Quinolones are a class of synthetic broad-spectrum antimicrobials. First generation quinolones like norfloxacin and ciprofloxacin are effective against gram-negative bacteria and are used to treat uncomplicated UTIs. Later generations have enhanced activity against pseudomonas and anaerobes. Quinolones work by inhibiting DNA gyrase in bacteria. They are well-absorbed orally, achieve high tissue concentrations, and have a low resistance risk. Common adverse effects include nausea, diarrhea, headache and phototoxicity. Quinolones can prolong the QT interval and interact with divalent cations. They are used to treat respiratory, gastrointestinal, skin and joint infections.

1. QUINOLONES

2. • Synthetic anti microbials
•
•
•
•
•
Bactericidal broad spectrum antimicrobial activity
Nalidixic acid, 1962-Lasher G-ve
1970s – Oxolinic acid & cinoxacin
Developed in 1980s
Increasingly used because of their relative safety,
their availability both orally and parenterally and
their favorable pharmacokinetics
• Comparatively slow rate of resistance to these
agents

3. Structure-Activity Relationships
4-quinolone-3-carboxylic acid
affect G(-ve)
activity
O
F
5
COOH
4
N
HN
1
N
8
R1
8-F- improve P.k
3
Cyclopropyl: inc. spectrum
Piperazine ring
:anti-pseudomonal activity

4. Generation
Drug Names
Clinical use
Uncomplicated
1st
Norfloxacin
Ciproflaxcin
Ofloxacin
Pefloxacin
Lomefloxacin
2nd
Levofloxacin
Fleroxacin
Clindafloxacin
Complicated UTI,
GIT infection
Prostatitis, STD
3rd
Gatifloxacin
Sparfloxacin
same+ community
acquried pneumonia
Atrofloxacin
Trovafloxacin
Alatrofloxacin
Major systems infection
(abdominal infections)
4th
UTI

5. M. O. A. :* ACT BY INHIBITING D. N. A. GYRASE IN
BACTERIA (PROKARYOTIC
CELLS).
*
*
ENZYME TOPOISOMERASE IV IN GRAM POSITIVE BACTERIA.
DO NOT AFFECT MAMMALS CELLS
(TOPOISOMERASE II ENZYME).
SPECTRUM :
* BROAD SPECTRUM.
* MORE ACTIVE AGAINST G -ve IN COMP. TO G+ BACTERIA.

6. MICROBIOLOGICAL FEATURES OF FQs:
•
•
•
•
•
Rapidly Bactericidal activity
Long Post-Antibiotic Effect
Low Frequency of Resistance
High Tissue Penetrability
Active against Beta-Lactum & Aminoglcoside
Resistant Bacteria.

7. PHARMACOKINETICS :
* ABSORBED P. O.
* DISTRIBUTED TO ALL BODY
COMPARTMENTS :
PROSTATE, BONE , LUNG, SPUTUM,
AQUEOUS HUMOR, NEUTROPHILLS
BUT CONC. IN C. S. F. IS POOR
* EXCRETION THROUGH KIDNEY
(Conc. Higher than Plasma)

8. Anti microbial spectrum
1st generation:
• Enterobacteriaceae (E. coli, Sallmonella, Shigella)
• G –ve: H.influenzae, H.ducreyi, P.aeruginosa, V.cholerae
• G-ve cocci :N. gonorrhoea, N. meningitidis
• G+ve bacilli : Bacillus anthracis (Modest activity)
• Other: M.tuberculosis, M. pneumoniae, Rickettsiae
2nd generation:
• Better activity against G+ve cocci
3rd generation:
• Enhanced activity against G –Ve cocci
4th generation:
• Enhanced activity against G+Ve cocci+ greater activity
against anaerobes

9. THERAPEUTIC USES :
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
R – RESP TRACT INF. Levofloxacin, sparfloxacin, ofloxacin
T – TYPHOID. Cipro, oflo,
F – FURUNCULOSIS
T – TUBERCULOSIS
O – OSTEOMYELITIS – ciproflo- long therapy 4-6week
U – U. T. I. Norfloxacin 4-6 weeks
C – CONJUNCTIVITIS.
B – BACILLARY DYSENTRY. - Nor, cipro, trallver’s-cotrimoxaz
O – OTITIS MEDIA.
L – LEPROSY
S – S. T. D. EXCEPT SYPHILLIS. 2nd line – Cipro, oflo, gati
M – MENINGITIS. ( 2nd line drugs)

