CEFADROXIL

3 important Antibiotics CephalosporinTetracyclines&FluoroquinolonesPresented by: Md.Mustahasin Karim

CephalosporinCephalosporins are grouped into "generations" by their antimicrobial properties. Cephalosporins are categorizedchronically, and are therefore divided into first, second, and third generations. Currently, three generations ofcephalosporins are recognized and a fourth has been proposed. Each newer generation of cephalosporins hasgreater gram negative antimicrobial properties than the preceding generation. The later-generationcephalosporins have greater effect against resistant bacteria.

Cephalosporin

Cephalosporins are beta-lactam compounds in which the beta-lactam ring is fused to a 6-membered dihydrothiazine ring, thus forming the cephem nucleus. Side chain modifications to the cephem nucleus confers 1)an improved spectrum of antibacterial activity,2) pharmacokinetic advantages, and 3) additional side effects. Based on their spectrum of activity, cephalosporin's can be broadly categorized into four generations.

Structure:

Cephalosporin

Mechanism of action:Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins) but are less susceptible to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic() the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan.

CLASSIFICATION

A. First Generation

Cephaloridine-Loridine, Ceporan Cephalothin-Keflin Cephalexin-Keflex, Ceporex Cefazolin-Cefacidal Cephradine-Velosef Cepharpirin-Cefadyl Cephadroxil-Doricef, Cefamox

Second GenerationCefaclor-CeclorCefoxitin MefoxinCefuroxime Zinacef, ZinnatCefonicid MonocidCefotetan - CefotanCefamdandole MandolCefprozil CefzilLoracarbef Lorabid Cefmetazole Zefazone Ceforanide

Third Generation

Cefotaxime ClaforanCefoperazone CefobidMoxolactam MoxamCeftizoxime CefizoxCeftriaxone RocephinCeftazidime FortumCefotiam CeradolanCefixime SupraxCefetamet GlobocefCefpodoxime VantinCeftibuten CedaxCefdinir OmnicefCefditoren

Fourth Generation Cefepime Maxipime Cefpirome Cefrom

CEFADROXILIndication:It has been successfully used for the treatment of upper respiratory tract infection.It is also used in U.T.I.Community acquired pneumonia() is well treated by cefadroxil.It is effective against Gram-positive and Gram-negative organisms.

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Contraindication:It is not used in an individuals with porphyria(rare inherited or acquired disorder).If the patient hypersensitive to cephalosporin.

Adverse effect:Diarrhoea.Nausea , Vomiting.Allergic reaction may occur.Blood disorders; including thrombocytopenia(abnormally low amount of platelets).Leucopenia(Decrease of white blood cell).Aplastic anemia(damage of bone marrow).

Dose:Adult: 500mg twice daily for skin, soft tissue and U.T.I.Child: 250mg twice daily , soft tissue and U.T.I.(Age: 1-6 years).

Brand Name:Adora Incepta.Trubid Opsonin.Arocef SKF.

CEFALEXIN/CEPHALEXINIndication:It has highly activity against Gram-positive organisms and moderate activity against Gram-negative organism such as E.coli , Klebseilla and proteus.It is useful for U.T.I. and R.T.I.It is effective in Sinusitis and Skin and Soft tissue infection.

Contraindication:It should not be used in infection caused by H. influenza.It should not used in Syphilis(sexually transmitted infection).Cephalosporin hypersensitivity.

Adverse effect:Diarrhea, Vomiting.Abdominal discomfort are relatively common.Neurological disturbances may occur rarely.

Dose:Adult: 500mg twice daily for severe infection.Child: 250mg twice daily for U.T.I.Prophylaxis of recurrent U.T.I , 125mg at night.

Brand Name:Ceporin Square.Keflin Opsonin.Alexin Reneta.

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CEFOXITINIndication:It is effective against betalactamase producing strains of Haemophilus influenzae.It is effective against Gram-negative organisms , except pseudomonas.It can also be used in the treatment of U.T.I and lower respiratory tract infections.It is useful in otitis ( ) media.

Contraindication:Hypersensitive to cephalosporin.Porphyria.

