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2. ANTIBIOTICS
• Substances produced by microorganisms
which suppress the growth or kill the
microganisms at very low concentrations.
HISTORY
• The phenomenon of antibiosis was
demonstrated by Pasteur (1877):growth of
anthrax bacilli in urine was inhibited by air
born bacteria.
• Flemming (1929) found that diffusible
substance was elaborated by penicillium
mould which could destroy staphylococcus.
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3. CLASSIFICATION
1.
2.
3.
4.
BASED ON TYPE OF ORGANISM THEY ACT UPON:
Antibacterial – penicillin
amino glycosides
erythromycin
Antifungal griseofulvin
amphotericin
ketoconazole
Antiviralacyclovir
amantidine
zidovudine
Antiprotozoal- metronidazole
chloroquine
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4. BASED ON MECHANISM OF ACTION:
1.
2.
3.
4.
5.
6.
7.
Inhibit cell wall synthesis: penicillins
cephalosporins
cyclosporins
Cause leakage from cell membrane:
polypeptides-polymixin, bacitracin
polyenes- amphotericin B ,nystatin
Inhibits protein synthesis:
tetracyclines,
chloramphenicol,
erythromycin,
clindamycin.
Causes misreading of m.RNA: aminoglycosides
Inhibits DNA gyrase:
fluoroquinolones
Interfere with DNA function : rifampin,
metronidazole.
Interfere with DNA synthesis: acyclovir,
idoxuridine.
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5. INTRODUCTION
• The selection of an appropriate antibiotic for
head and neck infections requires the
integration of many factors related both to
the host and the pharmacology of the
antibiotic it self.
• Empiric antibiotic selection is based on a
knowledge of the flora of orofacial infections
in the non compromised host and
dependence on laboratory studies.
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6. •
•
•
•
•
•
•
•
Pharmacokinetic & pharmacodynamic
issues in the use of antibiotics include:
Spectrum of activity,
Absorption,
Bioavailability,
Serum half life & duration of action,
Tissue penetration,
Distribution,
Metabolism and clearance,
Concentration dependent and
concentration independent killing of
organisms.
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7. THE DECISION TO USE OF ANTIBIOTIC
THERAPY
• An appropriate decision about whether the
antibiotic therapy is necessary or not will
depend on some of the factors like:
A) PRESENCE OF INFECTION:
Locally the classic signs and symptoms of
pain, swelling, surface erythema, pus
formation and limitation of motion.
systemically ,fever, lymphadenopathy,
malaise, elevated WBC count.
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8. • Noninfectious conditions similar to the
infectious conditions to be carefully
diagnosed are:
• Painful tooth
• Removal of 3rd molar(2nd day)
• Major maxillofacial procedures
performed under G.A. etc
• These must be excluded as possible
causes of patients discomfort.
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9. B) STATE OF HOST DEFENSES:
• antibiotics help in situations in which
the host has been overwhelmed by
bacteria or especially virulent bacteria
are involved, and when patient’s
defenses are impaired.
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10. Cause of depressed defense:
• 1) physiological :shock, disturbances in
circulation caused in old ages or obesity and
fluid imbalances.
• 2) Disease related: malnutrition syndrome
(alcoholism), cancers, leukemia, poorly
controlled diabetics.
• 3) Defective immune system related:
congenital defects such as
agammaglobulinemia,
multiplemyeloma, total body irradiation
therapy, children who have had splenectomy.
• 4) Drug suppression related:
cytotoxic drugs in malignancies,
glucocorticoids, cyclosporine.
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11. PRINCIPLES FOR CHOOSING
THE APPROPRIATE ANTIBIOTIC
• Once the decision has been made to
use antibiotics as an adjunct to treating
an infection ,the antibiotic should be
properly selected.
• Some of the guide lines which can be
helpful in antibiotic selection are:
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12. IDENTIFICATION OF
CAUSATIVE ORGANISM:
• The typical odontogenic infection is
caused by a mixture of aerobic and
anaerobic bacteria.
• Approximately 70%-mixed flora
5%-pure aerobic
25%-pure anaerobic
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13. • AEROBIC: with in the viridans group of
facultative streptococi, streptococus
milleri group is most frequently
associated with orofacial cellulitis and
abscess.
• All most all the these aerobic groups
are sensitive to penicillins.
