Penicillins

Inhibitors of Bacterial Cell Wall Synthesis: 

Inhibitors of Bacterial Cell Wall Synthesis Dr. M. Khurram mahmood Assistant Professor

Inhibitors of Bacterial Cell Wall Synthesis: 

Inhibitors of Bacterial Cell Wall Synthesis Beta Lactam drugs—because of their unique 4 membered Beta LACTAM ring Non Beta Lactam drugs.

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs : 

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs Beta Lactam drugs Non Beta Lactam drugs I. Beta Lactam drugs Penicillins Cephalosporins & Cephamycins Monobactam --- Aztreonam

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs: 

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs d. Beta lactamase inhibitors Sulbactam Sodium Tazobactam Sodium Clavulanate potassium. e. Carbapenems Ertapenem Imipenem Meropenem

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs: 

Inhibitors of Bacterial Cell Wall Synthesis or Membrane-active drugs II. Non-Beta Lactam drugs Vancomycin Teicoplanin Daptomycin Fosfomycin Bacitracin Cycloserine

PENICILLINS: 

PENICILLINS

PENICILLINS: 

PENICILLINS Constitute one of the most important primitive groups of antibiotics that are still being widely used for the treatment & prophylaxis of infections caused by susceptible micro-organisms High margin of safety & lack organ toxicity Acute anaphylaxis – imp AE; needing immediate attention Major antibiotics and new derivatives of the basic penicillin nucleus still are being produced Many of these have unique advantages such that members of this group of antibiotics are currently the drugs of choice for a large number of infectious diseases.

PENICILLINS - HISTORY: 

PENICILLINS - HISTORY Discovered in 1928 by Alexander Fleming while studying Staphylococcus variants in the laboratory at St. Mary's Hospital in London. He observed that a mold contaminating one of his cultures caused the bacteria in its vicinity to undergo lysis. Broth in which the fungus was grown was markedly inhibitory for many microorganisms. Because the mold belonged to the genus Penicillium, Fleming named the antibacterial substance penicillin (meaning brave). In 1941 Penicillin was developed as systemic therapeutic agent & tested on an old terminally ill lady having cancer 1944 on war soldier having multiple wounds

PENICILLINS - Chemistry : 

PENICILLINS - Chemistry The basic structure of the penicillins consists of a thiazolidine ring (A) connected to a β -lactam ring (B) to which is attached a side chain (R) -- 6 Aminopenicillanic acid The penicillin nucleus itself is the chief structural requirement for biological activity; metabolic transformation or chemical alteration of this portion of the molecule causes loss of all significant antibacterial activity Hydrolysis of the β -lactam ring by bacterial β -lactamases yields penicilloic acid, which lacks antibacterial activity.

PENICILLINS – Chemistry… : 

PENICILLINS – Chemistry… The side chain determines many of the antibacterial and pharmacological characteristics of a particular type of penicillin Several natural penicillins can be produced depending on the chemical composition of the fermentation medium used to culture Penicillium Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these and is the only natural penicillin used clinically. For penicillin G, the side chain is a phenyl-methyl substituent

Chemistry:: 

Chemistry:

Classification of Penicillins: 

Classification of Penicillins 1-     Natural Penicillin And Its Congener Penicillin G/ Benzylpenicillin Penicillin V /Phenoxymethylpenicillin. 2-     Semi-synthetic Penicillins a.  lactamase Resistant Penicillins i. Methicillin ii. Nafcillin iii. Isoxazolyl Penicillins Oxacillin, Cloxacillin Di-cloxacillin, Flucloxacillin.

Classification of Penicillins…: 

b. Extended Spectrum i. Aminopenicillins Amoxicillin, Ampicillin Ampicillin prodrugs: Piv-ampicillin Bac-ampicillin Tal-ampicillin Classification of Penicillins…

Classification of Penicillins…: 

ii. Antipseudomonal Penicillins a. Carboxypenicillins Carbenicillin , Ticarcillin b. Ureidopenicillins Azlocillin , Mezlocillin , Piperacillin Classification of Penicillins…

Slide 18: 

Combinations of Penicillins with  - Lactamase Inhibitors Amoxicillin / Clavulanate ( Augmentin) Ampicillin / Sulbactum Piperacillin / Tazobactum Ticarcillin / Clavulanate

Penicillin Units & Formulations: 

