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Lec 2: General Principles
Principles of Antimicrobials by D.r Frederick C. Loyola
of Antimicrobials
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June 23 , 2010
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June 23 , 2010
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I. Introduction (Gram staining)
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II.
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Chemotherapeutic Agents
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III.
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Factors in Antimicrobial Selection
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5. Aminoglycosides
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GRAM STAINING Characteristics of Ideal Anti-Infective Agent
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1. Selective toxicity, effective anti-infective
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stimulate microbial resistance
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4. Orally active
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 bacterial and fungal cell wall-synthesizing enzymes
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(Beta lactams & Anti-fungal)
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 bacterial ribosomes (Macrolides & Aminoglycosides)
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Iv FACTORS IN ANTIBIOTIC SELECTION
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clindamycin, streptogramins, and linezolid
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 e.g., the aminoglycosides
A. ANTIMICROBIAL PHARMACODYNAMICS
 MIC - (minimum inhibitory concentration)
minimum concentration of antibiotic to
inhibit the growth of bacteria
MIC50 (50%) or MIC90 (90%)
 PAE – (post antibiotic effect)
antibacterial activity persists beyond the
time during which measurable drug is present
 PALE – (post antibiotic leukocyte enhancing effect)
B. KINETICS OF BACTERIAL KILLING
 Concentration-dependent antibiotics
The higher the concentration, the greater the
bactericidal effect (e.g., Aminoglycosides and quinolones)
Prolonged PAE, significant PALE even at subminimal
inhibitory concentration ( phagocytosis is still there evn if level
of antibiotic has decreased beyond MIC
Less frequent dosing is more effective
 Time-dependent antibiotics
no much difference in the rate of killing with varying
concentrations of the drugs.
(e.g., Beta-lactams, Metronidazole, Vancomycin,
Macrolides,clindamycin, oxazolidinones)
Bactericidal efficacy is dependent on the length of
time the bacteria are exposed to free drug serum
concentrations of at least 4x the pathogen MIC
Goal: attain serum concentration of at least 4x MIC of
infecting organism at all times for at least 40-50% of the dosing
interval
Most cost-effective manner of administration: by
continuous IV infusion or choose an antibiotic with long half
life.
C. TISSUE PENETRATION
 Property of antibiotic
e.g., lipid solubility, molecular size
quaternary ions (with charge)- can’t enter the tissues
 Tissue
e.g., adequacy of blood supply, presence of
inflammation
 Rarely a problem in acute infection due to increased
microvascular permeability from local release of chemical
inflammatory mediators.
 Antibiotic tissue penetration is rarely a problem in acute
infections due to increased microvascular permeability from
local release of chemical inflammatory substances or
mediators.
 Chronic infections and infections caused by intracellular
pathogens often rely on chemical properties of an antibiotic
(e.g., high lipid solubility, small molecular size) for adequate
tissue penetration.
D. BACTERIAL RESISTANCE
• Natural
The bacteria has a natural resistance to the given
drug. Hence, it is ineffective.
• Acquired
Resistance is acquired when the bacteria has an
adapted exposure to the drug or to its environment
• Relative
With resistance but with increasing concentration the
drug it can effectively kill the organism
• Absolute
Absolute resistance with drug no matter what the
concentration
*Natural resistance can be relative and Acquired resistance
can be relative or absolute.
E. ANTIBIOTIC DOSING
 Renal Insufficiency
 Loading and Maintenance dosing in renal
insufficiency
 Aminoglycoside dosing
 For drugs eliminated by the kidneys, the initial/loading dose
(if required) is unchanged, and the maintenance dose/dosing
interval are modified in proportion to the degree of renal
insufficiency. If creatinine clearance is 40-60 ml/min, decrease
the dose of renally eliminated antibiotic by 50% and maintain
the usual dosing interval.
 If crea clearance is 10-40 ml/min, decrease dose of renally
eliminated antibiotic by 50% and double the dosing interval.
 Or alternatively, use antibiotic eliminated/ inactivated by the
hepatic route in usual dose.
 Hepatic Insufficiency
 Decrease daily dose of hepatically eliminated antibiotic by
50% in the presence of clinically severe liver disease.
 Alternatively use antibiotic eliminated/inactivated by the
renal route in usual dose.
 Combined Renal & Hepatic Insufficiency
 There are no good dosing adjustment guidelines for
patients with hepatorenal insufficiency. If renal insufficiency is
worse than hepatic insufficiency, antibiotic eliminated by the
liver are often administered at half the daily dose. If hepatic
insufficiency is more severe than the renal insufficiency, renally
eliminated antibiotics are usually administered and dosed in
proportion to renal function.
Page 2 of 9
 Mode of Antibiotic Excretion/Excretory organ toxicity
 The mode of elimination/excretion does not necessarily
predispose to excretory organ toxicity. (e.g., nafcillin
(hepatically eliminated) is not hepatotoxic.

