A substance that is :
1. produced by or synthesized from other microorganisms,
such as molds.
2. capable of destroying or weakening certain
microorganisms, especially bacteria or fungi , that cause
infections or infectious diseases.
3. inhibit pathogens by interfering with essential intracellular
processes as protein synthesis .
NB : Antibiotics are derived from three sources: moulds or
fungi; bacteria; or synthetic or semi-synthetic compounds.
And they don’t kill viruses.
Cell wall inhibitors,
such as Penicillin and
inhibitors, such as
Inhibitors of nucleic acid
synthesis, such as
such as the sulfa
Cell Membrane Damaging
Def. : Ability of a microorganism to withstand the effects of an antibiotic
through mutation or plasmid exchange between bacteria of the same species.
•Bacterium carries several resistance genes, it is called multiresistant or, informally, a
•What are Causes of Resistance ?? :
1. Antibiotic overuse, abuse, and in some cases, misuse, due to incorrect diagnosis.
2. Antibiotic use in animal husbandry .
3. Increased Globalisation (Movement and contact of people).
4. hospital settings often give rise to
antibiotic resistant bacteria.
prepared , are
Ex : Streptomyces
bacteria are ‘intrinsically’
resistance can be due to :
1. some genes responsible
for resistance to its own
2. lack a transport system or
a target for the antibiotics
3. increased efflux activity.
sensitive to antibiotics, but
are liable to develop
caused by mutations in
acquisition of mobile
genetic elements, such as
plasmids or transposons,
which carry the antibiotic
1. Reduced drug accumulation: by decreasing drug
permeability ,increasing active efflux (pumping
out) of the drugs across the cell surface.
2. Enzymatic inactivation ((β-lactamase inactivate
penicillin G )).
3. Alteration or over-expression of the drug target.
4. Loss of enzymes involved in drug activation. This
mechanism is relatively new.
5. Alteration of metabolic pathway((sulfonamide-
resistant bacteria ))
Is usually one that first appears three days after a patient is
admitted to a hospital or other health care facility.
1. Contact with contaminated hands of hospital staff
2. Contact with contaminated surfaces such as door handles,
overbed tables and call bells .
3. Contact with contaminated equipment, such as stethoscopes
and blood pressure cuffs.
4. Urinary bladder catheterization and respiratory procedures.
5. Surgery and wounds and intravenous (IV) procedures.
Examples on Hospital-Acquired Infetions :
a) Staphylococcus aureus .
b) Enterococcus (urinary tract infections).
c) Pseudomonas aeruginosa .
d) Acinetobacter baumannii .
e) proteus species .
•According to the CDC(Center for Disease Control) , the most
common pathogens that cause nosocomial infections are
Staphylococcus aureus, Pseudomonas aeruginosa, and E. coli.
•The common nosocomial infections are urinary tract
infections, respiratory pneumonia, surgical site wound
infections, bacteremia, gastrointestinal and skin infections.
Enterococci are part of the normal intestinal
flora of humans and animals .
important pathogens responsible for serious
includes more than 17 species but only a few
cause clinical infections in humans.
capable of cellular respiration in both
oxygen-rich and oxygen-poor environments.
Causes urinary tract infections, bacterial
endocarditis, and meningitis.
binds to the two D-alanine residues on the end of the peptide
chains No interaction with the cell wall cross-
linking enzyme inhibiting proper cell wall
Major side effects:
"Red man syndrome": RMS is characterized by :
flushing, erythema, and pruritus,
usually affecting the upper body,
neck, and face more than the lower body.
D-alanine residue replaced by a D-lactate, so vancomycin cannot bind
vancomycin cannot bind stable cross links are
formed successfully (normal cell wall synthesis)
Six different types of vancomycin resistance are shown by
Van-A, Van-B, Van-C, Van-D, Van-E and Van-F. Of these, only Van-A,
Van-B and Van-C have been seen in general clinical practice, so far.
Van-A VRE is resistant to both vancomycin and teicoplanin.
