Chapter 20

Antimicrobial Drugs

General Microbiology
Faculty of Medicine
Fall-2022
 Spectrum of Antimicrobial
Activity
 Narrow spectrum:
 Example: Penicillin affects gram positive , few gram negative
affected outermembrane highly selective

 Lipopolysaccharide and porins play role in the selectivity:

 Lipophilic drugs or large molecules don’t pass the outer
membrane of gram negative
 Broad spectrum: affects a broad range of gram positive and
gram negative bacteria

 In the past : Antibiotics was for drug from

microorganism, synthetic antimicrobial agent was for
chemicaly modified drugs, now both of them are called
Antibiotics
fliming: used penicillin
 Superinfection

 When a drug flourish the growth of a competitor

opportunistic microorganism
 Example: C. albicans overgrowth following use of
bacterial antibiotics part of oral and GIT normal flora (oppotunistic )

 Or growth of antibiotic resistant microorganism

‫م‬
broadspectrum AB ( ‫ د س تم دمزتس مزال‬㐁) : to prevent effect the normal flora so
prevent super infection

uncontrolled,false dose and uncompliance cause multidrug resistant

microorganisms
 The Action of Antimicrobial
Drugs
AB affect the cell wall permability osmptic pressure rupture

 Bactericidal :( kill microbes directly)

AB affect protein
 Bacteriostatic: ( prevent microbes from growing). synthesis

70s ribo

especially : florquinolones
1.Inhibiton of cell wall synthesis by affect
peptidoglycan synthesis : A.affect the cross linkage
B.affect add of N-acetyl glucoseamine
Result : weak cell wall

2.Inhibition of protein synthesis : affectig 30s

ribosmes(ex:erythromycinm,tetracyclin) or 50s ribosomes
(chlormphenicol) by changing the ribosome shape
(M-RNA‫ لك ما ي ات لاب‬㐁 ‫يلال‬
‫ ( لل لرق د‬㤦‫ م‬甀 
erythromysin +azithromysin macrolides group
gentamycin + streptomycin aminoglycosides

PAPA(para aminobenzioic acid ) dihydrofolic acid tetrahydropholic

acid (enzyme used in the synthesis of purin and pyrimidins for DNA and
RNA synthesis )

inhibited by sulfanilamide inhibited by trimethoporin

‫و‬ ‫د‬ ‫د‬

‫ك‬ 㤦 ‫ه‬ ‫ل‬
) ‫و ل  يت ل‬ ‫ب‬ 㤦‫م‬ ‫م‬ ‫ل‬ ‫ي‬ 㕫‫ أ ي ل ا ت ل ز ب‬㐁 ‫ يا‬㐁 ‫ ل ي‬㐁 ‫ ل‬㐁‫� ت‬἟絽
‫ا‬ ‫م‬ ‫ا‬ 㤦 甀 ‫ي‬ ‫ر‬‫د‬ ‫أ‬‫ل‬ ‫د‬ ‫ا‬ ‫ل‬‫و‬ ‫ا‬ 㤦‫م‬ ‫ي‬ ‫د‬ ⠀

 The Action of Antimicrobial
Drugs
 Inhibiting cell wall synthesis:
 Inhibiting synthesis of intact peptidoglycan, ex: penicillin
 Affect actively growing bacterial cells
 Inhibiting protein synthesis:
 Inhibiting 70s ribosomes in prokaryotes, ex: tetracyclines
 Eukaryotic 80s have no effect
 Eukaryotic mitochondria have 70s ,antibiotics against bacterial
ribosomes affect host cells
 Injuring plasma membrane ex:polymyxin B affect porin channels
 Change membrane permeability leading to uncontrolled
permeability of cations in an out ,or bind to sterols in fungal
membranes
AB affect bacteria plasma membrane not affect fungul plasma membrane
DNA&RNA structure structure in eu and pro are almist the same so some AB may affect
human DNA ................ (floroquinolnes is AB with minimal effect on human )
 The Action of Antimicrobial
Drugs
 Inhibiting Nucleic Acid Synthesis:(replication and transcriptions )
 Interfere with DNA replication and transcription in
microorganisms.
 Inhibiting the Synthesis of Essential Metabolites:
 Competitive inhibited by a substance similar to the normal
substrate for the enzyme
 Example: sulfanilamide (a sulfa drug)and para--aminobenzoic
 acid (PABA) the substrate for the synthesis of folic acid
 Tests to Guide Chemotherapy
 Diffusion methods(Kirby Bauer test):
 Qualitative method based on measuring the zone diameter of
bacterial growth inhibition around disks impregnated with
chemotherapeutic agents following incubation period.
 inhibition not cidal effect + can’t give the concentration of AB
 E--test:
 Quantitative method in which the minimal inhibitory
concentration (MIC)that prevents visible bacterial growth is
estimated from a scale printed on the antibiotic strip
sensitive
Inhibiting zone
‫د حب هلوط سحعع‬
R or S pgance

