Antibiotics - Principles and its Rationale (18-03-23).pdf

Antibiotics and its use should be done proficiently and carefully.
Indications and contraindications should be noted along with appropriate timing and dosage of drugs. Principles and rationale of its use and applications are enlisted and explained in the slides.

1. ANTIBIOTICS
PRINCIPLES & RATIONALE
DR. RIYA SHAH
DEPT. OF ORAL AND MAXILLOFACIAL SURGERY

2. CONTENTS
Introduction
History
Classification
Principles of
Antibiotic Therapy
principles of Antibiotic
Administration
Post Antibiotic effects
Conclusion
References

3. WHAT ARE ANTIBIOTICS?
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
These are substances produced by
microorganisms, which selectively
suppress the growth of or kill other
microorganisms at very low
concentration.
Antimicrobial - This term refers to both
antibiotics and synthetic agents active
against microbes.

4. Microstatic - (Bacteriostatic, Virostatic, Fungistatic) : The
organism is reversibly inhibited at specific metabolic processes
and multiplication of the organism is inhibited.
Narrow Spectrum Antimicrobial - An antimicrobial that acts on a
limited number of microbial species.
Broad Spectrum Antimicrobial - An antimicrobial that acts on a
wide range of species.
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
Microcidal - (Bacteriocidal, Vincidal, Fungicidal) The organism is lysed or
killed by direct damage on susceptible cell targets.

5. History
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
The period of empirical use: South American Indians
used the bark of the cinchona tree to extract quinine to
control malaria.
Mercury was known to cure syphilis in the late 1400's.
Mouldy curd’ by Chinese for boils.
The traces of tetracycline, have been found in human
skeletal remains from dating back to 350–550 CE.

6. Ehrlich’s phase of dyes and organometallic compounds
(1890–1935): He toyed with the idea that if certain dyes
could selectively stain microbes, they could also be
selectively toxic to these organisms, and tried
methylene blue, trypan red, etc.
History
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
He developed the arsenicals—atoxyl (arsanilic acid) for
sleeping sickness, arsphenamine in 1906 and
neoarsphenamine in 1909 for syphilis.
He coined the term "Chemotherapy".
The phenomenon of antibiosis was demonstrated by Pasteur in 1877,
when he observed that growth of anthrax bacilli in urine was inhibited by
air-borne bacteria.

7. History
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
Fleming (1929) found that a diffusible substance was
elaborated by Penicillium mould which could destroy
Staphylococcus on the culture plate.
The Modern Era of chemotherapy -by Domagk (1935):
demonstrating the therapeutic effect of prontosil , a
sulfonamide dye in pyogenic infection.

8. Antibiotics: An overview (article) | Khan Academy

9. ACCORDING TO THE 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, Moxifloxacin, etc
4. β-lactam antibiotics: Penicillins, Cephalosporins, Monobactams,
Carbapenems.
5. Tetracyclines: Oxytetracycline, Doxycycline, etc.
6. Glycylcycline: Tigecycline.
7. Nitrobenzene derivative: Chloramphenicol.
8. Aminoglycosides: Streptomycin, Gentamicin, Neomycin, etc.
CLASSIFICATION
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

10. 9. Macrolide antibiotics: Erythromycin, Clarithromycin,
Azithromycin, etc.
10. Lincosamide antibiotics: Lincomycin, Clindamycin.
11. Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin,
Tyrothricin.
12. Glycopeptides: Vancomycin, Teicoplanin
13. Oxazolidinone: Linezolid.
14. Nitrofuran derivatives: Nitrofurantoin, Furazolidone.
15. Nitroimidazoles: Metronidazole, Tinidazole.
16. Nicotinic acid derivatives: Isoniazid, Pyrazinamide,
Ethionamide.
17. Polyene antibiotics: Nystatin, Amphotericin-B, Hamycin.
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

11. 18. Azole derivatives: Miconazole, Clotrimazole,
Ketoconazole, Fluconazole.
19. Others: Rifampin, Spectinomycin, Sod. fusidate,
Cycloserine, Vincomycin, Ethambutol, Clofazimine,
Griseofulvin.
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

