ANTIMICROBIAL AGENTS
ANTIBIOTIC - low molecular substance produced by a microorganism that at a low
concentration inhibits or kills other microorganisms.
ANTIMICROBIAL - any substance of natural, semisynthetic or synthetic origin that kills or
inhibits the growth of microorganisms but causes little or no damage to the host.
All antibiotics are antimicrobials, but not all antimicrobials are antibiotics.
SOURCE OF ANTIBIOTICS
FUNGI
Penicillin's (penicillium notatum)
Cephalosporin's (cephalosporium)
Griseofulvin (penicillium gresiofuloum)
BACTERIA
Polymyxin B
Tyrothricin
Bacitracin
Colistin
ACTINOMYCETES
Erythromycin
Chloramphenicol
Aminoglycoside
Tetracyclin
Antibiotics do not include antimicrobial substances that are synthetic (sulfonamides and
quinolones), or semisynthetic (methicillin and amoxicillin), or those which come from plants
(quercetin and alkaloids) or animals (lysozyme).
A synthetic antimicrobial is a drug that is developed from a chemical not found in nature.
A semisynthetic antimicrobial is a chemically modified derivative of a natural antibiotic.
The chemical modifications are generally designed to increase the range of bacteria targeted,
increase stability, decrease toxicity, or confer other properties beneficial for treating
infections.
The term “antimicrobials” include all agents that act against all types of microorganisms
Bacteria (antibacterial)
Viruses (antiviral)
Fungi (antifungal)
Protozoa (antiprotozoal).
HISTORY
Sahachiro Hata (1909) - Compound 606 targeted the bacterium Treponema pallidum
Alexander Fleming (1928) - credited with the discovery of penicillin, the first natural
antibiotic antibacterial against streptococci, meningococci, and Corynebacterium
diphtheriae, the causative agent of diphtheria
Josef Klarer, Fritz Mietzsch, and Gerhard Domagk (1935) - discovered the antibacterial
activity of a synthetic dye, prontosil and sulfanilamide, that could treat streptococcal and
staphylococcal infections in mice.
The success of the sulfa drugs led to the discovery and production of additional important
classes of synthetic antimicrobials, including the quinolines and oxazolidinones.
TERMINOLOGY
Antibacterial spectrum: Range of activity of an antimicrobial against bacteria.
A broad-spectrum antibacterial drug can inhibit a variety of gram-positive and gramnegative bacteria
A narrow- spectrum drug is active against a limited variety of bacteria.
Bacteriostatic antibiotic: Antibiotic that inhibits the growth of bacteria but does not kill.
Bactericidal antibiotic: Antibiotic that kills bacteria.
Minimum inhibitory concentration (MIC): The lowest antibiotic concentration that
inhibits the growth of the bacteria is the MIC.
Minimum bactericidal concentration (MBC): The lowest antibiotic concentration that kills
99.9% of the population is referred to as the MBC.
Antibiotic combinations: Combinations of antibiotics that may be used to
 Broaden the antibacterial spectrum for empirical therapy or the treatment of
polymicrobial infections
 Prevent the emergence of resistant organisms during therapy
 Achieve a synergistic killing effect.
Antibiotic synergism: Combinations of two antibiotics that have enhanced activity when
tested together compared with the activity of each antibiotic. E.g., Sulphamethoxazole
and Trimethoprim
Antibiotic antagonism: Combination of antibiotics in which the activity of one antibiotic
interferes with the activity of the other (e.g., the sum of the activity is less than the activity
of the most active individual drug).e.g., Penicillin and Chloramphenicol
CLASSIFICATION OF ANTIBACTERIAL AGENTS
Antimicrobials are classified in several ways, including:
 Spectrum of activity
 Effect on bacteria
 Mode of action
SPECTRUM OF ACTIVITY
■ Narrow- spectrum Antibiotics: Act on a single/limited group of microorganisms e.g.
Isoniazid acts only on mycobacterium
■ Broad spectrum Antibiotics: Effective against a wide variety of microbial species e.g.,
chloramphenicol and tetracycline
– It can alter the nature of normal bacterial flora and precipitate a
superinfection of an organism e.g., Clostridium defficile
■ Extended-spectrum antibiotics: Effective against gram positive rganisms and also a
significant number of Gram negative bacteria e.g., Ampicillin
■
EFFECTS ON BACTERIA
Bactericidal drugs are those that kill target bacteria (99.9%).
