This document discusses the principles and therapeutics of antimicrobial agents. It covers the definitions of antibiotics and antimicrobials, the sources and classification of antibiotics, the mechanisms of action and ideal properties of antibiotics, and considerations for their appropriate use and potential disadvantages. The key points are: - Antibiotics are substances that inhibit or kill microorganisms, while antimicrobials have a broader definition to include any substance that inhibits microorganism growth with minimal host damage. - Antibiotics can be natural, semisynthetic, or synthetic, with natural sources mainly being fungi. They vary in toxicity and effectiveness across this spectrum. - Antibiotics work by bacteriostatic or bactericidal

1. Dr. V.K. GUPTA
Division of Medicine
Principles and therapeutics of antimicrobialsPrinciples and therapeutics of antimicrobials

2.  Antibiotic :
Is naturally produced substance or produced synthetically or
semi synthetically that inhibits the growth or kills a
microorganism.
 Antimicrobial agent :
has a broader definition than antibiotic. It includes any
substance produced naturally, synthetically or semi
synthetically that kills or inhibits the growth of micro
organisms, while ideally causing minimal or no damage to the
host.
Antibiotic

3. Sources of Antibiotics
• Natural - Mainly fungal sources
Benzylpenicillin and Gentamicin are natural antibiotics
• Semi-synthetic - Chemically-altered natural compound
Ampicillin and Amikacin are semi-synthetic antibiotics
• Synthetic - Chemically designed in the lab
Moxifloxacin and Norfloxacin are synthetic antibiotics
• There is an inverse relationship between toxicity and
effectiveness as you move from natural to synthetic
antibiotics

4. Role of Antibiotics
 To inhibit multiplication
 Antibiotics have a bacteriostatic effect
 Minimal Inhibitory Concentration = MIC
 MIC = lowest concentration of antibiotic that inhibits
growth
(Riviere 2009)

5. Role of Antibiotics
• To destroy the bacterial population
• Minimal Bactericidal Concentration = MBC
• MBC = lowest concentration of antibiotic that kills
bacteria
• Antibiotics have a bactericidal effect
(Riviere
2009)

6.  Mechanisms of Action
Antibiotics operate by inhibiting crucial life
sustaining processes in the organism: the synthesis
of cell wall material,DNA, RNA, ribosome's and
proteins.
 Target
The target of the antibiotic should be selective to
minimize toxicity for host but all antibiotics are
toxic to some degree
(Riviere 2009)

7. Ideal Antibiotics
 Selective target – target unique
 Narrow spectrum – does not kill normal flora
 High therapeutic index – ratio of toxic level to
therapeutic level
 Few adverse reactions – toxicity, allergy
 Various routes of administration – IV, IM, oral
 Good absorption from site of injection
 Good distribution to site of infection
 Emergence of resistance is slow
( Goodman & Gilman's 2006)

8. (A) Based on spectrum of activity
 Narrow spectrum
 Active against either gram-negative or gram-
positive bacteria e.g. penicillin,
streptomycin, erythromycin
 Broad-spectrum
 Active against both gram-positive and gram-
negative bacteria e.g. tetracycline &
chloramphenicol
(Riviere 2009)
Classification of antibiotics

9. (B)Based on effects of AB
(a)Bacteriostatics
 inhibit bacterial growth.
 The body requires an effective innate and acquired immune system in
the case of bacteriostatic antibiotics.
 For immuno-compromised patients bacteriostatic antibiotics usually
not effective.
 Antimetabolites and inhibitors of protein synthesis (except
aminoglycoside antibiotics) are usually bacteriostatic
(Riviere 2009)

10. (b) Bactericidal
Antibiotic kills bacteria.
Inhibitors of cell wall synthesis and agents
affecting cell membrane permeability are
bactericidal
(Riviere 2009)

11. (C) Based on mode of action
A. Antibacterial agents that inhibit the cell wall synthesis
B. Antibacterial agents that alter the function of the
cytoplasmic membrane
C. Antibacterial agents that inhibit the protein synthesis
D. Antibacterials that inhibit the nucleic acid synthesis
( Goodman & Gilman's 2006)

