The document discusses antimicrobial drugs and provides details about classification of antimicrobial agents. It describes various classes of antibacterial drugs including penicillin, cephalosporins, aminoglycosides, tetracycline, chloramphenicol and their mechanisms of action, spectrum of activity, indications and side effects. It also discusses ideal properties of antimicrobial drugs and history of antimicrobial therapy.

2. PRESENTATION LAYOUT
 Introduction to antimicrobial drugs
 Classification of antimicrobial drugs
 Antibacterial drugs:
- Classification
- Indications
- Side effects
 Antibacterial Resistance

4.  Antimicrobial drugs are chemotherapeutic drugs
 Two categories:
– Antibiotics : Antimicrobial drugs produced by
microorganisms
– Synthetic drugs : Antimicrobial drugs
synthesized in the lab

5. Have highly selective toxicity to the pathogenic
microorganisms in host body
Have no or less toxicity to the host
Low propensity for development of resistance
Not induce hypersensitivies in the host
Have rapid and extensive tissue distribution
Be free of interactions with other drugs
Be relatively inexpensive
Ideal antimicrobial drug

6. Where do antibiotics come from
 Several species of fungi including Penicillium and
Cephalosporium
E.g. penicillin, cephalosporin
 Species of actinomycetes, Gram +ve filamentous
bacteria
 Many from species of Streptomyces
 Also from Bacillus, Gram +ve spore formers
 A few from myxobacteria, Gram -ve bacteria
 New source explored : plants, fish

7. Sources of some common antibiotics and semisynthetics

8.  Ehrlich (1854–1915) coined the term
chemotherapy
 1929 Penicillin discovered by Alexander Fleming
 1940 Florey and Chain mass produced penicillin
for war time use, becomes available to the public
 1935 Sulfa drugs discovered
 1944 Streptomycin discovered by Waksman from
Streptomyces griseus
History of Antimicrobial Therapy
 Alexander Fleming was first to characterize
penicillin’s activity. He found mold
contaminating his culture plates, with clearing of
staphylococcal colonies all around the mold.
Fleming then isolated penicillin from the mold
 Thanks to work by Alexander Fleming

9. Classification of antimicrobial agent
Chemical
structure
Type of
organism to
be killed
Antimicrobial
agent

10. Based on chemical structure
Group Examples
Sulfonamide sulfadiazine, dapsone, paraminosalicylic acid
B-lactam penicillins, cephalosporins, monobactams
tetracycline oxytetracycline, doxycycline
aminoglycoside streptomycin, gentamycin, neomycin
Macrolide erythromycin, azithromycin, clarithromycin
polypeptide polymyxin-B, bacitracin
glycopeptide vancomycin
Quinolones ciprofloxacin, ofloxacin, moxifloxacin, gatifloxacin
Azole derivative miconazole, clotrimazole, ketoconazole, fluconazole
nitroimidazole Metronidazole, tinidazole

12. Antibacterial drugs
 Drugs active against bacteria
 Natural or synthetic
 Naturally, obtained from microorganisms which
suppress the growth or kill other microorganisms
are k/a antibiotics
 Synthetics are made in lab by bioengineering
 The term antibiotic was first used in 1942
by Selman Waksman

13. classification
Spectrum of activity
Type of action
Mechanism of action

14. Bacteriostatic
Sulphonamides
Tetracycline
Chloramphenicol
Macrolides
Bactericidal
Penicillins
Aminoglycosides
Cephalosporins
Vancomycin
Type of action

15. Narrow spectrum
Penicillin G
Streptomycin
Erythromycin
Broad spectrum
Tetracyclin
Chloramphenicol
Cephalosporins
Spectrum of activity

16. • Inhibit cell wall synthesis
• Cause leakage from cell membranes
• Inhibit protein synthesis
• Inhibit DNA gyrase
• Action as antimetabolite
Mechanism of action

17. Mechanism of action

18. Inhibit cell wall synthesis
 These are the drugs that interfere with the cell
wall synthesis process
 These drugs consist β-Lactam rings so called
β-lactam antibiotics
 Bactericidal in nature

