Antimicrobial Chemotheray

Monday, September 21, 2015 1:25 PM

Mechanism Clinical Use Mechanism of Resistance

All Classification based on:
antibiotics
the class and spectrum of
microorganisms it kills
the biochemical pathway it
interferes with and
the chemical structure of its
pharmacophore
active chemical moiety
of the drug that binds to
the microbial receptor
Prophylactic or preventive
therapy
Empirical therapy
Definitive therapy
Once the infecting
microorganism is identified.
A narrow-spectrum,
low-toxicity regimen
Major factor: Interactions:
Evulution Synergism
Clinical/environmental practices Additive
Poor clinical practice Superaddative
fail to incorporate the pharmacological properties of antimicrobials amplify the speed of development of drug
resistance.
Mechanisms:
1. reduced entry of antibiotic into pathogen
Porin mutation / loss/ absence
Entry of small polar molecules (e.g antibiotics)
2. enhanced export of antibiotic by efflux pumps
Overexpress efflux pumps
Expel antibiotics
Systems of pumps
the multidrug and toxic compound extruder (MATE)
the major facilitator superfamily (MFS) transporters
the small multidrug resistance (SMR) system
the resistance nodulation division (RND) exporters
ATP binding cassette (ABC) transporters
3. release of microbial enzymes that destroy the antibiotic
Resistance to aminoglycoside and lactan antibiotics due to:
aminoglycoside-modifying enzyme
lactamase,
4. alteration of microbial proteins that transform pro-drugs to the effective moieties
Antibiotics help in growth
e.g. Enterococcus with vancomycin
5. alteration of target proteins
single point or multiple point mutations is a change in amino acid composition and conformation of target
protein (Enzyme)
Mutation leads to reduced affinity for enzyme
Alteration to own cells (natural target)
Alteration to microbial enzyme
6. development of alternative pathways to those inhibited by the antibiotic
NRTI usually create chain termination by incorporating into viral DNA
Mutation of RT can lead to capacity to remove analogs by dephosphorylating and continue chain.

Classification Notes Mechanism Clinical Use Toxicity Mechanism of Resistance Pharmacokinetics

All Inhibitor Have beta-lactam ring inactivating family of Bacteriacide Hypersensitivity reactions Hydrolysis of the beta-lactam ring results in Administration:
Cell Wall E.g. enzymes located in the loss of antibacterial activity Oral
Cation toxicity: penicillins are
synthesis bacterial cell membrane, administered as Na+ or K + salts Formation of beta-lactamases (penicillinases) IV preferred
Penicillins
B-lactams which are involved in the Depot forms:
Cephalosporins third stage of cell wall Most staphylococci procraine penicillin G and benzathine
synthesis. Many Gram-negative organisms penicillin G
Cephamycins
Inhibit Cross- Absorption
Carbapenems Structural change in target PBPs
Linking Incomplete oral
Monobactams Changes in the porin structure in the outer cell (except Amoxicillin)
Bind Penicillin-binding wall membrane Impaired by food
Beta-lactamase proteins (transpeptidases)
Methicillin resistance in staphylococci Not extensively metabolized
inhibitors Block transpeptidase cross-
(MRSA) Distribution
linking of peptidoglycan in
cell wall. Penicillin G resistance in pneumococci High Vd
Activate autolytic enzymes Cross placenta
Time-dependent NOT teratogenic
killing Poor CNS penetration
Poor penetration into bone, eye, and
prostate
Excretion
Tubular secretion!
Probenecid block secretion
More penicillin available
Ampicillin and nafcillin cleared partly by
biliary excretion

