Antibiotic

Lecture Notes

Definitions:

chemotherapy: Drug treatment for the diseases caused by bacteria and

other pathologic microorganisms, parasite and even tumor cell.

Under this term comes the antimicrobial drugs.

antimicrobial drugs: drug used for treatment of infectious diseases.

Under this term comes the antibiotics.

Antibiotic: Substances produces by various species of microorganisms ,

bacteria , fungi and actinomyctes to kill or to suppresses the growth of
other microorganisms.

.It could be natural or semisynthatic .

Characteristic of ideal antibiotics :

1)Selective toxicity:

Ability to kill or inhibit the growth of harmful bacterial organism regardless

of site of infection with minimal or no harmful.

Kill bacteria but does not harm the host cell🙂.

It works on things that have different structure or function from the host !
So it is necessary that the bacteria has a different structure or function for
selective work .

2)Therapeutic dose:

Drug concentration require for clinical treatment,,

3)Spectrum of activity: broad, narrow, or extended spectrum of activity.

Wich describes whether the drugs work on a large or small group of targets.

4)Action : either be bactericidal,bacteriostatic or both.and this gives us 2

categories of antibiotics.

5)Favorable pharmacokinetics: should reach its target site at effective

concentration.

6)Side effects: have a tolerable side effects and little resistance

development.

7) Should have a tolerable residue

8) Should be affordable

9). MIC : Should have a defined Minimum Inhibitory Concentration (MIC)

Categories of antibiotics:

1)Bacteriostatic

- Reversibly inhibit growth: once you stop the drugs,, bacteria back to it's
growth again

- Duration of treatment sufficient for host defenses to eradicate infection

- the immunocompramised patients has no immune capacity to irradiated

the bacteria even if it's growth is inhibited so they better not be given
bacteriostatic drugs.

2)Bactericidal

- Kill bacteria

= Usually antibiotic of choice for infections in sites such

as endocardium or the meninges where host defenses

are ineffective.

This actions above depend on factors:

Concentration dependent killing . Depending on amount of the drug.

Time dependent killing . Depending upon time .

Post antibiotics effect.

CLASSIFICATION OF ANTIBIOTICS:
▪ Antibiotics have been classified in different ways, but the commonest
classification is based on :-

1)molecular structure

2)mechanism of action and

spectrum of activity.

3)route of administration.

4)whether it kills or inhibit the

growth of microorganisms.

Classification based on molecularstructure:

• Beta-lactams: Penicillins, Cephalosporins,Carbapenems, Monobactams.

• Tetracyclines and glycylcyclines: Tetracycline,

Tigecycline, Doxycycline, Minocycline,Chlortetracycline, Oxytetracycline.

Chloramphenicol:Chlorampheniol

•Aminoglycosides:Gentamicin,Amikacin,Tobramycin,Netilmicin,Streptomyci
n,Neomycin, Kanamycin.

•Quinolones:Ciprofloxacin,Norfloxacin,Levofloxacin,Moxifloxacin,
Gemifloxacin,Ofloxacin, Enrofloxacin.

•Macrolides and Ketolides:Azithromycin,Telithromycin,Erythromycin,

Clarithromycin

•Lincosamides: Lincomycin, Clindamycin,Pirlimycin.

•Glycopeptides:Vancomycin,Teichoplanin,Telavancin,ramoplanin,
decaplanin

•Streptogramins: Quinupristin/Dalfopristin,Pristinamycin, Virginiamycin

Sulfonamides: Sulfadiazine, Sulfamethizole,Sulfamethoxazol, Sulfasalazine,

Sulfisoxazole.

• Trimethoprim: Trimethoprim

Polymixins: Colistin, Polymixin B

Oxazolidinones: Linezolid,Tedizolid.

Lipopeptides: Daptomycin, Surfactin,Mycosubtilin.

Classification based on mechanism of action :

1) Interference with cell wall synthesis: Beta lactams, glycopeptides

2) Inhibition of protein synthesis: macrolides,aminoglycosides,tetracyclines.

3)Interference with nucleic acid synthesis:quinolones

4)Inhibition of folate biosynthesis and( one carbon unit metabolism

sulphonamides and co-trimoxazole).
5)Disorganizing the cell membrane structure or function.

Classification based on spectrum of activity:

1) Extended spectrum: antibiotics that have effect against bacterial,

rickettsial and protozoan organisms for example, tetracyclines.

2)Broad spectrum: antibiotics that are effective against both Gram-positive

andGram-negative

bacterial organisms for example quinolones.

3)Narrow spectrum: antibiotics that are only effective against either Gram-
positive or Gram-

negative bacterial organisms for example,macrolides.

Classification based on route of administration:

1) Oral: antibiotics that are administered through the oral cavity.

2)Parenteral: antibiotics that are administered through injection.

3)Topical: antibiotics that are administeredthrough application on body

surfaces.

Classification based on killing effect:

• Bactericidal: antibiotics that exert theirtherapeutic effect through killing

the bacterial agents.

• Bacteriostatic: antibiotics thatexert their therapeutic effect through

inhibiting the growth of bacterial agents.
Principles and Definitions:
Important Definitions:
Antimicrobial activity: the ability that a drug kills or suppresses the growth
of microorganisms.

The minimal inhibitory concentration (MIC):

The minimum amount of a drug required to inhibit the growth of bacteria in

vitro.

The minimal bactericidal concentration (MBC)

The minimum amount of a drug required to kill bacteria in vitro.

Combination therapy:
- Prevent emergence of resistant strains

* Act on different types to avoid resistance .

* When we take a sample of blood or urine from a patient .

-Temporary treatment until diagnosis is made

- Antibiotic synergism

• Penicillins and aminoglycosides

Effects of Combinations of Drugs:

Synergism occurs when the effect of two drugs together is greater than the
effect of either alone.

Usually when giving bacteriosidal with bacteriosidal both working at the

same time with different mechanisms .

Antagonism occurs when the effect of two drugs together is less than the
effect of either alone
Usually when giving bacteriosidal with bacteriostatic .

Common Bacterial Pathogens by Site of Infection :

Certain bacteria have a propensity to 1commonly cause infection in

particular body sites or fluids.

• Antibiotic may be chosen before results of theculture are available based

on some preliminary information

>> Site of infection and likely causative organism

» Gram-stain result (does result correlate with potential organism above).

Antibiotic (2)

Lecture Notes

Beta Lactams :
•Have Beta-lactam ring .

•Important groups are (PCCM)Paracetamol:

Penicillins.

Cephalosporins .

Monobactams .

Carbapenems.