19. Penicillin
Cephalosporin
Vancomycin
Inhibitor of cell wall synthesis

20. First antibiotic to be used clinically
Obtained from fungus Penicillium notatum
Structure
β-lactam is responsible for antimicrobial activity
Properties like antimicrobial spectrum, stability to
stomach acid and susceptibility to bacterial degradative
enzymes (β-lactamases) depends upon the side chain
Also, differ in structure by the side chain
Penicillin

22. Working of penicillin
NAM-NAG-NAM-NAG
Pep Pep
Pep Pep
NAM-NAG-NAM-NAG
Pep side chains are cross linked as the
final step in synthesis of peptidoglycan in
the presence of penicillin binding protein
(PBPs).Penicillin drugs inhibit this
process after binding with PBPS.
Pep=peptide linkage
NAM &NAG =N-acetyl muramic acid and N-
acety glucosamine
Penicillin
Binds to PBPs
Inhibition of cross linkage
Blockage of peptidoglycan
synthesis
Cell dies

23. Penicillin G
Penicillinase resistant
penicillins
Extended spectrum
penicillins
-Have side chain of benzyl group
-Active against Gram +ve
bacteria than Gram -ve
-Resistant against
penicillinase/β-lactamase
producing bacteria
eg. Methicillin, Cloxacillin
 The latter two are semisynthetic in nature
-Sensitive against wide range of
bacteria(Gram +ve/-ve)
eg. Ampicillin, Amoxicillin
Types

24. Coverage of Penicillins
Penicillin G
Penicillinase resistant
penicillins
Extended spectrum
penicillins
Gram Positive cocci:
Streptococcus pneumonia
Streptococcus pyogens
Gram Negative cocci:
Neisseria gonorrhoeae
Neisseria meningitidis
Gram Positive bacilli:
Bacillus anthracis
Corynebacterium
Clostridia, Listeria
Spirochetes
Penicillinase producing
Staphylococcus
Sensitive against all Gram
positive as well following
Gram negative bacteria
- E.coli
- Haemophilus
- Salmonella
- Proteus

25. o Pneumococcal infection
o Streptococcal infection
o Meningococcal infection
o Tetanus
o Gas gangrene
o Syphilis
o Gonorrhea
o Respiratory tract infection
o Sinusitis
o UTI
o Bacillary dysentery
o Gonorrhea
o Enteric fever
o Preseptal cellulitis
Penicillin G
Extended spectrum
penicillins
Indications

26.  Hypersensitivity reaction (rash, itching, urticarial,
fever)
 Pain at i.m. injection site, thrombophlebitis of
injected vein
 Oral penicillin can cause nausea, vomiting or diarrhea
 Toxicity to the brain: mental confusion, convulsions &
coma
Side Effects

27. Beta-lactamase inhibitors
 Some of the bacteria produces β-lactamase enzyme. This
enzyme causes hydrolysis of β-lactam ring so that the
antibiotic activity of penicillin/ β-lactam drug is destroyed
 This can be prevented by two inhibitors i.e. clavulanic acid
and sulbactam
 These are the enzyme with β-lactam ring but has no
antibacterial activity. It combines with the lactamase
enzyme and thus prevent the destruction of lactam ring of
antibiotic making it potent to show action

28. Cephalosporins
Have similar action to penicillin (bactericidal)
Semisynthetic antibiotics derived from
cephalosporin-C obtained from fungus
Cephalosporium

29. Cephalosporins
Classification

30. Cefazolin Cephalexin
Cephradine Cephadroxil
Includes
 Exhibits good activity against Gram positive
cocci like Staph.sps, Strep. sps & Gram –ve
rods like E.coli, Klebseilla
First Generation

31. Cefuroxime Cefoxitin
Cefaclor Cefuroxime Axetil
 Shows somewhat enhanced activity towards Gram –ve
bacteria compared to 1st generation
Coverage:
 Coverage of 1st generation &
 Additional -ve cocci like Neisseria gonorrhoea & -ve
rod H.influenza
Second Generation
Includes

32. Cefotaxime Ceftriaxone
Ceftizoxime Cefixime
 More potent than 2nd generation
 Shows augmented activity against:
 Enterobacteria
 β-lactamases producing bacteria
 Pseudomonas
Third Generation
Includes