OTHER CONSIDERATIONS IN ANTIMICROBIAL THERAPY

 Bactericidal VS Bacteriostatic Therapy
 For most infections, bacteriostatic and bacreticidal
antibiotics inhibit/kill organisms at the same rate and should
not be a factor in antibiotic selection. However, bactericidal
antibiotics has an advantage in certain infections such as
endocarditis, meningitis, febrile neutropenia.

 Monotherapy VS Combination Therapy

 Monotherapy is preferred to combination therapy for most
infections:
Cost saving, less chances of medication error, fewer
missed doses/drug interactions
 Combination is useful for drug synergy, extending spectrum
beyond what can be obtained with a single drug and
preventing drug resisance
 Intravenous VS Oral switch therapy
 Advantage of an early oral switch are: reduced cost, early
hospital discharge, less need for home IV therapy, elimination
of IV line infection
The outer membrane or outer envelope is present in gram
negative but not gram positive organisms.
 Relatively resistant to beta lactam antibiotics.
 Impaired penetration of the antibiotics to target PBPs
because of their impermeable outer cell wall membrane.
 Beta lactam can only enter via outer membrane protein
channels (porins). Absence of the proper channel or down
regulation of its production can greatly impair drug entry into
the cell.

 Duration of therapy
 Most bacterial infections in normal hosts are treated with
antibiotics for 1-2 weeks. Maybe extended in: impaired
immunity (diabetes, SLE, Alcoholic liver disease, neutropenic,
diminished splenic function), Chronic bacterial infections
(endocarditis & osteomyelitis), chronic viral & fungal infections
and certain bacterial intracellular pathogens

ANTIMICROBIALS

A. Beta-Lactam Compounds & Other Inhibitors of Cell Wall

Synthesis
 Penicillins
 Cephalosporins & Cephamycins
 Other Beta Lactam Drugs:
 Monobactams
 Beta-Lactamase Inhibitors
 Carbapenems
 Other Inhibitors of Cell Wall Synthesis
 Vancomycin
 Teicoplanin
 Daptomycin
BETA LACTAMS:
 Fosfomycin
1. PENICILLINS
 Bacitracin
6-Aminopenicillanic Acid
 Cycloserine

Cell Wall Lysis:

Page 3 of 9
 beta-lactamase producing staphylococci, T. pallidum,
Clostridium
 Pen V: oral form, indicated only for minor infections due to
poor bioavailabilty
 Benzathine/Procaine: IM yield low but prolonged drug
levels, for treatment of beta-hemolytic strep pharyngitis