Mechanism of Action :
(Inhibition of Peptidoglycan synthesis:cell wall):

• Bacterial cell wall comprised of Peptidoglycan having linear chains of 2 alternating

amino sugars : N acetyl glucosamine (NAG) , and N acetyl muramic acid (NAM) . Wich
are cross linked with peptide chains ( transpeptidation ) and gives rigid mechanical
stability to the cell wall .
• a transpeptidation reaction is responsible for cross linking to give strength. It's done
by a transpeptidase enzyme wich also has a carboxypeptidase activity.

• B lactams Prevent the cross linking peptides from binding to the tetrapeptide side.
They so exert their function by Inhibition of cell wall synthesis and disrupting it's
integrity.

• Action is bactericidal in a time dependent manner.

• the binding side of them is called Penicillin Binding Protein (PBP) and it's at the
enzyme that formes the cell wall .

• Penicillin inhibits cell wall synthesis by binding to the enzyme transpeptidase (PBP)
that cross links the sugar side chains .

This leads to :

- weakness of cell wall.

- swelling of the bacteria deu to endosmosis.

- bacterial cell membrane bursts.

- bacterial lysis.

Two additional factors are involved in the action of penicillin:

1. Penicillin binds to a variety of receptors in the bacterial cell membrane called

PBPS.Some PBPs are transpeptidase, the function of other is unknown.

2.Autolytic enzymes called murein hydrolase's are activated in P-treated

cell, degrade the peptidoglycan.

Mechanism of Resistant :
• Production of B lactamase enzyme: hydrolyzed B lactam ring causing
inactivation( most important and most common).

•altration of PBP leading to decreased binding affinity.

•alteration of outer membrane leading to decreased penetration.

 Penicillin :
Source:

-Was originally discovered by sir Alexander Fleming in the filtrate of culture mediam of
mold penicillium notatum having bactericidal action on staphylococci.

- p.chrysogenum a mutant of p.notatum is presently used for commercial production of

antibiotics.

- penicillin was the first antibiotic to be used clinically in 1941 signaling commencement
of golden Era in chemotherapy.

- The natural penicillin is benzyl penicillin (penicillin G) wich is 6-aminopenicilanic acid

with benzyl side chain.

Notes:

• basic structure of penicillin comprises of a thiazolidin ring (T) connected to Beta

lactam ring (B) to wich a side chain (R) is attached through an amid linkage .

•the natural penicillin known as benzyl penicillin is thermo labile and acid labile.

•the semisynthatic penicillins have been developed by adding different side chains to it
with unique antibacterial activity and variable pharmacokinetics.

Resistance against Penicillin

Natural:
•Target enzymes and PBPs are deeply located (Lipoprotein barrier in-ve).

•PBPs of organisms have low affinity for penicillin.

Aquired:
•Production of Penicillinase (Beta-Lactamase) enzyme, (>300 subtypes).

•Common organisms producing Beta-Lactamase are:

-Staphylococcus

-Bacillus subtilis

-Gonococci

-E. coli

-Enterococci

-Haemophilus influenza

•Loss or alteration of Porin channels in gram negative

•Modification of penicillin binding proteins (PBPs) -having low affinity.

•Activation of antibiotic efflux mechanism- Some gram negative bacteria.

Spectrum of activity :
Natural :
Acid labile: Penicillin G , procain penicillin, and bandaging penicillin.

Acid stable : Penicillin V ( phenoxymethyl penicillin) .

•Soluble Sodium or potassium salts of benzyl penicillin (Penicillin G): Destroyed by

gastric acid (orally inactive) and penicillinase. Given IV, IM, or SC, onset of action within
half an hour and duration of action only 3 hours.

• Sparingly soluble organic salts of penicillin G or repository penicillins.

•Procaine penicillin G: Administered IM (never IV), onset of action within 6-8 hours,
destroyed by gastric acid and by penicillinase and duration of action 12-24 hours.

Benzathine penicillin G: Administered IM (neverIV), onset of action slow and duration of

action 3- 4 weeks.

Penicillin G :
• Short duration.

• Acid unstable

• Penicillinase (B-lactamase) sensitive

• Used in infections caused by streptococci, meningococci, enterococci &
non-ß-lactamase- producing staphylococci.

Procaine penicillin :
• Long acting (every 12 h).

• Acid unstable (I.M.I).

•Penicillinase sensitive.

• Used to prevent subacute bacterial endocarditis due to dental extraction

or tonsillectomy in patients .with congenital or acquired valve disease.

Benzathine penicillin :
•Long acting (every 3-4 weeks).

•Acid unstable.

•Penicillinase sensitive

•Treatment of B-hemolytic streptococcal.

•Once a week for 1-3 weeks for treatment of syphilis (2.4 million units I.M.).

•Used as prophylaxis against reinfection with B- hemolytic streptococci to

prevent rheumatic fever.

Penicillin V ( acid resistant penicillin) :

• Less effective than penicillin G.

•Acid stable

•Penicillinase sensitive

•Short acting ( four times/day)

•Used in minor infections.

Semisynthatic :
Can be penicillinasd resistant, B lactamase Inhibitors and
extended spectrum.

Penicillinase resistant penicillin:

i). Acid labile penicillins:
Methicillin and nafcillin.
ii ) Acidresistant penicillins:
Flucoxacillin,oxacillin,cloxacillin, and dicloxacillin.

Penicillinase-Resistant Penicillins:(nafcillin, oxacillin,

methicillin) :
Developed to overcome thepenicillinase enzyme of S.
aureus which inactivated natural penicillins.
Gram-positive methicillin-susceptible : S. aureus , Group
viridans streptococci.

Extended spectrum penicillins:

•These are not penicillinase resistant.
i). amino penicillins: Effective against Gram positive
and Gram negative bacteria: Ampicillin,bacampicillin,
talampicillin, pivampicillin and amoxicillin.
ii). Carboxypenicillins: These are active against
Pseudomonas aeruginosa and proteus Spp, but
ineffective against Klebsiella and Gram positive
cocci:( Carbenicillin and ticarcillin).
iii)Ureidopenicillins: Active against Pseudomonas and
Klebsiella; - Mezlocillin and piperacillin
iv)Amidinopenicillin: Mecillinam and pivmecillinam: -
These are highly active against Gram negative bacilli
(E.coli, Salmonella, Klebsiella and Enterobacter, but not
against Pseudomonas and Gram positive cocci.
v) Amino penicillins: Ampicillin and Amoxicillin
•Therapeutic uses: ( H. influenza infections and E. coli)
•Ampicillin (not amoxicillin) is effective for shigellosis &
complicated salmonella infections.
• Prophylaxis of infective endocarditis.
• Urinary tract infections: Effective against penicillin-
resistant pneumococci.
Beta Lactamase inhibitors:
•Beta-lactamase inhibitors enhance the activity of beta-
lactam antibacterials against beta-lactamase-
producing bacteria.
•These agents cause irreversible inhibition of many
plasmid-mediated and some chromosomal beta-
lactamases. They result in successful inhibition of beta-
lactamases produced by gram-positive bacteria.
• Beta-lactamase inhibitors are generally less effective
against chromosomally mediated type 1 beta-lactamases.
Examples of B lactamase Inhibitors:
•Clavulanic acid : is used in combination with amoxicillin
and ticarcillin.
•Sulbactam: Sulbactam sodium is used in combination
with ampicillin and cefoperazone.
•Tazobactam: used in combination with piperacillin.

