INDIAN DENTAL ACADEMY
Leader in continuing dental education
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PRINCIPLES OF SURGICAL AND ANTIMIC...
DEFINITIONS
Antibiotics:
These are the substances produced by the
microorganisms , which suppress the growth or
kill other...
HISTORY
THE PERIOD OF EMPIRICAL USE


Mouldy curd by chinesechinese on boils



Chaulmoogra oil by hindus for leprosy

...
EHLIRCHS PHASE


Animal dung was used for wound dressing



Paul ehlrich initiated work on magic bullet 1900



Dyes an...
MODERN ERA OF CHEMOTHERAPY


1932 Dogmak protonsil red dye for streptococci



1928 Alexander Fleming pencillium



188...
PRINCIPLES OF THERAPY
 Presence
 State

of an infection

of host defenses



Physiological depression



Disease state...
PRESENCE OF INFECTION


Determine presence of infection



Pain, swelling , surface erythema,



pus formation, limitat...
PRESENCE OF INFECTION


Patient does not present with all symptoms



Could just be a inflammation



Ex: 1) Pulpitis
2...
STATE OF HOST DEFENSES
 PHYSIOLOGICAL


Inability to deliver the defending agents



Ex:- Shock
- Reduced circulation d...
STATE OF HOST DEFENSES
 DISEASE

STATES



Malnutrition syndrome



Cancers



Leukemia



Poorly controlled diabetes...
STATE OF HOST DEFENSES
 DEFECTIVE

IMMUNE SYSTEMS



Multiple myeloma



Total body radiotherapy



Agammaglobulinemia...
STATE OF HOST DEFENSES


VARIETY OF THERAPEUTIC AGENTS



Cytotoxic agents and Corticosteroids



Glucocorticoids,

Aza...
SURGICAL INCISION DRAINAGE


Presence of pus



Drain the pus (Dental considerations)



Tissue pressure relieved



B...
DECISION TO USE ANTIBIOTIC
THERAPY


Minor infections with depressed immunity
- Aggressive treatment



Normal immunity ...
PRINCIPLES FOR CHOOSING THE
APPROPRIATE ANTIBIOTIC


Organism related






Identification of the causative organism
D...
PRINCIPLES FOR CHOOSING THE
APPROPRIATE ANTIBIOTIC


Drug related


Use of narrow spectrum antibiotics



Use of least ...
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IDENTIFICATION OF CAUSATIVE
ORGANISM
 Identify

organism and treat

 Culture

and sensitivity

 Initial

empirical ther...
IDENTIFICATION OF ORGANISM
• Bacterial gram stain and culture
– Sterile samples (CSF, blood, urine, surgical tissue)
– Non...
IDENTIFICATION OF CAUSATIVE
ORGANISM


Odontogenic infections
- 70% of these are caused by mixed flora
- 5% aerobic bacte...
IDENTIFICATION OF CAUSATIVE
ORGANISM


Chronic non advancing abscess : Anaerobic



Cellulitis type of infection: Aerobi...
AEROBIC ORGANISMS


Gram positive (viridans group)



Streptococci – milleri, sanguis, salivaris mutans



α-hemolytic
...
ANAEROBIC ORGANISMS


Anaerobic gram positive cocci



Peptostreptococci





Streptococci
Susceptible to penicillin
...
ANAEROBIC ORGANISMS


Bacteroides



Orpharyngeal group



Porphyromonas


Asacchrolyticus



Gingivalis



Endodont...
ANAEROBIC ORGANISMS


Fusobacterium


Susceptible to penicillin



Resistant to erythromycin



Along with milleri cau...
PATHOBIOLOGY OF
ODONTOGENIC INFECTIONS


Entry – aerobic organisms



Invasion – Acidosis, Hypoxia – anaerobes



Antib...
FOCAL INFECTION


FOCUS OF INFECTION:
Refers to circumscribed area of tissue which is infected
with exogenous pathogenic ...
ORAL FOCUS OF INFECTION


Infected periapical lesions
granuloma, cyst, abscess



Teeth with infected root canals



Pe...
SIGNIFICANCE OF ORAL FOCI OF
INFECTION


Rheumatoid arthritis and rheumatic fever



Valvular heart disease SABE



Gas...
CULTURE SENSITIVITY


No improvement after 3 days



Postoperative infection



Infection is recurrent



Actinomycosi...
DETERMINATION OF
ANTIBIOTIC SENSITIVITY


Causative organism should be precisely defined



Development of resistance

...
DETERMINATION OF
ANTIBIOTIC SENSITIVITY


Erythromycin

–

streptococcus,

peptostreptococcus, prevotella no action on
fu...
CHOICE TO BE BASED ON
BACTERIOLOGICAL
EXAMINATION


Bacteriological services not available: empirical
therapy to cover al...
MINIMUM INHIBITORY
CONCENTRATION MIC


The

lowest

concentration

of

an

antibiotic

prevents visible growth of a bacte...
MINIMUM BACTERICIDAL
CONCENTRATION (MBC)


Subculturing from tubes with no visible growth.



Organism killed : No growt...
POSTANTIBIOTIC EFFECT
Lag period between growth of organism in antibiotic
free medium after brief exposure to antibiotic
L...
PATEINT FACTORS
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CHOICE OF AN ANTIBIOTIC


PATIENT FACTORS



AGE



Kinetics of AMA



Conjugation and excretion of chloramphenicol

...
EVEN IN MILD RENAL FAILURE


Cephalosporins



Metronidazole



Vancomycin



Amphotericin B



Ethambutol



Flucyt...
MODERATE-SEVERE RENAL FAILURE


Metronidazole



Cephalothin



Cephaloridine



Nalidixic acid



Cotrimoxazole
www....
DRUGS TO BE AVOIDED
DOSE REDUCTION NEEDED
IN LIVER DISEASES

DRUGS TO BE AVOIDED

DOSE REDUCTION
NEEDED

Erythromycin

est...
LOCAL FACTORS
The conditions prevailing at the site of infection greatly
affect the action of AMAS.
(a) Pus and secretions...
PREGNANCY


Penicillins,

many

cephalosporins

and

erythromycin are safe


TETRACYCLINES


Acute yellow atrophy of li...
PREGNANCY


Aminoglycosides : Foetal ear damage.



Fluoroquinolones



Cotrimoxazole



Chloramphenicol



Sulfonami...
GENETIC FACTORS


Primaquine



Nitrofurantoin



Sulfonamides



Chloramphenicol



Fluoroquinolones



Produce hae...
PATEINTS DRUG HISTORY


Allergic reaction



Toxic reaction



Cross reaction



H/O minor or major side effects



P...
DRUG FACTORS
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USE OF SPECIFIC NARROW
SPECTRUM ANTIBIOTIC


Development resistance



Many different bacteria are exposed



Reduced s...
USE OF LEAST TOXIC
ANTIBIOTIC

 To

prevent the host cell damage

Ex : penicillin / chloramphenicol

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USE OF BACTERICIDAL RATHER
THAN BACTERIOSTATIC DRUG


Less reliance on host defense



Killing of bacteria by antibiotic...
USE OF ANTIBIOTIC WITH
PROVEN HISTORY OF SUCCESS


Subtle toxicities are not proven



Initially sensitive organisms bec...
WHEN TO USE THE NEWER DRUG


Only effective drug



Active at low concentration, less toxic,



Less bothersome side ef...
COST OF ANTIBIOTIC

 High

cost antibiotic is the drug of choice

 Administration

costs

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PATIENT COMPLIANCE


ENCOURAGE PATIENT COMPLIANCE



Compliance decreased with increasing no of
pills/ day



Once a da...
DRUG FACTORS
 Pharmacokinetic


profile:

Present at the site of infection :





In sufficient concentration
Adequat...
PHARMACOKINETIC PROFILE
Distribution and protein binding
breakdown and excretion
Distribution
GI absorption
First pas...
PRINCIPLES OF ANTIBIOTIC
ADMINISTRATION


PROPER DOSES



Proper time interval(T1/2)



Proper route of administration
...
PROPER DOSE


Proper amount to achieve therapeutic effect



Sensitivity tests help to select the dose



Minimum inhib...
PROPER DOSES



Therapeutic levels / toxicity levels



High doses justified when site of infection sealed
off blood sup...
PROPER TIME INTERVAL


Adjust dose according to established plasma t 1/2



4 times the t1/2 is taken as the dosage



...
PROPER ROUTE OF
ADMINISTRATION



Fasting state/ food intake



IV/ oral

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61
CONSISTENCY IN ROUTE OF
ADMINISTRATION



Severe infection – start i.v antibiotic



Decision to shift to oral antibioti...
COMBINATION ANTIBIOTIC
THERAPY


Avoid when not necessary






Depression of normal host flora
Opportunistic bacteria...
COMBINED USE OF
ANTIMICROBIALS


To achieve synergistic



To reduce severity or incidence of adverse
effects



To pre...
DISADVANTAGES OF
ANTIMICROBIAL COMBINATIONS


They foster a casual rather than rational outlook
in the diagnosis of infec...
DISADVANTAGES OF
ANTIMICROBIAL COMBINATIONS


Increased chances of superinfections.



