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The Quinolones: Past, Present The Quinolones: Past, Present and Future and Future
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The wonder drug --Quinolones.

Aug 22, 2014

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Quinolones , The Quinolone are class of antimicrobial agents that was not isolated from living organisms but, rather, was synthesized by chemists.
They are a group of synthetic broad spectrum antibacterial drugs that target DNA Synthesis. The prolific development of the Quinolones began in 1962, when Lesher et al. made the accidental discovery of nalidixic acid as a by-product of the synthesis of the antimalarial compound chloroquine.
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Page 1: The wonder drug --Quinolones.

The Quinolones: Past, Present and FutureThe Quinolones: Past, Present and Future

Page 2: The wonder drug --Quinolones.

The Past…. The Past….

The Quinolone are class of antimicrobial agents that The Quinolone are class of antimicrobial agents that was not isolated from living organisms but, rather, was not isolated from living organisms but, rather, was synthesized by chemists. was synthesized by chemists.

They are a group of synthetic broad spectrum They are a group of synthetic broad spectrum antibacterial drugs that target DNA Synthesis.antibacterial drugs that target DNA Synthesis.

The prolific development of the Quinolones began in The prolific development of the Quinolones began in 1962, when Lesher et al. made the accidental 1962, when Lesher et al. made the accidental discovery of nalidixic acid as a by-product of the discovery of nalidixic acid as a by-product of the synthesis of the antimalarial compound chloroquine.synthesis of the antimalarial compound chloroquine.

Page 3: The wonder drug --Quinolones.

The Past….The Past…. Nalidixic acid became the lead compound for Nalidixic acid became the lead compound for

medicinal chemists for structural modifications medicinal chemists for structural modifications to get many newer fluoroquinolones in order to get many newer fluoroquinolones in order to get rid of its three major shortcomings…. to get rid of its three major shortcomings….

  Narrow spectrum covering Gr (-ve) organisms Narrow spectrum covering Gr (-ve) organisms only only

Achieves inadequate tissue levels for Achieves inadequate tissue levels for systematic infections and systematic infections and

Bacterial resistance development. Bacterial resistance development.

Page 4: The wonder drug --Quinolones.

The Past….The Past…. This discovery led to the development of a library of This discovery led to the development of a library of

quinolone compounds, especially the newer quinolone compounds, especially the newer quinolones in clinical use at the present time. quinolones in clinical use at the present time.

Fluoroquinolones are the derivatives of quinolones Fluoroquinolones are the derivatives of quinolones which are fluorinated at C-6 position of the quinolone which are fluorinated at C-6 position of the quinolone ring. They are broad-spectrum bactericidal agents ring. They are broad-spectrum bactericidal agents inhibiting DNA synthesis inhibiting DNA synthesis

They act on two enzymes involved in DNA synthesis: They act on two enzymes involved in DNA synthesis: DNA gyrase and topoisomerase IV and thereby DNA gyrase and topoisomerase IV and thereby block DNA replication and transcription, leading to block DNA replication and transcription, leading to cell deathcell death

Page 5: The wonder drug --Quinolones.

The Past….The Past…. The various derivatives of fluoroquinolone The various derivatives of fluoroquinolone

have varying levels of activity depending on have varying levels of activity depending on the various groups attached at different the various groups attached at different positions. positions.

Generating a derivative with increased activity Generating a derivative with increased activity helps to reduce the Minimum Inhibitory helps to reduce the Minimum Inhibitory Concentration (MIC), thereby reducing the Concentration (MIC), thereby reducing the possibility of developing resistance to it. possibility of developing resistance to it.

Page 6: The wonder drug --Quinolones.

The Present The Present Two main classifications for fluoroquinolones based on Two main classifications for fluoroquinolones based on

chemical structure  and biological properties  respectively has chemical structure  and biological properties  respectively has been described by Bryskier & Chantot , which logically been described by Bryskier & Chantot , which logically embraces the majority of active compounds known till date. embraces the majority of active compounds known till date.

Differences in the in-vitro activity of the fluoroquinolones Differences in the in-vitro activity of the fluoroquinolones against gram positive and gram negative organisms primarily against gram positive and gram negative organisms primarily form the basis of their biological classification, as shown in form the basis of their biological classification, as shown in

table 1.table 1. The first generation being the most narrow and the subsequent The first generation being the most narrow and the subsequent

ones having an increase in spectrum of activity and on the ones having an increase in spectrum of activity and on the novelty and complexity of the structures of quinolones.novelty and complexity of the structures of quinolones.

