Antibacterial

Waksman

proposed the widely cited definition that “an antibiotic is a substance produced by microorganisms, which has the capacity of inhibiting the growth and even destroying other microorganisms

Waksman

isolated Streptomycin from Streptomyces griseus

Dubois

responsible for the isolation of the antibacterial antibiotic Tyrocidin

Bacillus brevis

Tyrocidin came from the soil bacterium

• product of metabolism

• synthetic product produced as a structural analog of a naturally occurring antibiotics

• antagonizes growth or survival of one or more species of microorganisms

• effective in low concentration

• narrow spectrum

• bactericidal

• very selective mode of action

• low serum protein binding

• widely distributed especially in the CNS

• excreted by the kidneys

A product is considered antibiotic if these conditions are met

• bacteriostatic

• bactericidal

types of activity of antibiotics

narrow spectrum

acting only on a single or limited group of microorganisms

broad spectrum

affects a wide variety of microorganism species

Beta lactam antibiotics

can be destroyed by acylases and beta lactases

• penicillins

• beta lactamase inhibitors

• cephalosporins

• monobactams

Classification of beta lactam antibiotics

penicilins

MOA: selective inhibition of bacterial cell wall synthesis

transpeptidase enzyme

catalyzes the nucleophilic carbonyl substitution process required for the cross-linking of the peptidoglycan in bacterial cell walls.

penicillin-binding proteins

the cross linking reaction if catalyzed by a class of transpeptidase known as

D-Ala-D-Ala

β-lactams mimic the structure of the__________ link and bind to the active site of PBPs, disrupting the cross-linking process.

rash or itching, delayed CV collapse or shock

allerginicity to penicillins can manifest as

allergy

______ to penicillin occurs due to penicilloic acid reacting with lysine-amino group forming of PENCILLOYL PROTEINS

• natural

• antistapylococcal

• amino

• extended-spectrum
  

classification of penicillins

natural penicillins

• highly active against gram-positive cocci

  • very susceptible to B-lactamases

natural

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

Pen G

natural

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

Pen V

True

True or false

In natural penicillins, the inclusion of a side chain R-group that is Electron withdrawing group decreases the electron density of the side chain carbonyl and protects these penicillins from acid degradation.

V, G

Penicillin is more acid resistant than Penicillin __ since it contains an electronegative oxygen in the side chain

injection

if a ntural penicillin is not atleast partially acid resistant, then it can only be useful by

Pen G

benzylpenicillin

Pen V

phenoxymethylpenicillin

Pen V

natural penicillin that is administered orally

Pen G

natural penicillin that is administered through IV

Pen G

Pen V

penicillin

Pen G

Inactivated by the gastric juice and are not effective when administered orally unless antacid or buffer is taken along with

• Penicillin G procaine

• Penicillin G benzathine

Pen G salts

Pen V

• Resistance to hydrolysis by gastric juice

• It is able to form uniform concentration with blood

  • Very soluble in water

anti-staphylococcal

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

methicillin

anti-staphylococcal

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

oxacillin

anti-staphylococcal

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

cloxacillin

anti-staphylococcal

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

dicloxacillin

• oxacillin

• cloxacillin

• dicloxacillin

isoxazolyl penicillins

anti-staphylococcal penicillins

resistant to B-lactamase enzymes

anti-staphylococcal

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

nafcillin

methicillin

anti-staphylococcal penicillin that may cause nephrotoxicity and interstitial nephritis

nafcillin

may be used in infections caused solely by penicillin g-resistant staphylococci or when streptococci are also present

oxacillin

may be hepatotoxic and can cause bleeding

True

true or false

Penicillinase resistant penicillin, in general, there should be a increase in the steric hindrance at the α-carbon of the acyl group

True

true or false

• Oxacillin, Cloxacillin, and Dicloxacillin, in which a substituted isoxazoyl ring, diortho-substituted aromatic rings, naphthyl ring systems are used as a bioisosteric replacement for the benzyl group in Penicillin G.

