Antibiotics

Classification of
antibiotics
 Definition

Antibiotics are compounds produced by

various species of microorganisms and have
the capability to kill or inhibit the growth of
other microorganisms
 Classification of Antibiotics
Although antibiotics can be classified into
various ways, but the most commonly
antibiotics can be classified according to their
1.Mode of action
2.Mechanism of action
 According to mode of action
• Bacteriostatic
• Bactericidal
 Bacteriostatic
“These inhibit the growth of microorganisms
temporarily. the therapeutic success of
these agents depends upon the participation
of defense mechanism of the host”
The effect may be reversible when the drug
is stopped.
Infection can reoccur in immuno
compromised patient.
 Examples of bacteriostatic
drugs
• Tetracycline
• Sulfonamides
• Clindamycin
• Chloramphenicol
 Bactericidals
“This term is applied to describe those
agents which kill the microbes”
The treatment with bactericidal drugs
become mandatory in case of those
infections that cannot be eradicated by
host defence mechanism.
 Examples of bactericidal
drugs
• Penicillins
• Cephalosporins
• Aminoglycosides
• Monobactams
• However the term bacteriostatic and
bactericidal are relative and not absolute.
As sometimes the prolonged treatment with
or higher doses of bacteriostatic agent can
cause death of microbial population. E.g.,
Chramphenicol and meningiococci
• While bactericidal agents may fail to kill
microbes. E.g.,
Penicillin G and enterococci
According to Mechanism of
Action
Inhibitors of Cell Wall
Synthesis

Inhibitors of Protein
Synthesis

Inhibitors of Nucleic Acid

Synthesis and Functions

Inhibitors of
Metabolism
Inhibitors of cell wall synthesis
Inhibitors of cell wall Β-lactamase
synthesis inhibitors
•Clavulanic acid
•Sulbactam
Β-lactam antibiotics Other antibiotics •Tazobactam

Penicillins Cephalosporins Carbapenems Monobactams

•Meropenam •Aztreonam
•Amoxicillin •Ertapenam
•Ampicillin •Imipenam
•Cloxacillin
•Dicloxacillin
•Methicillin 1st generation 2nd generation 3rd generation 4th generation
•Oxacillin
•Penicillin G •Cefadroxil •Cefaclor •Cefotaxime •Cefepime
•Penicillin V •Cephalexin •Cefamandole •Ceftazidime
•Piperacillin •Cephradine •Cefonicid •Ceftriaxone
•Ticarcillin •Cephalothin •Ceforanide •Cefixime
•Cephaprin •Cefoxitin
•Cefazolin •Cefprozil
β-lactam antibiotics
Penicillins
 Antimicrobial Spectrum of
Penicillins
• Penicillins and its congeners
e.g., penicillin G and penicillin V
These show higher activity against sensitive strains of Gram +ve
Ineffective against Gram –ve bacilli
• Penicillinase resistant penicillin
e.g., methicillin, naficillin, cloxacillin, dicloxacillin, flucloxacillin
Are less potant against penicillin G sensitive MOs but are effective against penicillinase
producing staphylococcus aureus and S.epiderimdis
They are inactive against Gram –ve MOs
• Broad spectrum penicillins
e.g., ampicillin, amoxicillin, becampicillin
Have relatively high anti microbial activity against both Gram +ve and Gram +ve inc.
H.influenzae, E.coli, Proteus mirabilis bacteria but are readily destroyed by β-lactamases
• Extended spectrum penicillins:
e.g., carebenicillin, ticarcillin
Their antimicrobial activity is extended to include Pseudomonas, Enterobacter and
Proteus spp.
• Other extended spectrum penicillins:
e.g., Mezlocillin, Piperacillin
Against Pseudomonas, Klebsiella & other Gram –ve bacteria
• Reversed spectrum:
e.g., Mecillinam, Promicillinam
More Potent against Gram –ve enteric bacteria than against Gram +ve
Hydrolyzed by β-lactamase
• Β-lactamase inhibitors:
e.g., clavulanic acid, Sulbactam, Tazobactam
Most active against plasmid encoded β-lactamases (including the enzymes that
hydrolyze ceftizidime & cefotaxime)but are inactive at clinical achievable conc. against Type
1 chromosomal β-lactamases included in Gram –ve bacilli e.g., Enterobacter,
Acinectobacter & Citrobacter by treatment with 2 nd generation & 3rd generation
cephalosporins
Cephalosporins
 Antimicrobial spectrum of
1st generation: Cephalosporins
Good activity against Gram +ve bacteria & relatively modest activity against Gram –ve
microbes. Also active against Proteus mirabilis, E.coli, and Klebsiella pneumoniae (all Gram -ve)
Alternatively 1st generation cephalosporins are described as drugs which act as penicillin G
substitute that are resistant to Staphylococcal penicillinase & also posses acivity against
P.mirabolis, E.coli, K.Pneumoniae
2nd generation:
Show modest activity against Gram +ve bacteria (less active against gram +ve bacteria of 1st
generationdrugs) and show greater activity against three additional Gram –ve microbes named
Haemophilus influenzae, some Enterobacter aerogenes and some Neisseria spp (i.e., in
comparison to 1stgeneration they have some what increased activity against –ve bacteria)
3rd generation:
Less active against Gram +ve cocci as compared to 1st generation drugs but exhibit much
more activity against Gram –ve bacilli including those mentioned above plus most other
enteric organisms and β-lactamase producing strains.
The drugs of this group have superiority over the other two generations in having access to CNS
4th generation:
Have extended spectrum of activity as compared to 3rd generation and have increased stability
from hydrolysis by plasmid and chromosomally mediated β-lactamases. Aerobic gram –ve
bacilli resistant to 3rd generation agents can be successfully treated with these.
Other β-lactam
Antibiotics
 Antimicrobial spectrum of
Carbapenems