Adverse effects of penicillin:

• Hypersensitivity reactions ( including Anaphylaxis) most
commonly with procainpenicillin.so intradermal sensitivity
test must be done.
• high dose cause renal failure and seizures.
•nafcillin cause neutropenia
•Oxacillin cause hepatitis
•Methicillin cause nephritis
•Oral penicillin may lead to GIT upset
•Ampicillin associated with Pseumembranus colitis
•Increase in prothrombin time leading to bleeding.
•Jarmusch herxheimer reaction ( common in secondary
syphilis) .

Drug interactions:
-With tetracyclines , chloramphenicol, Erythromycin :
antagonism interaction .
- with Aminoglycosides: Synergism interaction .
- with hydrocortisone ( penicillin alone or penicillin with
aminoglycosides) : inactivate each other ; pharmaceutical.
- Ampicillin with Allopurinol: high incidance of
nonurticarial maculopapular rashes.
- penicillin with probenecid :prolonged action of penicillin
by decreased tubular secretion.

Antibiotic (3)
Lecture Notes
Cephalosporins:
• Cephalosporin antibiotics derived from "cephalosporin C"
obtained from fungus Cephalosporium acremonium.
•Cephalosporin nucleus Consists of dihydrothiazine ring
fused to a ß-lactam ring , and 7-aminocephalosporanic
acid.

Mechanism of Action :
- just the same mechanism of action of a B-lactam group
in general.
-All cephalosporins are bactericidal.
- MOA same as penicillin- Inhibit cell wall synthesis , in a
manner similar to penicillins . But , it Bind to different
proteins than those which bind penicillin. PBP-1 &PBP-3.
This explains diffrance is spectrum, potency & lack of
cance
- Inhibition of transpeptidation. So ,
• Imperfect cell wall

• Osmotic drive 》 hyperosmosis

•Activation of autolysin enzymes leading to Lysis of
bacteria
• So it is BACTERICIDAL.
(the same steps like what we said about pincillin. )
CLASSIFICATION:
Based on The following criteria,Cephalosporins are
classified into 5 generations :
1-antimicrobial spectrum (spectrum of activity )
As you go to the next generation you have wider spectrum.
2-Chronological sequence of development( No. 1 then No
2 and so on ) .
3-Divided into generations.
First generation Cephalosporins:
we have the following drugs:
-Cephalexin (0) , very famous drug : cephalex
-Cefadroxil (0)
-Cefazolin (i.m, i.v) , parental
-Cefalothin (withdrawn), no need to it.
oral , can be in Capsule or serum
Spectrum of activity : mainly they act against gram -
positive bacteria especially, gram - positive cocci. and
have a very moderate activity against gram- negative
bacteria especially, gram negative Bacilli. )
- Exhibit good activity against gram-positive bacteria but
modest activity against gram negative organisms.
- Most gram-positive cocci- Strepto,- Pneumo,-Methicillin
sens. Staph. are susceptible to first-
generationcephalosporins
- Modest activity against E. coli, K. pneumoniac & Proteus
mirabilis.
- most oral cavity anaerobes are sensitive .
Generally: spectrum is wide in gram-positive and not in
gram-negative.

Second generation Cephalosporins:

-Cefaclor (Oral)
-Ceforanide
-Cefuroxime acetil (0ral)
-Cefuroxime (i.m, i.v)
-Cefoprozil
-Cefamandole (Banned)
-Cefoxitin (Banned)
-Cefotetan (Banned)
• Cefaclor, Cefuroxime acetil(0ral),Cefuroxime (i.m, i.v) and
Cefoprozil , these are the commonest antibiotics in 2nd
generation
•Exhibit somewhat increased activity against gram
negative organisms,but much less active than third
generation agents.
• Less active against gram positive cocci & bacilli
compared to first gen. drugs.So use is declined .Clinically
replaced by 3rd & 4th generation drugs.
• and if infection is by gram-positive bacteria 1st
generation Cephalosporins is used.
Third-generation agents:
very important group of drug:-
-Cefpodoxime
-Ceftizoxime
-Ceftazidime
- Cefotaxime.
-Ceftriaxone ( very common used antibiotic )
-Cefdinir
-Cefibuten
-Cefoperazone (withdrawn).
• Cefotaxime and Ceftriaxone,are very important
drugs and commonly used , they has a lot of market
names.
•Ceftazidime also is very important . It has a
combination with B lactamase Inhibitors.
•High -augmented activity against gramnegative
organisms
•But Less active than first generation agents against
gram positive cocci & anaerobes so less active than
2nd generation against gram-positive bacteria
as it has activity against gram negative organisms
All are highly resistant to ß-lactamases from gram
negative bacteria.
• some of thdm can inhibit psuedomonas. Example :
Ceftazidime .
•some members of this group have enhanced ability
to cross the blood-brain barrier .so used in treatment
of Meningitis. Example : Ceftriaxone: is effective in
treating meningitis caused by pneumococci
,meningococci, H.influenzae and these are the most
common causes of the disease in children and
adolescents and susceptible gram negative rods. It's
sometimes given before investigation .

Fourth-generation agents:
-Cefpirome P/E (im/iv)
-Cefepime P/E (iv) 》 the common one .
-Cefozopran P/E.
•Highly active against G-ve organisms
•Similar to third gen drugs for g +ve bacteria . but
more resistant to hydrolysis by B-lactamases.
•effective against bacterial infections resistant to
earlier drugs. ( in earlier generations) .
• effective against psuedomonas
•as we go forward in generations drugs are more
effective in gram -ve bacteria,but best in Gram-
positive is first generation .So in prophylaxis in
surgery,first generation is given, because we are
concerned about wound infection wich is commonly
caused by drugs which can be used effectively first
generation therapy.

Fifth-generation agents:
- Ceftobiprole
- Ceftaroline
• Active against g +ve cocci especially MRSA,
penicillin resistant S. pneumoniae and
enterococci( not enterococci general but penicillin
resistant enterococci)
•Its called lather antibiotics.

