- - -Of- - *

UNIVERSTTY JORDAN
Faculty OF Medicine ,
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LECTURE NO: 8.

~~~ DONE BY:c~~1 ~

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 Anti-micro bial drugs

* There are different groups of anti-microbial dlUgS and each group is directed against mainly
one target of the bactelial cell, but also there are celtain drugs which affect more than one
target

• Features of anti-microbial drugs

1- In order to be effective they should have selective toxicity against celtain types of
microorganism, (not for the human body); i.e. to target parts of the bactelial cell either by
inhibition or by killing.
2- There is no single drug has 1000;() efficiency without cenain side effects.

• each drug after shon or long peliod might cause celtain side effects but these side
effects are calculated according to
a) The amount of doses.
b) Duration of the action ofthe dlUg.
c) The site of action, because for example there are drugs affect only the Ulinaly tract, or
only the intestines.

3- The dlUgS affect growing cells especially in the lag phase (back to the bactelial grO\\1h
curve) where the bactelia cel1 is velY 8ctive in replication ,doubling of the cell and building
of the cell membr8ne; so most types of drugs affect the b acteli al cells dUling this phase.

4- Their gi\'ing depend on:

• The age 0 fthe palient

• Tllelypeofinfeclion
• E\islence ofimlllunodeficiency diseases.
• The lype oflhe in fecling bacteliulll: ie i fit is gr,llll +\'e/ gralll-\'e or aerobic/

,lll aerobic.

5- The anti-microbial dmg not necessalY kills all types ofbactelia. And according to this we
have three impoI1ant telTI1S:

• Narrow spectrum the anti-microbial dmg affects a small range of bacteli a, ex:
affecting gram +ve bactelia only or mainly Such as Penicillin G and Penicillin V.

• Broad/ wide spectrum: the anti-microbial dmg affects a wide range ofbactelia. ex:
gram +ve and gram -ve.

• ·Moderate spectrum: betNeen the previous two spectmms.

**the expelience and training give you the ability to know \\Then to use these types.

6- Each one of anti-microbial dmgs has specific routelroutes of administration, for example
some dmgs can be inactivated by acids of stomach so we can't give them (the dmgs) orally,
but either intravenously or intramuscularly

** There is an important classification ofanti-microbial drugs:

1- Bactericidal: the dmgs that can kill the grmving microorganisms, and should not be
used together at the same time

2- Bacteriostatic the dmgs that inhibit the multiplication ormicroorganisms without ki11ing.

*** Types of anti-microbial dmgs

A) Beta-Iactanl drugs:

• Produce damage to the cell wall (affect ollly one targel).

• They cont~lin bela-Llcl~lm ring which include J carbon aloms ~llld 1 nitrogen ~llOJll

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 • Beta-Iactam drugs belong to the group of penicillin or cephalospOlin

• Any change in side chains can produce valiety of drugs

1- PENICILLIN:

1\1\ Penicillin G

• The first penicillin drug Oliginated from an organism cal1ed- Penicil1ium notatum- in
(1940-1941),

• Used in treatment of gram +ve bactelial infections especially aerobic ones

• Destroys the cel1 wall components so its action mechanism is bactelicidal.

