ANTIBIOTICS

JANUARY 29, 2008

 MAJOR PRINCIPLES AND
DEFINITIONS
 SELECTIVITY
SELECTIVE TOXICITY AGAINST THE
MICROBE ONLY

 THERAPEUTIC INDEX
RATIO OF THE TOXIC DOSE TO THE
EFFECTIVE THERAPEUTIC DOSE
THE HIGHER RATIO, BETTER ACTIVITY
 BACTERICIDAL VS BACTERIOSTATIC

2MEASURES FOR ANTIBIOTIC

SUSCEPTIBILITY TESTING
1.MINIMUM INHIBITORY
CONCENTRATION
2.MINIMUM BACTERIAL
CONCENTRATION
 MIC VS MBC
 MIC: LOWEST CONCENTRATION OF
THE ANTIBIOTIC THAT INHIBITS
VISIBLE GROWTH UNDER STANDARD
CONDITIONS
 MBC: LOWEST CONCENTRATION OF
THE ANTIBIOTIC THAT KILLS 99.99%
OF THE ORIGINAL INOCULUM IN A
GIVEN TIME
 DISK DIFFUSION TEST
 COMMON TEST FOR ANTIBIOTIC
SUSCEPTIBILITY
 DETECTS THE ZONES OF INHIBITION
 INVERSELY RELATED TO THE MIC
 >/= STANDARD: SENSITIVE
 < STANDARD: RESISTANT
 C AND S TEST
 COMBINATION THERAPY
 PREVENT EMERGENCE OF RESISTANT
STRAINS
 TREAT EMERGENCY CASES WHEN
THE ETIOLOGY IS STILL UNKNOWN
 ANTIBIOTIC SYNERGISM
 ANTIBIOTICSYNERGISM
EFFECTS OF THE COMBINATION
OF AN ANTIBIOTIC IS GREATER THAN
THE SUM OF THE EFFECTS OF THE
INDIVIDUAL ANTIBIOTIC
 ANTIBIOTICANTAGONISM
ONE ANTIBIOTIC INTERFERES
WITH THE EFFECT OF THE SECOND
ANTIBIOTIC
 INHIBITORS OF CELL WALL
SYNTHESIS
 INHIBITS
SYNTHESIS OF
PEPTIDOGLYCAN

 ENZYMATIC AUTOLYSIS OF THE CELL

WALL

 BACTERICIDAL
 BETA LACTAM DRUGS
 BINDTO AND INHIBIT EZYMES
(PENICILLIN BINDING PROTEINS)
INVOLVED IN THE
TRANSPEPTIDATION OF THE
PEPTIDOGLYCAN
 BETA LACTAM DRUGS
 OPENING OF THE RING ELIMINATES
ACTIVITY
 BETA-LACTAMASES FROM THE
BACTERIA
 CLAVULANIC ACID INHIBITS BETA-
LACTAMASES
 MODIFICATION OF THE PORINS
 BENZYLPENICILLIN

STAPH, STREP, NEISERRIAE,

SPIROCHETES
GASTRIC ACID BREAKDOWN
RAPID KIDNEY EXCRETION
BETA-LACTAMASE SUSCEPTIBILITY
RESTRICTED SPECTRUM
 PHENOXYPENICILLIN (PEN V)
 PROCAINE PENICILLIN
 FLUCLOXACILLIN
 TICARCILLIN,AZLOCILLIN,
PIPERACILLIN
 CEPHALOSPORINS
 BETA LACTAM RING IS FUSED TO A
SIX MEMBERED DIHYDROTHIAZINE
RING
 CARBONS MODIFY THEIR ACTIVITY
 STABLE AGAINST PENICILLINASES
 LACK ACTIVITY AGAINST
ENTEROCOCCI
 CEFALEXIN,CEFACLOR, ORAL
 CEFUROXIME, CEFOXITIN, STABLE TO
BETA LACTAMSES
 CEFOTAXIME, CEFTRIAXONE, HIGHER
STABILITY
 CEFTAZIDIME, CEFPIROME,
PSEUDOMONAS
 1STGENERATION
MODERATE SPECTRUM
STAPH, STREP, SOME E.COLI
KLEBSIELLA, PROTEUS
 2ND GENERATION
GREATER GRAM (-) SPECTRUM
MORE RESISTANT TO BETA-
LACTAMASES
 3RD GENERATION
BROADER SPECTRUM
MORE GRAM (-)
PSEUDOMONAS
 4TH GENERATION
CAN CROSS BLOOD-BRAIN BARRIER
PSEUDOMONAS
GREATER BETA LACTAMASES
RESISTANCE
 VANCOMYCIN