Penicillin Inhibitor Derivative of 6- With B-lactamase inhibitors Narrow spectrum Hemolytic anemia Resistant strains Vary in:
Cell Wall aminopenicillanic acid Penicillin G
pneumococci (penicillin-resistant Resistance to gastric acid
synthesis Amoxicillin-clavulanic acid Gram + Streptococcus pneumonia [PRSP] strains
B-lactams Prototype B-lactam (Augmentin): po Drug of choice for syphilis Oral bioavailability
antibiotic NO gonorrhea Staphylococcus aureus
Ampicillin-sulbactam: iv Penicillin V
Penicillase (B-lactamase) Neisseria gonorrhoeae
snesitive Ticarcillin-clavulanic acid Is the phenoxymethyl analog of penicillin G
(Timentin): iv Oral form of penicillin for oropharyngeal
infections
Piperacillin-tazobactam: iv The potassium salt of Penicillin V has
advantage in resistance to inactivation by
gastric acid.
It may be given with meals; but blood levels
are slightly higher given on empty stomach.
Average blood levels are two to five times
higher than the levels following the same
dose of oral penicillin G and also show much
less individual variation.
Dicloxacillin, Inhibitor Penicillinase-resistant Very narrow spectrum Methicillin , prototype, rarely use due to MRSA
nafcillin, Cell Wall Bulky R-group blocks S.aureus (exc.MRSA) nephrotoxicity potential Altered PBP target site
oxacillin synthesis access of B-lactamase Interstitial nephritis
Methicillin B-lactam to B-lactam ring

Ampicillin Inhibitor Penicillinase-sensitive Ampicillin is synergistic Wide-spectrum non-urticarial rash (most-common) Amoxillin, better oral absorption
Amoxicillin Cell Wall with amynoglycosides in Bacilli
Pseudomembranous colitis
(Aminopenicillins) synthesis Enterococcal and listeria
Clinical uses similar to penicillin G, but in
B-lactam infections Diarrhea and nausea
addition in infections resulting from
Amino (positive-charged) The intestinal flora is affected with
Helicobacter pilori oral penicillins
group enhances diffusion
through porin channels Haemophilus influenzae Overgrowth of yeast and gram
E.coli positive bacteria.
Listeria monocytogenes Ampicillin- implicated in
pseudomembranous colitis.
Proteus
Salmonella
Shiguella
Moraxella catarrhalis
Therapeutic Indications:
Sinusitis
Otitis
Lower respiratory infections
Urinary tract infections (UTIs)
Meningitis (N. meningitidis)

