Anti microbial agents-substances which are either natural or synthetic which can kill or inhibit the growth of suceptible

micro organisms. They include Antibacterial drugs Antiviral drugs Antifungal drugs Antiprotozoal drugs Antihelminthic drugs Antibiotics- natural chemical substances produced by living microorganisms eithe r to kill or to inhibit the growth of the other susceptible micro organisms.egs penicillin G, bacitracin , aminoglycosides . Chemotherapeutic Agents- are substances from synthetic or non living sources eit her to kill or to inhibit the growth of susceptible organisms.egs sulphonamide , chloramphenicol , macrolides. Anti microbial spectrum of a particular drug refers to the species of microorgan ism affected by that drug. Broad spectrum - which have extended activity against gm +ve and gram -ve organi sm. Eg quinolones, imipenem, piperacillin, tetracycline, amoxicillin. Narrow spectrum- drugs which have activity against a limited group of micro orga nisms usually either gram +ve or gram ve. Egs isoniazid ,anti staphylococcal pen icillin, penicillin G. Conc. effects relationship in antibiotic therapy. Minimum inhibitory concentration (MIC )- lowest conc. of drug that inhibits bact erial growth. Minimum bactericidal concentration (MBC)-lowest conc. of drug tht kills bacteria . MBC is 2 to 8 times that of MIC. Bactericidal- drugs which kill the susceptible microorganisms. Antimicrobial for which achievable blood conc. regularly exceeds MBC of the comm on pathogens. B- lactams, amino glycosides, polymixin, quinolones. Bacteriostatic- drugs which inhibit growth of microorganisms. Antimicrobial whose blood conc. regularly exceeds MIC but do not usually exceed MBC. Tetracycline , chloramphenicol ,sulphonamide , erythromycin . Penicillin - classically bactericidal but Bacteriostatic against enterococci. Chloramphenicol - Bacteriostatic but bactericidal against most strain of H. Infl uenza ,meningococci. Time dependent killing- antibacterial effects depend mainly on peak drug level c oncentration rather than time and continue with blood level. Eg. Penicillin. Conc. or Dose dependent killing- with increase dose or conc. of Antimicrobial ag ents ,increase killing of bacteria efficiently at more rapid rate. Eg. Amino gly cosides. Post antibiotic effects (PAE)- the antibacterial activity persists after the pla sma conc. of the antimicrobial agents has fallen below the MIC. Amino glycosides have several hrs post antibiotic effects, fluoroquinolones.

Classification of Antimicrobial agents A. Acc to mechanism of action. 1.Inhibition of cell wall synthesis -B lactams: Penicillin, Cephalosporin,Cephamycin, -Carbapenem: Imipenem, Meropenem, Ertapenem. -Monobactam: Aztreonam -Cycloserine -Bacitracin, -Vancomycin, -Teicoplanin, -Daptomycin.

2. Inhibition of cell membrane function -Amphoteric B, Azole, Polymixin, Polyene 3. Inhibition of protein synthesis Aminoglycosides, Tetracycline, Chloramphenicol, Macrolides ( Erythromycin, Clarithromycin, Azithromycin), Ketolides ( Telethromycin), Lincomycin, Clindamycin, Streptogramines ( quinapristin-dalfopristin), Oxazolidinones (Linezolid). 4. Inhibition of Nucleic Acid Synthesis Quinolone, ( Ciprofloxacin, Norfloxacin ,Ofloxacin ) Rifampicin, Sulphonamide, Trimethoprim , Pyrimethamine, Actinomycin, Mitomycin. B. Acc to spectrum of action 1. Narrow spectrum- Isoniazid , anti staphylococcal penicillin. 2. Broad spectrum- Fluoroquinolones, Tetracycline, Amoxicillin. C. Acc to mode of action 1. Bactericidal-B lactams ( Penicillin, Cephalosporin , Cephamycin), Aminoglycosi des, Fluoroquinolones. 2. Bacteriostatic- Tetracycline , Chloramphenicol, Macrolides, Sulphonamide. ANTIMICROBIAN COMBINATION THERAPY Types 1) Additive effects ie indifference 2) Synergism/ chemotherapeutic potentiation) a)blocking sucking step in metabolism- cotrimoxazole=combination of sulphamethox azole and trimethoprim b)one drug inhibits an enzyme (B lactamase) which destroys the 2nd drug. Eg. Amo xicillin+clavulanic acid, piperacillin+tazobactam,ampicillin +salbactam. c)one drug promotes the entry of 2nd drug through microbial cell wall. Eg. Amino glycosides+penicillin. 3) Antagonism (eg. Penicillin + tetracycline); bactericidal + bacteriostatic.

