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

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PRINCIPLES OF SURGICAL AND ANTIMICROBIAL INFECTION
MANAGEMENT


1

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



2

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


3

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


4

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

5

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

6

PRESENCE OF INFECTION


Determine presence of infection



Pain, swelling , surface erythema,



pus formation, limitation of motion



Fever, lymphadenopathy, malaise



Toxic appearance, increased WBC count

7

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

8

STATE OF HOST DEFENSES
 PHYSIOLOGICAL


Inability to deliver the defending agents



Ex:- Shock
- Reduced circulation due to age,
Obesity, fluid imbalances

9

 DISEASE

STATES



Malnutrition syndrome



Cancers



Leukemia



Poorly controlled diabetes

10

 DEFECTIVE

IMMUNE SYSTEMS



Multiple myeloma



Total body radiotherapy



Agammaglobulinemia



Splenectomy children

11



VARIETY OF THERAPEUTIC AGENTS



Cytotoxic agents and Corticosteroids



Glucocorticoids,

Azathioprine,

cyclosporine

depresses T- cell B-cell counts


Antibiotic prophylaxis


12

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

13

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

14

PRINCIPLES FOR CHOOSING THE
APPROPRIATE ANTIBIOTIC


Organism related






Identification of the causative organism
Determination of antibiotic sensitivity

Patient related


Age



Kinetics of drug in the body

15

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

16


17

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


18

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

19

ORGANISM


Odontogenic infections
- 70% of these are caused by mixed flora
- 5% aerobic bacteria
- 25 % pure anaerobic bacteria


20

ORGANISM


Chronic non advancing abscess : Anaerobic



Cellulitis type of infection: Aerobic



Infection becomes severe : Mixed flora



Infection contained by host : Anaerobic


21

AEROBIC ORGANISMS


Gram positive (viridans group)



Streptococci – milleri, sanguis, salivaris mutans



α-hemolytic

streptococci

–

susceptible

to

penicillin


22

ANAEROBIC ORGANISMS


Anaerobic gram positive cocci



Peptostreptococci





Streptococci
Susceptible to penicillin

Anaerobic gram negative cocci


Fusobacterium



Bacteriodes


23

ANAEROBIC ORGANISMS


Bacteroides



Orpharyngeal group



Porphyromonas


Asacchrolyticus



Gingivalis



Endodontalis

Prevotella
- melaninogenica
- Buccae


- Intermedia

24

ANAEROBIC ORGANISMS


Fusobacterium


Susceptible to penicillin



Resistant to erythromycin



Along with milleri causes severe mediastinitis


25

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

26

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.


27

ORAL FOCUS OF INFECTION


Infected periapical lesions
granuloma, cyst, abscess



Teeth with infected root canals



Periodontal disease with respect manipulation
and extraction of teeth

28

SIGNIFICANCE OF ORAL FOCI OF
INFECTION


Rheumatoid arthritis and rheumatic fever



Valvular heart disease SABE



Gastrointestinal diseases



Ocular diseases



Skin diseases



Renal diseases

29

CULTURE SENSITIVITY


No improvement after 3 days



Postoperative infection



Infection is recurrent



Actinomycosis is suspected



Osteomyelitis is present

30

DETERMINATION OF
ANTIBIOTIC SENSITIVITY


Causative organism should be precisely defined



Development of resistance



Penicillin – streptococcus/ anaerobes



Clindamycin – streptococcus, five anaerobes


31

DETERMINATION OF
ANTIBIOTIC SENSITIVITY


Erythromycin

–

streptococcus,

peptostreptococcus, prevotella no action on
fusobacterium


Cephalexin – streptococcus (less sensitive)
effective against anaerobes



Metronidazole – sensitive for anaerobes

32

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

33

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.

34

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.

MIC

and

MBC

35

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.


36

PATEINT FACTORS

37

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

38

EVEN IN MILD RENAL FAILURE


Cephalosporins



Metronidazole



Vancomycin



Amphotericin B



Ethambutol



Flucytosine

39

MODERATE-SEVERE RENAL FAILURE


Metronidazole



Cephalothin



Cephaloridine



Nalidixic acid



Cotrimoxazole

40

DRUGS TO BE AVOIDED
DOSE REDUCTION NEEDED
IN LIVER DISEASES

DRUGS TO BE AVOIDED

DOSE REDUCTION
NEEDED

Erythromycin

estolate Chloramphenicol

Tetracyclines

Isoniazid

Pyrazinamide

Metronidazole


41

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


42

PREGNANCY


Penicillins,

many

cephalosporins

and

erythromycin are safe


TETRACYCLINES


Acute yellow atrophy of liver



Pancreatitis



Kidney damage



Teeth and bone deformities


43

PREGNANCY


Aminoglycosides : Foetal ear damage.