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14. ANAEROBIC:
anaerobic preptostreptococci,
members of prevotella,
porphyromonas,
• provitella-sensitive to penicillins
• 25% of prevotella and
porphyromonas- are penicillin
resistant.
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15. • Penicillin-sensitive streptococci predominate
during the first 3 days of clinical symptoms
and the more resistant gram positive obligate
anaerobes appear in significant numbers
there after.
• In long standing cases aerobic bacteria can
not survive in hypoxic and acidic
environment and so anaerobes predominate.
• This fact suggests the selection of the
penicillins over other antibiotics in early
cases.
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16. DETERMINATION OF
ANTIBIOTIC SENSITIVITY
• In the treatment of an infection that has
not responded to initial antibiotic
therapy or a post opp wound infection,
the causative agent must be precisely
identified, and the antibiotic sensitivity
must also be determined.
• The results of this provides information
needed to prescribe most appropriate
antibiotic.
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17. USE OF SPECIFIC AND
NARROW SPECTRUM ANTIBIOTICS
• Antibiotic with the narrowest spectrum of
activity should be used, which will prevent
the development of resistant organisms.
• When broad spectrum antibiotics are used,
many different bacteria also present in the
body are exposed to antibiotic.
• But in the case of narrow spectrum
antibiotics only fewer organisms have
opportunity to become resistant.
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18. • Use of narrow spectrum antibiotics
also minimizes the risk of supra
infections.
• When large numbers of normal host
flora are eliminated, overgrowth of
resistant organisms occurs, and this
may result in clinical infection in some
patients
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20. USE OF LEAST TOXIC
ANTIBIOTICS
• Drugs which are having lower toxicity should
be used.
• Some antibiotics which are used to kill living
bacteria may also kill or injure human cells.
Thus can be highly toxic.
Exmp: in case of odontogenic infections
chloramphenicol is 2-3% more effective than
penicillins. But at the same time it causes
severe bone marrow depression. But
penicillins are least toxic.
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21. ALLERGY OR INTOLERANCE
• Penicillins are the antibiotic most frequently
prescribed for infections in the oral cavity.
• Between 1%-10% of patients who initially
take penicillins develop an allergic reactions.
• And 1% of chance of developing an allergic
reaction with reexposure , who did not have
allergic reaction for the first time.
• Approximately 10%-15% of penicillin allergic
patients are also sensitive to cephalosporins,
hence should be avoided in these patients.
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22. • History of adverse reactions or
intolerance of antibiotic would preclude
its subsequent use unless strictly
indicated. like:
Tetracycline –photo toxicity
Clindamycin – antibiotic associated
colitis
(omfs clinics of N.A vol 15 feb 2003)
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23. USE OF BACERICIDAL RATHER
THAN BACTERIOSTATIC
• Bactericidal drugs exert their influence after
they are incorporated into the bacterial cells
and the cell eventually dies.
• On other hand bacteriostatic exerts their
influence only when present in the patient’s
tissues. therefore bacteria acquire their
normal growth after the drug is eliminated .
So they should be used according to
rigorous time schedule.
• Patients who are pathologically and
therapeutically immunosupressed should be
given bactericidal.
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25. PREVIOUS
ANTIBIOTIC THERAPY
• The previous use of different antibiotics during
the course of an acute infection clouds the
bacteriological picture.
• In this situation the clinician has the choice of
changing the current antibiotic or increasing its
dose , perhaps by using the parenteral route.
• Increasing in efficacy afforded by the parenteral
route of administration may be more
advantageous than changing to another
antibiotic that is less effective.
(omfs clinics of N.A vol 15 feb
2003)
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26. TISSUE DISTRIBUTION OF THE
ANTI BIOTICS
• Although abscess cavities are not vascular,
some penetration of antibiotic dose occur.
• Clindamycin best penetrates in to an
abscess and attains abscess concentration
of 33% of serum levels. So it may be best in
odontogenic infections.
• Bone penetration of the antibiotics is an
important ,especially in osteomyelitis.
tetracyclins, fluroquinolones, clindamycin
best penetrates in to the bone.
(omfs clinics of N.A vol 15 feb 2003)
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27. • Cerebrospinal fluid penetration, or
ability of an antibiotic to cross bloodbrain barrier, is paramount in the
treatment of infections that threaten the
CNS, as in actual or impending
cavernous sinus thrombosis.