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 Meningitis (N. meningitidis)
Ureidopenicillin Antipseudom Penicillinase-sensitive Extended Spectrum Ticarcillin Therapeutic Indications:
(UP) onal Use with B-lactamase
For Gram negative rod Interference with platelet function Ureido penicillins (UP) : Mezlocillin
inhibitors
Ticarcillin and bleeding: and Piperacillin
Pseudomonas
Piperacillin An antipseudomonal Hematologic disturbances: more potent than carboxypenicillins
penicillin is frequently used Or impaired immunological defenses: eosinophilia, hemolytic although spectrum of action is
Mezlocillin in combination with an Bacteremias anemia similar
Carboxypenicillin aminoglycoside or have activity against Klebsiella and
fluoroquinolone for Pneumonias
(CP) enterococci.
infections outside the UTIs due to microorganisms resistant to
urinary tract penicillins G and ampicillin Both groups are Penicillinase-susceptible
drugs
Infections following burns
Clavulanic acid B-lactamase
Sulbactam inhibitors
tazobactam
All Inhibitor cell most frequently prescribed have the same mode of Each newer generation of cephalosporins has Hypersensitivity Less susceptible to penicillinases produced by Distribution
wall class of antibiotics action as other beta-lactam significantly, avoided or used with care in patients staphylococcus
Good throughout the body
synthesis antibiotics Greater, gram-negative antimicrobial allergic to penicillins Production of specific b-lactamases
Cephalospor have a beta-lactam ring Local pain after IM injection CSF penetration
properties than the preceding generation Decreased membrane permeability
in structure Thrombophlebitis after IV administration Tissue penetration including bone
in most cases, with decreased activity Changes in PBPs
against gram-positive organisms. Increased nephrotoxicity when
administered together with Excretion
Methicillin-resistant staphylococci (MRSA) are
Fourth generation cephalosporins, however, have aminoglycosides also resistant to cephalosporins glomerular filtration and tubular secretion
true broad spectrum activity.
The newer agents have much longer half-lives dosage must be reduced in patients
resulting in the decrease of dosing frequency with impaired renal function and
when using tubular secretory
blocking agents
may undergo hepatic metabolism
cefoperazone and ceftriaxone
excreted into bile
1st Gen Cefazolin, parenteral, Narrow spectrum similar to staphylococcal and streptococcal infections
Cefadroxil cephalosporin still in narrow spectrum penicillins;
skin and soft-tissue infections
Cephalexin general use sensitive to b-lactamases
Cephaloridine streptococcal pharyngitis
Drug of choice for
Cephalothin prophylaxis of
Cephapirin orthopedic,
Cefazolin abdominal, and
Cephradine pelvic surgeries.
Least toxic drug
Choice for persons
who are allergic to
penicillin.
Does not penetrate
CNS
2th Cefoxitin Increased activity toward They are useful agents for treating upper and Acetaldehyde accumulation
Cefaclor gram- lower respiratory tract infections, sinusitis and disulfiram-like effect with
anaerobic activity
negative organisms; increased otitis media cefamandole and cefotetan (2nd -
Cefoxitin (Cefotetan,
stability generation)
cefoxitin),
Cefprozil These agents are also active against E. coli,
although seldom Bleeding antivitamin K effects with
Cefuroxime used as a therapeutic Klebsiella and Proteus
cefotetan (2) or cefoperazone (3)
agent, it may be makes them potential alternatives for
useful for treating urinary tract infections caused
prophylaxis in by these organisms.
gastrointestinal
surgery.
3th Ceftazidime has useful Even broader in spectrum and Ability to penetrate blood-brain barrier Acetaldehyde accumulation
Cefdinir antipseudomonal activity more resistant to b-lactamases or cefoperazone (3rd-generation).
Except, cefoperazone and cefixime.
Cefixime Treatment of serious infections (e.g. Bleeding antivitamin K effects with
Drugs of choice for
Cefpodoxime bacterial meningitis) cefotetan (2) or cefoperazone (3)
gonorrhea
Ceftibuten Ceftriaxone
(Parenteral) (ceftriaxone and cefotaxime) have
Ceftriaxone
cefixime (Oral) excellent activity against most strains of
Cefotaxime Streptococcus pneumoniae,
including the vast majority of those
with intermediate and high level
resistance to penicillin.
4th Cefepime Gram-positive and gram- These drugs also have activity against
Cefepime negative nosocomial pathogens such as Enterobacter and
more gram-negative
activity (P. aeruginosa); Acinetobacter
Cefluprenam drug
includes
somewhat enhanced restricted to the setting of nosocomial
Cefozopran gram-negative and multiple-
activity against sepsis.
drug
Cefpirome pseudomonas but resistance patterns
Cefquinome slightly lesser
activity against
pneumococci.
Cefpirome
is more active
against
pneumococci and
has somewhat lesser
activity against
pseudomonas.
5th Ceftobiprole has been Ceftaroline (Teflaro, Cerexa) was approved by
labeled the fifth the FDA for the treatment of skin and skin
generation cephalosporin structure infections (SSSI), including MRSA and
with coverage for gram community-acquired pneumonia (CAP).
positives, including Ceftaroline is a broad-spectrum cephalosporin
MRSA and gram antimicrobial with extended gram-positive
negatives, including bacteria coverage.
Pseudomonas species.
It exhibits greater binding affinity than
The research strategy has ceftriaxone, oxacillin and penicillin G for PBPs in
focused heavily on this MRSA due to its increased affinity for the PBP2a.
agents anti-MRSA
coverage.
Ceftobiprole can be
distinguished from other
beta-lactams by its
increased binding to
penicillin-binding protein
2a.
Penicillin-binding
protein 2a is the
enzyme most
directly related to
MRSA
Carbapenems Imipenem is a broad- Drug of choice for enterococcus Nephrotoxic IV
spectrum, Always administered Penetrates CSF
-lactamase with cilastatin (inhibitor of renal
resistant carbapenem. dehydropeptidase I) to inactivation
of drug
in renal tubules
GI distress,
skin rash,
CNS toxicity
(seizures) at high plasma level

Monobactams Less susceptible to - Gram-negative rods onlyno activity against Usually nontoxic; occasional GI upset.
Aztreonam lactamases. Prevents gram-positives or anaerobes. For penicillin-
peptidoglycan cross-linking allergic

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 peptidoglycan cross-linking allergic
by binding to patients and those with renal insuficiency who
penicillinbinding protein 3. cannot tolerate aminoglycosides

Synergistic
with
aminoglycosides.