Penicillin Units & Formulations Activity of Penicillin G originally expressed in Units One unit =0.6 μ g; One million units =0.6 g Crystalline sodium Penicillins contains approx.-1600units / mg Semi synthetic penicillin are prescribed by weight Penicillins are dispensed as sodium / Potassium salts. Potassium Penicillin G contains K + 2.8 mEq/g Nafcillin contains K + 2.8 mEq/g Stability: Dry crystalline form stable at 4 o C for years. Solutions lose activity in 24 hrs at 20 o C --- must be prepared fresh

MOA of Penicillins : 

MOA of Penicillins Bactericidal Bacterial cell wall synthesis Inhibitors Only act when bacteria are rapidly growing & synthesizing cell wall. Have time dependent (Concentration independent killing) Entry in to G+ve bacteria through bacterial cell wall & G –ve bacteria through porins in the outer cell wall, which is absent in G+ve bacteria.

MOA of Penicillins… : 

MOA of Penicillins… Penicillins act by following steps 1. Binding to their receptors----specific enzymes, PBPs 2. Inhibition of transpeptidation reaction / cross linking of linear peptidoglycans chains of the cell wall. So synthesis of bacterial cell wall is inhibited. 3. Activation of autolysins, disruption of cell morphogenesis & Cell death.

MOA of Penicillins… : 

1.Binding to receptors Penicillin Binding Proteins (PBPs) are transpeptidase enzymes in bacterial cytoplasmic membrane. They catalyze the final step in the synthesis of peptidoglycan; important part of bacterial cell wall 2. Inhibition of transpeptidation reaction Bacterial cell wall consists of outer membrane & Peptidoglycan Peptidoglycan is unique to bacteria cell wall & is much thicker in G+ve than in G-ve bacteria. MOA of Penicillins…

MOA of Penicillins… : 

It consists of polysaccharides (N-acetylglucosamine & N-acetylmuramic acid) & polypeptides. A five amino acid peptide is linked to the N-acetylmuramic acid sugar. This peptide terminates in D-alanyl-D-alanine PBPs remove the terminal Alanine in the process of cross linking with a nearby peptide in transpeptidation reaction. β -lactam drugs are structural analogs of natural substrate. D-alanyl-D-alanine. Penicillins bind to active site of PBPs, this inhibits transpeptidation reaction -- cross linking So the synthesis of Peptidoglycans / cell wall is inhibited MOA of Penicillins…

MOA of Penicillins… : 

3 . Cell death Disinhibition /Activation of autolysins May bacteria produce autolysins (degradative enzymes) that participate in the normal remodeling of the cell wall. Otherwise they are inhibited. In the presence of Penicillins they are disinhibited & degradative action occurs in the absence of cell wall synthesis. --- Destruction of cell ---- lysis MOA of Penicillins…

Mech. Of bacterial resistance to penicillins : 

Mech. Of bacterial resistance to penicillins Enzymatic hydrolysis of drug ---- by beta lactamases Many hundred types. Those produced by Staph aureus , Hemophilus , & E coli have narrow substrate specificity Those produced by Pseudomonas & Enterobacter can hydrolyze Penicillins & Cephalosporins Altered target PBPs basis of Methicillin resistance in Staph (MRSA) & Penicillin resistance in Pneumococci & enterococci

Mech. Of bacterial resistance to penicillins : 

Mech. Of bacterial resistance to penicillins Impaired penetration of drug to target PBPs Only in G-ve bacteria due to resistant outer cell membrane– porins may be absent or decreased This is more important if bacteria is also beta lactamase producing. Active efflux pump May be produced in G-ve bacteria

Benzyl penicillin (Penicillin G): 

Benzyl penicillin ( Penicillin G)

Benzyl penicillin (Penicillin G): 

Benzyl penicillin ( Penicillin G) Natural penicillin Acid labile – not effective orally Source Obtained from fermentation of mold Penicillium chrysogenum in huge tanks. Structure: Next slide MOA --- already discussed

Chemistry:: 

Chemistry:

Ph. K - Benzyl Penicillin (Penicillin G) : 

Ph. K - Benzyl Penicillin (Penicillin G) Route of Administration acid labile, so given I/V. 4 – 24 million units/d I/V 4-6 in divided doses. I/V infusion may be given—for large doses. Never intrathecally--- convulsions Topical application avoided –risk of allergy I/M Injection only Repository preparations Procaine Penicillin – 1-2 inj /d Benzathine Penicillin 1.2 million units every 3-4 wks-for prophylaxis 2.4 million units once a week for 1-3 wks for treatment of syphilis.