12. Antibacterial: Penicillins, Aminoglycosides, erythromycin etc.
Antifungal: Griseofulvin, amphotericin B, ketoconazole etc
Antiviral: Acyclovir, Amantadine, Zidovudine etc
Antiprotozoal: Chloroquine, pyrimethamine, metronidazole etc
Antihelminthic: Mebendazole, nicosamide, diethyl carbamazine etc
According to the type of organisms against which they primarily act:
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

13. Narrow Spectrum:
Pencillin G
Erythromycin
Broad Spectrum:
Tetracycline
Chloramphenicol
Extended Spectrum:
Semisynthetic Pencillin, Cephalosporins,
According to the Spectrum of activity:
Aminoglycosides
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

14. Principle 1: To determine the severity of infection
Principle 2: To evaluate state of patient’s host defense mechanisms
Principle 3: To determine whether patient be treated by dentist or specialist.
Principle 4: To treat infection surgically
Principle 5 : To support the patient medically
Principle 6 : Choose and prescribe appropriate antibiotic
Principle 7 : Proper antibiotic administration
Principle 8 : Monitoring the patient
PRINCIPLES OF ANTIBIOTIC THERAPY
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

15. Some microbes are naturally resistant to certain drugs.
They lack their metabolic process or target site which is affected by this drug.
Development of resistance over a period of time.
DRUG RESISTANCE:

Refers to the unresponsiveness of a microorganism to an antimicrobial agent.

Natural resistance:
Examples:
Gram negative bacilli are normally unaffected by penicillin G.
Acquired resistance:

16. Mutation
It is stable & heritable genetic change that occurs spontaneously & randomly among
microorganisms. -Single step
-Multi step
Gene transfer from one organism to another
Conjugation: gram -ve
Transduction: bacteriophage
Transformation
Some bacteria like staphlococci, coliform, tubercle bacilli have acquired
resistance, whereas others like S. pyogens & spirochaetes – no resistant to
penicillin inspite of use over 50 years.

18. Principles of Antibiotic Therapy for Head, Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI
Antibiotic Resistance Mechanisms

19. An antibiotic prescription selects for resistant strains, not only in the patient, but
also in entire families.
In one study,
The oropharyngeal carriage of one or more penicillin resistant strains rose from
12 to 46% of patients, but also rose to 45% in the other family members.
After 3 months, carriage of resistant organisms had declined only to 27%.
Brook et al took throat swab cultures of pediatric patients with pharyngitis before
and after a 7-day course of penicillin. After treatment, cultures were taken of the
patients and their parents and siblings.
The implication of this study is that by prescribing antibiotics, clinicians increase the
incidence of antibiotic resistant strains, not only in their patients, but also in
their patients’ families and their entire communities, such as
schools and workplaces.
Head, Neck, and Orofacial Infections: An Interdisciplinary
Approach Elie M. Ferneini ,James R. Hupp

20. SUPERINFECTION:

Appearance of a new infection as a result of antimicrobial therapy.

21. It is commonly associated with the use of broad/ extended spectrum
antibiotics such as tetracyclines, chloramphenicol, ampicillin.
Tetracyclines – more prone than chloramphenicol
Ampicillin- more prone than amoxicillin.

Conditions predisposing to superinfection:
-Corticosteroid therapy
-Leukaemias and other malignancies
-AIDS
-Agranulocytosis
-Diabetes
-Disseminated Lupus Erythematosus

22. 1. Determination of the severity of infection:
Complete history:
Eliciting patient’s symptom
Physical examination
Time of onset
Duration of infection
Rapidity of progress
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

23. The clinician must correlate historical findings, such as
the history of pain, other symptoms, and prior treatment,
with physical examination to arrive at a clinical diagnosis of infection. For
example, fever occurring without indurated or fluctuant swelling may be the
result of postoperative dehydration or a viral infection.
Inflammation is not always infection
Postoperative edema, which is soft,
jellylike
in consistency, and only mildly tender,
is merely part of the
inflammatory response to surgical
trauma.
Principles of Antibiotic Therapy for Head, Neck, and
Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