If inadequate doses of nonsynergi...
PROBLEMS THAT ARISE WITH
ANTIBIOTIC USE
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67
LOCAL IRRITANCY


Site of administration



Gastric irritation



Pain and abscess - i.m. injection



Thromboflebitis...
SYSTEMIC TOXICITY


Some have a high therapeutic index



Doses over nearly 100 fold range administered



Penicillins,...
SYSTEMIC TOXICITY


Others have a lower therapeutic index –



Doses individualized and toxicity watched for,


Aminogl...
SYSTEMIC TOXICITY


Still others have a very low therapeutic index use highly restricted


Polymyxin B - Neurological an...
HYPERSENSITIVITY


All AMAs cause



Un-predictable



Unrelated to dose



Rashes to anaphylactic shock



Commonly ...
RESISTANCE

It refers to unresponsiveness of a microorganism
to an AMA and is akin to the phenomenon of
tolerance seen in ...
NATURAL RESISTANCE


Some are always resistant to AMAS.



They lack the metabolic process



The target site - affecte...
ACQUIRED RESISTANCE


Resistance by an organism over period of time.



Major clinical problem.



Dependent on microor...
RESISTANCE
MUTATION




stable and heritable genetic change
microorganisms higher concentration of the AMA for
inhibiti...
RESISTANCE


(ii) Multistep.



A number of gene modifications are involved



sensitivity decreases gradually in a ste...
GENE TRANSFER


Can occur by



Conjugation Sexual contact through bridge orsex pilus



Transduction

It

is

the

tra...
EFFECTS OF RESISTANCE


Drug tolerant



Drug destroying



:

Drug impermeable

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79
CROSS RESISTANCE


Resistance to one
resistance to other

antibiotic



They should be Chemically or mechanically
simila...
PREVENTION OF DRUG
RESISTANCE
 No indiscriminate and inadequate or
unduly prolonged use
 This

would

Minimise

the

sel...
INTOLERANCE
 It

is the appearance of characteristic

toxic

effects

of

a

drug

in

an

individual at therapeutic dose...
IDIOSYNCRASY
 It is genetically determined abnormal
reactivity to a chemical.
 Certain adverse effects of some drugs
are...
SUPERINFECTION
(SUPRAINFECTION)
 Appearance of new infection as a result
of new treatment
 This is because of Normal mic...
COMMON SUPERINFECTIONS
 Corticosteroid therapy
 Leukemias and other malignancies
 Treated with anticancer drugs
 Acqui...
MINIMISE SUPERINFECTIONS

 Use specific (narrow spectrum)
 Avoid

in

trivial,

self

limiting

or

untreatable (viral) ...
NUTRITIONAL DEFICIENCIES
 B complex and Vit K synthesized by the
intestinal flora
prolonged use cause eliminates flora

...
MASKING OF AN INFECTION
A short course briefly suppress one
infection but can not suppress another one
contracted concurr...
PROPHYLACTIC ANTIBIOTICS

The difference between
treating
and
preventing
infections is that treatment is
directed against ...
PROPHYLAXIS AGAINST SPECIFIC
ORGANISMS



Rheumatic

fever:

group

A

Streptococci: long penicillin G


Tuberculosis: c...
PROPHYLAXIS AGAINST
SPECIFIC ORGANISMS
d) Gonorrhea /syphilis: procaine penicillin.
e) Rickettsial infections : Tetracycli...
PREVENTION OF INFECTION IN
GENERAL
(a) Neonates, specially after prolonged or
instrumental delivery.
(b)To prevent postpar...
PRINCIPLES OF
PROPHYLACTIC ANTIBIOTICS

TIMING, PRE-OP:

 present at therapeutic levels at the
site time of contamination...
PRINCIPLES OF
PROPHYLACTIC ANTIBIOTICS

 TIMING, PRE-OP
 Therapeutic levels maintained for the
duration of the procedure...
PRINCIPLES OF
PROPHYLACTIC ANTIBIOTICS

 Post-op:
 Post-operatively have little effect on
wound infections.
 After 24 h...
FAILURE OF ANTIBIOTIC
THERAPY

 Improper selection of drug, dose, route
or duration of treatment.
 Treatment begun too l...
FAILURE OF ANTIBIOTIC
THERAPY
 Poor host defense
 Infecting

organism

present

behind

barriers
 Trying to treat untre...
CLASSIFICATION
SYSTEMS OF
ANTIBIOTICS
98

….s

….…

s sj.d..
CHEMICAL STRUCTURE

1.SULFONAMIDES AND RELATED DRUGS:
Sulfadiazine and others,
Sulfones-Dapsone (DDS),
Paraaminosalicylic ...
CHEMICAL STRUCTURE

4. Β-LACTAM ANTIBIOTICS:
Penicillins, Cephalosporins,
Monobactams,Carbapenems

5. TETRACYCLINES:
Oxyte...
CHEMICAL STRUCTURE
7.Aminoglycosides:
Streptomycin, Gentamicin, Neomycin etc.

8.

Macrolides antibiotics:
Erythromycin, R...
CHEMICAL STRUCTURE
12. Nicotinic acid derivalives:
Isoniazid
,Ethionamide.

,Pyrazinamide

13. Polyene antibiotics:
Nystat...
MECHANISM OF ACTION
1.

Inhibit cell wall synthesis:
Penicillin, Cephalosporins, Cycloserine,
Vancomycin, Bacitracin,

2.
...
MECHANISM OF ACTION
5.

Inhibit DNA gyrase:
Fluoroquinolones-Ciprofloxacin.

6.

Interfere with DNA function:
Rifampin, Me...
TYPE OF ORGANISMS AGAINST
WHICH PRIMARILY ACTIVE

1. Antibacterial.
Penicillins, Aminoglycosides,
2. Antifungal.
Griseoful...
SPECTRUM OF
ACTIVITY

Narrow spectrum
 Penicillin G
 Streptomycin

Broad spectrum
Tetracyclines
Chloramphenicol

 Eryth...
TYPE OF ACTION

Primarily
bacteriostatic

Sulfonamides
Tetracyclines

Primarily
bactericidal
Penicillins
Cephalosporins
Na...
ANTIBIOTICS ARE OBTAINED FROM

FUNGI

BACTERIA ACTINOMYCETES

Penicillin

Polymyxin B

Aminoglycosides

Cephalosporin

Col...
ANTIBIOTICS THAT INHIBIT
CELL WALL SYNTHESIS

 ß-lactam Antibiotics
 Major Classes
 Penicillins
 Cephalosporins
 Carb...
MECHANISM OF ACTION OF ßLACTAM ANTIBIOTICS

Inhibit cell wall synthesis blocking
the action of transpeptidases, also
known...
PREPARATIONS
 Sodium penicillin (crystalline penicillin) 0.5-5 MU
i.m/i.v 6-12 hourly It is available as dry powder in
vi...
PREPARATIONS
A- Fortified procaine penicillin G inj:
contains 3 lac U procaine penicillin and 1
lac U sod. penicillin G to...
PENICILLIN AND RELATED ßLACTAMS

Penicillin, ampicillin (amoxicillin)
Gram positive (eg, S. pneumoniae,
enterococcus)
Exte...
1.Acid resistant alternative to penicillin
G: penicillin V
2.Penicillinase resistant penicillins: methicillin ,
Oxacillin
...
USES

 Streptococcal infections
 Pneumococcal infections
 Meningococcal infections
 Gonorrhoea
 Syphillis
 Diptheria...
ADVERSE INFECTIONS

 Local irritancy and direct toxicity
 Hypersensitivity
 Superinfections
 Jarisch Herxheimer reacti...
CEPHALOSPORINS (ß-LACTAM)

 First

generation

(S.

aureus,

Streptococci)
– Cefazolin
 Second generation (H. influenzae...
CEPHALOSPORINS (ßLACTAM)
 Third generation (CSF penetration, iv)
– Ceftriaxone, cefotaxime (Streptococci,
GNR)
– Ceftizox...
ADVERSE EFFECTS