Ph. K - Benzyl Penicillin (Penicillin G)…: 

Ph. K - Benzyl Penicillin (Penicillin G)… Distribution: Distributed in body fluids but poor conc in the cells as it is polar. Penetration into brain, eye & prostate poor. Crosses BBB only if meninges are inflamed. Crosses placental barrier Also excreted in breast milk & sputum. PPB: low

Ph. K - Benzyl Penicillin (Penicillin G)…: 

Ph. K - Benzyl Penicillin (Penicillin G)… Metabolism Not metabolized significantly in host, but in impaired renal function some metabolism of Penicillin G has been shown to occur. (Bacteria may hydrolyze 6APA to Penicilloic acid which has no bacterial activity but is antigenic)

Ph. K - Benzyl Penicillin (Penicillin G)…: 

Ph. K - Benzyl Penicillin (Penicillin G)… Excretion: Rapid excretion by kidneys—10% GF 90% --Active tubular secretion via organic acid transporter, competitively inhibited by Probenecid So co-admintration of 0.5g Probenecid can raise the blood levels& ↓the frequency of injections. Elimination less effective in neonates. Plasma half life (t 1/2 ) Short—30 minutes prolonged in renal failure—10 hrs. Dosage adjustment according to creatinine clearance.

Spectrum Of Activity of Penicillin G: 

Active against following Penicillin susceptible organisms Streptococci: pyogenes & viridans Meningococci Pneumococci Gonococci (Non –  lactamase producing) Staphylococci (Non –  lactamase producing) Treponema Pallidum & other spirochetes Clostridium perfringes Actinomyces Non β -lactamase producing G-ve anaerobic organisms. Spectrum Of Activity of Penicillin G

USES OF BENZYLPENICILLIN: 

USES OF BENZYLPENICILLIN Dose 4 – 24 million units/d I/V 4-6 divided doses. I/V infusion may be given—for large doses - Haemolytic Streptococcal (Strept. pyogenes) infections such as: Acute Tonsillitis & Pharyngitis Scarlet fever Pneumonia Arthritis Meningitis Endocarditis Strepcoccal toxic shock & Necrotizing Fascitis with clindamycin.

USES OF BENZYLPENICILLIN…: 

Strep. viridans Endocarditis ( The viridans streptococci are the most common cause of infectious endocarditis ) Pneumococcal Pneumonia , Pneumococcal Meningitis Meningococcal meningitis (Massive doses). Staphylococcal Infections (non - lactamase producing strains only). 6. Enterococcal endocarditis with aminoglycosides 7. Syphilis: Single inj of Benzathine Penicillin G I/M 2.4 million units once a week for 1-3 wks. No antibiotic resistance has been reported. Actinomycosis Clostridial infections (gas gangrene) USES OF BENZYLPENICILLIN…

Prophylactic Uses of Penicillin G : 

Prophylactic Uses of Penicillin G Prophylaxis Benzathine Penicillin I/M 1.2 million units once /3-4 wks Streptococcal infections Recurrences of rheumatic fever Surgical procedures in Pt. with Valvular heart disease.

PHENOXY METHYL PENICILLIN (Penicillin V) : 

PHENOXY METHYL PENICILLIN (Penicillin V) Differences from Penicillin G Gastric acid resistant--- Orally effective, but poor bioavailability. Narrow antibacterial spectrum. Less potent Therapeutic Uses Only for mild streptococcal & pneumococcal infections Pharyngitis , Sinusitis , Otitis media.

SEMISYNTHETIC PENCILLINS : 

SEMISYNTHETIC PENCILLINS

a.  lactamase Resistant Penicillins : 

a .  lactamase Resistant Penicillins i. Nafcillin ii. Isoxazolyl Penicillins Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin iii. Methicillin is not used; due to renal toxicity - interstitial nephritis

Ph.K -  lactamase Resistant Penicillin: 

Ph.K -  lactamase Resistant Penicillin All are acid stable; Effective orally except Nafcillin (erratic abs) Abs: Well absorbed, abs is delayed by food so given 1-2 hrs before of after meals. Flucloxacillin– best absorbed Elimination: Oxacillin , Cloxacillin , Dicloxacillin , Flucloxacillin. Eliminated both by kidney & biliary excretion Nafcillin - biliary excretion & highly PPB

THERAPEUTIC USES  lactamase Resistant Penicillins : 

THERAPEUTIC USES  lactamase Resistant Penicillins Infections by beta lactamase (Penicillinase) producing staphylococcus aureus (except methicillin resistant Staph-aureus ---- MRSA) For mild Infection Oxacillin, Cloxacillin, Dicloxacillin, Flucloxacillin orally. For severe Infection Oxacillin or Nafcillin by intermittent I/V infusion. .

