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Aminoglycoside, Chloramphenicol, Tetracycline.pptx

  1. AMINOGLYCOSIDE CHLORAMPHENICO L TETRACYCLINE Dr. Maynard O. Galingana 1st Year Pediatric Resident
  2. LEARNING OBJECTIVE To discuss the clinical relevance of: • Aminoglycosides • Chloramphenicol • Tetracyclines 20XX PRESENTATION TITLE 2
  4. AMINOGLYCOSIDES 20XX PRESENTATION TITLE 4 • Members include Streptomycin, Neomycin, Kanamycin, Amikacin, Gentamicin, Tobramycin, Sisomicin, Netilmicin • Terminate bacterial protein synthesis by attaching to and inhibiting the function of 30S subunit of bacterial ribosome • Bactericidal
  5. MECHANISMS OF RESISTANCE 1. Deficiency of ribosomal receptor 2. Enzymatic destruction of the drug 3. Lack of permeability to the drug molecule/ Lack of active transport into the cell 20XX PRESENTATION TITLE 5
  6. PHARMACOKINETICS • absorbed very poorly from the intact gastrointestinal tract • Cleared by the kidney, excretion is directly proportional to creatinine clearance 20XX PRESENTATION TITLE 6
  7. PHARMACOKINETICS Concentration-dependent Killing • Higher concentrations kill a larger proportion of bacteria and at a more rapid rate Post-antibiotic effect • Antibacterial activity persists beyond the time during which measurable drug is present 20XX PRESENTATION TITLE 7
  8. CLINICAL SIGNIFICANCE • Most widely used against aerobic Gram- negative bacteria or sepsis is suspected. • In the treatment of bacteremia or endocarditis, a penicillin or vancomycin facilitates entry of the aminoglycoside • Some are used as antimycobacterial drugs 20XX PRESENTATION TITLE 8
  9. ADVERSE EFFECTS • Ototoxicity (auditory damage, vestibular damage) • Nephrotoxicity • Curare-like effect in very high doses 20XX PRESENTATION TITLE 9
  10. STREPTOMYCIN 20XX PRESENTATION TITLE 10 • First aminoglycoside • Oral administration: poorly absorbed from the gut • IM injection: Rapidly absorbed and widely distributed in tissues except the CNS • Clinical uses: • Effective for streptococcal and enterococcal endocarditis (in combination with a penicillin) • Second-line agent for treatment of tuberculosis • Adverse effects: fever, rash, vestibulotoxicity, nephrotoxicity
  11. STREPTOMYCIN 1g powder for injection Infant, Child, and Adolescent (<15 yr or <40kg) Child, adolescent, and adult (>15 yr or >40kg) Daily Therapy 20-40 mg/kg/24hr IV/IM OD 15 mg/kg/24hr IV/IM OD Twice weekly Therapy 20 mg/kg/24hr IV/IM twice weekly 15 mg/kg/24hr IV/IM twice weekly 20XX PRESENTATION TITLE 11
  12. GENTAMICIN 20XX PRESENTATION TITLE 12 • Bactericidal for many Gram-positive and Gram-negative bacteria, including many strains of Proteus, Serratia and Pseudomonas. • Acts in synergy with Penicillins • Can be used topically for infected burns, wounds or skin lesions and ocular infections
  13. GENTAMICIN Post conceptional age (weeks) Post natal Age (Days) Dose (Mg/kg/dose) Interval (hr) <29 0-7 5 48 8-28 4 36 >28 4 24 30-34 0-7 4.5 36 >7 4 24 >35 ALL 4 24 20XX PRESENTATION TITLE 13
  14. GENTAMICIN 20XX PRESENTATION TITLE 14 Injection: 10 mg/ml, 40 mg/ml Pre-mixed injection: 40mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 120 mg Ophthalmic ointment: 0.3% Ophthalmic drop: 0.3% Topical cream: 0.1% Topical ointment: 0.1% Dose Child 7.5mg/kg/24hr Q8 Adult 3-6 mg/kg/24hr Q8 Cystic Fibrosis 7.5-10.5 mg/kg/24hr Q8 Ophthalmic ointment Q8-12 Ophthalmic drops 1-2 drops Q2-4 Topical cream or ointment Apply TID-QID
  15. NEOMYCIN AND KANAMYCIN 20XX PRESENTATION TITLE 15 • Clinical uses: • Reduction of intestinal flora before large bowel surgery • Topical application on infected skin and wounds • Injection into joints, pleural cavity, tissue spaces or abscess cavities • Poorly absorbed from the intestinal tract • Known ototoxic and neurotoxic
