Document 6430716

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Bacteriostatic: Inhibits growth and replication.
• Viable bacteliai numbers remain unaffected.
~
Bactericidal:
lMvcc,,1
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Kills replicating bacteria.
TI...
• Viable bacteria decrease in number.
• Requires replicating cells (do not use with
bacteriostatic drugS)
Therapeutic spectra:
~
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ad.. d<uo
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Narrow· acts on a single organism or type of organisms.
• Isoniazid (INH), Rlfampln. Ethambutol, Pyrazinamide onlY Mycobacteria.
~
Extended· works on gram pos. aerobes and also some gram negs.
• Ampicillin and amoxlcillin
~
Broad· affect a wide variety of organisms.
• Tetracyclines, c1indamycln and chloramphenicol.
• Tend to cause ·superinfections· of unaffected microbes or fungi.
~
Coed
Rods
Cocci
StreptoeoctUS
Staphylococcus
Coed
Enterococcus
Corynebacterium
Rods
I Neisseria
Elkenella(corrodensl
I HaemophUus
Campylobacter
Pseudomonas $p.
Enterobacteriaceae
Aggregatlbacter (Actinobacillus)
actlnomycetemcomltans (facultative)
Peptoeoccus
Coed
I VeUionel'.
Actinomyces
Lactobadllus
Clostridium
Eubacterium (notatuml
Rods
I Tannereli. (Bacteroides) (forsythensls I
OdontogeniC Infections:
• (Acute InfectionJ-l> Gram Pos aerobes (strep) -l> (Mixed Infection) -l>
facultatlves & t anaerobic gram pos bacilli -l> (Chronic) Gram Neg anaerobes.
• Empiric selection of antibiotics depends on age of Infection.
• Therapy should never be delayed. (Drainage, debridement)
• Most circumstances don't allow for culturing. (Culturing can and should be done if patient is not responding) I
Acute infeciion
Ii Mixed
Ir!e{.:i~~f
Ii
Peptostreptococcus
Rods
Porphyromonas (glnglvalls)
Prevotella (Intermedla)
Fusobacterium nucleatum
Capnocytophaga
E.COII
Klebsiella
1
... Cellulitis: Diffuse inftammation of soft
tissues: represents 'spreadlng'through
connective tissue (dermis. subcutaneous tissue
or fascial spaces in muscle).
.... Periodontal Disease:
• Plaque bacomes more gram negative and anaerobic -'pathogenic' Porphyromonas, Prevotella, Bacteroides, TannereHa forsythensis, Actinobacillus. Eikenella. • Most Common: Staph aureus and Strep
pyogenes. Virulence factors: (InvaslnS)
streptokinase. streptodomase,
hyaluronidase, streptolyslns. exotoxins.
• Cellulitis not mutually exclusive - it can be a
part of any infection. Bllllllmllsubrmmdlbularlsubingual
.... ANUG (necrotizing): Sprirochetes
(Treponema)-Structurally Gram neg. cell
wall (facultative) and Gram-neg anaerobes.
ecut8 celluHIIs -~Ludwlg" Angina"
-
... Localized Juvenile Periodontitis:
(Aggressive Periodontitis) - Gram Negs:
.... Pyogenic space Infections (abcesses): Staph (localiZed) and strap
(spreading) both pyogenic, esp. staph. Accumulation of neutrophlls (pus)lserum.
=
• Aggregatibacter actinomycetemcomitans ."M" -aerobe
• Capnocytophagia - anaerobe
• Spirochetea
• Eariy space abcess mixed aerobic/anaerobic
• > 3 days old: 30% space abscesses pure anaerobic.
~-.W'~;;~./
• G neg. anaerobes: PrevoteHa, Porphyromonas,
Fusobacterium, Peptostreptococcus, Bacteroides spp.,
TennereHs forsythensis
~....
{~'.: >"~."
.... Generalized Chronic Perlodontltls: Gram neg anaerobes
.... Dose-Dependent Antibiotic!
prua Resistance: Mutations
develop new strains with
reSistance to antibiotics.
.. Resistance gene Is transferred to
other bacteria by plasmids.
(acquired resistance)
• Characterized by concentratlon • dependent killing:
• Higher the drug concentration, the greater the rate of killing.
• Therapeutic ObJective:
• Maximize peak concentration (Cmax) maximize bactericidal effect.
