ANTISEPSIS.ppt

Lecture for general surgery
Chorna I.A.
2019

1846-70
The removal of pain made doctors
over confident. They took too long
and infection rates went right up

Made doctors wash their
hands (in lime chloride)

Noticed that
CARBOLIC ACID was
used in sewers to kill
the smell. Started to use
it in operations to kill
germs. It was sprayed
all over the place.

Very expensive
 Very uncomfortable –
acid burnt
the skin

ASEPTIC SURGERY
Instead of killing germs, remove
them altogether by sterilising
everything

There are four types of antisepsis:
• - mechanical antisepsis - all mechanical means directed to
eliminate the necrotic tissue, foreign bodies, to drain the
secretion of the wound;
• - physical antisepsis - when there are developed
conditions suppressing bacterial activity: cold, heat,
wound dressings, drainage tubes, physiotherapy.
• - chemical antisepsis - when there are used various
chemical substances with a bactericidal or bacteriostatic
activity;
• - biological antisepsis - all methods that helps to raise the
immune activity of the organism and helps to maintain
the physiology of the wound: antibiotics, bacteriophages,
serums, vaccines, immobization, rest of the patient;
•

Mechanical Antisepsis is the
mechanical removal of infected and
non-viable tissue.
• In essence - the primary debridement. Timely
made, it turns the infected wound in aseptic
operating wound healing by first intention.
• Manual is used as an antiseptic surgical wound
toilet, which removes foreign bodies, necrotic and
nonviable tissue is performed the autopsy streaks
and pockets, the washing of wounds, and other
manipulations aimed at cleansing of infected
wounds.

Mechanical
Antisepsis
Toilet
of wound
Secondary
debridement
Other
manipulation
Primary
debridement

Is the creation of unfavorable conditions for
development of microorganisms in a wound and for suction
of microbe toxins and products of tissue decay by an
application of physical factors
Physical antisepsis starts from the law of capillarity,
hygroscopicity, diffusion, osmosis, siphoning, heat, moist
heat , dry heat , filtration, low temperature, radiation,
ultrasound, laser effects and other.
hygroscopic bandaging material
Hypertonic solution
Drainage of wounds
Sorbent
Technical agents (means)
environment factors

Physical antisepsis
hygroscopic bandaging material
Technical agents (means)
environment factors
Sorbent
Drainage of wounds
Hypertonic solution

Dressings materials - a material intended to protect the wound
from secondary infection, they are drying, processing the
operational field, stop bleeding, as well as for immobilization of
organs, tissues.
By dressing materials and finished dressing products include:
cotton, gauze, alihnin, bandages, dressings packs, gauze wipes,
aseptic bandages, gauze, cotton swabs, etc..
They put a number of requirements, namely: they must have good
suction capacity, be flexible, should not irritate the body tissues, the
application should not constitute separate fibers which can clog the
wound should undergo sterilization to be cheap and accessible to a
broad and wide application.

The drainage provides the outflow of wound contents
and promotes the removal of toxins, microbes and
products of tissue decay. Irrigation of gauze with
hypertonic solutions highly increases its hydroscopic
quality. But tampons with wound exudation prevent
the outflow from the wound, which is why they are
not good for drainage. Can be
Passive
Active
Continuous
irrigation drainage

Application sorpbents is based on the removal biological
fluid, toxins, microbes from the septic wounds, ulcers,
burns. The following indications for the use of sorbents in treatment
of septic wounds:
Phase of inflammation
• 1. High exuding wounds: gelling agents based on
polyvinyl alcohol - gelevin, kollavin, lizosorb, geleyodon
(Russia); Melolin (UK); TenderWet, Comprigel (Germany).
• 2. With moderate exuding wounds: products based on
carboxymethylcellulose fine - geletsel, tsellosorb
(Uzbekistan) hydrogel dressings - Geliperm, Wigilon,
Algoplaque, Traumasive (Germany), DermaDress (SSHA),
Scarlet Red (Canada), Opragel, Hydrocoll (Germany);
dextran preparations - Debrisan, (Sweden), oxidized
cellulose (Oxydized cellulose) and its modifications
(Belarus, Russia, SSHA, Germany); profezim, silica,
Aerosil; polymethylsiloxane (Russia), carbon materials -
Vaul (Belarus, Russia), SKN , AUVM "Dnepr" MN, Out M,
SUMS-1 (Russia, Ukraine), polyurethane coating - SYSpur-
derm (Germany).

