TOPIC OBJECTIVES

At the end of the session, the student should be able to:

▪ Classify the different antibiotics.
▪ Identify the mechanism of action involved in each class of antibiotics.
▪ Enumerate examples from each class of antibiotics and give the uses
 WATCH THESE VIDEOS:

What causes antibiotic resistance? - Kevin Wu

How antibiotics work

How can we solve the antibiotic resistance crisis? - Gerry Wright

 HISTORY OF
ANTIBIOTICS

▪ 1929- Fleming – discovered P. notatum

▪ 1938- Florey and Chain – isolated and introduced penicillins in therapy
▪ Pasteur and Joubert – discovered that anthrax culture were killed by another living organism-
antibiosis
▪ 1942- Waksman – gave the formal definition
 ANTIBIOTICS
Substance produced by microorganisms which has the capacity to inhibit even destroy other
microorganism
Modern definition:
– A product of metabolism
– Synthetic product produced by living organism as structural analog of a naturally occurring
antibiotic
– Effective in low concentration

A. According to spectrum of activity:

– Broad Spectrum
– Narrow spectrum
B. According to action:
– Bactericidal
– Bacteriostatic
ANTIBIOTICS
A. According to spectrum of activity:

The scope of a drug to kill or suppress the growth of microorganisms.

Narrow-spectrum: The drugs that only act on one kind or one strain of bacteria.

Broad-spectrum: The drugs that have a wide antimicrobial scope.

ANTIBIOTICS
B. According to action:

BACTERIOSTATIC
Drugs which arrest the growth and replication of bacteria at serum urine levels achievable in the
patient, thus limiting the spread of infection until the immune system attacks, immobilizes, and
eliminates the pathogen.

BACTERICIDAL
Drugs which kill bacteria at drug serum levels achievable in the patient.
ANTIMICROBIAL
RESISTANCE

DRUG RESISTANCE
The susceptibility of pathogenic MOs to drugs
becomes lower or even loses after contact with the
drug many times.

CROSS RESISTANCE
When the bacteria show resistance to one drug, they
are also resistant to some other drugs.

‹#›
‹#›
CELL WALL
SYNTHESIS INHIBITORS

BETA LACTAMS
GLYCOPEPTIDES
BACITRACIN

‹#›
 BETA LACTAMS
- The active component
- Cyclic amide with four atoms in its ring
- When fused with 5-membered thiazolidine ring it produces PENICILLIN
- When fused with 6-membered dihydrothiazine ring it produces CEPHALOSPORIN
 BETA LACTAMS
MECHANISM:

PBPs – these are the beta-lactam receptors

PBP 1 – cell lysis (amoxicillin, cephalosporin)
PBP 2 – non-rigid, oval-shaped cells, no cell division (methicillin and cefotaxime)
PBP 3 – long, filamentous-shaped (mezlocillin and cefuroxime)
PBP 4 – 6 no lethal effects

❑ Selectively and irreversibly inhibits the enzymes processing the developing peptidoglycan layer.
❑ Autolysins cleave the N-acetylmuramic acid-peptide bond to L-ala.
BETA LACTAMS

Beta Lactam ring mimics the shape of the terminal D-Ala-D-Ala peptide sequence that serves as the
substrate for cell wall transpeptidases that form covalent bonds between different peptidoglycan chains during
periods of cell growth.

‹#›
 BETA LACTAMS
HYPERSENSITIVITY REACTION

❑ Beta lactam ring produces an inactive penicilloic acid

ALLERGENICITY:
- Rash or itching, or delayed onset CV collapse or shock
- Due to penicilloic acid reacting with lysine-amino group forming Penicilloyl proteins.

❑ Beta lactams are also acid sensitive, and degrade at low pH by a more complex mechanism.
 BETA LACTAMS
INACTIVATION CAUSED BY BACTERIAL ENZYME

Beta lactams form allergenic haptens in vivo.

PENICILLINASES
1. B-lactamases are group of enzymes specifically designed to degrade and inactivate beta lactam
antibiotics by directly attacking the beta lactam bond which leads to ring opening and inactivating the
antibiotic.
BETA LACTAMS
INACTIVATION CAUSED BY BACTERIAL ENZYME

2. Acylases are also a variety enzymes that have been isolated from some bacteria, and
these enzymes cleave the acylamino sidechain of the antibiotic inactive
 BETA LACTAMS
PROTEIN BINDING

due to lipophilic structures

Nafcillin is the most protein bound (90%)

Amoxicillin and Ampicillin – 25 – 30%

Acylamino side chain-responsible for protein binding

BETA LACTAMS
RESISTANCE OF BACTERIA

production of beta lactamases

mutation of PBP's to a form with lower affinity for
the antibiotic
decreased permeability of the cell wall to beta
lactams
Presence of efflux pump
 BETA LACTAMS
RESISTANCE OF BACTERIA

PORINS
The opening in porins is too small to allow diffusion of large molecules, such as vancomycin (resulting
in an inherent or intrinsic form of gram-negative resistance against glycopeptide antibiotics.
Some gram-negative bacteria express porins having an altered pore structure that does not
permeation of smaller drugs (such as beta-lactams or carbapenems).
Peptidoglycan is absent
Some bacteria (e.g. mycobacteria) lack a cell wall, and can multiply in the presence of β-lactam
antibiotics, potentially resulting in serious infection (e.g. atypical pneumonia).

