Professional Documents
Culture Documents
21oct Copy 150118071331 Conversion Gate02 PDF
21oct Copy 150118071331 Conversion Gate02 PDF
Presentation by:
Saurav Chandra Sarma
Int. Ph.D NCU 3rd Sem.
Outline
• What is Antibiotic???
• Bacterial cell structure
1
Bacteriostatic Bactericidal
Based on their
spectrum of
action
Narrow
Broad-spectrum
Spectrum
Source: Google Images
Types of Antibiotics
(Based on their mode of action)
Bacteriostatic Antibiotics Bactericidal Antibiotics
• Tetracyclines • Penicillins
• Spectinomycin • Cephalosporins
• Sulphonamides • Fluoroquinolones
• Macrolides (Ciprofloxacin)
• Chloramphenicol • Glycopeptides (Vancomycin)
• Trimethoprim • Monobactams
• Carbapenems
Types of Antibiotics
(Based on their structural similarities)
Antibiotics: Mode of Action
•Inhibitors of DNA synthesis
β-lactam ring
•Cephalosporins
--Cephamycins
--Carbapenems
--Oxacephalosporins
--β-Lactamase inhibitors
--Monolactams
Beta-Lactam Structure
How do they work?
1. The β-lactam binds to Penicillin Binding
Protein (PBP)
2. PBP is unable to crosslink peptidoglycan
chains
3. The bacteria is unable to synthesize a stable
cell wall
4. The bacteria is lysed
Mechanism of β-Lactam Drugs
• The amide of the β-lactam ring is unusually
reactive due to ring strain and a conformational
arrangement which does not allow the lone pair of
the nitrogen to interact with the double bond of
the carbonyl.
• β-Lactams acylate the hydroxyl group on the serine
residue of PBP active site in an irreversible manner.
• This reaction is further aided by the oxyanion hole,
which stabilizes the tetrahedral intermediate and
thereby reduces the transition state energy.
Discovery of Penicillin(First beta-
lactam drug)
•Discovered in 1928.
• While working in his lab, trying to kill a deadly bacteria,he noticed a
blue mold growing on the dish
•Learned that it was the mold Penicillum Notatum.
•Penicillin is found in this mold.
•Noticed that the bacteria around the mold was dissolving.
Source: Google Images
How it is was Developed
Ampicillin R=Ph
Amoxicillin R= Ph-OH
Ampicillin
EFFECTIVE AGAINST:
• Gram positive + Gram negative
bacteria
TREATMENT FOR:
• Ear infection
• Sinusitis
• Urinary tract infections Ampicillin
• Meningitis +
CHARACTERISTICS:
• Broad spectrum
• Can be given orally and
parenterally
Sulbactam
• Prone to beta-lactamase
ll
Unasyn
Amoxicillin
EFFECTIVE AGAINST:
• Gram positive + Gram negative
bacteria
TREATMENT FOR:
• Skin infection
• Sinusitis
• Urinary tract infections
• Streptococcal pharyngitis Amoxicillin
CHARACTERISTICS: +
• Broad spectrum
• Can be given orally and parenterally
• Prone to beta-lactamase
SIDE-EFFECTS:
• Rash, diarrhea, vomiting, nausea, Clavulanic Acid
edema, stomatitis, and easy
fatigue.
ll
Augmentin
Anti-Staphylococcal Penicillin
Methicillin
EFFECTIVE AGAINST:
• Gram positive bacteria
TREATMENT FOR:
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given parenterally
SIDE-EFFECT:
• Interstitial nephritis
Oxacillin
EFFECTIVE AGAINST:
• Gram positive bacteria
TREATMENT AGAINST:
• penicillin-resistant Staphylococcus
aureus
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given parenterally
SIDE-EFFECT:
• Hypersensitivity and local reactions
• In high doses, renal, hepatic, or
nervous system effects can occur
Nafcillin
EFFECTIVE AGAINST:
• Gram positive bacteria
TREATMENT AGAINST:
• Staphylococcal infections
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given parenterally
SIDE-EFFECT:
• Allergic reactions
• Nausea and vomiting
• Abdominal pain
Cloxacillin
EFFECTIVE AGAINST:
• Staphylococci that produce
beta-lactamase
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given orally
SIDE-EFFECT:
• Allergic reaction
Dicloxacillin
EFFECTIVE AGAINST:
• Gram positive bacteria +
Staphylococci that produce beta-
lactamase
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given orally
SIDE-EFFECT:
• Allergic reaction
• Diarrhoea, nausea, rash, urticaria
pain and inflammation at
injection site
Flucloxacillin
EFFECTIVE AGAINST:
• Gram positive bacteria +
Staphylococci that produce beta-
lactamase
CHARACTERISTICS:
• Very narrow Spectrum
• Should be given orally
SIDE-EFFECT:
• Allergic reaction
• Diarrhoea, nausea, rash, urticaria