,.,. (II
Four Main Mechanisms:
Most Common:
1. Increased efflux. (pumps)
! ..
fi
2. Decreased permeability.
• Azlthromycln
3. New, modified enzymes destroy
antibiotic. (13-lactamase-pen.
transacetylase- chloramphenicol)
• Metronidazole
• Fluoroqulnolones
• Amlnog!ycoslcles
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4. Altered targets & enzymes: Macrolide resistance - ribosomes no longer allow binding of antibiotic. Fluoroquinolones-single mutatlon alters DNA gyrases. ""'c....,
_
-6.
or
CmaxlMlC
(lnhlblloty Ratla)
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UM
11m. (HourI)
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• No advantage to higher serum concentrations. (> toXicity)
• Time above MIC (T>MIC) Serum conc. are more effective. Magnitude by which Cmax exceeds MIC
,
400888 of
Gentamycln
E. coUexpoaed to 1.5,3.0,6,12 x MIC
8
10
'
Most valuable predictor of
success CmaxlMIC
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Time (h)
Dose Dependent
Killing curves for S. _reus ATCC 29213
exposed to 2. 4. 8. 18. and 84 x MIC of
vancomycin
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Most valuable predictor of
success T> MIC
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S Different Doles - Same Effect
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20
_1il1J1lBjJlft~_
... Tlme.Dependent Antibiotics
Mod-Severe Renal Dysfunction or Elderly (>65):
• Activity has little relationship to concentration, as long as the cone. is
above the MIC.
II- Renal functton decreases IInearty with age.
• Doses> MIC do not kill any faster or extensively:
• Saturation of the killing rate occurs at the MIC.
... No Need for Reductions:
• Therapeutic Objective:
• Maintain concentration at or above the MIC of the organism.
.~"'actams
Time Dependent, but
"Concentration Enhanced"
• Vancomycin
• Erythromycin
• Tetracyclines
• Cllndamycln
• Clarlthromycln
• Time-Dependent AB's:
• PenVK
• Dicioxaclilln & Hafelllin
• Cllndamyeln
• Azlthromyeln
• Doxycycline
... All other antibiotics:
AaeGnIlPtr>
GJI'R
....,lii&0i1.13,.'
2O-J!I
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118.0lI0
60-89
13,7%
30-59
.
1!'.-29
•
.I- Doses or t
4f-59
5$,7%
42,7%
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38,5%
25.5%
5$,....
...t.8.5%
.~
1.8%
(7,1%
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24,~
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Dose reduction If GFR < 30
Dose intervals
3
.. CO-TRIMOXAZOLE (Sulfamethoxazole and trfmethoprlm; Badrlm1V , SepttaTM)
• Bacteriostatic. Inhibits folic acid synthesls.
-..,.
Cet:>h• ....,.".,.
• Bacteria must mllke folic acid for de novo synthesis of two DNA nudeosides
thymidine and urtdine. PABA is a precursor for folic acid synthesis.
Cell_I
=:r:"
-
~ a:::.
----~-~.
FOlIc acid
meIaIIOIIam
DNA
DNA-d
Fluoroquiflotones
RNA poIymel1l
• Sulfa drugs similar to PABA (para-aminobenzoic acid)- Act as false substrates.
• Combined with another folic acid inhibitor. Trlmethoprim. 11 efl'ective. Binds
dihydrofolate reductase In same pathway blocks synthesis of tetrahydrofollc acid.
RIIIImpIn
• Antibiotic Synergy: Combined effect on two sequential steps: 1) Belter efficacy than either drug alone. 2) Less chance for resistance to develop. dIhj<fnl/.....
Proetln 8yn111e.
1308 Inltlbilonl)
• High incidence of allerpy (allergy to PABA) - skin rashes, hives.
Te1I'O<:ydine
:="Tobr....
y<in
(omInogI~1cI<Io1
.. Sulfamethoxazole and trlmethoprlm, Spectrum and Uses:
-~~[~I
• Gram Negatives only:
• Actinomycetes
• Chlamydia
• E.coll
• Proteus
• Salmonella. Shigella
• Haemophilus
• Pneumocystis & Toxoplasma Cotptozoal infections In HIV patients).
• Susceptible Strep. (otitis media. bronchitis)
... BETA·LACTAMS (Panlcllllns and Cephalosporin.)