Adverse effect:Diarrhea.Nausea , Vomiting.Allergic reaction may also occur.GI upset.

Dose:200 400 mg daily in 1-2 divided dose.

Brand Name:Cef-3Square.CefidOpsonin.RokimSKF

CEFDINIRIndication:It is very active against Staphylococci , Streptococci and H. influenza.It is used in the treatment of gonrrhoea ( sexuall transmitted infections).It is also used in R.T.I.

Contraindications:Hypersensitive to cephalosporin.Porphyria.

Adverse effect:Diarrhea.Allergic reaction.Gastrointestinal upset.Uncomfortable abdomen.

Dose:200-400mg daily in 1-2 divided doses.

Brand Name:Efdinir-Incepta.Cednir-SKF.Cefida-Beximco.

CEFOTAXIMEIndication:It is widely used in in respiratory infection.It is effective in meningitis( ).It is used in the treatment of Typhoid fever , U.T.I.It is useful in gonorrhoea and intra-abdominal sepsis.

Contraindication:Hypersensitive to cephalosporin.Porphyria.

Adverse effect:Dermatological problem.Hematological problem may occur.Diarrhea.Allergic reaction.

Dose:I.M,I.V 1-2g every 8hours depends on severity of infection.

Brand Name:Cefotax Renata.Maxcef Square.Taxim Acme.

CEFPODOXIMEIndications:It is used in upper respiratory tract infection.It is used in the treatment of lower respiratory tract infection including bronchitis , pneumonia , skin and soft tissue infection.It is used in the treatment of gonorrhoea.

Contraindication:Cephalosporin sensitivity.Porphyria.

Adverse effect:GI upset.Diarrhea.Nausea , Vomiting.Allergic reaction also occur.

Dose:100-200mg every 12hours for R.T.I. and U.T.I.

Brand Name:Vanprox Square.Vercef Beximco.Ximeprox Incepta.Cefdox ACI.

CEFTRIAXONE(INJ.)Indication:It is effective in uncomplicated gonorrhoea and genital ulceration.It has been commanded for the treatment of enteric fever.It is also used in meningitis.It is used in osteomyelitis ( ).

Contraindication:Cephalosporin sensitivity.Porphoria.

Adverse effect:Abdominal pain , Diarrhea.Rush , fever.Thrombocytopenia , thrombocytosis , leucopenia.

Dose:A single 250mg dose is effective for gonorrhoea and genital ulceration.I.M , I.V 1 g/day as a single dose in moderate infaction.

Brand Name:Traxon opsonon.Arixon Baximco.Ceftron Square.Axon Aristopharma.

CEFEPIME(INJ.)Indication:It is indicated for the treatment of serious infection due to organism resistance to cefotaxime.It is used in the treatment of respiratory tract infection.It is useful in gonorrhoea.It is effective in enteric fever.

Contraindication:Hypersensitivity to cephalosporin.Porphyria.

Adverse effect:Allergic reaction occurs.Nausea , Vomiting.GI upset.

Dose:I.V 2g of cefepime is given over 30min.

Brand Name:Xenim Opsonin.Ultrapime Incepta.Ceftipime Reneta.

MAFENIDEIndication:It is used extensively in burns(second and third degree burn)It is bacteriostatic against many Gram-positive and Gram-negative organisms.Its capacity to inhibit carbonic anhydrous which could potentially result in metabolic acidosis(when body produce much acid or when the kidney remove enough acid).

Contraindications:Renal impairment.Mefenide is contraindicated in those with sulfonamide hypersensitivity.

Adverse effect:Super infection.Pain.Rash.Pruritus.

Dose:It should apply topically to a thickness of approx. 1.6mg to cleaned and debrided wound once or twice per day.

Brand Name:Mafanil.Sulphamylar.Sulfamylon.

CEFTOBIPROLEIndications:It is effective against MRSA.It is also used in the treatment of complicated skin and skin structure infections.It gives better result in community acquired pneumonia (it is pneumonia acquired infectious from normal social contact)compared to ceptriaxone.

Contraindications:Hypersensitivity to cephalosporin.Hepatic failure.Renal impairment.

