1.
Macrolides,
Aminoglycosides, Polyene
& polypeptide antibiotics

2.
Contents
 Macrolide
 Mechanism & Resistance
Pharmacokinetic
Therapeutic uses, adverse effect and drug interaction
Aminoglycoside
Mechanism & Resistance
Pharmacokinetic
Therapeutic uses, adverse effect and drug interaction
Polyene and polypeptide

3.
Resistance

4.
• Streptococcus pneumoniae, strepto. Pyrogenes
• Staphylococci
Gram positive cocci
• N. gonorrhoea
• Moraxella catarrhalis
Gram negative cocci
• Bacillus anthracis, Corynebacterium diphtheriae
• Clostridium tetani
Gram positive bacilli
• Legionella pneumophila, Bordetella pertussis
• H. pylori
Gram negative bacilli
• Mycobacterium leprae
• M. avium intracellulare
Acid fast bacilli
Peptostreptococcus,
Actinibacilus, Pasteurella, B.
fragilis, MRSA

5.
• Moraxella catarrhalis
• Less potent- Bordetella pertussis
Roxithromycin
• Legionella pneumophila, H. influenzae
• Chlamydia trochomatis, M leprae
Clarithromycin
• Moraxella catarrhalis, Chlamydia trochomatis
• H. influenzae, M. pneumoniae
Azithromycin
• Toxoplasma gondii
• Cryptosporidium
Spiramycin

6.
Pharmacokinetics erythromycin
Absorption
• Oral
• Destroy by gastric acid
Distribution
• Tonsillar tissue
• middle ear fluid
• prostatic fluid
• CSF
Excretion
• Bile
• 5% Urine

7.
Acid stable macrolides
Roxithromycin Clarithromycin Azithromycin Spiramycin

8.
Therapeutic uses- Erythromycin
FIRST CHOICE OF DRUG
1) Atypical pneumonia
2) Pneumonia
3) Whooping cough
SECOND CHOICE OF DRUG
1) Campylobacter gastroenteritis
2) Chancroid
3) Chlamydial conjunctivitis

9.
 Non- Chemotherapeutic uses
 Anti-inflammatory
Rheumatoid arthritis, cystic fibrosis, asthma

10.
Clarithromycin
• Lung disease
Mycobacterium avium
complex
• Pneumonia, epiglottis
• Meningitis
H. influenzae
• Toxoplasma
Toxoplasma gondii
• Leprosy
Mycoplasma leprae

11.
Azithromycin
H. influenzae Moraxella catarrhalis Legionella
Pneumonia
epiglottis
Meningitis
Otitis media
COPD
Acute bacterial
rhinosinusitis
lung infection
Pontiac fever

12.
 Spiramycin – Toxoplasma gondii
 Adverse Effect
Cholestatic hepatitis
 Epigastric pain
 Ototoxicity
 Tinnitus

13.
Drug interactions
Erythromycin
Clarithromycin
Theophylline,
Carbamazepine,
warfarin
Macrolide Digoxin

14.
Aminoglycoside

15.
How Cidal action is achieved
Ans-
Defective proteins incorporated in cell membrane.
Due to secondary changes in the integrity of bacterial cell
membrane. (Increase permeability for ions, amino acids, proteins- Leading to
leaking of these out side)
Bonus of incorporation of defective protein in cell membrane
More entry of antibiotic occurs in to the cell. Further
increasing affectivity
Death Of Bacteria

16.
Resistance
1. Inactivation through enzymes
2. Mutation / deletion of porin channels
3. Alteration of the receptor protein on
30s ribosome

17.
 Aminoglycoside exhibit
Concentration Dependent Killing
 Aminoglycoside also posses
post-antibiotic effect

18.
Pharmacokinetics
 Oral drugs
Highly polar, basic drugs
Poor oral bioavailability
 Excreted in faeces
IV
Kidney
Urinary tract infection
Dose for a
case of renal =
insufficiency

19.
Antibacterial spectrum
Gram negative
aerobic bacilli
• E.coli
• Klebsiella
• Shigella
• Proteus
Gram positive
cocci
• Staph. aureus
• Streptococcus
viridans
Gram positive
bacilli, gram
negative cocci,
anaerobes

20.
Streptomycin
1. Plague
2. Tularemia
3. Brucellosis
- -Subacute bacterial
endocarditis
1 g/day IM + Tetracycline

21.
Gentamicin
 Combination with other antibiotics
• Septicaemia
• Sepsis
• Fever
Ampicillin
• Pelvic infection
Metronidazole
• Subacute Bacterial Endocarditis (SABE)
Benzathine penicillin G
• UTI
Ampicillin/ ceftriaxone

22.
Gentamycin Sisomicin
Greater
efficacy
against
Pseudomonas
Beta-
haemolytic
streptococci
Tobramycin
Proteus,
pseudomonas
acinetobacter
Netilmicin
Resistant to aminoglycoside inactivating enzyme
Proteus, pseudomonas, klebsiella, E.coli, Staph.
aureus

23.
 Kanamycin
Arbekacin
 Stable in presence of aminoglycoside inactivating enzyme
Effective against gram positive and gram negative bacteria
 MRSA, P.aeruginosa, E.coli, K. Peumoniae,
Enterobacter cloacae
Serratia marcescens
 proteus mirabilis, proteus rattegiri
proteus vulgaris
morganelloa morganii

24.
Amikacin: resistant to enzyme inactivation, used in combination with antitubercular drugs
Neomycin
With bacitracin- prevent infection in wound and cuts
1. As preoperative intestinal antiseptic
 framycetin
 skin infection, burns
 ophthalmic infection

25.
Adverse Effects
1. Nephrotoxicity
2. Ototoxicity
3. Neuromuscular blockage

26.
Polyene & polypeptide
antibiotics

27.
 Polymyxin-B
 Colistin / Polymyxin-E

28.
Cationic detergent
displace calcium and magnesium from membrane
Disrupt bacterial cell membrane osmotic integrity
Leakage of contents
Cell death

29.
 Polymyxin-B sulfate used primarily topically
Used in treatment of skin, ear and eye infection
 Colistin sulfate- GIT infection
 Colistimethane sodium- Respiratory infection
Effective against
Gram negative bacilli
Except
Proteus, serratia, Bacteroides
fragalis

30.
Adverse effect
Nephrotoxicity
 Bronchoconstriction