Resistance:
just like resistant in pincillin.
1- Impermeability to the antibiotic. ( difficult to
antibiotic to reach its target) to reach its site of
action.
2-Alteration in PBPS- So antibiotics bind with low
affinity.
3-Elaboration of ß-lactamases; that can hydrolyze
the B-lactam ring and inactivate the cephalosporin
(the most prevalent mech)

Common Adverse reactions:

1• Pain after im injection.
2• Thrombophlebitis of injected vein.
3• Diarrhoea more common with certain drugs:
- oral Ceferadine 1st gen

- P/E Cefoperazone (Banned)

Hypersensitivity reactions:
- Identical to penicillins, but the incidence is lower
than penicillins, shared ß-lactam structure
- Allergic to penicillins ; allergic to cephalosporins.
And we call this CROSS-REACTIVITY.or cross-
allerginisity .
- Rashes, frequent, anaphylaxis, angioedema,asthma,
urticaria have also occurred.

Cephalosporins potentially nephrotoxic drugs:

-Cephaloridine (withdrawn) RTN
-Cephalothin (withdrawn) Acute tubular necrosis
Serious bleeding:
-Cefoperazone(Banned),
-Moxalactam(Banned).
- Due to hypoprothrombinemia.
So they are not used anymore.

General overview of Therapeutic Uses of these

drugs is that its very commonly used antibiotics in
treatment and prevention.

First Gen agents:

• Excellent for skin & soft tissue infections because
it's
commonly caused by gram positive cocci. (strep or
stap)
• Surgical prophylaxis first generation drugs are
the preferred for prophylaxis in procedures in which
skin flora are likely pathogens. So the best antibiotic
for prophylaxis is the 1st generation drugs.

HeNS
H. Flu
Second Gen agents:- N . Miningitidis
Seraatia

• Displaced by third generation agents for Gram

negative infections.
• Oral-RTI (replaced by augmentin)
*augmentin : Amoxicillin +clavulanic acid*
Third Gen agents:-
• With/without aminoglycosides.

DOC :
For severe G-ve infections(in compination with or
without aminoglycosides) caused by:-
Kleibsiella
Enterobacter
Proteus
Providencia
Serratia & haemophillus species.

Ceftriaxone:
- is the therapy of choice for
all forms of Gonorrhea.
- 250 mg i.m as single dose.
Or :-
- i.v ceftriaxone for enteric fever
Cefotaxime & ceftriaxone:
-Community aquired pneumonia as it's common
caused by S.pneumoniae.
- For initial treatment of Meningitis. Because :-
# Antimicrobial activity of it can cover all bacteria
that causes meningitis.
# can cross the blood-brain barrier.
They are DOC - Meningitis due to
• H. influenzae
• Sensitive S. pneumonae
• N. meningitidis
And some other G-ve enteric bacteria.
# Ceftazidime can work against psuedomonas .
Ceftazidime + aminoglycosides:
- Psuedomonas meningitis DOC
Fourth Generation Agents:-
Same as third generation drugs But :
• Indicated for hospital acquired
• infections resistant to commonly used antibiotics.
Hospital acquired is usually deu to psuedomonas/
MRSA , together with Acinetobacter baumannii.
Antibiotics(4)
Lecture Notes
Other B-lactam antibiotics

Newer classes of ß-lactam antibiotics are the

•Monobactams
•Carbapenems
•Carbacephems(the newest)
• Important therapeutic agents with a ß-lactam
structure & are neither penicillins nor cephalosporins.
Monobactams:-
■ Aztreonam :
• Isolated from fungi ( chromobacterium violaceum)
• Only monobactam currently in clinical use ß-lactam
ring, lacking the thiazolidine ring that is present in
penicillin and cephalosporins.
•Antimicrobial activity differs from those of other B-
lactam antibiotics & more closely resembles that of
an aminoglycoside
Primarily affects :
-Aerobic gram negative microorganisms
- resistant to gram positive and anaerobic bacteria.
-Preferred in all sorts of gram negative infections in
patients with renal impairment where
aminoglycosides are to be avoided .
-Stable to most ß-lactamases elaborated by gram
negative bacteria.
Monbactams does not show cross reactivity with
penicillin thats why it is used in severe infectins in
people with penicillin allergy
Note :
•It is given i.m/i.v
• Therapeutic conc. in CSF in the presence of
inflammed meningitis (Meningitis before using the
drugs to be more effective ) , Alternative to
cephalosporins for therapy of meningitis caused by
G-ve bacilli

■Carbapenems:
-The common drug that we use this days
-B-lactam antibiotic
-Broader spectrum of activity: more than most other
B-lactams.So given to patients in the ICU when we
don't know the causative agent (gram-negative rods
or gram-positive bacteria or anaerobes.)
-buf has high cost .
Examples of Carbapenems:
-Imipenem ( not preferred)
• Derived from compound produced by
Streptomyces cattleya.
• Mechanism same as penicillins (Bactericidal)
•Resistant to hydrolysis by ß-lactamases ( work on
gram +ve , -ve and anaerobes)
• Marketed in combination with cilastin ( to prevent
renal degradation by dehydropeptidases) Without
cilastin renal dehydropeptidases inactivate the drug
which results in low urinary tract concentrations.
Adverse effects:
• Nausea, vomiting.
•Seizures or convulsions, some sort of confusion,
psychosis, so patients must be aware that this drug
causes psychological effects. Doctors must be
careful especially in patients in ICU / PICU
• Patients allergic to other ß-lactam antibiotics may
have hypersenstivity reactions when given imipenem.

-Meropenem(the most common one)

• Therapeutic equivalence with imipenem. But
Coadministration with cilastin not required.
•Meropenem is less seizure producing compared to
imipenem.

Ertapenem:
New drug
• Differs from imipenam & meropenem larger
serum half life, OD. So can be given daily for a month.
•Co-administration with cilastin not required
•less seizure producing compared to imipenem.

Notes
■ All are parenteral.
- i.v, im painful
•Imipenem 6 hrly
• Meropenam 8 hrly
■All are resistant to ß-lactamases
• All bactericidal
• MOA samebPatients allergic to other ß-lactam
antibiotics mayhave hypersenstivity reactions when
given imipenem/carbapenems.