• Bacteri~
• Most used and effective antibiotics wi least toxicity.
• Side-chains account for differences: acid stability. ebsorption, spectrum.
susceptibility to bela-Iactamases.
,..._-,
• J3-Lactamases deslroy the jJ-Iectam ring at the nitrogen.
(Penicillinase Is one type of jJ-I.actamase)
• Therapeutic uses:
. _""=£
:~~~OPOC<
G+
"'''''doSly­
• Penicillins block cell wall synthesis. Covalently bond Pen.
binding proteins (PBP's) needed to make peptldoglycans.
• Urinary (UTI) (E.coIi. Proteus)
• Gllnfections (salmonella. shigellosis)
• Only replicating cells. making peptidoglycan wails (Not
mycobacteria or gram negatives).
• Respiratory infections (Strep. pneumonae. haemophilus)
• Gram negs have LPS outer layer that prevents water·
soluble penicillins \'Tom entering and have no PBP's.
• Adjunctive treatment of periodontal diseaseslabcesses.
Perip.smic apact:
"""-al}'CIU
Outer mtmbtan~
(lipopo1yMCChIuidt:
todprott'in)
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l
4..,
4
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IIIDBJDIIItIIIII&l1SJJlBltiIIIII
• p.lsetam Spectrum: Gram PositJve8. (aerobic and some anaerobic)
• Streptococcus, Bacillus, Clostridium, Corynebacterium, Neisseria
(gonorrhea and meningitis), Treponema (spirochetes)
• Since 1970's, No longer effective against staph (penicillinase).
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I
Penicillins
/--Drug name
I
I Penlclllfna.. I
I RoulH
1
r..
. ..!enlcilllnG,_dal _ _'"
Penicillin VI< (Pen -
PO.IMoIV
po
K. V..clllln K)
• Most Important adverse effect: d!.!!.rll:l
Ampicillln/amox produces an "ampicillin rash" in 5% of patients.
• Cro....llergenlcty: All penicillins, 1st Gen. Cephalosporins (~150/0).
bf'!At:n-Um
• Irreversibly bonds with
beta-Iactamase.
• "TIes up" ail beta­
lactamase.
• A
~ Ce phalo8POnni
1"'9
.~R2
II
~
PH ntl9
o ..
II
...
Hle~SCH'l'HzlVH
bfLJ',tll<bim
f D N i l.. CHelf.OH
imlpenem
CQOH
davulanato
0
COOH
Also sulbaclam & tazobectam
• Allows the antibiotic to persist and extends the spectrum to staph.
.... Augmentln 1M. amoxicillin + dal/ulanate = mOlW gram negatives/anaerobes:
• Gram Pos Aerobes:
~-Lactamase
II
V..
15
I
75-80
AmolClolllln (AmoKIII
PO
AIogmlntln (.moxlclUln & oIavullnlc
lold)
PO
Antlstaph Penicillins:
l
DlololUlclllln (Dynapen. Dy.n"
Nilelilin
~~ ~v..
V..
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~
7540
1-
> 85
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20
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PlnlcUlln_ R<I.ltttant -Ruorwd for Sblphylococcellnr.ctfon.
OlUlClllln IProataphHln. Bactoclll)
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(Unlpen. Natelll
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. PO.IM,IV
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PO
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IV. 1M. PO
1-­
V..
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V..
20-30
85,
V..
v..
4D.80
118
v..
v..
< 30
.. _
bf>t;\-lactam
II
~JI.IKloIlft
~W-l
0
"t-t-.
coot<
No
Glycopeptides • Not Beta Lectsms
II
R-C-H
• Mechanism of action:
. ~q.nd \'1101
'.Iy\'llol
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_~~I! _I~~
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~,... ~;.,
_._'"-,
• Metabolism: Pen&Amox-None- Active Renal Tubular Secretion (Organic
anion transporter (OAT) In prox. convoluted tubule)
• Beta-Iactam wlo activity.
_.0"'
..
,"01M 8I'11III nag: H..mophll.... Salmonelll, P,........ Ente_ _, _l!.ooII)
• Synergism: Aminoglycosides (streptomYCin, gentamycin) facilitate entry
into the cell.
"fCl'"'9CH)
eli) penlcliUn
I.