No cross-allergenicity with
penicillins
Vanvomycin Inhibit cell Backup drug for Bactericidal glycoprotein For serious infections caused by Nephrotoxic Adsorption & Distribution
wall synthesis treatment of infections Prevents polymerization of Ototoxicity
drug-resistant gram-positive organisms, Not absorbed from GIT; given for
caused by Clostridium linear peptydoglycan: bacterial enterocilitis.
difficile including MRSA Thrombophlebitis
inhibits transglycosylation
Inhibits cell wall In combination with a 3rd generation Inflammation wall of veins Given parenterally penetrates most
peptidoglycan cephalosporin (Ceftriazone) for treatment of tissues.

formation by binding infections due to penicillin-resistant Slow i.v. injection penetrates inflamed
pneumococci (PRSP). Red man/red neck syndrome
D-ala D-ala portion of meninges.
cell wall precursors. Sudden redness that spreads over the
Excretion
Bactericidal. Not upper body and neck
susceptible to - due to histamine release. mainly by the kidney
lactamases.
Bacitracin Inhibit cell Binds to a lipid carrier that Nephrotoxicity
wall synthesis transports cell wall precursors
Because of this, it is restricted to
interfering with wall
topical application
synthesis in gram-positive
organisms
Cycloserine An antibiotic effective against Mycobacterium Potential neurotoxicity:
tuberculosis.
tremors. seizures, psychosis.
For the treatment of tuberculosis, it is classified as
a second line drug
only considered if one or more first line
drugs cannot be used.
Fosfomycin May be synergistic with Inactivates the bacterial Effective against Excreted unchanged in the urine
beta-lactam and quinolone enolpyruvate transferase gram-negative bacteria that infect the
antibiotics in specific Prevents formation urinary tract.
infections of N-acetyl-muramic
acid
essential
precursor for
peptidoglycan
chain formation.
Daptomycin A novel lipopeptide antibiotic used in the myopathy
treatment of certain infections caused by Gram- Creatinine phosphokinase should be
positive organisms. monitored
Active against vancomycin-resistant strains of
enterocci and staphylococci.
ALL Protein Most of the antibiotics in Is a substance which stops or
inhibitors this group are slows the growth or
bateriostatic inhibitors proliferation of cells by
of protein synthesis disrupting the processes
acting at the ribosomal that lead directly to the
level. generation of new proteins
With exception of
tetracyclines and
aminoglycosides, the
binding sites for these
antibiotics are on the 50S
ribosomal subunit.
Tetracycline Bacteriostatic They are broad-spectrum Active against gram-positive and gram-negative Four general mechanisms of Tc GI disturbances Limited CSF penetration
The action is agents that inhibit binding facultative bacteria including anaerobes, resistance are known: The clinical use of tetracyclines is generally
From mild nausea, vomiting, and
bacteriostatic and can of the aminoacyl tRNA to mycoplasma, chlamydiae, and some protozoa. A. prevention of cytoplasmic confined to adults.
diarrhea, to life-threatening enterocolitis.
therefore be reversed the 30S ribosomal subunit accumulation, e.g., by an energy-
Alternative drugs in treatment of syphillis, Disturbances in normal flora may lead to This is because tetracyclines affect bone
upon removal of the in bacteria dependent efflux of Tc from the cell
acne vulgaris, chronic bronchitis. candidiasis (oral and vaginal), to development and can cause staining of teeth
drug
Doxycyclin B. chemical modification of Tc bacterial superinfections. in children.
Rocky mountain spotted fever C. a mutation in the 16S rRNA Deposition in growing bones and primary Absorption
(rickettsiae), cholera, Lyme (tick-borne affecting the binding site teeth in small children Impaired by food (except doxycycline
disease). D. ribosomal protection by a soluble Contraindicated in pregnancy : and minocycline)
Drug of choice for: protein
tooth enamel dysplagia and Impaired by divalent cations (Ca 2+,Mg2
Prevention of malaria and Ribosomal Protection irregularities in bone growth +,,Fe2+), Al3+, antacids, dairy products

