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Antibacterial agentsMaharajgunj Medical Campus, IOM, NepalBikash SapkotaB. Optometry16th Batch

Presentation LayoutIntroduction to antimicrobial drugsClassification of antimicrobial drugsAntibacterial drugs: - Classification - Indications - Side effectsAntibacterial Resistance

Antimicrobial drugs Very low concentrationTherapy : chemotherapyMinimum or no effect on the recipientKill or inhibit microorganisms Naturally obtained & synthetic drugs

Antimicrobial drugs are chemotherapeutic drugsTwo categories: Antibiotics : Antimicrobial drugs produced by microorganisms Synthetic drugs : Antimicrobial drugs synthesized in the lab

Have highly selective toxicity to the pathogenic microorganisms in host bodyHave no or less toxicity to the hostLow propensity for development of resistanceNot induce hypersensitivies in the hostHave rapid and extensive tissue distributionBe free of interactions with other drugsBe relatively inexpensiveIdeal antimicrobial drug

Where do antibiotics come from

Several species of fungi including Penicillium and Cephalosporium E.g. penicillin, cephalosporinSpecies of actinomycetes, Gram +ve filamentous bacteriaMany from species of Streptomyces Also from Bacillus, Gram +ve spore formersA few from myxobacteria, Gram -ve bacteriaNew source explored : plants, fish

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Sources of some common antibiotics and semisynthetics

Ehrlich (18541915) coined the term chemotherapy1929 Penicillin discovered by Alexander Fleming1940 Florey and Chain mass produced penicillin for war time use, becomes available to the public1935 Sulfa drugs discovered1944 Streptomycin discovered by Waksman from Streptomyces griseusHistory of Antimicrobial TherapyAlexander Fleming was first to characterize penicillins activity. He found mold contaminating his culture plates, with clearing of staphylococcal colonies all around the mold. Fleming then isolated penicillin from the mold

Thanks to work by Alexander Fleming

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Based on chemical structure Group ExamplesSulfonamide sulfadiazine, dapsone, paraminosalicylic acidB-lactampenicillins, cephalosporins, monobactamstetracyclineoxytetracycline, doxycyclineaminoglycosidestreptomycin, gentamycin, neomycinMacrolideerythromycin, azithromycin, clarithromycinpolypeptidepolymyxin-B, bacitracinglycopeptidevancomycinQuinolonesciprofloxacin, ofloxacin, moxifloxacin, gatifloxacinAzole derivativemiconazole, clotrimazole, ketoconazole, fluconazole nitroimidazoleMetronidazole, tinidazole

antihelmenthicantiprotozoalantiviralantifungalantibacterial

antimicrobial

Antibacterial drugsDrugs active against bacteriaNatural or synthetic Naturally, obtained from microorganisms which suppress the growth or kill other microorganisms are k/a antibioticsSynthetics are made in lab by bioengineeringThe termantibioticwas first used in 1942 bySelman Waksman

Type of action

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Spectrum of activity

Mechanism of action

Mechanism of action

Inhibit cell wall synthesisThese are the drugs that interfere with the cell wall synthesis processThese drugs consist -Lactam rings so called -lactam antibioticsBactericidal in nature

Inhibitor of cell wall synthesis

First antibiotic to be used clinicallyObtained from fungus Penicillium notatum Structure -lactam is responsible for antimicrobial activityProperties like antimicrobial spectrum, stability to stomach acid and susceptibility to bacterial degradative enzymes (-lactamases) depends upon the side chainAlso, differ in structure by the side chainPenicillin

Working of penicillin NAM-NAG-NAM-NAG

Pep Pep

Pep Pep NAM-NAG-NAM-NAG

Pep side chains are cross linked as the final step in synthesis of peptidoglycan in the presence of penicillin binding protein (PBPs).Penicillin drugs inhibit this process after binding with PBPS.Pep=peptide linkageNAM &NAG =N-acetyl muramic acid and N-acety glucosamine

PenicillinBinds to PBPsInhibition of cross linkageBlockage of peptidoglycan synthesisCell dies

Penicillin GPenicillinase resistant penicillinsExtended spectrum penicillins-Have side chain of benzyl group-Active against Gram +ve bacteria than Gram -ve-Resistant against penicillinase/-lactamase producing bacteria eg. Methicillin, CloxacillinThe latter two are semisynthetic in nature-Sensitive against wide range of bacteria(Gram +ve/-ve) eg. Ampicillin, AmoxicillinTypes