Extended Spectrum: AmpIcUliniAmoxlclilin
• Antlstaphylococcal penicillins: methicillin (niB), oxacillin,
dicioxacillin, nafclllin (resistant to bela-lactamese)
• Reserved for confirmed staph. Infections
• MRSA (methicillin-resistant Staphylococcus aureus)
o
I .•tabla
I AlI.orbed ~profaln
PenlcllQn: StrepIococ...., _II.... CI""trldlum, .,.,.,.......... _arlo
pMMIlY·"""1JI1 II at."lum ... Clavulanlc acid
.....llIIanl
Acid
... VANCOMYCIN (Inj. Vancocln™)
•
•
•
•
Bactericidal
Narrow Spectrum: Gram pOSitive Cocci: Strep and Staph.
last traditional agent not affected by staph and strep resistance.
Poor GI absorption - IV only
• Uses:
• When Beta lectams fail- for resistant staph infections
• Tx of endocarditis. (IV)
• Tx of pseudomembranous colitis (C. diflicle infections)
(Oral- Vancocin""')
producing Staph and Strep, Enterococcus
• Gram Neg Aerobes: Haemophilus, E.coli, Klebsiella, Enterobacter, Proteus
• Anaerobes: Bacteroides, Tannerella. Fusobacterium, Peptostrep.
• Uses: OtItis, Sinusitis, Lower Resp. Tract, UTI, Skin
... BACITRACIN
• Topical only - no oral absorption
• Gram positive aerobes only
5
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z~,;'e~ ~ r~"-""1
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1~'if"l,.~ft;~~:¥11'~~~~t~
" w~JtJ,t::".tJJJ"
IJJ~J ~;.t;J~~,.~~, '~0-").>~
III- CEPHALOSPORIN SPECTRUM
... CEPHALOSPORINS:
e1st Gen:
Are Pen G substitutes- Strap and Staph, three G·: Proteus,
E.coli. Klebsiella (PEcK)
• 10t Generation: (3 oral) cephalexin (Keflex); cephradine (Velosef):
cefadroxil (Duricef)
• 2nd Generation: (4 oral) cefaclor (Ceclor): cefprozil (Cefzil);
cefuroxime (Ceflln); loracarbef (Lorabid) .--.;.-~_ _ _ _ __
IR2
H
• 2nd Gen: three more gram neg: Haemophilus, Enterobacter. Neisseria,
(HENPEcK)
• WIder spectrum of Go activity. Weaker against staph and strap.
• Can be used for orofaclal (dental) infections.
u
• Beta-Lactams wI same properties
(bactericidal) and mechanisms of action
e 3rd Gen: Aerobic, Gram negative only· for serious infections.
as penicillins.
• Shott half-lives - 1-2 hours.
• Little or no gram positive activity.
• Only 3'" Gan penetrates CSF· have much longer half lives.
• Esp. uaeful for Gram neg. Meningitis
• Poor against oral anaerobes, no PAE. Not drugs of choice for dantal
infections.
• Little dantal use.
• Ceftriaxone (Rocephin) for A.A., Haemophilus Endocarditis.
• More resistant to Beta-Iactamases.
• -15% CrossAilergenlclty w/1 ot Gen. « 2% for 2nd Gen. Cephs)
.,. Primary uses: (Gram negatives & Atyplcals)
• Chlamydial infections
• Rocky mountain spotted fever (Rickettsia)
• Lyme Disease (Spirochetes)
• Mycoplasma pneumonia
• Cholera (Vibrio\Gram Neg)
TETRACYCLINES, AMINOGLYCOSIDES, MACROLIDES, CLiNDAMYCIN
All target bacte1ialribosome ancIlnhlbit protein synthesis.
TETRACYCUNES: (Tetr&cycline-Achromycln 111, Doxycycllne­
Vlbramycln 111, Mlnocycllne-Mlnocln 111)
l1li- Classification by Elimination Half-lIfe:
• Short-acting: tetracycline, oxytetracycline, chlortetracycline: T112 = -8 hr
• Intermediate acting: demeclocycllne T112 =12 hrs
.,. Adverse Effects:
• Teratogen, BInds 10 calcifying tissues - teeth and bones. Use In chUdren,
nursing mothers. and during pregnancy Is contraindicated. prwg cat D.
