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.