They are broadest-spectrum β-lactam antibiotics currently available.

Imipenam resists hydrolysis by most β-lactamases, but not the metallo-β-lactamases.
The drug plays an important role in emperic therapy, bcz it is active against
penicillinase producing Gram +ve & Gram –ve organisms, anaerobes, and
Pseudomonas aeroginosa (although other pseudomonas strains are resistant, and
resistant strains P.aeroginosa have been reported to arise during therapy)
Meropenam has antibacterial activity similar to that of Imipenam.
 Antimicrobial spectrum of
Monobactams

Aztreonam is primarily active against Enterobacteriaceae but it also acts against

aerobic Gram –ve rods, including P.aeroginosa.
It lacks activity against Gram +ve organisms and anaerobes.
It is resistant to action of β-lactamasaes.
Antimicrobial spectrum of β-
lactamase inhibitors
These contain a β-lactam ring but by themselves, do not have significant antibacterial
activity.
Instead, they bind to and inactivate β-lactamases thereby protecting the antibiotics
that are normally substrates for for these enzymes.
Other inhibitors of cell
wall synthesis
• Vancomycin
• Teicoplanin
• Fosfomycin
• Bacitracin
• Cycloserine
 Antimicrobial spectrum of
Vancomycin
It is bactericidal for Gram +ve bacteria in concentrations of
0.5-10 μg/ml. Most pathogenic Staphylococci, including those
producing β-lactamase and those resistant to naficillin and
methicillin are killed by 4 μg/ml or less.
Vancomycin kills Staphylococci relatively slowly and only if cells
are actively dividing; the rate is less than that of the penicillins
both in vitro and in vivo.
Vancomycin is synergistic with gentamycin and
streptomycin against E.faecium and E,faecalis strains that do
not exhbit high levels of aminoglycoside resistance.
 Inhibitors of Protein synthesis
Protein synthesis
inhibitors

Tetracyclines Aminoglycosides Macrolides

•Demeclocycline •Amikacin •Azithromycin Chloramphenicol

•Doxycycline •Gentamycin •Clarithromycin
•Minocycline •Neomycin •Erythromycin
•Tetracycline •Netilmycin •Telithromycin
•Streptomycin Clindamycin
•Tobramycin

Quinupristin

Linezolid
Tetracyclines
 Antimicrobial spectrum of
Tetracyclines
Broad spectrum, bacteriostatic antibiotics
These are effective against Gram +ve and Gram –ve bacteria as well as other Mos
than bacteria.
It is effective against Chlamydia spp, M.pneumoniae, Borrella burdorferi (a spirochete
that causes lyme disease).
Also effective against Rickettsia rickettsii that causes rocky mountain spotted fever.
Against Vibrio cholerae, Yersinia pestis, Brucella spp.
Against Clostridium perfringens and Clostridium tetani
Aminoglycosides
 Antimicrobial spectrum of
Aminoglycosides
Bactericidal
Aminoglycosides are effective in empirical treatment of
infections suspected of being due to aerobic Gram –ve
bacilli, including Pseudomonas aeroginosa.
To achieve an additive effect, these are combined with
a β-lactam antibiotic, or vancomycin, or a drug active
against anaerobic bacteria.
Aminoglycosides are only effective against aerobic
organisms, bc strict anaerobes lack oxygen-requiring
transport system.these are effective against:
• Brucella spp(gentamycin+doxycycline)
• Streptococcus agalactiae (gentamycin+penicillin G)
• Enterococcus spp (gentamycin+penicillin G)
• Klebsiella spp (gentamycin+an antipseudomonial
penicillin)
• Pseudomonas aeroginosa
(tobramycin+antipseudomonial penicillin)
• Yersinia pestis (streptomycin+doxycycline)
Macrolides
 Antimicrobial spectrum of
Macrolides