Van-B VRE is resistant to vancomycin but sensitive to teicoplanin.
Van-C VRE is only partly resistant to vancomycin, and sensitive to
NB : In the US, Linezolid is commonly used to treat VRE, as teicoplanin
is not available.
Vancomycin is contraindicated in patients with known hypersensitivity
to this antibiotic
via inhibition of protein synthesis by binding 23S
ribosomal RNA of the 50S subunit.
Major side effects:Diarrhea headache nausea.
MOR: point mutation , in which a guanine base is replaced
with thymine in base pair 2576 of the genes coding for
hypersensitivity to linezolid or any of the other product
Or patients with carcinoid syndrome .
or in patients taking directly and indirectly acting
sympathomimetic agents, vasopressive agents
with the presence of bacterial motility and fimbriae
Urease production by Proteus may favor the
production of upper urinary tract infections (UTIs)
by organisms such as Proteus.
1st Usually used for UTIs Methenamine (anti-bacterial agent).
Methenamine, an inactive weak base, slowly hydrolyzes in
acidic urine to ammonia and the nonspecific antibacterial
Urinary formaldehyde concentrations may be bactericidal or
1. An allergic reaction (shortness of breath).
2. Lower back or side pain.
3. Blood in urine.
4. Painful or difficult urination.
a. rod shaped bacterium has the ability to produce high levels
of urease,Urease hydrolyzes urea to ammonia (NH3).
b. makes the urine more alkaline stop Methenamine hydrolysis
and HCHO release
inhibit the topoisomerase II leaving the two
nuclease domains intact leads to DNA
Quinolones can enter cells easily via porins ,
therefore, are often used to treat intracellular
pathogens such as Legionella pneumophila and
For many Gram-negative bacteria, DNA gyrase is
By three Mechanisms :
1. efflux pumps act to decrease
intracellular quinolone concentration.
2. Gram-negative bacteria, plasmid-mediated
resistance genes, produces proteins that bind to
DNA gyrase, protecting it from quinolones.
3. mutations at key sites in DNA gyrase or
topoisomerase IV can decrease binding affinity to
with patient takes drugs metabolized by CYP1A2 as they
leads to increased plasma concentrations of Quinolones drugs Thus,
leads to clinically significant adverse events of the coadministered
For your Knowledge :
Proteus is a genus of Gram-negative Proteobacteria.
Widely distributed in nature .
Found in decomposing animal
matter, in sewage, in manure soil,
and in human and animal feces.
They are opportunistic pathogens
responsible for urinary and septic infections,
Most common pathogen isolated from
patients who have been hospitalized longer
than 1 week.
frequent cause of nosocomial infections such
as pneumonia, urinary tract infections (UTIs),
complicated and can be life threatening.
administered intravenously and intramuscularly. Some are used in
topical preparations for wounds.
Oral administration can be used for gut decontamination (e.g., in
act by binding to the aminoacyl site of 16S ribosomal RNA within
the 30S ribosomal subunit, leading to misreading of the genetic
code and inhibition of translocation.
Aminoglycosides should not be used in patients with:
a) previous vestibular or auditory toxicity due to an
b) serious hypersensitivity reaction to an
AMGs cross placenta ,not used in case of pregnancy
Major side effects:
a) Irreversible ototoxicity: loss of hearing, dizziness
b) Reversible nephrotoxicity.
c) Neuromuscular blockade may lead to respiratory
across the cell wall
mechanism of this
type of resistance is
up-regulation of the
have been shown to
2nd Treatment :
combination of an antipseudomonal beta-lactam
(eg, penicillin or cephalosporin) and an
3rd Carbapenems (eg, imipenem, meropenem)
with antipseudomonal quinolones may be used in
conjunction with an aminoglycoside.
MOA: Carbapenems act as penicillins on cell wall
destruction of bacteria.
Major side effects:
1-GI distress and skin rashes.
2-CNS toxicity at very hight plasma lvl.
one of the leading causes of infections acquired in the
community and after surgery or hospital.