pain and inflammation at
injection site
Anti-Pseudomonal Penicillin
Piperacillin
EFFECTIVE AGAINST:
• Gram positive +Gram negative
CHARACTERISTICS:
• Extended Spectrum
• Should be given
by intravenous or intramuscular injection
SIDE-EFFECT:
• Hypersensitivity
• Gastrointestinal
• Renal
• Nervous system
*Piperacillin+Tazobactam=Zosyn
Carbenicillin
EFFECTIVE AGAINST:
• Gram negative + Limited Gram
positive
TREATMENT FOR:
• Urinary tract infections
CHARACTERISTICS:
• Highly soluble in water and acid-
labile
SIDE-EFFECT:
• High doses can cause bleeding
• Hypokalemia
Ticarcillin
EFFECTIVE AGAINST:
• Mainly gram negative bacteria
particularly Pseudomonas aeruginosa
TREATMENT FOR:
• Stenotrophomonas maltophilia
infections
CHARACTERISTICS:
SIDE-EFFECT:
• Diarrhoea
• Bleeding
• Fever
• Fainting
Cephalosporin
These has been conventionally classified into four
generations based on Generation system
Cefalothin Cefalexin
Cefadroxil Cefazolin
Second Generation Cephalosporins
Cefuroxime(Oral) Cefotetan
Third Generation Cephalosporins
Cefotaxime Ceftriaxone
Ceftazidime
Fourth Generation Cephalosporins
Cefepime
Carbapenem
What are carbapenems
• Carbapenems are a class of beta-lactam
antibiotics with a broad spectrum of
antibacterial activity. They have a structure
that renders them highly resistant to beta-
lactamases. Carbapenem antibiotics were
originally developed from thienamycin, a
naturally-derived product of Streptomyces
cattleya.
Dr.T.V.Rao MD 57
Carbapenems common uses
• Imipenem
– Broad spectrum, covers Gram-positive, Gram-negative
(including ESBL-producing strains), Pseudomonas and
anaerobes
• Meropenem
– Less seizure-inducing potential, can be used to treat CNS
infections
• Ertapenem
– Lacks activity vs. Acinetobacter and Pseudomonas
– Has limited activity against penicillin-resistant
pneumococci
Dr.T.V.Rao MD 58
Imipenem
EFFECTIVE AGAINST:
• Aerobic and anaerobic, Gram
positive and gram negative
bacteria
CHARACTERISTICS:
• Broad Spectrum
• Intravenous
• Resistant to beta-lactamase
enzymes
SIDE-EFFECT:
• Seizuregenic at high doses
Meropenem
EFFECTIVE AGAINST:
• Aerobic and anaerobic, Gram
positive and gram negative
bacteria
CHARACTERISTICS:
• Ultra Broad Spectrum
• Intravenous
• Resistant to beta-lactamase
enzymes
SIDE-EFFECT:
• Diarrhoea
• Vomiting
• headache
Ertapenem
EFFECTIVE AGAINST:
• Gram positive and gram negative
bacteria
CHARACTERISTICS:
• Broad Spectrum
• Intravenous
• Resistant to beta-lactamase
enzymes
• Not active against MRSA
SIDE-EFFECT:
• Convulsions
• Seizures
• headache
Monobactam
Aztreonam
EFFECTIVE AGAINST:
• Gram positive +Gram
negative+Anaerobic bacteria
CHARACTERISTICS:
• Broad Spectrum
• Intravenous
• Resistant to beta-lactamase
enzymes
• Not active against MRSA
SIDE-EFFECT:
• Diarrhoea
• Nausea
• Vomiting
BETA-LACTAMASE INHIBITORS
What is Resistance?
Acquired Resistance:
•It is the development of resistance by an organism which was sensiive before
due to the use of antimicrobial agent over a period of time.
•This can happen with any microbe and is a major clinical problem.
However, the development of resistance is dependent on the microorganism
as well as the drug.
MECHANISMS OF RESISTANCE
Porins
Altered penicillin binding proteins
b-lactamases
MECHANISMS FOR ACQUIRING
RESISTANCE
69
CHALLENGES OF b-LACTAMASES
1940 : Introduction of penicillins
1940 : First description of b-lactamases published
1944 : Strains of staphylococcus aureus producing
b-lactamase
1960s : Clinical use of expanded spectrum penicillins
- such as ampicillin and carbenicillin
1970s : plasmid mediated b-lactamases assumed prominence in
enterobacteriaceae and gram-negative bacteria
1980-90 : Development of broad-spectrum cephalosporins, cephamycins,
monobactams and carbapenems
1990 : Increased resistance among gram-negative bacteria with inducible
chromosomally-mediated b lactamases
JAC (1993); suppl A: 1-8
Beta–lactamases
Beta-Lactamase Enzyme
Functional
Classification
Group 1 Group 4
(Cephalosporinases*) (Penicillinases*)
Group 2 Group 3
(Penicillinases,
(Metalloenzymes*)
Cephalosporinases)
Molecular
Classification
Metallo
Serine Based
B-lactamases
Molecular
Classification
Metallo
Serine Based
B-lactamases