Antibiotics and antibacterial drugs

1. ANTIBIOTICSANTIBIOTICS
Dr. V.RAMKUMAR
CONSULTANT DENTAL
&FACIOMAXILOFACIAL SURGEON
REG. NO.4118. TAMILNADU-
INDIA( ASIA)

2. Principles of rational antibiotic
therapy
•Presence of substantiated indications for prescription
of an antibiotic
•Choosing of the most effective and the least toxic
drug, in time administration
•Introduction of optimal doses with optimal frequency,
taking into consideration complexity of the disease
•Choosing of the optimal way of introduction
•Estimation of duration of treatment
•Control after treatment
• Monitoring and prophylaxis of negative side effects
•Decision on expediency of combined antibiotic therapy

3.  Mechanism of the antibioticsMechanism of the antibiotics

4. ANTIBIOTICS
•Beta-lactam antibiotics:
•А. Penicillins
•Б. Inhibitors of beta-lactamases and combined drugs,
•В. Cephalosporins
•Г. Monobactams
•Д. Tienamycin (carbapenems).
•Macrolides, azalides, streptogramins, prystinamycines.
•Linkozamides.
•Tetracyclines.
•Aminoglycosides.
•Chloramphenicols.
•Glycopeptides.
•Cyclic polipeptides (polimixins).
•Other antibiotics

5. ANTIBIOTICS
Dose-dependent Time-dependent
Antibacterial effect directly
depends on their
concentrations in the locus of
inflammation
(high doses 1-2 times/24h)
Aminoglycosides
Fluoroqinolones
Metronidazol
Amphotericin B
Effectiveness depends on a
period of time, during which
concentration in blood
overwhelms MIC for a
particular causative agent
(constant i.v. infusion or 3-6
times/24h)
Beta-lactames
Glycopeptides
Macrolides
Linkozamides

6. PENICILLINS
Natural (biosynthetic) penicillins:
•benzylpenicillin (penicillin G), phenoxymethylpenicillin (penicillin
V), novocain salt of benzylpenicillin (benzylpenicillin procain),
bicillin-1 (benzatyn benzylpenicillin), bicillin-3, bicillin-5.
Semisynthetic penicillins:
•1 antistaphylococci penicillinase resistant penicillins –
izoxazolil-penicillins (oxacillin, dicloxacillin, methicillin);
•2 of a spread spectrum – aminopenicillins (ampicillin,
amoxicillin);
•3 antipseudomonade – carboxypenicillins (carbenicillin,
ticarcillin); ureidopenicillins (azlocillin, piperacillin, sulbenicillin);
•4 combined with inhibitors of beta-lactamases -
“protected” penicillins (amoxicillin/clavulanate,
ampicillin/sulbactam, ticarcillin/clavulanate,
piperacillin/tazobactam).

7. Nucleus of penicillin molecule
L – beta-lactame ring, T – thiazoline ring
N
T
L
S
C
O
OH
CH3
CH3
O
H2N

8. Mechanism of penicillins actionMechanism of penicillins action
They form complexes with enzymes - trans-
and carboxypeptidases (PCP), which control
synthesis of peptidoglycan – component of
cell-wall of microorganisms

9. Spectrum of action of biosynthetic penicllins
Gram-positive
microorganisms
Gram-negative
microorganisms
Streptococci
Bacillus anthracis
Causative agents of
tetanus, gas
gangrene
Actinomycets
Listeria
Gonococci
Meningococci
Moraxella
Causative agent of
syphilis
Leptospiras

10. Complications of biosynthetic
penicillins
•Allergic reactions (10 %)
•Endotoxic shock
•Disorders of electrolyte balance
•Neurotoxic reactions (in using of big doses)
– encephalopathy (hyperreflexia, seizures,
hallucinations, coma)
• Daily dose of BP during intratecal
introduction should not overcome 10 000 U
(5 000 U – for children)
•Interstitial nephritis

11. OxacillinOxacillin

Antistaphylococci penicillinase-resistant
semisynthetic penicillin, acid stable

Administration: intramuscular, intravenously,
oraly 3-6-8 g/24 hours (4-6 times of injections)

12. .
Spectrum of action of aminopecillins
(ampicillin, amoxicillin)
wide spectrum, destroyed by beta-lactamases

Influence on: streptococci, Haemophilus influenzae, causative
agent of wooping cough, gonococci, meningococci, proteus,
Escherichia coli, salmonella, shigella

13. Ampicillin

14. Amoxicillin

15. Differences between ampicillin and amoxicillin Differences between ampicillin and amoxicillin
Parameters

Ampicillin Amoxycillin
Activity towdards
- pneumococci
- H. pylori
- salmonella
- shigella
Bioavailability after oral
administration
Influence of food on
bioavailability
Level in sputum
Level in urine
Appearance of diarrhea
++
+
++/+++
+++
40 %

dicreases in 2 times
low
high
frequently
+++
+++
+++
+
90 %
no influence
high
very high
rarely