• Regeneration phase
• Sorbents based on alginates - sipralin, algimaf, algipor,
teralgim (Russia), Sorbasan, Sorbalgon (SSHA), Tegagel,
Kaltastat, Fibracol (UK), collagen - digispon, gentatsikol,
kombutek-2 (Russia), Taurolin-Gel (UK ).
Analyzing the results of laboratory research and
clinical application of medical sorbents should be
noted that an active mechanism of sorption, effective
conditioning outflow microflora and wound discharge
from the wound provides a pronounced anti-
inflammatory, nekrolitik and analgesic effects,
prevents the development of super-infection in the
wound, thus creating favorable conditions for course
of reparative processes.

Heat: Kills microorganisms by denaturing
their enzymes and other proteins. Heat
resistance varies widely among microbes.
Thermal Death Point (TDP): Lowest
temperature at which all of the microbes in a liquid
suspension will be killed in ten minutes.
Thermal Death Time (TDT): Minimal length of time in
which all bacteria will be killed at a given
temperature.
 Decimal Reduction Time (DRT)(десятичное
сокращение): Time in minutes at which 90% of
bacteria at a given temperature will be killed. Used in
canning industry. (консервная)

Moist Heat :
Pasteurization: Developed by Louis Pasteur
to prevent the spoilage of beverages. Used to
reduce microbes responsible for spoilage of
beer, milk, wine, juices, etc.
 Classic Method of Pasteurization: Milk was
exposed to 65oC for 30 minutes.
 High Temperature Short Time Pasteurization
(HTST): Used today. Milk is exposed to 72oC
for 15 seconds.
 Ultra High Temperature Pasteurization
(UHT): Milk is treated at 140oC for 3 seconds
and then cooled very quickly in a vacuum
chamber.
 Advantage: Milk can be stored at room
temperature for several months.

Dry Heat: Kills by oxidation effects.
Direct Flaming: Used to sterilize inoculating
loops and needles. Heat metal until it has a
red glow.
 Incineration: Effective way to sterilize
disposable items (paper cups, dressings) and
biological waste.
 Hot Air Sterilization: Place objects in an
oven. Require 2 hours at 170oC for
sterilization. Dry heat is transfers heat less
effectively to a cool body,
than moist heat.
The open method of treatment can be
used. The wounds are dried; as a
result, unfavorable conditions for
development of
microorganisms are created.

Light photons from the laser penetrate
deep into targeted tissues and accelerate
cellular reproduction and growth. Laser
light also increases cellular energy and
ATP levels allowing injured cells to utilize
nutrients better and remove waste
faster. As a result, all types of cells,
including skin, tendons, ligaments and
muscles, heal quicker. Even better,
research proves that laser light
stimulates fibroblast formation.
Fibroblasts are the building blocks of
collagen, the cells responsible for closing
wounds and repairing injured tissues.
Laser treatment has proven especially
helpful in treating open wounds
and burns.
In surgery laser scalpel
very widely used

Filtration:
Removal of microbes by passage of a liquid or gas
through a screen like material with small
pores. Used to sterilize heat sensitive
materials like vaccines, enzymes, antibiotics,
and some culture media.
 High Efficiency Particulate Air Filters (HEPA):
Used in operating rooms and burn units to
remove bacteria from air.
 Membrane Filters: Uniform pore size. Used in
industry and research. Different sizes:
 0.22 and 0.45um Pores: Used to filter most
bacteria. Don’t retain spirochetes,
mycoplasmas and viruses.
 0.01 um Pores: Retain all viruses and some
large proteins.

Low Temperature: Effect depends
on microbe and treatment applied.
 Refrigeration: Temperatures from 0 to 7oC.
Bacteriostatic effect. Reduces metabolic rate of most
microbes so they cannot reproduce or produce toxins.
Freezing: Temperatures below 0oC.
Flash Freezing: Does not kill most microbes.
Slow Freezing: More harmful because ice crystals
disrupt cell structure.
 Over a third of vegetative bacteria may survive 1
year.
 Most parasites are killed by a few days
of freezing.

Osmotic Pressure: The use of high
concentrations of salts and sugars in
foods is used to increase the osmotic
pressure and create a hypertonic
environment.
Plasmolysis: As water leaves the cell,
plasma membrane shrinks away from
cell wall. Cell may not die, but usually
stops growing.
Yeasts and molds: More resistant to
high osmotic pressures.
 Staphylococci spp. that live on skin
are fairly resistant to high osmotic
pressure.