Fluoroquinolones



Cotrimoxazole



Chloramphenicol



Sulfonamides



Nitrofurantoin : Avoided in 3rd trimester.

44

GENETIC FACTORS


Primaquine



Nitrofurantoin



Sulfonamides



Chloramphenicol



Fluoroquinolones



Produce haemolysis in G-6PD deficient patient.

45

PATEINTS DRUG HISTORY


Allergic reaction



Toxic reaction



Cross reaction



H/O minor or major side effects



Potential drug interaction

46

DRUG FACTORS

47

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

48

USE OF LEAST TOXIC
ANTIBIOTIC

 To

prevent the host cell damage

Ex : penicillin / chloramphenicol


49

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


50

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


51

WHEN TO USE THE NEWER DRUG


Only effective drug



Active at low concentration, less toxic,



Less bothersome side effects



Less expensive


52

COST OF ANTIBIOTIC

 High

cost antibiotic is the drug of choice

 Administration

costs


53

PATIENT COMPLIANCE


ENCOURAGE PATIENT COMPLIANCE



Compliance decreased with increasing no of
pills/ day



Once a day for 4-5 days


54

DRUG FACTORS
 Pharmacokinetic


profile:

Present at the site of infection :





In sufficient concentration
Adequate length of time.

Penetration site of infection : pharmacokinetic
properties

55

PHARMACOKINETIC PROFILE
Distribution and protein binding
breakdown and excretion
Distribution
GI absorption
First pass metabolism


56

PRINCIPLES OF ANTIBIOTIC
ADMINISTRATION


PROPER DOSES



Proper time interval(T1/2)



Proper route of administration



Consistency in route of administration



Combination antibiotic therapy

57

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


58

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

59

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


60

PROPER ROUTE OF
ADMINISTRATION



Fasting state/ food intake



IV/ oral


61

CONSISTENCY IN ROUTE OF
ADMINISTRATION



Severe infection – start i.v antibiotic



Decision to shift to oral antibiotic


62

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


63

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

 Treatment of mixed infection

64

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.

65

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.

66

PROBLEMS THAT ARISE WITH
ANTIBIOTIC USE

67

LOCAL IRRITANCY


Site of administration



Gastric irritation



Pain and abscess - i.m. injection



Thromboflebitis – i.v



Practically all AMAS irritants

68

SYSTEMIC TOXICITY


Some have a high therapeutic index



Doses over nearly 100 fold range administered



Penicillins, some cephalosporins erythromycin.


69

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.

70

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,


bone

marrow

and

71

HYPERSENSITIVITY


All AMAs cause



Un-predictable



Unrelated to dose



Rashes to anaphylactic shock



Commonly involved - penicillins, cephalosporins,
sulfonamides.

72

RESISTANCE

It refers to unresponsiveness of a microorganism
to an AMA and is akin to the phenomenon of
tolerance seen in higher organisms

73

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 .

74

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.

75

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.

76

RESISTANCE


(ii) Multistep.



A number of gene modifications are involved



sensitivity decreases gradually in a stepwise
manner



erythromycin, tetracyclines and chloramphenicol

77

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

78

EFFECTS OF RESISTANCE


Drug tolerant



Drug destroying



:

Drug impermeable


79

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.


conferring

80

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

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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

….…

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82

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

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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

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84

COMMON SUPERINFECTIONS
 Corticosteroid therapy
 Leukemias and other malignancies
 Treated with anticancer drugs
 Acquired immunodeficiency syndrome
(AIDS)
 Agranulocysis
 Diabetes
 Disseminated Lupus erythematosus

85

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MINIMISE SUPERINFECTIONS

 Use specific (narrow spectrum)
 Avoid

in

trivial,

self

limiting

or

untreatable (viral) infections.
 Do not unnecessarily prolong treatment

86

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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

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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

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88

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

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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

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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

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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

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PRINCIPLES OF

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

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PRINCIPLES OF

 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

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PRINCIPLES OF

 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

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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

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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

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CLASSIFICATION
SYSTEMS OF
ANTIBIOTICS
98

….s

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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

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CHEMICAL STRUCTURE

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

5. TETRACYCLINES:
Oxytetracycline, Doxycycline etc.

6. NITROBENZENE DERIVATIVE:
Chloramphenicol.
100

….s

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s sj.d..

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

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s sj.d..