10. RESERVED THERAPY FOR TREATMENT OF
UNTREATABLE CONDITION BY OTHER
LONG STANDING MICROBICIDALS.

11. Ciprofloxacin
•
Administration [Usual Dosage]: IV, PO [500 – 750 mg]
•
Spectrum: Gram- aerobic rods, and Legionella pneumophila, and other
atypicals. Poor activity against Strep. pneumoniae.
•
Indications:
-- Nosocomial pneumonia
-- Intra-abdominal infections
– Uncomplicated/complicated UTI
– Anthrax exposure and prophylaxis
•
Unique Qualities:
– Binds divalent cations (i.e. Ca & Mg) which decreases absorption
-- Increased effects of warfarin
•
ADRs
– QTC prolongation, arrhythmias
– Nausea, GI upset
– Interstitial nephritis

12. Levofloxacin
•
Administration [Usual Dosage]: IV, PO and ophthalmic [500-750 mg ]
•
Spectrum: Gram-, Gram+ (S. aureus including MRSA & S. pneumoniae) and
Legionella pneumophila, atypical resp. pathogens, Mycobacterium tuberculosis
•
Indications:
– Chronic bronchitis
– Nosocomial pneumonia
– Intra-abdominal infections
•
Unique Qualities:
– Binds divalent cations (i.e. Ca & Mg) which decreases absorption
ADRs
– Blood glucose disturbances in DM patients
– QTC prolongation, arrhythmias
– Nausea, GI upset
– Interstitial nephritis

13. Moxifloxacin
•
•
Administration [Usual Dosage]: IV, PO and ophthalmic
[400mg ]
•
Spectrum: Gram-, Gram+ (S. aureus including MRSA & S. pneumoniae) &
atypicals (L. pneumophila, C pneumonia & M. pneumoniae),
Mycobacterium tuberculosis, gram-negative anaerobes
•
Indications:
– Chronic bronchitis
– Bacterial conjuctivitis
– Sinusitis
•
Unique Qualities:
– Binds divalent cations (i.e. Ca & Mg) which decreases absorption
– Safety and efficacy not established in patients <18
•
ADRs
–
–
–
–
Blood glucose disturbances in DM patients
QTC prolongation, arrhythmias
Nausea, GI upset
Interstitial nephritis

14. Fluoroquinolones
Adverse Effects
• Gastrointestinal – 5 %

Nausea, vomiting, diarrhea, dyspepsia
• Central Nervous System


Headache, agitation, insomnia, dizziness, rarely,
hallucinations and seizures (elderly)
• Hepatotoxicity

LFT elevation (withdrawal of trovafloxacin)
• Phototoxicity
 levofloxacin, pefloxacin
• Cardiac


Variable prolongation in QTc interval
withdrawal of grepafloxacin, sparfloxacin

15. Fluoroquinolones
Adverse Effects
• Articular Damage
 Arthropathy,
Growing cartilage damage,
arthralgias, and joint swelling
 Led to contraindication in pediatric patients and
pregnant or breast feeding women
 Risk versus benefit
• Other adverse reactions: tendon rupture,
hypersensitivity

16. Fluoroquinolones
Drug Interactions
• Divalent and trivalent cations – ALL FQs



Zinc, Iron, Calcium, Aluminum, Magnesium
Antacids, Sucralfate, enteral feedings
Impair oral absorption of orally-administered FQs –
may lead to CLINICAL FAILURE
• Theophylline and Cyclosporine - cipro
 inhibition
of metabolism,
levels,
• Warfarin – idiosyncratic, all FQs
toxicity

17. Dose of commonly used quinolones
Drug
Norfloxacin
Ciproflaxcin
Ofloxacin
Pefloxacin
Lomefloxacin
Sparfloxacin
Gatifloxacin
Moxifloxacin
Gemifloxacin
Dosage per day
400mg twice
500-750mg twice
200-400mg twice
400mg twice
400mg once
200-400mg
400mg once
400mg once
320mg once

18. Introduction
• UTIs are defined by the presence of micro
organisms within the urinary tract that may
be difficult to distinguish between
contamination, colonisation or infection

19. ● UTIs mainly contain gram negative
aerobic organisms originating from the
gut flora
● Proteus, other Enterobactericiae,
S. saprophyticus, enterococci, group B Strep
and Chlamydiae cause ~ 20% of
uncomplicated UTIs