‹#›
 PENICILLINS
CLASSIFICATION OF PENICILLINS:
Natural Penicillins
Penicillinase-Resistant Penicillins
Aminopenicillins
Anti-pseudomonal Penicillins

ALEXANDER FLEMING
Discoverer of Penicillum notatum
 NATURAL
PENICILLINS
Natural penicillin are Pen G and Pen V which are highly active against gram (+) cocci

Unit of activity is based on the antibiotic activity of 0.5µg of USP Pen G RS

◦ 1 mg PEN G Na = 1,667 U
◦ 1 mg of PEN G - 1,530 U
◦ 1 mg of PEN Procaine – 1,009 U
NATURAL
PENICILLINS
Degradation may be due to water, alkaline or acid solutions and enzymes
In basic media penicilloic acid penilloic acid
In acid media penicillamine, penilloic acid and penilloaldehyde
These solutions should not be exposed to sources of metal ions (accelerate the chemical degradation
process
Degradation reactions can be retarded clinically by buffering solution of penicillins between pH 6.0
and 6.8.
Refrigerate or use promptly
Use inert plastics for lid of containers
PENICILLINASE RESISTANT
PENICILLINS
Antistaphylococcal Penicillins

❑These are less potent against bacteria that do not produce beta lactamase, but are effective against
those that do.
❑They are sufficiently acid stable to be taken orally.

Examples:
1) Methicillin
2) Nafcillin
3) Oxacillin
4) Cloxacillin
5) Dicloxacillin

Use: Infection by β-lactamase producing staphylococci

PENICILLINASE RESISTANT
PENICILLINS

Adverse Effects:

Methicillin may cause nephrotoxicity and interstitial nephritis.

Oxacillin may be hepatotoxic.
All inhibit platelet aggregation, which may result in bleeding.

Isoxazolyl penicillins are eliminated by both kidney and biliary excretion.

* no dosage adjustment is required in renal failure

AMINOPENICILLINS
Broad spectrum penicillin

Antimicrobial activity include such gram (-) microorganisms such as H. influenzae, E. coli and P.
mirabilis.

Includes:
Ampicillin
Amoxicillin
Cyclacillin
Bacampicillin
AMINOPENICILLINS
❑ Ampicillin and amoxcillin are the most commonly associated with drug-induced rash and
diarrhea.

❑ Ampicillin is equivalent in activity to Pen G, widely used for out-patients for uncomplicated
community –acquired UTI.

❑ Amoxcillin – more acidic better oral absorption enhanced blood levels, less GI disturbance.
Antimicrobial activity and spectrum similar to ampicillin.
ANTIPSEUDOMONAL
PENICILLINS

Activity is extended against Pseudomonas, Enterobacter and Proteus sp., klebsiela sp. and other
gram (-) microorganisms.

Includes:
Carbenicillin
Ticarcillin
Mezlocillin
Piperacillin

* effective against Klebsiella pneumoniae

- Generally used in combination with an aminoglycoside for pseudomonal infections.
BETA LACTAMASE
INHIBITORS

❑ Used to produced synergistic activity against resistant strains

❑ Inhibits the enzymes that inactivates or hydrolyzes the lactam ring resulting to inactivation

Classified to:
– Class I
– Class II
• Amoxicillin + Clavulanic acid
Augmentin®

Unasyn® • Ampicillin + Sulbactam

• Piperacillin + Tazobactam
Piptaz®
BETA LACTAMASE
INHIBITORS

Class I inhibitors
▪ Prolongs inactivation of enzymes
▪ Used with extended-spectrum spectrum and β-lactamase-sensitive penicillins
▪ Sulbactam, clavulanic acid and tazobactam

Class II inhibitors
▪ possess potent antibacterial activity in addition to its ability to cause transient inhibition of some β-
lactamases
▪ Carbapenem, Monobactams
CLASS I β LACTAMASE
INHIBITORS

1. Clavulanic acid – naturally occurring, from S. clavuligeris

Has weak antibacterial activity
Combined with Amoxicillin for skin, respiratory, ear and UTI
Combined with Ticarcillin for septicemia, lower RTI and UTI
CLASS I β LACTAMASE
INHIBITORS
2. Sulbactam
– Has weak antibacterial activity but potentiates activity of
ampicillin and carbenicillin against β-lactamase
producing staphylococcus and enterobacteriaceae
– Non-synergistic with Carbenicillin
– Sulbactam + Ampicilln- Sultamicillin (Unasyn)
 CLASS I β LACTAMASE
INHIBITORS
3. Tazobactam
– More potent than sulbactam, slightly broader in spectrum than clavulanic acid, weak antibacterial
activity
– With piperacillin for appendicitis, post-partum endometriosis and pelvic-inflammatory infections
CLASS II β LACTAMASE
INHIBITORS
A. CARBAPENEMS
Imipenem, Meropenem, Ertapenem

