Beruflich Dokumente
Kultur Dokumente
Anjali Savita
Post graduate 1ST year
Dept of Conservative dentistry
and endodontics
CONTENTS
DEFINITION OF ANTIBIOTICS
HISTORY
CLASSIFICATION OF ANTIBIOTICS
MECHANISM OF ACTION
PRINICIPLE OF ANTIBIOTIC THERAPY
CHOICE OF AN ANTIMICROBIAL AGENTS
COMBINED USE OF ANTIMICROBIAL AGENTS
ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS
PROPHYLACTIC ANTIBIOTICS
ANTIBIOTIC RESISTANCE
PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS
SUMMARY
CONCLUSION
2
REFERENCES
What is
•Substances producedAntibiotic?
by microorganisms,
•Selectively suppress the growth , kill other microorganisms at very
low concentrations.
1941 - Chain and Florey found out the clinical use of penicillin.
Chemical
7
A. Chemical
structure
1.Sulfonamides and related drugs: Sulfadiazine, Sulfones— Dapsone
(DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines: Trimethoprim, Pyrimethamine.
3. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin, etc.
4. β-lactam antibiotics: Penicillins, Cephalosporins, Monobactams.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Nitrobenzene derivative: Chloramphenicol.
7. Aminoglycosides: Streptomycin, Gentamicin, Neomycin, etc.
11
C. Type of organisms against which primarily active :
12
D. Spectrum of activity
13
SULFONAMIDES
•First antimicrobial agents (AMAs)
•Effective against pyogenic bacterial infections.
•Primarily bacteriostatic - gram positive , gram negative bacteria.
•Individually-bacteriostatic
•Combination-Bacteriocidal.
•Orodental infections,
•Patients allergic to β-lactam antibiotics.
Septran.
Mechanism of action
FLUOROQUINOLONES
16
CIPROFLOXACIN
Uses:
•Most potent first generation FQ.
• Urinary tract infection,
•Rapid bactericidal activity.
typhoid fever.
•β-lactam and aminoglycoside •Ciprofloxacin +
Ofloxacin
•Intermediate between ciprofloxacin and norfloxacin.
•Suited for orodental infections as it is active against certain anaerobes.
•ZANOCIN 100, 200, 400 mg tab. 18
NITROIMIDAZOLES
Pharmacokinetics
METRONIDAZOLE
•completely absorbed from the
•Broad spectrum antiprotozoal drug. small intestines.
•Selectively toxic to anaerobic microorganisms. •metabolized in liver primarily
by oxidation
Bacteriostatic
•excreted in urine
Adverse effects
•Most common : anorexia, nausea, bitter or metallic taste.
•Less frequent side effects are—headache, glossitis, dryness of mouth,
•Contraindicated in the first trimester of pregnancy.
FLAGYL, METROGYL, METRON, 200, 400 mg tab. 19
USES
or tetracycline).
days.
20
•Amoebic infection.
Ornidazole
21
Beta-Lactam Antibiotics
22
•Narrow spectrum
•Activity is limited primarily to gram-positive bacteria and few others.
•Streptococci , gram-positive bacilli and spirochetes are highly
pneumococci sensitive.
•Many bacteria are
inherently insensitive to
PnG .
•Acquired resistance through
production of penicillinase. 27
Adverse effects:
•Produced by chemically combining specific side chains (in place of benzyl side chain of PnG)
or by incorporating specific precursors in the mould cultures.
•Eg. Procaine penicillin and Benzathine penicillin are salts of PnG and not
semisynthetic penicillins.
•The aim of producing semisynthetic penicillins has been to overcome the shortcomings
of PnG, which are:
1. Poor oral efficacy.
2. Susceptibility to penicillinase.
3. Narrow spectrum of activity.
4. Hypersensitivity reactions 29
Phenoxymethyl penicillin (Penicillin
V)
•Acid stable.
•Better oral absorption.
