General Rules On Use of Antimicrobial Agents

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

• ANTIBIOTICS
• NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH
  INHIBIT THE GROWTH OF OTHER .
• CHEMOTHERAPY
• SYNTHETIC COMPOUNDS.

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SELECTIVE TOXICITY

• THE ABILITY TO KILL OR INHIBIT THE GROWTH OF
  MICROORGANISM WITHOUT HARMING THE HOST CELLS.

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• BACTERICIDAL KILLS BACTERIA
• BACTERIOSTATIC PREVENTS MULTIPLICATION.
• SPECTRIM OF ACTIVITY
• BROAD SPECTRUM GVE G-VE
• NARROW SPECTRUM SELECTIVE ORGANISM.

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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

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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.

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MECHANISMS OF ACTION
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ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS

• BETA LACTAMS
• PENICILLINS
• CEPHALOSPORINS
• CARBAPENEMS
• MONOBACTAM
• VANCOMYCIN
• BACITRACIN

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? - LACTAM ANTIBIOTICS

• BETA LACTAM RING ORGANIC ACID.
• NATURAL SEMISYNTHETIC
• CIDAL ACTION
• BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION
  REACTION
• TOXICITY
• HYPERSENS.
• ANAPHYLAXIS,
• DIARRHOEA, ..ETC.

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ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS

• AMINOGLYCOSIDES
• TETRACYCLINES
• CHLORAMPHENICOL
• MACROLIDES

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ANTIMICROBIALS THAT ACT ON NUCLEIC ACID

• RIFAMOICIN
• QUINOLONES
• METRONIDAZOLE

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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

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ANTITUBERCULOUS AGENTS

• FIRST LINE INH
• RIFAMPICIN
• ETHAMBUTOL
• PYRAZINAMIDE

• SECOND LINE
• STREPTOMYCIN
• PASA
• CYCLOSERINE,
• CAPREOMYCIN

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ANTIBIOTIC RESISTANCE IN BACTERIA

• INDISCRIMINATE USE OF ANTIMICROBIALS
• SELECTIVE ADVANTAGE OF ANTIBIOTICS
• TYPES OF RESISTANCE
• PRIMARY
• INNATE eg. STREPT. ANAEROBES RESISTANT TO
  GENTAMICIN

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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

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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.
• PABA FOILC ACID BY PLASMID MEDIATED DFR.

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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

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• 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).

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• Pseudomonas are resistant to all antibiotic
  EXCEPT
• Aminoglycosides
• Third generation cephalosporins
• e.g. ceftazidime
• Quinolones e.g. ciprofloxacin
• Ureidopenicillin. E.g. pipericillin
• Carbapenems e.g. imipenem and meropenem

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• 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.
• ß-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.

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• 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.

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

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• Antimicrobial prophylaxis should be
• Directed to a known organism as far as possible.
• 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

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

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• Choice of Antibacterial Agents According to
  Clinical Syndromes
• 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

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

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• Choice of Antibacterial Agents According to
  Clinical Syndromes
• Pneumonia
• 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

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• 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)

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• 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

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

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

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• Treatment of Dental Infection
• Generally penicillin, but now replaced by
  amoxycillin as it is better absorbed.
• In patient allergic to penicillin use
• Clindamycin Or
• 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.