  16. NEOMYCIN T: 500mg Oral Sol.: 125mg/5ml Hepatic encephalopathy Bowel preparation Child 50-100 mg/kg/24hr Q6-8 for 5-6 days 90mg/kg/24hr Q4 for 2-3 days Adult 4-12 g/24hr Q4-6 for 5-6 days 1g Q1 for 4 doses then 1g Q4 for 5 doses 20XX PRESENTATION TITLE 16
  17. AMIKACIN 20XX PRESENTATION TITLE 17 • Semisynthetic derivative of kanamycin • Clinical uses: • CNS infections (intrathecal, intraventricular injections) • Multidrug-resistant MTB • Nephrotoxic and ototoxic
  18. AMIKACIN Post conceptional age (weeks) Post natal Age (Days) Dose (Mg/kg/dose) Interval (hr) <29 0-7 18 48 8-28 15 36 >28 15 24 30-34 0-7 18 36 >7 15 24 >35 ALL 15 24 20XX PRESENTATION TITLE 18
  19. AMIKACIN 20XX PRESENTATION TITLE 19 Injection: 250mg/ml Dose Infant and child 15-22.5 mg/kg/24hr Q8 IV/IM Adult 15 mg/kg/24hr Q8-12 IV/IM Cystic Fibrosis 30 mg/kg/24hr Q8 IV Initial max dose 1.5g/24hr
  20. TOBRAMYCIN 20XX PRESENTATION TITLE 20 • Properties are almost identical with those of Gentamicin • With slightly enhanced activity against Pseudomonas aeruginosa • Ototoxic, less nephrotoxic than Gentamicin
  21. TOBRAMYCIN 20XX PRESENTATION TITLE 21 Post conceptional age (weeks) Post natal Age (Days) Dose (Mg/kg/dose) Interval (hr) <29 0-7 5 48 8-28 4 36 >28 4 24 30-34 0-7 4.5 36 >7 4 24 >35 ALL 4 24
  22. TOBRAMYCIN 20XX PRESENTATION TITLE 22 Injection: 10 mg/ml, 40 mg/ml Pre-mixed injection: 80mg Powder injection: 1.2g Ophthalmic ointment: 0.3% Ophthalmic drop: 0.3% Nebulizer: 300mg/5ml Powder for inhalation: 28mg capsule Dose Child 7.5mg/kg/24hr Q8 Adult 3-6 mg/kg/24hr Q8 Cystic Fibrosis 7.5-10.5 mg/kg/24hr Q8 Ophthalmic ointment 0.5 inch ribbon BID TID Ophthalmic drops 1-2 drops Q4 Inhalation 300mg Q12 x 28 days
  23. NETILMICIN 20XX PRESENTATION TITLE 23 • Used in immunocompromised and severely ill patients at very high risk for gram-negative bacterial sepsis
  24. SPECTINOMYCIN 20XX PRESENTATION TITLE 24 • Aminocyclitol antibiotic • Rapidly absorbed after intramuscular administration • Used as single-dose treatment of gonorrhea caused by β-lactamase- producing gonococci or in individuals with hypersensitivity to penicillin • Given as 40 mg/kg IM
  26. PHARMACOKINETICS • A: rapidly absorbed from the gastrointestinal tract • D: widely distributed in tissues and body fluids, including the CNS and CSF; with good cell membrane penetration • M: inactivated in the liver • E: mainly in the urine, small amount is excreted into bile and feces 20XX PRESENTATION TITLE 26
  27. MECHANISM OF ACTION • Potent inhibitor of microbial protein synthesis • Interferes with the action of peptidyl transferase, blocking the attachment of amino acids to the nascent peptide chain on the 50S subunit of ribosomes • Bacteriostatic • May be bactericidal to H influenzae, Neisseria meningitidis and some species of bacteroides 20XX PRESENTATION TITLE 27
  28. MECHANISM OF RESISTANCE • Enzymatic destruction by chloramphenicol acetyltransferase, a plasmid-encoded enzyme 20XX PRESENTATION TITLE 28
  29. CLINICAL SIGNIFICANCE • Active against both aerobic and anaerobic gram-positive and gram-negative organisms • Can be an alternative to β-lactam antibiotic for the treatment of bacterial meningitis • Can be used as topical treatment for eye infections • Rarely used because of potential toxicity, bacterial resistance and availability of many effective alternatives 20XX PRESENTATION TITLE 29
  30. ADVERSE EFFECTS • Gastrointestinal upset • Oral or vaginal candidiasis • Hematologic effects: disturbance in red blood cell maturation, elevation of serum iron and anemia • Aplastic anemia (idiosyncratic) • Gray-baby syndrome in premature and newborn infants • Vomiting, flaccidity, hypothermia, gray color, shock and vascular collapse 20XX PRESENTATION TITLE 30
  31. CHLORAMPHENICOL 20XX PRESENTATION TITLE 31 Dose Neonate IV Loading dose: 20 mg/kg Maintenance Dose <7 days 25mg/kg/24hr Q24 >7 days <2kg: 25 mg/kg/24hr Q24 >2kg: 50mg/kg/24hr Q12