12. 1. Cause misreading of mRNA code and affect
permeability e.g. streptomycin & gentamicin
2. Inhibit DNA gyrase e.g. fluoroquinolones
3. Interfere with DNA function e.g. Rifampin
4. Interfere with DNA synthesis e.g. acyclovir

14. (D) Uses of antibiotics
Antibacterial
A. Gram positive bacteria Penicillin, Erythromycin
B. Gram negative bacteria Streptomycin, Gentamicin
C. Broad spectrum Chloramphenicol, Tetracycline,fluroquinalones
D. Antitubercular Streptomycin, rifampicin
kanamycin capriomycin
(Riviere 2009)

15. Prophylactic – prior to surgical procedure best time half an hr prior to
surgery e.g. Penicillin
Use a growth promoter – use in adult ruminants
monencin & salinomycin
Antifungal -systemic antifungal agent amphotericin-B
-topical antifungal agent Griseofulvin,
(Riviere
2009)

16.  Antiviral antibiotics- inhibit viral mRNA
polymerase and interfere viral protein and
maturation e.g. Rifampin
interfere viral protein synthesis e.g. Mytomycin,
Puromycin
 Antineoplastic – prevent RNA transcription and
protein synthesis e.g. actinomycin-D
inhibition of RNA & DNA synthesis e.g.
Doxorubincin, Daunorubicin
( Riviere 2009)

17. Uses of antibiotics (contd.)
• Potentiation of inhibitory neurotransmitters in
nematodes and ectoparasite e.g. Ivermectin,doramectin.
• Milbemycin-D & Milbemycin oxime active against
HWP(Heart worm parasites) in dog
• Moxidectin active against nematodes and ectoparasite in
cattle
( Riviere 2009)

18. Uses
Anticoccidial
 inhibit coccidial protein synthesis
e.g. Oxytetracycline (curative) and chlortetracycline
(prophylactic)
 Use as preventive e.g. Monencin
Antianaplasmic
 Tetracycline
Antitheilerial
 Oxytetracycline & rolitetracycline
( Riviere 2009)

19. Advantages
 Easily available, cheap and least toxic
 Easily distributed in body tissues and fluids
 least untoward reaction
 If used properly drugs resistant does not developed
 Antibiotics have saved countless lives
 Broad-spectrum antibiotics which work equally well on
bacteria and fungus
 Each antibiotic is effective only for some types of
disease
 Right antibiotic cures the disease in the shortest span of
time

20. Disadvantages
Toxicity
 Pain, abscess formation on I/M injection
 Thrombophlebitis on I/V injection
Tetracycline, erythromycin &
chloramphenicol
 Ototoxic & nephrotoxic
Aminoglycoside
 Hepatotoxic & nephrotoxic
Tetracycline
 Bone marrow depression and aplastic anemia
Chloramphenicol
(Adams 2001)

21. Disadvantages
 Allergic reaction -hypersensitivity reaction
Penicillins, aminoglycosides & cephalosporin
 Superinfection - Tetracycline,
Chloramphenicol
 Microbial resistance-
Staphylococcus to penicillin
Enterococci to streptomycin
 Vitamin deficiencies- vitamin-B & vitamin-K
 Production of residues in animal products
( Adams 2001)

22.  Disadvantages of combination
 Increase chance of toxicity
 Increase intensity of toxicity of a drug by another drug
 Increase in nephrotoxicity (gentamycin + cephaloridine)
 Chance of Superinfection increase
 Increase cost of therapy
( Adams 2001)

23. Do’s and don’t antibiotics
Newborn can not metabolized and excreted because
lack of metabolizing enzyme e.g. Chloramphenicol &
tetracycline
Young animal accumulate in developing teeth and bone
e.g. tetracycline
Old animal poor renal function slow excretion
e.g. aminoglycoside

24. Pregnancy penicillin and erythromycin can safely
given
avoid all antibiotic in first trimester period of
organogenesis
× tetracycline, aminoglycoside
Milking animal
Iprinomectin nil milk withholding period
(radostits 2000)
× Chloramphenicol & ivermectin