CLINICAL USES OF PENICILLIN, RESISTANT TO STAPH

BETA-LACTAMASE
 thiozolidine ring is attached to the beta lactam ring that  The sole indication is infection by beta-lactamase –
carried the secondary amino group producing staphylococci (Methicillin, Nafcillin)
 For mild, local infections: Isoxazolyl (oxacillin) – 15-25
CLASSIFICATION OF PENICILLINS mg/kg/d
 Penicillins (e.g. Penicillin G)  For serious systemic staph infection: oxacillin or nafcillin 8-
VS gram-positive organism, gram-negative cocci & 12 g/d (50-100 mg/kg/d)
non-beta lactamase anaerobes
have little activity against gram negative rods and Clinical Uses of Extended-Spectrum Penicillins
they are susceptible to hydrolysis by beta-lactamases  Aminopenicillins
 Carboxypenicillins, Ureidopenicillins- good for
 Antistaphylococcal penicillins (e.g. Nafcillin) pseudomonas
VS staphylococci and streptococci  Greater activity against gram-negative bacteria
 Amoxicillin is better absorbed from the gut
 Extended-spectrum penicillins (e.g. ampicillin &  Ampicillin is effective for shigellosis but not for
antipseudomonal penicillins) salmonellosis
VS gram-negative organisms  For Pseudomonas: Carboxypenicillins + aminoglycosides
 Beta-lactamase inhibitors ( clavulanic acid, sulbactam,
LIMITATIONS
tazobactam): VS beta-lactamase-producing strains of Staph
 Instability at acidic pH aureus & other g- bacteria
 Susceptibility to destruction by beta-lactamase Minimal antibacterial activity but good bata-lactam
(penicillinase) inhibitors
 Relative inactivity against gram-negative bacilli SUICIDE INHIBITORS:
UNITS ( clavulanic acid, sulbactam, tazobactam)
 Pen G: 1600 units/mg (1M unit = 0.6 g) Preaparations:
MECHANISM OF ACTION 1. Amoxicliin + clavulanic acid (co-amoxiclav) in oral form
 Inhibit bacterial cell wall synthesis 2. Ampicillin + Sulbactam (Unasyn)
3. Piperacillin + Tazobactam (Tazosyn)
PHARMACOKINETICS OF PENICILLIN
 Oral absorption differs greatly for different penicillins, B-Lactamase
depending on acid stability and protein-binding (impaired
by food)
 Widely distributed in the body fluids and tissues
 Excreted into sputum and milk
 Poor penetration in the eye, prostrate and CNS except
with active inflammation of meninges if given in high
doses
 Rapidly excreted by the kidneys
 Normal half-life: approx. 30 mins
 Blood levels raised by giving probenecid
RESISTANCE
 Inactivation by B lactamase
 Modification of target PBPs
 Impaired penetration of drug to target PBPs
 Presence of an efflux pump
-Does not attain therapeutic concentration inside

CLINICAL USES OF PENICILLINS

 Pen G: drug of choice for infections caused by
streptococci, meningococci, enterococci, pneumococci, non-

Page 4 of 9
2. CEPHALOSPORINS  Ceftazidime & cefoperazone: VS P. aeruginosa
 Ceftizoxime & Moxalactam: VS B fragilis
 Cefixime & Ceftriaxone: first line drug for treatment of N.
gonorrhea
 Ceftriaxone & Cefotaxime: active against Meningitis
also with severe infections due to (PRSP*)

Fourth – Generation Cephalosporins

 Cefepime, Cefpirome
 More resistant to hydrolysis by beta-lactamase
 Active VS P aeruginosa, enterobacter, S aureus, and S
 7-aminocephalosporanic acid (betalactam ring fused with 6- pneumoniae (PRSP)
membered dihydrotiazine ring)  Half-life: 2 hours
 Adverse effects:
 Soluble in water Allergy
 Stable to pH and temperature changes Toxicity – Renal, Hypoprothrombinemia, severe
 Not active against enterococci and Listeria disulfiram-like reactions
monocytogenes Superinfection

First-Generation Cephalosporin None of the Cephalosporins is active against Enterococcus,

 Cefadroxil, cefazolin, cephalexin, cephalotin, cephapirin,
cephradine
 very active against g+ cocci such as pneumococci,
streptocci and staph. They are not active against MRSA.
 Tubular secretory blocking agents (probenecid) may
increase serum levels
 Cefazolin is almost the only first –generation parenteral
cephalosporin: drug of choice for surgical prophylaxis,
alternative to an antistaphylococcal penicillin
 Rarely the drug of choice for any infection
Listeria monocytogenes and MRSA
ADVERSE EFFECTS & TOXICITIES
 Sensitizing, may cause cross reactions in some with pen
allergy
 Patients with anaphylactic reactions to pen should not
receive cephalosporins
 Cephalosporins with methylthiotetrazole group
( cefamandole, cefmetazole, cefotetan, cefoperazone)
causes hypoprothrombinemia and bleeding---give Vit K.
also causes disulfiram-like effect

As we go up to the ladder, the gram- coverage becomes broader.