Adverse effect:NauseaDiarrheaAllergic reaction.

Dose:400 mg daily for MRSA.

Brand Name:Zeftera-UK,EU

CEFTAROLINE FOSAMILIndications:It has activity against MRSA(Methicillin-resistant Staphylococcus aureus)It is also used in treatment of complicated skin and skin structure infections.It gives better result in community acquired pneumonia compared to ceftriaxone.

Contraindications:Known serious hypersensitivity to ceftarolin.Porphyria.

Adverse effect:Diarrhea.Nausea.Rush.

Dose:400mg daily for M.R.S.A.; in serve case it may be two time daily.

Brand Name:Teflaro in US.Zinforo in Europe.

Tetracyclines- Tetracyclines are a group of broad-spectrum antibiotics- They are natural product derived from Streptomyces sp

- Tetracyclines are so named for their four (tetra) hydrocarbon rings

Tetracyclines- The general usefulness of tetracyclines has been reduced with the onset of antibiotic resistance. Despite this, they remain the treatment of choice for some specific indications

General Consideration- Source: Streptomyces grasius, a soil organism- Spectrum: Broad spectrum of activity i.e., active against both gm(+) and gm(-) bacteria- Mode of action: Bacteriostatic in nature- Mechanism of ACTION: Protein synthesis inhibition

History The development of the tetracycline antibiotics was the result of a systemic screening of soil specimens collected from many parts of the world for antibiotic-producing microorganisms. The first of these compounds chlortetracycline was introduced in 1948 followed by oxytetracycline and tetracycline in 1950 and 1952 respectively.

TypesTetracyclines are of two types:

1. Natural Tetracycline: (Short acting) - Chlortetracycline (S.aureofaciens ) - Oxytetracycline (S. rimosus ) - Demeclocycline (S. aureofaciens )

Types2. Semisynthetic Tetracycline: (long acting) -Doxycyclicline - Methecycline - Minocycline

3. Both natural and semisynthetic: -Tetracycline : Natural from S. grasius Semisynthetic from Chlortetracycline

Mechanism of ActionTetracycline

Enters into bacteria by -passive diffusion -Active transport

Binds reversibly to receptor on the 30s ribosomal subunit

Block the binding of charged aminoacyl tRNA to the A site of the ribosome mRNA complex

(-) addition of aminoacid in growing peptide chain

(-) Protein synthesis

(-) Bacterial growth & multiplicationNote: At high conc. they can inhibit protein synthesis of mammal cell

Mechanism of Tetracycline resistance >>The drug is not actively transported into the cell>>The drug leaves the cell so rapidly that the required conc. Of the drug is not maintained>>Enzymatic inactivation of tetracycline>>Production of protein that interferes binding of tetracycline to ribosome

Therapeutic usesDrug of first choice Rickettsial infection -Rocky mountain spotted fever -Typhus -Rickettsialpox Mycoplasma infection -Mycoplasma pneumonia Borrelia infection -Lyme disease -Relapsing fever Vibrio infection -Cholera Plague, brucellois ( with aminoglycoside)

Therapeutic usesDrug of second choice Diarrhoea Dysentery Mixed bacterial infection e.g. repiratory tract infection Acne SIADH (Syndrome of inappropriate ADH secretion) Leptospiral infection Tularemia (An acute plague like infectious disease Caused by Francisella tularensis transmitted to the human by the bite of an infected tick or other blood sucking insect Weils disease

Adverse effectA) Organ/ system toxicity GIT -Nausea -Vomiting -Diarrhoea -Alteration of intestinal flora Hepatotoxicity Nephrotoxicity (due to inhibition of protein synthesis) -Renal tubular acidosis -Nephrogenic diabetes insipidus -Fanconis syndrome Bony stucture and teeth: -Discoloration and hypoplasia of teeth Vestibular toxicity: -Dizziness -Vertigo

Adverse effectB) Super infection: -Candida or resistant staphylococci

C) Hypersensitivity: -Urticaria -Anaphylaxix -Angioedema

ContraindicationPregnancy and lactationYoung children ( upto 8 years)Renal failureHistory of hypersensitivity