 Pain after i.m injection
 Diarrhoea
 Hypersensitivity reactions
 Nephrotoxicity
 Bleeding
 Neutrop...
USES

 As an alternative to PnG
 Respiratory,
urinary,
soft
tissue
infections
 Penicillinase producing staphylococcal
i...
OTHER ß-LACTAMS

• Carbapenems (Very broad spectrum)
Imipenem
Meropenem
ß-lactams-ß-lactamase inhibitor
combinations
A...
GLYCOPEPTIDE ANTIBIOTICS

• Vancomycin
 Inhibits

cell

wall

synthesis

by

blocking
transpeptidase and transglycosylase...
ADVERSE EFFECTS

 Nerve defects : dose dependant
 Kidney damage
 Skin allergy fall in BP during i.v
injections
 Rapid ...
ANTIBIOTICS THAT INHIBIT
PROTEIN SYNTHESIS

 mRNA 50S 30S
 Nascent polypeptide 50S 30S

124

….s

….…

s sj.d..
COMMONLY USED PROTEIN
SYNTHESIS INHIBITORS

 AMINOGLYCOSIDE(gentamicin,
tobramycin)
– Inhibits protein synthesis but also...
USES

 Tuberculosis
 SABE
 Plague
 Tularemia
 In treating Pseudomonas, Proteus
or Klebsiella infections
 Meningitis ...
ADVERSE EFFECTS
 Ototoxicity
 Nephrotoxicity
 Neuromuscular blockade

127

….s

….…

s sj.d..
PRECAUTIONS AND
INTERACTIONS
(i) Avoid during pregnancy: risk of foetal
ototoxicity.
(ii) Avoid concurrent use of other ot...
(lv) Cautious use in patients past middle age
and in those with kidney damage(v) Cautious use of muscle relaxants in
patie...
MACROLIDES

 Erythromycin,

clarithromycin,

azithromycin
 Static;

often

used

for

respiratory

infections (eg, Strep...
ADVERSE REACTIONS
Gastrointestinal : epigastric pain ,
diarrhoea
Reversible hearing impairment
Hypersensitivity
Hepati...
USES

 As an alternative to penicillin
 Atypical pneumonia
 Whooping cough
 Chancroid
 Compylobacter enteritis
 Lego...
TETRACYCLINES

 Tetracyclines (tetracycline,
doxycycline)
 Broad activity v/s respiratory
pathogens, atypical bacteria (...
ADVERSE EFFECTS

 Kidney damage
 Liver damage
 Phototoxicity
 Teeth and bones
 Antianabolic effect
 Increased intrac...
PRECAUTIONS

 Not to use in pregnant women
 Avoid in pateints with diuretics :
blood urea rises
 Renal and hepatic insu...
USES

 Lymphogranuloma venerum
 Granuloma inguinale
 Atypical pneumonia
 Cholera
 Brucellosis
 Plague
 Relapsing fe...
USES

Listeria infections
Penicillin resistant penicillin
Chlamydia infections
Chancroid
Tularemia

137

….s

….…

s ...
USES

 UTI
community acquired pneumonia
 Amoebiasis
 Malaria
 Acne
 COPD

138

….s

….…

s sj.d..
OTHER INHIBITORS OF PROTEIN
SYNTHESIS

CHLORAMPHENICOL
Broad activity, penetrates CSF
Idiosyncratic and irreversible bon...
CHLORAMPHENICOL

 Active

against

Staphylococci

resistant to methicillin (nafcillin)
 Active against resistant Enteroc...
ADVERSE REACTIONS

 Bone marrow depression
 Hypersensitivity reactions
 Irritative effects
 Superinfections
 Gray bab...
USES












Enteric fever
H.influenzae meningitis
Anaerobic infections
Intraocular infections
SECOND DRUG I...
ANTIBIOTICS THAT AFFECT
NUCLEIC ACIDS

 FLUOROQUINOLONES(CIPROFLOXICIN,
GATIFLOXICIN,
LEVOFLOXICIN,,MOXIFLOXICIN)

– Inhi...
USES













….s

….…

UTI
Gonorrhoea
Chancroid
Bacterial gastroenteritis
Typhoid
Bone,
soft
tissue,
gynae...
ADVERSE REACTIONS

 Gastrointestinal : nausea, vomiting,
bad taste, anorexia
 CNS:

dizziness,

restlessness,

anxiety,
...
ANTIBIOTICS THAT AFFECT
NUCLEIC ACIDS

 Nitroimidazoles (metronidazole)
– Anaerobes and some protozoa (eg,
giardia, amebi...
ADVERSE EFFECTS

 Anorexia, nausea, metallic taste
 Headache ,glossitis
 Peripheral neuropathy
 Thrombophlebitis
 Dis...
USES

 Amoebiasis
 Giardiasis
 Trichomonas vaginitis
 Anaerobic bacterial infections
 Pseudomembranous enterocolitis
...
ANTIMETABOLITES

 Sulfonamides (Sulfamethoxazole,
sulfadiazine)
 Interfere with microbial folic acid
synthesis
 Ultimat...
TRIMETHOPRIM +
SULFAMETHOXAZOLE

 Used primarily in UTI, but E. coli
resistance is increasing
 Respiratory tract infecti...
Adverse effects













….s

….…

Nausea, vomiting, epigastric pain
Crystalluria
Hypersensitivity reaction...
RIFAMYCINS (RIFAMPIN)

 Inhibits

DNA-dependent

RNA

polymerase; bactericidal
 Forms a critical part of therapy for
tub...
RIFAMYCINS (RIFAMPIN)

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Adverse effects

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 Respiratory syndrome: shock
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ANTIFUNGAL AGENTS

 POLYENES (AMPHOTERICIN B)
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disrupt cell membrane
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ANTIFUNGAL AGENTS

 AZOLES
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Principles of surgical and antimicrobial infection managemen /certified fixed orthodontic courses by Indian dental academy

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The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.

Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
0091-9248678078

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Principles of surgical and antimicrobial infection managemen /certified fixed orthodontic courses by Indian dental academy