•Plasma t½ is 30–60 min.
•Antibacterial spectrum is similar to penicillin G but it is about 1/5 as active
against Neisseria, other gram-negative bacteria and anaerobes.
•Dose: 250–500 mg, children 125–250 mg; given 6 hourly.
30
PENICILLINASE-RESISTANT PENICILLINS
•Have side chains that protect the β-lactam ring from attack by staphylococcal
penicillinase.
Methicillin
Cloxacillin
Ampicillin
•Active against all organisms sensitive to PnG.
•More active than PnG for Strep. viridans and enterococci (therefore better suited
for dental infections).
•Dose: 0.5–2 g oral/i.m./i.v. depending on severity of infection, every 6
hours; children 25–50 mg/kg/day.
30
USES:
1. Urinary tract infections
2. Respiratory tract infections
3. Meningitis
4. Subacute bacterial endocarditis: preferred over PnG.
Adverse effects:
Diarrhoea is frequent after oral administration of ampicillin
Interactions:
Hydrocortisone inactivates ampicillin if mixed in the i.v. solution.
31
AMOXICILLIN
Clavulanic acid
35
Classification of Cephalosporins
First generation Second generation Third generation Fourth generation
More active against More selective against Highly active against Similar antibacterial
gram positive gram positive and gram negative activity as that of
organism gram negative organisms third generation but
organisms highly resistent to
beta lactamases
Cefadroxil
39
FIRST GENERATION CEPHALOSPORINS
•1960 , high activity against gram-positive but weaker against gram-negative
bacteria.
Cefazolin
Cefadroxil
•Close congener of cephalexin.
•Good tissue penetration including that in alveolar bone (tooth socket)
•Exerts more sustained action at the site of infection.
•Dose: 0.5–1 g BD. DROXYL 0.5, 1 g tab, 41
Third generation Cephalosporins
Cefotaxime:
• 3rd generation
• anaerobic & some gram positive bacteria
• meningitis (gram negative bacilli),
• life threatning /hospital aquired infections.
• septicaemias and infections in immunocompromised patients.
42
BROAD SPECTRUM ANTIBIOTICS
TETRACYCLINE
• Broad spectrum antibiotic.
ADMINISTRATION
• Primarily bacteriostatic. •Orally taken ½ hr before or 2 hr after food
• Inhibit protein synthesis by binding •Not recommended by i.m. route.
PRECAUTIONS:
•Tetracyclines given between 3 months and 6 years of age affect the crown of
permanent anterior dentition.
•Given during late pregnancy or childhood, tetracyclines can cause temporary
suppression of bone growth.
44
Uses in Orodental conditions :
a) Periodontal inflammation
b) Chronic periodontitis General medical uses:
c) Juvenile periodontitis The drug of first choice in:
(a) Atypical pneumonia due to
Mycoplasma pneumoniae
(b) Cholera
(c) Brucellosis.
(d)Relapsing fever due to Borrelia
recurrentis.
(g) Rickettsial infections: typhus , Q fever,
etc.
45
CHLORAMPHENICOL
•Broad-spectrum antibiotic.
•Gram-positive and negative bacteria, rickettsiae, chlamydia, mycoplasma etc.
•Inhibits bacterial protein synthesis.
•Attaches to the 50S ribosome and hinder the access of aminoacyl-tRNA to the
acceptor site for amino acid incorporation.
•Primarily bacteriostatic , high concentrations - cidal effect.
•Rapidly and completely absorbed after oral ingestion.
•Oral administration —as capsules; 250–500 mg 6 hourly
44
Adverse effects USES
•No indication in dentistry despite
1. Bone marrow depression its broad-spectrum antimicrobial
2.Hypersensitivity reactions action.
