This document discusses fluoroquinolone antibiotics. It describes their spectrum of activity, mechanism of action, pharmacokinetics, uses, and adverse effects. Fluoroquinolones are broad-spectrum antibacterial drugs used commonly due to their oral availability and favorable pharmacokinetics. However, there is increasing concern about emerging resistance. Common fluoroquinolones discussed include norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, and moxifloxacin.

1. Dr.Rahul
Asso. Prof. pharmacology
RMC, PIMS (DU)

2.  Bactericidal broad spectrum drugs
 Increasingly used because of their relative
safety, their availability both orally and parenterally
and their favorable pharamacokinetics
 There is increasing concern about the emergence of
resistance to these agents
 Parent drug: nalidixic acid

4. Generation Drug Names Spectrum
1st
Nalidixic acid
Cinoxacin
Gram- but not Pseudomonas
2nd
Norfloxacin
Ciprofloxacin
Ofloxacin
Gram-(including Pseudomonas)
some Gram+ (S. aureus)
some atypicals
3rd
Levofloxacin
Sparfloxacin
Moxifloxacin
Gemifloxacin
Same as 2nd generation:
extended Gram+ and atypical
coverage
4th
*Trovafloxacin Same as 3rd generation:
broad anaerobic coverage*withdrawn from the market in
1999

5. Older agents with poor activity; newer FQs with
enhanced potency
• Methicillin-susceptible Staphylococcus aureus
• Streptococcus pneumoniae (including PRSP)
• Group and viridans streptococci – limited activity
• Enterococcus sp. – limited activity

6. (cipro=levo>gati>moxi)
• E. coli, Klebsiella sp,
• Enterobacter sp, Proteus sp
• Salmonella Shigella,
• Serratia marcescens, H. influenzae,
• M. catarrhalis, Neisseria sp.
• Pseudomonas aeruginosa
significant resistance has emerged; ciprofloxacin
and levofloxacin with best activity

7. – All FQs have excellent activity against atypical
bacteria including:
 Legionella pneumophila - DOC
 Chlamydia sp.
 Mycoplasma sp.
 Ureaplasma urealyticum

8.  Enzymes required for DNA replication
1.Topoisomerase II (DNA gyrase): GyrA and GyrB
2.Topoisomerase IV: ParC and ParE
 Mechanism of DNA gyrase

9.  Inhibit bacterial DNA synthesis by
inhibiting DNA gyrase and topoisomerase
IV  rapid cell death
 Mostly Topo II inhibition in G- bacterias
 Topo IV inhibition more in G+ bacterias
 Post antibiotic effect: lasts 1 to 2 hours,
increases with increasing concentration

10.  Absorption - good oral availability, but food
will inhibit, as well as Al, Ca, Mag, Fe.
 Distribution - good tissue penetration,
including prostate, bile, lung. Poor CNS
coverage
 Elimination – renal (for 1st generation)
 PD: Concentration dependent killing

11.  UTI
 Bacterial gastroenteritis
 Intra abdominal infections
 Typoid fever
 Gonorrehea
 MDR- tuberculosis
 Leprosy
 Osteomyelitis
 Invasive otitis media
 Nosocomial pneumonia
 Septicemia
 Bacterial conjuctivitis
 Chronic bronchitis
 Sinusitis
 Anthrax

12.  Most commonly used antimicrobials
 Very effective against E.coli, proteus,
Enterobacteriace
 Higher urine conc. than serum conc.good for
complicated renal cysts & recurrent UTI from
prostatitis
 Ciprofloxacin 750mg bd X 3 wks

13.  Very effective against shigella, salmonella,,
E.coli.
 Norfloxacin, ciprofloxacin , ofloxacin are
effecive

14. (Comparative studies)
1) ciprofloxacin + metronidazole
2) Imipenem
3) Trovafloxacin
4) amoxicillin/clavulanate
similar activity

15.  Ciprofloxacin 750mg BD X 10 days
 Pefloxacin, Ofloxacin can also be used

16.  Cervicitis
 Urethritis
 PID
 Single dose :Cipro..500mg, Oflox. 400mg
 Problem : resistance
 So Ceftriaxone first drug of choice

17.  MDR tuberculosis
 MAC infections
 Leprosy (ROM theraphy)

18.  Trovafloxacin
approved by the FDA for treatment
of soft-tissue infections, including
DM foot
 Levofloxacin
Superior to ciprofloxacin in SSTI
caused by S. aureus

19. Community-acquired Pneumonia
 Outpatients : new fluoroquinolones
 Hospitalized
General wards : new FQs monotherapy
ICU : -lactam + new FQs
Upper respiratory infections
: acute sinusitis, chronic bronchitis

20.  Prophylaxis and treatment of infections in
neutropenic patients
 Conjunctivitis due to G-ve bacteria
 Invasive otitis media
 Prophylaxis and exposure Anthrax
 Respiratory infection : (Levofloxacin)
 Chronic bronchitis
 Nosocomial pneumonia
 Sinusitis

21.  Gastrointestinal – 5 %
 Nausea, vomiting, diarrhea, dyspepsia
 Central Nervous System
 Headache, agitation, insomnia, dizziness, rarely,
 hallucinations and seizures (elderly)
 Hepatotoxicity
 LFT elevation (led to withdrawal of trovafloxacin)
 Phototoxicity (uncommon with current FQs)
 More common with older FQs (halogen at position 8)
 Cardiac
 Variable prolongation in QTc interval
 Led to withdrawal of grepafloxacin, sparfloxacin

22.  Articular Damage
 Arthopathy including articular cartilage damage,
arthralgias, and joint swelling
 contraindication in pediatric patients and pregnant or
breast feeding women
 Risk versus benefit
 Other adverse reactions:
 Tendon rupture,
 Dysglycemias,
 Hypersensitivity

23. Fluroquinolone Doses Preferred Uses
Norloxacin 400mg OD/BD UTI
Bacterial Diarrheoas
Ciprofloxacin 250-750mg BD UTI
Typhoid
Bacterial diarrheoas
Gonorrhea…etc
Ofloxacin 200-400mg BD Tuberculosis
Leprosy
Atypical Pneumonia
Chlamydial infections
Levofloxacin 500mg OD Community aquired pnumonia
Bronchitis, UTI
Skin & soft tissue infections
Gatifloxacin Community aquired pnumonia
Bronchitis, UTI
Gonnococcal infections
Moxifloxacin Community aquired pnumonia