Fluoroquinolones

• Introduction
• Newer quinolones
• Pharmacological aspects of newer quinolones
• Major clinical applications
• Adverse effects
• Drug Interactions
• Pharmacological outline of Sparfloxacin
• Further Developements of Quinolones
• Conclusion

SPARFLOXACIN:

Sparfloxacin is an orally effective and it is a new diflourinated quinolone with structure similar to ciprofloxacin with broad antibacterial spectrum including improved activity against Grampositive, Mycobacteriae, Chlamydiae, Mycoplasmae, and anaerobes with good tissue penetration and long elimination half life. Its effect is superior against Staphylococci epidermides, E.fecalis, Streptococci pneumonia, C.perfringes & other anaerobes. It is the most appropriate agent for treatment of Urinary Tract Infection, Respiratory tract infection and other systemic infection having both improved patient compliance and greater efficacy .

Clinical trials with Sparfloxacin:

1. Sparfloxacin is well tolerated and effective against obstetric & gynecological  infection
2. Sparfloxacin exerted strong antimicrobial activity against Shigellae, Salmonellae, Camphylobacter, and marked clinical efficacy against enteritis induced by the above organisms.
3. Sparfloxacin found to be very useful in post- surgical infections.
4. Sparfloxacin in respiratory infections – Excellent activity against S.aureus, Streptococci pneumoniae, Br.catarrhalis,H.influenzae, Mycoplasmae and therefore indicated in URI, ACEB, Diffuse panbronchiolitis, Bronchiectasis, & pneumonia.
5. Sparfloxacin has excellent activity in the following dermatological conditions viz., Folliculitis, Pustular acne, Furunculosis, carbuncles, Impetigo, Erysipelas, Cellulitis, Felon, Lymphangitis, paronychia,SC abscess, Hidradenitis, Infected atheroma, Infected pilinoidal sinus etc.,
6. Sparfloxacin in Leprosy:
   • Radio respirometric activity undetectable after 4 weeks of therapy
   • Serum phenolic glycolipid 1 antigen diminished in all patients
   • Among 20 quinolones, Sparfloxacin was the most active in leprosy
7. Sparfloxacin exerted very good effect in Mycobacterial infections with the exception of M.scrofulaceum and M.chelonae.
8. Sparfloxacin exhibits highest antimicrobial potency against Legonellairs infection because of its enhanced penetration into human neutrophils with Intra Cellular concentrations exceeding extracellular concentrations several times. Therefore sparfloxacin is superior bactericidal against M.homins, M.pneumoniae, M.genitaklium, U.urealyticum, M.fermentans.
9. Sparfloxacin has good activity against MAC infection but the role of quinolones in multi- drug regimen for opportunistic infections by MAC in AIDS remains unclear.

Recent Advances with Newer Quinolones:

1. Grepafloxacin in o/d regimen is superior to ciprofloxacin in Streptococci pneumoniae
2. Gatifloxacin o/d is highly effective in Respiratory & UTI and did not exhibit any phototoxicity.
3. Sitfloxacin useful in treatment of Catheter associated nosocomial and other infections by Pseudomonas species with less chance for resistance induction.
4. Oral Trovafloxacin is very effective against MDR respiratory pathogen because of its greater penetration into respiratory fluids and secretion.
5. Moxifloxacin is highly effective in M. catrrhalis, Chlamydiae, Mycoplasmae, Legionellae because of its 10 fold Intra Cellular concentrations on oral administration.

6. Moxifloxacin is highly active against str. peumoniae (Penicillin/macrolide resistant)

7. Newer quinolones have greater activity than macrolide or cephalosporins against common respiratory pathogens and therefore useful in;

   -community acquired pneumonia

   -Penicillin resistant Streptococci pneumonia

   -Beta-lactamase resistant H.influenzae

   -Beta-lactamase resistant
    Mor.catarrhalis.

H. Once /day alatrovafloxacin/Trovafloxacin IV to oral treatment is clinically effective as twice/day IV to oral ciprofloxacin for treatment of nosocomial infections with no additional anaerobic coverage.

Future Quinolones:

• Greater potency
• Reduced frequency of resistance selection
• Better CNS/CSF penetration
• Improved safety & tolerability
• Greater activity against gram+ve species
• Effective against IC pathogens
• Enhanced activity against anaerobes
• Suitable for paediatric use.

Conclusion:

NEWER QUINOLONES APPEAR TO HAVE A HEALTHY FUTURE ?

Glossary

MBC - Min bactericidal concentration @ which no colony forms after 24 hrs of incubation @ 35’ C

MIC – Defined as the lowest concentration of antibacterial agent that inhibits the development of visible growth in the broth.

PAE – Post Antibiotic Effect is the term used to describe suppression of bacterial growth that persists after short exposure of organism to antimicrobial agent. PAE may have a clinical effect on antimicrobial dosage.

Dr. T.R.RAMANUJAM. M.D.,
Professor & Head, Dept of Pharmacology,
Sri Ramachandra Medical College & Research Institute,   
Porur ,   
Chennai - 600 116 
SOUTH INDIA.