33. Cefepime
Cefpirome
 Similar to 3rd generation
 Shows increased resistance to β-lactamase
producing bacteria
Fourth Generation
Includes

34.  Alternative to penicillin allergic patient
 Respiratory , urinary and soft tissue infection
caused by Gram –ve organism
 Septicaemia by Gram –ve bacterai
 Surgical prophylaxis
 Gonorrhoea
 Typhoid
 Preseptal cellulitis & endophthalmitis
Indications

35.  Pain on intramuscular injection
 Diarrhoea due to alteration of gut ecology
 Hypersensitivity reaction( rashes, asthma,
angioedema and urticaria)
 Nephrotoxicity
Side effect

36. Vancomycin
 Highly effective against Gram +ve cocci
 Uses : used for serious infections
 Drug of choice for treating:
 Methicillin resistant staphylococci
 Penicillin resistant S. pneumoniae
 Recommended for topical, intravitreal &
subconjunctival therapy for bacterial
endophthalmitis

37.  If used with other ototoxic or nephrotoxic drugs
can cause impaired renal function and lead to
permanent deafness
 Contraindicated in hypersensitivity reaction
Side effect

38. Drugs
inhibiting
Protein
synthesis
Tetracycline
Chlorem-
phenicol
Macrolide
Aminoglycoside

39. Mechanism of action

40. Tetracycline
 Broad spectrum antibiotics
 Have nucleus of four cyclic rings, so named
tetracycline
 1st tetracycline to be obtained was
chlortetracycline
 Bacteriostatic in nature

41. Class I
• Tetracycline
• Oxytetracycline
Class II
• Methacycline
Class III
• Doxycycline
• Minocycline
Gram -ve Gram +ve Spirochaetes Chlamydiae
Rickettsiae Entamoeba Mycoplasm
Division of Tetracycline
Coverage of Tetracycline

42. Atypical pneumonia due to
mycoplasma
Cholera
Brucellosis
Plague
Rickettsial infection
To penicillin for tetanus,
actinomyces
To ciprofloxan for gonorrhoea
To ceftriaxone for syphilis
To azithromycin for chlamydial
infection
Drug of first choice Drug of second choice
Indications

43. Ocular Use
Trachoma
Conjunctivitis
Ophthalmia
neonatorum
 Preferred over silver nitrate because it does not cause
chemical conjunctivitis.

44.  Epigastric pain, nausea, vomiting and diarrhoea (irritation
from mucosa )
 Liver toxicity
 Renal toxicity
 Vestibular toxicity (due to drug accumulation in
endolymph)
 Affect teeth and bone: tetracycline get deposited in
developing teeth and bone hence cause discoloration and
ill formation. so contraindicated
 Contraindicated in pregnant, lactating woman and
child<8yrs
 Also contraindicated in pt. with renal dysfunction
Side effects

45. Chloramphenicol
 Broad spectrum
 Nitrobenzene substitute
 Bacteriostatic in nature
 Initially obtained from Streptomyces, now
synthesized chemically

46. Though static in nature, its high concn can be
cidal too
Active against
Gram +ve cocci & bacilli
Chlamydia
Gram –ve cocci & bacilli
Coverage of chloramphenicol

47.  Because of serious bone marrow toxicity use of this drug
has been reduced much
 Not used for infection that can be treated by other
antibiotics. However, some of its use are:
- Enteric fever
- H. Influenza meningitis
- Anaerobic infection by fragillis
 Has extended ocular use as the topical application is less
hazardous than systemic use
 Primarily used in oint. as well gtt. form for conjunctivitis,
blepharitis etc.
Indications

48.  Chloramphenicol available in ointment and
eye drop form
 Ointment 1%
 Eyedrop 0.5%
Indications

49.  Bone marrow depression
 Aplastic anaemia, thrombocytopenia
 Hypersensitivity reaction
 Rashes, fever, angioedema
Gray baby syndrome
 Occurs when high doses=1oomg/kg to neonate as
prophylactic
 Baby stops feeding, vomit, abdomen distended,
hypothermic, irregular respiration
 An ashen gray cyanosis appear with complication of
cardiovascular collapse
 It occurs due to poor renal development in neonate
which results in accumulation of drug
Side effects