Page 7: The wonder drug --Quinolones.

Table one ….Table one ….

GenerationGeneration DrugsDrugs Antibacterial Antibacterial spectrumspectrum

First First Nalidixic acidNalidixic acid aerobic, gram-aerobic, gram-negativebacteria.negativebacteria.

SecondSecond NorfloxacinNorfloxacinCiprofloxacinCiprofloxacinEnoxacinEnoxacinFleroxacinFleroxacinLomefloxacinLomefloxacinOfloxacinOfloxacinLevofloxacinLevofloxacin

RufloxacinRufloxacin

antimicrobial activity antimicrobial activity against aerobic gram-against aerobic gram-positive bacteria and positive bacteria and improved activity against improved activity against gram-negative bacteriagram-negative bacteria

Page 8: The wonder drug --Quinolones.

Table one…Table one…GenerationGeneration DrugsDrugs Antibacterial spectrumAntibacterial spectrum

Third Third TosufloxacinTosufloxacinGatifloxacinGatifloxacinGemifloxacinGemifloxacinTemafloxacinTemafloxacin

GrepafloxacinGrepafloxacin

gram-positive bacteria, gram-positive bacteria, particularly pneumococci; they particularly pneumococci; they also had good activity against also had good activity against anaerobicanaerobic

Fourth Fourth BesifloxacinBesifloxacin,,ClinafloxacinClinafloxacinGarenoxacin, GGarenoxacin, GemifloxacinemifloxacinMoxifloxacinMoxifloxacinGatifloxacin‡Gatifloxacin‡SitafloxacinSitafloxacinTrovafloxacin‡/Trovafloxacin‡/AlatrofloxacinAlatrofloxacin‡‡PrulifloxacinPrulifloxacin

anaerobes and increased activity anaerobes and increased activity against pneumococciagainst pneumococci

FifthFifth DelafloxacinDelafloxacin

Page 9: The wonder drug --Quinolones.

StructureStructure All fluoroquinolones have a basic All fluoroquinolones have a basic

4-quinolone structure, with a 4-quinolone structure, with a fluorine atom at C-6 position.fluorine atom at C-6 position.

Differences between the various Differences between the various fluoroquinolones are usually due fluoroquinolones are usually due to various groups that are attached to various groups that are attached at positions 1, 5, 7 and 8.at positions 1, 5, 7 and 8.

The addition of specifically The addition of specifically selected substituents at these key selected substituents at these key positions on the quinolone positions on the quinolone nucleus made it possible to target nucleus made it possible to target specific groups of bacteria and to specific groups of bacteria and to improve theimprove the pharmacokinetics of pharmacokinetics of the earlier quinolone compoundsthe earlier quinolone compounds

Page 10: The wonder drug --Quinolones.

…….Structure.StructureSome of the key structural modifications are :Some of the key structural modifications are :

addition of a fluorine atom at position C-6, which increased DNA gyrase addition of a fluorine atom at position C-6, which increased DNA gyrase inhibitory activity, facilitated penetration into the bacterial cell, and inhibitory activity, facilitated penetration into the bacterial cell, and provided activity against staphylococci.provided activity against staphylococci.

The addition of a piperazine group at position C-7 provided the greatest The addition of a piperazine group at position C-7 provided the greatest activity against aerobic gram-negative bacteria and increased the activity activity against aerobic gram-negative bacteria and increased the activity against both staphylococci and against both staphylococci and Pseudomonas Pseudomonas species and also increased species and also increased the elimination half-life and improved bioavailability.the elimination half-life and improved bioavailability.

The addition of a second fluorine group at position C- 8 resulted in The addition of a second fluorine group at position C- 8 resulted in increased absorption and a longer elimination half-life but also increased increased absorption and a longer elimination half-life but also increased phototoxicity.phototoxicity.

In addition, increased activity against In addition, increased activity against Mycoplasma Mycoplasma and and Chlamydia Chlamydia species species was achieved by adding an amino group at C-5 and a fluorine group at C-8 was achieved by adding an amino group at C-5 and a fluorine group at C-8 to quinolone compounds that possessed a cyclopropyl group at N-1 as to quinolone compounds that possessed a cyclopropyl group at N-1 as seen in ciprofloxaxin, sparfloxacin and gatifloxacin.seen in ciprofloxaxin, sparfloxacin and gatifloxacin.