  1. 1. INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com PRINCIPLES OF SURGICAL AND ANTIMICROBIAL INFECTION MANAGEMENT www.indiandentalacademy.com 1
  2. 2. DEFINITIONS Antibiotics: These are the substances produced by the microorganisms , which suppress the growth or kill other microorganisms at very low concentrations  Chemotherapy : Treatment of systemic infections with specific drugs that selectively suppress the infecting microorganisms without significantly affecting the host  www.indiandentalacademy.com 2
  3. 3. HISTORY THE PERIOD OF EMPIRICAL USE  Mouldy curd by chinesechinese on boils  Chaulmoogra oil by hindus for leprosy  Chenopodium by aztecs for intestinal worms  Mercury by paracelsus for syphilis  Cinchona bark for fevers www.indiandentalacademy.com 3
  4. 4. EHLIRCHS PHASE  Animal dung was used for wound dressing  Paul ehlrich initiated work on magic bullet 1900  Dyes and organometallic compounds  Atoxyl for sleeping sickness  Arsphenaramine for for syphilis www.indiandentalacademy.com 4
  5. 5. MODERN ERA OF CHEMOTHERAPY  1932 Dogmak protonsil red dye for streptococci  1928 Alexander Fleming pencillium  1885 Fredrick Dennis similar findings  Ernst chain original preparations of penicillin  Giuseppe brotzu in 1948 cephalosporin  Selman Waksman 1953 Streptomycin www.indiandentalacademy.com 5
  6. 6. PRINCIPLES OF THERAPY  Presence  State of an infection of host defenses  Physiological depression  Disease states  Defective immune systems  Variety of therapeutic drugs  Surgical incision and drainage  Decision to use antibiotic therapy www.indiandentalacademy.com 6
  7. 7. PRESENCE OF INFECTION  Determine presence of infection  Pain, swelling , surface erythema,  pus formation, limitation of motion  Fever, lymphadenopathy, malaise  Toxic appearance, increased WBC count www.indiandentalacademy.com 7
  8. 8. PRESENCE OF INFECTION  Patient does not present with all symptoms  Could just be a inflammation  Ex: 1) Pulpitis 2) 3rd molar extraction 3) Patients undergoing maxillofacial procedure under GA www.indiandentalacademy.com 8
  9. 9. STATE OF HOST DEFENSES  PHYSIOLOGICAL  Inability to deliver the defending agents  Ex:- Shock - Reduced circulation due to age, Obesity, fluid imbalances www.indiandentalacademy.com 9
  10. 10. STATE OF HOST DEFENSES  DISEASE STATES  Malnutrition syndrome  Cancers  Leukemia  Poorly controlled diabetes www.indiandentalacademy.com 10
  11. 11. STATE OF HOST DEFENSES  DEFECTIVE IMMUNE SYSTEMS  Multiple myeloma  Total body radiotherapy  Agammaglobulinemia  Splenectomy children www.indiandentalacademy.com 11
  12. 12. STATE OF HOST DEFENSES  VARIETY OF THERAPEUTIC AGENTS  Cytotoxic agents and Corticosteroids  Glucocorticoids, Azathioprine, cyclosporine depresses T- cell B-cell counts  Antibiotic prophylaxis www.indiandentalacademy.com 12
  13. 13. SURGICAL INCISION DRAINAGE  Presence of pus  Drain the pus (Dental considerations)  Tissue pressure relieved  Better vascular flow established  Prevention of deeper penetration  Cellulitis – incision – pressure relieved www.indiandentalacademy.com 13
  14. 14. DECISION TO USE ANTIBIOTIC THERAPY  Minor infections with depressed immunity - Aggressive treatment  Normal immunity with minor infection – No treatment  Ex: penicillin  Benefit V/S Risk www.indiandentalacademy.com 14
  15. 15. PRINCIPLES FOR CHOOSING THE APPROPRIATE ANTIBIOTIC  Organism related    Identification of the causative organism Determination of antibiotic sensitivity Patient related  Age  www.indiandentalacademy.com Kinetics of drug in the body 15
  16. 16. PRINCIPLES FOR CHOOSING THE APPROPRIATE ANTIBIOTIC  Drug related  Use of narrow spectrum antibiotics  Use of least toxic antibiotic  Use of bactericidal rather than static drug  Use of antibiotic with proven history of success  Cost of antibiotic  Pharmacokinetic and dynamic properties  Encourage patient compliance www.indiandentalacademy.com 16
  17. 17. www.indiandentalacademy.com 17
  18. 18. IDENTIFICATION OF CAUSATIVE ORGANISM  Identify organism and treat  Culture and sensitivity  Initial empirical therapy - Site and features of infection have been well defined - Circumstances leading to infection are well known - organisms which commonly cause infection are known www.indiandentalacademy.com 18
  19. 19. IDENTIFICATION OF ORGANISM • Bacterial gram stain and culture – Sterile samples (CSF, blood, urine, surgical tissue) – Non-sterile samples (sputum, wound, stool) • Antigen detection & nucleic acid hybridization – Group A Streptococcus, N. gonorrheae, Legionella www.indiandentalacademy.com 19
  20. 20. IDENTIFICATION OF CAUSATIVE ORGANISM  Odontogenic infections - 70% of these are caused by mixed flora - 5% aerobic bacteria - 25 % pure anaerobic bacteria www.indiandentalacademy.com 20
  21. 21. IDENTIFICATION OF CAUSATIVE ORGANISM  Chronic non advancing abscess : Anaerobic  Cellulitis type of infection: Aerobic  Infection becomes severe : Mixed flora  Infection contained by host : Anaerobic www.indiandentalacademy.com 21
  22. 22. AEROBIC ORGANISMS  Gram positive (viridans group)  Streptococci – milleri, sanguis, salivaris mutans  α-hemolytic streptococci – susceptible to penicillin www.indiandentalacademy.com 22
  23. 23. ANAEROBIC ORGANISMS  Anaerobic gram positive cocci   Peptostreptococci   Streptococci Susceptible to penicillin Anaerobic gram negative cocci  Fusobacterium  Bacteriodes www.indiandentalacademy.com 23
  24. 24. ANAEROBIC ORGANISMS  Bacteroides  Orpharyngeal group  Porphyromonas  Asacchrolyticus  Gingivalis  Endodontalis Prevotella - melaninogenica - Buccae www.indiandentalacademy.com - Intermedia 24
  25. 25. ANAEROBIC ORGANISMS  Fusobacterium  Susceptible to penicillin  Resistant to erythromycin  Along with milleri causes severe mediastinitis www.indiandentalacademy.com 25
  26. 26. PATHOBIOLOGY OF ODONTOGENIC INFECTIONS  Entry – aerobic organisms  Invasion – Acidosis, Hypoxia – anaerobes  Antibiotics helpful in odontogenic infections – (streptococcal/ anaerobes)  In cellulitis – Antistreptococcal activity  In Abscess – antianaerobic activity important www.indiandentalacademy.com 26
  27. 27. FOCAL INFECTION  FOCUS OF INFECTION: Refers to circumscribed area of tissue which is infected with exogenous pathogenic microorganisms and which is usually located near mucous or cutaneous surface.  FOCAL INFECTION : Refers to metastasis from the focus of infection of organisms or their toxins that are capable of injuring tissue. www.indiandentalacademy.com 27
  28. 28. ORAL FOCUS OF INFECTION  Infected periapical lesions granuloma, cyst, abscess  Teeth with infected root canals  Periodontal disease with respect manipulation and extraction of teeth www.indiandentalacademy.com 28
  29. 29. SIGNIFICANCE OF ORAL FOCI OF INFECTION  Rheumatoid arthritis and rheumatic fever  Valvular heart disease SABE  Gastrointestinal diseases  Ocular diseases  Skin diseases  Renal diseases www.indiandentalacademy.com 29
  30. 30. CULTURE SENSITIVITY  No improvement after 3 days  Postoperative infection  Infection is recurrent  Actinomycosis is suspected  Osteomyelitis is present www.indiandentalacademy.com 30
  31. 31. DETERMINATION OF ANTIBIOTIC SENSITIVITY  Causative organism should be precisely defined  Development of resistance  Penicillin – streptococcus/ anaerobes  Clindamycin – streptococcus, five anaerobes www.indiandentalacademy.com 31
  32. 32. DETERMINATION OF ANTIBIOTIC SENSITIVITY  Erythromycin – streptococcus, peptostreptococcus, prevotella no action on fusobacterium  Cephalexin – streptococcus (less sensitive) effective against anaerobes  Metronidazole – sensitive for anaerobes www.indiandentalacademy.com 32