• Long acting: doxycycline, minocycline T112. -18hrs
• Superinfection: overgrowth of fungus Is common.
• Tetracyclines are generally antagonistic with other antibiOtics.
• RenaUy- impaired patients can only use doxycycline.
• Photoloxiclty (skin reshes) can occur with tetracyclines.
• Bacte~
• Broad spectrum activity but used mostly against gram negatives
• Requires active transport to get into cells
• Wkiespread resistance: Efflux pumps most common. Subject to 3 of 4
resistance mechanisms.
• Chelate/Bind divalent cations. Absorption inhibited if taken with Ca++,
Mg++, antacids, minerels or dairy products.
'-. • Minocycllne can produce otoloxiclty.
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[E Dental Use of Tetracyclines:
• Adjunctive Periodontal uses only.
• No longer used for maxillofacial infactions due to resistance:
• Management of localized Juvenile periodontitis (Aggressive Periodontitis)
- Aggregatlbacter actinomycetemcomitans (AA).
• Low-dose tetracycline therepy inhibits binds to zinc In collagenase (MMP).
• Periostat™ (10 mgtetracycllne qd)
• Bacteria don't become resistant wllime
• Local application as adjunctive therapy
for resistant periodontitis:
• Atridox™ gel (doxycycline)
• ArestinTIII (minocycline
microspheres)
• Effective conc. - 2wks.
• Not effective method for AA.
[AMINOGI.YCOSIDES~ (G~_y~l;'- st;-pt~;~J;. Ne-;;-;Yclr\n,bra-';yCill}J
• Aerobic gram negative organisms only: Pseudomonas, Vibrio cholerae.
Yersinia pestis, E. coli, Enterobacter. Klebsiella, Proteus.
• Bactericidal-No anaerobes. (needs 021R1pendent transport into cell)
• Synergy with beta laetams- allows amlnoglycoside Into cell to bind to ribosome. • Parenteral use only
• Therapeutic Uses: (No dental uses)
• Serious abdominal infections! Good Anti-Pseudomonal efficacy.
• Tx of Infective streptococcal endocarditis (Streptomycin combined
with penicillicin)
• Tuberculosis (TB), Cholera, Bubonic plague
• Chronic urinary tract infections
• Ototoxicity and renal toxicity occur at therapeutic dotes!
• Curare-like NMJ blockade. (Myasthenic syndrome) Caution in Myasthenia grevls or wi NMJ blockers. 'Being replaced by newer cephalosporins and ftuoroquinolones-due to toxicities.
MACROLIDES: Erythromycin, Clarithromycin(Biaxin), AzithromyCin(Zithromax)
50s ribosome InhibItorS
... ERTHYROMYCIN:
• "Penicillin substitute" - similar spectrum (aerobes only)
• Bacteriostatic
• Narrow spectrum: Aerobic gram + plus some "atyplcals":
• Chlamydia, Mycoplasma, Spirochetes, and legionella
• Medical Uses:
• Strep and staph
• SyphiliS, gonorrhea, chlamydia
• Mycoplasma pneumonia
• Diphtheria
• legionnaire's Disease (all macrolides)
• Adverse effects: GI pain, diarrhea. cramping, etc.
• Extensively metabolized by Phase I enzymes.
• Erythromycin strong inhibitor of CYP3A. Many drug interactions.
Erythromycin, con't:
• Inhibits metabolism of drugs using CYP3A:
benzodiazepines, theophylline, etc.
t coumadin, fluconazole,
• Dental uses: long hx of use in orofacial infections in early infections.
• little activity against gram neg.
• Used as an altemative antibiotic. Poor 2nd choice to (3- lactams.
• Endocarditis prophylaxis in penicillin-allergic patient.
• Staph Resistance to macrolides common - cross resistance with clarithro and azithro. ... AZITHROMYCIN:
• Less activity against: Strep and staphylococcus.
• Mora activity against: Gram negatives (Haemophilus, Moraxella. Neisseria, Campylobacter, legionella, also Mycoplasma) • Better for late dental infections.
7
,----
AzIIImomycln, con't:
ADVANTAGES:
---'---------­
'--­
.. CLINDAMYCIN: (Cleocinl1l) - not true macrolide, but similar activity.
• No phase I metabolism. Eliminated by biliary eXcretion unmetabolized ­
no drug interactions - no cytochrome inhibition.