Extended spectrum Penicillins : 

Extended spectrum Penicillins Excreted more slowly than Penicillin G. Enhanced ability to penetrate outer membrane of Gram –ve bacteria -- So greater activity than Penicillin G against Gram –ve bacteria. They are inactivated by most Beta lactamases. May be combined with Beta lactamase inhibitors

AMINOPENCILLINS AMOXICILLIN, AMPICILLIN & PRODRUGS : 

AMINOPENCILLINS AMOXICILLIN, AMPICILLIN & PRODRUGS Pharmacokinetics All are acid stable, effective orally. Can be used I/M or I/V Abs: Well absorbed, delayed by food (except amoxicillin) so given 1-2 hrs before of after meals. Amoxicillin better abs than Ampicillin, so Amoxicillin 250-500 mg 8 hrly = Ampicillin 250-500 mg given 6 hrly As Ampicillin is less completely absorbed so is effective in Shigella dysentery & can disturb the normal flora also. Elimination: Renal —10% GF &90% --Active tubular secretion Ampicillin also excreted in feces.

Antibacterial spectrum - Aminopenicillins : 

Antibacterial spectrum - Aminopenicillins Have antibacterial spectrum of penicillin G, but more active against G-ve bacilli ---extended spectrum Resistance due to plasmid –mediated penicillinases is a major problem Combined with a beta lactamase inhibitor -- Clavulanic acid / sulbactum Pneumococci (resistant to Pen. G) Listeria monocytogenese -- Ampicillin is the DOC H-influanzae (Non-  lactamase producing--- resistance developing) Salmonella Shigella E-coli Gonococci Helicobacter pylori

Therapeutic Uses - Aminopenicillins : 

Therapeutic Uses - Aminopenicillins Respiratory Tract Infections Specially Streptococcal , Pneumococcal & H- Influenzae infections: Sinusitis Otitis media in children. Bronchitis , Pneumonia . Bacterial Meningitis Specially in Children by S. Pneomonias or N. Meningitidis In immunocompromised persons by Listeria. monocytogenes (Ampicillin) Uncomplicated UTI by E. Coli (Ampicillin) (Fluoroquinolones / co-trimoxazole are preferred because of resistance) Gonorrhea (Amoxicillin + clavulanate)

Therapeutic Uses – Aminopenicillins…: 

Therapeutic Uses – Aminopenicillins… Bacillary dysentery by Shigella ---Ampicillin (but Should not be used for Salmonella diarrhea as it may prolong the carrier state) Typhoid fever (Amoxicillin). Prophylaxis of Subacute bacterial endocarditis in abnormal valves by dentists before extensive oral surgery.. E. Coli Septicaemia with gentamicin. Eradication of H-pylori as a part of regimen in peptic ulcer (Amoxicillin).

Antipseudomonal Penicillins: 

Antipseudomonal Penicillins Carboxypenicillins : Carbenicillin, Ticarcillin Ureidopenicillins: Azlocillin, Mezlocillin, Piperacillin As they are susceptible to penicillinases --- combined with Beta lactamase inhibitors Synergistic with an Aminoglycosides

Carboxypenicillins: 

Carboxypenicillins Carbenicillin –First carboxy penicillin is obsolete Now Carbenicillin Indanyl sodium is used orally - congener is the indanyl ester of carbenicillin Ticarcillin – I/V

Carboxypenicillins….: 

Carboxypenicillins…. Antibacterial spectrum Pseudomonas aeruginosa & Proteus Therapeutic Uses UTI caused by pseudomonas aeruginosa / Proteus In other pseudomonal infections with Aminoglycosides

Ureidopenicillins: 

