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1st Generation
Gram -ve
2nd Generation
Gram-ve Gram +ve (Except S. pneumoniae)
3rd Generation
Gram -ve Gram +ve Gram +ve (including S. pneumoniae) Intracellular bacteria Anaerobic bacteria Levofloxacin, Sparfloxacin
4th Generation
Same as 3rd generation with extended anaerobic coverage
Nalidixic acid
LEVOFLOXACIN
with
side effects.
has > affinity for the target molecule DNA gyrase & has 128 times affinity than the D-isomer.
Spectrum of Activity
Gram-positive Newer FQs like Levofloxacin have enhanced
potency against Gram positive aerobes
Methicillin-susceptible Staphylococcus aureus Streptococcus pneumoniae (including PRSP) Group and viridans streptococci limited activity Enterococcus sp. limited activity
Spectrum of Activity
Gram-Negative FQs have activity in following
order(cipro=levo>gati>moxi)
Enterobacteriaceae including E. coli, Klebsiella sp, Enterobacter sp, Proteus sp, Salmonella, Shigella, Serratia marcescens, etc. H. influenzae, M. catarrhalis, Neisseria sp.
Pseudomonas aeruginosa significant resistance has emerged; ciprofloxacin and levofloxacin with best activity
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Spectrum of Activity
Anaerobes only trovafloxacin has adequate activity against Bacteroides sp. Some activity demonstrated also for Levofloxacin Atypical Bacteria all FQs have excellent activity against atypical bacteria (Intracellular organisms) including:
Legionella pneumophila - DOC Chlamydia sp. Mycoplasma sp. Ureaplasma urealyticum
Spectrum of Activity
Broad spectrum activity against gram-positive, gram-negative and atypical bacteria Active against both penicillin-susceptible and penicillin resistant Streptococcus (prevalence of S.pneumoniae resistant to Levofloxacin is <1%) Efficacy established in treatment of infection of respiratory tract, genitourinary tract, skin and skin structure.
Spectrum of activity
encountered pathogens in RTIs such as Strep. Pneumoniae as well as H. influenzae, M. catarrhalis & against intracellular organisms.
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Levofloxacin-Mechanism of Action
Bacterial topoisomerases
Packaging of DNA to make it fit
Unpackaging DNA during replication
dependent killing
Cmax:MIC MIC
postantibiotic effect
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Broad spectrum antibacterial with bactericidal activity Binds & inhibits bacterial DNA-gyrase.
This enzyme (a type II topoisomerase) produces negative super-coiling of cellular DNA, needed for bacterial DNA synthesis.
This prevents DNA replication & results in bacterial cell death
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Pharmacokinetics Profile
Offers nearly 100% bioavailability after oral
administration, making it possible to administer the drug at the same dosages either orally or intravenously. Hence ideal for sequential therapy in CAP.
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Levofloxacin
exerts Concentration-dependent killing and prolonged persistent effects noticed at higher ratio of AUC/MIC or Peak/MIC ratio
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Achieves steady state plasma level that exceed MIC values for key pathogens for 24 hours
Achieves plasma levels that are above (MIC) values for 24 hours
for most of the common pathogens after a single 500 mg oral or intravenous dose.
Clinical & microbiological outcomes can be predicted by the site
Levofloxacin. Following oral administration, 80 to 86% of the dose was recovered in urine as unchanged drug within 24 hours & 2% recovered unchanged in faeces.
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Dosage
7-10 days
7 days
Impaired renal clearance (creatinine clearance < 3 L / h or <50 ml /min ) Dosage adjustment is needed
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Clinical studies
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Dosage (mg)
Comparative studies LVFX 500 od AMC 500/125 tid LVFX 500 od CLR 500 bid Non-Comparative studies LVFX 500 od
88.3
92
Drugs 1998, 56 (3) pg 487-515
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Dosage (mg)
Comparative studies LVFX 500 od CXM 500 bid LVFX 500 od CRO 4000 od IV Non-Comparative studies LVFX 500 od IV or PO
94.7
95.1
Drugs 1998, 56 (3) pg 487-515
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Dosage (mg)
Comparative studies LVFX 500 od CXM 250 bid LVFX 500 od CEC 250 tid
Dosage (mg)
Comparative studies LVFX 250 od CIP 250 bid
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Dosage (mg)
Comparative studies LVFX 500 od CIP 500 bid LVFX 500 od CIP 500 tid
Findings support the efficacy of oral Levofloxacin for uncomplicated skin & skin structure infections due to S. aureus & S. pyogenes. (Int J Clin Pract 1998; 52(2): 69-74)
IJCP, March 1998 Vol. 52 No. 2
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Salient Features
Nearly 100% bioavailability making it equivalent to IV
quinolones
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Salient Features
Broad spectrum of activity covering gram +ve, gram-
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Salient Features
other quinolone (Ciprofloxacin) hence better activity against gram +ve & gram-ve organisms.
MIC equals bactericidal concentrations.
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Salient Features
unchanged in urine.
Bioavailability is not affected by food
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Salient Features
inflammatory exudates.
First quinolone to be approved for the treatment of
acute sinusitis.
Phototoxicity is infrequent & is <1% while it is 8% with
Sparfloxacin.
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Salient Features
Incidence of seizures, tendinitis, pseudomembranous
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