Therapeutic uses:
• Urinary tract infections
• Lower respiratory tract infections
•Intra-abdominal & gynaecological infections.
What is the causative agents in Intra-abdominal
infection
Most likely by anaerobes (gram +ve or gram -ve)
anaerobes like bacteriod non spore-forming , gram
+ve or gram -ve ( eg a person after abdominal
surgery)
• Skin, bone, joint, & soft tissue
infections
•Especially cephalosporin/ penicillin resistant
nosocomial bacteria.( hospital infections.)
■Carbacephems:
The Newest antibiotic
- Loracarbef
-Synthetic ß-lactam antibiotic Similar to cefaclor
-Antibacterial activity resembles II generation
cephalosporins.

What are the anti-psuedomonal B-lactams ? (Very

common question)
1- Anti-psuedomonal penicillin:-
carboxypenicillins (carbenicillin and ticarcillin),
acylureidopenicillins (azlocillin and mezlocillin), and
one piperazine penicillin derivative (piperacillin).
2- Anti-psuedomonal cephalosporin:-
Ceftazidime 》 3rd generation
4th and 5th generations
3- Anti-psuedomonal Carbapenems:-
Imipenem , meropenem and Ertapenem.
On osmosis was said this is the only
one thats not effective against
pseudomonas

Inhibitors of Nucleic Acid Synthesis: RNA

/ DNA
1- Inhibition of DNA synthesis:-
■Fluoroquinolones:
The quinolones are a family of synthetic broad
spectrum antibiotics.
The first important class is nalidixic acid, had limited
spectrum ( Narrow ) of antimicrobial active against
G ( - ) , than G ( + ) bacteria .
They added a group of fluorine to quinolones to
make fluoroquinolone »New class of Quinolones
Fluoroquinolones «
The Available FQs:
» Norfloxacin
» Ciprofloxacin
» Levofloxacin
» Gatifloxacin
» Moxifloxacin
>> trovafloxacin
>> grepafloxacij
>> sparfloxacin
Mechanism Of Action :
Inhibit bacterial topoisomerases which are
necessary for DNA synthesis ( inhibit DNA synthesis )
DNA gyrase - removes excess positive supercoiling
in the DNA helix .
Topoisomerase IV - essential for separation of
interlinked dauguter DNA molecules .
Bactericidal activity .
‹ If it asks you to talk about the fluoroquinolones
mechanism of action , DON'T write inhibiting the
DNA synthesis only ,
YOU MUST TO BE SPECIFIC AND Detailed ›

Mechanism Of Resistance :
Altered target sites : Chromosomal mutations in
genes that code for DNA gyrase or topoisomerase IV
.
Most important and most common mechanism of
resistance .
Altered cell wall permeability : Decreased porin
expression
Porins are located in the cell membrane .

Spectrum Of Activity :
Gram positive Gram negative :
Including Pseudomonas aeruginosa ( anti -
Pseudomonal effects )
Anaerobes :
Only trovafloxacin has adequate activity against
Bacteroides sp.
Atypical Bacteria :
All FQs have excellent activity against atypical
bacteria including :
» Legionella pneumophila - DOC .
» Chlamydia sp .
» Mycoplasma sp .
» Ureaplasma urealyticum .
Other Bacteria Mycobacterium tuberculosis (2nd line)
Bacillus anthracis ./

Fluoroquinolones Adverse Effects :

gastrointestinal - 5% :
– Nausea , Vomiting , Diarrhea ,Dyspepsia .
Central nervous system :
– Headache, agitation, insomnia, dizziness, rarely
hallucinations and seizures (elderly) .
Hepatotoxicity :
LFT elevation (lead to withdrawal of trovafloxacin) .
Phototoxicity : ( Uncommon with current FQs)
Common with older FQs (halogen at position 8) .
Cardiac :
Variable prolongation in QTc interval .
Led to withdrawal of grepafloxacin, sparfloxacin .
Articular damage :
Arthopathy including articular cartilage damage,
arthralgias, and joint swelling .
Observed toxicology studies in immature dogs .
Led to contraindications in pediatric patients and
pregnant or breastfeeding women .
– Risk versus benefit .
Other Advers Reaction :
Tendon rupture , Dysglycemias , Hypersensitivity
■Metronidazole:
Is a synthetic nitroimidazole antibiotic ( flagyl )
derived from neomycin . First found to be active
against protozoa , and then against
anaerobes(specially against abdominal infections)
where it is still extremely useful .
Mechanism Of Action :
Ultimately inhibits DNA synthesis In anaerobic
bacteria not aerobic
Metronidazole displays concentration - dependent
bactericidal activity .
Mechanism of resistance well documented but is
relatively uncommon .

Spectrum Of Activity :
Anaerobes Bacteria : Anaerobes Protozoa
Bacteroides sp. (ALL) Specially fragilis(abdominal
Surgery) Trichomonas Vaginalis Fusobacterium
Entamocba histolytica Prevotella sp.Giardia Lamblia
Clostridium sp. (ALL) Gardnerella Vaginalis
Helicobacter pylori(microaerophilic)

2-RNA synthesis inhibitor :

■Rifampin:
Interacts with the bacterial DNA- dependent RNA
polymerase(RNA polymerase), inhibiting RNA
synthesis .
Antibacterial Spectrum :
Mycobacteria, gram positive, gram negative .
Used to treat carriers of meningococcal or
H.Fluenzeae (prophylactic use)
Also used for treatment of :
mycobacterum tuberculosis
Leprosy
brucellosis (2nd drug)

Resistance : very important

Develops rapidly during therapy . Should use in
combination with other drugs to decrease resistance
rates .
Decreased affinity of the polymerase .
Metabolized in the liver and may induce the
cytochrome p 450 system . ( Hepatotoxic drug and
change color of urine )
2 - fidaxomicin

Antibiotic (5)
Lecture Notes
Protein synthesis inhibitors
Target the bacterial ribosome .
Bacterial - 70s (50s/30s)
Mammalian - 80s (60s/40s)
High level may interact with mammalian ribosomes .
50s binders - Macrolides , Clindamycin ,
Chloramphenicol , streptogramins.
30s binders - Aminoglycosides, Tetracyclines ,
Spectinomycin .
Chloramphenicol :
( Bacteriostatic ) Mode Of Action :
Inhibit protein synthesis by binding to the 50s
ribosomal subunit and blocking the action of
peptidyltransferase , this prevent the synthesis of
new peptide bonds .