  32. CHLORAMPHENICOL 20XX PRESENTATION TITLE 32 Injection: 1g Dose Infant/Child/Adult 50-75 mg/kg/24h IV Q6 Meningitis 75-100 mg/kg/24h IV Q6 Max dose 4g/day
  34. TETRACYCLINES 20XX PRESENTATION TITLE 34 • Chlortetracycline • Oxytetracycline • Tetracycline • Demeclocycline • Methacycline • Doxycycline • Minocycline
  35. PHARMACOKINETICS 20XX PRESENTATION TITLE 35 • A: readily absorbed from the intestinal tract • Can be impaired by food, multivalent cations, dairy products, antacids, alkaline pH • D: widely distributed to tissues and body fluids; poor penetration into CSF • Minocycline can reach high concentrations in tears and saliva, hence can be used in meningococcal carrier states • Can cross the placenta • E: bile, urine, stool, breastmilk
  36. MECHANISM OF ACTION 20XX PRESENTATION TITLE 36 • Inhibit protein synthesis by preventing the binding of amino-acyl- tRNA to the 30S unit of bacterial ribosomes • Bacteriostatic; inhibit the growth of susceptible gram-positive and gram-negative bacteria
  37. MECHANISM OF RESISTANCE 20XX PRESENTATION TITLE 37 1. Impaired influx or increased efflux by active transport protein pump 2. Production of proteins that interfere with tetracycline binding to the ribosome 3. Enzymatic inactivation
  38. CLINICAL SIGNIFICANCE 20XX PRESENTATION TITLE 38 • Excellent in the treatment of chlamydiae, Mycoplasma pneumoniae and some spirochetes • Drugs of choice in infections caused by rickettsiae • Used in combination regimens for gastric and duodenal ulcer disease caused by H pylori • Can shorten the excretion of vibrios in cholera • Effective in most chlamydial infections, including sexually transmitted infections • Doxycycline + Ceftriaxone – alternative treatment for gonococcal disease • Sometimes used in the treatment and prophylaxis of protozoal infections • Can be used with Streptomycin to treat Brucella, Yersinia and Francisella infections
  39. CLINICAL SIGNIFICANCE 20XX PRESENTATION TITLE 39 • Low doses of Tetracycline can suppress both skin bacteria and their lipases, hence, useful in acne. • Minocycline • Can eradicate the meningococcal carrier state • active against Nocardia infections
  40. ADVERSE EFFECTS 20XX PRESENTATION TITLE 40 • Gastrointestinal upset • Nausea • Vomiting • Diarrhea • Alteration of normal microbiota
  41. ADVERSE EFFECTS 20XX PRESENTATION TITLE 41 Bony structures and teeth • Fluorescence, discoloration and enamel dysplasia • Bone deformity or growth inhibition Vennila V, Madhu V, Rajesh R, et al. Tetracycline-induced discoloration of deciduous teeth: case series. Journal of International Oral Health : JIOH. 2014 Jun;6(3):115-119. PMID: 25083046; PMCID: PMC4109251.
  42. ADVERSE EFFECTS 20XX PRESENTATION TITLE 42 • Skin rashes, mucous membrane lesions, fever • Hepatic damage or necrosis • Renal tubular acidosis, Fanconi syndrome, nephrotoxicity • Venous thrombosis (IV injection) • Local irritation (IM injection) • Marked vestibular disturbance (Minocycline)
  43. DOXYCYCLINE 2023 NORMAL FLORA 43 C: 50, 75, 100, 150 mg T: 20, 25, 75, 100, 150 mg S: 50mg/5ml Injection: 50 mg Children > 8 yr 2.2mg/kg/24hr PO OD Adult 100 mg PO once daily
  44. REFERENCES 20XX PRESENTATION TITLE 44 • Brooks, G. F., et al. (2013). Jawetz, Melnick, & Adelberg’s Medical Microbiology 26th Edition. United States of America: The McGraw-Hill Companies, Inc. • Hughes, H.K., KAHL, L.K. 2018. The Harriet Lane Handbook 21st Edition. The Johns Hopkins Hospital. Elsevier Mosby Publishing • Katzung, B. G., Trevor. A. J. (2015). Basic and Clinical Pharmacology 13th Edition. United States of America: McGraw-Hill Education • Vennila V, Madhu V, Rajesh R, et al. Tetracycline-induced discoloration of deciduous teeth: case series. Journal of International Oral Health : JIOH. 2014 Jun;6(3):115-119. PMID: 25083046; PMCID: PMC4109251.