Examples of bactericidal drugs include aminoglycosides, cephalosporins,
penicillins, and quinolones.
Bacteriostatic drugs inhibit or delay bacterial growth and replication.
Examples of such include tetracyclines, sulfonamides, and macrolides.
Some antibiotics can be both bacteriostatic and bactericidal, depending on the dose,
duration of exposure and the state of the invading bacteria.
For example, aminoglycosides, fluoroquinolones, and metronidazole exert
concentration-dependent killing characteristics; their rate of killing increases as the
drug concentration increases.
MODE OF ACTION
Different antibiotics have different modes of action, owing to the nature of their structure
and degree of affinity to certain target sites within bacterial cells.
Inhibitors of cell wall synthesis.
A drug that targets cell walls can therefore selectively kill or inhibit bacterial
organisms. Examples: penicllins, cephalosporins, bacitracin and vancomycin.
Inhibitors of cell membrane function.
A disruption or damage to this structure could result in leakage of important
solutes essential for the cell’s survival.
Structure found in both eukaryotic and prokaryotic cells, the action of this class of
antibiotic are often poorly selective and can often be toxic for systemic use in the
mammalian host.
Most clinical usage is therefore limited to topical applications. Examples: polymixin
B and colistin.
Inhibitors of protein synthesis.
Protein synthesis is an essential process necessary for the multiplication and
survival of all bacterial cells.
Disruption of the normal cellular metabolism can lead to the death/inhibition of
growth and multiplication of bacteria.
Examples: Aminoglycosides, macrolides, lincosamides, streptogramins,
chloramphenicol, tetracyclines.
Inhibitors of nucleic acid synthesis.
Some antibiotics bind to components involved in DNA or RNA synthesis, which
causes interference of the normal cellular processes which will ultimately
compromise bacterial multiplication and survival.
Examples: quinolones, metronidazole, and rifampin.
Inhibitors of other metabolic processes.
Other antibiotics act on selected cellular processes essential for the survival of the
bacterial pathogens.
For example, both sulfonamides and trimethoprim disrupt the folic acid pathway,
which is a necessary step for bacteria to produce precursors important for DNA
synthesis.
INHIBITION OF CELL WALL SYNTHESIS
The most common mechanism of antibiotic activity is interference with bacterial cell wall
synthesis.
Most of the cell wall–active antibiotics are classified as β-lactam antibiotics (e.g.,
penicillins, cephalosporins, cephamycins, carbapenems, monobactams, β-lactamase
inhibitors), so named because they share a common β-lactam ring structure.
Other antibiotics that interfere with construction of the bacterial cell wall include
vancomycin, daptomycin, bacitracin,
Antimycobacterial agents: isoniazid, ethambutol, Cycloserine, and ethionamide.
NATURAL PENICILLINS
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Act by binding Penicillin binding proteins found in the cell wall
Some of these PBPs are transpeptidases – enzymes that catalyze the final crosslinking step of synthesis of peptidoglycan
They are bactericidal but kills cells only when growing
More active during the log phase of bacterial cell growth than during the
stationary phase
Penicillin G is available in three main forms:
 Aqueous penicillin G, which is metabolized most rapidly.
 Procaine penicillin G, in which penicillin G is conjugated to procaine.
o This form is metabolized more slowly
o Less painful when injected intramuscularly because procaine acts as
anaesthetic
 Benzathine penicillin G, in which penicillin G is conjugated to benzathine.