Imipenem
– penetrates bacterial porins well, and is stable to and inhibitory for many beta lactamases.
– It is not orally active
– with cilastin sodium, an inhibitor of renal dehydropeptidase 1, which attacks and inactivates
imipenem.
 CLASS II β LACTAMASE
INHIBITORS
B. MONOBACTAMS

❑ Sulfacezin, Aztreonam
❑ A product of fermentation of unusual microorganisms
– Aztreonam is the only important example.
– It is a totally synthetic parenteral antibiotic which is active almost entirely against gram negative
bacteria.
– Its mechanism is similar to the penicillins
 CEPHALOSPORINS
Derivatives of 7- amino-cephalosporanic acid and are closely related in structure to penicillin.
Isolated from Cephalosporium sp.
C. acremonium which inhibits the growth of a variety g(+) and g(-)
Cephalosporins is appended to a 6 rather than a 5 membered ring, the system is less strained
and hence less reactive.
 CEPHALOSPORINS
MOA:
▪ It inhibit bacterial cell wall synthesis, reducing cell wall stability, thus causing membrane lysis.
▪ The cephalosporins are considered broad-spectrum antibiotics
▪ exhibit uniquely potent activity against most species of Klebsiella pneumoniae (causative agent of
sepsis and pneumonia)

GENERATION GRAM (+) GRAM (-)

First +++ +

Second +++ ++

Third + +++

Fourth ++ ++++
 CLASSES OF
CEPHALOSPORINS
GENERATION Examples
1st Generation 2X- Cefalexin, Cefadroxil
1 Z- Cefazolon
2 IN- Cefalothin, Cefaparin
DINE- Cephradine
2nd Generation ceFURoxime, CeFOXitine, CeFORanide, ceFONicid, cefoTEtan,
cefMandole, cefMetazole
3rd Generation Cefotaxime, ceftizoxime, ceftriaxone, ceftazidime, cefoperazone,
cefixime, cefpodoxime, cefdinir, ceftibuten, ceftamet, Moxolactam
4th Generation CefePime, CefePirome
5th Generation Ceftobiprole, Ceftaroline
 CEPHALOSPORINS
Susceptible cephalosporins can be hydrolyzed by beta lactamases, and in fact some beta
lactamases are more efficient at hydrolyzing cephalosporins than penicillin itself.

◦ Cephalotin and cefoxitin are the most resistant to beta lactamase

◦ Cephaloridine and cefazolin are the least resistant to beta lactamase

It causes cross sensitivity with penicillin.

Allergic reactions are not as common in this chemical class as in the penicillin class.

Cephalosporins are taken orally.

• Cephradine is the ONLY cephalosporin derivative that is available in oral and parenteral preparation
 INDICATION OF
CEPHALOSPORINS
GENERATION USES

1st Gen ▪ G (+) and G (-) infections in px with mild allergy

▪ Serious Klebsiella infection
▪ Cefazolin- Surgical prophylaxis
2nd Gen ▪ UTI (E.coli)
▪ Cefaclor- Otitis media
▪ Cefuroxime- Community Acquired Pneumonia
3rd Gen ▪ Can penetrate the CSF
▪ Meningitis
▪ Sepsis (unknown cause)
▪ Empiric therapy for life threatening condition
4th Gen ▪ Pneumonia
▪ Skin infections
▪ Empiric therapy for neutropenic patients
▪ Most resistant to Beta lactamase
 ADVERSE EFFECTS
OF CEPHALOSPORINS

Generally non-toxic, with high degree of selective toxicity.

Allergy and hypersensitivity reactions are the most common
Hypoprothrombinemia
Intolerance to alcohol is due to NMTT (N-methyl-5-thiotetrazole) group.

– All cephalosporins (except cefoperazone) are eliminated renally , cross-sensitivity may occur. May develop
hypersensitivity

– Other adverse effects include nausea, vomiting, superinfections, nephrotoxicity, clostridium difficile induced
colitis
 BACITRACIN
❑Cyclic peptide mixture obtained from Tracey strain of
Bacillus subtilis
❑ Active against gram positive microorganisms

NOTES:
▪ Topical used only
▪ Highly nephrotoxic when administered
systematically
▪ Poorly absorbed
▪ Combined with other antibiotics
 GLYCOPEPTIDES
Glycopeptide antibiotics are a type of antibiotic that inhibits bacterial cell wall formation by inhibiting
peptidoglycan synthesis.

They are used for treating multi-resistant Staphylococcus aureus (MRSA) infections and
enterococcal infections, which are resistant to beta-lactams and other antibiotics.