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…….Structure .Structure The most recent key modification was the The most recent key modification was the

observation that the addition of a methoxy observation that the addition of a methoxy group, instead of a halide, at the C-8 position group, instead of a halide, at the C-8 position specifically targets both topoisomerase II and specifically targets both topoisomerase II and IV, which also may decrease the possibility of IV, which also may decrease the possibility of the development of resistance to quinolones .the development of resistance to quinolones .

Of the currently available agents, only Of the currently available agents, only gatifloxacin and moxifloxacin have a C-8 gatifloxacin and moxifloxacin have a C-8 methoxy group in their chemical structure.methoxy group in their chemical structure.

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Mechanism of actionMechanism of action Fluoroquinolones enter the cells Fluoroquinolones enter the cells

by porins and target two enzymes: by porins and target two enzymes: DNA gyrase and topoisomerase DNA gyrase and topoisomerase IV. DNA gyrase or topoisomerase IV. DNA gyrase or topoisomerase II helps in producing negative II helps in producing negative superhelical twists.superhelical twists.

When fluoroquinolones bind to When fluoroquinolones bind to these enzymes, it blocks the these enzymes, it blocks the activity of these enzymes and activity of these enzymes and hence stops replication, hence stops replication, transcription, repair as well as transcription, repair as well as recombination. recombination.

Page 13: The wonder drug --Quinolones.

……..Mechanism of action…....Mechanism of action….. The fluoroquinolones bind to the enzyme-DNA complex and The fluoroquinolones bind to the enzyme-DNA complex and

forms a stable ternary complex. The complex of drug, forms a stable ternary complex. The complex of drug, topoisomerase IV and DNA collides with the DNA replication topoisomerase IV and DNA collides with the DNA replication complex and forms a physical barrier that blocks the further complex and forms a physical barrier that blocks the further progression of the replication fork.progression of the replication fork.

On the other hand, the complex of drug, DNA gyrase and On the other hand, the complex of drug, DNA gyrase and DNA blocks the passage of RNA polymerase and leads to the DNA blocks the passage of RNA polymerase and leads to the premature termination of transcription.premature termination of transcription.

In gram negative organisms like In gram negative organisms like Escherichia coliEscherichia coli, , fluoroquinolones bind to DNA gyrase as a primary target and fluoroquinolones bind to DNA gyrase as a primary target and topoisomerase IV as the secondary target.topoisomerase IV as the secondary target.

In contrast,in gram positive organisms like In contrast,in gram positive organisms like Staphylococcus Staphylococcus aureusaureus, fluoroquinolones bind to topoisomerase IV as the , fluoroquinolones bind to topoisomerase IV as the primary target and DNA gyrase as the secondary target.primary target and DNA gyrase as the secondary target.

Page 14: The wonder drug --Quinolones.

Pharmacokinetics and Pharmacokinetics and pharmacodynamics pharmacodynamics

Most of the fluoroquinolones are available in the intravenous or oral form. Such Most of the fluoroquinolones are available in the intravenous or oral form. Such fluoroquinolones include ciprofloxacin, ofloxacin, levofloxacin and alatrofloxacin fluoroquinolones include ciprofloxacin, ofloxacin, levofloxacin and alatrofloxacin (alatrofloxacin is metabolized in the body into trovafloxacin). (alatrofloxacin is metabolized in the body into trovafloxacin).

The bioavailability of the fluoroquinolones from an oral administration is the same The bioavailability of the fluoroquinolones from an oral administration is the same as the intravenous administration, and hence gives the same effect as one as the intravenous administration, and hence gives the same effect as one administered intravenously.administered intravenously.

The bioavailability of fluoroquinolones ranges from 70% to greater than 90%. The bioavailability of fluoroquinolones ranges from 70% to greater than 90%. Comparison of different fluoroquinolones show that the fourth and higher Comparison of different fluoroquinolones show that the fourth and higher

generations, like trovafloxacin and moxifloxacin have better bioavailability, higher generations, like trovafloxacin and moxifloxacin have better bioavailability, higher plasma concentrations, greater tissue penetration, longer elimination half life and plasma concentrations, greater tissue penetration, longer elimination half life and higher volume of distribution . higher volume of distribution .

The fourth generation fluoroquinolones have been shown to have higher protein The fourth generation fluoroquinolones have been shown to have higher protein binding than the third generation.binding than the third generation.