•Enteric fever
Rashes, fever etc
•Meningitis
3.Irritative effects Nausea,
•As second choice drug
vomiting, diarrhoea, pain on
injection. (a)to tetracyclines for brucellosis,
4. Superinfections cholera,
5.Gray baby syndrome : at rickettsial and chlamydial infections.
high doses (~100 mg/kg) (b)to erythromycin for
whooping cough
45
MACROLIDE
•ANTIBIOTICS
Antibiotics having a macrocyclic lactone ring with attached sugars.
ERYTHROMYCIN
•Isolated from Streptomyces erythreus.
•Widely employed, mainly as an alternative to penicillin.
•Narrow spectrum.
•Active against gram-positive and a few gram-negative organisms.
Mechanism of Action
Erythromycin is bacteriostatic at low concentration but cidal at
high concentrations. Erythromycin acts by inhibiting bacterial
combines with 50S ribosomeprotein
subunit and interferesItwith ‘translocation’.
synthesis. 48
Uses :
Second choice drug to penicillins for:
•Periodontal/ periapical abscesses
•Necrotizing ulcerative gingivitis
•Postextraction infections
•Cellulitis, etc.
In patients allergic to penicillins, or those with penicillin resistant
infections.
49
NEWER MACROLIDES
AZITHROMYCIN
•Has an expanded spectrum.
•Improved pharmacokinetics.
•Better tolerability and drug interaction profiles.
•More active than other macrolides against H. influenzae, certain
and anaerobes like Peptostreptococcus, few Clostridia.
•Better activity against oral spirochetes and gram negative anaerobes.
•Can be used in orodental infections in place of erythromycin.
50
•Dose: 500 mg once daily 1 hour before or 2 hours after food.
CLINDAMYCIN
•Ototoxicity
-Cochlear damage
-Vestibulaar damage
•Nephrotoxicity
•Neuromuscular blockade
51
ANTIFUNGAL DRUGS
Polyenes: Amphotericin B (AMB), Nystatin,
AMPHOTERICIN B (AMB)
•Combine with ergosterol present in fungal cell membrane, and create micropores
through which ions, amino acids and other water-soluble substances move out.
•Candida albicans, Histoplasma capsulatum,, aspergillus etc.
•Not absorbed orally, excretion occurs slowly both in urine and bile.
•Uses: can be used topically for oral, vaginal and cutaneous candidiasis
52
NYSTATI
N
•Used only locally.
•In dentistry, topically applied nystatin is the 2nd choice drug to clotrimazole for oral thrush,
denture stomatitis, antibiotic associated stomatitis, corticosteroid associated oral
candidiasis and mucocutaneous candidiasis of lips, etc
•1 mg tablet is placed in the mouth to dissolve slowly 4 times a day, or it can be crushed and
suspended in glycerine for application on the lesions.
•Bitter foul taste and nausea are the side effects.
53
PRINCIPLES OF ANTIBIOTIC THERAPY
2.Organism related
considerations
• Spectrum of activity
• Type of activity
• Sensitivity of the organism
3.Drug factors • Relative toxicity
• Pharmacokinetic profile 55
Age :
•Larger doses of chloramphenicol - grey baby syndrome.
56
Renal and hepatic function
57
Local factors :
(a) Presence of pus and secretions
(b)Presence of necrotic material or foreign body
(c)Haematomas foster bacterial growth
(d)Lowering of pH at site of infection
Drug allergy :
•In an individual with normal host defence, a bacteriostatic AMA may achieve
cure; while intensive therapy with cidal drugs is imperative in those with
impaired host defence.
59
Pregnancy
60
Genetic factors:
•Sulfonamides, chloramphenicol and fluoroquinolones are likely to produce
haemolysis in G-6PD deficient patient.
Organism-related considerations
Antibiotic susceptibility test
61
Minimum inhibitory concentration (MIC)
•For treatment purposes, the dosage of antibiotic given should yield a peak
body fluid concentration 3-5 times higher than the MIC or MIC x 4 = dosage to
obtain peak achievable concentration.
62
Minimum bactericidal concentration (MBC)
•MBC is the concentration of the antibiotic which kills 99.9% of the bacteria.
