Principles of Antimicrobial Therapy Revised
-
Upload
moha-bin-ladiif -
Category
Documents
-
view
224 -
download
0
Transcript of Principles of Antimicrobial Therapy Revised
-
8/8/2019 Principles of Antimicrobial Therapy Revised
1/22
PRINCIPLES OFANTIMICROBIAL
THERAPY
-
8/8/2019 Principles of Antimicrobial Therapy Revised
2/22
LEARNING OBJECTIVESDescribe th e va rious m ec han ism by wh ichant ibio t ics/ ant im icrobi al d rugs work
Discuss th e rat ional use/ appl icat ions of ant im icrobi al d rugs at fie ld leve l.Enhan ce skills of th e tec hn ical and clin ical use of ant im icrobi al d rugs in th e fu ture .
-
8/8/2019 Principles of Antimicrobial Therapy Revised
3/22
Course cont entMec han ism / m ode of act ionSpec t ru m of act ivity
Bacterici dal and bacterios tat icCom binat ion of ant ibio t ic th er ap y
-
8/8/2019 Principles of Antimicrobial Therapy Revised
4/22
INTRODUCTIONDefine antimicrobials/Antibiotic and antibacterial drugs?
Antimicrobial drugs:Is an y subs tan ce of nat ural, synth e t ic or se m i-synth e t ic origin
that kills or inh ibits th e gro wth of a m icroorg an ism bu t causes littl e or no hos t dama ge .
Antibiotic:Is a subs tan ce produce d by a m icroorg an ism that, at l ow
conce nt rat ion, inh ibit or kills o th er m icroorg an ism s
Remark: Antimicrobial and antibiotic are often times used
interchangeably
Antibacterial:Drugs that inh ibit or des troy th e gro wth of bacteri a
-
8/8/2019 Principles of Antimicrobial Therapy Revised
5/22
Successful antimicrobial therapy is
based on 4 principles:-1. Ident ificat ion and cha racteris t ic of th e
path oge n(s), includes its ant im icrobi al se nsit ivity and se lec t ion of a d rug base d on th e sites of infec t ion
2. Effec t ive conce nt rat ion of th e ind icat edant im icrobi al a ge nt for sufficie nt p erio d at th e site of infec t ion.
-
8/8/2019 Principles of Antimicrobial Therapy Revised
6/22
3 . A dose rat e , Freque ncy, and, rou te of adm in ist rat ion of th e ant im icrobi al a ge nt, a s we ll as
durat ion of th er ap y, that max im izes th e like lihoo dof a cure , p re vent s re lap se and m in im izes th e risk of resis tan ce w ith ou t causing an y ha rm fu l drugind uce d effec ts in th e an imal.
4. Sp ecific and app ro p riat e su pp or t ive th er ap y to enhan ce th e an imal s ability to overco m e th e infec t ion and a ssoci at ed d ise ase cond it ion
-
8/8/2019 Principles of Antimicrobial Therapy Revised
7/22
Classes of antibioticsClassificat ion of ant ibacteri al d rugs that a re maj or use inve t. m ed icine Are of six maj or classes of ant ibio t ics:
1. Aminoglycosides (Stre pt omycin, n eo mycin, Kanam ycin,gentam icin) .
2.Cephalosporins (ce pha ce tril, ce phal oride , cef achlor e tc.3 .Macrolides (ery th romycin, Tylosin, sp iram ycin, t im icosin)4. Penicillins (Benzylpen icillns, Cloxacillin, am inobe nzyl-
pen icillins )5.Quinolones (nalidixic acid, ciprofloxacin, etc)6. Tetracyclines (oxyte tracycline , Te tracyclines L.A and
Doxycline e tc.
-
8/8/2019 Principles of Antimicrobial Therapy Revised
8/22
W hat are the mechanisms of action of antimicrobial/antibiotics?
The m ec han ism s of act ion of ant ibacteri al f all int o four cat egories or grou ps:
a ) Inh ibit ion of ce ll wall synth esis ,
b) Alter at ion of ce ll mem bran e per m eability,
c) Inh ibit ion of nuc leic acid synth esis or funct ion, and
d ) Inh ibit ion of p ro tein synth esis .
-
8/8/2019 Principles of Antimicrobial Therapy Revised
9/22
I) Inhibition of cell wall synthesis
An inta ct bacteri al ce ll wall kee ps th e bacteriu mfro m filling w ith wat er and burs t ing, th us th e d rug acts by inh ibit ing of an enzym e in th e
synth esis of th e ce ll wall
Sever al a ge nt s affec t ce ll-wall synth esis , th e
m os t imp or tant bei ng Pen icillins,Cephal os porins, Bacit ricin and Van comycin
-
8/8/2019 Principles of Antimicrobial Therapy Revised
10/22
II) Alteration in cell membranepermeability
They act on th e ph os ph o lip id la yer of th e ce llm em bran e to alt er per m eability
For instan ce po lymyxins int er act w ithph os ph o lip ids and cause leakage , pa rt icu larly in gram n egat ive bacteri a
Ex. Po lymyxin B
-
8/8/2019 Principles of Antimicrobial Therapy Revised
11/22
III) Inhibition of protein synthesis
Aminog lycosi des , Te t racyclines , Chloramph en icol, Ma cro lides and L incomycin all a ct by int erferi ng w ith th e nor maldeve lopm ent of th e pro tein com binat ions necess a ry for bacteri al gro wth.In th e gro wth pha se , th e process of linking toge th er am ino acids to for m a n ew bacteri al ce ll ha s to procee d in a cyclicalf ash ion and an y int erru pt ion of th e cycle locks th e process atth e point of int erfere nce and gro wth is halt ed.