o This form is metabolized very slowly and is often called a “depot”
preparation
SEMISYNTHETIC PENICILLINS
■ Categories
of
semisynthetic
penicillins: antistaphylococcal
penicillins,
aminopenicillins, carboxypenicillins, ureidopenicillins,
■ antistaphylococcal penicillins/ ß-lactamase-resistant penicillins. _ (Narrow spectrum
Penicillins)- Methicillin, isoxazolyl penicillins-oxacillin, cloxacillin, dicloxacillin, and
flucloxacillin-and nafcillin
■ alpha-aminobenzylpenicillin – (Extended Spectrum Penicillins)- Ampicillin and
Amoxicillin
■ ureidopenicillins (Extended Spectrum Penicillins (Antipseudomonal Penicillins)
- Azlocillin, Piperacillin and Mezlocillin
carboxypenicillins(Extended Spectrum Penicillins )– Ticarcillin and carbenicillin
■ Disadvantages of penicillins
■ Limited effectiveness against many Gram-negative rods
– Ampicillin and Amoxicillin effective against several Gramnegative rods except K. pneumoniae and P. aeruginosa
■ Hydrolysis by gastric acids, so that it cannot be taken orally
– Modified penicillins e.g., Penicillin V & Ampicillin resistant to
acid hydrolysis
■ Inactivation by β-lactamases e.g., S. aureus
– Oxacillin, Nafcillin block enzyme
– Clavulanic acid, tazobactam, avibactam, sulbactam bind
strongly to beta-lactamases
– Amoxicillin and Clavulanic acid (Augmentin)
■ Hyper- sensitivity, especially anaphylaxis, in some recipients of the drug
CEPHALOSPORINS
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Most are product of mold Cephalosporium a few from Streptomyces
Similar to penicillins but stucturally different
Effective against a broad range of organisms
Well tolerated - fewer hypersensitivity reactions than penicillins
First generation primarily active against Gram positive cocci
Newer generations have expanded activity against Gram negative rods
First generation (Narrow spectrum)
– cefazolin, cephalothin, cephapirin, cephradine, cefadroxil, and cephalexin
– Active coverage against most gram-positive cocci
– Susceptible Gram –ves are Proteus mirabilis, E. coli, and Klebsiella pneumoniae
– Uncomplicated skin and soft tissue infections: cellulitis and abscesses due to
staphylococci spp. or streptococci spp. Infection
Can be used for bone, respiratory tract, genitourinary tract, biliary tract, bloodstream
infection, otitis media, and surgical prophylaxis (cefazolin).
Second-generation cephalosporins (Expanded spectrum)
– Divided into two subgroups: the second-generation and the cephamycin
subgroup.
– Second-generation subgroups include cefuroxime and cefprozil.
– Cephamycin subgroup includes cefmetazole, cefotetan, and cefoxitin.
– Cefuroxime has increase coverage against H. influenza.
– Cephamycin subgroup has increased coverage against Bacteroides species.
– Have less activity against gram-positive cocci but have increase activity against
gram-negative bacilli
– Prescribed to treat respiratory infections such as bronchiolitis or pneumonia.
Have coverage against H. influenza, Enterobacter aerogenes, Neisseria species and Serratia
marcescens
Third generation cephalosporins (Expanded spectrum)
– Include cefotaxime, ceftazidime, cefdinir, ceftriaxone, cefpodoxime, and
cefixime.
– Treat gram-negative infection resistant to first /second generation or other
beta-lactams
– Can penetrate the blood-brain barrier and cover bacteria in the cerebral spinal
fluid, especially ceftriaxone and cefotaxime when given IV,
– Ceftriaxone can be given to treat meningitis caused by H. influenza, Neisseria
meningitidis, or Streptococcus pneumoniae.
– Ceftriaxone is also used to treat gonorrhoea and disseminated Lyme disease.
Ceftazidime, very importantly, has Pseudomonas aeruginosa coverage
Fourth-generation cephalosporin (Broad spectrum) includes cefepime.
– Cefepime can penetrate the cerebral spinal fluid.
– Cefepime can penetrate the outer membrane of gram-negative bacteria better.
– Similar to the activity of cefotaxime and ceftriaxone, cefepime can
cover Streptococcus pneumoniae and methicillin-sensitive Staphylococcus
aureus (MSSA).
– Similar to ceftazidime, cefepime, very importantly, can cover
for Pseudomonas aeruginosa.
– Can cover against beta-lactamase-producing gram-negative bacilli.
Cefepime is reserved for serious systemic infection in patients who are likely to have multiresistance organisms
Fifth generation cephalosporins (Extended spectrum) include ceftaroline.
– Ceftaroline unique from the rest of the cephalosporins is that it has coverage
against methicillin-resistant Staphylococcus aureus (MRSA).
– Ceftaroline can also cover Listeria monocytogenes and Enterococcus faecalis.
Cefazoline does not cover Pseudomonas aeruginosa
CARBAPENEMS
– Are Beta-lactam drugs structurally different from penicillins and cephalosporins.
– Example is imipenem, meropenem, ertapenem, doripenem.