Ureidopenicillins Antibacterial spectrum Klebsiella pneumoniae , Proteus & Pseudomonas aeruginosa Therapeutic Uses Serious infections by sensitive G -ve Bacteria UTI Infections after burns Bacteremia In neutropenic & immunocompromised Patients May be combined with Aminoglycosides

Adverse Reactions - Penicillins : 

Adverse Reactions - Penicillins Penicillins are remarkably safe Mainly Hypersensitivity reactions

Adverse Reactions - Penicillins : 

Adverse Reactions - Penicillins Hypersensitivity / Allergic reactions Manifestations include maculopapular rash, urticarial rash, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens-Johnson syndrome, and anaphylaxis The most important A/E. ---5% Major antigenic determinant: Metabolite Penicilloic acid - act as haptens after covalent reaction with proteins -- causes immunological reaction. Cross allergenic with Beta lactams Desensitization may be done

Adverse Reactions – Penicillins…: 

Adverse Reactions – Penicillins… A: Acute anaphylaxis /Anaphylactic shock. 0.5% ,may be fatal. B. Skin rashes of various types. C. Serum sickness like syndrome —7-10 d after exposure. D. Allergic Renal disturbances (Interstitial nephiritis specially with methicillin.. E. Allergic Blood disturbances. Eosinophilia hemolytic anemia F. Vasculitis.

Adverse Reactions – Penicillins…: 

Adverse Reactions – Penicillins… Other A/E of Pen. G: Pain after IM injection. Thrombophlebitis after I/V injection. Seizures . Large doses in renal failure Arachnoiditis encephalopathy - after Intrathecal inj. Hyperkalemia in renal dysfunction with large doses of Pen. G potassium Dizziness, tinnitus, headache, hallucination, seizures -- Pen. G procaine .

Adverse Reactions – Penicillins…: 

Adverse Reactions – Penicillins… Cation Toxicity: Penicillins are generally given as Sodium or Patassium salts So when used in large doses-- Sodium or Potassium toxicity may occur. Hyperkalemia in renal dysfunction with large doses of Pen. G potassium. Hypokalemia with sodium excess. It can be avoided by using the most potent drug – in lower doses

Adverse Reactions – Penicillins…: 

Adverse Reactions – Penicillins… Jerisch Herxhimier Reaction: Symptoms: Several hours after the first inj in syphilis patient --chills, fever, headache, myalgias, arthopathy & prominence of cutaneous lesions. Remedy: Discontinue penicillin Give Inj Hydrocortisone Cause: Due to killing of a large number of spirochetes, libration of toxins

Adverse Reactions – Penicillins…: 

Adverse Reactions – Penicillins… Nafcillin --- neutropenia Oxacillin --- hepatitis Methicillin --- interstitial nephritis Ampicillin GIT upset , nausea, vomiting, and diarrhea. Super infection i.e. Pseudomembranous colitis , Vaginal candidiasis. Ampicillin and Amoxicillin can cause skin rashes that are not allergic in nature.

Beta lactamase inhibitors (Clavulanic acid, Sulbactam, & Tazobactam) : 

Beta lactamase inhibitors (Clavulanic acid, Sulbactam, & Tazobactam)

Slide 67: 

Beta lactamase inhibitors (Clavulanic acid, Sulbactam, & Tazobactam) Resemble β -lactam molecule. Almost NO antibacterial action. Potent inhibitors of many but not all β -lactamases. Protect hydrolyzable penicillins from inactivation

Slide 68: 

Most active against Ambler class A β -lactamases. produced by staphylococci, H. influenzae, N. gonorrhoeae, salmonella, shigella, E coli & K Pneumoniae. Not good inhibitors of class C β -lactamases , which typically are chromosomally encoded and inducible. Produced by enterobacter, citrobacter, serratia, and pseudomonas . They do inhibit chromosomal β -lactamases of legionella, bacteroides, and branhamella .

Slide 69: 

Available only in fixed combinations with specific penicillins. Antibacterial spectrum --- determined by the penicillin, not the β -lactamase inhibitors. Extend the spectrum of a penicillin. Combinations of Penicillins with  - Lactamase Inhibitors Amoxicillin / Clavulanate ( Augmentin) Ampicillin / Sulbactum Piperacillin / Tazobactum Ticarcillin / Clavulanate

Slide 70: 

Th. Indications for penicillin - β -lactamase inhibitor combinations are: Empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised & immunocompetent patients. Treatment of mixed aerobic & anaerobic infections i.e. intra-abdominal infections. Dosage adjustment according to the penicillin.

