Chloramphenicol,

Streptogramins, Linezolid
Dr. M. Owais Ismail
 ANTIMCROBIALS
Protein Synthesis inhibitors in Bacteria

Target is bacterial ribosome

Attached to 50s unit
Interferes with translation
Protein
synthesis
 1947 (Streptomyces venezeulae)

synthesised 1949.

Narrow margin of safety

Liver, resistance and availability of good drugs

Now rarely used in the developed countries.

Not used as first line drug

MOA
It inhibits peptidyl transferase

High levels may

inhibit human
ribosome
Properties
Bacteriostatic
Have hexose ring
Poor Water soluble
Soluble in lcohol
IV --- chloramphenicol succinate

RESISTANCE

Enzyme
Acetyl Co A transferase

Impaired entry
PK profile

Dose = 50-100 mg/kg/d

good absorption from GIT, lipophillic
Widely distributed to all body tissues
Usually given oral or IV
Dosage = TID to QID
Level achieved in most tissues are high
Good in CSF
Metabolized in liver
Accumulated in liver
excreted via urine
Can cross placenta
Inhibits mixed function oxidases ---
Drug dug interactions
SPECTRUM

BROAD SPECTRUM

BACTERIOSTATIC
AEORBIC AND ANAEROBIC ORGANISMS

GRAM POSITIVE ( MIC=1-10µg/mL)

GRAM NEGATIVE (MIC=0.2-5 µg/mL)

ACTIVE AGAINST
CHLAMYDIAE.
RICKETTSIAE

Bactericidal for
Hemophilus
Nisseria
THERAPEUTIC USES AN INDICAIONS
Typhus,
Rocky mountain spottedfever
Meningitis

Topically in eye

ENTERIC FEVER.
H.INFLUENZAE MENINGITIS
ANAEROBIC INFECTIONS
INTRAOCULAR INFECTIONS
UTI
TOPICAL.
ADVERSE EFFECTS
Bone marrow depression.

REVERSIBLE Idiosyncratic serious fatal

IRREVERSIBLE.
Mitochondrial enzyme inhibition
Hypersensitivity
Irritant effects
Superinfections.
Gray Baby Syndrome..

Inhibits mixed function oxidase ----

Drug dug interactions
Combination of Quinopristin and dalfopristin 30 : 70
Bactericidal, slow activity
Post antibiotic effect (10 hrs)
Obtained from streptomycete
 MOA

Binds to the separate site

on 50s unit and interferes
with the protein synthesis
PK profile

Dose = 7-8 mg/kg/d

given IV
GOOD TISSUE DISTRIBUTION
Low CSF levels
slow IV
rapidly metabolized by liver
Products are less ctive
Dosage = BID toTID
PAE
Accumulated in liver
excreted via bile
Inhibits mixed function oxidase ---
Drug dug interactions
RESISTANCE

Efflux pump
St. Change in ribosomal unit
Enzymatic inactivation
THERAPEUTIC USES AN INDICAIONS

Vancomycin resistant infections

Bacteremia
RTIs
G +ve cocci
ADVERSE EFFECTS

Phlebitis
Abnormal LFT’s and hyper bilirubinemia
Myopathies
Arthralgia
D D Is
Inhibitor of cyto p450
Member of axazolidinones family
bacteriostatic
g +ve
Strept Listeria
C B Dipth
Staph
C. perf
entero

Myobacterium tuberculosis
Dose = 600 mg * BID, oral or IV
Good oral absorption
½ life = 4-6 hrs
 MOA

Preventing the formation

-
of mRNA ribosomal
complex
USES
Vancomycin resistant infections
RTIs (pneumonia)
Skin infections
G +ve bacteremia
TOXICITY
Hematological toxicity (thrombocytopenia)
Bone marrow suppression
Headache
Rash