But the coverage on g+ are sometimes compromised. But in 2nd
gen, generally speaking, the coverage against by 1st gen is
retained and with the addition of some other g- organisms.
Second Generation Cephalosporins
 Cefaclor, cefamandole, cefonicid, cefuroxime(axetil),
cefprozil, loracarbef, ceforanide, cephamycins (cefoxitin),
cefmetazole, cefotetan)
 Extended gram-negative coverage
 Dose: (oral) 10-15 mg/kg/d
 VS beta-lactamase producing H. influenza or Moraxella
catarrhalis
 Tx of sinusitis, otitis or lower RTI
 Cefoxitin, Cefotetan, Cefmetazole- peritonitis or
diverticulitis
 Cefuroxime: for community-acquired pneumonia
-The only second-generation drug that crosses blood-
brain barrier.
Third–Generation Cephalosporins
 Cefoperazone, cefotaxime, ceftazidime, ceftriaxone,
cefixime, cefpodoxime proxetil, cefdinir, cefditoren pivoxil,
ceftibuten, ceftizoxime, moxalactam
 Expanded gram-negative coverage
 Some can cross blood brain barrier
 Active VS citrobacter, serratia & providencia(*)
OTHER BETA-LACTAMS
 Monobactams (monocyclic B-lactam ring)
Aztreonam : VS gram-negative rods
 Beta-lactamase Inhibitors (suicidal inhibitors)
Clavulanic acid, sulbactam, tazobactam
Treatment of mixed aerobic and anaerobic infections
(intraabdominal infections)
 Carbapenems
beta-lactam ring is attached to a five-membered ring,
substitution of carbon for sulfur and unsaturation in the five
membered ring
Imipenem, meropenem, doripenem,ertapenem
Choice for treatment of infection caused by
enterobacter
3. VANCOMYCIN
 For staphylococcal infection (MRSA)
 Bactericidal
 Primarily active against gram positive bacteria
 MOA: Inhibits cell wall synthesis by binding firmly to the D-
ala-D-Ala terminus of nascent peptidoglycan
 Poorly absorbed in GIT
 Tx of enterocolitis due to Clostridium difficile
 Indication: sepsis, endocarditis due to methicillin-resistant
staphylococci, with gentamicin, as alternative regimen for