25. Renal dysfunction
× tetracycline, aminoglycoside, amphotericin-B
Hepatic dysfunction
Don’t- erythromycin, chloramphenicol, & rifampin
Drug allergy
 Erythromycin is alternative to penicillin allergy
× Penicillin, aminoglycoside, erythromycin & trimethoprim

26. Presence of blood, pus, CSF
penicillin
× aminoglycoside
Food animal
 follow withdrawal time
× chloramphenicol

27. Penicillin, aminoglycoside,& chloramphenicol
Do’s- parenterally
× Don’t- orally
Meningitis
 Do’s- chloramphenicol, cefotaxime & rifampin
× Don’t- aminoglycoside
Pleural& peritoneal membrane
Do’s- chlortetracycline
× Don’t- penicillin

28. Toxicity
 prefer penicillin, cephalosporin's & erythromycin
× Aminoglycoside, tetracycline chloramphenicol,
vancomycin
Follow directions
 Dos- full course of antibiotics
× Don’t - stop antibiotics too early
Spectrum
 narrow spectrum drugs
× Broad spectrum drugs
Combination
 bacteriostatics + bacteriostatics or bactericidal +
bactericidal
× bacteriostatics + bactericidal

29. Mechanism by which small doses of an antimicrobial can lead toMechanism by which small doses of an antimicrobial can lead to
propagation/selection of resistant strains of bacteriapropagation/selection of resistant strains of bacteria

30. 1. ß-LACTAM ANTIBIOTICS
 Kidneys/bladder/genitourinary tract → exceed MIC
(Rock, 2007; Bill, 2006)
CNS infections (Vaden , 2001)

31. PENICILLINS
• Penicillin G (natural); ampicillin, amoxycillin (aminopenicillins; broad-
spectrum ); cloxacillin (penicillinase-resistant; narrow-spectrum),
carbenicillin, ticarcillin (extended-spectrum)
• Procaine penicillin G (1 day) and benzathine penicillin G (7 days): not IV →
affect cardiac conduction system
(Vaden , 2001)
• Aminopenicillins: empty stomach (Bill, 2006)
Eye/brain/prostate/intracellular bacteria
(Bill, 2006; Vaden, 2001)
Resistant: Pseudomonas, Staphylococci; cross-resistance

32.  Cloxacillin: staphylococcal infections (Bill, 2006)
 Add clavulanic acid and sulbactam → potentiated compound
 Kidneys/liver/lung (Rock, 2007)
• Hypersensitivity reactions most common ADR → record; mild skin rash to
life-threatening anaphylactic shock; injectable > oral; emergency
treatment (epinephrine + corticosteroids); cross-reactivity
(Rock, 2007; Bill, 2006)
• Hydrolysis → degradation (main) (Vaden , 2001)
• Clavulanate packaged individually in foil → absorbs moisture
(Bill, 2006)

33. CEPHALOSPORINS
• 4 generations: ↑ → ↓G+; ↑ G- (Bill, 2006)
• Cephadroxil, cephalexin, cefpodoxime (PO), cefotaxime & ceftazidime
• Stable in solutions for short time, unless frozen
• False + reaction: glucosuria and proteinuria (Vaden , 2001)
• Reactions: much less (Bill, 2006)

34. 2. AMINOGLYCOSIDES
• Neomycin (topical), amikacin (broadest spectrum) & gentamicin
(Riviere, 2001)
• ↓ cross-resistance (Bill, 2006)
• Usually administered parenterally (Riviere, 2001)
• t1/2:2-5 h; post antibiotic effect (PAE) (Bill, 2006)
Eye/brain/prostate/respiratory tract (Strausbaugh, 1983)
Cellular debris (pus) → flush thoroughly (Bill, 2006)
Anaerobic bacteria/conditions (Riviere, 2001)
Denuded skin/surgical sites → renal failure (Mealey, 1994)

35.  DOC for serious G- infections (Riviere, 2001)
 + penicillin (Bill, 2006)
• ↑ toxicity potential; accumulate within kidneys (PCT) and inner ear by
pinocytosis (active) → nephrotoxicity and ototoxicity (auditory: dogs;
vestibular toxicity: cats) (Bill, 2006; Bennett, 1982)
• Monitoring renal function: urine sediment (casts or increased protein are
early signs) & urine SG (not for cats)
(Bill, 2006; Grauer,1995)
• Hydrophilic → steep gradient for diffusion; OD → much safer
(Freeman, 1997)