Spectrum of activity :very limited use

They have a broad - spectrum antimicrobial activity
against G ( + ) , G ( - ) including anaerobes ,
Chlamydia .
Oily form is used in gonococcal meningitis In developing
countries
Resistance to Chloramphenicol :
Resistance to Chloramphenicol is by two
mechanism :
Enzyme acetyl transferase acetates into acetyl
esters .
Reduce nitro group on the molecule .
Chloramphenicol Toxicity :
Irreversible plasticity anemia .
Transient bone marrow depression .
( These hematologic changes reverse rapidly when
the drug is stopped ).
‹ It was used as Typhoid treatment before but NOT
anymore

Macrolides:
( Bacteriostatic )
Nature Macrolides : Erythromycin
Semisynthetic Macrolides : Clarithromycin
Azithromycin
Mechanism Of Action :
They act by inhibition of protein synthesis of cell wall
proteins , they bind the 50s subunit and block the
translocation step .
Mechanism Of Resistance :
Active efflux : Pumps the macrolides out of the cell
away from the ribosome. Altered binding sites .
Cross - resistance occurs between all macrolides .
( If there is resistance to erythromycin for sure it
gets resistance against azithromycin or
clarithromycin ) .
Macrolides Spectrum Of Activity :
Gram positive aerobics :
Erythromycin and Clarithromycin display the best
activity . ( Clarithro » Erythro » Azithro )
Gram negative aerobics :
Newer macrolides with enhanced activity .
( Azithro » Clarithro » Erythro )
H.influenzae ( Not erytho ) M.catarrhalis , Neisseria
sp.
Do not have activity against any Enterobacteriaceae .
Anaerobes :
Activity against upper airway anaerobes . Atypical
bacteria :
All macrolides have excellent activity against
atypical bacteria including :
Legionella pneumophila – DOC .
Chlamydia sp .
Mycoplasma sp .
Ureaplasma urealyticum . Other bacteria :
Mycobacterium avium complex ( MAC - only A and C
)
,Treponema palladium , Campylobacter , Borrelia ,
Bordetella
, Brucella , Pasteurella .

Clindamycin:
Clindamycin is a semisynthetic derivative of
lincomycin .
Mechanism Of Action :
Inhibits protein synthesis by binding exclusively to
the 50s ribosomal subunit .
Bind in close proximity to macrolides - competitive
inhibition.
Clindamycin typically displays bacteriostatic activity .
Mechanism Of Resistance :
Altered binding sites .
Active reflux .
Clindamycin Spectrum of Activity :
Gram positive aerobes :
Methicillin - Susceptible Staphylococcus Aureus
(MSSA only ) .
Streptococcus Pneumoniae (only PSSP) - resistance
is developing .
Group and viridians Streptococci
Anaerobes :
Activity against above the diaphragm anaerobes
( ADA )
Peptostreptococcus some Bacteroides sp.
Actinomyces Prevotella sp.
Propionibacterium Fusobacterium Clostridium sp.
( Not C. difficile )
Other bacteria :
Pneumocystis caring , Toxoplasmosis gondii ,
Malaria .
50s binding antibiotics:

Macrolides:
-Natural macrolides(very cheap) :
•Erythromycin
-semisynthetic macrolides:
•Clarithromycin
•Azithromycin
•Roxithromycin(semisynthetic, long acting, acid
stable, spectrum =erythromycin, and given in BD
doses)
mechanism of action:
•macrolides act by inhibition protein synthesis in the
bacterial cell, binds to 50s subunit and block the
translocation steps. (-Bacteriostatic.)
mechanism of resistance :
•active efflux: most common, pump the macrolide
out of the cell away from the ribosome.
•altered target sites
•Cross resistance occurs between all macrolides.
spectrum of activity :
•Gram positive Aerobes-> erythromycin and
Clarithromycin display the best activity ( clarithro>
erythro> azithro)
•Gram negative Aerobes-> newer macrolides with
enhanced activity( azithro>clarithro> erythro). e.g. H.
Influenzae(not erythro), M catarrhalis, Neisseria.
*don't have activity against any
enterobacteriaceae( except campylobacter jejani)
•Anaerobes->upper respiratory tract anaerobes..
•Atypical bacteria -> have excellent activity against
atypical bacteria including :
-Legionella pneumophilia-DOC
-Chlamydia sp
-Mycoplasma sp
-Ureaplasma urealyticum
-Other bacteria : mycobacterium avium complex,
treponema pallidum, campylobacter jejani , borrelia,
bordetella, Brucella, pasteurella.
Clindamycin:
-is a semisynthetic derivative of lincomycin.
mechanism of action
•inhibits protein synthesis by binding exclusively to the 50s
ribosomal subunit(binds in close proximity to macrolides-
competitive inhibition)
•typically Bacteriostatic

-mechanism of resistance:
•altered target sites(most common) .
• active efflux

-spectrum of activity :
•Gram positive Aerobes->
-methicillin susceptible staphylococcus Aureus
(MSSA) -streptococcus pneumoniae
-viridans streptococci
•Anaerobes ->activity against above the
diaphragm Activity :-peptostreptococcus
-actinomyces
-propionibacterium
-some bacteroids sp
-prevotella sp
-fusobacterium
-clostridium sp(not C. Diffic
•other bacteria ->pneumocystic carinii,
toxoplasmosis gondii(fungal and parrasital
infection), malaria .

Oxazolidinones:
-linezolidis the first available agent.
-linezolid is a semisynthetic oxazolidinone
which is a structural derivative of earlier agents
in this class.
-mechanism of action of linezolid :
•binds to the 50s ribosomal subunit near to surface
interface of 30s subunit, causes inhibition of 70s
initiation complex which inhibits protein synthesis.
•Bacteriostatic

-mechanism of resistance :
•alteration in ribosomal binding sites (RARE).
-spectrum of activity :
•Gram positive bacteria ->
-methicillin susceptible, methicillin resistant , vancomycin
resistant staph aureus, and coagulase negative
staphylococcus.
-streptococcus pneumoniae, viridans streptococcus, group
streptococcus.
-enterococcus faecium and faecalis (including VRE)
-bacillus, listeria, clostridium sp except C. Difficile,
peptostreptococcus, p.acnes.
•Gram negative Aerobes -> relatively inactive
•Atypical bacteria -> Mycoplasma, Chlamydia, Legionella.

30s binding antibiotics :

Aminoglycoside:
-gentamycin, streptomycin, and amikacin.
-mechanism of action :
•multifactorial, but ultimately involves inhibition of protein
synthesis
•irreversibly bind to 30s ribosome disrupting initiation of
protein synthesis, decreasing overall protein synthesis,
and produce misreading of mRNA
•are bactericidal
-mechanism of resistance :
•alteration in Aminoglycoside uptake( decrease
penetration of Aminoglycoside)
•synthesis of Aminoglycoside-modifying enzymes
(plasmid mediated, modifies the structure of the
Aminoglycoside which leads to poor binding to ribosomes
• alteration in ribosomal binding sites
-spectrum of activity :
•Gram positive Aerobes ->
•Gram negative Aerobes->
•Mycobacteria->
-Tuberculosis : first line(streptomycin), second line
( injectable Aminoglycoside) -atypical :streptomycin or
amikacin.