Effective against
• Chlamydial spp. (azithromycin, erythromycin)
• Mycoplasma pneumoniae, Ureaplasma urealyticum (erythromycin,tetracycline)
• Treponema pallidum (erythromycin)
• Bordetella pertussis, Campylobacter jejuni, Haemophilus inflenzae, Legionella
pneumophila (azithromycin)
• Corynebacterium diphtheriae (erythromycin)
• Staphylococcus aureus
• Streptococcus pyogenes
• Streptococcus pneumoniae
Chloramphenicol
Antimicrobial spectrum of
Chloramphenicol

It is a broad spectrum antibiotic.

It is active not only against bacteria but also
against other microbes, such as
• Rickettsiae
• Anaerobes (excellent activity)
It is not effective against Pseudomonas
aeroginosa and Chlamydiae
The drug is bacteriostatic (more commonly) or
bactericidal, depending upon the organism.
Clindamycin
Antimicrobial spectrum of
Clindamycin

• Anaerobic bacteria such as Bacteroides fragilis

• Enterococcal Gram +ve cocci
Clostridium difficile is always resistant to Clindamycin.
 Inhibitors of nucleic acid
function or synthesis
Inhibitors of nucleic acid
function or synthesis

DNA-gyrase RNA-polymerase
inhibitors inhibitors

Fluoroquinolones Rifampin

1st generation 2nd generation 3rd generation 4th generation

•Nalidixic acid •Ciprofloxacillin •Gatifloxacin •Trovafloxacin

•Norfloxacillin •Levofloxacin
•Ofloxacin •Moxifloxacin
•Sparfloxacin
Fluoroquinolones
 Antimicrobial spectrum of
fluoroquinolones
Effective against:
• Escherichia coli •Chlamydia trachomatis
•C.psittaci
• Shigella dysenteriae
•C.pneumoniae
• Shigella sonnei •Mycoplasma pneumonia
• Salmonella typhi •Brucella melitensis
• Klebsiella pneumoniae •Brucella abortus
• Enterobacter cloaceae •Brucella swis
•Mycobacterium tuberculosis
• Serratia mercescence
•Mycobacterium kansasii
• Proteus mirabilis •Mycobacterium fortuitum
• Yersinia pestis •Mycobacterium avim
• Haemophilus influenza •Staphylococci
• Legionella pneumophilia •Campylobacter spp
•Neisseria gonorrhoeae
• Pseudomonas aeroginosa
 Inhibitors of metabolism
Inhibitors of
metabolism

Combination of inhibitors
Inhibitors of folate Inhibitors of folate
of folate synthesis and
synthesis (Sulfonamides) reduction
reduction

•Mafenide •Pyrimethamine •Co-trimoxazole

•Silver sulfadiazine •Trimethoprim
•Succinylsulfacetamide
•Sulfadiazine
•Sulfamethoxazole
•Sulfasalazine
•Sulfisoxazole
Sulfonamides
 Antimicrobial activity of
Sulfonamides
Sulfonamides inhibit growth of:
• Gram +ve and Gram –ve bacteria
• Nocardia
• Chlamydia trachomatis
• Some protozoa
• Some enteric bacteria as E.coli, Klebsiella,
Salmonella, Shigella, and Enterobacter
Interestingly, rickettsiae are not inhibited by
sulfonamides but are actually stimulated in their
growth.
Trimethoprim
 Antimicrobial spectrum of
Trimethoprim
Antimicrobial spectrum of trimethoprim
is similar to that of sulfamethoxazole.
However, trimethoprim is twenty to fifty
folds more potent than sulfonamide.
Trimethoprim may be used alone in the
treatment of:
• Acute UTIs
• Bacterial prostitis (although
fluoroquinolones are preferred)
• Vaginitis
Co-trimoxazole
Antimicrobial spectrum of Co-
trimoxazole
Active against
• Pneumocystis carinii
• Haemophilus influenzae
• Legionella pneumoniae
• Eccherichia coli
• Proteus mirabilis
• Salmonella typhi
• Shigella
• Listeria monocytogenes
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