Antibiotics and antibacterial drugs


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  • * Not use in pregnancy. Vancomycin IV too rapid-> decrease blood pressure. BP monitor is needed.
  • Antibiotics and antibacterial drugs

    2. 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. 3.  Mechanism of the antibioticsMechanism of the antibiotics
    4. 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. 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. 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. 7. Nucleus of penicillin molecule L – beta-lactame ring, T – thiazoline ring N T L S C O OH CH3 CH3 O H2N
    8. 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. 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. 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. 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. 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. 13. Ampicillin
    14. 14. Amoxicillin
    15. 15. Differences between ampicillin and amoxicillinDifferences 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. 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. 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. 18. Inhibitors of beta-lactamases  Clavulanic acid Sulbactam Tazobactam
    19. 19. Unasyn (ampicillin/sulbactam)
    20. 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. 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. 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. 23. Cefazolin-sodium (C I)
    24. 24. Cezolin (Cefazolin, C I)
    25. 25. Cefalexin ( C I)
    26. 26. Zinnat (Cefuroxime, C II)
    27. 27. Cefotaxime (C III)
    28. 28. Claphoran (cefotaxime, C III)
    29. 29. Cefobid (Cefoperazone, C III)
    30. 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 + +++ + +
    31. 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. 32. CephalosporinesCephalosporines NNot recommendedot recommended to combine with other nephrotoxic drugs (aminoglycosides) ContraindicatedContraindicated to combine with loop diuretics (furosemid, etacrinic acid)
    33. 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. 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. 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. 36. Erythromycin
    37. 37. Macropen (midecamycin)
    38. 38. Sumamed (azithromycin)
    39. 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. 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. 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. 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. 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. 44. Linkomycini hydrochloridum
    45. 45. Dalacyn C (clindamycini hydrochloridum)
    46. 46. Tetracyclines 1. Natural - biosynthetic: chlortetracycline, oxytetracycline, tetracycline, dimethylchlortetracycline. 2. Semisynthetic: doxycycline (vibramycin), metacycline (rondomycin), minocycline.
    47. 47. Tetracycline
    48. 48. Doxycycline
    49. 49. Vibramycin (doxycycline)
    50. 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. 51. Pharmacokinetics of tetracyclines when combined withPharmacokinetics 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. 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. 53. Photosensitization - tetracyclines
    54. 54. Tetracyclines
    55. 55. AMINOGLYCOSIDES • І generation: streptomycin, neomycin, monomycin, kanamycin • ІІ generation: gentamycin (garamycin), tobramycin, syzomycin • ІІІ generation: netilmycin (netromycin), amikacin.
    56. 56. Gentamycin
    57. 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. 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. 59. Concentration of aminoglycosides in blood should not overcome: • Amikacin, kanamycin – 35-40 mkg/ml • Gentamicin, tobramycin – 10-12 mkg/ml
    60. 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. 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. 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. 63. DIAGNOSIS (CON’T) • Determine cellulitis versus abscess
    64. 64. PROPHYLAXIS (CON’T) • Dental procedures recommended for prophylaxis Updated JADA 2004
    65. 65. DIAGNOSIS: Infection • Determine etiology > odontogenic > trauma wound, animal bite > TB, fungi, actinomycoses
    66. 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. 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. 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. 69. PROPHYLAXIS • Indications
    70. 70. PROPHYLAXIS (CON’T) • Dental procedures recommended for prophylaxis Updated JADA 2004
    71. 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. 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. 73. • Side Effect of Commonly Used Antibiotics 1. Penicillin hypersensitivity 2. Cephalosporin hypersensitivity 3. Clindamycin diarrhea, 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. Erythromycin mild GI disturbance
    74. 74. • THANK -U