-Adverse effect(side effect, bc of long use) :

•ototoxicity (8th cranial nerve damage, vestibularand
auditory toxicity, irreversible)
Nephrotoxicity
Countraindicated in pregnant women
And myathenia gravis because of its nmj activity

Tetracycline :-
Natural:
•chlortetracycline
•oxytetracycline
•tetracycline
-semisynthetic :
•doxycycline
•minocycline
-mode of action :
Reversibly bind to the 30s ribosome, and inhibit binding of
aminoacyl-t-RNA to the acceptor site on the 70s ribosome.
-Bacteriostatic
-spectrum of activity
• a broad spectrum antimicrobial activity against Gram (-)
& (+), including : Chlamydia, Mycoplasma, Legionella.
-Adverse effects
•tetracycline are deposited in growing bones and teeth
with depression of linear bone growth. *so not given
during pregnancy or to young children.
•suppression of normal flora of the bowel flora resulting in
increased secondary infections

Spectinomycin:
-Mode of action :
•spectinomycin Reversibly interferes with m-RNA
interaction with the 30s ribosome.
•It is structurely similar to the Aminoglycosides but
doesn't cause misreading of mRNA
•Bacteriostatic
-spectrum of activity
•Used in treatment of penicillin resistant Neisseria
gonorrhoea. -resistance :
•rare in Neisseria gonorrhoea.

Newer Drugs:Ketolids:
-Telithromycin:
•it is a macrolide with ketogroup, that binds with ribosome
with greater affinity, and resists efflux mediated, and
methylase mediated resistance => thus is effective
against many macrolide resistant organisms.
•approved for multidrug resistant respiratory tract
infection.

Glycopeptides:
Vancomycin(produced by streptococcus orientalis) :
-effective against staph(second choice due to
toxicity),streptococci and clostridium.
Staph aueres
Staph epider.
Strep pyo genus
Cl . Dificile
-it is-bactericidal by interrupt cell wall synthesis.
-it inhibits cell wall synthesis by binding firmly to the D-Ala-
D-Ala terminus of nascent peptidoglycan pentapeptide,
this will interrupt transglycolase preventing further
elongation of peptidoglycan and cross linking, and thus
cell become susceptible to lysi

Miscellaneous:
-poor oral absorption, so given as IV infution( used orally
only for local effect in git
-more than 90% excreted by kidney.
-used in MRSA, pneumococcal infections, and Vancomycin
resistant enterococci(VRE)

Antibiotic (6)
Lecture Notes

Miscellaneous and Newer antibiotics:

- Drugs with poor orally absorption, so it is given as I.V infusion
(used orally only for local effect on G.I.T)(Dose is usually -1 gm IV
12 hourly )
-More of 90% of it excreted by kidney .
-Indications (uses of drug ):
 Methicillin resistant staph infections(MRSA)
Antibiotic associated Colitis
Enterococcus endocarditis
Penicillin resistant pneumococcal infection .
-Side effects :
Fever , chills, phlebitis
Extreme Flushing(called RMS-red man/neck
syndrome)(caused by massive release of histamine by rapid
infusion of drug )
-Other histamine liberators are: Morphine, tubocurarine ,
polymyxin B
Nephrotoxicity
Ototoxicity
Newer Antibiotics :
1/Teicoplanin:
-It is similar to Vancomycin but safer(very expensive )
- used only in vancomycin allergy .
-Can be administered by I.M route
-Adverse reaction : Headache, etc
2/Cycloserine :
-It is produced by streptomyces orchidaceous.
-It inhibit cell wall synthesis.
-Used orally.
-It is used as 2nd line for E.coli and T.B
3/fusidic acid:
Similar to prednisolone Inhibt the protein synthesis through inhibition of elongation factor 2

-It is steroidal antibiotic (usually given tropically)

-It is effective against penicillinase producing staph.
-Mechanism of action : reduce a factor necessary for elongation
of peptide chain.
-It is used as reserved drug for osteomyelitis because it has good
bone penetration.
-It has dual interaction with Penicillin .
Polypeptide Antibiotics:
-They have low molecular weight.
-They are peptides but lack antigenicity(they don’t act like
antigens)
-They are: Polymyxin B, Polymyxin E, Bacitracin , Capreomycin
1/Polymyxin B and E:
-They are narrow spectrum bactericidal antibiotics
-Not absorbed orally.
Negative
-They are effective against gram + organisms(like : pseudomonas
except proteus and Neisseria)
-Side effects :They are systematically nephrotoxic (that is why
used only locally)
-Polymyxin E is also called Colistin .It is used for infective diarrhea
in a child or to alter gut flora in hepatic failure .
-They are surface active , cationic detergent .
-Mechanism of action : They interact with phospholipid of
bacterial cell membrane and alter its permeability so the vital
substances will leak out and cell dies.
-Indications of polymyxin B: local infection of eyes, skin, ears,
mucous membrane.
2/Bacitracin:
-It is bactericidal antibiotic
-Mechanism : It is inhibit cell wall synthesis Bactoprenol inhibitor
Used tropicaly

