These are umbrella terms for drugs with activity against
They include antibacterials, antivirals, antifungals, and
Chemical Substance m.os./chemical synthesis
kill or inhibit growth of m.os. low concn
Chloramphenicol Streptomyces venezuelae
For example: tetracyclines are active against many gram-
negative rods, chlamydiae, mycoplasmas, and rickettsiae.
For example: vancomycin is active against certain gram-
positive cocci, namely, Staphylococci and Streptococci.
Antibiotics have one of two effects on the growth and viability
Bacteriostatic - slows growth or prevents multiplication; not
the cure; cure results from combined action of drug and host's
defense mechanisms, like phagocytosis.
Bacteriocidal - usually effective only for growing microbes;
ineffective dormant cells.
Penicillins produced by mold Penicillium
Cephalosporins produced by mold Cephalosporium
Bacitracin produced by Bacillus licheniformis
Polymyxins produced by Bacillus polymyxa
Aminoglycosides produced by Streptomyces griseus
Tetracyclines produced by Streptomyces
Chloramphenicol produced by Streptomyces venezuelae
Macrolides - (Erythromycin) produced by Streptomyces erythreus
Rifamycins produced by Streptomyces mediterrani
1. Selective toxicity: against target pathogen but not against host.
LD50 vs. MIC
Therapeutic index: (the lowest dose toxic to the patient divided by the dose
typically used for therapy).
High therapeutic index less toxic
2. Bactericidal vs. Bacteriostatic. (Static rely on normal host defences to kill
or eliminate the patogen after its growth has been inhibited. (UTIs) CIDAL
given when host defenses cannot be relied on to remove or destroy pathogen.)
1. Favorable pharmacokinetics: reach target site in body with effective
2. Spectrum of activity: broad vs. narrow.
3. Little resistance development.
4. Lack of “side effects” allergic, toxic side effects, suppress normal flora.
5. There is no perfect drug
Can be classified as:-
1) Cell wall synthesis inhibition
2) Acting on Cytoplasmic Membrane
3) Protein synthesis inhibition
4) Nucleic acid synthesis inhibition
DRUGS MECHANISM OF ACTION
Bind to receptors (penicillin binding proteins
present on the inner layer of cytoplasmic
membrane) and leads to interference with
the synthesis of peptidoglycan of cell wall.
Cell membrane vulnerable to damage by
solutes of the plasma.
Binds to plasma membrane & disrupts its
structure and permeability properties.
DRUGS MECHANISM OF ACTION
Protein Synthesis Inhibition
A. Inhibitors of
Inactivates DNA-dependent RNA polymerase
thus inhibiting transcription.
B. Inhibitors of
Inhibit 30S ribosome
Inhibit 50S ribosome
Combine with 30S and 50S components of
ribosomes and lead to malfunctioning of
ribosomes. Affects initiation, elongation or
termination of peptide chain leading to
inhibition of protein synthesis and cell dies.
(Streptomycin, kanamycin, amikacin,
tobramycin, tetracycline, doxycycline)
(Erythromycin, Azithromycin, Chloramphenicol
DRUGS MECHANISM OF ACTION
Nucelic Acid Synthesis
Inhibition (Quinolones &
Inhibit DNA gyrase and thus blocking DNA
Inhibit folic acid synthesis by competing with
p-aminobenzoic acid (PABA).
Blocks folic acid synthesis by inhibiting the
enzyme tetrahydrofolate reductase .
Thought to interfere with folic acid synthesis.
Mechanisms of action of antibiotics
Penicillins Polymyxin Streptomycin Nalidixic acid Sulphonamide
Cephalosporins Nystatin Kanamycin Norfloxacin Dapsone
Bacitracin Amphotericin B Amikacin Ciprofloxacin PAS
Vancomycin Neomycin Novobiocin Isoniazid
Cycloserine Tobramycin Metrozidazole Trimethoprim
Bacteriocidal and inhibits
synthesis of cell wall.
Toxicity to humans - has least of
any antimicrobial drug for host
cells, most serious side-effect is
Both natural and semi-synthetic
Common β-lactam ring nucleus for
all penicillins; side groups vary.
Naturals are very narrow spectrum and susceptible to penicillinases, which cleave
the β-lactam ring rendering the drug inactive.
PenicillinV is preferred for oral administration as it is resistant to acid hydrolysis.
Semi-synthetic penicillin’s are designed to:
* increase range of action to include effectiveness against Gram-
negative bacteria (e.g. Ampicillin); or
* resistance to Penicillinases (e.g. Methicillin).
Related to penicillins.
Bacteriocidal and their MOA is similar to
Broad spectrum (active against both Gram
positive and Gram negative).
Cephalosporins Antibacterial spectrum
Cephalexin, Cephaloridine, Cefadroxil,
Cepharadine, Cephalothin, Cephazolin
Staph. aureus, Streptococci (other than
enterococci), E. coli, Klebsiella, Proteus mirabilis
and H. influenzae
Cefamandole, Cefoxitin, Cefuroxime,
Cefonicid, Ceforanide, Cefaclor, Cefprozil,
Cefmetazole, Cefotetan etc.
