2. ⢠Synthetic anti microbials
â˘
â˘
â˘
â˘
â˘
Bactericidal broad spectrum antimicrobial activity
Nalidixic acid, 1962-Lasher ď G-ve
1970s â 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
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:
â˘
â˘
â˘
â˘
â˘
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 âve: 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 âVe 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 â RESP TRACT INF. Levofloxacin, sparfloxacin, ofloxacin
T â TYPHOID. Cipro, oflo,
F â FURUNCULOSIS
T â TUBERCULOSIS
O â OSTEOMYELITIS â ciproflo- long therapy 4-6week
U â U. T. I. Norfloxacin 4-6 weeks
C â CONJUNCTIVITIS.
B â BACILLARY DYSENTRY. - Nor, cipro, trallverâs-cotrimoxaz
O â OTITIS MEDIA.
L â LEPROSY
S â S. T. D. EXCEPT SYPHILLIS. 2nd line â Cipro, oflo, gati
M â MENINGITIS. ( 2nd line drugs)
10. RESERVED THERAPY FOR TREATMENT OF
UNTREATABLE CONDITION BY OTHER
LONG STANDING MICROBICIDALS.
11. Ciprofloxacin
â˘
Administration [Usual Dosage]: IV, PO [500 â 750 mg]
â˘
Spectrum: Gram- aerobic rods, and Legionella pneumophila, and other
atypicals. Poor activity against Strep. pneumoniae.
â˘
Indications:
-- Nosocomial pneumonia
-- Intra-abdominal infections
â Uncomplicated/complicated UTI
â Anthrax exposure and prophylaxis
â˘
Unique Qualities:
â Binds divalent cations (i.e. Ca & Mg) which decreases absorption
-- Increased effects of warfarin
â˘
ADRs
â QTC prolongation, arrhythmias
â Nausea, GI upset
â Interstitial nephritis
12. Levofloxacin
â˘
Administration [Usual Dosage]: IV, PO and ophthalmic [500-750 mg ]
â˘
Spectrum: Gram-, Gram+ (S. aureus including MRSA & S. pneumoniae) and
Legionella pneumophila, atypical resp. pathogens, Mycobacterium tuberculosis
â˘
Indications:
â Chronic bronchitis
â Nosocomial pneumonia
â Intra-abdominal infections
â˘
Unique Qualities:
â Binds divalent cations (i.e. Ca & Mg) which decreases absorption
ADRs
â Blood glucose disturbances in DM patients
â QTC prolongation, arrhythmias
â Nausea, GI upset
â Interstitial nephritis
13. Moxifloxacin
â˘
â˘
Administration [Usual Dosage]: IV, PO and ophthalmic
[400mg ]
â˘
Spectrum: Gram-, Gram+ (S. aureus including MRSA & S. pneumoniae) &
atypicals (L. pneumophila, C pneumonia & M. pneumoniae),
Mycobacterium tuberculosis, gram-negative anaerobes
â˘
Indications:
â Chronic bronchitis
â Bacterial conjuctivitis
â Sinusitis
â˘
Unique Qualities:
â Binds divalent cations (i.e. Ca & Mg) which decreases absorption
â Safety and efficacy not established in patients <18
â˘
ADRs
â
â
â
â
Blood glucose disturbances in DM patients
QTC prolongation, arrhythmias
Nausea, GI upset
Interstitial nephritis
14. Fluoroquinolones
Adverse Effects
⢠Gastrointestinal â 5 %
ď
Nausea, vomiting, diarrhea, dyspepsia
⢠Central Nervous System
ď
ď
Headache, agitation, insomnia, dizziness, rarely,
hallucinations and seizures (elderly)
⢠Hepatotoxicity
ď
LFT elevation (withdrawal of trovafloxacin)
⢠Phototoxicity
ď levofloxacin, pefloxacin
⢠Cardiac
ď
ď
Variable prolongation in QTc interval
withdrawal of grepafloxacin, sparfloxacin
15. Fluoroquinolones
Adverse Effects
⢠Articular Damage
ď Arthropathy,
Growing cartilage damage,
arthralgias, and joint swelling
ď Led to contraindication in pediatric patients and
pregnant or breast feeding women
ď Risk versus benefit
⢠Other adverse reactions: tendon rupture,
hypersensitivity
16. Fluoroquinolones
Drug Interactions
⢠Divalent and trivalent cations â ALL FQs
ď
ď
ď
Zinc, Iron, Calcium, Aluminum, Magnesium
Antacids, Sucralfate, enteral feedings
Impair oral absorption of orally-administered FQs â
may lead to CLINICAL FAILURE
⢠Theophylline and Cyclosporine - cipro
ď inhibition
of metabolism,
levels,
⢠Warfarin â 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. â UTIs mainly contain gram negative
aerobic organisms originating from the
gut flora
â 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 (+)â
âsignificant bactertiuriaâ
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 âve 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
23. SULFONAMIDES
â˘
â˘
â˘
â˘
â˘
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
â˘
â˘
â˘
â˘
â˘
â˘
Sybthetic agent, active G-& +ve .
proteus, P.aureginosa resistence
Rapid g.i. absorption, high urinary concentration.
Bacteriostatic against common pathogens.
Pseudomonas, proteus resistant.
For âChronic suppressive therapyââ
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. âKlebsiella 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.
Hinweis der Redaktion
Nalidixic acid is not used for systemic infection because more (98.5%) protein bindingOxolinic acid â marginal better than Nalidixic acid
Bacillaryď these drug donotdistrub normal flore ď useful in acute entric bacterial infection. TravellerâsdiahrroeacotrimoxazoleThphoid â 3rd generation cephalosporinsSTD- ceftiaxone for N.Gonorrheae