• Mechanism of action (binding 50s riboSomes) similar to the macrolides, but
structurally a lincomycin.
• ~10% excreted unchanged in the urine - no reduction in renal disease.
• No cross-allergenicity with Macrolides.
• Extensive tissue distribution- tissue cone. exceed plasma cone.
-
,-
• Bacteriostatic at low doses (-cidal at higher doses).
• Long half..fife (60hrs) - once a day dosing. Must use loading dose.
• Broad spectrum: All classes of bacteria
• AerobIc and anaerobic gram positives (strep and staph)
• Anaerobic gram negatives such as Actinomyces, Bacillis,
TannereUa (Bacteroides) and many anaerobes.
.. CLARITHROMYCIN: "Erythromycin SubstHute"
• Spectrum same as erythro wlactivlty against Haemophilus.
• Superior to azithromycin in anti-strep and staph activity.
• Few drug interactions.
• Excellent for Anaerobic Infections.
• Penetrates bonet concentrates in WBC's. and abscessed tissues.
• Alters GI flora rapidly- 25% incidence of diarrilea. cramps, etc.
• less gram neg. activity than azithromycin
• Clarlthromycin heavily metabolized in liver and kidney.
• More drug-drug interactions than azlthro but less than erythromycin.
(ciprofloxacln-Cipro 1M, oflaxacin- Floldn 1M ,
•
101
Une in medicine: Anaerobic infections above the diaphragm.
• Newest, fastest growing class (1980's)
• 1- Gen: the quinilone nalidixic acid a urinary tract antiseptic.
• In dentistry:
• 1st-Line for late, or sevel8 dental infections & abscesses.
Fluoroquinolones developed from nalidixic acid.
• Binds DNA gyraseltopoisomerase complex. (unwind DNA during
replication)
• Resistance is beginning to be a problem.
• Stops replicationlDNA synthesis.
• Pregnancy Cat. B.
• Bactericidal
• Associated with severe diarrhea: pseudomembranous colitis. (anaerobe­
Clostridium difficile)
• Spectrum: Gram negative aerobes and anaerobes only- esp. 1st and 2nd
Gen. agents. Good Anti-Pseudomonal activity.
• Treated with oral metronidazole or vancomycin.
l. • 2ndGen: Urinary tract Infections, prostatitis, sexually-transmitted
diseases• • ofIoxacin- Floxin 111. tl l2'" 6hr, Some Gram neg activity • clprofloxacln-Clpro 111. t1'2 = 4 hr, better Gram neg activity
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_i,jjIr_ • 3rd Gen: Same Gram neg with SlIVP actlvllJ + Improved Gram +,
• levofloxacln-Levaquln1M. t 112 = 6 hr
• Rapid resistance develops: Single point mutations in DNA gyrase or
topoisomerase blocks binding. Widespread resistance already.
• Cross resistance is 100%.
• 2 X Gram neg. activity of 1'" Gen, plus strep and more staph activity.
• Some moderate anaerobic activity also.
• Medical Uses: Above dlaphram: Lung, skin, sinus, ear, eye infections.
• Little hepatic metabolism - few drug:drug interactions.
• 4thGen: Very broad-spectrum: Gram -, Gram +, and antl-anaerobe.
• Most important Cipro interactions: t effect of Warfarin. theophylline,caffeine.
• Can't take with metal cations like Ca. Mg, Fe, Zn. Etc.
• Damages cartilage (chondrotoxlclty). Not for use under 18 ylo.
Dental Uses: Clpro1M; Levofloxacin (Levaquln1M).
• Same G- coverage, improved G+ coverage, gain anaerobic activity.
• Long half-lives - q12h dosing (1x daily dosing)
• More liver metabolism than earty generations - more potential interactions,
liver toxicity problems, prolong or more than other FO.
• Not for acute infections in dentistry.
• Refractory chronic periodontitis for gram negative aerobes.
• Substitutes for penicillin-allergiC pis who cannot take
cephalosporins or macrolides.
• Moxafloxacln (Avelox)-anaerobes -some liver toxlcitylprolongs aT
• Gemifloxacin (Factive) - multidrug resistant strap.
• Reserved for severe respiratory and anaerobic abdominal infections. Strep
and staph, GI anaerobes: Bacteroides, Prevotella. Fusobacterium.