50. Aminoglycosides
 Bactericidal in nature
 Includes neomycin, gentamicin, tobramycin,
amikacin, streptomycin
 good coverage for Gram –ve bacilli like P.
aeruginosa, Proteus, Klebseilla, E. coli

51. Neomycin
 Broad spectrum among all the aminoglycoside
 But, cannot show effectivity against P. aeruginosa
 Widely used in ophthalmology in the form of drop
and ointment
 Ointment 0.5%
 Eyedrop 0.5%

52. Gentamicin
 Mainstay in the treatment of serious Gram –ve
bacilli infection
 Frequently used for empiric therapy in presumed
Gram –ve bacilli infection
 Choice of drug for EOD like corneal ulcer
 Ointment 0.3%
 Eyedrop 0.3%

53. Tobramycin
 Same coverage as gentamicin
 Also effective against Staphylococci
 Potent to P.aeruginosa
 In ophthalmology preferred for paediatric use
 Ointment 0.3%
 Eyedrop 0.3%

54. Amikacin
 It is semisynthetic
 Preferred in Gram –ve infection resistant
to gentamycin and tobramycin

55.  Gram –ve bacillary infection
 Septicaemia, abdominal and pelvic sepsis
 Bacterial endocarditis
 TB
 Plague
Indications

56.  Ototoxicity: these drugs get accumulated in the
endolymph and perilymph of inner ear and destroy
the hair cell in organ of corti
 Nephrotoxicity: retention of these drugs in proximal
tubular cells disrupts Ca mediated transport system
and cause renal damage
 Neuromuscular paralysis: these drugs cause decrease
in release of Ach
 Allergic reaction: Contact dermatitis
Side effects

57. Macrolides
 Bacteriostatic in nature
 Protein synthesis inhibitor
 Are compounds having a macrocyclic lactone ring to
which deoxy sugars are attached
 Includes erythromycin, clarithromycin and
azithromycin

58. Erythromycin
 First member of this group
 Effective against many of the same organism as
penicillin G
 So, used in patient allergic to penicillin
 For ocular use
 oral erythromycin are preferred in treatment of
chlamydia infection in children where tetracycline is
contraindicated
 Also used in treatment of trachoma
 Ointment 0.5%
250mg X PO X QID X 3-4 weeks

59. Azithromycin
 Far more active against respiratory infections
due to H.influenza and Moraxella catarrhalis
 Nowadays preferred in Chlamydial infection too
 For trachoma single dose of 1 gm
Clarithromycin
 Same effectivity as erythromycin
 But effective against Haemophilus influenza and
chlamydia too

60.  Epigastric distress
 Ototoxicity
 Cholestatic jaundice
 In patient with hepatic dysfunction because of their
accumulation in liver as well compromised renal
function because their metabolite are excreted from
renal
Contraindications
Side effects

61. Fluoroquinolones
Drug interfering with DNA

62. Fluoroquinolones
 Inhibit bacterial DNA
synthesis
 Are synthetic fluorinated
analogs of quinolones
(Nalidixic acid)
 Bactericidal in nature

63. Mechanism of action
 Fluoroquinolones block the bacterial DNA
synthesis by inhibiting bacterial topoisomerase II
(DNA gyrase) and topoisomerase IV
 Inhibition of DNA gyrase prevents the relaxation
of positively supercoiled DNA that is required for
normal transcription and replication
 Inhibition of topoisomerase IV interferes with
separation of replicated chromosomal DNA into
the respective daughter cells during cell division

65. Classification
Ciprofloxacin Ofloxacin
Pefloxacin Cinafloxacin
Lomefloxacin
Norfloxacin
2ndGeneration
1st Generation

66. Moxifloxacin Gatifloxacin
Trovafloxacin
Levofloxacin3rd Generation
4thGeneration

67. Ciprofloxacin
 Broad spectrum( most susceptible are aerobic
Gram –ve bacilli)
 Rapid in action
 Relatively long post-antibiotic effect
 Low frequency of mutational resistance
 Active against many β-lactam and aminoglycoside
resistant bacteria
Widen use due to