Radiation: Three types of radiation kill
microbes:
1. Ionizing Radiation: Gamma rays,
X rays, electron beams, or higher
energy rays. Have short
wavelengths (less than 1 nanometer).
Dislodge electrons from atoms and form
ions. Cause mutations in DNA and produce
peroxides.
Used to sterilize pharmaceuticals and
disposable medical supplies. Food
industry is interested in using ionizing
radiation.
Disadvantages: Penetrates human
tissues. May cause genetic
mutations in humans.

Radiation: Three types of radiation kill microbes:
2. Ultraviolet light (Nonionizing Radiation):
Wavelength is longer than 1 nanometer.
Damages DNA by producing thymine dimers,
which cause mutations.
Used to disinfect operating rooms, nurseries, cafeterias.
Disadvantages: Damages skin, eyes. Doesn’t penetrate
paper, glass, and cloth.

Radiation: Three types of radiation kill microbes:
3. Microwave Radiation: Wavelength ranges
from 1 millimeter to 1 meter.
Heat is absorbed by water molecules.
May kill vegetative cells in moist foods.
Bacterial endospores, which do not contain
water, are not damaged by microwave
radiation.
Solid foods are unevenly penetrated by
microwaves.
Trichinosis outbreaks have been associated
with pork cooked in microwaves.

Washing the wound. To avoid the development
of septic complications wound should be cleaned
Dessication(высушивание):
In the absence of water, microbes cannot grow or
reproduce, but some may remain viable for years.
After water becomes available, they start growing
again.
Susceptibility to dessication varies widely:
Neisseria gonnorrhea: Only survives about one hour.
Mycobacterium tuberculosis: May survive several
months.
Viruses are fairly resistant to dessication.
Clostridium spp. and Bacillus spp.: May survive
decades.

• Synthetic antibacterial agents are used to
combat bacterial infection in the wound or
inflammatory foci. These are both effective
for therapy and prophylaxis and help achieve
antibacterial effect inside the human body.
• There are many chemical antiseptics; they
are section into the following groups:

1. Halogens: Effective alone or
in compounds.
A. Iodine:
 Tincture of iodine (alcohol solution) was one of first
antiseptics used.
 Combines with amino acid tyrosine in proteins and
denatures proteins.
 Stains skin and clothes, somewhat irritating.
 Iodophors: Compounds with iodine that are slow
releasing, take several minutes to act. Used as skin
antiseptic in surgery. Not effective against
bacterial endospores.
 Drags of an iodine: Iodonatum of 1% sol.,
Iodinolum of 1% sol., 1% iodopironi sol ,
iodobak, iodoskin, Betadine, Isodine

2. Oxidants = Peroxygens (Oxidizing Agents):
 Oxidize cellular components of treated microbes.
 Disrupt membranes and proteins.
A. Ozone:
 Used along with chlorine to disinfect water.
 Helps neutralize unpleasant tastes and odors.
 More effective killing agent than chlorine, but less
stable and more expensive.
 Highly reactive form of oxygen.
 Made by exposing oxygen to electricity
or UV light.

2. Peroxygens (Oxidizing Agents):
C. Benzoyl Peroxide:
 Used in acne medications.
D. Peracetic Acid:
 One of the most effective liquid sporicides available.
 Sterilant :
- Kills bacteria and fungi in less than 5 minutes.
- Kills endospores and viruses within 30 minutes.
 Used widely in disinfection of food and medical instruments
because it does not leave toxic residues.
E. Perhydrolum, contains about 33 % of peroxide of
Hydrogenous, is used for preparation of a solution pervomur;
F. Permanganate of a potassium (potassium
permanganate) - apply to a lavage of the wounds - 0,1 %
sol., for a lavage of an oral cavity and a stomach - 0,01 sol.;
• Oxidizers are especially effective at anaerobic and
putrefactive diseases.

