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broad anaerobic coverage*withdrawn from the market in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