Advantages/ Purpose/indications of combination therapy 1)to provide broad coverage in polymicrobial infections-intraabdominal, hepatic, brain abcess,PID. 2)therapy of severe infections in which specific cause is unknown. 3)enhancement of Antimicrobial activity in the treatment of infections.eg. Penic illin+Aminoglycoside in enterococcal endocarditis. 4)prevention of emergence of resistance. Eg. Tb, leprosy. Disadvantages 1)risk of toxicity 2)antagonism- bactericidal+bacteriostatic 3)increase cost to the patient. Empiric (presumptive) antimicrobial therapy:- the antimicrobial agents are frequ ently used in critically ill patients before the pathogen responsible for partic ular infection is known. It is based on experience with a particular clinical en tity. Hazards of indiscriminate use of Antimicrobial agents 1) drug resistance 2)super infection 3)cross resistance 4)chronicity 5)relapse 6)allergic or hypersensitivity reaction 7)opportunistic infection 8)masking of infection. Drug resistance-bacteria are said to be resistant if growth is not halted by max imal dose of antibiotic that is tolerated by the host. Types 1)non-genetic:-anaerobic bacteria lack O2 dependent transport mechanism required for aminoglycosides to enter the bacterial cell. 2)genetic a)chromosomal-mutation (less common) b)extra chromosomal- plasmid mediated (most common) --conjugation (main M/A) --transduction --transformation --transposors Different mechanism of drug resistance 1) production of enzymes that inactivate the drugs 2) alteration of drug binding sites- bacteria may change target Plasmid mediated:-50s subunit-macrolides Chromosomal mediated- PBP (penicillin, other B lactam antibiotics); DNA dependent DNA polymerase(Rifampicin); DNA Gyrase(fluoroquinolones) 3) decrease accumulation within the bacteria Plasmid mediated:- increase energy dependent efflux (tetracycline, macrolides, fl uoroquinolones, rifampicin) Chromosomal mediated:- decrease uptake(fluoroquinolones) ;altered permeability(am picillin);mutation affection envelop components and affect accumulation( B lacta ms,aminoglycosides,tetracycline,chloramphenicol) 4) development of pathway that bypass the reaction inhibited by antibiotics Plasmid mediated:- dihydrofolate reductase- trimethoprim ;dihydrofolate synthase -sulphonamide Chromosomal mediated:-production of PABA-sulphonamide

Super infection- phenomenon where there is appearance of bacteriological and cli nical evidence of new infection during chemotherapy of infection. Causative organisms. Candida and other fungi(most common) Enterobacteraeceae Pseudomonas Staphylococcus Mechanism of action -Due to antimicrobial therapy,there is removal of inhibitory influence of drug s ensitive flora that normally inhabits the oropharynx and other body orifices. -As a result of alteration of normal microbial flora of the host, there is incre ase in growth of exogenously derived microorganisms or overgrowth of endogenous organism which are relatively not sensitive to that particular antibiotic. -So 2ndary infections superimpose on primary infections. -many members of flora appear to produce bacterocins which is antibacterial subs tance and compete for essential nutrients. Incidence Highest with broad spectrum antibiotics Higher with tetracycline, chloramphenicol Lowest with narrow spectrum antibiotics like penicillin G Chemoprophylaxis:- use of antibiotic in healthy person to prevent infection by a n organism eg. Benzylpenicillin for group A streptococcus But Chemoprophylaxis also extended for suppression of existing infection. Categories 1)true prevention of infection -Penicillin G-group A streptococcus infection, gonorrhoea , syphilis -Cotrimoxazole -E. Colin causing UTI -Rifampicin and Minocycline -meningococcal infection. 2)to prevent 2ndary bacterial infection in patient ill with other diseases -quinolones--immunocompromised patients to prevent gm -ve septicaemia. 3)suppression of existing infection before it causes overt diseases. -TB, malaria, animal bite, trauma 4)prevention of spread among contacts -influenza A-amantadine -meningitis-Rifampicin -pertusis-erythromycin 5)surgical Chemoprophylaxis -to prevent endocarditis in valvular disease who are undergoing dental and surgi cal procedures -colorectal surgery-to prevent high incidence of infection with E. Colin, clostr idium ,bacteroids -gastroduodenal surgery- cephalosporin -gynaecological surgery -cephalosporin and metronidazole -leg amputation-risk of gas gangrene (metronidazole) -insertion of prosthetic joints-staphylococcus aureus.