Oxytetracycline Indications: -treatment of Spirochaetal infection. -treatment of Non-Specific-Urethritis. -treatment of Clostridial wound infection and Anthrax. Contraindication: -Renal impairment -Pregnancy & breast feeding -SLE (Systemic lupus eryyhematosus)Side effects: -Local irritation after intramuscular injection. -Gastrointestinal:-anorexia, nausea, vomiting. -Renal toxicity. -Hypersensitivity reactions:Urticaria. -Blood:Hemolytic anemia, thrombocytopenia, neutropenia

OxytetracyclineDose: 250-500 mg every 6 hoursMarket preparations -Renamycin (Renata) -Oxecylin (ACME) -Oxycap (Globe Pharma)

DoxycyclineIndications: -Treatment of chronic adult periodontitis. -Chronic prostatitis -BrucellosisContraindication: -Renal impairment -Pregnancy & breast feeding -SLE (Systemic lupus eryyhematosus)Side effects: -Watery diarrhea -Bloody stools -photosensitivity, rash

DoxycyclineDose: -By mouth 200 mg on first day, then 100 mg daily -In severe infections 200 mg daily for 4 days

Market preparations: -Doxin (Opsoni) -Doxy-A (ACME) -Servidoxyne (Novartis)

TetracyclineIndications: -Tetracycline's primary use is for the treatment of acne vulgaris and rosacea. -It is also used to treat a very wide range of infections.Contraindication: -Renal impairment -Pregnancy & breast feeding -SLE (Systemic lupus eryyhematosus)Side effects: -Superinfection -Enamel dysplasia -Impairment in bone growth

TetracyclineDose: -By mouth 250 mg every 6 hours -Increased in severe infections to 500 mg every 6-8 hours

Market preparations: -Jmycin (Jayson) -Tetracycline (Opsonin) -Tetracyn (Renata) -Tetrax (Square)

FluoroquinolonesFluoroquinolones are known as broad-spectrum antibiotics, meaning they are effective against many bacteria.Fluoroquinolones are used to treat most common urinary tract infections, skin infections, and respiratoryinfections (such as sinusitis, pneumonia, bronchitis). Common side effects of fluoroquinolones include mainlythe digestive system: mild stomach pain or upset, nausea, vomiting, and diarrhea. These are usually mild and goaway over time. Fluoroquinolones should not be given during pregnancy.Fluoroquinolones inhibit bacteria by interfering with their ability to make DNA. This activity makes it difficultfor bacteria to multiply. This effect is bacteriocidal.

QuinolonesThe quinolones are family of synthetic broad spectrum antibacterial drugsQuinolones exert their antibacterial effect by preventing bacterial DNA fom unwinding and duplicatingThe majority of quinolones in clinical use belong to the subset fluroquinolones

HistoryThe first generation of quinolones began with the introduction of nalidixic acid in 1962 for treatment of urinary tract infections in humans. Nalidixic acid was discovered by George Lesher and coworkers in a distillate during an attempt at chloroquine synthesis.

TypesA) First generation:Non flurinated quinolone Narrow spectrum -Nalidixic acid

B) Second generation: Flurinated quinolones, 6o times more active then nalidixic acidBroad spectrumNot effective against anaerobes and community acquired pneumonia caused by Streptococcus pneumoniae -Ciprofloxacin -Enoxacin -Lomefloxacin -Acrosoxzacin -Norfloxacin -Ofloxacin

TypesC) Third generation:Broad spectrumEffective against anaerobes and community acquired pneumonia caused by Streptococcus pneumoniae -Sparfloxacin -Levofloxacin D) Fourth generation:More effective against anaerobes and community acquired pneumonia caused by Streptococcus pneumoniae -Moxifloxacin -Trovafloxacin

Mechanism of ActionMechanism of action: -Inhibit bacterial DNA synthesis by inhibiting DNA gyrase and topo-isomerase IV resulting to rapid cell death -Post antibiotic effect: lasts 1 to 2 hours, increases with increasing concentration

Mechanism of ActionQuinolone

Enter into cell via passive diffusion

(-) Rejoining of DNA

(-) Supercoiling of DNA

Cell death

Note: Quinolone (-) human DNA gyrase only at much higher conc. i.e., 100-1000 gm/ml