2. Peroxygens (Oxidizing Agents):
G. ETHYLENE OXIDE
• Mode of action: It is an alkylating agent. Denature
proteins, by replacing functional groups with alkyl groups.
• It acts by alkylating sulfydryl-, amino-, carboxyl- and
hydroxyl- groups.
• EtO is liquid at temp below 10.8oC. Above this temp. , it
vaporizes rapidly.
• Excellent penetration capacity & sporicidal activity.
• Toxic & highly explosive.
• Since it is highly flammable, it is usually combined with
CO2 (10% CO2+ 90% EO)
 Kills all microbes and endospores, but requires exposure
of 4 to 18 hours.
 Chemicals that sterilize in a chamber similar to an
autoclave
Continue…

Continue…ETHYLENE OXIDE
• It is an effective sterilizing agent for heat &
moisture sensitive materials.
• EtO is used to sterilize papers, leather, wood,
metal and rubber products as well as plastics.
• In hospitals, it is used to sterilize catheters,
artificial heart valves, heart-lung machine
components & other optical equipment.

4. Aldehydes:
B. Glutaraldehyde:
 Less irritating and more effective than
formaldehyde.
 One of the few chemical disinfectants that is a
sterilizing agent.
 A 2% solution of glutaraldehyde
(Cidex) is:
 Bactericidal, tuberculocidal,
and viricidal in 10 minutes.
 Sporicidal in 3 to 10 hours.
 Commonly used to disinfect hospital instruments.
 Also used in mortuaries for embalming.

5. Phenols and Phenolics:
 Phenol (carbolic acid) was first used by Lister
as a disinfectant.
 Rarely used today because it is a skin irritant and has
strong odor.
 Used in some throat sprays and lozenges.
 Acts as local anesthetic.
 Phenolics are chemical derivatives of phenol
 Cresols: Derived from coal tar (Lysol).
 Biphenols (pHisoHex): Effective against gram-positive
staphylococci and streptococci. Used in nurseries.
Excessive use in infants may cause neurological
damage.
 Destroy plasma membranes and denature
proteins.
 Advantages: Stable, persist for long times after
applied, and remain active in the presence of
organic compounds.

6. Dyes
• — Brilliant green is used as a 1—2%
alcohol solution for superficial
wounds, abrasions and suppurative
skin infections.
• — Methylene blue is used for
superficial wounds and abrasions (3%
alcohol solution), burns (1-2% alcohol
solution) and for washing purulent
cavities (0,02% aqueous solution).

7. Heavy Metals:
Include copper, selenium, mercury, silver, and zinc.
 Oligodynamic action: Very tiny amounts are
effective.
A. Silver:
 1% silver nitrate used to protect infants against
gonorrheal eye infections until recently. Salts of
silver: a colloid silver and Protargolum
B. Mercury
 Mercury compounds exert antibacterial action by
reversible binding to sulfhidryl enzymes in
microorganisms. However, they are highly toxic to
tissues, and penetrate poorly. Organic mercury
compounds like merthiolate and mercurochrome
are used to disinfect skin wounds. Mercuric oxide
ointment 1%, amoniated mercury ointment,
thimerosal, nitromersol and merbromin.
THIMEROSAL (mercury derv.), previously
used as a preservative in vaccine

4. Heavy Metals:
C. Copper
 Copper sulfate is used to kill algae in pools
and fish tanks, to control the growth of
fungi.
D. Zinc Treatment and prevention of foot-
rot and foot scald. Treatment and prevention
of dermatophilosis (mycotic dermatitis or
lumpy wool)
 Zinc chloride is used in mouthwashes.
 Zinc oxide is used as antifungal agent in
paints.
Е. Selenium
 Kills fungi and their spores. Used for fungal
infections.
 Also used in dandruff (перхоть) shampoos.

8. Detergents:
• Detergents are synthetic chemicals acting as strong
wetting agent & surface tension reducers.
• While soaps are always negatively charged, some
detergents are negatively charged while others are
positively charged.
• One example of a positively charged detergent are
quaternary ammonium compounds (also known as quats)
Chlorhexidine begluconat. The main aqueous solution contains 20% of
chlorhexidine bigluconate. For cleaning wounds, a 1:400 solution is
available, for washing infected body’s cavities a 1:1,000 may be
used. These are strong surface-active compound.
• for processings of an abdominal cavity at a peritonitis - 1 % an
aqueous solution.
• Apply to processing hands of the surgeon - 0,5 % alcogol solution
• Cerygel - apply to processing hands of the surgeon.
Roccalum - 10 % and 1 % an aqueous solution.

8. Detergents. Quaternary Ammonium Compounds (Quats):
 Widely used surface active agents.
 Cationic (positively charge) detergents.
 Effective against gram positive bacteria, less effective
against gram-negative bacteria.
 Also destroy fungi, amoebas, and enveloped viruses.