EXAMPLES:
. Vancomycin
. Teicloplanin
 VANCOMYCIN
❑ Vancomycin is an antibiotic produced by
Streptococcus orientalis.
❑ A glycopeptide antibiotic

MECHANISM OF ACTION
▪ Binds to precursor units of bacterial cell walls,
inhibiting cell wall synthesis
Bactericidal
Synergistic with gentamicin and streptomycin against
enterococcus
 VANCOMYCIN
CLINICAL USES:

Parenteral vancomycin
▪ Sepsis or endocarditis caused by methicillin-resistant
staphylococci
▪ In combination with gentamicin (alternative for enterococcal
endocarditis)

Oral vancomycin
▪ Antibiotic associated enterocolitis caused by Clostridium
difficile
 ADVERSE EFFECTS
OF VANCOMYCIN

. Phlebitis (at the site of injection)

. Nephrotoxicity and Ototoxicity (rare)
. Red man or red neck syndrome
flushing, pruritus, erythematous rash on face and upper torso
related to RATE of intravenous infusion

TEICOPLANIN (similar with vancomycin)

Actinoplanes teichomyceticus
 TEICLOPLANIN
▪ Actinoplanes teichomyceticus
▪ Given IM and IV
▪ A mixture of five related fermentation products related to vancomycin
▪ More lipid soluble, highly protein bound
▪ Less irritating than vancomycin
PROTEIN
SYNTHESIS INHIBITORS
30S RIBOSOMAL UNIT INHIBITOR
50S RIBOSOMAL UNIT INHIBITOR
tRNA INHIBITORS

‹#›
PROTEIN SYNTHESIS
INHBITORS
30s inhibitor
Aminoglycosides
Tetracycline

50s inhibitor
Chloramphenicol
Macrolides
Lincomycins

tRNA inhibitor
Mupirocin Due to differences in ribosomes:
Eucaryotic cells
80S (60S + 40S subunits) ribosomes.
Procaryotic cells
70S (50S + 30S subunits) ribosomes

‹#›
‹#›
AMINOGLYCOSIDES
1,3-diaminocyclohexane central ring consisting of either deoxystreptamine or streptadine

Isolated from:
MYCIN- Streptomyces
MICIN- Micromonospora

Broad spectrum - Primarily used against gram (-) enterobacteria and in suspected sepsis. They
have little activity against anaerobic and facultative organisms.

The only protein synthesis inhibitor that is BACTERICIDAL

 AMINOGLYCOSIDES
Properties:
▪ Are freely water soluble, basic and form acid addition
salts (sulfates)
▪ Highly water soluble, tends to concentrate in the
kidneys.
MOA:
inhibiting bacteria protein synthesis by binding to and
impeding the function of the 30s ribosomal subunit –
(Bactericidal)
AMINOGLYCOSIDES
from Streptomyces sp.

STREPTOMYCIN
produced from Streptomyces griseus

▪ the first aminoglycoside antibiotic to be used in Chemotherapy

▪ active against both gram (+) and gram (-)
▪ Administered via IM

Uses:
▪ used for the treatment of tularemia
▪ bacterial endocarditis and tuberculosis
▪ long term use may cause an overgrowth of C. albicans
 AMINOGLYCOSIDES
from Streptomyces sp.

Kanamycin is isolated from S. kanamyceticus:

– available as IV but painful
– occasionally used in TB.

Amikacin is made semisynthetically from kanamycin A:

– with enahnced spectrum
– used competitively with gentamicin against susceptible strains
 AMINOGLYCOSIDES
from Streptomyces sp.

Tobramycin is produced from S. tenebrarius:

– available as IV
– useful as less-toxic substitute for gentamicin-resistant P.aeruginosa

Spectinomycin is from S. spectabilis

– bacteriostatic in activity
– particularly useful patients with pen-allergy

Neomycin is derived from S. fradiae

– sometimes used in the preoperative bowel sanitation
– treatment of (EPEC) enteropathogenic E. coli infections
 AMINOGLYCOSIDES
from Micromonospora sp.

Netilmicin is from M. inyoensis

◦ with clinical properties similar to gentamicin and tobramycin

Gentamicin is derived from M. purpurea

– the most important aminoglycosides still in use
– with enhanced antibacterial activity, useful against susceptible g(-) bacteria
 ADVERSE EFFECTS
OF AMINOGLYCOSIDES

① Hypersensitivity reactions
❑ Special attention should be paid to the anaphylactic shock caused by streptomycin

② Nephrotoxicity
❑ Neomycin is the most nephrotoxic
❑ Streptomycin is the least one
❑ Due to their water solubility, it tends to concentrate in the kidneys
 ADVERSE EFFECTS
OF AMINOGLYCOSIDES

③ Ototoxicity
Cranial nerve damage - cochlea and ear vestibule toxicity (irreversible)
❑ Neomycin, kanamycin, and amikacin are the most ototoxic drugs
❑ Streptomycin and gentamicin are the most vestibulotoxic.
❑ Netilmicin is the least ototoxic

④ Neuromuscular junction blockade

❑ take place at high doses or in combination with curareform drugs
❑ ANTIDOTES:
Calcium gluconate
Neostigmine
TETRACYCLINE
Consist of four annelated
6-membered ring (octahydronapthacene)