24. PETERSON'S PRINCIPLES OF ORAL AND MAXILLOFACIAL SURGERY SECTION 4, 3RD EDITION
EMPIRICAL ANTIBIOTICS' OF CHOICE FOR
ODONTOGENIC INFECTIONS

25. Head, Neck, and Orofacial Infections: An Interdisciplinary Approach Elie M. Ferneini ,James R. Hupp

26. 1.Uncontrolled metabolic diseases: decreased function of
leucocytes, decreased Chemotaxis, decreased phagocytosis,
decreased bacterial killing.
e.g. – uremia, alcoholism, malnutrition, severe diabetes
2. Immuno Suppressing diseases: Interfere with host defense
mechanism e.g.- leukemias, lymphomas, malignant tumours
3. Immuno Supressing drugs : e.g.- cancer chemotherapeutic drugs
Immunosuppressive agent
2. To evaluate state of patient’s host defense mechanisms:
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

27. 3. To determine whether patient should be treated by general
dentist or specialist:
Criteria for referral to a specialist :
1.Rapid progressive infection
2.Difficulty in breathing
3.Difficulty in swallowing
4.Fascial space involvement
5.Elevated temperature (>101 degree F)
6.Severe jaw trismus (<10mm)
7. Toxic appearance
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

28. 4. To treat infection surgically:
GOALS :
1.To remove the cause of infection
2.To provide drainage of accumulated pus and necrotic debris
MODES :
1.Endodontic treatment
2.Extraction
3.Incision and drainage +extraction+ endodontic treatment
Drainage of pus
Reduction in tissue tension
Improved local supply and
Increased delivery of host defenses

29. Because most head and neck infections are caused by the abscess-forming
combination of gram-positive cocci and anaerobes, and because this region
has abundant hard tissues, consisting of teeth and bone, on which biofilms
form easily, source control is paramount in the management of these
infections.
In addition, the head and neck are rich with cavities that require drainage to
the external environment to cleanse them of accumulated bacteria and
secretions, such as the sinuses, nose, ears, and the lacrimal apparatus.
Surgery is often necessary to establish drainage of normal and pathologic
cavities in the head and neck.
As bacterial resistance to antibiotics increases, head and neck surgeons will
be less able to rely on medical therapy and will return to surgery as the
primary management of head and neck infections. Surgery is primary;
antibiotics are adjunctive.
Principles of Antibiotic Therapy for Head, Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

30. Odontogenic infection

Pain and swelling

No adequate fluid and nutritional intake

Depressed host defenses

Adequate analgesics and fluid intake
5. To support the patient medically:

31. 6. Choose and prescribe appropriate antibiotic:
Identification of causative organism
Determination of antibiotic sensitivity
Use of a specific, narrow spectrum antibiotic
Use of the least toxic antibiotic
Patient drug history
Use of a bactericidal rather than a bacteriostatic drug
Use of the antibiotic with a proven h/o success
Cost of the antibiotic
Encourage patient compliance
Principles for choosing appropriate antibiotic :
1.
2.
3.
4.
5.
6.
7.
8.
9.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

32. It is Scientifically determined either in the laboratory, where the organism can
be isolated from pus, blood or tissue or Empirically based upon the knowledge of
the pathogens and clinical presentation of specific infection.
Typical odontogenic infection is caused by a mixture of aerobic & anaerobic
bacteria (70%).
Aerobic bacteria – 5% (gram positive cocci) .
Pure anaerobic bacteria – 25% (gram positive cocci – 30% & gram negative rods –
50%).
All are sensitive to penicillin & penicillin like drugs, but fusobacterium frequently
resistant to erythromycin (apprx. 50%)
I. Identification of causative organism:
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

33. Clinical case of medication-related osteonecrosis of the maxilla 4 months after
dental extractions in a woman treated with denosumab for metastatic breast
cancer.
She had chronic right maxillary pain and multiple draining
sinus tracts in the attached gingiva and alveolus. Exposure of the infected necrotic bone
identified a gray-black discoloration of the bone.
Resection of the necrotic bone resulted in exposure of the maxillary sinus, with inflamed
antral mucosa and suppuration within the sinus. Because of the
likelihood of black-pigmented oral anaerobes, such as Prevotella melaninogenica, plus the
exposure and infection of the maxillary sinus, amoxicillin-clavulanate was chosen as the
initial empiric antibiotic. Cultures yielded viridans streptococci and oral gram-negative
anaerobes susceptible to amoxicillin-clavulanate. The antibiotic was continued for
6 weeks because of bone infection, resulting in successful
closure of the surgical defect, without oroantral fistula, and
resolution of pain.