Slide 71: 

Monobactams: Drugs with β -lactam monocyclic ring Aztreonam: MOA: inhibition of bacterial cell wall synthesis. Binds to PBP 3 & synergistic with aminoglycosides. Resistant to β -lactamases Active only against G-ve rods including Pseudomonas & Serretia. No cross allergenicity with penicillin. So penicillin allergic patients tolerate Aztreonam very well.

Slide 72: 

Carbepenems: Ertapenem , Imipenem/cilasatin , meropenem: β -lactam drugs Resistant to most β -lactamases except Metallo β -lactamases Active against G-ve rods including Pseudomonas, G+ve organisms. & anaerobes . Cross allergenic with Penicillins

Slide 73: 

Th. uses: Enterobactor infection.--- DOC Infections by Penicillin resistant pneumococci. Pseudomonal infection with Aminoglycoside. A/E: NVD , skin rashes ,Reaction at infusion site, Seizures in renal failure. (imipenum) Cross allergenic with Penicillins

Slide 74: 

Non- β -lactam Inhibitors of bacterial cell wall synthesis Vancomycin: Source: Glycopeptide Antibiotic --- Streptococcus orientalis. Antibacterial spectrum: Narrow ,against resistant micro-org. G +ve bacteria, specially Staphylococcus, even MRSA Clostridium difficile.

Slide 75: 

Ph.K: Poorly absorbed form intestine. Orally effective only for enterocolitis. For systemic infections--by I/V infusion. 90% excreted by GF Drug is not removed by hemodialysis

Slide 76: 

MOA: Bactericidal Binds to the D-Ala-D-Ala terminal of the nascent peptidoglycan pentapeptide side chain Inhibits transglycosylation. So prevents elongation of the peptidoglycan chain & interferes with cross linking. MOR: Alteration of D-Ala-D-Ala binding site & loss of affinity & activity.

Slide 77: 

Therapeutic uses: Narrow spectrum , Serious infection by drug resistant G +ve organisms. Sepsis or endocarditis by MRSA / severe penicillin allergy. I/V Pneumococcal Meningitis with 3 rd gen .Cephalosporins (Cefotaxine, Ceftriaxone) or Rifampin. I/V Antibiotic induced Enterocolitis by Clostridium difficile. Orally for refractory cases. First DOC -- Metronidazole

Slide 78: 

A/E: Rapid I/V infusion , “ Redman” or “Red neck” syndrome due to histamine release . Phlebitis Chills & fever , Ototoxicity & Nephrotoxicity. (rare) Teicoplanin: Similar to Vancomycin. Can be given I/M , I/V.

Slide 79: 

Daptomycin: Source: Streptomyces roseoporus Cleared renally Spectrum of activity similar to vancomycin, even effective against vancomycin resistant strains of enteroccoci & S. aureus. MOA: Not clear. Binds to & depolarizes the cell membrane, potassium efflux & cell death Th. Uses: Alternative to vancomycin. A/E: Myopathy.

Slide 80: 

Fosfomycin: Analog of Phosphoenolpyruvic acid. MOA: Inhibits early stage of bacterial cell wall synthesis Inhibits cytoplasmic enolpyruvate transferase. Prevents formation of N-acetylmuramic acid --- precursor of Peptidoglycan . MOR: Inadequate transport into bacteria.

Slide 81: 

Ph. k.: Given orally, 40% bioavailability. Half life 4 hrs. Renally excreted Spectrum of activity: G +ve & G -ve Th. Uses: Uncomplicated lower UTI in women– single 3 g dose. Safe in pregnancy.

Slide 82: 

Bacitracin: Source: Bacillus subtilis. No cross resistance with other Antimicrobial drugs. Markedly nephrotoxic. Th. Uses: Not used systemically Used topically as ointment on skin / MM , with polymyxin & neomycin for mixed bacterial flora. Saline solutions for irrigation of joints, wounds or pleural cavity.

Slide 83: 

Cycloserine: Antibiotic -- streptomyces orchidaceus. MOA: Structural analog of D-alanine ,blocks the incorporation of D-Ala in to Peptidoglycan chain. Th. Uses: 2 nd line anti TB drug. A/E: Serious CNS toxicity ---- headache, tremor, acute psychosis & convulsions.