Amphoteric, the basic function is the 4-α-dimethylamino, and the acidic group is the conjugated
trione. Available as hydrochlorides
MOA:
These are broad-spectrum antibiotics with mechanism of action such as inhibition of bacterial protein
synthesis by binding with 30s ribosomal subunit. (Bacteriostatic)
 TETRACYCLINE
Broadest spectrum antibiotic
Effective against G+ and G-
They have the favorable effects on:
▪ Rickettsiae
▪ Mycoplasma
▪ Chlamydiae
DURATION OF ACTION DRUG
▪ Spirochete
Short-acting Chlortetracycline
Tetracycline
Oxytetracycline

Intermediate-acting Demeclocycline
Methacycline

Long-acting Doxycycline
Minocycline

‹#›
 TETRACYCLINE
PHARMACOKINETICS:

Absorption:
▪ All tetracylines are administered orally EXCEPT tigecycline
▪ Chelated and inactivated by calcium (milk), magnesium, aluminum (antacids) and iron
▪ Should be taken when the stomach is empty

Distribution:
▪ Widely distributed in body
▪ Bind in tissues undergoing calcification
▪ All cross placenta and concentrate in fetal bones and teeth
Minocycline best CSF penetration
*Concentrated in saliva and gingival fluid
 CLINICAL USES
OF TETRACYCLINE

. First choice for rickettsial infections (typhus), chlamydial infections, and Mycoplasma
pneumonia.

. Effective for many spirochetal infections, including relapsing fever (first choice), Lyme
diseases, and syphilis.

. Brucellosis, cholera, and tularemia can be treated with tetracyclines as the first choice.

. Intestinal amebiasis, acne and actinomycosis

. Reserved for life-threatening infections, can cause superinfection

CLINICAL USES
OF TETRACYCLINE

Demeclocycline – inhibits action of ADH in the renal tubule and has been used in the tx of
inappropriate secrtion of ADH.

Minocycline – can eradicate meningococcal carrier state

Doxycycline – DOC for leptospirosis, prophylaxis for traveller’s diarrhea and for patients with
renal impairment
 ADVERSE EFFECTS
OF TETRACYCLINE

. Gastrointestinal discomfort
▪ Anorexia, epigastric pain, abdominal distention, nausea, vomiting, diarrhea,
sore mouth, perianal irritation
▪ The most common adverse effect

B. Liver toxicity
▪ Increased during pregnancy
 ADVERSE EFFECTS
OF TETRACYCLINE

Kidney toxicity
▪ Renal tubular necrosis impairment in the proximal tubular
function of the kidney.

. Teeth and depression of bone growth

▪ Discoloration enamel and hypoplasia of teeth
▪ Deposition in fetal and growing bones, stunted growth
▪ Should not be given to children under 8 years old
 ADVERSE EFFECTS
OF TETRACYCLINE

. Photosensitization
▪ Demeclocycline is the photosensitive

. Hypersensitivity
It is manifested by skin rash, urticaria,
generalized exfoliative dermatitis.
 CHLORAMPHENICOL

Isolated by Paul Ehrlich in 1947

A nitrobenzene derivative isolated from Streptomyces venezuelae but can be fully synthesized in the
laboratory.
Bacteriostatic, with broad spectrum of activity

MOA:
binds to the 50S unit of ribosomes and appears to act by inhibiting the peptidyl transferase
reaction by which the peptide chain is extended.
CHLORAMPHENICOL
USES:
For the treatment of typhoid fever, infections due to penicillin-resistant strains of
Haemophilus influenzae
Meningococcal infections
Severe ricketsial infections
 CHLORAMPHENICOL

Toxic effect includes:

Damage of the bone marrow leading to aplastic
anemia.
Long-term use can cause inflammation of the
optic and other nerves, confusion, delirium and
mild to severe GI symptoms.
Gray-baby syndrome
 MACROLIDES
Derived from actinomycetes, picromycin as the first identified macrolide
It contains: large lactone ring, ketone group, glycosidically linked amino sugar.

MOA:
❑ Bind to the 50s subunit of the bacterial
ribosomes.
❑ The main effect seems to be inhibition of
the translocation step in protein
synthesis, so that the synthesis itself is
inhibited.
 MACROLIDES
A. Erythromycin
▪ Prototype among the macrolides
▪ Obtained from Streptomyces erythreus
▪ Acid-labile

SALT FORMS:
- Erthromycin stearate
- Erthromycin estolate
- Erthromycin lactobionate
 MACROLIDES
CLINICAL USES:
- DOC for corynebacterial infections
- DOC for legionnaire’s disease
- Prophylaxis against endocarditis
- Substitute for penicillin

ADVERSE EFFECTS:
- GI intolerance
- Estolate salt can produce acute cholestatic hepatitis
- Enzyme inhibitor
- DI: increase bioavailability of digoxin
 MACROLIDES
B. Clarithromycin
▪ the 6-methyl ester of erythromycin
▪ Improved acid stability and oral absorption
▪ More active against Mycobacterium avium,
Mycoplasma leprae, Toxoplasma gondii