Mechanism of Quinolone resistanceChromosomal: -Alter target enzymes: DNA gyrase and topoisomerase IV -Decreased drug penetration: Pseudomonas, E. coliPlasmid: seen in some K. pneumoniae and E. coliMutations in both target enzymes are needed to produce significant resistance

Therapeutic usesUrinary tract infectionsGastrointestinal infections -Enteric fever -Bacillary dysentery -SepticaemiaRespiratory tract infections (but not in pneumococcal pneumoniaGynecological infectionIntraabdominal infectionSevere systemic infection

Adverse effect -Tendon inflammation -Arthralgia -Myalgia -Hypersensitivity reactions (sometimes involving blood cells -Photosensitivity -Nausea, Vomiting

Contraindication -Epilepsy -myasthenia gravis -Pregnant and lactating women -Children

Nalidixic acidIndications: -In complicated UTIContraindication: -Hypersensitivity to drug -Porphyria -Liver disease -Renal impairmentSide effects: -Psychosis -Cranial nerve palsy -Metabolic acidosis

Nalidixic acidDose: By mouth 1g every 6hours for 7 days

Market preparations: -Naligram (ACME) -Nebactil (Beximco) -Utirex (Opsonin)

CiprofloxacinIndications: - Nosocomial pneumonia - Intra-abdominal infections -Uncomplicated/complicated UTI -Anthrax exposure and prophylaxisContraindications: -Pregnant and lactating women -myasthenia gravis -HypersensitivitySide effects: -CNS toxicity -GIT upset -Hypersensitivity

CiprofloxacinDose By mouth, -In RTI 250-500 mg every 12 hours -In pseudomonal lower RTI 750 mg twice daily -In UTI 250-500 mg twice daily

Market preparations: -Beuflox (Incepta) -Cipro-A (ACME) -Flontin (Renata) -Neofloxin XR (Beximco)

LomefloxacinIndications: -Treatment of bronchitis due to H. inflenzae -UTIContraindications: -Pregnant and lactating women -myasthenia gravis -HypersensitivitySide effects: -Phototoxicity -CNS toxicity -GIT upset -Hypersensitivity

LomefloxacinDose: 400 mg once daily

Market preparations: -Lomeflox (Aristopharma) -Mexio (Square) -Namicin (Nipa)

OfloxacinIndications: -UTI -Lower RTI -Gonrrhoea -CervicitisContraindications: -Hepatic and renal impairment -History of psychiatric illnessSide effects: -Hypersensitivity reactions (sometimes involving blood cells -Photosensitivity -Nausea, Vomiting

OfloxacinDose:By mouth, -UTI: 200-400 mg daily in the morning. Increased upto 400 mg twice daily for upper UTI -Chronic prostatitis 200 mg twice daily for 28 days -Lower RTI 400 mg daily in the morning

Market preparations: -Oflacin (Drug Intl.) -Rutix (Square)

Levofloxacin Indications: -Chronic bronchitis and CAP - Nosocomial pneumonia -SSTIs -Intra-abdominal infectionsContraindictions: -Renal impairment -Pregnant and lactating women -Children Side effects: -Asthenia -Rarely tremor -Anxiety -Tachycardia -Hypotension -Hypoglycemia

Levofloxacin Dose: Oral, -Acute sinusitis: 500mg daily for 10-14 days -Exacerbation of chronic bronchitis: 250-500 mg daily for 7-10 days -Community acquired pneumonia: 500 mg once or twice daily for 7-14 days

Market preparations: -Evo (Beximco) -Exolev (Novartis) -Levoking (Renata) -Trevox (Square)

MoxifloxacinIndications: -Chronic bronchitis -Bacterial conjuctivitis -Sinusitis Contraindications: -Should be avoided in patients with existing QT prolongationside effects: -CNS toxicity -GIT upset -Hypersensitivity

MoxifloxacinDose: Adult dose is 400 mg daily

Market preparations: -Maximox (Orion) -Odycin (Beximco) -Optimox (aristopharma)