  33. 33. CHOICE TO BE BASED ON BACTERIOLOGICAL EXAMINATION  Bacteriological services not available: empirical therapy to cover all likely organisms  Bacteriological services available, but treatment cannot be delayed:  Bacteriological services are available and treatment can be delayed www.indiandentalacademy.com 33
  34. 34. MINIMUM INHIBITORY CONCENTRATION MIC  The lowest concentration of an antibiotic prevents visible growth of a bacterium  Determined in microwell culture plates  Using serial dilutions of the antibiotic is more informative  Not estimated routinely. www.indiandentalacademy.com 34
  35. 35. MINIMUM BACTERICIDAL CONCENTRATION (MBC)  Subculturing from tubes with no visible growth.  Organism killed : No growth  If inhibited grow on subcultures  MBC kills 99.9% of the bacteria.  Small difference between indicates bactericidal,  Large difference indicates bacteriostatic action. www.indiandentalacademy.com MIC and MBC 35
  36. 36. POSTANTIBIOTIC EFFECT Lag period between growth of organism in antibiotic free medium after brief exposure to antibiotic Long postantibiotic effect Fluoroquinolones, Aminoglycosides β-lactam antibiotics. www.indiandentalacademy.com 36
  37. 37. PATEINT FACTORS www.indiandentalacademy.com 37
  38. 38. CHOICE OF AN ANTIBIOTIC  PATIENT FACTORS  AGE  Kinetics of AMA  Conjugation and excretion of chloramphenicol  Blood brain barrier V/S sulfonamide  Elderly pts t1/2 of aminoglycosides www.indiandentalacademy.com 38
  39. 39. EVEN IN MILD RENAL FAILURE  Cephalosporins  Metronidazole  Vancomycin  Amphotericin B  Ethambutol  Flucytosine www.indiandentalacademy.com 39
  40. 40. MODERATE-SEVERE RENAL FAILURE  Metronidazole  Cephalothin  Cephaloridine  Nalidixic acid  Cotrimoxazole www.indiandentalacademy.com 40
  41. 41. DRUGS TO BE AVOIDED DOSE REDUCTION NEEDED IN LIVER DISEASES DRUGS TO BE AVOIDED DOSE REDUCTION NEEDED Erythromycin estolate Chloramphenicol Tetracyclines Isoniazid Pyrazinamide Metronidazole www.indiandentalacademy.com 41
  42. 42. LOCAL FACTORS The conditions prevailing at the site of infection greatly affect the action of AMAS. (a) Pus and secretions (b) Necrotic material or foreign body : eradication of infection (c) Haematomas foster bacterial growth (d) Lowering of pH : macrolide and aminoglycoside antibiotics. (e) Anaerobic environment aminoglycosides in the bacterial cell. (f) Penetration barriers www.indiandentalacademy.com 42
  43. 43. PREGNANCY  Penicillins, many cephalosporins and erythromycin are safe  TETRACYCLINES  Acute yellow atrophy of liver  Pancreatitis  Kidney damage  Teeth and bone deformities www.indiandentalacademy.com 43
  44. 44. PREGNANCY  Aminoglycosides : Foetal ear damage.  Fluoroquinolones  Cotrimoxazole  Chloramphenicol  Sulfonamides  Nitrofurantoin : Avoided in 3rd trimester. www.indiandentalacademy.com 44
  45. 45. GENETIC FACTORS  Primaquine  Nitrofurantoin  Sulfonamides  Chloramphenicol  Fluoroquinolones  Produce haemolysis in G-6PD deficient patient. www.indiandentalacademy.com 45
  46. 46. PATEINTS DRUG HISTORY  Allergic reaction  Toxic reaction  Cross reaction  H/O minor or major side effects  Potential drug interaction www.indiandentalacademy.com 46
  47. 47. DRUG FACTORS www.indiandentalacademy.com 47
  48. 48. USE OF SPECIFIC NARROW SPECTRUM ANTIBIOTIC  Development resistance  Many different bacteria are exposed  Reduced super infections  Host flora affected – overgrowth of resistant strains  Moniliasis to gram –ve pneumonias www.indiandentalacademy.com 48
  49. 49. USE OF LEAST TOXIC ANTIBIOTIC  To prevent the host cell damage Ex : penicillin / chloramphenicol www.indiandentalacademy.com 49
  50. 50. USE OF BACTERICIDAL RATHER THAN BACTERIOSTATIC DRUG  Less reliance on host defense  Killing of bacteria by antibiotic it self  Faster results  Greater flexibility with dosage intervals www.indiandentalacademy.com 50
  51. 51. USE OF ANTIBIOTIC WITH PROVEN HISTORY OF SUCCESS  Subtle toxicities are not proven  Initially sensitive organisms become resistant  Resistance slowed down by limiting the use www.indiandentalacademy.com 51
  52. 52. WHEN TO USE THE NEWER DRUG  Only effective drug  Active at low concentration, less toxic,  Less bothersome side effects  Less expensive www.indiandentalacademy.com 52
  53. 53. COST OF ANTIBIOTIC  High cost antibiotic is the drug of choice  Administration costs www.indiandentalacademy.com 53
  54. 54. PATIENT COMPLIANCE  ENCOURAGE PATIENT COMPLIANCE  Compliance decreased with increasing no of pills/ day  Once a day for 4-5 days www.indiandentalacademy.com 54
  55. 55. DRUG FACTORS  Pharmacokinetic  profile: Present at the site of infection :    In sufficient concentration Adequate length of time. Penetration site of infection : pharmacokinetic properties www.indiandentalacademy.com 55
  56. 56. PHARMACOKINETIC PROFILE Distribution and protein binding breakdown and excretion Distribution GI absorption First pass metabolism www.indiandentalacademy.com 56
  57. 57. PRINCIPLES OF ANTIBIOTIC ADMINISTRATION  PROPER DOSES  Proper time interval(T1/2)  Proper route of administration  Consistency in route of administration  Combination antibiotic therapy www.indiandentalacademy.com 57
  58. 58. PROPER DOSE  Proper amount to achieve therapeutic effect  Sensitivity tests help to select the dose  Minimum inhibitory concentration(3-4 times)  Blood levels to be achieved www.indiandentalacademy.com 58
  59. 59. PROPER DOSES  Therapeutic levels / toxicity levels  High doses justified when site of infection sealed off blood supply  Sub therapeutic doses mask only infection  Clinician fears of toxicity www.indiandentalacademy.com 59
  60. 60. PROPER TIME INTERVAL  Adjust dose according to established plasma t 1/2  4 times the t1/2 is taken as the dosage  Preexisting disease states www.indiandentalacademy.com 60
  61. 61. PROPER ROUTE OF ADMINISTRATION  Fasting state/ food intake  IV/ oral www.indiandentalacademy.com 61
  62. 62. CONSISTENCY IN ROUTE OF ADMINISTRATION  Severe infection – start i.v antibiotic  Decision to shift to oral antibiotic www.indiandentalacademy.com 62
  63. 63. COMBINATION ANTIBIOTIC THERAPY  Avoid when not necessary    Depression of normal host flora Opportunistic bacteria emerge When to use combination therapy  Life threatening sepsis  Infection due to enterococcus www.indiandentalacademy.com 63
  64. 64. COMBINED USE OF ANTIMICROBIALS  To achieve synergistic  To reduce severity or incidence of adverse effects  To prevent emergence of resistance  To broaden the spectrum of antimicrobial action www.indiandentalacademy.com  Treatment of mixed infection 64
  65. 65. DISADVANTAGES OF ANTIMICROBIAL COMBINATIONS  They foster a casual rather than rational outlook in the diagnosis of infections and choice of AMA.  Increased incidence and variety of adverse effects.  Toxicity of one agent may be enhanced by another failure. www.indiandentalacademy.com 65
  66. 66. DISADVANTAGES OF ANTIMICROBIAL COMBINATIONS  Increased chances of superinfections.  If inadequate doses of nonsynergistic drugs are used -emergence of resistance may be promoted.  Increased cost of therapy. www.indiandentalacademy.com 66
  67. 67. PROBLEMS THAT ARISE WITH ANTIBIOTIC USE www.indiandentalacademy.com 67
  68. 68. LOCAL IRRITANCY  Site of administration  Gastric irritation  Pain and abscess - i.m. injection  Thromboflebitis – i.v  Practically all AMAS irritants www.indiandentalacademy.com 68
  69. 69. SYSTEMIC TOXICITY  Some have a high therapeutic index  Doses over nearly 100 fold range administered  Penicillins, some cephalosporins erythromycin. www.indiandentalacademy.com 69
  70. 70. SYSTEMIC TOXICITY  Others have a lower therapeutic index –  Doses individualized and toxicity watched for,  Aminoglycosides 8th cranial nerve and kidney toxicity.  Tetracyclines liver and kidney damage, antianabolic effect.  Chloramphenicol bone marrow depression. www.indiandentalacademy.com 70