This results in higher concentration of the drugs in the tissues and fluids. This results in higher concentration of the drugs in the tissues and fluids. Penetration of the fluoroquinolones into various tissues like kidney, lung, bronchial Penetration of the fluoroquinolones into various tissues like kidney, lung, bronchial mucosa, gallbladder, genital tract and prostate are found to be very high.mucosa, gallbladder, genital tract and prostate are found to be very high.

All the fluoroquinolones undergo either renal or hepatic eliminationAll the fluoroquinolones undergo either renal or hepatic elimination

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Development of Resistance Development of Resistance

In the recent,  past there have been increasing number of In the recent,  past there have been increasing number of cases of resistance against fluoroquinolones due to cases of resistance against fluoroquinolones due to many reasons such as many reasons such as

Incomplete treatment with required doses and Incomplete treatment with required doses and duration duration

Overdosage Overdosage Excessive and improper use of fluoroquinolones Excessive and improper use of fluoroquinolones

when not  required when not  required Development of mutant strains of causative bacteria Development of mutant strains of causative bacteria

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Mechanism of developing Mechanism of developing resistanceresistance

Progress in our understanding of the role of SARs, along with the application of current research techniques, has indicated that bacterial resistance to quinolones occurs due to many reasons :

Alteration in DNA gyrase and Alteration in DNA gyrase and topoisomerase IV and decreased topoisomerase IV and decreased intracellular accumulation of the drug due intracellular accumulation of the drug due to modifications of membrane proteins . to modifications of membrane proteins .

Single point mutation in gyr A that codes Single point mutation in gyr A that codes for a type II topoisomerase subunit A is for a type II topoisomerase subunit A is most common37. most common37.

Reduction of gyrase affinity for drug Reduction of gyrase affinity for drug Decreased penetration due to loss of key Decreased penetration due to loss of key

membrane proteins membrane proteins Cross resistance among fluoroquinolones Cross resistance among fluoroquinolones

-- resistance to one quinolone usually -- resistance to one quinolone usually confers resistance to entire class. confers resistance to entire class.

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Adverse reactions….Adverse reactions…. The rate of adverse events associated with both oral and intravenous fluoroquinolonesappears to be dose related, with an increasing incidence of adverse events associated with

increasing doses and duration of therapy:

Achilles Tendonitis :-Achilles Tendonitis :- Both older and newer fluoroquinolones have been shown to be associated with Both older and newer fluoroquinolones have been shown to be associated with arthropathy in weight bearing joints . Studies have shown erosion and permanent lesions of cartilage due to arthropathy in weight bearing joints . Studies have shown erosion and permanent lesions of cartilage due to quinolone use in animals . quinolone use in animals .

Cardiac :- Cardiac :- QT prolongation is thought to be due to halogen substitution at the number 8 position ( e.g QT prolongation is thought to be due to halogen substitution at the number 8 position ( e.g Moxifloxacin ) Moxifloxacin )

Gastrointestinal :- Gastrointestinal :- Most common side-effects are nausea , vomitting and diarrhoea , with an occurrence Most common side-effects are nausea , vomitting and diarrhoea , with an occurrence rate ranging from 3 to 17 percent . rate ranging from 3 to 17 percent .

CNS :- CNS :- Effects such as insomnia , dizziness and anxiety have been reported in 0.9 to 11 percent Effects such as insomnia , dizziness and anxiety have been reported in 0.9 to 11 percent patients .Seizures are a rare occurrence but have been increasingly reported when used with Theophylline patients .Seizures are a rare occurrence but have been increasingly reported when used with Theophylline or with NSAID's . or with NSAID's .

Crystaluria :- Crystaluria :- Associated with fluoroquinolones except Levofloxacin , Gatifloxacin34,Moxifloxacin , and Associated with fluoroquinolones except Levofloxacin , Gatifloxacin34,Moxifloxacin , and Trovafloxacin . Patients are instructed to drink plenty of water. Trovafloxacin . Patients are instructed to drink plenty of water.

Liver Toxicity :Liver Toxicity :-  In 18 months post-approval follow up by US Food and Drug Administration  (FDA)  for -  In 18 months post-approval follow up by US Food and Drug Administration  (FDA)  for Trovafloxacin 140 cases of liver toxicity were found . Trovafloxacin 140 cases of liver toxicity were found .

Phototoxicity :Phototoxicity :- Most likely to occur with the use of Ciprofloxacin , Lomefloxacin , Norfloxacin- Most likely to occur with the use of Ciprofloxacin , Lomefloxacin , Norfloxacin, fleroxacin, and sparfloxacin. .

