Fluroquinolones

Dr. Tejas Patel

Classification
First generation

Ciprofloxacin
Norfloxacin
Oloxacin
Pefloxacin

Second generation

Lomefloxacin
Levofloxacin
Sparfloxacin
Gatifloxacin
Moxifloxacin
Trovafloxacin

Mechanism of action
FQs inhibit the DNA gyrase enzyme
DNA gyrase consists of : A and B
subunit

 A subunit carries out nicking of DNA

B introduces negative supercoils
A subunit reseals the strands

 Damaged DNA activates the exonucleases

In GM+ve bacteria, it inhibits topoisomease IV

Mammalain cells possess topoisomerase II

less chnces of host toxicity

Mechanism of resistance
Reduced affinity of DNA gyrase or
topoisomerase IV for FQs
Reduced permeability
Increased efflux

Ciprofloxacin
Highly suceptible

E.coli
Klebsilla
Proteus
Salmonella
Shigella
Enterobacter

H. influenza
H. ducreyi
Campylobacter jejuni
Yersinia entrocolitica
Vibrio cholera
N. Meningitidis
N. Gonorrhea

Moderately susceptible

Pseudomonas
Staph aureus (MRSA)
B. catarrhalis

Legionella
Brucella
Listeria
Bacillus anthracis
M. tuberculosis

Variable susceptibility

Strept. Pyogenes
Strept. faecalis
Pneumococci

Mycoplasma
Chlamydia
M. kansasii
M. avium

Resistant

B. fragilis

Clostridia
Anaerobic cocci

Important feature
Rapid bactericidal activity
Long post-antibiotic effect
Low frequency of resistance
Intestinal anaerobes are not affected
Active against many lactam and
aminoglycosides resistant bacteria
Less active at acidic pH

PK
Food delays absorption
First pass metabolism
Excreted in urine
Elimination half life: 3 to 4 hr

Important PK feature
Conc > plasma

Lung
Sputum
Muscle
Bone
Prostate
Phagocytes
Urine
Bile

Conc. < plasma

CSF
aqueous

ADR
GI tract:
CNS: Impairment of concentration
Seizure (GABA antagonstic action)
Hypersensitivity:
Tendonitis and tendon rupture
Cautious use in children
Contraindicated in pregnancy

Therapeutic uses
Typhoid fever:
Ciprofloxacin DoC
500-750 mg BD for 10 d
200 mg iv 12 hrly

Quick relief
Prevention of carrier state

Alternative: Ceftriaxone (MDR cases)

Chlramphenicol
Cotrimaxazole
Ampicillin

 Urinary tract infection

Gonorrhea
Chancroid
Gastroenteritis

 Bone and soft tissue infections:

Osteomyelitis
Wound infections Diabetic foot: along
with metronidazole
Gyanecological infections

 Anthrax
Tuberculosis: Part of combination
therapy against MDR TB
Septicemia

 Meningitis
Prophylaxis in neutropenic /cancer pt
Conjuctivitis
Respiratory infections

Norfloxacin
Not effective against pseudomonas and
gram positive organisms
Low concentration in tissues
Uses: UTI and genitourinary inf
Gastroenteritis

Pefloxacin
Higher CSF passage
Partly metabolised to norfloxacin
Cumulates on repeated use
Less effective against Gm positive cocci

Ofloxacin
Effective against
Gm +ve > Gm ve
S. typhii
Chlamydia
Mycoplasma
M. tuberculosis
M. leprae

 Food does not interfere with its

absorption
Excreted unchanged in urine

Levofloxacin
Effective against
Pneumococci
Legionella
Mycoplasma
Chlamydia
Pseudomonas
Proteus

Uses
Acute exacerbation of chronic
bronchitis
Community acquired pneumonia
Nosocomial pneumonia
Acute sinusitis
UTI

 100% bioavailability
Excreted unchanged in urine

Lomefloxacin
More active against Gm ve organisms
Good tissue penetration
Excreted unchanged in urine

Thank you