treatment of amebiasis. Tet(M) as well as Tet(O) catalyze (crown deformation) (bind calcium), and alkaline pH.
For patients with renal the release of Tc from the usually in breast-feeding women Distribution
insufficiency. ribosome in a GTP-dependent (although there may be situations
manner. in which benefit outweigh the Good to tissues, body fluids except CSF
Tetracycline risk). Minocycline
Treatment of gastric and duodenal ulcer Photosensitivity High levels in saliva and tears
disease caused by Helicobacter pylori
Tetracycline (demeclocycline) may Excretion
Minocycline enhanced skin sensitivity to UV light.
Mainly in the urine (except doxycycline)
Treatment of meningococcal carrier Hepatic toxicity
state. All partially excreted in the bile
Fatal acute fatty degeneration of the
liver.
Impair liver function and lead to hepatic
necrosis.
Renal toxicity
Though no directly nephrotoxic, may
exacerbate preexisting renal dysfunction.
Fanconis syndrome has been attributed
to the use of oudated Tc.
Vestibular toxicity
dose-dependent reversible dizziness and
vertigo (doxycycline and minocycline).
Aminoglycoside Protein Bacteriocidal bind irreversibly to the 30S Severe gram - rod infections Nephrotoxic Bacterial transferase enzymes inactivate the Highly polar, polycations drugs, poorly
Gentamicin synthesis subunit of bacterial Synergistic with B-lactam antibiotics. drug by acetylation, phosphorylation, or absorbed orally.
inhibitors acute tubular necrosis.
Neomycin ribosomes and interfere with lack activity against anaerobes and most gram- adenylating. All except neomycin (topical) must be
Amikacin protein synthesis in at least positive bacteria, except for most staphylococci Also common in those concurrently
Changes in ribosomal binding site. parenterally administered.
Tobramycin 3 ways: receiving Amphotericin B,
Usually used with a broad-spectrum -lactam Cephalosporins, or Vancomycin Decrease uptake of drug when the oxygen Once-daily dosing (ODD) schedule
Streptomycin Block the formation for severe infection suspected to be due to a gram- recommended:
Most common nephrotoxic: dependent transport system for
of the initiation negative bacillus.
Gentamycin and Tobramycin aminoglycosides or porin channels are absent. concentration-dependent bactericidal
complex However, because of increasing aminoglycoside
Neuromuscular blockade activity.
Misreading of the resistance, a fluoroquinolone can be substituted
code on the mRNA for the aminoglycoside in initial empiric A curare-like block may occur at postantibiotic effect, allows continued
template regimens. high doses efficacy even when serum concentrations
fall below expected minimum inhibitory
Inhibition of Streptomycin in combination with penicillins is Contra-indicated in patients with concentrations.
translocation often more effective in enterococcal carditis than myasthenia gravis
regimes that include other aminoglycosides. decreased risk of adaptive resistance.
Usually reversible by treatment with
These combination is also used in the treatment of calcium and neostigmine diminished accumulation in renal tubules
tuberculosis, plague (Yersinia pestis) and Ototoxicity (especially when used with and inner ear.
tularemia (Francisella tularensis loop diuretic) Are distributed well into ECF
Auditory impairment
except for vitreous humor, CSF,
amikacin
respiratory secretions, and bile
kanamycin (particularly in patients with biliary
Vestibular dysfunction- obstruction).
gentamycin
excreted by glomerular filtration and have a
tobramycin
serum half-life of 2 to 3 h.
Teratogen
Cross placenta and may cause fetal The half-life increases exponentially as
CN VIII damage and thus should the GFR falls (eg, in renal insufficiency,
not be used in pregnancy in the elderly).Dosage adjustments must
be made in renal insufficiency to prevent
Ototoxicity may be increased by the use of toxic accumulation.
other ototoxic drugs
Loop diuretics