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…….Adverse reactions.Adverse reactions Three adverse events associated with

quinolones—cardiotoxicity (e.g., prolongation of the corrected QT interval), hepatotoxicity,

and hypoglycemia—currently command the most attention.

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The Present The Present A number of infectious diseases are

successfully treated with quinolones administered orally or intravenously.

Clinical efficacy has been demonstrated for respiratory tract infections,including acute bacterial exacerbations of chronic bronchitis,

community-acquired pneumonia, nosocomial pneumonia, and bacterial sinusitis.

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Approved clinical uses for selected fluoroquinolones.Ciprofloxacin

Acute uncomplicated cystitis in females (oral use only) Urinary tract infections Chronic bacterial prostatitis Uncomplicated cervical and urethral gonorrhea Skin and skin-structure infections Bone and joint infections Infectious diarrhea (oral use only) Typhoid fever (oral use only) Complicated intra-abdominal infections, in combination with metronidazole Acute sinusitis Lower respiratory tract infections Nosocomial pneumonia (iv use only) Empirical therapy for patients with febrile neutropenia, in combination with piperacillin sodium (iv use only) Inhalational anthrax (after exposure) Complicated urinary tract infections and pyelonephritis in pediatric patients (1–17 years

old)

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Levofloxacin Uncomplicated urinary tract infections (mild to moderate) Complicated urinary tract infections (mild to moderate) Acute pyelonephritis (mild to moderate) Chronic bacterial prostatitis Uncomplicated skin and skin-structure infections (mild to

moderate) Complicated skin and skin-structure infections Acute maxillary sinusitis Acute bacterial exacerbation of chronic bronchitis Community-acquired pneumoniaa Nosocomial pneumonia

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Moxifloxacin Acute bacterial sinusitis Acute bacterial exacerbation of chronic

bronchitis Community-acquired pneumoniaa Uncomplicated skin and skin-structure

infections

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Gatifloxacin Uncomplicated urinary tract infections Complicated urinary tract infections Pyelonephritis Uncomplicated urethral and cervical gonorrhea Acute uncomplicated gonococcal rectal infections in

women Uncomplicated skin and skin-structure infections Acute sinusitis Acute bacterial exacerbation of chronic bronchitis Community-acquired pneumoniaa

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Gemifloxacin Acute bacterial exacerbation of chronic

bronchitis Community-acquired pneumonia (mild to

moderate).

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The FutureThe Future The future prospects of newer Quinolones depends on:(1) greater potency, particularly against staphylococci and

enterococci; (2) better penetration into the CNS and cerebrospinal fluid;(3) broader and more potent activity against anaerobic bacteria;(4) greater activity against infections caused by mycobacteria and

Stenotrophomonas, Pseudomonas, and Alcaligenes species, which currently are difficult to treat;

(5) decreased drug-drug interactions; and (6) better patient tolerability, with lower incidences of adverse

reactions and serious toxicity

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The Future….The Future…. In addition, newer quinolones may be developed with greater

activity against targets in infectious agents responsible for Lyme disease, malaria, nocardiosis, toxoplasmosis, pneumocystosis, leishmaniasis, fungi, and DNA viruses.

Other poorly poorly explored, area is the development of new compounds with a high and specific affinity for the DNA (eukaryotic topoisomerases) in human malignant cells, which could be used alone or in combination with other chemotherapeutic agents. This potential would provide sufficient economic and humane rewards to justify the investment in such an effort

Page 27: The wonder drug --Quinolones.

……..The Future..The Future If the use of quinolones in clinical medicine is

to continue,the emergence of bacterial resistance to the quinolones should remain of primary importance as an area of current and future research.

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GarenoxacinGarenoxacin Garenoxacin is a synthetic, des-F(6)-quinolone antibacterial Garenoxacin is a synthetic, des-F(6)-quinolone antibacterial

agent. The molecule does not contain fluorine at the C-6 agent. The molecule does not contain fluorine at the C-6 position, which is present in all the fluoroquinolone position, which is present in all the fluoroquinolone antibacterial agents. antibacterial agents.

Garenoxacin is presented for clinical use as 400 mg and 600 Garenoxacin is presented for clinical use as 400 mg and 600 mg film-coated tablets and for infusion mg film-coated tablets and for infusion

Garenoxacin demonstrates unique Structure-Activity Garenoxacin demonstrates unique Structure-Activity Relationship to offer one of the lowest MICs against Relationship to offer one of the lowest MICs against respiratory pathogens with low potential for resistance respiratory pathogens with low potential for resistance development. development.

