The document summarizes key information about the phenicol class of antibiotics. It describes the discovery and production of chloramphenicol as the first broad-spectrum phenicol antibiotic. It discusses the absorption, distribution, metabolism and excretion of chloramphenicol and other phenicols like florfenicol and thiamphenicol. The mechanism of action involves binding to the bacterial ribosome. Phenicols are used to treat various infections in animals and humans, though chloramphenicol use is restricted in food animals due to human health concerns. Bacteria can develop resistance through several mechanisms.

1. Antibiotics Groups
Phenicols

2. History
1947
 Ehrlich and coworkers reported the isolation of
chloramphenicol (known at that time as chloromycetin) from
Streptomyces venezuelae, a Gram-positive soildwelling
actinomycete.
Today
 The drug is produced for commercial use by chemical
synthesis.

3. Cont. …
 Chloramphenicol was the first broad-spectrum antibiotic
developed.
 Other members of the phenicol class are thiamphenicol and
florfenicol.
1. The antibacterial activity of thiamphenicol is less than that of
chloramphenicol.
2. The activity spectrum of florfenicol is similar to that of
chloramphenicol but is more active.
3. Florfenicol is not approved for use in humans.

4. Pharmacokinetics
Absorption
 Chloramphenicol base is rapidly absorbed following oral
administration to non-ruminant animals.
 In ruminants, reduction of the nitro moiety of
chloramphenicol by ruminal microflora results in inactivation
and very low bioavailability.
 Chloramphenicol is un-ionized at physiological pH and is
lipophilic; it readily crosses membranes.
Distribution
 The drug is widely distributed to virtually all tissues and body
fluids, including the central nervous system, cerebrospinal
fluid, and the eye.

5. Cont. …
Metabolism
 The principal metabolic pathway for chloramphenicol is
hepatic metabolism to the inactive metabolite,
chloramphenicol glucuronide.

6. Cont. …
Elimination
 5–15% of chloramphenicol dose is excreted unchanged in
urine.
 Florfenicol penetrates most body tissues but to a lesser extent
than does chloramphenicol in the case of cerebrospinal fluid
and the eye.
 In cattle, 64% of florfenicol dose is excreted in unchanged in
urine.
 100% of thiamphenicol does not undergo significant
metabolism and is excreted unchanged in urine.

7. Mechanism of Action
 The phenicols are transported into bacterial cells by passive or
facilitated diffusion.
 They bind to the 50S subunit of ribosome and impair
peptidyltransferase activity.
 Thereby, interfering with the incorporation of amino acids
into newly formed peptides.

8. Spectrum
 Time-dependent
 Bacteriostatic, and bactericidal at high concentrations.
 Most Gram-positive and many Gram-negative aerobic
bacteria.

9. Side Effects
 Chloramphenicol causes two distinct forms of toxicity in
humans.
1. Irreversible aplastic anaemia
2. Dose-dependent and reversible bone marrow suppression

10. Resistance
 Bacteria develop resistance to chloramphenicol by four main
mechanisms:
1. Mutation of the 50S ribosomal subunit
2. Decreased membrane permeability to chloramphenicol;
3. Elaboration of chloramphenicolacetyltransferase (CAT), an
inactivating enzyme.
4. Increased expression of efflux pumps.

11. Indications
Chloramphenicol
 It is used to treat a variety of local and systemic infections in
small animals and horses.
 Its use in food-producing species is banned in most countries
because of human health implications.

12. Cont. …
 Therapeutic uses include:
1. Chronic respiratory infections
2. Bacterial meningoencephalitis
3. Brain abscesses
4. Ophthalmitis and intraocular infections
5. Pododermatitis
6. Dermal infections
7. Otitis externa
8. Salmonellosis and Bacteroides sepsis

13. Cont. …
Florfenicol
 It is an effective therapy for bovine respiratory disease in
cattle caused by Mannheimia, Pasteurella, and Histophilus.
 It is also approved in some countries for use in pigs and fish.
Thiamphenicol
 It is approved for use in Europe and Japan.