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 Furosemide
Cisplatin
Allergic skin reactions
Neomycin, most common
Occasionally antagonism of factor V
may result in bleeding.
Macrolides Protein Bacteriostatic Inhibit protein synthesis by For Atypical Pneumonia Toxic effects (MACRO) Three (3) mechanisms have been identified: Absorption:
inhibitors blocking translocation It is impaired by food.
Group of compounds (macroslides); bind to the
Motility issue Severe GI distress reduced permeability of the cell
characterized by a 23S rRNA of the 50S dose-related membrane or active efflux. Part of the dose is destroyed due to acid
macrocyclic lactone ring ribosomal subunit. production of esterases that hydrolyzed lability.
to which deoxy sugars are most common side effect
especially associated with macrolides. Metabolism
attached.
erythromycin, less with Modification of the ribosomal binding
All drugs concentrate in the liver.
clarithromycin. site (so-called ribosomal protection)
nausea and vomiting Methylation of 23S rRNA-binding Extensively metabolized in the liver
site (erythromycin and clarithromycin)
Arrhythmia (prolong QT)
Drug interactions
Cholestatic Jaundice
Metabolites inhibit the cytochrome P-450
Hypersensitivity reaction to system (except azythromycin)
the ester form of erythromycin
Increase serum concentration of numerous
Contraindicated in patients drugs
with hepatic dysfunction
Theophylline
Rasd
Oral anticoagulants
Ototoxicity
Cyclosporine
Associated with erythromycin
at high doses Methylprednisone
Erythromycin, Erythromycin Absorption
prototype Mycoplasma infections oral, as enteric coated tablets or esterified
Community-acquired pneumonia forms
Legionnaire's disease
To minimize destruction and
Chlamydial infections (respiratory, enhance absorption
neonatal, ocular or genital)
Diphteria (Corynebacterium diphtheriae) IV administration is associated with
Pertussis (Bordetella pertussis) thrombophlebitis
Distribution
well throughout the body except CSF
Crosses placenta membranes
Diffuses into prostatic fluid and
accumulates in macrophages
Excretion:
bile
Clarithromycin Clarithromycin & Azithromycin Clarithromycin & Azithromycin : more
(Biaxin) Spectra of activity similar to erythromycin, stable to gastric acid.
semisynthetic but greater activity against species of Excretion
derivative of Chlamydia
Mycobacterium avium (MAC) complex. Clarithromycin and its metabolites are
erythromycin
Taxoplasma excreted largely by the kidney and the
liver.

Azithromycin Clarithromycin & Azithromycin Clarithromycin & Azithromycin : more

(Zithromax) Spectra of activity similar to erythromycin, stable to gastric acid.
but greater activity against species of
Chlamydia Distribution
Mycobacterium avium (MAC) complex. Longest half-life (t1/2)
Taxoplasma
Penetrates into most tissues and
phagocytic cells, except CSF.
Largest volume of distribution.
Tissue levels exceed serum concentrations
by 10-100 fold.
These unique properties permit 0nce-daily
dosing (ODD) and shortening of duration
of treatment in many cases

Excretion
bile
Ketolides Semisynthetic 14- Same as macro penicillin-resistant Hepatic dysfunction
Telithromycin membered-ring Prolongation of the QTc interval
macrolide-resistant pneumococci
macrolides
may cause worsening of symptoms,
Differing from including breathing problems, when taken
erythromycin by community-acquired pneumonia (of mild to
moderate severity) due to by people with myasthenia gravis (a
substitution of a 3- disease that causes muscle weakness).
keto group for the Streptococcus pneumoniae, (including
neutral sugar L- multi-drug resistant isolates, Haemophilus These breathing problems may be severe
cladinose influenzae, Moraxella catarrhalis, or life-threatening and may cause death
Chlamydophila
pneumoniae, or Mycoplasma
pneumoniae, for patients 18 years and
older.*