– Widely prescribed broad-spectrum antibiotics that are active against many groups of
organisms.
– It has excellent bactericidal activity against many gram-positive, gram- negative
(Pseudomonas), and anaerobic bacteria e.g. Bacteroides, Clostridium).
MONOBACTAMS
– Are Beta-lactam drugs structurally different from penicillins and cephalosporins.
– Example is Aztreonam
– Narrow-spectrum antibiotics that are active only against select aerobic, gram-negative
bacteria.
– Anaerobic bacteria and gram-positive bacteria are resistant.
– Monobactams are not widely used
VANCOMYCIN
– Glycoproten that inhibits cross-linkage of peptidoglycan layers
– Unlike other Beta-lactam drugs, it binds directly to pentapeptide instead of
transpeptidase
– Bactericidal against infections caused by S. aureus strains resistant to nafcillin and
methicillin (MRSA).
– Vancomycin is also used in the treatment of infections caused by Staphylococcus
epidermidis, penicillin-resistant Streptococcus pneumoniae, and enterococci.
– A well-known adverse effect of vancomycin is “red man” syndrome.
– “Red” refers to the flushing caused by vasodilation induced by histamine release from mast
cells and basophils.
– Telavancin a synthetic derivative of vancomycin used in treatment of skin infection caused
by MRSA
– Oritavancin a derivative of vancomycin & teicoplanin used to treat VRE, MRSA &
Enterococcus infections
BACITRACIN
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Polypeptide isolated from Bacillus licheniformis
Block regeneration of the lipid carrier & inhibit cell wall synthesis
Treatment of superficial skin infections (Staphylococcus and group A Streptococcus)
Topically applied products (e.g., creams, ointments, sprays)
Too toxic for systemic use
POLYMYXINS
– Group of cyclic polypeptides derived from Bacillus polymyxa.
– These antibiotics insert into bacterial membranes like detergents perforate the outer
membrane, producing increased cell permeability and eventual cell death.
– Polymyxins B and E (colistin) are capable of causing serious nephrotoxicity.
– Their use limited to external treatment of localized infections e.g., external otitis, eye
infections, and skin infections caused by sensitive organisms.
– Acinetobacter and Pseudomonas are only susceptible to colistin, this antibiotic is used to
treat some systemic infections.
– Most active against gram-negative rods, because gram-positive bacteria do not have an
outer membrane
ISONIAZID, ETHIONAMIDE, ETHAMBUTOL, AND CYCLOSERINE
– Group of cyclic polypeptides derived from Bacillus polymyxa.
– These antibiotics insert into bacterial membranes like detergents perforate the outer
membrane, producing increased cell permeability and eventual cell death.
– Polymyxins B and E (colistin) are capable of causing serious nephrotoxicity.
– Their use limited to external treatment of localized infections e.g. external otitis, eye
infections, and skin infections caused by sensitive organisms.
– Acinetobacter and Pseudomonas are only susceptible to colistin, this antibiotic is used to
treat some systemic infections.
– Most active against gram-negative rods, because gram-positive bacteria do not have an
outer membrane
PROTEIN SYNTHESIS INHIBITION
– The primary action of the agents in the second largest class of antibiotics is inhibition
of protein synthesis
– Several drugs inhibit protein synthesis in bacteria without significantly interfering with
protein synthesis in human cells.
– This selectivity is due to the differences between bacterial and human ribosomal
proteins, RNAs, and associated enzymes.
– Bacteria have 70S ribosomes with 50S and 30S subunits, whereas human cells have
80S ribosomes with 60S and 40S subunits.
– Chloramphenicol, macrolides such as azithromycin and erythromycin, clindamycin,
and linezolid act on the 50S subunit
– Tetracyclines such as doxycycline and aminoglycosides such as gentamicin act on the
30S subunit.
AMINOGLYCOSIDES
– Bactericidal drugs useful against many gram-negative rods.
– Produce premature release of peptide chains from 30S ribosome
– The most commonly used antibiotics in this class are amikacin, gentamicin, and
tobramycin.
– All three amino- glycosides are used to treat systemic infections caused by susceptible
gram-negative bacteria.
– Amikacin has the best activity and is frequently reserved for treatment of infections
caused by gram-negative bacteria that are resistant to gentamicin and tobramycin.