It was developed in Japan that was further researched and It was developed in Japan that was further researched and developed by Toyoma Ltd in collaboration with Bristol developed by Toyoma Ltd in collaboration with Bristol Meyers Squibb, USAMeyers Squibb, USA

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GarenoxacinGarenoxacin Garenoxacin demonstrates wide spectrum of Garenoxacin demonstrates wide spectrum of

antibacterial activity against Gm positive, Gm antibacterial activity against Gm positive, Gm negative, Atypical and Anaerobic pathogens. negative, Atypical and Anaerobic pathogens.

The novel structure resulted in complete The novel structure resulted in complete bacteriological eradication rates against bacteriological eradication rates against Quinolone-resistant (100%), β-lactam resistant Quinolone-resistant (100%), β-lactam resistant

(97.7%) and Macrolide resistant (98.7%) (97.7%) and Macrolide resistant (98.7%) strains of Strep. pneumoniaestrains of Strep. pneumoniae

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Garenoxacin—Clinical use and Garenoxacin—Clinical use and Indications.Indications.

Garenoxacin is a novel des-fluoro 6-quinolone with unique Garenoxacin is a novel des-fluoro 6-quinolone with unique Pharmacokinetic profile that promises to cover a wide spectrum Pharmacokinetic profile that promises to cover a wide spectrum of organisms commonly encountered in community acquired of organisms commonly encountered in community acquired infections including Gm positive, Gm negative, Atypical & infections including Gm positive, Gm negative, Atypical & Anaerobic organisms with negligible potential for resistance Anaerobic organisms with negligible potential for resistance development. development.

Garenoxacin has been associated with high clinical success rates Garenoxacin has been associated with high clinical success rates in patients with Bronchitis, Pneumonia and in patients with Bronchitis, Pneumonia and otorhinolaryngological infections when used as initial- or second otorhinolaryngological infections when used as initial- or second line settings.line settings.

Garenoxacin is indicated for the following bacterial infections Garenoxacin is indicated for the following bacterial infections caused by susceptible microorganisms including Pharyngitis, caused by susceptible microorganisms including Pharyngitis, Sinusitis Laryngitis, Tonsillitis, Otitis media, Acute bronchitis, Sinusitis Laryngitis, Tonsillitis, Otitis media, Acute bronchitis, Pneumonia and Secondary infection in chronic respiratory Pneumonia and Secondary infection in chronic respiratory lesion.lesion.

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Garenoxacin- ContraindicationsGarenoxacin- Contraindications

Garenoxacin should be administered with Garenoxacin should be administered with caution in:caution in:

High-risk patients who have convulsive High-risk patients who have convulsive disorders such as epilepsy, and elderly disorders such as epilepsy, and elderly patients. patients.

Patients who have a history of hypersensitivity Patients who have a history of hypersensitivity to any component of the formulationto any component of the formulation

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Garenoxacin- Adverse reactionsGarenoxacin- Adverse reactions The most frequent adverse effects reported in clinical The most frequent adverse effects reported in clinical

trials were diarrhea, nausea, and headache.trials were diarrhea, nausea, and headache.

Garenoxacin is a well tolerated drug with its Garenoxacin is a well tolerated drug with its safety profile well differentiated due to lack of any safety profile well differentiated due to lack of any

significant concerns on Photosensitivity, Abnormal significant concerns on Photosensitivity, Abnormal hepatic functioning, Seizures, Arthropathy and QTc hepatic functioning, Seizures, Arthropathy and QTc prolongation. prolongation.

..

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Garenoxacin –Place in therapyGarenoxacin –Place in therapy Garenoxacin with its Pharmacodynamic and Garenoxacin with its Pharmacodynamic and

pharmacokinetic correlates promises to have the pharmacokinetic correlates promises to have the therapeutic efficacy while treating Skin and Skin therapeutic efficacy while treating Skin and Skin Structure infections, Urinary tract infections, Structure infections, Urinary tract infections, Intraabdominal infections and Gastrointestinal Intraabdominal infections and Gastrointestinal infections including Enteric fever though the clinical infections including Enteric fever though the clinical data is sparse.data is sparse.

Garenoxacin has been associated with high clinical Garenoxacin has been associated with high clinical success rates in patients with Bronchitis, Pneumonia success rates in patients with Bronchitis, Pneumonia and Otorhinolaryngological infections when used as and Otorhinolaryngological infections when used as initial- or secondline settings,initial- or secondline settings,

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Thank you Thank you