34. Medication-related osteonecrosis of the jaws, preceded by therapy with denosumab for
metastatic breast cancer.
A, Inflamed mucosa and multiple sinus tracts draining the right and left anterior maxilla.
B, Exposure of the maxillary alveolar process, with gray-black discoloration of necrotic
bone, suggesting black-pigmented oral anaerobic infection.
C, Resection of the anterior maxilla,resulting in a large exposure of the maxillary sinus.
D, Successful healing at 6 months after debridement.

35. Cultures should be performed especially when :
1. Patient with an infection has compromised host defenses
2. Received appropriate treatment for 3 days without improvement
3. Postoperative wound infection
4. Recurrent infection
5. Actinomycosis is suspected
6. Osteomyelitis is present

36. II. Determination of Antibiotic Sensitivity:-
Not responded to initial antibiotic therapy or a postoperative wound infection –
causative agent identified & the antibiotic sensitivity determined.
DISK DIFFUSION METHOD RATIONALE :
Antibiotics diffuse into the agar and inhibit the growth of sensitive bacteria in a
semicircular zone around the disc.
When the resistance to a given agent is present, the zone radius will be reduced or
these will be no zone at all.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

37. Kirby Bauer Disc Diffusion Method For Antibiotic Susceptibility Testing
May 18, 2022 by Reeju Sharma

38. Penicillin - excellent for treatment of streptococcus infection & is good to
excellent for the major anaerobes of odontogenic infections.
Erythromycin - streptococcus, peptostreptococcus & prevotella but is ineffective
against fusobacterium.
Clindamycin – streptococcus & major anaerobic groups.
Cephalexin – moderately active against streptococcus & is good to excellent
against anaerobes.
Metronidazole – no activity against streptococcus but has excellent activity
against anaerobes.
The result of these studies provide the information needed to prescribe
the most appropriate antibiotic.

Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

39. III. Use of a specific, narrow spectrum antibiotic:
Advantages –
Less chances of developing resistant organisms.
e.g. Streptococcus sensitive to penicillin , cephalosporin and tetracycline
Minimizes the risk of super infections.
e.g. Moniliasis and gram negative pneumonias.
IV. Use of the least toxic antibiotic:-
Equally effective but less toxic drugs have to be used.
e.g . bacteria causing odontogenic infection susceptible to both penicillin and
chloramphenicol but more toxicity present with the latter drug.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

40. V. Patient drug history:-
Previous allergic or toxic reactions
Allergy rate to penicillin - 5 %
Cross sensitivity of penicillins and cephalosporins.
Toxic reactions - identify the drug and precise reaction

VI. Use of a bactericidal rather than a bacteriostatic drug:-
Advantages:
1. Less reliance on the host resistance
2. Killing of the bacteria by the antibiotic itself
3. Faster results
4. Greater flexibility with dosage intervals.
Used especially when the host defenses are low.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

41. frequency of treatment success and failures
frequency of adverse reactions
frequency of side effects
VII. Use of the antibiotic with a proven h/o success:-
Critical observation of the clinical effectiveness over a prolonged period.
Assessment of :

VIII. Cost of the antibiotic:-
Difficult to place a price tag on health.
In some situations, more expensive antibiotic is the drug of choice.
In other situations, there may be a substantial difference in price for drugs
of equal efficacy.
Surgeon should consider the cost of the antibiotic prescribed.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

42. IX. Encourage patient compliance:-

Dosage interval that encourages compliance:
OD 80%
BID 69%
TID 59%
QID 35%
Non-compliant start feeling better :
3-5 days 50%
>7 days 20%
Antibiotic that would have the highest compliance would be the
drug given OD for 4 or 5 days.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