Porphyromonas.
• Cipro often combined with metronidazole for anaerobes & AA.
[
I.. . RIFAMPIN: (Rlfadln®) Antitubercular- taken with isoniazid (INH) J
• Inhibits mRNA synthesis. Binds RNA polymerase.
• Bactericidal
• Narrow Spectrum: only mycobacteria (M. tuberculosis and M. leprae)
• Uses: Leprosy and Tuberculosis, Mycobacterium in HIV pts.
• Inducer of Phase I enzymes:
• ./. Effects of many Drugs:
• Coumadin
• Prednisone
• Phenytoin
• Digoxin
• Oral contraceptives
• Sulfonylureas
• Tums saliva (and other body fluids) slightly reddish-orange.
~METRONIDAZOLE:
(Flagyl®)- - - -
- - ---]
• Bactericidal against all obligate anaerobes.
• Breaks DNA structure directly.
• Antlprotozoal: amoeba (Entamoeba), Trichomonas, Giardia.
• Med Uses: Deep space abcesses, including those in brain.
• Concentrates in gingival crevicular fluid (like tetracyclines).
• Tx of antibiotic induced diarrhea -C. difficiJe • anaerobes.
(pseudomembranous colitis)
DENTAL USES:
• Combined with j3-Lactams, macrolides,fluorquinolones - 1st Line for
serious orafacial infections.
• Most effective antibiotic for A. actinomycetemcomitans.
ADVERSE REACTIONS:
• Metallic taste, dark urine, skin rashes.
• Use of ethanol leads to "Antabuse"-type reaction: AVOID ALL
ALCOHOL, even in mouthwashes.
9
... Acute Periodontal Abscess - exacerbation of existing periodontitis
.... Early Infection « 3 days)
• -10-15% of all dental emergencies.
• Beta-Lactam, cephalosporin, new macrolide
• Microbial content qualitatively simMar to adult periodontitis .
• 74% anaerobes, 67% G- rods, w/strep at base of the abscess.
(J Periodontics, Newman and Sims, 1979)
.... No Improvement (beta lactamase?) (48 hrs)
• Discontinue Beta Lactem
• Augmentin, clindamycin. azithromycin
• Tx Is 1&0 and SC\RP. However. systemic signs or refractrory
infections require AB.
.... Late Infection (anaerobes) (swelling or > 3 days)
• High dose. short tarm AB regimen used wHh Tx:
• Clindamycin
• Beta-Lactem + metronidazole
• Macrolide + metronidazole
• Fluoroquinolone + metronidazole
• Amoxicillin (or Augmentin) for 7 days
• Clindamycin for 5 days
• Azithromycin for 3 days
J Periodontol, Nov 2004, vol 75, Position Paper. 'Systemic antibiotics In periodontiCS'
... Infection of endocardium or valves from bloodborne bacteria.
... Native valve- 85% are streptococci and staphylococci:
• Streptococcus viridans, 60% of cases.
• Staphylococcus aureus - 25% of cases.
• AA, Haemophilus. Eikenella (perio pathogens) -5%
... Prosthetic valve endo. (PVE): <2 mos Staph. >2mos-lika native valve.
• Ptosthetk ClnIac:""
• Prtor Hx of In't'ectM I.ndGcanaIIs
... Incubation period is 10-14 days:
• ~ HHrtDlsl!ases:
• Flu-like symptoms: chills. fever. jOint pains, malaise and tiredness.
........_
II
I
Wi
I'-~~~.~
.....
........
..,......,...,....."..................
.............
,.......
..................."""............................ ... BE not closely correlated w\ invasive procedures - medical or dental.
• ~hIMt .................. "",,~ .........
... Bacteremias are common daily occurrences, toothbrushing, chewing.
... Incidence of BE has not declined since the use of antibiotic prophylaxis
was started in 1955.
• .,...0IdIatk:1IJIIIdI.~""
... 2007: Antibiotic prophylllXls aimed at those who have riM factors:
• Cardiac Transplants and development of cardiac valvulopathy.
• Damage or congenital defects to heart or heart valv..
(..
__
t. (.