16. Indications for administration of amoxicillin
Localisation of ifection Drug of choice Alternative drug
Respiratory tracts Acute midlle otitis
Bacterial sinusitit
Acute bronchitits
Extrahospital
pneumonia of light or
medium-severe
complexity
Acute pharingitis
Chronical bronchitis
Kidneys and urinary
tracts
Acute pielonephritis
Acute cystitis
Bacteriouria in
children and pregnant
women
Chronical pielonephritis
Acute prostatitis
Gonorrhea
Digestive tract Cholangitis, cholecystitis
Typhoid fever
Other pathology Borreliosis Leptospirosis

17. Side effects of semisynthetic
penicillins
•Irritation of mucous membrane of digestive tract
(diarrhea)
•Disbacteriosis
•Superinfection (colonizing of gut with Candida fungi,
enterococci, Pseudomonas aeruginosa, clostridia)
•Pain in injection area, aseptical inflammation,
phlebitis
•Allergic reactions
•Granulocytopenia (oxacillin)
•Reduction of platelets agregation (ampicillin)
•Disorders of liver function
•Encephalopathy (in introduction of high doses)

18. Inhibitors of beta-lactamases 
Clavulanic acid Sulbactam

Tazobactam

19. Unasyn (ampicillin/sulbactam)

20. Inhibitor-protected (“screened”, “protected”) Inhibitor-protected (“screened”, “protected”)
penicillinspenicillins
Amoxicillin/clavulanateAmoxicillin/clavulanate
(amoxyclav, augmentin)(amoxyclav, augmentin)
AmpicillinAmpicillin/sulbactam/sulbactam
(sultamycillin, unasin)(sultamycillin, unasin)
TicarcillinTicarcillin/clavulanate/clavulanate
(timentin)(timentin)
PiperacillinPiperacillin/tazobactam/tazobactam

21. Structure of cephalosporins
L – beta-lactame ring, D – dihydrothiazine ring
CH2 O CO CH3
C
O
H2N
O
OH
S
L D
N

22. Classification of cephalosporinsClassification of cephalosporins
Way of
introduction
Generation of cephalosporin antibiotics
first I second II third III fourth IV
Injection Cefaloridin
Cefadroxil*
Cefazolin*
Cefalexin*
Cephradin*
Cefamandol
e*
Cefoxytyn*
Cefuroxime*

Cefotaxime*
Ceftriaxone*
Cefoperazon
e*
Ceftazidime*
Cefpirome
*
Cefepime*


Oral Cephalexin *
Cefadroxil*
Cefuroxime
axetyl*
Cefaclor *
Cefixime *
Ceftibuten * -

23. Cefazolin-sodium (C I)

24. Cezolin (Cefazolin, C I)

25. Cefalexin ( C I)

26. Zinnat (Cefuroxime, C II)

27. Cefotaxime (C III)

28. Claphoran (cefotaxime, C III)

29. Cefobid (Cefoperazone, C III)

30. Antimicrobial spectrum of cephalosporins
Generation of
cephalosporins
Active towards Stability towards
beta-lactamase
Gram-
positive
bacteria
Gram-
negative
bacteria
Staphylo
cocci
Gram-
negative
bacteria
І +++ +/-++ -
ІІ ++ + ++ +/-
ІІІ + +++ + +
ІV ++ +++ ++ ++

31. Complications, caused by
cephalosporins
•Irritation of mucous membrane of digestive tract,
infiltrates after intromuscular introduction , phlebitis
after inrtavenous introduction
•Disbacteriosis, superinfection
•Allergic reactions, including cross allergy with
penicillins
•Granulocytopenia (in case of treatment during more
than 2 weeks)
•Hemorrhages (inhibition of synthesis of factors of
blood coagulation in liver) – cephalosporins ІІІ
•Nephrotoxicity (accumulation in epithilial cells of
kidney canalicules)
•Encephalopathy (hyperreflexia, seizures, coma)

32. Cephalosporines Cephalosporines
NNot recommendedot recommended
to combine with other nephrotoxic drugs
(aminoglycosides)
ContraindicatedContraindicated
to combine with loop diuretics (furosemid,
etacrinic acid)

33. MonobactamsMonobactams
Aztreonam
Action spectrum - Gram (-) bacteria, including
Escherichia coli, Clebsiellas, Proteus, Haemophilus
influenzae (activity is equal to the activity of cephaloporins
of third generation)
Ways of introduction: oral (20% are being absorbed),
intramuscular, intravenous
Clinical uses: sepsis, infection of urinary tract, soft
tissues, meningitis and others (often combined with
aminoglycosides , clindamycin, metronidazole,
vankomycin).

