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
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
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
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
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.
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
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.
Anaerobic bacteria are often resistant to aminoglycosides because transport through the cell membrane is an energy requiring process that is oxygen dependent
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
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
Penicillins facilitate entry of aminoglycoside into streptococci and gram-negative rods, which is beneficial in sepsis and endocarditis
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
Tigecycline – poorly absorbed orally and must be administered intravenously
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
Tetracyclines adversely affect the bony structures and teeth.
- Tetracyclines are readily bound to calcium deposited in newly formed bone or teeth in young children