Page 5 of 9
treatment of enteroccocal endocarditis in patient with serious
penicillin allergy
 Drug of choice for treatment of serious staphylococcal
infections resistant to usual antistaphylococcal antibiotics
 Adverse Reaction: “Red man” or “red neck” syndrome
3. OTHER INHIBITORS OF CELL WALL SYNTHESIS
 Teicoplanin – glycopeptide
Long half-life: 45 – 70 hours
 Daptomycin (mechanism unknown)
o Cyclic lipopeptide, same spectrum with vanco
o More rapidly bactericidal in vitro
o Dose: 4 mg/kg for skin infection, 6 mg/kg for
bacteremia and endocarditis
 Fosfomycin – stable salt of phosphonomycin
o inhibits enolpyruvate transferase
o tx of uncomplicated LUTI
o Oral bioavailability: 40%
o Half – life: 4 hours
o Dose: single 3g for AUC
o Safe for use in pregnancy
 Bacitracin - cyclic peptide
o interfere with dephosphorylation in cycling of the lipid
carrier
o no cross-resistance
o Useful for suppression of mixed bacterial flora in
surface lesions
 Cycloserine
o Water-soluble, unstable at acid pH
o Almost exclusively to treat tuberculosis resistant to
first-line agents
o Inhibits alanine racemase (L-alanine to D-alanine) &
ligase enzyme
B. PROTEIN SYNTHESIS INHIBITORS
Tetracyclines, Macrolides, Clindamycins, Chloramphenicol,
Aminoglycosides & Streptogramins
STEPS IN BACTERIAL PROTEIN SYNTHESIS
TARGETS OF SEVERAL ANTIBIOTICS
1. The charged tRNA unit carrying amino acid 8 binds to the
acceptor siteA on the 70s ribosome. The peptidyl tRNA at the
donor site, with amino acid 1 through 7,
2. Then binds the growing amino acid chain to amino acid 8
(transpeptidation,).
3. The uncharged tRNA left at the donor site is released
4. The new 8-amino acid chain with its tRNA shifts to the
peptidyl site (translocation). The antibiotic binding sites are
shown schematically as triangles.
 Chloramphenicol (C) and Macrolides (M) bind to the 50s
subunit and block transpeptidation by inhibiting peptidyl
transferase(step 2) and translocation reaction and formation of
initiation complex.
 The tetracyclines (T) bind to the 30s subunit and prevent
binding of the incoming charged tRNA unit at the acceptor site
on the mRNA-ribosome complex(Step 1).
 Aminoglycosides bind to specific 30s subunit ribosomal
proteins.
 Protein synthesis is inhibited by aminoglycosides in at least
3 ways:
1. Interference w/ initiation complex of peptide
formation,
2. Misreading of mRNA which causes incorporation of
incorrect amino acid into the peptide,
3. Breaking of polysomes into nonfunctional
monosomes.
1. TETRACYCLINES
 Binds to 30s ribosomal subunit blocking attachment of
aminoacyl tRNA to acceptor site
 Static
 Resistance: decrease intracellular accumulation
(impaired influx or increased efflux), ribosomal
protection to cause interference with binding, enzymatic
inactivation
 Broad-spectrum Bacteriostatic
 Chelate divalent metal ions/damage growing bones & teeth
 40-80% protein bound
 Cross the placenta and excreted in milk
 Choice for patient with renal insufficiency: Doxycycline –
once daily/ Tigecycline as well not renally excreted
 Minocycline-maybe used for meningococcal carrier state
 Drug of choice for: Mycoplasma pneumoniae, chlamydiae,
rickettsiae, spirochetes, helicobacter pylori(+)
 Avoid in pregnant women and children below 8 years old,
to avoid deposition in growing bones and teeth
 Tigecycline
o First glycylcycline to reach the clinic,
o Newest among the group
o Effective even with tetracycline resistant strains
o Broad spectrum: even with MRSA, VISA,VRE, g-
enterics, anaerobes(B+/-), atypical agents
o Proteus and P aeroginosa- intrinsically resistant
o No dosage adjustment required for renally impaired
patients, elimination is primarily biliary
AND
ADVERSE REACTIONS
o GI effects
Page 6 of 9
 o Bony structures and teeth- Chelates, binds enamel
dysplasia, bone deformity
o Liver toxicity- with concomitant liver problem or with
pregnancy / can impair hepatic functions
o Kidney toxicity- nitrogen retention, diuretics also
causes nitrogen retention, may give
doxycycline or tigecycline
o Local Tissue toxicity- Venous thrombosis to iv site
o Photosensitization
o Vestibular reactions- Dizziness, vertigo, nausea with
high doses
2. MACROLIDES AND CLINDAMYCIN
 Bind to 50s subunit inhibiting translocation of peptidyl-
tRNA from acceptor to donor site
 Static / cidal in high doses
 Resistance: reduced permeability or efflux pump; form
methyltransferases that alters 50s drug binding (gram + cocci)
(MLS-type B resistance) & drug-inactivating enzymes (gram –
rods)-esterases
 The macrolides are a group of closely related compounds
characterized by a macrocyclic lactone ring (usually containing
14 or 16 atoms) to which deoxy sugars are attached. The
prototype drug is erythromycin and the semi synthetic
compounds are clarithromycin and azithromycin.
Clindamycin is a chlorine-substituted derivative of lincomycin
2.A. MACROLIDES: Erythromycin
 Poorly soluble in water
 Unstable at acid pH
 VS gram –positive organisms
 Destroyed by stomach acid (needs enteric coating)
 Drug of choice: corynebacterial infection, respiratory,
neonatal, ocular or genital chlamydial infection, community-
acquired pneumonia, alternative for penicillin-allergic
individuals
 Prophylaxis against endocarditis during dental procedures
with valvular heart disease
2.B. MACROLIDES: Clarithromycin
 More active against mycobacterium avium complex
 250-500 mg BID
 Longer half-life: 6 hours
 Lower frequency of GI intolerance
 Less frequent dosing
2.C. MACROLIDES: Azithromycin
 15-atom lactone ring
 Highly active against chlamydia
 High tissue & phagocytic cells level – renal elimination
 Half-life is > 4 days
 Once-daily dosing and short duration of treatment
 Given 1 hour before or after meals
 Does not inactivate cytochrome P450 enzymes
2.D. MACROLIDES: Ketolides – (Telithromycin)
 Semisynthetic 14-membered-ring
 Oral bioavailability: 57%
 Dose: 800 mg OD
 Treatment of respiratory tract infections
 Reversible inhibitor of the CYP3A4
 May slightly prolong the QTc interval
Many macrolide resistant strains are susceptible to ketolides
because the structural modification of these compounds renders
them poor substrates for efflux pump mediated resistance.and
they bind with ribosomes of other bacteria with higher affinity
than other macrolides
3. CLINDAMYCIN
 Chlorine –substituted lincomycin
 VS strep, staph, pneumococci
 For severe anaerobic infection due to bacteroides & other
anaerobes
 Can be used for penetrating wounds of the abdomen (+
amino or cephalosporin)
 For prophylaxis of endocarditis with valvular heart disease
undergoing dental procedures rather than erythromycin
 10-20 mg/kg/d (0.15-0.3g every 6 hrs)
 Causes drug induced colitis (C. difficile)
4. CHLORAMPENICOL
 Bind to 50s ribosomal subunit, inhibits peptidyltransferase
 Static
 Resistance: formation of acetlytransferases (transacetylase)
 Soluble in alcohol, neutral, stable
 Bacteriostatic, broad-spectrum
 Dose: 50-100 mg/kg/d
 Completely and rapidly absorbed orally
 Eye infections
MECHANISM OF ACTION:
Page 7 of 9
 Reversible binds to 50S ribosomes subunits of 5.E. Netilmicin
susceptible organisms and inhibits the peptidyl tranferase step  5-7 mg/kg/d
(transpeptidation) preventing aminoacids from being  Maybe active against genta and tobra resistant bacteria
transferred to growing peptide chains thus inhibiting protein
synthesis 5.F. Kanamycin & Neomycin
 Bowel preparation for elective surgery
ADVERSE REACTIONS  For topical and oral use only (too toxic for parenteral use)
 GI disturbances
 Bone marrow disturbances 5.G. Spectinomycin
Aplastic anemia  Aminocyclitol
 Toxicity with newborn infants  Alternative treatment for gonorrhea for penicillin-allergic
Gray baby syndrome: lack of effective glucoronic patients
acid conjugation  2 g IM (40 mg/kg)
 Interaction with other drugs
- Inhibits hepatic microsomal enzymes AMINOGLYCOSIDES
BIODISPOSITION AND TOXICITY
5. AMINOGLYCOSIDES  Polar compound, not absorbed orally or widely distributed
 Bind to 30s ribosomal subunit-  Renal clearance proportional to GFR--- decrease dose in
dec. initiation codon function- renal dysfunction
formation of initiation complex (static)  Short half-lives (2-3 hours) – conventionally given at 6-12
 Misreading of code- formation of inactive proteins (cidal) hours intervals, but once-daily dosing regimens now more
 Resistance: formation of drug-inactivating transferases common
 Adverse effects- nephrotoxicity: includes proteinuria,
 Bactericidal, accumulated intracellularly via O2 dependent hypokalemia, acidosis and ATN. Ototoxicity:from hair cell
uptake (anaerobes innately resistant) damage includes deafness and vestibular dysfunction, NM
 Water-soluble, stable, more active at alkali blockade, contact dermatitis (neomycin)
 Irreversible inhibitors of protein synthesis – binds to specific
30S subunit ribosomal proteins ONCE DAILY DOSING OF AMINOGLYCOSIDES
 Absorbed poorly in GI tract  Once-daily administration is clinically effective and causes
 Ototoxic and nephrotoxic less toxicity than conventional dosing regimens
 In high doses: curare-like effect with neuromuscular  Antibacterial effects depend mainly on peak blood level
blockade (rather than time) and continue with blood levels < MIC. A post
 VS gram-negative (often in combination), enteric bacteria, antibiotic effect (PAE)
synergistic with penicillins in enterococcus and P.  Toxicity depends both on blood level & the time such levels
aeroginosa are > than a specific threshold (ie, total dose)