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29. COST OF THE ANTIBIOTIC
• Clinician should consider the cost of
the antibiotics prescribed.
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30. PRINCIPLES OF ADMINISTRATION
OF ANTIBIOTIC
• Once it has been established that the
patient has an infection that requires
antibiotic therapy, and the kind of
antibiotic has chosen it must be
administrated properly.
• Some of principles must be fallowed in
administration of antibiotics.
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31. PROPER DOSE
• The goal of any drug therapy should be to prescribe
or administer sufficient amount to achieve the
desired therapeutic effect but not enough to cause
injury to the host.
• The dosage prescribed must be capable of
establishing a concentration of antibiotic that is 3 to
4 times the MIC .
• Therapeutic levels greater than 3 to 4 times the MIC
generally do not improve the therapeutic results. But
increases the toxicity and is wasteful
• Increased dose may be indicated in cases like
abscess formation or non vital tissues.
• Under dosing – gives rise to resistant bacteria.
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32. PROPER TIME INTERVAL
• The frequency of doing is also of importance in
administration of antibiotics.
• Plasma half life (t 1/2): is the time with in which one
half of the absorbed dose of drug is excreted. The
time interval has been established for various
antibiotics.
• The usual dosage interval for the therapeutic use of
antibiotics is four times the t ½.
• Because most antibiotics are eliminated by the
kidneys, the patients with preexisting renal disease
and subsequent decreased clearance may require
longer intervals between the doses to avoid
overdosing.
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33. PROPER
ROUTE OF ADMINISTRATION
• Oral route is the most common route and
comfortable to both clinician and the patient.
• But some of the bacteria are not susceptible
to the drug plasma concentrations produced
by oral administrations. but they are
achieved by parenteral routes.
• Most of the oral antibiotics should be taken
in fasting state (30min before or 2hrs after
the meal) for maximum absorption.
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34. CONSISTENCY OF
ROUTE OF ADMINISTRATION
• If the infection is mild enough oral administrations
are sufficient.
• When treating a serious, established infections,
parenteral antibiotic therapy is frequently the
method of choice.
• After an initial response has been achieved
immediate, discontinuation of parenteral therapy,
and oral administration should not be done, which
can lead to fall in blood levels of the antibiotic
causing recurrence of the infection.
• Bacteria usually are not eradicated until the
antibiotic is given for 5 to 6 days.
• So after 5th day of parenteral administration , the
blood levels achievable with oral administrations are
sufficient.
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35. COMBINATION
ANTIBIOTIC THERAPY
• In routine infections the combination
therapy should be avoided to prevent
the opportunity for resistant bacteria to
emerge.
• Antibiotic combinations are clearly
indicated in situations like:
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36. • A) when it is necessary to increase the antibacterial
spectrum in the patients with life threatening sepsis
of unknown cause.
• B) increased bactericidal effect against a specific
organism is desired.
eg: treatment of enterococus infection
(penicillins & aminoglycocides)
• C) prevention of the rapid emergence of resistant
bacteria . (like in tuberculosis)
• D) emphiric treatment of odontogenic infections like
cellulitis/abscess which can progress to more
serious like retropharyngeal space infections.
(penicillin and metronidazole)
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37. RESPONSE TO THE
TREATMENT
• Most commonly, the response begins by the 2nd day
and initially is a subjective sense of feeling better.
• There after objective signs of improvement occur,
including a decrease in temperature, swelling, pain
and lessening of trismus.
• DURATION OF A.THERAPY:
usually
eradication of infection generally is reached by the
3rd day and the patient becomes relatively
asymptomatic. and additional 2 days course will
complete 5 days which will be more safer.
(omfs clinics of N.A vol 15 feb 2003)
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38. CAUSES OF FAILURE OF TREATMENT.
1. Inadequate surgical treatment,
2. Depressed host defense,
3. Presence of foreign body,
4. Antibiotic problems:
Drug not reaching infection,
Dose not adequate,
Wrong bacterial diagnosis,
Wrong antibiotic.
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39. ADVERSE REACTIONS
• Adverse reactions occur all too commonly.
• Hypersensitivity reactions occur with all
antibiotics.(penicillins, cephalosporins)
• These reactions may include accelerated
anaphylactic reactions (type 1) or less
severe reactions associated with edema,
utricaria, and itching.