68. From first to fourth generation
-ve +ve coverage
Ofloxacin
 Active against gram negative
 Also shows more potency against gram +ve cocci +
chlamydia, mycoplasma too
Moxifloxacin
 Active against gram –ve bacilli, gram +ve cocci, β-
lactam and macrolide resistant ones and anaerobic
bacteria

69.  Prophylaxis and treatment of urinary tract infection
 Bacillary desentry
 Enteric fever
 Diarrhoea due to E.coli
 Gonorrhoea
 Septicaemia
 Respiratory infection
Indications

70. Generic name Trade name indication
Ciprofloxacin(0.3
%)
Ciloxan Conjuctivitis,
keratitis
Ofloxacin (0.3%) Exocin Conjuctivitis,
keratitis
Levofloxacin Quixin Conjuctivitis
Ophthalmic use
Topical ophthalmic drops can be used for children from one
year old

71. GI upset most common nausea, vomiting, diarrhoea
Hypersensitivity reaction rash, photosensitivity
CNS disturbances dizziness, headache, confusion
 Tendinitis in children (damage growing cartilage). Ophthalmic
drops do not show such toxicity. Hence is safer to use
 Contraindicated in patient with known hypersensitivity to
these drugs
Side effects

72.  Bacteriostatic
 Binds and blocks enzymes mainly pteridine
synthetase, dihydrofolate reductase responsible for
folic acid synthesis
 Folic acid enzymes are nessary for the synthesis of
amino acids, hence necessary for bacterial protein
Metabolic inhibitors
Sulfonamides

73. Mode of action - These antimicrobials are analogues of para-
aminobenzoic acid (PABA) and competitively inhibit formation
of dihydropteroic acid
Spectrum of activity - Broad range activity against Gram +ve
and Gram -ve bacteria; used primarily in urinary tract and
Nocardia infections
Combination therapy - The sulfonamides are used in
combination with trimethoprim; this combination blocks two
distinct steps in folic acid metabolism and prevents the
emergence of resistant strains

74. p-aminobenzoic acid + Pteridine
Dihydropteroic acid
Dihydrofolic acid
Tetrahydrofolic acid
Pteridine
synthetase
Dihydrofolate
synthetase
Dihydrofolate
reductase
Thymidine
Purines
Methionine
Trimethoprim
Sulfonamides

75. Ocular infections Antibacterial drugs Route of
administration
Blepharitis chloramphenicol, Topical
Meibomianitis Tetracycline Oral
Conjunctivitis :
Acute mucopurulent
Hyper acute
Chlamydial
Gentamycin ,ciprofloxacin,
ofloxacin,tobramycin
cefriaxone
tetracycline ,erythromycin
Topical
Parenteral
Oral
Hordeolum cloxacillin, dicloxacillin Topical
Dacryocystitis Amoxicillin ,erythromycin Oral , topical
Keratitis Gentamycin & cepazolin
,ciprofloxacin
Topical
Endopthalmitis Vanomycin & amikacin Intravitreal
Preseptal cellulitis Ampicillin, cloxacillin, cefaclor oral
Antibacterial Drugs of choice for initial treatment of
ocular infection

76. A variety of mutations can lead to antibiotic resistance
Mechanisms of antibiotic resistance
 Enzymatic destruction of drug
 Prevention of penetration of drug
 Alteration of drug's target site
 Rapid ejection of the drug
Resistance genes are often on plasmids or transposons
that can be transferred between bacteria
Antibiotic Resistance

77. Mechanism of Resistance
In cell wall synthesis
inhibitor
Penicillinases: break the beta
lactam ring structure
( staphylococci)
Structural changes in PBP:
S.aureus, S. pneumococci
Change in porin structure:
concerns the Gram Negative
organism
In protein synthesis inhibitor
 A mutation of ribosomal binding site
 Enzymatic modification of antibiotic
 An active efflux of antibiotic out of cell
In nucleic acid synthesis inhibitor
 An alteration of alpha subunit of DNA
gyrase (chromosomal)
 Beta subunit of RNA polymerase
(chromosomal) is altered

79. oTextbook of microbiology by Ananthanarayan & Paniker
o Essentials of Medical Pharmacology KD Tripathi
o Basic & Clinical Pharmacology by Bertram G. Katzung
o Ophthalmic Drugs by Graham Hopkins and Richard Pearson
o Internet
References