20. TYPES
ACUTE
• Infection localized to
urethra and bladder.
• frequency,urgency,dysuria,
pain in perineum.
• No fever chills leucocytosis
• Pus cells (+++)
• Urine culture (+)–
“significant bactertiuria”
CHRONIC
• General loss of health
anaemia,hypertension.
• Chronic PylonephritisChronic hypertension &renal
failure.
• Pus cells (+)
• Significant bacteriuria

21. BACTERIOLOGY
• 95% of UTI are due to gram –ve bacilli.
-80% E.coli (commonest)
-15% Proteus
Klebsiella
Pseudomonas
• 5% of UTI are due to gram +ve cocci
Enterococci
Staphylococci
Streptococci
• Mixed infections are likely to be present in chronic cases, in
diabetics, obstructive uropathies,indwelling catheters

22. DRUG THERAPY
• BACTERIOSTATIC AGENT
Sulfonamides
Tetracycline
Nitrofurantoin
• URINARY ANTISEPTICS
Nalidixic acid
Methenamine mandelate
Nitrofurantoin
• BACTERICIDAL AGENTS
Cotrimoxazole
Ampicillin
Extended spect. Penicillin
Aminoglycosides
Fluroquinolones
Cephalosporins

23. SULFONAMIDES
•
•
•
•
•
Effective against E.coli
effective only un complicated UTIs
Cheap, easily available,and effective orally
Bacterial resistance major problem.
DOC: Sulfisoxazole 2g initially 1g for 7-10
days
• Prerequisite-Alkaline urine, liberal fluid intake.

24. NITROFURANTOIN
•
•
•
•
•
•
Sybthetic agent, active G-& +ve .
proteus, P.aureginosa resistence
Rapid g.i. absorption, high urinary concentration.
Bacteriostatic against common pathogens.
Pseudomonas, proteus resistant.
For ‘Chronic suppressive therapy’—
50-100 mg /day for several wks.
• Mainly useful for resistant infections, mixed infections,
infections associated with obstructive uropathy.

25. METHENAMINE MANDELATE
• Mandelic acid +methenamine
Formaldehyde (acid PH 5.5)
Active against g-ve pathogens
• Not effective in acute ,upper UTI,aginst
proteus & pseudomonas
• Dose:1 g qid

26. NALIDIXIC ACID
• Used as reserved drug for occasional cases (esp.
proteus resistant to other drugs)
• Dose: 1gm qid x 7-10 days

27. COTRIMOXAZOLE
• Highly potent and cost effective bactericidal
combination used aginst E.coli & proteus.
• Dose: acute UTI-2 tab bd x 7-10 days
chronic UTI-1 tab twice a wk.
• Contraindicated in pregnancy.
• Successful in recurrent UTI in men (prostatic
focus)
• Ineffective in renal insufficiency.

28. AMPICILLIN
• Effective bactericidal to E.coli ,aerobacter.
• Proteus,pseudomonas resistant.
• Ineffective against penicillinase producing
staph. aureus.
• Safe in pregnancy
• Dose:.0.5 g qid x 7-10 days.
• Resistant strains of E.coli esp..hospital
acquired has been found.

29. AMINOGLYCOSIDES
• Gentamicin is the only aminoglycoside used in
UTI.
• Effective against E.coli,proteus,pseudo.
• Disadv.- parental use
renal toxicity
ototoxicity
• Reserved for complicated UTI

30. FLUROQUINOLONES
• Ideal agents and drug of choice.
• Useful in nosocomial pylonephritis,
complicated UTI.
• Present status: first line drug for all UTI.

31. CEPHALOSPORINS
• Valuable in infections resistant to other
antibiotics (E.coli, Proteus ,Pseudomonas)
• Doc. –Klebsiella infections.
• Indicated in septicemic UTI.

32. UPPER UTI
1.Acute uncomplicated pylonephritis:
Drug regimen :
Cotrimoxazole /Gentamicin with/ without Ampicillin /
Cephalosporins
2.Complicated UTI :
Minimal symptoms- Cipro. 500mg bd
Severe illness :
(Inj. Cefotaxime 2g qid iv & Inj.Genta 5 mg/kg od iv) x7-14 days
3.Chronic Pylonephritis ;
cause to be searched.