  71. 71. SYSTEMIC TOXICITY  Still others have a very low therapeutic index use highly restricted  Polymyxin B - Neurological and renal toxicity.  Vancomycin - Hearing loss, kidney damage.  Amphotericin B neurological toxicity. Kidney, www.indiandentalacademy.com bone marrow and 71
  72. 72. HYPERSENSITIVITY  All AMAs cause  Un-predictable  Unrelated to dose  Rashes to anaphylactic shock  Commonly involved - penicillins, cephalosporins, sulfonamides. www.indiandentalacademy.com 72
  73. 73. RESISTANCE It refers to unresponsiveness of a microorganism to an AMA and is akin to the phenomenon of tolerance seen in higher organisms www.indiandentalacademy.com 73
  74. 74. NATURAL RESISTANCE  Some are always resistant to AMAS.  They lack the metabolic process  The target site - affected by drug.  Gram negative bacilli‘ are - penicillin G  M. tuberculosis – Tetracyclines  not pose significant clinical problem . www.indiandentalacademy.com 74
  75. 75. ACQUIRED RESISTANCE  Resistance by an organism over period of time.  Major clinical problem.  Dependent on microorganism and drug  Some bacteria rapid resistance  Staphylococci, Strep. pyogenes penicillin  Gonococci resistance to sulfonamides  Slowly and low grade resistance to penicillin. www.indiandentalacademy.com 75
  76. 76. RESISTANCE MUTATION    stable and heritable genetic change microorganisms higher concentration of the AMA for inhibition. These are selectively preserved (i)Single step    A single gene mutation may confer high degree of resistance Emerges rapidly e.g. enterococci to streptomycin, E. coli and Staphylococci to rifampin. www.indiandentalacademy.com 76
  77. 77. RESISTANCE  (ii) Multistep.  A number of gene modifications are involved  sensitivity decreases gradually in a stepwise manner  erythromycin, tetracyclines and chloramphenicol www.indiandentalacademy.com 77
  78. 78. GENE TRANSFER  Can occur by  Conjugation Sexual contact through bridge orsex pilus  Transduction It is the transfer by bacteriophage  Transformation release DNA into the medium : imbibed another organism www.indiandentalacademy.com 78
  79. 79. EFFECTS OF RESISTANCE  Drug tolerant  Drug destroying  : Drug impermeable www.indiandentalacademy.com 79
  80. 80. CROSS RESISTANCE  Resistance to one resistance to other antibiotic  They should be Chemically or mechanically similar  EXAMPLES: sulfonamide , Tetracycline  Aminoglycosides may not extend to another  Partial cross resistance  Tetracyclines and chloramphenicol,  Erythromycin and lincomycin. www.indiandentalacademy.com conferring 80
  81. 81. PREVENTION OF DRUG RESISTANCE  No indiscriminate and inadequate or unduly prolonged use  This would Minimise the selection pressure  Resistant strains get less chance to propagate  Prefer rapidly acting and selective AMAs  Combination of AMAs  Infection by Notorious organisms : Treat intensively. 81 ….s ….… s sj.d..
  82. 82. INTOLERANCE  It is the appearance of characteristic toxic effects of a drug in an individual at therapeutic doses.  It is the converse of tolerance and indicates a low threshold of the individual to the action of a drug.  One tablet of Chloroquine may cause vomiting and abdominal pain in an occasional patient. ….s ….… s sj.d.. 82
  83. 83. IDIOSYNCRASY  It is genetically determined abnormal reactivity to a chemical.  Certain adverse effects of some drugs are largely restricted to individuals with a particular genotype  In addition, certain uncharacteristic or bizarre drug effects due to peculiarities of an individual (for which no definite genotype has been described)  Quinine/ quinidine cause cramps , diarrhoea, purpura, asthma and vascular collapse in some patients. 83 ….s ….… s sj.d..
  84. 84. SUPERINFECTION (SUPRAINFECTION)  Appearance of new infection as a result of new treatment  This is because of Normal microbial flora altered  As they provide Defence by bacteriocins  For ordinary pathogen Competition lost with the normal flora  Due to Incomplete absorption Higher amounts reach the lower bowel  Inhibit colonic bacteria and cause they cause Diarrhoeas ….s ….… s sj.d.. 84
  85. 85. COMMON SUPERINFECTIONS  Corticosteroid therapy  Leukemias and other malignancies  Treated with anticancer drugs  Acquired immunodeficiency syndrome (AIDS)  Agranulocysis  Diabetes  Disseminated Lupus erythematosus 85 ….s ….… s sj.d..
  86. 86. MINIMISE SUPERINFECTIONS  Use specific (narrow spectrum)  Avoid in trivial, self limiting or untreatable (viral) infections.  Do not unnecessarily prolong treatment 86 ….s ….… s sj.d..
  87. 87. NUTRITIONAL DEFICIENCIES  B complex and Vit K synthesized by the intestinal flora prolonged use cause eliminates flora  thus causes deficiency  Neomycin abnormalities of intestinal mucosa  It may cause Steatorrhoea Malabsorption syndrome 87 ….s ….… s sj.d..
  88. 88. MASKING OF AN INFECTION A short course briefly suppress one infection but can not suppress another one contracted concurrently. The other infection will be masked initially will manifest later in a severe form Syphilis masked by penicillin which is sufficient to cure gonorrhea. Tuberculosis masked by streptomycin given for trivial respiratory infection. ….s ….… s sj.d.. 88
  89. 89. PROPHYLACTIC ANTIBIOTICS The difference between treating and preventing infections is that treatment is directed against a specific organism infecting an individual patient, while prophylaxis is often against all organisms capable of causing infection 89 ….s ….… s sj.d..
  90. 90. PROPHYLAXIS AGAINST SPECIFIC ORGANISMS  Rheumatic fever: group A Streptococci: long penicillin G  Tuberculosis: children or open cases Isoniazid alone or rifampin  Meningococcal meningitis: epidemic or contacts; rifampin / sulfadiazine may be used. 90 ….s ….… s sj.d..
  91. 91. PROPHYLAXIS AGAINST SPECIFIC ORGANISMS d) Gonorrhea /syphilis: procaine penicillin. e) Rickettsial infections : Tetracyclines. f) Malaria: endemic :chloroquine pyrimethamine. g) Influenza A2 :Epidemic or Contacts: amantadine. 91 ….s ….… s sj.d..
  92. 92. PREVENTION OF INFECTION IN GENERAL (a) Neonates, specially after prolonged or instrumental delivery. (b)To prevent postpartum infections in the mother after normal delivery. (c)Viral upper respiratory tract infections: to prevent secondary bacterial invasion. (d)To prevent respiratory infections in unconscious patients or in those on respirators. (e) Clean elective surgery. 92 ….s ….… s sj.d..
  93. 93. PRINCIPLES OF PROPHYLACTIC ANTIBIOTICS TIMING, PRE-OP:  present at therapeutic levels at the site time of contamination  If given orally: 1 hour pre-op.  If given intravenously IV: "on-call" to the operating room or shortly BEFORE anesthetic induction. 93 ….s ….… s sj.d..
  94. 94. PRINCIPLES OF PROPHYLACTIC ANTIBIOTICS  TIMING, PRE-OP  Therapeutic levels maintained for the duration of the procedure.  extended procedures (over 6 hours) may require a second dose  since contamination re-occurs at skinclosure. 94 ….s ….… s sj.d..
  95. 95. PRINCIPLES OF PROPHYLACTIC ANTIBIOTICS  Post-op:  Post-operatively have little effect on wound infections.  After 24 hours : Not protective.  Some continue until wound drainage  Incision-line leakage has stopped  Packing is removed from wounds 95 ….s ….… s sj.d..
  96. 96. FAILURE OF ANTIBIOTIC THERAPY  Improper selection of drug, dose, route or duration of treatment.  Treatment begun too late.  Failure to take necessary adjuvant measures,  Improper treatment of underlying cause 96 ….s ….… s sj.d..
  97. 97. FAILURE OF ANTIBIOTIC THERAPY  Poor host defense  Infecting organism present behind barriers  Trying to treat untreatable infections  Presence of dormant or altered organisms 97 ….s ….… s sj.d..
  98. 98. CLASSIFICATION SYSTEMS OF ANTIBIOTICS 98 ….s ….… s sj.d..