Because of th e cont inuat ion of process wh ich ma y hav e bee naffec ted by th e int erru pt ing m ec han ism, th e over allint egr at ion of ce ll me ta bo lism is d isru pt ed and th e long-ter meffec t is so se vere that th e ce ll dies .
-
8/8/2019 Principles of Antimicrobial Therapy Revised
12/22
IV) Inhibition of nucleic acid
synthesisMa y block synth esis of nuc leo t ides , inh ibit re plicat ion or stoptran script ionSulfonam ides and t rim e th oprim block enzym es require d for
DNA and RNA synth esisIn so m e cases drug also comp e tes w ith n or mal subs t rat e for enzym es act ive site
-
8/8/2019 Principles of Antimicrobial Therapy Revised
13/22
-
8/8/2019 Principles of Antimicrobial Therapy Revised
14/22
-
8/8/2019 Principles of Antimicrobial Therapy Revised
15/22
Spec t ru m of act ion of ant ibio t ics
Ant ibio t ic spec t ru m of act ion refers to th e ran ge of bacteri a on wh ich a specific class of ant ibio t ic is effec t ive .
1. Na rro w spec t ru m Drugs act ing only on a single or lim ited grou p of m icroorg an ism s. i.e . isona zidis only act ive aga inst m ycob acteri a, p en icillinsa re prima rily effec t ive aga inst gram (+ ) bacteri a.
2. Bro ad spec t ru m d rugs act ing on a w ide varie ty of m icroorg an ism s. Ex. Te t racyclines ,chloramph en ical, e tc
-
8/8/2019 Principles of Antimicrobial Therapy Revised
16/22
Spec t ru m cont.
-
8/8/2019 Principles of Antimicrobial Therapy Revised
17/22
Activity (range) of various antimicrobial classes .
Bacteria Mycoplasma Rickettsia Chlamydia Protozoa
Aminoglycosides + +
Beta-lactams +
Chloramphenicol + + + +
Lincosamides + + +
Macrolides + + +
Pleuromutilins + + +
Tetracyclines + + + +
Quinolones + + + +
Sulfonamides + + + +
Trimethoprim + +
-
8/8/2019 Principles of Antimicrobial Therapy Revised
18/22
Bacterici dal and Ba cterios tat icBacterici dal ant ibio t ics KILL the bacteri a and th e to tal n um ber of viab le org an ism s decre ases .Baterici dal a ct ivity ma y occur if conce nt rat ion of th ese ant ibio t ics are h igh enoug h.In add it ion th e RATE and EXTENT of an im icrobi al a ct ivity ma y be :-
- Conce nt rat ion d epend ent ( aminoglycosides)- conce nt rat ion and t im e depend ent ( floroquinolones )- Tim e depend ent ( beta-lactams)
Exampl e of bacreici dal d rugs , Chloramph en ico l, Cephal os porins,Po lym oxin, Van comycin, Be ta la ctam s, Am inog lycosi des , e tc.
-
8/8/2019 Principles of Antimicrobial Therapy Revised
19/22
Bacterios tat ic ant ibio t ics ARREST the GROWTH andREPLICATIONof bacteri a at seru m leve ls ach ievab le
in th e pat ient, th us lim it ing th e sp re ad of infec t ionwh ile th e bo dy s imm une system atta cks,imm obi lizes and e lim inat es th e path oge n
Ex. Te t racyclines , Lincomycin, Ma cro lides
-
8/8/2019 Principles of Antimicrobial Therapy Revised
20/22
All ant im icrobi als a re bacterios tat ic at so m e conce nt rat ion
Som e ant im icrobi als a re bacterios tat ic at alm os t allconce nt rat ions, i.e . Te tracyclines Som e ant im icrobi als a re capa b le of bacterici dal a ct ivity if concentrations are high enough (and maintained for
long enough in some cases)Som e ant ibacteri al a ge nt s inh ibit th e gro wth of th e bacteriu m at one conce nt rat ion, th e m in im um inh ibitory conce nt rat ion (MIC ) (es , 0.2 5 ug/ ml ), bu t a h igher
conce nt rat ion, th e m in im um bacterici dal conce nt rat ion(MBC), is necess a ry to kill it (eg , 4.0 ug/ ml ).
-
8/8/2019 Principles of Antimicrobial Therapy Revised
21/22
Ant im icrobi al d rug com binat ion
Knowledge of th e d iffere nt m ec han ism s of act ion of ant im icrobi als provides so m e ability to pre d ict th eir int er act ion wh en th ey a re use d in com binat ion.
Indifferent or additiveThis is wh en th e com bined effec ts of th e drugs equ al th e
su m of th eir ind epend ent a ct ivit ies m easure d se pa rat e ly.Synergistic
Act ion of th e com binat ion a re sign ificantl y gre at er than th e ind epend ent effec ts.
For instan ce f acilitat ion of drug ent ry of one ant ibio t ic by an o th er, i.e . p en icillin and am inog lycoside
-
8/8/2019 Principles of Antimicrobial Therapy Revised
22/22
Anta gon istAct ion of th e com binat ion is sign ificantl y less than th e su m
of th e act ions of each comp onentMos t comm only cited is "bacterios tat ic drug inh ibits act ion of bacterioci dal".Anta gon ism ma y occur if ant ibacteri al com binat ions invo lve
1 . Inh ibit ion of bacterici dal a ct ivity in wh ich a bacterios tat ic drug pre vent s th e bacterici dal a ct ivity of an o th er
2. Comp e t it ion for drug-bi nd ing sites suc h a s ma cro lide-Chloramph en icol com binat ions