30% of individuals carry S. aureus in their nose, pharynx or
back of throat and on their skin.
presence of S. aureus does not always indicate infection.
S. aureus can survive from hours to months, on dry
environmental surfaces, depending on strain.
Although it is not always pathogenic, it is a common cause of
skin infections (e.g. boils), respiratory disease (e.g. sinusitis),
and food poisoning.
The emergence of antibiotic-resistant forms of pathogenic S.
aureus (e.g. MRSA(Methicillin-resistant S.A) is a worldwide
problem in clinical medicine.
1st treatment of choice for S.aureus infection
is penicillins :
By binding to specific penicillin-binding proteins
(PBPs) located inside the bacterial cell wall,
inhibits the third and last stage of bacterial cell
Cell lysis is then mediated by bacterial cell wall
autolytic enzymes such as autolysins; it is
possible that penicillin G interferes with an
autolysin inhibitor. (( increased effect))
the bacterium produces the enzyme β-
lactamase or the enzyme penicillinase which
will hydrolyse the β-lactam ring of the
antibiotic, rendering the antibiotic ineffective.
Major side effects:
A. Hypersensitivity: difficulty breathing,
skin rash, hives, itching.
B. Stomach upset, diarrhea, nausea, and
like Methicilin or flucloxacillin or β-lactam antibiotics may be
co-administered with a β-lactamase inhibitor.
For example, Augmentin is made of amoxicillin, a β-lactam
antibiotic, and clavulanic acid, a β-lactamase inhibitor.
modification in the mecA gene of the bacteria which codes for
an altered penicillin-binding protein leads to a lower affinity
for binding β-lactams (penicillins, cephalosporins and
carbapenems). This allows for resistance to all β-lactam
3rd vancomycin is used.
stop the growth and reproduction of bacteria by disrupting
translation of messenger RNA (mRNA) into proteins in the
MOR: The intrinsic resistance of most Gram-negative bacteria
to linezolid is due to the activity of efflux pumps, which
actively "pump" linezolid out of the cell faster than it can
Gram-positive bacteria usually develop resistance in which a
guanine base is replaced with thymine in base pair 2576 of
the genes coding for 23S ribosomal RNA .
Acinetobacter baumannii is a species of pathogenic bacteria
involved in most nosocomial infections.
Aerobic gram-negative bacterium resistant to
Ventilator-associated pneumonia (VAP) is a sub-type of
hospital-acquired pneumonia (HAP) which occurs in people
who are receiving mechanical ventilation.
Many of the typical symptoms of pneumonia will either be
absent or unable to be obtained in VAP why ??
Ans. : because People who are on mechanical ventilation are
often sedated and are rarely able to communicate.
The most important signs are fever, low body temperature,
new purulent sputum, and hypoxemia (decreasing amounts of
oxygen in the blood).
inhibits bacterial wall synthesis like other B-lactam antibiotics. In
contrast to other B-lactams, it is highly resistant to degradation
1. Resistance generally arises due to mutations in penicillin binding
proteins. or resistance to diffusion across the bacterial outer
2. The most widespread B-lactamases with carbapenemase activity in
A. baumannii are carbapenem-hydrolysing class D beta-
lactamases (CHDLs) that are mostly specific for this species.
Unlike imipenem, it is stable to dehydropeptidase-1 and can
therefore be given without cilastatin.
Limiting the Spread of Drug Resistant
A. Ensure that antibiotics are used only when
B. Ensure that they are used for the
appropriate amount of time.(( Complete to
be fully effective and not breed resistance))
C. Third strategy for limiting drug resistance is
to use antibiotics combinations.
Development of New Antibiotics.
Mobilisation of Host Defence Mechanisms,This
can be achieved through :
1. the mobilisation of innate immunity such as
defensins((They are small Cysteine-rich cationic
proteins, and function as host defense peptides
Cells of the immune system contain these
peptides to assist in killing phagocytosed
2. through the development of vaccines, which
make antibiotics less necessary.