some GNR
Resistance d/t enzymatic
inactivation

Hepatically metabolized

Main use: VRE/MRSA

infxns in patients who cant
take other agents
Drug interactions:
CYP3A4 inhibitor

- Staphylococci
(including MRSA)

- Streptococci (including
PCN-resistance
strains)
- Enterococcus faecium
(NOT E. faecalis)
including VRE
- Atypicals

Bone marrow
suppression: 2
types
- dose related,
reversible
- idiopathic
irreversible
- Phlebitis (should
be infused via
central line)
- Severe myalgias
- Hepatotoxicity
- Line
crystallization
- Drug interactions

OXAZOLIDINONES

Linezolid

Binds to 23S
rRNA of 50S
subunit,
preventing
protein
synthesis by
blocking
formation of
70S initiation
complex
Bactericidal
vs.
streptococci

Dual hepatic metabolism (not via

CYP450) and renal elimination
Weak inhibitor (MOA)

Main use: MRSA/VRE

infxns
Monoamine oxidase
inhibition:

Resistance d/t altered

target site
- Gram + aerobes
- Staphylococci
(including MRSA)
- Streptococci
(including PCNresistance strains)
- Enterococci
(including VRE)
- Resistance d/t altered
target site

- tyraminecontaining
foods,
sympathomimeti
cs
- Myelosuppressio
n, particularly
thrombocytopeni
a