65
1. Spectrum of activity:
2. Type of activity:
4. Pharmacokinetic profile:
1. To achieve synergism:
Eg.:
1. combination of a β-lactamase inhibitor clavulanic acid or sulbactam with amoxicillin or ampicillin for β-
lactamase producing H. influenzae.
66
2. To reduce severity or incidence of adverse effects.
67
Disadvantages of antimicrobial combinations
•Incidence of postoperative infection is higher when oral surgery had lasted 2 hours or more
eg. prosthesis insertion into the bone or soft tissue, such as dental implants and extensive
reconstructive surgeries.
•All orodental procedures which disturb/ damage mucosa including extractions, scaling, etc.
need to be covered by prophylaxis in diabetics, corticosteroid recipients and other
immunocompromised subjects
70
71
PROPHYLAXIS OF DISTANT INFECTION
•Gentamicin 120 mg (2 mg/kg) i.m./i.v. may be given just before the dental
procedure in addition to amoxicillin (or its substitute) and another dose of
amoxicillin 500 mg (12.5 mg/kg) be repeated 6 hours after the procedure.
1. Penicillins.
2. Cephalosporins.
3. Erythromycins.
4. Clindamycin and Lincomycin.
5. Metronidazole.
6. Aminoglycosides.
7. Fluoro quinolones – ciprofloxacin.
8. Sulfonamides and trimethoprim
74
AHA RECOMMENDATIONS
Pericoronitis :
•Acute pericoronitis, if severe, may require antibiotic therapy.
•Treatment - debridement, drainage of the site,
penicillin 500 mg qid,
amoxacillin 500mg qid,
clindamycin 300mg
qid
Dento Alveolar Abscess: 78
cephalosporins.
ANUG
Topical measures with systemic antibiotic penicillin, metronidazle 400mg qid, 79
Antibiotic regimen for osteomyelitis
For hospitalalized/ when inta-venous therapy is indicated-
Aqueous penicillin, 2 million Units IV Q6h, metronidazole 500mg q6h for 4 - 6 weeks
OR
Ampicillin/sulbactum 1.5 to 3.0 gm IV q6h for 2 days then amoxacillin/clavulanate
(augmentin)875, 125.mg PO bd for 4 to 6 weeks.
penicillin V 2gm + metronidazole 500mg q8h for 2 to 4 weeks after last sequestrum removal
and patient with out symptons.
OR
cefoxitin 1 gm q8h IV OR IM
cephalexin 500mg q6h PO for 2 to 4 weeks
OR
clindamycin 600, 900mg q6h IV then clindamycin 300, 450 mg PO. 80
Regimen for fracture
•therapeutic doses for 10 to 14 days.
Pre-operatively
penicillin 2 million units or cefazolin 0.5 gm-1.5 gm 12 hr [25- 50 mg/kg].
Post-operatively
82
PUBLC HEALTH IMPORTANCE OF THE ANTIBIOTICS
85
An overview of antimicrobial resistance and its public health significance, Brazilian journal of Microbiology 45, 1, 1-
DEFINITION OF ANTIBIOTICS
S HISTORY
U CLASSIFICATION OF ANTIBIOTICS
A ANTIBIOTIC RESISTANCE
R
86
PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS
CONCLUSIONS
Antibiotics are used to treat infections and are also responsible for making
them more difficult to treat because of their misuses and development of
resistance.
The only way to keep antibiotics useful is to use them appropriately and
judiciously.
85
REFERENCES
THE PHARMACOLOGIC BASIS OF THERAPEUTICS GOODMAN & GILMAN 11THED
ESSENTIALS OF MEDICAL
PHARMACOLOGY K.D.TRIPATHI 5TH ED
TEXTBOOK OF PHARMACOLOGY -
TOPAZIAN
TEXTBOOK OF MUCROBIOLOGY- C. P.
BAVEJA 3RD ED.