• Was given only by injection; because it was easily inactivated by the acidity of

stomach so wasn't given orally~ therefore they modified penicillin G structure and

produced after n:vo years the folJo\ving type

''\''\penicillin V:

• Acid stable penicillin drug so can be taken orally,

• Also used in treatment ofgrame +ve aerobic bacteria,

*** The action olpenicillin

As you Know the cell \\~lll 01 gr,1111 +\e ,ll1d gram -\'e bacteria contain a peptidoglycan
byer \\llich composed olunbranched heteroploys,lcha,ide Ch,lillS Witll cross-linKing
polypeptides consist of'sm,I11 number ol,lmino ,lcic\s i111portlllt Illl' rigidity and G\,ltion of'
tile cell \\,111. also IlX 1',lcing the bl'gc osmotic pre:;slIl'C llil tile CytUIlbsl1lic melllhr,llle

\11\1111l":C eJ('ss lillkillg ,111lill(1 ,ll'ids I'I'l',dllU:L1 11> CIl/\lllL" 11l:111l,I\C :llfinll\, Illl'lil'l1ll'illill

c:llk,IIJ C11 illlllll UillLlillg hl\ICllh (IJIWs)

Therefore exposing the bactelia to the penicillin win lead to binding ofPBPs to penicillin
resulting in inhibition of these PBPs and damage to the cell wall, leading to the death of
the bactelia

** As I mentioned before that penicillin G andY are examples ofnalTow spectrum because
they affect mainly the grame +ve bactelia, so we need drugs that can affect both gram
+ve and gram-ve ;therefore they modifJed the structure of penicillin by changing the
side chains to produce like these dmgs Thus they produced }unpicillin and Amoxicillin
in (1965) as example of wide spectmm bactelia, which have and additional effect on
facultative aerobic bactelia especially that found in the intestines

** Before that in few years they found that bacteria began to produce celtain enzymes that
can break the beta-Iactam ring called penicillinase or beta-lactamase; and that because the
fact that bactelia have a huge potential in their genes to produce specific polypeptide and
proteins canied by its plasmid and can easily spread to other types of bacteli a for using it
in developing resistance against celtain drugs,

** and they found that Penicillin became less effective against gram +ve staphylococcus
(25% pfall infections related to our body whether skin, nose, respiratOly and urinary
tracts" ,etc, all caused by staphylococcus); so penicillin drugs \vere then modifJed to
produce ANTI-PENICILLINASE dmgs, such as;

] -Methicillin in (1961)

• The fJrst drug produced to affect penicininase,

* It is not being used any more,

• it si not stable and it will be inacti\'ated a\ roomtemperClture. and has cel1Clin side
errec\s~ so they modiGed it to produce the next to types:

2- Oxacillin

• We use it in the labora\ory. and in the c1inical practice

J- Cloxacillin

• (}\:leillin, e[,l\:leillill :II'[cetlll:lilll\ ~1:11ll+ Il' h:ll'tui:l. Illliell Iml\IIIl!\.' 11l'llieillill:l:'l'

l'lI/\'IllC:;

4
4-Augmentin it's composed of amoxicillin and c1avulanic acid (clavulanic acid is not
anti-microbial dmg, it is a chemical stmcture), and this dmg ( augmentin) has a broad
spectmm used for gram +ve and gram -ve bactelial infections (remember that
amoxicillin and ampicillin are not beta-lactamase inhibitors)

** Although amoxicillin and ampicillin are affecting both gram +ve and gram -ve
bactelia, but they affect gram-ve in relation to certain group called Enterobactelia.
So they produced dmgs that affect mainly gram-ve, especially 'vvhich produce infections
in the hospital, such as pseudomonas which cause sedous infections to the patients in the
environment ofthe hospital called Nosocomial infections (nosocomial= hospital; i.e:
hospital acquired infections)

• and here some important examples of these dmgs which developed in the mid of
seventies

1- Carbencillin
2- Piperacillin
3- Ticarpacillin

• in 1990s and because ofvaliety of infections they developed new penicillin (beta­
lactam) dmgs which are resistant to penicillinase and affect mainly gram-ve bactelia,
for example:

A) Monobactam

• Represented by Aztreonam.

• More effective than carbencil1in, piperacil1in, tecaracillin.

B) carbapenem

• Represellted by Imipellem.
• 'ntrod L1ced 7 yelrs ~lgO
• E\pensi\e. \\ide spectrulll dnlg lh~ll arTecls gr;llll -\e(lll~lilll:') ~IllJ gr~md\T h~IC1C1'i~1
cspeci~111\ \\Ilich ~lre resisLlllt tll \ll:llicillinllrugs
• l !:;l'd Illlrc~i\ SlTI(llI.S iJlrl'clil)lls

s
** Despite all penicillin types
and wide spectum activity we have a microorganism called
acinetobactar that manages to resist all types of penicillin and cephalospOlins dmgs.

• The history of cephalospOlins is almost parallel to the history of penicillins

• cephalospOlins dmgs have been anange into generations (according to the date of
development).

The (irst generation:( beginning o(1960s).

* Ex Cephradine, Cephalexin, Cephalothin.
• Their using is being decreased with time because they have nanower spectmm than
other dmgs and they are not effective witl1 developing bactelia.

• Their activity is similar to ampicil1in and amoxicil1in.