34. Carbapenems (tienamytsin)Carbapenems (tienamytsin)
Tienam (imipenem + cylastatin) Tienam (imipenem + cylastatin)

MeropenemMeropenem

The widest spectrum of antibacterial action
most of aerobe and anaerobe Gram (+) and
Gram (-) bacteria, including those which
produce beta-lactamase

35. І. Natural substances: erythromycin,
oleandomycin, spiramycin,
jozamycin, midecamycin.
ІІ. Semi-synthetic substances:
roxythromycin, clarithromycin,
flurythromycin, dyrythromycin,
miokamycin, rokitamycin.
III. Azalides (neutrogen atom is
introduced in lacton ring):
azithromycin.
CLASSIFICATION OF MACROLIDES

36. Erythromycin

37. Macropen (midecamycin)

38. Sumamed (azithromycin)

39. spectrum of action of maclrolides
and azalides
•staphylo-, strepto-, hono-, anaerobe
cocci, enterobacteria
•H.influenzae (clarythromycin,
azithromycin)
• intracellular situated microorganisms
(strains of Helicobacter, Chlamydia,
Legionellа, M. pneumoniae, U.
urealyticum etc.)

40. Pharmacokinetics of macrolides
Quiclkly and fully distributed through the
tissues (do not pass through HEB OR
BBB)
Correlation concentration tissues/blood:
•Erythromycin – (5-10) : 1
•Azithromycin – (100-500) : 1
•Their concentration in phagocyting
cells prevails concentration in blood
pasma in 12-20 times, they get
accumulated in source of inflammation
- macrolides paradoxis

41. Indications for usage of macrolides and
azalides
LOR- infections, infections of upper
respiratory tracts, gynecological
infections, skin and soft tissues
infections; ulcer disease; dyphteria;
whooping-cough; honorrhea; syphilis;
typhoid fever (azithromycin).
Drugs of choice for: mycoplasma,
chlamidia, legionella pneumonia

42. Side affects of macrolides
•Dispeptic disorders, disbacteriosis, superinfection
•Cholestasis, cholestatic jaundice (erythromycin)
•Depression of liver microsome enzyme activity
(erythromycin, oleandomycin can not be combined
with theophylline, ergot alkaloids, carbamazepine)
• Development of resistance in process of treatment

43. Linkosamides
Linkomycin Clindamycin
•Action spectrum: Gram positive aerobe
cocci, grampositive and gramnegatvie
anaerobes
•Penetrate all the tissues (don’t pass
through HEB) including intracellurally
•Usage: usually in heavy infections, caused
by anaerobe microorganisms
•A lot of side effects

44. Linkomycini
hydrochloridum

45. Dalacyn C (clindamycini
hydrochloridum)

46. Tetracyclines
1. Natural - biosynthetic:
chlortetracycline, oxytetracycline,
tetracycline, dimethylchlortetracycline.
2. Semisynthetic:
doxycycline (vibramycin), metacycline
(rondomycin), minocycline.

47. Tetracycline

48. Doxycycline

49. Vibramycin (doxycycline)

50. Shemes of tetracyclines
administration
•Tetracycline - 0,25-0,5 g 4 times per 24
hours
•Methacycline – 0,3-0,6 g 2 times per 24
hours
•Doxycycline – 0,2 g (first day), 0,1g
(next days) 1 time per 24 hours

51. Pharmacokinetics of tetracyclines when combined with Pharmacokinetics of tetracyclines when combined with
other drugsother drugs
Drugs Results of combined
administration
Antacides (Ca+, Mg+
etc.)
Iron preparations
Rifampicin
Decrease of absorbtion

Decrease of absorbtion

Increase of elimination

52. Side effects of tetracyclines
•Dispeptic disorders, stomatitis, glositis,esophagitis,
pruritus etc).
•Disbacteriosis and superinfection with Candida fungi,
proteus, pseudomonadas or staphylococci.
•Photodermatosis.
•Liver toxicity.
•Absorbtion by bones and teeth of a featus or a child:
hipoplasia of dental enamel, disorder of teeth formation,
tendency for caries.
•Antianabolic action, damage of kidneys (when using
tetracyclines with long termed storage, using big doses).
Tetracyclines are forbidden for children under the age of
8/12, during pregnancy, liver diseases, kidney
insufficiency, miastenia

53. Photosensitization - tetracyclines

54. Tetracyclines

55. AMINOGLYCOSIDES
•І generation: streptomycin, neomycin,
monomycin, kanamycin
•ІІ generation: gentamycin (garamycin),
tobramycin, syzomycin
•ІІІ generation: netilmycin (netromycin),
amikacin.

