Other protein synthesis inhibitors

1. Chloramphenicol

a. Pharmacokinetics

. (1) Well absorbed from all routes 


. (2) CNS levels equal serum levels 


. (3) Glucuronidation in liver is rate-limiting step for

inactivation/clearance. 


. (4) 100% excreted in urine 
 (a) 10% filtration of parent 
 (b) 90%
tubular secretion of glucuronide 


b. Mechanism of action (see Fig. 27-4) 
 (1) Inhibits protein synthesis at the 50S
ribosome (2) Inhibits peptidyl transferase
 (3) Bacteriostatic 


c. Uses

. (1) Therapyshouldbelimitedtoinfectionsforwhichthebenefitsoutweighther
isks. 


. (2) Ampicillin-resistant H. influenzae meningitis 


. (3) Alternative drug for infections caused by: 
 (a) Bacteroides
 (b)
Neisseria meningitidis (c) Rickettsia
 (d) Salmonella 


d. Adverse effects

. (1) Aplastic anemia (idiosyncratic with oral administration) 


. (2) Dose dependent inhibition of erythropoiesis 


. (3) Gray baby syndrome 
 • Deficiency of glucuronyl transferase at birth



. (4) Inhibits cytochrome P-450s 


2. Clindamycin (oral, IV, topical)

a. Mechanism of action (see Fig. 27-4) 
 (1) Inhibits protein synthesis at the 50S
ribosome 
 (2) Bacteriostatic 


b. Uses

. (1) Severe gram-positive anaerobic infections (Bacteroides and others)




. (2) Aspiration pneumonia 


. (3) Bacterial (Gardnerella, Mycoplasma, Prevotella) vaginosis (vaginal

cream, 
 vaginal suppository) 


. (4) Pelvic inflammatory disease (IV) 


. (5) Topically in treatment of severe acne 


c. Adverse effects
 (1) Severe diarrhea
 (2) Pseudomembranous colitis (C.

difficile) 


3. Linezolid (oral, IV)

a. Mechanism of action 
 (1) Binds to the 50S ribosome
 (2) Interferes with
protein synthesis
 (3) Bacteriostatic against enterococci and staphylococci
(4) Bactericidal against most strains of streptococci. 


b. Uses
 (1) Treatment of VRE infections
 (2) Nosocomial pneumonia caused by

S. aureus including MRSA or Streptococcus 
 pneumoniae

. (3) Skin infections (including diabetic foot infections without

concomitant osteomyelitis) 

. (4) Community-acquired pneumonia caused by susceptible gram-
positive organisms 


c. Adverse effects
 (1) Diarrhea, nausea and vomiting
 (2) Headache
 (3)
Thrombocytopenia and neutropenia