-Side effect : Highly nephrotoxic so it is used locally only in

combination with Neomycin and/or Polymyxin (the drug of this
combination is called Nebasulf =Neomycin +bacitracin+
sulfacetamide -powder and ointment)
3/Capreomycin:
-It is bacteriostatic .
-It can be used for 2nd line drug for T.B
-Side effect : Highly nephrotoxic and vestibular toxicity .
4/Mupirocin(pseudomonic acid):
-It is rapidly inactivated after absorption so it is used mainly
tropically .
-Indication : It is used for staph(highly sensitive to it) so it is
effective against impetigo (but can become resistant if applied to
large surface area )
Small note : MRSA carriers can carry S.Aureus in their nose.So
they can be given Mupirocin .
5/Quinupristin and Dalfopristin :
5/Quinupristin and Dalfopristin :
-It is combination drug of Streptogramin A(Daflopristin ) and
Streptogramin B (Quinopristin ) in ratio of 70:30
‫الشغلة عكس التوكسينس هنا الضالفة بتفتح للكوين‬
-Mechanism of action : Daflopristin increase sensitivity of 50s
ribosome to enhance the binding of it to Quniopristin , this lead to
decrease in polypeptide elongation and terminate protein
synthesis due to decrease in 50s ribosome.
-This combination has rapid bactericidal effect which remain for
longer time period .
-Indications : Serious MDR-multiple drug resistant- staph and
strep, and pneumococcal infection
-They are soluble semisynthetic derivatives of Pristinamycins.
-It is used as I.V infusion in 5% dextrose solution for an hour, but
injections can cause pain, arthralgia , phlebitis, myalgia .
6/Linezolid :
-It is synthetic oxazolidinone with unique site of action (23S
ribosomal subunit of 50s ribosome )
-Mechanism of action: It binds to 23S ribosomal subunit of 50s
ribosome and prevent formation of 70s ribosome complexes so
inhibit assembly.
-There is no cross resistance (due to its unique site of action).
-Effective against gram + aerobic and anerobic organisms but not
against gram – ones.
-Indications : Last resort for MDR staph and strep , and
pneumococcal infections.
-Its oral and I.V doses are the same (oral bioavailability is 100%).
7/Fosfomycin :
-It is safe for pregnancy
-Mechanism : it decrease cell wall synthesis and transported by
G6PD transport system .
-It is used for selective cases of UTI.
8/Spectinomycins :
-It isn’t bactericidal .
-Mechanism of action: Similar to aminoglycosides(binds to 30s
subunit of ribosome in gram – bacteria )
-Indications: It is reserved drug for resistant N.Genorrhea (single
dose)
Other glycopeptides :
1/Oritavancin and Dalbavancin :
-It is used for GISA (Glycopeptide intermediate susp. And Staph
Aureus ) and MRSA (Methicillin resistant staph aureus )
-Oritavancin is analog of Vancomycin also effective against
Vancomycin resistant enterococci (VRE)
-Dalbavancin is similar but not effective against VRE.
-Regarding administrations :
Oritavancin has long t1/2 so it permits once a day
administration.
Dalbavancin has prolonged retention in organisms so can be
administered once a week.
Pleuromutilins :
 Pleuromutilins :
-It is newer class of antibiotics .
-Mechanism of action : It binds to 50S subunit of ribosome
inhibiting protein synthesis
-Example of approved drug : Retapamulin
-It is topical antibiotic
-Indications: Used for skin infection such as impetigo by Staph
aureus(methicillin susceptible only ) or step pyogenes.
Macrocyclic antibiotic drug :
1/Fidaxomicin (dificid )-2011:
-It is narrow spectrum bactericidal agent
-Mechanism of action : It inhibits bacterial enzyme RNA
polymerase
-Indications: selective eradication of clostridium difficile .

Antimicrobial therapy :
Disease (pathogen) Drug of 1st Alternative drug
choice
Gram + cocci : TMP-SMZ, Eryth, Quinols,
cephalosporin(II, Azithromycin ,
Morxaxella catarrh
III) Clarithromycin

N.Genorrhea Ceftriaxone Cefoxitin , Spectinomy

,Cefixime,
Quinol
N.meningitidis Penicillin G Chloramph,
 cephalosporins III
Gram – rodes(aerobic) Cephalosporin Quinols, Aminog.s
I/II, TMP-SMZ
E.coli, proteus, klebsiella
Enterobacter, Serrt TMP-SMZ, Antipseud. ,
quinols,Imipene Penicillin,Aminoglycosi
m des, Cefepime,
Shigella Quinols, TMP-SMZ, Ampicillin ,
Cefixime ,Ceftriaxone
Salmonella TMP-SMZ, Chloramphenicol
quinols, ,Ampicillin
Cephalosporin III
Campylobacter Jejuni Quinols , Tetracycline , furazolid
erythromycin
Brucella Sp Doxycycline , Chloramphenicol +
Rifampicin , aminoglycoside or
aminoglycoside TMP-SMZ
s
H.Pylori Bismuth+Metro+ Omeprazol
tetracyclin or +Amoxicillin or
amoxicillin clarithromycin
Vibrio Sp Tetracycline , Quinols
TMP-SMZ
P.Aeruginosa Antipseudomon Antipseudomonal
al penicillin+Quinols,
penicillin+Amino Ceftazidime ,
glycosides imipenem/Meropenem
or Aztreonam
+Aminglycoside
Legionella Sp Erythromycin Quinols
+Rifamp (+rifamp),clarithromyci
 n
Gram + cocci (aerobic): Penicillin Ceftriaxone
,Cefatox,vancomycin
Strep pneumonia
,TMP-
SMZ,Eryhthromycin ,
imipenem/Meropenem
S.pyogenus Penicillin, Erythromycin ,
clindamycin cephalosporin
S.agalact Penicillin Vancomycin
(+aminoglycosid
e)
S.Viridans Penicillin Vancomycin ,
cephalosporin
Staph. Aureus (beta lactamase Penicillin Vancomycin ,
-ve) Cephalosporin

Staph. Aureus (beta lactamase Penicillinase

+ve) resistant
Penicillin

Staph. Aureus (methicillin Vancomycin TMP-SMZ,Minocyc

resistant )
Enterococcus sp: Penicillin Vancomycin
+aminoglycosid +Aminoglycoside
e
Gram +ve bacilli : Vancomycin Imipenem/Meropenem
,Quinols,Clindamycin
Bacillus (non anthrax)
Listeria Sp Ampicllin+Amin TMP-SMZ
oglycoside
Nocardia Sp Sulfadizine ,TMP Minocyc,
-SMZ Imipenem/Meropenem
, Amikacin
Anaerobic bacteria: Penillin Vancomycin ,
,Clindamycin Amikacin ,
Gram
Imipenem/Meropenem
+ve(clostridium,peptococcus,ac
tinomyc,peptostreptococcus
Cl.difficile Metro Vancomycin
,bacitracin
Bacteroids fragilis Metro, Imipenem/Meropenem
clindamycin , chloramphenicol
,beta lactamase drugs
Fusobacterium Metro, Vancomycin
clindamycin , ,bacitracin,
penicillin Imipenem/Meropenem
, chloramphenicol
,beta lactamase drugs
M.Tuberculosis Isoniazid Streptomyc, Quinols
+Rifampin+etha ,Amikacin
mbutamol ,cycloser,PAS,
,pyrazinamide ethionamide
M.Leprae (Multibacillary ) Dapsone+Rifam
pin+clofazimine
M.Leprae (paucibacillary ) Dapsone+Rifam
pin
M.Pneumoniae Tetracycline , Azithromycin ,
erythromycin clarithromycin
Chlamydia.Trachomatis Tetracycline , Azithromycin ,
erythromycin clindamycin, Ofloxac
Chlamydia.pneumoniae Tetracycline , Azithromycin ,
 erythromycin Clarithromycin
Spirochetes : Doxycline, Erythromycin ,
penicillin chloramphenicol
Borellia recur
Leptospira sp Penicllin Tetracycline
Treponema sp Penicllin Tetracycline ,
erythromycin