36. 3. FLUOROQUINOLONES
• Enrofloxacin, difloxacin, orbifloxacin and marbofloxacin
• Broad-spectrum; aerobic bacteria (Papich, 2007)
• Well absorbed PO; not affected by food; reduced (90%) with ulcer treatment
medication (Bill, 2006; Nix, 1989)
First-choice antibiotics (WHO, 1997)
Streptococcal infections (Bill, 2006)

37.  Infections: prostate/skin/soft tissue/wounds/bone/ear/ respiratory & urinary
tract (DeManuelle, 1999; Paradis, 1990)
 ↑ intracellular concentrations → ↑ concentrations in infected tissue e.g.,
pyoderma (WHO, 1997; Garaffo, 1991)
 Pregnancy (Papich, 2001)
• Very safe drugs; but affect developing joint cartilage → not in young
• Cats: retinal degeneration → enrofloxacin dose reduced to 5 mg/kg OD
• ↑ seizure activity → avoid in epileptics (Papich, 2007; Bill, 2006)

38. 4. TETRACYCLINES
• TC, OTC (hydrophilic) and minocycline/ doxycycline (lipophilic)
• Irritating: give PO or IV; slow IV or dilute (Riviere, 2001)
• PO preferred: chelation decreases absorption
(Bill, 2006; Aronson, 1980)
• Distribution ~ lipid solubility (Riviere, 2001)
• TC/OTC → not metabolised; enterohepatic circulation; doxycycline largely
excreted into the intestine
(Bill, 2006; Kunin, 1961)
• OTC: light-sensitive drug (Rock, 2007)

39.  Doxycycline/minocycline → eye/CNS/prostate/ intracellular bacteria/↓ renal
function (Bill, 2006; Shaw, 1986)
• Yellow, mottled tooth discoloration; slow bone development (first few weeks)
(Bill, 2006; Moffit, 1974)
• Dogs: irritation of GIT; cats less tolerant; ® doxycycline + food
(Rock, 2007)
• Expired TC/OTC → nephrotoxic compound → Fanconi’s syndrome
(Bill, 2006)

40. 5. SULPHONAMIDES/SULPHA DRUGS
• Sulphasalazine, sulphadiazine, sulphadimethoxine & sulphamethoxazole
• Many bacteria resistant (Bill, 2006)
• Potentiated sulphonamides → + TMP→ ↓ MIC of both drugs → ↓ SE, ↑
efficacy, bactericidal → OD/ BID (Rock, 2007; Bill, 2006)
Necrotic tissue (Rock, 2007)
Topical use: except silver sulphadiazine & mafenide
(Spoo, 2001)
 Serosal/synovial/ocular/CS fluid/prostate/respiratory & urinary tract
(Rock, 2007; Bill, 2006)
 Sulfasalazine → IBD → 70% in LI → sulfapyridine (sulphonamide) + 5-
aminosalycilic acid (local anti-inflammatory effect) (Rock, 2007)

41. • Dogs: decreased tear production (KCS, or “dry eye”)
(Bill, 2006; Collins, 1986)
• Dog develops new CS → suspect ADR’s (notorious: 82%); Dobermanns
predisposed; dermal reactions (drug eruptions); hypersensitivity: type III
(Rock, 2007; Noli, 1995)
• Cats: PO: salivation
• Sulfasalazine: cautious in cats & aspirin hypersensitive animals
• Crystalluria (dehydration or acidic urine) → concern in small animals
(Bill, 2006)

42. Sulfonamide crystals are typically yellow in color

43. 6. LINCOSAMIDES
• Lincomycin and clindamycin (↑ used)
• ® G+ infections when penicillin resistance/intolerance
(Rock, 2007)
 Clindamycin: anaerobic bacteria (Bill, 2006; Noli, 1999)