– Streptomycin has been used for the treatment of tuberculosis, tularemia, and
gentamicin-resistant streptococcal or enterococcal infections (in combination with a
penicillin)
– Aminoglycosides have certain limitations in their use:
o They have a toxic effect both on the kidneys and on the auditory and vestibular
portions of the eighth cranial nerve
o They are poorly absorbed from the gastrointestinal tract and cannot be given
orally
o Poor penetration into the spinal fluid; must be given intrathecally in the
treatment of meningitis.
Ineffective against anaerobes: their transport into the bacterial cell requires oxygen
TETRACYCLINES
– Broad-spectrum, bacteriostatic antibiotics that binds reversibly to the 30S ribosomal
subunits
– Tetracycline, doxycycline, minocycline are effective in the treatment of infections
caused by Chlamydia, Mycoplasma, and Rickettsia species
– Effective against other selected gram- positive and gram-negative bacteria.
– Have low toxicity
– Can suppress normal flora and cause overgrowth of resistant bacteria/diarrhoea
– Can suppress lactobacillus leading to overgrowth of Candida albicans in vagina
– Deposition in developing teeth resulting in staining of teeth in fetuses and young
children
– Photosensitivity can occur during therapy
GLYCYCLINES
– Tigecycline, the first representative of this new class of antibiotics.
– Inhibits protein synthesis in the same manner as the tetracyclines.
– Tigecycline has a higher binding affinity for the ribosome and is less affected by efflux
or enzymatic modification.
– It has a broad spectrum of activity against gram-positive, gram-negative, and
anaerobic bacteria
– Proteus, Morganella, Providencia, and P. aeruginosa are generally resistant.
– Used to treat skin infections caused by MRSA, VRE, group A &B Streptococci,
Bacteroides fragilis and E. coli
LINEZOLID
– Binds to 50s RNA subunit and distort binding of tRNA
– Linezolid has activity against staphylococci, streptococci, and enterococci (including
those strains resistant to penicillins, vancomycin, and the amino- glycosides).
– Use of linezolid is generally reserved for multidrug-resistant enterococci which are
difficult to treat
– Bacteriostatic against Enterococci but bactericidal against Streptococci
MACROLIDES
– Erythromycin, derived from Streptomyces erythreus, is the model macrolide antibiotic
– Modification of the macrolide structure led to the development of azithromycin,
clarithromycin, and roxithromycin.
– Macrolides exert their effect by their reversible binding to the 23S ribosomal RNA
(rRNA) of the 50S ribosomal subunit, which blocks polypeptide elongation.
– Macrolides are bacteriostatic antibiotics with a broad spectrum of activity.
– They have been used to treat pulmonary infections caused by Mycoplasma,
Legionella, and Chlamydia species
– Clarithromycin used to treat H. pylori infections
– Treat infections caused by Campylobacter species and gram-positive bacteria in
patients allergic to penicillin.
– Erythromycin has more adverse effects especially in the gastrointestinal tract
– Most gram-negative bacteria are resistant to the macrolides.
CHLORAMPHENICOL
– Has a broad antibacterial spectrum similar to that of tetracycline but is not commonly
used.
– It disrupts protein synthesis in human bone marrow cells and can produce blood
dyscrasias, such as aplastic anaemia.
– Chloramphenicol exerts its bacteriostatic effect e.g. Salmonella typhi
– Binds reversibly to the peptidyl transferase component of the 50S ribosomal subunit,
thus blocking peptide elongation
– Bactericidal against important encapsulated organisms that cause meningitis:
Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis.
CLINDAMYCIN
– Derivative of lincomycin, which was originally isolated from Streptomyces lincolnensis.
– Like chloramphenicol and the macrolides, clindamycin blocks protein elongation by
binding to the 50S ribosome.
– It inhibits peptidyl transferase by interfering with the binding of the amino acid–acyltRNA complex.
– Clindamycin is bacteriostatic against staphylococci and anaerobic gram-negative rods
but is generally inactive against aerobic gram-negative bacteria.
– The most important side effect of clindamycin is pseudomembranous colitis, which, in
fact, can occur with virtually any antibiotic, whether taken orally or parenterally.
– The pathogenesis is suppression of the normal flora of the bowel and overgrowth of a
drug-resistant strain of C. difficile.