The second generation:( between 1970s and 1980s)

• E:; Cefaxitill, Cefuroxill1e

• Broad speclmm activity and aflect facu1tati\e ~lerobic bacteria.

• Stl11 in use especially in surgeries.

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The third generation:( mid 1980s to mid 1990s).
• Ex: Ceftriazone~ Cefotaxime~ Ceftazidime.

• Mainly against gram-ve bactelia.

• Doctor (3asem) expects that these dmgs in the next 5 years will not be available.

The fourth generation:(in 1995).

• Ex: cefepime.

• This cefepime affects mainly gram -\Ie bactelia like pseudomonas

• Still used in hospital.

******* General information about cepltalosporins:

1- cephalospOlins were used mainly in 1970s and 1980s in the treatment ofrespiratOly,
Ulinaly tract infections, blood sepsis also wound infections.

2- The problem with the cephalospOlins, firstly they can't affect anaerobic bactelia well.
Secondly they can't affect the enterococcus group which been recognjzed as a UlinalY
tract infecting agent after the introduction of cephalospOlins because they are
naturally resistant to cephalospOlins.

3- Cephalosp01ins Oliginated lrom an orange rJ1amentous Fungus called

cephalospolium

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 ** The bactelia that produce Beta-lactamase are developing with the time and becoming
more dangerous. And they are divided into the fol1owing

1- Specific beta- lactamase bactelia; i.e resistant for certain types ofbeta-lactam dlUgS
such as penicillin G.

2- extended beta-lactamase bactelia (more dangerous);

• Related to mainly to gram -ve bactelia especially intestinal bacteria.

• It will inhibit all type of beta-lactam dlUgs except the Carbapenem group so it can be
used for treatment of this type but as a final solution because it is velY expensive.

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** Side effects of beta-lactam dlUgS

• Sensitization, fever, selUm sickness, penicillin allergy, anaphylactic shock,

nephlitis.
• Note there are 1-3% of the population have a hypersensitivity to penicillin
which is very dangerous especially ifit given by injection

B) Other types of anti-microbial drugs that cause damage to the bactelial cell wall by affecting
the cross-linking amino acids. Such as"

1- peptidog/rcal1 drugs, ex: Bacitracil1.

• ,4.. lIects gram+ve ,md gram-ve.

• Composed ollarge # of amino acids (almost 60)

• This bacitracin is excellent to be use as topical treatment for skin in fections: i.e
should not be gi\en orally or by IV or 1M injections or lor a long time because it has
se\er side effects tllat couldld be controlled

, g/l'co{Jc{Jridc drl/!;s, ex: /·II1ICOlllpill, TcicojJ/(/lIill.

 • Very useful dmgs in clinical practice.

• They used in case that gram+ve bactelia (like enterococcus) are resistant to a]] type of
penicillin dmg including methicillin.

• They are used as injectable not as oral fmID.

• If the staphylococcus group is resistant to penicillin G and V then secondary to

ampicillin and amoxicillin and finally to methicillin, then you should use the
vancomysin.

• Fortunately in Jordan a]] staphylococcus considered as susceptible to vancomysin

• Recently a case has been discovered in another countly shmving that there a type of
bactelia begins to develop a resistance to vancomysin and this is velY dangerous
leading to quick death

C) Third type of anti-microbial dmgs \'/hich affect the integlity of the cell membrane considered
as bactelicidal Represent by

J- Colistin:

• O1iginated from large group called polymixen

• Has an amino and nitro groups

• it is a \'ery to\.ic drug.

• Used for treatment of serio liS infections ex acinetobacter (which CJuse septicemia)
and in topical treatments

• Remember \\e alw,l)'s treat acinetobacter \\itl1 co list ill despite its side e fTects
2- Antifungal drugs:

• They are complex stlUctures of floro, nitro, hydro, chJoro groups.

• Used for fungal infections caused either by yeast or by filamentous fungi.

* considered as toxic dlUgS.

• These antifungal dlUgs divided in 3 types

1- polyene drugs, ex:

/\ M, nystatin(used for topical treatment by oral means for skin and hair infections).

/\'/\/\amphotercin(used for systematical infections)

2- imdazole group.

3- triazole group, ex: tluconazol (used for systematical infections)

Best wishes,

Suhaib Sa\\ajneh
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