• Thus, these are less potent against bacteria that do not produce β lactamase, but are effective against those that do.

methicillin

nafcillin

oxacillin

cloxacillin

dicloxacillin

aminopenicillins

These antibiotics are orally active, and have a broader spectrum than Penicillin G, but are quite susceptible to β lactamases, they are often given with Clavulanic acid to avoid enzymatic degradation.

amino

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

amoxcillin

amino

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

ampicillin

ampicillin

amoxicillin

extended spectrum penicillins

They are susceptible to β lactamases that is why they are usually combined with another drug “β lactamase inhibitors”

• Pseudomonas aerginosa

• Enterobacter

• Proteus

• Klebsiella

• other gram negative bacteria

extended spectrum penicillins have extended activity against what microorganisms

• Carbenicillin

• Ticarcillin

carboxypenicillins

extended spectrum

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

carbenicillin

extended spectrum

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

ticarcillin

extended spectrum

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

mezlocillin

extended spectrum

identify the classification of the penicillin (natural, anti-staphylococcal, amino, extended-spectrum)

azlocillin

• mezlocillin

• azlocillin

ureidopenicillins

carboxypenicillin

•  contains Carboxylate moiety in the sidechain portion of the molecule that enhances their activity against gram negative bacteria

ureidopenicillin

• contains the Acylureido group that mimics the peptidoglycan chain that enhances activity against gram negative bacteria

• Class 1

• Class 2

classification of beta lactamase inhibitors

Class 1 inhibitors

• Prolongs inactivation of the enzyme

• Commonly used with extended spectrum penicillin and beta lactamase-sensitive penicillins

Class 1

identify the classification of the beta-lactamase inhibitor

sulbactam

Class 1

identify the classification of the beta-lactamase inhibitor

clavulanic acid

Class 1

identify the classification of the beta-lactamase inhibitor

tazobactam

Augmentin

amoxicillin + clavulanic acid

Timentin

ticarcillin + clavulanic acid

unasyn

ampicillin + sulbactam

zosyn

piperacillin + tazobactam

Class 1

identify the classification of the beta-lactamase inhibitor

amoxicillin + clavulanic acid

Class 1

identify the classification of the beta-lactamase inhibitor

ticarcillin + clavulanic acid

Class 1

identify the classification of the beta-lactamase inhibitor

Ampicillin + sulbactam

Class 1

identify the classification of the beta-lactamase inhibitor

Piperacillin + tazobactam

Class 2 inhibitors

Possess potent antibacterial activity in addition to its ability to cause transient inhibition of some beta-lactamases

Class 2

identify the classification of the beta-lactamase inhibitor

carbapenems

Class 2

identify the classification of the beta-lactamase inhibitor

monobactam

Class 2

identify the classification of the beta-lactamase inhibitor

theinamycin

Class 2

identify the classification of the beta-lactamase inhibitor

meropenem

Class 2

identify the classification of the beta-lactamase inhibitor

biapenem

theinamycin

isolated from Streptomyces cattleya

Imipenem

first ever marketed theinamycin

meropenem

•  exhibits greater potency against gram negative and anaerobic bacteria than imipenem does, but is slightly less active against most gram positive

biapenem

•  the strongest for gram negative, gram positive, and anaerobes.

7-aminocephalosporanic acid

Cephalosporin

• Isolated from Cephalosporium acremonium which inhibits the growth of a variety gram positive and gram negative

dihydrothiazine ring

• Cephalosporin is a close congener of Pen, which contains the

3-acetoxylmethyl group

• The most reactive site with acetoxyl group undergoing solvolysis inacid medium

• Acylases

1st and 2nd gen

(cephalosporin)

gram +

3rd gen

(cephalosporin)

gram +, gram -

4th gen

(cephalosporin)

pseudomonas

5th gen

(cephalosporin)

MRSA

1st gen cephalosporin

The optimum activity of all first generation cephalosporin drugs is against gram-positive bacterias such as Staphylococci and Streptococci.

Cephradine

the ONLY cephalosporin derivative that is available in oral and parenteral preparation

Cefadroxil

prolonged DOA, Once a day dosing

Cephalexin

acid-stable