inoculation ‫ساي ولل ل‬

not straeking
E--test
Kirby Bauer test
TO ensur AB actvity use AB suceotibility testing (just for bacteria)
example: for healthy indivisual use kirby method diffusion

the report form

urin samole
E.coli
‫د‬
>1000 cfu/ml ( ‫ دل ك دير و اش له مر ما ليي‬⠀‫ ما 
ر ر و‬㑺吀 ‫)⚏ ور‬
CIP S
GNS S (ONLY INJECTION)
FR

So the doctor choose one of the S AB based on age,pregnancymsite

of infection,drug taken by the patient

E-test used for diabetes,chemotheraby,osteomyelitis because they are

immune compramized so MIC should used to prevent toxcisity

spread pure isolated bacteria

gradual increase of AB

MIC
 Tests to Guide Chemotherapy
 Broth Dilution Tests: used for cidal effect
(active ‫ جري كبلا رجرت‬inhibiton ‫) نتش رناش لمل نت ي اأ كب جار كبأ لمند‬
 Diffusion methods don’t determine whether a drug is bactericidal or
just bacteriostatic.
 A broth dilution test is used to determine MIC and the minimal
bactericidal concentration (MBC) of an antimicrobial drug.
 A sequence of decreasing concentrations of a drug in a broth
inoculated with the test bacteria is prepared.
 The wells that don’t show growth (higher concentration than
the MIC) can be cultured in broth or on agar plates free of the drug.
 If growth occurs in this broth, the drug was not bactericidal,
and the MBC can be determined.
 Broth Dilution Tests
 Minimizes the chance of toxic reactions that larger--than--
necessary doses might cause.
inoculation of certain turbidity of bacteria in each tube ( inhibiton ‫) ديل 
و دير  ب ف دلش لا‬

then to
cultur
media
M.cidal.conc ‫ا ديل 
و دير لا‬
MIC=16ug/ml, MBC=32 ug/ml cidal
 Mechanisms of Resistance
 Prevention of Penetration to the Target
Site within the Microbe:
 Gram negative bacteria modify porin
openings preventing antibiotic
penetration through the cell wall
 B--lactamases degrade antibiotics
before reaching to their targets
 Enzymatic Destruction or Inactivation
of the Drug:
 Affects mainly natural antibiotics such
as the penicillins and cephalosporins
 B--lactam ring is hydrolyzed by pump AB outside
affect peptidoglycan layer
b--lactamase enzymes
 Example: S.pneumoniae
Mechanisms of Resistance

B-LACTAM AB Inhibited :
A. B-lactmases
B. chanching the cell membrane that binds B-lactam AB
(PBP penicillin binding protein )

Methicillin (one of synthetic B-lactam ABs)

Methicillin resistant S.aureus (MRSA):
Mec A gene that encode for synthesis PBP-2a replace it with PDP
and the AB will not bind to PDP

Gram negative have porins

some molecule and AB pass porin
pseudomonase incraese porin channel selectivity to AB so become R

Some bacteria produce more of the enzymes that are used to

produce tetrahydropholic in pholic acid pathway so AB will not be
enough to inhibit all enzymes
 Mechanisms of Resistance

 Alteration of the Drug’s Target Site:

 Minor modifications protein synthesis site on
ribosomes can neutralize the effects of
antibiotics without significantly affecting
cellular function.
 MRSA gains resistant to antibiotics mainly by
)
modifying the penicillin--binding protein (PBP
on he cell’s membrane
 Rapid Efflux (Ejection) of the Antibiotic:
 Gram negative bacteria have plasma
membrane proteins that pump out drugs and
toxic substances from the cell
 Increase synthesizing of large amounts of
the enzyme against which the drug is targeted
 Prevention of resistance
Never prescribe antibiotics when not needed : e.g:
treat headache, common cold, etc….
 The patient should finish antibiotic regimens
 Never use leftover antibiotics to treat new illnesses
 Never use antibiotics prescribed to someone else
Antibiotic dosage should be appropriate to the
situation
 Use specific antibiotics rather than broad spectrum.
Prevention of resistance

use two groups of AB :

example AB affect cell wall but there is little resistance
(minimum effect ) with AB affect protein so this syngristic
use of ABs can over come the resistant of certain bacteria

addition of chemical group to an AB can overcome the

inhibitory effect of certain enzyme like B-lactamase :
calvulinic acid is added to amoxicillin (B-lactam AB ) will
degrade B lactamase in the resistante bacteria