44. 7. MACROLIDES
• Erythromycin, azithromycin, clarithromycin & tylosin
(Papich, 2007)
• Spectrum ~ penicillin → substitutes (Bill, 2006)
• PO: preferred; food affects absorption (Kirst, 1989)
CSF (Wilson, 1984)
Acidic environment (Sabath, 1968)
 Respiratory tract (Papich, 2001)
 Well distributed (prostate) (Bill, 2006)
• Inhibits cytochrome P-450; erythromycin ~ motilin
(Papich, 2001; Lester, 1998)
• Vomiting/regurgitation → most common adverse effects
(Bill, 2006; Kunkle, 1995)

45. 8. CHLORAMPHENICOL
• Broad spectrum (Papich, 2001; IARC, 1990)
Lactating animals (Papich, 2001)
Serious CNS infections (Rahal, 1979)
 Well distributed (eye/CNS/prostate) → new agents
(Bill, 2006; Hird, 1986)
• SE: myelosuppression (cats) → ↓ dose than dogs → ↓ liver metabolism + ↓
elimination; neonates (Bill, 2006)
• Inhibits cytochrome P-450; ↑ half lives e.g., pentobarbital
(Adams, 1970)
• Myelosuppression → avoid repeated contact or inhalation
(Bill, 2006; Yunis, 1988)

46. 9. METRONIDAZOLE
• Bactericidal
• Anaerobic conditions (Bill, 2006)
• Neurologic side effects (Longhofer, 1988)

47. REQUISITES FOR RATIONAL ANTIBACTERIAL THERAPY
1) Lesion management and supportive care (Davis,1985)
2) Following the “five rights” of drug administration:
a) Right drug
b) Right dose
c) Right patient
d) Right route
e) Right time (Galbraith, 1999)
3) Monitoring of patient
4) Client education
5) Monitoring response to therapy (Rock, 2007)

48. a. RIGHT DRUG
• Necessary conditions:
 In vitro susceptibility: by CST/AST (Rock, 2007)
 In vivo susceptibility
 Host tolerance (Bill, 2006)
• Other considerations:
 Cost, client compliance, ease of administration & convenient dosage interval
(Bill, 2006)
 Risks/ interactions: avoid compounding (never mix cationic & anionic drugs)
(Papich, 2007; Mir, 1998)
 Impact of the disease process on drug pharmacokinetics (e.g.,
aminoglycosides) and pharmacodynamics (e.g., sulfonamides)
(Novotny 1993; Wilcke 1986)
• Check name (Rock, 2007)

49. b. RIGHT DOSE
• Optimum concentrations at site of infection (Bill, 2006)
• Formula:
• Under doing (larger dogs) → more serious
• Over dosing (cats) (Barragry, 1994)
No diuretics (Mir, 1998)
 Check strength (Rock, 2007)

50. c. RIGHT PATIENT
• Neonatal & pediatric patients:
Tetracyclines, sulfonamides, and fluoroquinolones (Novotny, 1993)
 ↓ hepatic biotransformation → avoid chloramphenicol (Short, 1984)
 ↑ Vd → ↑ dose (Novotny, 1993)
• Pregnancy:
 Basic drugs concentrate in fetal plasma (Novotny, 2001)

51. • Geriatric patients:
 Water-soluble drugs: ↓ Vd
 ↓ elimination (Ritschel, 1987)
• Liver failure:
 ß-lactams
Lincosamides, macrolides, sulfonamides, and chloramphenicol
(Bunch, 1995; Tams, 1984)
• Renal failure:
 Aminoglycosides → same dose; ↑ interval (Bill, 2006; Polzin, 2000)
 Sulphonamides (prevent crystalluria) (Spoo, 2001)

52. d. RIGHT ROUTE
• PO:
 Giving a drink of water before administration
 Enteric-coated formulations/capsules : do not break
(Rock, 2007)
 Empty stomach (Scherer, 1992)
Vomiting
Suspensions : SC or IM
• Severe dehydration: ↓ SC absorption (Novotny, 2001)

53. e. RIGHT TIME
• Frequency: t1/2= 2-3 h: time & concentration dependent (Bill, 2004)
• Time dependent drugs: 100% contact time → compromised IS; ≥ 50%
contact time → working IS (Aucoin, 2002)
• Duration (Novotny, 2001)

54. Thank
you……