C. Azithromycin (Zithromax)
▪ Active against M avium complex and T gondii
▪ Highly active against Chlamydia
MACROLIDES
D. Telithromycin
a semisynthetic derivative of erythromycin

E. Dirithromycin
is a more lipid-soluble prodrug, an alternative to erythromycin therapy.

F. Troleandomycin
is mostly used for upper respiratory tract infections cause by S. pyogenes and S. pneumoniae
 LINCOMYCIN
CLINDAMYCIN
❑ Chlorine-substituted derivative of lincomycin
❑ An antibiotic that is elaborated by Streptomyces
lincolnensis

MECHANISM OF ACTION:
Inhibit protein synthesis at the 50s ribosomal subunit
LINCOMYCIN
CLINICAL USES:
Indicated for the treatment of skin and soft-tissue infections caused by streptococci and
staphtylococci
Indicated for treatment of anaerobic infections caused by Bacteroides sp
Clindamycin + primaquine = alternative to co-trimoxazole for moderate to moderately
severe Pneumocystis jiroveci pneumonia

ADVERSE EFFECTS:
Diarrhea, nausea, and skin rashes
Fatal pseudomembranous colitis caused by overgrowth of C. difficile
Treatment: Metronidazole or Vancomycin
 MUPIROCIN
Mupirocin (Bactroban)

From P. fluorescens, used only as topical preparation against staph and strep skin infections

MOA:
It primarily works by inhibiting bacterial protein synthesis. Its unique mode of action is inhibiting
the activity of bacterial isoleucyl-tRNA synthetase.

Uses:
. an antibacterial cream/ointment which is used to treat small areas of skin infection.
. It is sometimes used to treat infections such as impetigo in children.

‹#›
CELL MEMBRANE
SYNTHESIS INHIBITORS

POLYMXIN
COLISTIN

‹#›
 POLYMYXIN B
Derived from Bacillus polymyxa
MOA:
▪ Bactericidal- Disrupt the negatively charged lipopolysaccharide (LPS) of the outer membrane of
Gram-negative bacteria, allowing the passage of the polymyxin (and of other drugs) into the
periplasmic space.
 COLISTIN
Also from polymyxa variety colistinus,used for refractory UTI

MOA:
▪ It competitively displaces divalent cations
(Ca2+ and Mg2+) from the phosphate groups of
membrane lipids.
▪ This leads to disruption of the outer cell
membrane, leakage of intracellular contents and
bacterial death
DNA SYNTHESIS
INHIBITORS

DNA GYRASE INHIBITORS

FOLIC ACID SYNTHESIS INHIBITORS

‹#›
 FLUOROQUINOLONES
❑ This comprise a series of synthetic antibacterial agents patterned after nalidixic acid.

❑ MOA: inhibition of DNA synthesis due to inhibition of DNA gyrase (Topoisomerase II and IV).
 QUINOLONES
❑ The majority of quinolones in clinical use belong to the subset of fluoroquinolones which
have a fluoro group attached to the central ring system typically at the 6-position.

❑ They are usually administered orally but some can be given IV for the treatment of serious
infections.
QUINOLONES
GENERATION DRUGS
First Nalidixic Acid- parent compound
Oxolinic Acid
Cinoxacin
Second Ciprofloxacin- most potent
Norfloxacin- least active
Ofloxacin
Third Levofloxacin- levo-isomer of ofloxacin
Gatifloxacin
Trovaflaxcin- assoc. with hepatitis
Gatifloxacin- assoc. with hyperglycemia
Fourth Moxifloxacin
 QUINOLONES
NALIDIXIC ACID
▪ It intereferes with DNA gyrase and inhibit DNA synthesis during bacterial replication. Active
against gram (-) bacteria but not effective against pseudomonas organisms
▪ Introduced for the treatment of UTI.
 FLUOROQUINOLONES
NORFLOXACIN
▪ It is a broad spectrum antibacterial agent. Fluoride atoms provide increase in potency against
gram (+). Activity generally is not effective against obligate anaerobic bacteria.
▪ It is used for uncomplicated gonorrhea in 800 mg single oral dose.
 FLUOROQUINOLONES
CIPROFLOXACIN (Ciprobay)
It is the most potent fluoroquinolone
Available as oral and intravenous preparation.

Uses:
. used for treatment of UTI, lower RTI, sinusitis, diarrhea, bone, joint & skin structure
infection.
. With ceftriaxone, it is used for disseminated gonorrhea.
. With doxycycline, it is used for gonococal urethritis.
 FLUOROQUINOLONES
OFLOXACIN
▪ Shows greatest activity against Chlamydia, with the same therapeutic uses as ciprofloxacin
but with a difference in providing higher concentration in CSF .
▪ It is used also for the treatment of pelvic inflammatory disease.