– The organism secretes an exotoxin that produces the pseudo- membrane in the colon
and severe, often bloody
STREPTOGRAMINS
– A class of cyclic peptides produced by Streptomyces species.
– Administered as a combination of two components, group A and group B
streptogramins, which act synergistically to inhibit protein synthesis.
– Cause premature release of the growing peptide chain from the 50S ribosomal
subunit.
– Used for the treatment of bloodstream infections caused by vancomycin-resistant
Enterococcus faecium (but not vancomycin-resistant Enterococcus faecalis)
– It is also approved for use in infections caused by Streptococcus pyogenes, penicillinresistant S. pneumoniae, methicillin-resistant S. aureus, and methicillin- resistant S.
epidermidis.
INHIBITION OF NUCLEIC ACID SYNTHESIS
QUINOLONES
– One of the most widely used classes of antibiotics.
– Synthetic antimicrobials that inhibit bacterial DNA topoisomerases type II (gyrase) or
topoisomerase type IV, which are required for DNA replication, recombination, and
repair.
– The DNA gyrase-A subunit is the primary quinolone target in gram- negative bacteria,
whereas topoisomerase type IV is the primary target in gram-positive bacteria.
– Quinolones include ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin.
– Active against wide variety of bacteria that cause soft tissue infections, UTI, lower
respiratory tract, skeletal and gastric intestinal infections
– Cause damage in growing bones and cartilage
– Rapid resistance by Pseudomonas can occur
METRONIDAZOLE
– Originally introduced as an oral agent for the treatment of Trichomonas vaginitis.
– Found to be effective in the treatment of amebiasis, giardiasis, and serious anaerobic
bacterial infections (including those caused by B. fragilis).
– No significant activity against aerobic or facultatively anaerobic bacteria
– Reduction of its nitro group by bacterial nitroreductase, thereby producing cytotoxic
compounds that disrupt the host DNA.
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RIFAMPIN AND RIFABUTIN
– Rifampin, a semisynthetic derivative of rifamycin B produced by Streptomyces
mediterranei,
– Binds to DNA- dependent RNA polymerase and inhibits initiation of RNA synthesis.
– Rifampin is bactericidal for Mycobacterium tuberculosis and is very active against
aerobic gram-positive cocci, including staphylococci and streptococci.
– Resistance can develop rapidly, rifampin is usually combined with one or more other
effective antibiotics.
– Rifabutin, a derivative of rifamycin, has a similar mode and spectrum of activit
– It is particularly active against M. avium.
TRIMETHOPRIM
– Antimetabolite that interferes with folic acid metabolism thus blocks the formation of
thymidine and some purines.
– Trimethoprim is commonly combined with sulfamethoxazole to produce a synergistic
combination active at two steps in the synthesis of folic acid.
– Trimethoprim-sulfamethoxazole – used in treatment of acute and chronic UTI,
chancroid, shigellosis, nocardiosis
– Also effective in the treatment of infections caused by Pneumocystis jirovecii, bacterial
infections of the lower respiratory tract, otitis media, and uncomplicated gonorrhoea.
PYRAZINAMIDE
– Active against M. tuberculosis at a low pH, such as that found in phagolysosomes.
– The active form of this antibiotic is pyrazinoic acid, produced when PZA is hydrolyzed
in the liver.
– The mechanism by which PZA exerts its effect is unknown.
ANTIBACTERIAL STEWARDSHIP
Antimicrobial stewardship is of the utmost importance as a way to optimize the use of
antimicrobials to prevent the development of resistance and improve patient outcomes.
o Targeted treatment – Cultures done before antimicrobial therapy to minimize
used of broad-spectrum antibacterial agents reducing the ability of bacteria to
develop resistance
o Inappropriate use of antimicrobial agents- E.g., lack of compliance can result
in development of resistance
o Limit adverse effects- Use of antimicrobial agents as clinically indicated/
recommended duration
 Identify any antibiotic allergies
Further reading
1. Surbhi. L (2011). General principles of antimicrobial therapy. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031442/
2. Peter D. (2015) Antimicrobial chemotherapy Retrieved from
https://www.pdfdrive.com/antimicrobial-chemotherapy-d158223969.html
3. Chanel S.S (2017, 8 June) Mechanisms of antimicrobial action Received from
https://www.youtube.com/watch?v=BGELx7vaYAk