Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

Cause of diseaseMeansInvasivenessToxigenesis

StagesColonizationAdherenceNonspecific (dock)Specific (anchor)InvasionEnzymes and Toxins

Natural Source-Fungal molds-Actinomycetes , Bacteria Bacillus,Chemotherapeutic- ChemicalSemi-synthetic-Hybrid

Those that inhibit cell wall synthesis:Isoniazid; pyrizinamide: Mycolic acid synthesis inhibitorsEthambutol: Inhibits MA incorporation to cell wallThose that affect nucleic acid metabolism:

Rifampin; rifabutin: DNA dependent RNA polymeraseinhibitors

Clofazimine: Binds to DNA and inhibits the template functionof DNA

Those that inhibits intermediary metabolism:Dapsone; sulfoxone: The same as that of sulfonamides.

Aminoglycosidesβ-lactams-Penicillins-Cephalosporins-Carbapenams-Monobactams-Fluoroquinolones-Glycopeptides

KetolidesLincosamidesMacrolidesOxazolidinonesStreptograminsSulphonamidesTetracyclines

ConsiderationsIdentification of microbeDrug sensitivity of microbe

Host factorsSite of infectionImmune statusEmpirical therapy

Ability of an antibiotic to destroy target cells withoutdamaging host cellsDifferences between microbes and host

Prokaryotic vs EukaryoticCell wallInhibition of microbial enzymesDisruption of bacterial protein synthesis

Host defense (immune system, skin)Site of infectionBBB, vascularity, heart valves, abscessAgePregnancy & LactationPrevious Allergic ReactionGeneticHost defense mechanism: A chemotherapeutic regimen that

is perfectly adequate for immuno-competent patientmay be totally ineffective for immuno-incompetentpatient. Immuno-incompetence may be due todeficiencies in Immunoglobulin, phagocytic cells andcellular immune system.

Hepatic function: Erythromycin, clindamycin, rifampin,Chloramphenicol depend on liver metabolisms forthe inactivation of antimicrobial mechanisms.Patients with impaired liver function may accumulatein the body active form of the drugs to a toxic levelif the dosage adjustment is not made.

Kidney function: Normal kidney function is essential fordisposal of -lactams, aminoglycosides, vancomycin,Active form of these drugs may accumulate in thepatient with renal diseases.

SurgeryBacterial endocarditisNeutropeniaOther

MIC: Minimum inhibitory concentration if drug does notget the concentration, then drug is ineffective

MechanismsDrug inactivating enzymesCease uptake of drugChange in bacterial receptorsSynthesize drug antagonistsAcquisitionSpontaneous mutation – single resistanceConjugation –multiple drug resistance

Natural (Inherent)Lack target or transport

AcquiredMutationHorizontal transfer

VerticalHorizontal

TransformationTransductionConjugation

Prevent cross linkingBinds to transpeptidases

Add new monomersReseal wall

Osmotic LysisBacterial Resistance

Penicillinase, MRSAVRSA

Beta LactamasesCephalosporinases

Use of antibiotics to treat viral infectionsInadequate pathogen coverageExcessive use of broad spectrum agentsSub-optimal dosingRetaining unfinished antibiotic for later use

Increased rate of treatment failurePoor patient complianceIncreased mortalityNeed for combination therapyIncreased cost of treatment

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