Clindamycin Bacteriostatic Blocks peptide transfer
(translocation) at 50S
ribosomal subunit.
Anaerobic infections (e.g., Bacteroides spp.,
Clostridium perfringens) in aspiration
pneumonia, lung abscesses, and oral infections.
Also effective against invasive group A
streptococcal infection
Drug of choice for
Severe anaerobic infections in
abdomen, female genital tract, &
aspiration pneumonia.
Use in combination with
cephalosporins and
amynoglycosides .
Prophylaxis of endocarditis in valvular
disease patients who are allergic to
penicillin.
Moderate to moderate-severe Pneumocystis
carinni pneumonia in AIDS patients; in
combination with primaquine.
AIDS-related toxoplasmosis; in combination with
pyrimethamine
Common: Diarrhea, nausea, and skin Administration
rashes
Oral and parenteral
Impair liver function (with or without
Distribution
jaundice)
Neutropenia All body fluids except CSF
Its major disadvantage is its propensity to Good tissue penetration including bone
cause antibiotic-associated diarrhea, Excretion
including Clostridium difficile colitis.
Metabolized to inactive products and
It may range in severity from mild excreted into the bile or urine.
diarrhea to fatal colitis.
Pseudomembranous colitis (C. Resistance
difficile overgrowth) Mutation of the ribosomal receptor site
Modification of the receptor by a
methylase
Enzymatic inactivation of clindamycin

Streptogramins Binds to 50S ribosome,
Quinupristin/da inhibiting protein synthesis
lfopristin
Linezoid Inhibits protein synthesis
Binds to 23S
ribosomal RNA of the
50S ribosomal unit
Chloramphenicol Reversible binds to 50S
ribosomal subunits
Block peptidyltranferase at
50S
Drug reserved for treatment of vancomycin- Adverse Effects: IV, penetrates macrophages and PMN.
resistant Enterococcus faecium (VRE). Hyperbilirubinemia Metabolized in liver and excreted in the bile
Venous irritation
Arthralgia and Myalgia
Reserved for treatment of multidrug-resistant Adverse Effects: Oral and IV preparation
gram-positive bacteria. GIT upset
Nausea
Diarrhea
Trombocytopenia
Neutropenia
For treatment of serious rickettsial infections: Anemia (dose dependent), Plasmid-encoded acetyltransferase inactivates Administration
aplastic anemia (dose independent), the drug.
Typhus Oral
gray baby syndrome (in premature
Rocky Mountain spotted fever infants because they lack liver UDP- Drug Interactions chloramphenicol palmitate
Backup drug for severe infections caused by glucuronyl transferase). prodrug hydrolyzed in intestine to
Anticonvulsants yield free drug
Salmonella species and for the treatment of
pneumococcal and meningococcal meningitis in Gastrointestinal: Diarrhea, enterocolitis, Chloramphenicol may decrease the

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 pneumococcal and meningococcal meningitis in
beta-lactam-sensitive persons
Use topically for the treatment of eye infections
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Gastrointestinal: Diarrhea, enterocolitis, Chloramphenicol may decrease the
glossitis, nausea, stomatitis, vomiting metabolism of anticonvulsants
(Hydantoin).
Anticonvulsants (Hydantoin) may
decrease the serum concentration of
Chloramphenicol.
Barbiturates:
Chloramphenicol may decrease the
metabolism of barbiturates.
Barbiturates may increase the
metabolism of Chloramphenicol
Rifampin: May increase the metabolism of
chloramphenicol
Sulfonylureas: Chloramphenicol may decrease
the metabolism of sulfonylureas
IV
chloramphenicol succinate
Distribution
To most tissues and body fluids
Crosses the placental and BBB readily
Protein binding:
~60%
decreased with hepatic or renal
dysfunction and in newborn infants
Metabolism
Most of the drug is inactivated by hepatic
glucuronosyltransferase
Converted to an inactive
glucuronide
Inhibits the hepatic mixed function
oxidases
CYP2C9 (weak), 3A4 (weak)
Half-lives of several drugs are
prolonged:
Phenytoin,Tolbutamide,
Chlorpropamide, and
Warfarin
Excretion
~90% : glucuronide inactive products;
~10% : active (parent) drug in the urine.
Resistance
the formation of acetyltransferase
(inactivates antibiotic)
inability of drug to penetrate the organism