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

….…

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102

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

….…

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103

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

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

….…

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105

SPECTRUM OF
ACTIVITY

Narrow spectrum
 Penicillin G
 Streptomycin

Broad spectrum
Tetracyclines
Chloramphenicol

 Erythromycin

106

….s

….…

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TYPE OF ACTION

Primarily
bacteriostatic

Sulfonamides
Tetracyclines

Primarily
bactericidal
Penicillins
Cephalosporins
Nalidixic acid

Chloramphenicol

Ciprofloxacin‘

Vancomycin

Cotrimoxazole.

Ethambutol
107

….s

….…

s sj.d..

ANTIBIOTICS ARE OBTAINED FROM

FUNGI

BACTERIA ACTINOMYCETES

Penicillin

Polymyxin B

Aminoglycosides

Cephalosporin

Colistin

Polyenes

Griseofulvin

Aztreonam

Chloramphenicol

Bacitracin

Tetracyclines

Tyrothricin

Macrolides
108

….s

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ANTIBIOTICS THAT INHIBIT
CELL WALL SYNTHESIS

 ß-lactam Antibiotics
 Major Classes
 Penicillins
 Cephalosporins
 Carbapenems.

109

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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..

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

….…

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111

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

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

….…

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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

USES

 Streptococcal infections
 Pneumococcal infections
 Meningococcal infections
 Gonorrhoea
 Syphillis
 Diptheria
 Tetanus and gas gangrene
 Prophylaxis
115

….s

….…

s sj.d..

ADVERSE INFECTIONS

 Local irritancy and direct toxicity
 Hypersensitivity
 Superinfections
 Jarisch Herxheimer reaction

116

….s

….…

s sj.d..

CEPHALOSPORINS (ß-LACTAM)

 First

generation

(S.

aureus,

Streptococci)
– Cefazolin
 Second generation (H. influenzae,
Moraxella)
– Cefuroxime
117

….s

….…

s sj.d..

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..

ADVERSE EFFECTS

 Pain after i.m injection
 Diarrhoea
 Hypersensitivity reactions
 Nephrotoxicity
 Bleeding
 Neutropenia
 Disulfiram like reactions
119

….s

….…

s sj.d..

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..

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

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..

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..

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
disrupts cell permeability (cidal)
– Gram negatives; Synergy with ßlactams

vs

gram

positive

(eg,

Enterococci)
125

….s

….…

s sj.d..

USES

 Tuberculosis
 SABE
 Plague
 Tularemia
 In treating Pseudomonas, Proteus
or Klebsiella infections
 Meningitis by gram negative bacilli

126

….s

….…

s sj.d..

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 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..

(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..

MACROLIDES

 Erythromycin,

clarithromycin,

azithromycin
 Static;

often

used

for

respiratory

infections (eg, Streptococci)
 Resistance is developing.

130

….s

….…

s sj.d..

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..

USES

 As an alternative to penicillin
 Atypical pneumonia
 Whooping cough
 Chancroid
 Compylobacter enteritis
 Legonnaire’s pneumonia
 Chlamydia trachomatis
 Penicillin resistant staphylococci
132

….s

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s sj.d..

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..

ADVERSE EFFECTS

 Kidney damage
 Liver damage
 Phototoxicity
 Teeth and bones
 Antianabolic effect
 Increased intracranial pressure
 Diabetes insipidus
 Vestibular toxicity

….s

….…

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134

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

….…

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135

USES

 Lymphogranuloma venerum
 Granuloma inguinale
 Atypical pneumonia
 Cholera
 Brucellosis
 Plague
 Relapsing fever
 Rickettsial infections
136

….s

….…

s sj.d..

USES

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

137

….s

….…

s sj.d..

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 bone
marrow toxicity limit its use
Active

against

vancomycin

resistant

Enterococcus

faecium

(VRE) but not E. faecalis
139

….s

….…

s sj.d..

CHLORAMPHENICOL

 Active

against

Staphylococci

resistant to methicillin (nafcillin)
 Active against resistant Enterococci
and Staphylococci

140

….s

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s sj.d..

ADVERSE REACTIONS

 Bone marrow depression
 Hypersensitivity reactions
 Irritative effects
 Superinfections
 Gray baby syndrome
 Inhibits

tolbutamide,

cyclophosphamide
metabolism

….s

….…

s sj.d..

Warfarin,
,

phenytoin
141

USES












Enteric fever
H.influenzae meningitis
Anaerobic infections
Intraocular infections
SECOND DRUG IN
Brucellosis
Whooping cough
Pneumococcal meningitis
UTI
Topical eye installation

142

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s sj.d..

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..

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

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..

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..

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..

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

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..

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..

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

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..

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..

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..

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

….…

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155

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

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

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