• The less sever reactions that develops as a
rash or utricaria may begin immediately or
many hours after exposure (type 2 & 3)
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40. • Delayed hypersensitivity reactions (type 4)
are mediated by T-lymphocytes,
most common sign is persistent low grade
temperature even after pain, swelling and
other problems subsides.
DC-eosinophil count is increased
the temperature elevation resolves in 24 to
48 hrs after the drug is withdrawn.
• Antibiotics frequently causes
gastrointestinal distress.
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41. ANTIBIOTIC ASSOCIATED COLITIS:
•
it is one of the toxic reaction which is
associated with antibiotics.
clindamycin
ampicillin/amoxicillin
cephalosporins
• The pseudomembranous colitis is caused by
toxins from clostridium difficile.
• Patients receiving antibiotics that alter
colonic flora may have an overgrowth of
c.difficile, which leads to ACC.
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42. • Usually occur in
medically compromised patients
inpatients
Elderly people
females
• C/F- profuse watery diarrhea that may be bloody
cramping abdominal pain
fever and leukocytosis
• Treatment :discontinuation of anti biotic
restoration of fluid and electrolyte balance
administration of ant-clostridia antibiotics
(oral vancomycin, metronidizole)
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43. Common adverse reactions associated
with commonly used antibiotics
1.
2.
3.
4.
5.
Penicillins :hypersensitivity
direct toxicity
(convulsions,muscular twitchings)
Cephalosporins :nephrotoxicity(cephaaloridine)
hypersensitivity
neutropenia & thrombocytopenia
Aminoglycosides: ototoxicity
nephrotoxicity
neuromuscular blockede
Macrolides: GI pain ,
hypersensitivity.
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Quinolones: neurological
45. SUPERINFECTIOSNS AND
RECURRENT INFECTIONS
• Refers to the appearance of a new infection as a
result of antibiotic therapy.
• In normal state, the normal flora present in the body
live in peaceful coexistence with the host and by
their physical presence prevent bacteria capable of
producing disease from growing in large numbers.
• Thus normal flora acts as a defense mechanism
against infections, but when the indigenous flora is
eliminated or altered by an antibiotic, the pathogenic
bacteria resistant to antibiotics may cause
secondary infection, or super infection..
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46. • CADIDIASIS: (thrush)
overgrowth of Candida occur when high doses of
long term penicillin therapy is given , which
eliminates gram-positive cocci.
patients treated for osteomyelitis or
actinomycosis with high doses of antibiotics are
more susceptible to thrush .
thrush should be treated with anti fungal
agents like cotrimazole.
• HOPITALIZED PATIENTS:
high incidence of secondary infections. such
infections may be related to:
use of broad spectrum antibiotics
high percentage of patients taking broad
spectrum antibiotics
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47. • Jarisch-herxheimer reaction:
- produced by penicillin when injected in
syphilitic patients( secondary syphilis)
- shivering, fever, myalgia, exacerbation of
lesion, vascular collapse
- dose not need interruption of therapy
-Aspirin & sedation gives relief.
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48. RECURRENT INFECTIONS:
recurrent infections occasional in odontogenic
infections .careful monitoring of the patients is
needed even after the clinical signs of infection are
subsided.
treatment of osteomyelitis, actinomycosis are
usually associated with recurrent infections,
because non vital bone provides barrier to antibiotic
effectiveness and potential site of focus of infection.
in these cases reculture and readministration of
antibiotic therapy and surgical intervention are
needed.
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51. ANTIBIOTIC RESISTANCE
1.
2.
3.
4.
Generally bacteria acquires antibiotic
resistance in any one of the fallowing
ways
Alteration of drug’s target site
Inability of a drug to reach its target.
Inactivation of an antimicrobial agent
Active elimination of an antibiotic
from the cell.
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52. •
1.
2.
3.
4.
Acquisition of antibiotic resistant
gene by bacteria occurs in these 4
specific mechanisms:
Spontaneous mutations
Gene transfer
Bacteriophages
Mosaic genes
(omfs clinics of N.A vol 15 feb 2003)
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53. ANTIBIOTIC RESISTANCE
MECHANISM
1. Drug inactivation or modification:
destruction or inactivation by induction
of specific drug inactivating enzymes.
eg; staphylococus aureus
enterococcus
pseudomonas
bacteroids & prevotella
penicillins , aminoglycosides are affected.
ability to produce neutralizing enzymes
like penicillinase and like in methylation of
erythromycin , clindamycin.