5.A. Streptomycin
 Second line agent for tuberculosis tx NEWER AGENTS
 With penicillin: for enterococcal endocarditis
 With tetracycline: tularemia, plague, brucellosis 1. Streptogramins
 Most serious toxic effect: vestibular disturbance – vertigo  Quinupristin-dalfopristin
and loss of balance  Bactericidal (rapid) except with E faecium (slow)
 Active against g+cocci, MDR-strep, PRSP,MRSA
5.B. Gentamicin  Resistance : MLS-B type/inactivation of A and efflux
 Gram-positive and gram-negative  IV 7.5 mg/kg every 8-12 hrs
 For severe infections (sepsis and pneumonia)  Adverse effect: pain at infusion site, athralgia-myalgia
 5-6 mg/kg/d syndrome

5.C. Tobramycin 2. Oxazoladinones

 More active against pseudomonas++  Linezolid: bacteriostatic except for strep
 Also available in inhalational form (TOBI)  Inhibits protein synthesis by binding on 23 S
 (P. aeroginosa complicating cystic fibrosis) ribosomal RNA of the 50S subunit (unique-no cross resistance)
 High oral bioavailability:100%
5.D. Amikacin  Half-life: 4-6 hours
 For resistant organisms  For vancomycin-resistant E. faecium
 500 mg BID IV  Toxicity: thrombocytopenia and neutropenia

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MECHANISMS OF ACTIONS

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