43. Rapidly progressive swelling
Diffuse swelling
Compromised host defenses
Involvement of facial spaces
Severe pericoronitis
Osteomyelitis
Use of antibiotics is not
necessary in:


Chronic well localized abscess
Minor vestibular abscess
Dry socket
Mild pericoronitis
Bassetti, M., Montero, J.G. & Paiva, J.A. When antibiotic treatment fails. Intensive Care Med 44, 73–75 (2018).
Indications for use of
antibiotics

44. PRINCIPLES OF
ANTIBIOTIC
ADMINISTRATION
•Proper dose

•Proper time
interval

• Proper route
of
administration
•Consistency
in route of
administration

•Combination
antibiotic
therapy

7. Proper Antibiotic Administration
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

45. Prescribe or administer sufficient amounts to achieve the
desired therapeutic effect but not enough to cause injury to the host.

- For therapeutic purposes the peak concentration of the antibiotic at the
site of infection should be 3 – 4 times the MIC.

- Administration of doses above that level increases the likelihood of
toxicity .
- Subtherapeutic levels may mask an infection.
A) PROPER DOSE:
MINIMAL INHIBITORY CONCENTRATION : Is the lowest antibiotic
concentration that prevents growth of microorganism after an incubation
period of 18 – 24 hours
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

46. Drug dose calculation :
BASED ON BODY SURFACE AREA
Individual dose = BSA[m2 ] x adult dose
1.7
BASED ON BODY WEIGHT
Individual dose = BW[kg] x average adult dose
70
In Pediatric patients:
YOUNG’S FORMULA :
CHILD DOSE = Age x adult dose
Age + 12
DILLING’S FORMULA :
CHILD DOSE = Age x adult dose
20
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

47. Loading dose: This is a single or few quickly repeated doses given in the beginning to
attain target concentration capacity.
Maintainance dose: This is the dose repeated at specific interval after attainment of
target cycles per second.
Antibiotic loading doses
Indications :
1.The half-life of the antibiotic is longer than 3-hours.
2. A delay of longer than 12-hours to achieve therapeutic blood levels is
unacceptable.
Because most acute orofacial infections begin and peak rapidly
Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.

48. Prolonged antibiotic therapy destroys resistant bacteria.
Prolonged antibiotic therapy is necessary to prevent rebound infections.
The dosage and duration of therapy can be extrapolated from one infection to
another.
The prescriber knows how longer the infection will last
Misconceptions in longer duration of antibiotics :
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

49. Principles of Antibiotic Therapy for Head,
Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

50. In the present case report, patient underwent
extraction of offended tooth to eradicate the
infection, however inadequate drainage of the
abscess, inadvertent use of antibiotics and lack
of proper postoperative follow-up leads to
persistence of residual infection.

51. B) PROPER TIME INTERVAL
Each antibiotic has an established plasma half life , during
which ½ of the absorbed drug is excreted.
Usual dosage interval for the therapeutic use of antibiotics is
4 times the t½.
At 5 times the t½, 95% of the drug has been excreted.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

52. In some infections, only parental administration
produces the necessary serum level of antibiotics.
Oral route results in the most variable absorption.
Most antibiotics should be taken at in fasting state (
30mins before or 2 hrs after meal) for maximum
absorption.
C) PROPER ROUTE OF ADMINISTRATION

For e.g. Penicillin V oral - 2 gm Plasma level - 4 µG/ mL

53. After initial response , immediate discontinuation of parenteral route -
Recurrence .
Maintenance of peak blood levels of antibiotic for an adequate period is
important – max. tissue penetration & effective bactericidal action.
When treating a serious, established infection, parental antibiotic therapy is
frequently method the choice.
Recurrence of infection is more likely by switching from parenteral to oral route
on the 2nd or 3rd day of antibiotic therapy.
After 5th day of parental administration , the blood levels achievable with oral
administration are usually sufficient.
D) CONSISTENCY IN ROUTE OF ADMINISTRATION:
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

