General Rules On Use of Antimicrobial Agents Consultant Microbiologist & Head of the Bacteriology By: Prof. A.M.Kambal

ANTIMICROBIAL AGENTS ANTIBIOTICS:  NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH INHIBIT THE GROWTH OF OTHER. CHEMOTHERAPY:  SYNTHETIC COMPOUNDS.

SELECTIVE TOXICITY:  THE ABILITY TO KILL OR INHIBIT THE GROWTH OF MICROORGANISM WITHOUT HARMING THE HOST CELLS.

BACTERICIDAL: KILLS BACTERIA BACTERIOSTATIC: PREVENTS MULTIPLICATION. SPECTRIM OF ACTIVITY:  BROAD SPECTRUM: G+VE& G-VE  NARROW SPECTRUM: SELECTIVE ORGANISM.

THERAPEUTIC INDEX:  THE RATIO OF THE DOSE TOXIC TO THE HOST TO THE EFFECTIVE THERAPEUTIC DOSE. EXAMPLES:  PENICILLIN: HIGH  AMINOGLYCOSIDES: LOW  POLYMYXIN B: THE LOWEST

MECHANISMS OF ACTION OF ANTIMICROBIALS 1) INHIBITION OF CELL WALL SYNTHESIS. 2) ALTERATION OF CELL MEMBRANES 3) INHIBITION OF PROTEIN SYNTHSIS 4) INHIBITION OF NUCLEIC ACID 5) ANTIMETABOLIC OR COMPETITEVE ANTAGONISM.

MECHANISMS OF ACTION

ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS  BETA LACTAMS  PENICILLINS  CEPHALOSPORINS  CARBAPENEMS  MONOBACTAM  VANCOMYCIN  BACITRACIN

 - LACTAM ANTIBIOTICS:  BETA LACTAM RING &ORGANIC ACID.  NATURAL &SEMISYNTHETIC  CIDAL ACTION  BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION REACTION TOXICITY:  HYPERSENS.  ANAPHYLAXIS,  DIARRHOEA,..ETC.

ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS  AMINOGLYCOSIDES  TETRACYCLINES  CHLORAMPHENICOL  MACROLIDES

ANTIMICROBIALS THAT ACT ON NUCLEIC ACID  RIFAMOICIN  QUINOLONES  METRONIDAZOLE

ANTIMETABOLITES:  SULFONAMIDES  TRIMETHOPRIM  COMBINATION: BACTRIM/ SEPTRIN  BLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESIS  NOCARDIA,CHLAMYDIA,PROTOZOA,P.CRANII  UTI LRTI, OM..  GIT.HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITY

ANTITUBERCULOUS AGENTS FIRST LINE: INH  RIFAMPICIN  ETHAMBUTOL  PYRAZINAMIDE SECOND LINE:  STREPTOMYCIN  PASA  CYCLOSERINE,  CAPREOMYCIN

ANTIBIOTIC RESISTANCE IN BACTERIA  INDISCRIMINATE USE OF ANTIMICROBIALS  SELECTIVE ADVANTAGE OF ANTIBIOTICS TYPES OF RESISTANCE: PRIMARY:  INNATE eg. STREPT. &ANAEROBES RESISTANT TO GENTAMICIN

ANTIBIOTIC RESISTANCE IN BACTERIA (Continue) AQUIRED:  1-MUTATION: MTB R TO SRTEPTOMYCIN  2- GENE TRANSFER: PLASMID MEDIATED OR TRANSPOSONES CROSS RESISTANCE:  R TO ONE GROUP CONFER R TO OTHER OF THE SAME GROUP  EG ERYTHROMYCIN & CLINDAMYCIN DISSOCIATE R:  R TO GENTA. DOES NOT CONFER R.TO TOBRAMYCIN

MECHANISMS OR RESISTANCE 1-PERMIABILITY CANGED 2-MODIFICATION OF SITE OF ACTION, EG. MUTATION 3-INACTIVATION BY ENZYMES.EG. BETA LACTAMASE, AMINOGLYCOSIDES INACTIVATING ENZYMES BYPASSING BLOCKED METABOLIC REACTION EG. PABAFOILC ACID BY PLASMID MEDIATED DFR.

PRINCIPLES OF ANTIMICROBIAL THERAPY:  INDICATION  CHOICE OF DRUG  ROUTE  DOSAGE  DURATION  DISTRIBUTION  EXCRETION  TOXICITY  COMBINATION  PROPHYLAXIS: SHORT TERM:  MENINGITIS LONG TERM:  TB, UTI, RHEUMATIC FEVER

  All anaerobes are susceptible to flagyl   All Streptococci are resistant to aminoglyclosides   All anaerobes are resistant to aminoglycosides e.g. Gentamicin.   All anaerobes EXCEPT Bacteriodes fragilis are susceptible to penicillin.   All gram negative organisms are resistant to vancomycin.   All gram positive organisms are susceptible to vancomycin EXCEPT Vancomycin Resistant Enterococci (VRE).

