"عسى ان تكون علما ينتفع به" Antibiotic groups Ciprofloxacin Enerofloxacin

1. Antibiotics Groups
Quinolones

2. Members
 Ciprofloxacin
 Danofloxacin
 Diflofloxacin
 Norfloxacin
 Orbifloxacin
 Enrofloxacin
 Oxolinic acid
 Sarafloxacin

3. Description
 The quinolones are a family of synthetic broad-spectrum
antimicrobial drugs.

4. History
1962, the first generation quinolones
 Lesher and coworkers discovered naladixic acid which was a
dervative of chloroquine.
 Naladixic acid, as well as the whole first generation
quinolones, had a narrow spectrum of activity compared to
those in later generations.
 Today, naladixic acid and other first-generation quinolones
such as flumequine and oxolinic acid are used primarily in
aquaculture.

5. Cont. …
Fluoroquinolones
 Successive generations of quinolones have a fluorine atom in
the quinolone ring structure, typically at the C6 position.
 They include;
1. Danofloxacin
2. Difloxacin
3. Enrofloxacin (which is deethylated to form ciprofloxacin)
4. Marbofloxacin
5. orbifloxacin
6. Sarofloxacin
 These are used in veterinary but not human medicine.

6. Spectrum
 Concentration-dependent killing activity.
 Because quinolones accumulate in the cytosol of
macrophages and neutrophils, they are often used to treat
intracellular pathogens.
 The preponderance of macrophages and neutrophils in
infected tissues compared to healthy tissues may explain the
higher concentrations of fluoroquinolones attained in infected
tissues.
 Fluoroquinolones can produce a post-antibiotic effect,
suppressing bacterial growth after local drug concentrations
have fallen below the MIC of the target pathogen.

7. Cont. …
 Fluoroquinolones are active against some Gram-negative
bacteria, including:
1. E. coli
2. Enterobacter species
3. Klebsiella species
4. Pasteurella species
5. Proteus species
6. Salmonella species.
7. Pseudomonasaeruginosa , variable susceptibility
 They are also active against some Gram-positive bacteria and
chlamydia, mycobacteria and mycoplasma.

8. Mechanism of Action
 The fluoroquinolones enter bacterial cells via porins and:
– Inhibit bacterial DNA gyrase in many Gram negative bacteria or
topoisomerase IV in many Gram positive bacteria
 Thereby inhibiting DNA replication and transcription.
 Fluoroquinolones also cause the cessation of cellular
respiration and disruption of membrane integrity.

9. Cont. …
 Although mammalian topoisomerase II is a target for a variety
of quinolone-based drugs, concentrations approximately 100-
fold higher than those recommended for bacterial activity are
needed for the enzyme to be inhibited.

10. Resistance
 Resistance to quinolones can evolve rapidly
 The most common mechanism involves
– Mutation of DNA gyrase (topoisomerase II) in Gram-negative bacteria.
– A similar mechanism alters topoisomerase IV in Gram-positive
bacteria.
 These mutations result in reduced binding affinity to
quinolones, which decreases bactericidal activity.

11. Cont. …
 A second mechanism of resistance involves increased
expression of efflux pumps that actively transport drug out of
bacterial cells, resulting in decreased intracellular drug
concentration.

12. Indications
 In some regions, the use of fluoroquinolones is approved for
the treatment of:
1. Colibacillosis of chickens and turkeys
2. Fowl cholera in turkeys
3. Bovine respiratory disease caused by Mannheimia haemolytica,
Pasteurella multocida, Haemophilus somnus, and other susceptible
organisms.

13. Administration
 Fluoroquinolones are administered as:
1. Oral solutions to chickens and turkeys
2. Injection to cattle
3. Tablets or by injection to dogs and cats

14. Side Effects
 Fluoroquinolone administration during rapid growth has been
associated with arthropathies and cartilage erosions in
weight-bearing joints in immature cats, dogs, and horses.
 Retinal degeneration has been associated with the
administration of enrofloxacin at high doses in cats.