56. Gentamycin

57. spectrum of action of aminoglycosides
wide
•gram-negative bacteria (escherichia coli,
salmonella, klebsiella, especially K.
рneumoniae, proteus, iersinia, brucella,
campilobacteria, helicobacters, serratsia,
shigella etc.).
• some gram-positive microorganisms,
including staphylococci which are resistant
to other antibiotics

58. Indications for usage of aminoglycosides
- at the beginning stage of infectious processes of unknown
ethiology and severe complexity (combined with beta-
lactamase);
- considerable purulent-inflammatory component of heavy
infections (peritonitis, sepsis, mediastinitis, abscesses and
flegmones of soft tissues);
- acute attack of chronical purulent-inflammatory diseases,
including secondary immune defficiency;
- early stage of development of secondary bacterial meningitis;
- bacterial endocarditis;
- infections of urinary tracts;
- for prophilaxis of postoperative pustural complications
(combined with beta-lactamase antibiotics, metronidazole or
other antianaerobe drugs);
- skin infections and subcutaneous fat tissue infections, burns.

59. Concentration of aminoglycosides
in blood should not overcome:
•Amikacin, kanamycin –
35-40 mkg/ml
•Gentamicin, tobramycin –
10-12 mkg/ml

60. Complications in administration of
aminoglycosides
•Ototoxicity
•Nephrotoxicity
•Neurotoxicity
According to extent of toxicity
netilmicin < gentamicin <tobramycin <
amikacin < neomycin < streptomycin <
monomycin < kanamycin
•Leuko-, thrombocytopenia, hemmorhages,
hemolisis
•Allergic reactions

61. Chloramphenicol –
levomycetin
Indications:
meningitis, typhoid fever, paratyphoid fever,
brucellosis, tularemia
Side effects:
•Hypochrome and aplastic anemia
•Granulocytopenia, thrombocytopenia
•«Grey syndrome of a featus»
•Disbacteriosis and superinfection

62. SUPER RESISTANT
MICRO ORGANISMS (BUGS)
•MRSA- Methicilin resistant stapylococcus
aureus
•VISA- vancomycin intermediate resistant
staphylococci aureus
•ESBLS- Extended spectrum beta
lactamase
•VRE- vancomycin resistant enterococci
• penicillin resistant streptococcus
pneumonia

63. DIAGNOSIS (CON’T)
•Determine cellulitis versus abscess

64. PROPHYLAXIS (CON’T)
•Dental procedures recommended for
prophylaxis
Updated JADA 2004

65. DIAGNOSIS: Infection
•Determine etiology
> odontogenic
> trauma wound, animal bite
> TB, fungi, actinomycoses

66. TREATMENT of INFECTION
•Remove the cause of infection is the most
important of all, by either spontaneously
or surgically drain the pus.
•Antibiotics are merely an adjunctive
therapy.
Host defense
Drainage
Antibiotics

67. SELECTION of A/B
•Use Empiric therapy routinely
•Use the narrowest spectrum antibiotics
•Use the antibiotics with the lowest toxicity
and side effects
•Use bactericidal antibiotics if possible
•Be aware of the cost of antibiotics

68. •Empiric Antibiotics in OMF Infection
■ First-line
Penicillin 3MU IVA q6h -> Cefazolin 1000mg q6h
Gentamycin 60-80mg IVA q8h-q12h
■ Second line (3A)
Augmentin 1200mg q8h + Amikin 375mg q12h +
Anegyn

■ Mild infection
Amoxicillin 250mg #2 PO q8h
Clindamycin 300mg PO q6h

69. PROPHYLAXIS
•Indications

70. PROPHYLAXIS (CON’T)
•Dental procedures recommended for
prophylaxis
Updated JADA 2004

71. ANTIFUNGAL AGENT
•Most of fungal infection are from candida
•Commonly used drugs:
(1) Nystatin (Mycostatin)= PO 4-600,000 U
qid
(2) Amphotericin B= IV for severe systemic
infec.
(3) Fluconazole, Ketoconazole

72. MOUTH RINSES
•0.2% Chlorhexidine gluconate
•Against G(+), G(-), fungus
•Reduce pain and inflammation, enhance
healing
•Indication: immunocompromised patient,
C/T R/T
(prophylaxis mouthrinse reduce oral
mucositis)
•Use: 2-3 times daily,10-20cc/ time, 20-
30sec.

73. •Side Effect of Commonly Used Antibiotics

1. Penicillin hypersensitivity
2.
Cephalosporin
hypersensitivity
3. Clindamycindiarrhea, pseudomembrane
colitis
4.
Aminoglycoside
damage to kidney, 8th
neurotoxicity
5.
Metronidazole*
GI disturbance, seizures
6. Vancomycin 8th neurotoxicity,
thrombophlebitis
7.
Chloramphenico
l
bone marrow suppression
8. Erythromycinmild GI disturbance
9. Tetracyclin*tooth discoloration,
photosensitivity

74. • THANK -U