  Pseudomonas are resistant to all antibiotic EXCEPT: a) a)Aminoglycosides b) b)Third generation cephalosporins e.g. ceftazidime c) c)Quinolones e.g. ciprofloxacin d) d)Ureidopenicillin. E.g. pipericillin e) e)Carbapenems e.g. imipenem and meropenem

  Flucloxacillin/cloxacillin is the best therapy for methicillin sensitive Staphylococcus aureus, first generation cephalosporins e.g. cephalex, cephidine can be used for the same purpose.   Patients allergic to penicillin can be treated with microlides. e.g. Erythromycin   Staphylococcus aureus resistance to methicillin are also resistant to flucloxacillin, other penicillins, some macrolides. These are better treated with vancomycin.   β-haemolytic Streptococci – e.g. Group A,B,C etc are always susceptible to penicillin, first, second and third generation cephalosporins and of course Vancomycin.   Patients allergic to penicillin can be treated with macrolides. e.g. Erythromycin.

  Enterococci e.g. Enterococcus faecalis are generally Resistant to penicillin, but susceptible to ampicillin.   Enterococci resistant to ampicillin can be treated by vancomycin or teichoplanin.   Enterococci resistant to vancomycin (VRE) are treated by Linozolid, dalphopristin or quinopristin.

  Ceftriaxone a (3 rd generation cephalosporin) is active against. a) a)Streptococcus pneumoniae b) b)Neisseria meningitidis c) c)H. influenzae This makes it the best empirical therapy of meningitis before knowing the causative agents.   Typhoid fever is treated by: a) a)Amoxycillin b) b)Cotrimoxazole (Septrin) c) c)Chloramphenicol   If resistant to these, then use Ciprofloxacin or Ceftriaxone.

  Antimicrobial prophylaxis should be a) a)Directed to a known organism as far as possible. b) b)It should not be given for more then 3 doses. Few exceptions are known e.g. urinary tract infection.   In site where immune system does not work well, use bactericidal antibiotic e.g.   Endocarditis   Meningitis

Choice of Antibacterial Agents According to Clinical Syndromes: 1. 1.Infections of Skin, Soft tissue and Bone: a) a) Cellulitis   Uncomplicated: Causative agents:   Staph. aureus   Strepto. pyogenes   Strepto. agalactiae Drugs = Cloxacillin, 1 st generation cephalosporin For MRSA = Vancomycin   Complicated: e.g. in burns Causative agents = E.coli, Pseudomonas etc. Drugs= Piperacillin / Tazobactam, Imipenem etc.

Choice of Antibacterial Agents According to Clinical Syndromes: b) b) Bone and Joints: Oesteomyelitis: Causative agents   Staph. aureus   Strepto. pyogenes Drugs as in cellulitis Septic arthritis   Staph. aureus   Haemophilus influenzae – Ampicillin, Ceftriaxone   Salmonella in sickle cell disease – Ampicillin, Ceftriaxone

Choice of Antibacterial Agents According to Clinical Syndromes: 2. 2.Meningitis: a) a)Primary causatives agents in children and adults   Strept. pneumoniae   N. meningitidis   H. influenzae Drugs = Ceftriaxone Or amoxycillin b) b)Neonatal meningitis 1. 1.Group B β-haemolytic streptococci 2. 2.Gram negative faecal organisms e.g. E.coli, Klebsiella etc Listeria monocytogenes Emperic Drugs Therapy:   Ampicillin + gentamicin   Ampicillin + Cefotaxime sometimes (Gentamicin)

Choice of Antibacterial Agents According to Clinical Syndromes: Pneumonia a) a)Causative agents: Community acquired Typical   Strep. pneumoniae   Haemophilus influenzae Drugs = Ceftriaxone Or Cefuroxime Atypical:   Mycoplasma pneumoniae   Chlamydia pneumoniae   Legionella pneumophilic Empiric Drugs Therapy:   Ceftriaxone and Erythromycin Or Azithromycin

Choice of Antibacterial Agents According to Clinical Syndrome: Hospital Acquired Pneumonia Causative agents:   Gram negative rods (Enterobactericae)   MRSA   Pseudomonas Drugs = Piperacillin / Tasobactam Or Ceftazidime + Aminoglycoside + Vancomycin for (MRSA)

Urinary Tract Infection: Causative agents:   E.coli (85% of cases)   Klebsiella   Proteus   Enterococcus faecales Drugs (Emperic)   Ampicillin / Amoxycillin   Cephalex   Trimotheprim / Sulphamethaxole   Others according to susceptibility testing

Septicemia / Bacterionema: ( Blood Stream Infection) Any Organism: Drugs   Ampicillin + Aminoglycoside   Ceftazidime + Aminoglycoside and (Vancomycin for gram +ve)

Organisms Causing Dental Infection: There are usually members of the mouth flora: A. A.Streptococci e.g. Other Viridans streptococci B. B.Anaerobes   Bacteroides   Prevotella   Viellonella C. C.Spirochaetes D. D.Others spiral organisms E. E.Other organisms in immunocompromised patients e.g. Gram negative rods

Treatment of Dental Infection:   Generally penicillin, but now replaced by amoxycillin as it is better absorbed.   In patient allergic to penicillin use A. A.Clindamycin Or B. B.Macrolides e.g. erythromycin   In severely ill patient with severe infection vancomycin may be used plus flagyl   In severe infections in immunocompromised patients take specimens for culture and give therapy according to susceptibility testing.