54. Combining multiple antibiotics can increase toxicities and costs, select for
resistant organisms, and cause antagonistic interactions between the
antibiotics. For example, vancomycin has minimal renal toxicity when used
alone. In combination with an aminoglycoside, such as gentamicin, renal toxicity
is significantly increased.
E) COMBINATION ANTIBIOTIC THERAPY:-

Combination therapy with two or more antibiotics is used in special cases:
- Prevent the emergence of resistant strains.
- To treat emergency cases during the period when an etiological diagnosis is
still in progress.
- To take advantage of antibiotic synergism.
Principles of Antibiotic Therapy for Head, Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

55. A classic example of mutual antibiotic antagonism is the
combination of a bactericidal agent with a bacteriostatic antibiotic.
In general, the bactericidal antibiotics are effective during the rapid growth and
cellular division phases of the bacterial life cycle, often by interfering with cell wall
synthesis; therefore, their action is antagonized by antibiotics that suppress rapid
bacterial growth. Most antibiotics that interfere with protein synthesis slow bacterial
growth without a killing effect. Thus, combining a protein synthesis inhibitor, such as
a macrolide, with a cell wall synthesis inhibitor, such as a penicillin or cephalosporin,
has a net bacteriostatic effect
Principles of Antibiotic Therapy for Head, Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

56. Principles of Antibiotic Therapy for Head, Neck, and Orofacial Infections
THOMAS R. FLYNN AND RABIE M. SHANTI

57. Should be avoided when not specifically indicated.
Usual result – broad spectrum exposure that leads to depression of the normal
host flora & increase opportunity for resistant bacteria to emerge.
For routine infections, the disadvantages of combination therapy outweigh the
advantages.
Principles of combination antibiotic therapeutic dose:
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

58. Minimal Inhibitory Concentration
Post-antibiotic effects
Microbial persistence and regrowth
Dosing and resistance
FACTORS INFLUENCING ANTIBIOTIC THERAPY:
Rule of thumb:
The concentration of the antibiotic in the blood should exceed the
MIC by a factor of 2-8 times to offset the tissue barriers that restrict
access to the infected site.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

59. Is the persistent supression of microbial growth after short time exposure to an
antimicrobial agent.
Mechanism: Is the time necessary to recover from sublethal structural and
metabolic alterations that prevents resumption of bacterial regrowth.
The particular organism
Inoculum size
Growth medium
Organism growth phase
Mechanism of action of antibiotic
Duration of exposure to the drug
Postantibiotic effects
Factors influencing PAE:
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

60. Microbial persistence and regrowth.
The subpopulation of organisms that is not inhibited or killed during a given dose
interval which can then reestablish themselves and continue growth.
Factors determining :
1.Initial inoculum size
2.Bactericidal activity
3.Organism MIC
4.Post-antibiotic effects
5.Antibiotic pharmacokinetics
6.Doubling time of the organism.
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

61. 8. Monitoring the patient:
1) Response to treatment.
Reasons for treatment failure:
-Inadequate surgical treatment
-Depressed host defences.
-Presence of foreign body.
-Antibiotic problems:
Drugs not reaching infection.
Dose not adequate
Wrong bacterial diagnosis.
Wrong antibiotic.
2) Development of adverse reactions
3) Superinfection and recurrent infection
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company, Philadelphia

62. These principles will certainly evolve as our knowledge increases, yet they can
serve as a starting point for a new approach to the wise use of antibiotics by
head and neck surgeons in the current era of increasing antibiotic resistance, the
declining systemic reserve of our aging population, ever more complicated
antibiotic drug interactions with our patients’ concurrent medications, and
increasing costs of care.
conclusion
Antibiotic selection remains as much of an art as it is a science. It requires the
integration of many factors that are host specific, pharmacologic, and even geo-
graphic. Much more research is necessary in this field to solve the current
problems with the need for more timely culture and sensitivity results, increasing
antibiotic resistance, and best practices in antibiotic usage.

63. References
ESSENTIALS OF PHARMACOLOGY ;KD TRIPATHI 3RD EDITION
Topazian, R.G., Goldberg, M.H. and Hupp, J.R. (2002) Oral and Maxillofacial Infections. 4th Edition, WB Saunders Company,
Philadelphia
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