Levofloxacin (Levox, Levaquin) - levo isomer of ofloxacin. More potent than ofloxacin
 FLUOROQUINOLONES
LOMEFLOXACIN
▪ A 2nd generation quinolone.It is indicated for acute bacterial exacerbations of chronic
bronchitis caused by H influenzae or moxarella catarrhalis.
▪ causes the highest incidence of phototoxicity

SPARFLOXACIN
▪ With long elimination half-life, used for the treatment of bacterial gastroenteritis and
cholecystitis.
▪ It shows lowest incidence of phototoxicity
 FLUOROQUINOLONES
CLINICAL USES: ADVERSE EFFECTS:
UTI
– EXCEPT moxifloxacin
❑ Photosensitivity
Respiratory fluoroquinolones Lomefloxacin and Pefloxacin
– Levofloxacin, Gatifloxacin, Gemifloxacin,
Moxifloxacin ❑ Gatifloxacin – hyperglycemia
– For atypical pneumonia ❑ Nephrotoxicity (crystalluria)
– Treatment of upper and lower respiratory
tract infections ❑ Damage on growing cartilage and
arthropathy
– CI: under 18 years old
pregnant
 NOVOBIOCIN
From S. niveus, works synergistically with fluoroquinolones
MOA:
Inhibit the GyrB subunit of the bacterial DNA gyrase enzyme involved in energy transduction.

Use:
1. Novobiocin test is used to differentiate
coagulase-negative staphylococci (CONS) and
presumptively identify the isolate as Staphylococcus
saprophyticus (novobiocin resistant)

2. It is also used to treat MRSA

‹#›
 SULFONAMIDES
HISTORY:
❑ Gerhard Domagk (1932)
Discovered protective aspects of Prontosil (azo dye).
❑ Sulfanilamide derivatives synthesized (Late 1930’s )
❑ 1968 Sulfa combined with Trimethoprim

❑Prontosil breaks down to form sulfanilamide.

– Sulfanilamide is similar in shape to PABA.
– PABA is part of folic acid.
– Sulfonamides are synthetic derivatives of
Sulfanilamide
 SULFONAMIDES
A synthetic anti-bacterial drug that is related to PABA. (p-amino benzoic acid)

Major sulfonamides include:

. Sulfadiazine
. Sulfamethoxazole
. Sulfisoxazole
. Sulfamethazole
. Sulfacytine
SULFONAMIDES
MOA:
Acts as competitive enzyme inhibitors (DHPS) and
blocks the synthesis of the vitamin folic acid in
bacterial cells.
 SULFONAMIDES
SULFADIAZINE
In burn therapy to prevent bacterial infection (Silver sulfadiazine)
With pyrimethamine (for histoplasmosis)

SULFISOXAZOLE
With erythromycin used for the treatment of otitis media.
 SULFONAMIDES
SULFAMETHOXAZOLE
With trimethoprim (used for tx of first attack of UTI , shigella
and DOC for P. carinii pneumonia.

Trimethoprim-Sulfamethoxazole
- DOC for Pneumocystis jiroveci (P carinii) pneumonia,
toxoplasmosis, nocardiosis
- DOC for UTI
- Prostatitis
SULFONAMIDES
SULFADOXIME
With pyrimethamine and quinine, used for the treatment of chloroquine-resistant malaria.
Sulfadoxime + pyrimethamine (Fansidar)

SULFACETAMIDE
Treatment of conjunctivitis and related superficial ocular infections.

Sulfasalazine- ulcerative colitis, enteritis and other bowel dx.

Mafenide acetate- a sulfonamide that is also used for burn tx.
 ADVERSE EFFECTS
OF SULFONAMIDES

ADVERSE EFFECTS:
All sulfonamides and their derivatives (ex. Carbonic anhydrase inhibitors, thiazide diuretics, and
sulfonylurea hypoglycemic agents) are cross-allergenic:
SJS
Kernicterus
Crystalluria
Photosensitivity
Hematopoetic disturbances
 ADVERSE EFFECTS
OF SULFONAMIDES

SJS
A particularly and potentially fatal type of skin and mucous
membrane eruption.

KERNICTERUS
Form of brain damage caused by excessive jaundice. (should
never be taken near the end of pregnancy)
 ADVERSE EFFECTS
OF SULFONAMIDES

CRYSTALLURIA
After acetylation metabolism pathway of sulfonamides, it forms less water soluble metabolites that
have the potential of crystallizing out in renal tubules thereby causing kidney damage.

HEMATOPOETIC DISTURBANCES:
Aplastic anemia
Granulocytopenia
Thrombocytopenia,
G6PD deficiency resulting to hemolytic reactions
NITROFURANS
NITROFURANTOIN
NITROFURAZONE
FURAZOLIDONE

‹#›
NITROFURANS

MOA: Protein synthesis, aerobic energy metabolism, DNA and RNA synthesis, and cell wall
synthesis are inhibited.