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54. 2. Alteration of microbial membrane permiability:
causes decreased uptake or increased efflux of
antibiotic.
-E.coli ,salmonella
3.Alteration of target site:
enzymes responsible for cell wall synthesis
(transpeptidase) are altered to produce less affinity
for penicillins.
-s.aureus, s.pneumoniae
4.Alteration in concentration of drug target receptors:
.coli, proteus, enterobacter,
these have the ability to alter the number of drug
receptors that bind the antibiotic.
(omfs clinics of N.A vol 15 feb 2003)
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55. PRE OPERATIVE USE OF
PROPHYLACTIC ANTIBIOTICS
Principles of prophylactic antibiotics:
1. Intended procedure must carry a
significant risk of post op infection.
2. Correct antibiotic must be selected.
3. Proper administration.
(omfs clinics of N.A vol 15 feb 2003)
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56. • JOMFS vol 10 1990
by LARRY J.PETERSON
OHIO UNIVERSITY ,CLOMBUS.
ANTIBIOTIC PROFILAXIS AGAINST WOUND
INFECTION IN OMFS.
principles of antibiotic prophylaxis:
1)surgical procedure should have significant risk
of infection.
2)select correct antibiotic for surgical procedure.
3)the A.B level must be high
4)time A.B administration correctly.
5)use the shortest effective A.B exposure.
•
short term (1 day ) prophylactic usage has little or
no influence on the growth of resistant bacteria.
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57. THERAPEUTIC USES OF A.B IN
OROFACIAL INFECTIONS
1. ODONTOGENIC INFECTIONS:
penicillin,
clindamycin,
metronidazole,
cephlosporins,
amoxicillin+clavunate.
tetracyclins & quinalones are not effective
towards severe anaerobic infections.
erythromycin –poorly absorbed and less
efffective in odontogenic infections.
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58. 2.OSTIOMYELITIS OF THE JAWS:
regimen 1:for hospitalized, medically
compromised or when i.v therapy is
indicated.
penicillin 2 millon U I.V Q4th + metronidazole
500mg,Q 6h.
when improved for 48 to 72 hrs switch to:
penicillin v, 500mg po Q4th + metronidazole
500mg po Q 6h, for an additional 4 to 6
weeks.
or
ampicillin/salbactum 1.5 to 3 g iv Q6h
when improved for 48 to 72 hrs switch to :
amoxycillin/clavulanate 875/125 mg po bid
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for additional
4 to 6 weeks.
59. Regimen 2:for out patients
penicillin v 2g + metronidazole 0.5g Q8h po, for 2 to
4 weeks after last sequestrum removed and patient
with out symptoms.
or
clindamycin 600 to 900 mg Q6h iv then:
clindamycin 300 to 450 mg Q6h po.
or
cefoxitin 1 g Q8h iv or 2g Q 4h im or iv
untill no symptoms, then switch to,
cephalexin 500 mg Q 6h po, for 2 to 4 weeks.
for penicillin allergic patients :clindamycin.
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60. 3. Head & neck surgery:
•
parenteral therapy instituted
before the skin incision and maintained
for no longer than 48hrs.
Ampicillin + Sulbactum 1.5g Q 6h
Clindamycin 900mg Q 6h
Cefazolin 2g Q 8h
Metronidazole 500mg Q8h
• if the wound is contaminated :
irrigation with Clindamycin 900mg in
1lt normal saline solution.
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61. • JOMFS VOL 49 1991:
• SURVEY OF ANTIBIOTIC PROPYLAXIS FOR
INTRA ORAL ORTHOGNATHIC SURGERY:
• survey done with 114 omfs residency
programs.
•
conclusion: rapid I.V administration of
penicillin G 600,00 U achieves a peak of
7micro.gm/ml, which is greater than 3 to 4
times more than the MIC for susceptible
organisms.
•
penicillin should be given parenterally in
dose of 1 or 2 million U preoperatively and an
additional dose every 11/2 to 2 hrs. least A.B
dose should be given in recovery room.
•
it can prevent prolonged use of A.B
coverage.
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