Coverage of Penicillins Penicillin GPenicillinase resistant penicillinsExtended spectrum penicillinsGram Positive cocci:Streptococcus pneumoniaStreptococcus pyogensGram Negative cocci: Neisseria gonorrhoeae Neisseria meningitidisGram Positive bacilli:Bacillus anthracisCorynebacteriumClostridia, ListeriaSpirochetes Penicillinase producing StaphylococcusSensitive against all Gram positive as well following Gram negative bacteria- E.coli- Haemophilus- Salmonella- Proteus

Pneumococcal infectionStreptococcal infectionMeningococcal infectionTetanusGas gangreneSyphilisGonorrheaRespiratory tract infectionSinusitisUTIBacillary dysenteryGonorrheaEnteric feverPreseptal cellulitisPenicillin GExtended spectrum penicillinsIndications

Hypersensitivity reaction (rash, itching, urticarial, fever)

Pain at i.m. injection site, thrombophlebitis of injected vein

Oral penicillin can cause nausea, vomiting or diarrhea

Toxicity to the brain: mental confusion, convulsions & comaSide Effects

Beta-lactamase inhibitorsSome of the bacteria produces -lactamase enzyme. This enzyme causes hydrolysis of -lactam ring so that the antibiotic activity of penicillin/ -lactam drug is destroyed

This can be prevented by two inhibitors i.e. clavulanic acid and sulbactam

These are the enzyme with -lactam ring but has no antibacterial activity. It combines with the lactamase enzyme and thus prevent the destruction of lactam ring of antibiotic making it potent to show action

Cephalosporins

Have similar action to penicillin (bactericidal)Semisynthetic antibiotics derived from cephalosporin-C obtained from fungus Cephalosporium

Cephalosporins1st generation2nd generation4th generation3rd generationClassification

IncludesExhibits good activity against Gram positive cocci like Staph.sps, Strep. sps & Gram ve rods like E.coli, KlebseillaFirst Generation

Shows somewhat enhanced activity towards Gram ve bacteria compared to 1st generation Coverage:Coverage of 1st generation &Additional -ve cocci like Neisseria gonorrhoea & -ve rod H.influenzaSecond GenerationIncludes

More potent than 2nd generationShows augmented activity against:Enterobacteria-lactamases producing bacteriaPseudomonasThird GenerationIncludes

Similar to 3rd generationShows increased resistance to -lactamase producing bacteriaFourth GenerationIncludes

Alternative to penicillin allergic patientRespiratory , urinary and soft tissue infection caused by Gram ve organismSepticaemia by Gram ve bacteraiSurgical prophylaxisGonorrhoeaTyphoidPreseptal cellulitis & endophthalmitis

Indications

Pain on intramuscular injection

Diarrhoea due to alteration of gut ecology

Hypersensitivity reaction( rashes, asthma, angioedema and urticaria)

NephrotoxicitySide effect

Vancomycin Highly effective against Gram +ve cocciUses : used for serious infections

Drug of choice for treating:Methicillin resistant staphylococciPenicillin resistant S. pneumoniae

Recommended for topical, intravitreal & subconjunctival therapy for bacterial endophthalmitis

If used with other ototoxic or nephrotoxic drugs can cause impaired renal function and lead to permanent deafness

Contraindicated in hypersensitivity reaction Side effect

TetracyclineChlorem-phenicolMacrolideAminoglycoside

Mechanism of action

TetracyclineBroad spectrum antibiotics Have nucleus of four cyclic rings, so named tetracycline1st tetracycline to be obtained was chlortetracyclineBacteriostatic in nature

Division of TetracyclineCoverage of Tetracycline

Drug of first choiceDrug of second choiceIndications

Ocular Use Preferred over silver nitrate because it does not cause chemical conjunctivitis.Regime for trachoma treatmentTopical:1% oint X QID X 6weeksSystemic: 250 mg oral XQID X3-4 weeks

Epigastric pain, nausea, vomiting and diarrhoea (irritation from mucosa )Liver toxicity Renal toxicityVestibular toxicity (due to drug accumulation in endolymph)Affect teeth and bone: tetracycline get deposited in developing teeth and bone hence cause discoloration and ill formation. so contraindicatedContraindicated in pregnant, lactating woman and child