BINDS TO THE D-ala-D-ala SIDE

CHAIN THUS INHIBITING
TRANSPEPTIDATION
 DRUG OF CHOICE FOR MRSA
 INHIBITORS OF PROTEIN
SYNTHESIS
 BACTERIOSTATIC/BACTERICIDAL
 BINDS
TO THE 30S SUBUNIT
AMINOGLYCOSIDES
TETRACYCLINES
SPECTINOMYCIN
 AMINOGLYCOSIDES
 IRRVERSIBLY BIND TO THE 16S
RIBOSOMAL RNA, THUS FREEZING
THE 30 INITIATIN COMPLEX
 NO PROTEIN SYNTHESIS
 MAY ALSO DESTABILIZE THE CELL
MEMBRANE
 AG
 GRAM (-), GRAM (+)
 NOT GOOD FOR ANAEROBES
 COMMON RESISTANCE
 SYNERGIZES WITH BETA-LACTAM
DRUGS
 TETRACYCLINE

REVERSIBLY BINDS TO 30S

GOOD FOR INTRACELLULAR
BACTERIA
DESTROYS NORMAL GIT FLORA
BONE, TEETH STRUCTURE
 ANTIMICROBIALS THAT BIND
TO 50 S SUBUNIT
 CHLORAMPHENICOL

INHIBIT PEPTIDYL TRANSFERASE

BONE MARROW SUPPRESSION
RESISTANCE COMMON
BROAD SPECTRUM
 MACROLIDES (ERYTHROMYCIN)
INHIBIT TRANSLOCATION
GRAM (+),
MYCOPLASMA,LEGIONELLA
 ANTIMICROBIALS THAT
INTERFERE WITH ELONGATION
FACTORS

 FUSIDIC
ACID
INHIBITS RELEASE OF EF-GDP
FROM THE EF-G/GDP COMPLEX
STOPS ELONGATION
GRAM (+) COCCI
 INHIBITORS OF RNA
SYNTHESIS
 BIND TO DNA-DEPNDENT RNA
POLYMERASE
 STOPS RNA SYNTHESIS
 WIDE SPECTRUM
 RESISTANCE COMMON
 RIFAMPICIN-PTB
INHIBITORS OF RNA SYNTHESIS
 INHIBITION OF DNA
SYNTHESIS AND FUNCTION
 QUINOLONES

BIND TO THE A SUBUNIT OF DNA

GYRASE
PREVENTS SUPERCOILING
STOPS DNA SYNTHESIS
 NALIDIXIC ACID, CIPROFLOXACIN
 INHIBITORS OF FOLIC ACID
SYNTHESIS
 BACTERIA
CANNOT USED PRE-
FORMED FOLIC ACID

 SULFONAMIDES, SULFONES
 TRIMETHOPRIM, METHOTREXATE,
PYRIMETHAMINE
 ANALOGUES OF PARA-
AMINOBENZOIC ACID
 COMPETITIVE INHIBITION OF
PTERIDINE SYNTHETASE
 BLOCKS FORMATION OF
DIHYDROPTEROIC ACID
 BROAD SPECTRUM
 ESPECIALLY FOR UTI, NOCARDIA
INFECTIONS
 USED IN COMBO WITH
TRIMETHOPRIM
BIND TO DIHYDROFOLATE
REDUCTASE, INHIBIT FORMATION OF
TETRAHYDROFOLIC ACID
 COMMON RESISTANCE
INHIBITORS OF FOLIC ACID
SYNTHESIS
 INHIBITION OF DNA
 NITROIMIDAZOLES CAUSES BREAKS
IN THE DNA
 GOOD FOR ANAEROBES,
PROTOZOANS
METRONIDAZOLE
 RESISTANCE
 OCCURS WHEN THE MIC OF THE
DRUG EXCEEDS THAT WHICH IS
CAPABLE OF BEING ACHIEVED WITH
SAFETY IN VIVO
 GENE MUTATION
 EXTRACHROMOSOMAL DNA
ACQUISITION WHICH HAS A
RESISTANT GENE (PLASMIDS)
 CROS RESISTANCE
A SINGLE MECHANISM CONFERS
RESISTANCE TO MULTIPLE
ANTIMICROBIAL AGENTS (CLOSELY
RELATED)
 MULTIPLE RESISTANCE

UNRELATED; MULTIPLE
MECHANISMS
 ALTERED PERMEABILITY TO THE
ANTIMICROBIAL
 INACTIVATON OF THE
ANTIMICROBIAL
 ALTERED TARGET SITE
 REPLACEMENT OF A ENZYME,
PATHWAY
PLASMID RESISTANCE