  99. 99. CHEMICAL STRUCTURE 1.SULFONAMIDES AND RELATED DRUGS: Sulfadiazine and others, Sulfones-Dapsone (DDS), Paraaminosalicylic acid (PAS). 2. DIAMINOPYRIMIDINES: Trimethoprim, Pyrimethamine. 3.QUINOLONES: Nalidixic acid, Norfloxacin, Ciprofloxacin etc. 99 ….s ….… s sj.d..
  100. 100. CHEMICAL STRUCTURE 4. Β-LACTAM ANTIBIOTICS: Penicillins, Cephalosporins, Monobactams,Carbapenems 5. TETRACYCLINES: Oxytetracycline, Doxycycline etc. 6. NITROBENZENE DERIVATIVE: Chloramphenicol. 100 ….s ….… s sj.d..
  101. 101. CHEMICAL STRUCTURE 7.Aminoglycosides: Streptomycin, Gentamicin, Neomycin etc. 8. Macrolides antibiotics: Erythromycin, Roxithromycin, Azithromycin etc. 9. Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin. 10. Nitrofuran derivatives: Nitrofurantoin, Furazolidone. 11.Nitroimidazoles: Metronidazole, Tinidazole. 101 ….s ….… s sj.d..
  102. 102. CHEMICAL STRUCTURE 12. Nicotinic acid derivalives: Isoniazid ,Ethionamide. ,Pyrazinamide 13. Polyene antibiotics: Nystatin, Amphotericin-B ,Hamycin. 14. Imidazole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole. 15. Others: Rilailipin, Lincomycin, Clindamycin, Spectinomycin, Vancomycin, Sod. fusidate, Ethambutol, Thiacetazone, Clofazimine ….s ….… s sj.d.. 102
  103. 103. MECHANISM OF ACTION 1. Inhibit cell wall synthesis: Penicillin, Cephalosporins, Cycloserine, Vancomycin, Bacitracin, 2. Cause leakage from cell membranes: Polypeptides - Polymyxins, Colistin, Bacitracin. Polyenes - Amphotericin B, Nystatin, Hamycin. 3. Inhibit protein synthesis: Tetracyclines, Chloramphenicol, Erythromycin Clindamycin. 4. Cause misreading of m-RNA code and affect permeability. Aminoglycosides - Streptomycin, Gentamicin etc. ….s ….… s sj.d.. 103
  104. 104. MECHANISM OF ACTION 5. Inhibit DNA gyrase: Fluoroquinolones-Ciprofloxacin. 6. Interfere with DNA function: Rifampin, Metronidazole. 7. Interfere with DNA synthesis: Idoxuridine, Acyclovir, Zidovudine. 8 . Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS, Trimethoprim, Ethambutol. ….s ….… s sj.d.. Pyrimethamine, 104
  105. 105. TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE 1. Antibacterial. Penicillins, Aminoglycosides, 2. Antifungal. Griseofulvin, Amphotericin B, 3. Antiviral. Idoxuridine, Acyclovir, 4.Antiprotozoal. Chloroquine, Pyrimethamine, 5.Anthelmintic Mebendazole, Pyrantel, Niclosamide, ….s ….… s sj.d.. 105
  106. 106. SPECTRUM OF ACTIVITY Narrow spectrum  Penicillin G  Streptomycin Broad spectrum Tetracyclines Chloramphenicol  Erythromycin 106 ….s ….… s sj.d..
  107. 107. TYPE OF ACTION Primarily bacteriostatic Sulfonamides Tetracyclines Primarily bactericidal Penicillins Cephalosporins Nalidixic acid Chloramphenicol Ciprofloxacin‘ Vancomycin Cotrimoxazole. Ethambutol 107 ….s ….… s sj.d..
  108. 108. ANTIBIOTICS ARE OBTAINED FROM FUNGI BACTERIA ACTINOMYCETES Penicillin Polymyxin B Aminoglycosides Cephalosporin Colistin Polyenes Griseofulvin Aztreonam Chloramphenicol Bacitracin Tetracyclines Tyrothricin Macrolides 108 ….s ….… s sj.d..
  109. 109. ANTIBIOTICS THAT INHIBIT CELL WALL SYNTHESIS  ß-lactam Antibiotics  Major Classes  Penicillins  Cephalosporins  Carbapenems. 109 ….s ….… s sj.d..
  110. 110. MECHANISM OF ACTION OF ßLACTAM ANTIBIOTICS Inhibit cell wall synthesis blocking the action of transpeptidases, also known as penicillin binding proteins (PBPs) 110 ….s ….… s sj.d..
  111. 111. PREPARATIONS  Sodium penicillin (crystalline penicillin) 0.5-5 MU i.m/i.v 6-12 hourly It is available as dry powder in vials to be dissolved in sterile water at the time of injection. BENZYL PEN 0.5, 1 MU inj.  Repository penicillin G injections These are insoluble salts of PnG which must be given by deep i.m. (never i.v.) injection. They release PnG slowly at the site of injection, which then meets the same fate as soluble PnG.  1.Procaine penicillin g inj. hourly as aqueous concentrations 0.5-1 MU i.m. 12-24 suspension. attained are lower, Plasma but are sustained for 1-2 days; PROCAINE PENICILLIN-G 0.5, 1 MU dry powder in vial. ….s ….… s sj.d.. 111
  112. 112. PREPARATIONS A- Fortified procaine penicillin G inj: contains 3 lac U procaine penicillin and 1 lac U sod. penicillin G to provide rapid as well as sustained blood levels. FORTUMD P.P. INJ 3+1 lac U vial. 2. Benzathine penicillin GI 0.6-2.4 MU i.m. every 2-4 weeks as aqueous suspension. It releases penicillin extremely slowlyplasma concentrations are very low but remain effective for prophylactic purposes for up to 4 weeks: PENIDLTRELA (long acting), LONGACILLIN, PENCOM, 0.6, 1.2, 2.4 NW as dry powder in vial. ….s ….… s sj.d.. 112
  113. 113. PENICILLIN AND RELATED ßLACTAMS Penicillin, ampicillin (amoxicillin) Gram positive (eg, S. pneumoniae, enterococcus) Extended spectrum penicillins – Nafcillin: S. aureus – Piperacillin: P. aeruginosa, other GNRs Clearance: predominantly renal 113 ….s ….… s sj.d..
  114. 114. 1.Acid resistant alternative to penicillin G: penicillin V 2.Penicillinase resistant penicillins: methicillin , Oxacillin 3. Extended spectrum peniciliins (a) Aminopenicillins: Ampicillin, Amoxicillin'. (b) Carboxypenicillins: Carbenicillin, Carbenicillin (Carfecillin), Ticarcillin. (c) Ureidopenicillins: Piperacillin, Mezlocillin (d) Mecillinam (Amdinocillin). β- lactamase inhibitors Clavulanic acid Sulbactam. ….s ….… s sj.d.. 114
  115. 115. USES  Streptococcal infections  Pneumococcal infections  Meningococcal infections  Gonorrhoea  Syphillis  Diptheria  Tetanus and gas gangrene  Prophylaxis 115 ….s ….… s sj.d..
  116. 116. ADVERSE INFECTIONS  Local irritancy and direct toxicity  Hypersensitivity  Superinfections  Jarisch Herxheimer reaction 116 ….s ….… s sj.d..
  117. 117. CEPHALOSPORINS (ß-LACTAM)  First generation (S. aureus, Streptococci) – Cefazolin  Second generation (H. influenzae, Moraxella) – Cefuroxime 117 ….s ….… s sj.d..
  118. 118. CEPHALOSPORINS (ßLACTAM)  Third generation (CSF penetration, iv) – Ceftriaxone, cefotaxime (Streptococci, GNR) – Ceftizoxime (GNRs, not P. aeruginosa) – Ceftazidime (P. aeruginosa, GNRs)  Fourth generation (GNR, P. aeruginosa, S. aureus) – Cefepime (iv, nosocomial infections) 118 ….s ….… s sj.d..
  119. 119. ADVERSE EFFECTS  Pain after i.m injection  Diarrhoea  Hypersensitivity reactions  Nephrotoxicity  Bleeding  Neutropenia  Disulfiram like reactions 119 ….s ….… s sj.d..
  120. 120. USES  As an alternative to PnG  Respiratory, urinary, soft tissue infections  Penicillinase producing staphylococcal infections  Septicemias  Surgical prophylaxis  Meningitis  Gonorrhea  Typhoid  Mixed aerobic anaerobic infections  Infection by odd organisms and hospital acquired infections 120 ….s ….… s sj.d..
  121. 121. OTHER ß-LACTAMS • Carbapenems (Very broad spectrum) Imipenem Meropenem ß-lactams-ß-lactamase inhibitor combinations Amoxicillin-clavulanate Piperacillin-tazobactam Monobactams (Gram negative only) – Aztreonam ….s ….… s sj.d.. 121
  122. 122. GLYCOPEPTIDE ANTIBIOTICS • Vancomycin  Inhibits cell wall synthesis by blocking transpeptidase and transglycosylase.  Only gram positive bacteria.  Resistance among Staphylococci and Enterococci 122 ….s ….… s sj.d..
  123. 123. ADVERSE EFFECTS  Nerve defects : dose dependant  Kidney damage  Skin allergy fall in BP during i.v injections  Rapid i.v injection has caused chills ,fever, urticaria intense flushing –RED MAN SYNDROME 123 ….s ….… s sj.d..
  124. 124. ANTIBIOTICS THAT INHIBIT PROTEIN SYNTHESIS  mRNA 50S 30S  Nascent polypeptide 50S 30S 124 ….s ….… s sj.d..
  125. 125. COMMONLY USED PROTEIN SYNTHESIS INHIBITORS  AMINOGLYCOSIDE(gentamicin, tobramycin) – Inhibits protein synthesis but also disrupts cell permeability (cidal) – Gram negatives; Synergy with ßlactams vs gram positive (eg, Enterococci) 125 ….s ….… s sj.d..
  126. 126. USES  Tuberculosis  SABE  Plague  Tularemia  In treating Pseudomonas, Proteus or Klebsiella infections  Meningitis by gram negative bacilli 126 ….s ….… s sj.d..