  46. REVIEW QUESTION # 1 20XX PRESENTATION TITLE 46 What are the adverse effects prominently associated with Aminoglycosides? (A)Neurotoxicity and Hepatoxicity (B)Aplastic anemia and jaundice (C)Nephrotoxicity and Ototoxicity (D)Stevens-Johnson Syndrome and fever
  47. REVIEW QUESTION # 2 20XX PRESENTATION TITLE 47 R.M., 9-month old male, came in for his vaccination. You also noticed yellowish discoloration of teeth. Upon review of his birth and maternal history, his mother was given with unrecalled antibiotic for an unrecalled infection during the 2nd trimester of pregnancy. Among the choices, which antibiotic may account for the yellowish discoloration? (A)Cefuroxime (B)Chloramphenicol (C)Amikacin (D)Doxycycline
  48. REVIEW QUESTION # 3 20XX PRESENTATION TITLE 48 What is the idiosyncratic adverse effect prominently associated with Chloramphenicol? (A)Aplastic anemia (B)Red man syndrome (C)Osteonecrosis (D)Pseudomembranous enterocolitis
  49. REVIEW QUESTION # 4 20XX PRESENTATION TITLE 49 Which aminoglycoside is commonly used as a second-line agent for treatment of tuberculosis? (A)Gentamicin (B)Kanamicin (C)Streptomycin (D) Neomycin
  50. REVIEW QUESTION # 5 20XX PRESENTATION TITLE 50 You were in charge of Patient R.S., 2 day-old male, born term at 38-39 weeks AOG to a 24 year-old G1P1 (1001) via Vaginal Spontaneous Delivery. Prenatal history was unremarkable and there were no labor complications noted. However, on the 29th hour of life, fair suck and activity with jaundice at head progressing to chest were noted. R.S. was then started on aminoglycoside in combination with a β-lactam antibiotic. What is the rationale why the aminoglycoside is given concurrently with a β-lactam cell wall antibiotic? (A) β-lactam prevents enzymatic degradation of the aminoglycoside (B) Aminoglycoside acts in synergism with β-lactam. β-lactam facilitates entry of aminoglycoside into the cell (C)β-lactam prolongs the half-life of aminoglycoside (D)β-lactam converts the aminoglycoside into a more active, biologic form

Notas del editor

  1. Good afternoon, Dr. De Castro, Dr. Cantimbuhan, fellow residents, interns and clerks. For our Infectious Diseases Hour for today, we will be learning about Aminoglycoside, Chloramphenicol and Tetracycline.
  2. Anaerobic bacteria are often resistant to aminoglycosides because transport through the cell membrane is an energy requiring process that is oxygen dependent
  3. Adverse effects are more likely to be encountered when therapy is continued for more than 5 days, at higher doses, in the elderly and in the setting of renal insufficiency. Auditory damage – tinnitus, initially high-frequency hearing loss Vestibular damage – vertigo, ataxia, loss of balance Marked dosage adjustments must be made in renal failure Curare-like effect in very high doses – with neuromuscular blockade that results in respiratory paralysis
  4. Prototype of this class of drugs Discovered in the 1940s as a product of Streptomyces griseus Streptomycin should not be used alone to treat any infection
  5. Penicillins facilitate entry of aminoglycoside into streptococci and gram-negative rods, which is beneficial in sepsis and endocarditis
  6. Oral or vaginal candidiasis – due to alteration of normal microbial flora Hema effects are reversible upon discontinuance of the drug Gray baby syndrome: glucuronide conjugation in the liver for degradation and detoxification is not yet well developed
  7. Tigecycline – poorly absorbed orally and must be administered intravenously
  8. Due to direct local irritation of the intestinal tract Can be controlled by administering the drug with food or carboxymethylcellulose, reducing drug dosage or discontinuing the drug
  9. Tetracyclines adversely affect the bony structures and teeth. - Tetracyclines are readily bound to calcium deposited in newly formed bone or teeth in young children
  10. (C)
  11. (D)
  12. A
  13. (C)
  14. (B)