NITROFURANTOIN
It prevents and treats UTI.
A/E: colors the urine brown. Common adverse effect
includes nausea, vomitting, and diarrhea and
hypersensitivity reactions .
NITROFURANS
NITROFURAZONE (Furacin)
It is employed topically for the treatment of burns, or may used for the prevention of infection in
skin grafts.
It is bactericidal against most of bacteria causing surface infections

FURAZOLIDONE (Furoxone)
It has bactericidal activity and also antiprotozoal activity, specifically against Giardia lamblia.
The usual adult dosage is 100 mg 4 times daily.
It can inhibit alcohol dehydrogenase
MISSED DOSE?

1 Advise the patient to NOT double the next dose of antibiotics if they’ve the
missed a dose. Taking a double dose of antibiotics will increase the risk of
getting side effects.

2 Advise them to take the missed dose as soon as they remember or, if it's
nearly time for the next dose, skip the missed dose altogether

3 Always refer to the patient information leaflet (PIL) that comes with
antibiotics, as it provides information and advice about the specific
antibiotic. .

‹#›
ANTITUBERCULAR
Drugs for Mycobacterium Tuberculosis Infection

‹#›
 TUBERCULOSIS
It is a chronic infectious disease caused by Mycobacterium
tuberculosis and usually affects the lungs but can also affect
other parts of the body.

Signs and Symptoms:

Cough (more than 2 weeks)
Sputum production (may be blood stained)
Chest pain, shortness of breath
Fever, loss of appetite, loss of weight, a general
feeling of tiredness and weakness.

* If a patient has any of the above, consider him a

“TB Suspect”
 TUBERCULOSIS
Tuberculosis is CURABLE and the best way to do it is
with DOTS.

❑ If left untreated, it can lead to disturbing conditions

even death.
❑ If partial treatment- it will cause MDRTB

Combination drug therapy has become a standard in

the treatment of TB.
 FIRST LINE
ANTI-TB DRUGS
ISONIAZID (INH)
A synthetic antibacterial agent which is bactericidal against replicating organisms, but
bacteriostatic against nonreplicating organisms.
MOA:
Inhibit mycolic acid synthesis, which interferes with cell wall synthesis, thereby producing a
bactericidal effect
 FIRST LINE
ANTI-TB DRUGS

ISONIAZID (INH)
The exact mechanism of action for INH is unknown, but it is thought that INH enters the cell wall and
is metabolized to isonicotinic acid

Adverse Effects:
Hepatotoxic
Periperhal neuropathy (due to competition of INH with pyridoxal phosphate for the enzyme
apotryptophanase.
FIRST LINE
ANTI-TB DRUGS

PYRAZINAMIDE (PZA)
Resistance to this anti-TB drug can develop quickly. (Used in combination with other agents)
Must be hydrolyzed enzymatically to pyrazinoic acid
MOA:
It inhibits the synthesis of fatty acids; this disrupts the cell membrane and disables energy production
which is necessary for the survival of the TB bacteria.
 FIRST LINE
ANTI-TB DRUGS
RIFAMPIN
A semi-synthetic agent which is derived from rifamycin B, an antibiotic that was originally isolated from
Streptomyces mediterranei.
MOA: inhibition of bacterial DNA-dependent RNA polymerase resulting to the cessation of the initiation
phase of RNA synthesis

Adverse Effects:
Hepatotoxicity (with isoniazid or ethambutol)
Red-orange coloration of body secretions.
FIRST LINE
ANTI-TB DRUGS

ETHAMBUTOL
is administered as the d-isomer form, which is 200-500 times more potent than the l-isomer,
suggesting a specific receptor site for its action.

A/E: optic neuritis

 FIRST LINE
ANTI-TB DRUGS

STREPTOMYCIN
▪ was isolated by Waksman and coworkers in 1944 from Streptomyces griseus.
▪ The only aminoglycoside used for TB.
▪ Able to penetrate the cell wall and inner membrane of M. tuberculosis, and binds to the 30S subunit of
the ribosome.
▪ Streptomycin has no metabolites in humans, and 50-60% of a dose of the drug can be recovered
unchanged.
BRANDS FOR
FIX DOSE COMBINATION

‹#›
 2ND LINE
ANTI-TB DRUGS

ETHIONAMIDE
❑ a synthetic nicotinamide analogue that may act by inhibiting the incorporation of cysteine and
methionine into proteins.

P-AMINO SALICYLIC ACID

❑ this agent was once quite popular, until significant resistance to the drug developed.
 2ND LINE
ANTI-TB DRUGS
CYCLOSERINE
❑ isolated from Streptomyces orchidaceus as the D-isomer. Interestingly, the L-isomer is also active,
and the racemic mixture is more potent than either isomer.
❑ In enolic form, cycloserine is sterically and stereochemically analogous to D-alanine and thus is
bactericidal by inhibiting cell wall synthesis.
 2ND LINE
ANTI-TB DRUGS

CLOFAZAMINE
❑ a basic red dye that exerst a slow, bactericidal effect on M. leprae. This is used in the treatment of
lepromatous leprosy, including the dapsone-resistant forms.

OTHER EXAMPLES:
❑ Capreomycin,
❑ Kanamycin and
❑ Rifabutin