  127. 127. ADVERSE EFFECTS  Ototoxicity  Nephrotoxicity  Neuromuscular blockade 127 ….s ….… s sj.d..
  128. 128. PRECAUTIONS AND INTERACTIONS (i) Avoid during pregnancy: risk of foetal ototoxicity. (ii) Avoid concurrent use of other ototoxic drugs, e.g. high ceiling diuretics, Minocycline. (iii) Avoid concurrent use of other nephrotoxic drugs, e.g. amphotericin B, vancomycin, cephalothin, cyclosporin and cisplatin. 128 ….s ….… s sj.d..
  129. 129. (lv) Cautious use in patients past middle age and in those with kidney damage(v) Cautious use of muscle relaxants in patients receiving an aminoglycoside (vi)Do not mix aminoglycoside with any drug in the same syringe/ infusion bottle. 129 ….s ….… s sj.d..
  130. 130. MACROLIDES  Erythromycin, clarithromycin, azithromycin  Static; often used for respiratory infections (eg, Streptococci)  Resistance is developing. 130 ….s ….… s sj.d..
  131. 131. ADVERSE REACTIONS Gastrointestinal : epigastric pain , diarrhoea Reversible hearing impairment Hypersensitivity Hepatitis with cholestatic jaundice INTERACTIONS Rises plasma levels of theophylline, carbamazepine, valproate, ergotamine, warfarin Terfanidine, astemizole, cisapride Several cases of Q –T prolongation serious ventricular arrythmias and death by torses de pontes 131 ….s ….… s sj.d..
  132. 132. USES  As an alternative to penicillin  Atypical pneumonia  Whooping cough  Chancroid  Compylobacter enteritis  Legonnaire’s pneumonia  Chlamydia trachomatis  Penicillin resistant staphylococci 132 ….s ….… s sj.d..
  133. 133. TETRACYCLINES  Tetracyclines (tetracycline, doxycycline)  Broad activity v/s respiratory pathogens, atypical bacteria (eg, Rickettsia)  Static; not indicated in pregnant women or children < 8 yrs 133 ….s ….… s sj.d..
  134. 134. ADVERSE EFFECTS  Kidney damage  Liver damage  Phototoxicity  Teeth and bones  Antianabolic effect  Increased intracranial pressure  Diabetes insipidus  Vestibular toxicity ….s ….… s sj.d.. 134
  135. 135. PRECAUTIONS  Not to use in pregnant women  Avoid in pateints with diuretics : blood urea rises  Renal and hepatic insufficiency  Never use beyond the expiry  Never mix with penicillins  Do not inject intrathecally ….s ….… s sj.d.. 135
  136. 136. USES  Lymphogranuloma venerum  Granuloma inguinale  Atypical pneumonia  Cholera  Brucellosis  Plague  Relapsing fever  Rickettsial infections 136 ….s ….… s sj.d..
  137. 137. USES Listeria infections Penicillin resistant penicillin Chlamydia infections Chancroid Tularemia 137 ….s ….… s sj.d..
  138. 138. USES  UTI community acquired pneumonia  Amoebiasis  Malaria  Acne  COPD 138 ….s ….… s sj.d..
  139. 139. OTHER INHIBITORS OF PROTEIN SYNTHESIS CHLORAMPHENICOL Broad activity, penetrates CSF Idiosyncratic and irreversible bone marrow toxicity limit its use Active against vancomycin resistant Enterococcus faecium (VRE) but not E. faecalis 139 ….s ….… s sj.d..
  140. 140. CHLORAMPHENICOL  Active against Staphylococci resistant to methicillin (nafcillin)  Active against resistant Enterococci and Staphylococci 140 ….s ….… s sj.d..
  141. 141. ADVERSE REACTIONS  Bone marrow depression  Hypersensitivity reactions  Irritative effects  Superinfections  Gray baby syndrome  Inhibits tolbutamide, cyclophosphamide metabolism ….s ….… s sj.d.. Warfarin, , phenytoin 141
  142. 142. USES           Enteric fever H.influenzae meningitis Anaerobic infections Intraocular infections SECOND DRUG IN Brucellosis Whooping cough Pneumococcal meningitis UTI Topical eye installation 142 ….s ….… s sj.d..
  143. 143. ANTIBIOTICS THAT AFFECT NUCLEIC ACIDS  FLUOROQUINOLONES(CIPROFLOXICIN, GATIFLOXICIN, LEVOFLOXICIN,,MOXIFLOXICIN) – Inhibit DNA gyrase and topoisomerase; not used in children – Active against enteric gram negative rods and P. aeruginosa – “Respiratory quinolones” (levo, gati, moxi, not cipro) active vs S.pneumoniae; Also some activity against Staphylococci – Concentrate intracellularly (eg, versus Salmonella typhi) 143 ….s ….… s sj.d..
  144. 144. USES            ….s ….… UTI Gonorrhoea Chancroid Bacterial gastroenteritis Typhoid Bone, soft tissue, gynaecological and wound infections Respiratory infections Tuberculosis Gram negative septicaemias Meningitis conjuctivitis s sj.d.. 144
  145. 145. ADVERSE REACTIONS  Gastrointestinal : nausea, vomiting, bad taste, anorexia  CNS: dizziness, restlessness, anxiety, headache, insomnia (GABA antagonistic activity)  Skin and hypersensitivity reactions  Tendonitis and tendon rupture 145 ….s ….… s sj.d..
  146. 146. ANTIBIOTICS THAT AFFECT NUCLEIC ACIDS  Nitroimidazoles (metronidazole) – Anaerobes and some protozoa (eg, giardia, amebiasis) – Reduced intermediate free radicals damage DNA (cidal) – Relatively contraindicated in pregnancy 146 ….s ….… s sj.d..
  147. 147. ADVERSE EFFECTS  Anorexia, nausea, metallic taste  Headache ,glossitis  Peripheral neuropathy  Thrombophlebitis  Disulfiram like reactions  Phenobarbitone, rifampin reduce its therapeutic effects  Reduce renal elimination of lithium 147 ….s ….… s sj.d..
  148. 148. USES  Amoebiasis  Giardiasis  Trichomonas vaginitis  Anaerobic bacterial infections  Pseudomembranous enterocolitis  Ulcerative gingivitis, trench mouth  Helicobacter pylori gastritis  Guinea worm infestations ….s ….… s sj.d.. 148
  149. 149. ANTIMETABOLITES  Sulfonamides (Sulfamethoxazole, sulfadiazine)  Interfere with microbial folic acid synthesis  Ultimate effect is decrease in bacterial nucleotide pool.  Most commonly used drug is a combination of trimethoprim +sulfamethoxazole 149 ….s ….… s sj.d..
  150. 150. TRIMETHOPRIM + SULFAMETHOXAZOLE  Used primarily in UTI, but E. coli resistance is increasing  Respiratory tract infections  Typhoid  Bacterial diarrheas and dysentry  Chancroid  Granuloma inguinale  Agranulocytosis  Pneumocystitis carinii infections 150 ….s ….… s sj.d..
  151. 151. Adverse effects            ….s ….… Nausea, vomiting, epigastric pain Crystalluria Hypersensitivity reactions Hepatitis Bleeding in G6-PD deficiency Kernicterus COTRIMOXAZOLE Folate deficiency Renal impairment Bone marrow hypoplasia Thrombocytopenia when used with diuretics s sj.d.. 151
  152. 152. RIFAMYCINS (RIFAMPIN)  Inhibits DNA-dependent RNA polymerase; bactericidal  Forms a critical part of therapy for tuberculosis, leprosy  Also used in combination with other agents to treat  Staphylococcus, Legionella and some atypical pneumonia  Brucellosis along with doxycycline 152 ….s ….… s sj.d..
  153. 153. RIFAMYCINS (RIFAMPIN)  Mycobacteria; prophylaxis for Neisseria meningitidis  Rarely used alone due to rapid development of resistance  Significant drug interactions via P450 induction 153 ….s ….… s sj.d..
  154. 154. Adverse effects  Hepatitis  Respiratory syndrome: shock collapse, breathlessnes  Cuteneous syndrome : flushing, pruritis and rash, redness and watering  Abdominal syndrome : nausea, vomiting abdominal cramps  Orange red colored body secretions 154 ….s ….… s sj.d..
  155. 155. ANTIFUNGAL AGENTS  POLYENES (AMPHOTERICIN B) – Bind sterols (ergosterol) and disrupt cell membrane – Active against yeast (candida, cryptococcus) and fungi (aspergillus, histoplasmosis, coccidiomycosis, mucormycosis) – Significant renal toxicity ( Cr, K, Mg) and acute reactions post-infusion (fever, chills, tachypnea) are reduced with lipid preparations ….s ….… s sj.d.. 155
  156. 156. ANTIFUNGAL AGENTS  AZOLES (FLUCONAZOLE,ITRACONAZOLE ; KETO LARGELY REPLACED) – Inhibit ergosterol synthesis and selectively disrupt fungal cell membrane – Fluconazole commonly used for candida, cryptococcus, cocci – Itraconazole active against aspergillus, blasto, histo, cocci (not in CSF) ….s ….… s sj.d.. 156
  157. 157. 157 ….s ….… s sj.d..

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