First generation spectrum and Proteus,
Enterobacter, Citrobacter, Serratia and Gram
Cefotaxime, cefoperazone, ceftizome,
ceftazidime, Ceftriaxone, Cefixime,
Ceftibuten, Cefpodoxime etc.
Second generation spectrum and N. gorrhoeae
including beta lactamase producing strains, Ps.
Cefepime, Cefpriome, Ceftaroline,
Third generation spectrum including enhanced
activity against Enterobacter and Citrobacter
spp. that are resistant to third generation
Act as cationic detergents; integrate
within & disrupt outer membrane.
Causes loss of osmotic function &
selective membrane permeability.
Unique in being Bacteriocidal in absence
of cell growth.
More effective against gram negatives
than gram positives (due to more LPS in
Toxicity - damages kidneys
Toxicity - occasional rashes,
platelet decrease & some
decline in liver function may
Imparts an orange color to
urine and sweat.
MAO is by inhibiting protein synthesis of
Side effects: nephron- and oto-toxicity
MAO is by inhibiting protein synthesis of bacteria.
Broad-spectrum; inhibits only rapidly multiplying bacteria
Highly effective against rickettsial and chlamydial
Problems with tetracyclines are:
1. inhibition of normal flora leads to "superinfection“
2. weakening of bone structure (esp. true in growing
3. photosensitivity in some hosts.
Example: Tetracycline, Doxycycline, Minocycline
MAO is by inhibiting protein
synthesis of bacteria.
Less effective than penicillins,
yet good alternative in cases of
Problem - numbers of resistant
mutants arise with use.
Binds and inhibits activity of DNA gyrase.
Bacteriostatic & Bacteriocidal.
p-aminobenzoic acid (PABA) is the substrate in the essential synthesis of
folic acid in most bacteria.
Sulfonamides are structural analogs of PABA; act as competitive
No effect on human cells; we cannot synthesize folic acid, but rather
obtain folic acid in diet.
Inhibits conversion of dihydrofolic acid to tetrahydrofolic acid.
Refers to development of resistance to an antimicrobial agent by
Emergence of resistance in bacteria ordinarily susceptible
to antimicrobial agents by acquiring the genes coding for
Most of AMR shown by bacteria belongs to this group.
Infection caused by resistant microorganisms often fail to
respond to the standard treatment, resulting in
Higher healthcare expenditures
Greater risk of death
Overuse and misuse of antimicrobial agents single most
important cause of development of acquired resistance. (natural
Resistant bacterial populations flourish in areas of high
antimicrobial use where they enjoy a selective advantage over
Resistant strains then spread in the environment and transfer the
genes coding for resistance to other unrelated bacteria.
Other factors favouring AMR
Poor infection control practices in hospitals
▪ e.g. Poor hand hygiene practices facilitate transmission of resistant
Inadequate sanitary conditions
Irrational use of antibiotics by doctors not following AST
Uncontrolled sale of antibiotics over the counters without
Refers to the innate ability of a bacterium to resist a class of
antimicrobial agents due to its inherent structural or functional
characteristics, (e.g. Gram negative bacteria resistant to
In +ce of selective antibiotic pressure, bacteria acquire new genes
by two methods:-
Transferrable drug Resistance
Resistance developed due to mutation of the
E.g. Mycobacterium tuberculosis – ATT
Usually, Low level resistance, developed to one drug
at a time-overcome by using combination of different
classes of drugs.
is plasmid coded - transferred by
conjugation or rarely transduction, transformation.
Resistance coded plasmid (called R plasmid) –
carry multiple genes,
each coding for resistance to one class of antibiotic.
Results in high degree of resistance to multiple drugs, which
cannot be overcome by using combination of drugs.
Mutational drug resistance Transferable drug resistance
1 Resistance to one drug at a
Multiple drug resistance at the
2 Low-degree resistance High-degree resistance
3 Resistance can be overcome by
combination of drugs
Cannot be overcome by drug
4 Virulence of resistance mutants
may be lowered
Virulence not decreased
5 Resistance is not transferable
to other organisms but
spread to off- springs by
vertical spread only
Resistance is transferable to
Spread by: Horizontal spread
(conjugation, or rarely by
Decreased Permeability across the Cell Wall :
Bacteria modify their cell membrane porin channels - either in
frequency, size, or selectivity Preventing the antimicrobials from
entering into the cell.
Seen in Pseudomonas, Enterobacter and Klebsiella species against drugs,
such as imipenem, aminoglycosides and quinolones.
Mediate expulsion of the drugs from the cell - thereby preventing the
intracellular accumulation of drugs.
Escherichia coli and other Enterobacteriaceae against tetracyclines,
Staphylococci against macrolides and streptogramins
Staph aureus and Strept pneumoniae against fluoroquinolones.
By Enzymatic Inactivation :
β lactamase enzyme production - It breaks down the β lactam rings
inactivating the β lactam antibiotics.
Aminoglycoside modifying enzymes - destroy the structure of
Chloramphenicol acetyl transferase - destroys the structure of
By Modifying target sites:
MRSA -Target site of penicillin i.e. penicillin binding protein (PBP)
gets altered to PBP-2a.
Streptomycin resistance in Mycobacterium tuberculosis- due to
modification of ribosomal proteins or 16S rRNA.
Rifampicin resistance in Mycobacterium tuberculosis- due to
mutations in RNA polymerase.