10 . r
r
(
EtEfif~rmmlr.mwf±ltli't1l'61I§MdMMMM Condition
Autogenous vein
grafts
Stent
Surgically piKed
metal plates, wires,
pins, screws
vascular Grafts
IY Ac:cess Devices
(Shunts/catheters)
i
PntMed
Description
CoroRll!'y Artery Byp8$S Gl'llfts
(CABG)
No
Angloplasty with slent after .. weeks.
No
History of fadal fractures, orthopathlc sUl'lery
No
... Guidelines updated by the American Academy of
Orthopedic Surgeons (AAOS) in 2009:
"Given the potential advft/'$e outcomes and cost of treating an Infected
Joint replacement, the AAOS recommends that clinicians consider
antibiotic prophylaxis for all total/olnt replacement patients prior to any
Invasive procedure that may cause bacteremIa."
... Procedures that produce bacteremia:
NonautOienous (Bovlne.etc)
Yes
SynthetIc (Dacron, PTFE)
Palliative sylltemlc'pulmonary shunts between a
sylltemlc army and the pulmonary artery (IT shunt).
Renal Hemodialysis with arteriovenous (AV) shunt or
(Udall) cathll1er
Hydrocephalle shunts
Chemotherapy In!twelKng catheters (Hlckman/arovlac)
CentrallY lines
Usually
Yes
Med
Consult
•
•
•
•
•
•
•
•
Extractions; perio surgery procedures. scaling and root planing. probing
Subgingival placement of antibiotic fibers/strips
Recall maintenance
Dental implant placement and replantation of avulsed teeth
Endodontic Instrumentation or surgery only beyond the apex
Initial placamen! of orthodontic bands but not brackets
Intrallgamentary and intraosseous local anesthetic injections
Prophylactic cleaning of teeth or implants where bleeding is anticipated.
Yes
ProsthetiC: joints
... Prosthetic Joint infection (1 st Yr): >80% Staph.llureus and
Staph. epidermldis.
... Later infections (> 1st Yr): Mostly Staph w/sorne gram.negatlve
... Already taking an antibiotic for endocarditis prophylaxis:
• Select a drug from a different class rather than Increasing the
dose of the currant antibiotic.
rods (E. coli, Bacteroides, Haemophllus) and Pseudomonas.
... Recommended Antibiotics (ADA):
• 1&t Gen. Cephalosporlns: Cephalexln (Keflex), cephradlne
(Velosef), cefadroxll (Durlcef) - little gram neg. or Enterococcus
coverage.
• Amoxlclllln/Augrnantin 2 gms • penlclilinase.producing Staph,
streptococci; Enterococcus.
.... Taking daily beta·lactams for prevention of rheumatic fever
or for other purposes:
•
Have virldans strep resistant to penicillin, amoxlclllln, already.
•
Use clindamycln, azlthromycln, or clarlthromycln Instead.
....If possible, delay elective procedures until at least 10 days
after completion of a first antibiotic:
• Cllndamycln (Cleocln) 600 mg
• Clarlthromycln (Blaxln) 500mg
• This allows the usual oral flora to be reestablished.
• Azlthromycln (Zlthromax) 500 mg
JM. Dug;an. MD. M.n.....nt of P _ Jofnt l""'ctIono. Infect _
18(12):534-541. 2001.
11
Situation
Standard
Prophylaxis
Unable to take Oral
Medication
Agent
Regimen
Amoxicillin
Adults: 2.0 grams orally 1 hr before procedure
Children: 50 mg/kg orally 1 hr before procedure
Ampicillin
Adults: 2.0 grams 1M or IV 30 min before
procedure
Children:
50 mg/kg 1M or IV 30 min before procedure
Clindamycin (Cleocin)
Allergic to Penicillin
Clarithromycin (Biaxin)
or Azithromycin
(Zithromax)
Cephalexin (Keflex) or
Cefadroxil (Duricef)
(1st Gen)
Allergic to Penicillin
and Unable to
take Oral
Medications
Clindamycin (Cleocin)
Adults: 600 mg orally 1 hr before procedure
Children: 20 mg/kg orally 1 hr before
procedure
Adults: 500 mg orally 1 hr before procedure
Children: 15 mg/kg orally 1 hr before
procedure
Adults: 2.0 grams orally 1 hr before procedure
Children: 50 mg/kg orally 1 hr before
procedure
Adults: 600 mg IV 30 min before procedure
Children: 20 mg/kg IV 30 min before
procedure
L
\...
~
12-