8. Detergents. Quaternary Ammonium Compounds
(Quats):
Zephiran, Cepacol, also found in our lab spray
bottles.
 Pseudomonas strains that are resistant and can
grow in presence of Quats are a big concern in
hospitals.
 Advantages: Strong antimicrobial action, colorless,
odorless, tasteless, stable, and nontoxic.
 Diasadvantages: Form foam(пена). Organic
matter interferes with effectiveness. Neutralized
by soaps and anionic detergents. Quats do not
kill endospores, Mycobacteria spp., nor non-
enveloped viruses

9. 5-Nitroimidazole derivatives
 Metronidazole is a synthetic, nitroimidazole-derivative antibacterial
and antiprotozoal (Amebiasis, Giardiasis, Trichomoniasis) agent trade
names — trichopol, Trichazol, Clont,Danizol, Flagyl, Gineflavir,
Metric, Metrodzhil, MetroGel, Metrogyl, Trichopol
 Bacterial Infections
Metronidazole has potent antibacterial activity against
anaerobes, including bacteroides and clostridium species
Metronidazole is indicated for treatment of anaerobic or mixed
intra-abdominal infections, vaginitis (bacterial vaginosis),
antibiotic-associated enterocolitis, acute gingivitis and other
dental infections
Metronidazole is indicated for treatment of vaginitis due to
bacterial Gardnerella or Mycoplasma hominis infection in
symptomatic patients
Helicobacter pylori eradication therapy, as part of a multi-drug
regimen in peptic ulcer disease
It is effective against non-clostridial anaerobes and can be given
intravenously (0,5 g in 100 ml of solvent).

10. Dioxydin. This is a derivative of oxychinolin.
0,1 — 1% aqueous solutions are indicated for
purulent wounds, for washing the urinary
bladder, empyema or abscess cavities, and
purulent fistulae. It is available as 10 ml
ampoules with 1 % solutions of the drug. In
severe purulent infections (sepsis, purulent
peritonitis), it can be infused intravenously as
much as 60—90 ml 2—3 times a day (30 ml of
the solution diluted in 500 ml of 5% glucose
solution). It should be avoided in patients
with impaired renal function.

11. Sulphonamides or Sulfonamides is the basis of
several groups of drugs. The original antibacterial
sulfonamides (sometimes called sulfa drugs or sulpha
drugs) are synthetic antimicrobial agents that contain
the sulfonamide group. (streptocide, ethazol, sulfacyl)
• Derivatives of sulfacyl with prolonged activity
(sulfadimethoxin, sulfalen, sulfapiridazin,
streptocidum) are available as tablets, pudres.
• Short-acting - (5-11 hours) Sulfadiazine
(Microsulfon)
Sulfamethizole (Thiosulfil), Sulfisoxazole (Gantrisin)
Sulfamethoxazole, Sulfisomidine
Intermediate-acting (11-12 hours)
Sulfacetamide,Sulfadoxine,
Sulfamethoxazole (Gantanol)
Sulfasalazine (Azulfidine) ,
Trimethoprim sulfamethoxazole

TRIPRIM is a sterile, aqueous
injectable solution of
trimethoprim and a
sulfadimethylpyrimidine
compound. The aqueous
solution is unique and is far
better tolerated, locally and
generally, than injectable
solutions made with the more
conventional organic solvents
TRIPRIM
Description
Sulfadimidine 200mg
Trimethoprim 40mg/100mL
TRIPRIM is a broad spectrum
bactericidal agent which is rapidly
absorbed from blood into sites of infection!

12.Soaps
• A soap is a chemical compound of fatty
acids combined with potassium or hydrogen
peroxide.
• The pH of the compound is usually about 8.0
& some microbial destruction is therefore
due to the alkaline conditions established on
the skin.
• However, the major activity of the soap is as
a degerming agent for the mechanical
removal of m.org. from the skin surface.
• Soaps are ‘wetting agents’, i.e. they emulsify
& solubilize particles clinging to a surface.

13. ACIDS
• Benzoic acid
• Salicylic acid
• Boric acid is weekly germicidal and nonirritating. But it is
readily absorbed if applied to large denuded areas, and
can cause severe systemic toxicity with gastrointestinal
disorders, hypothermia, renal impairment, vascular
collapse, shock and death. It can be limitedly used only in
ophthalmology.
• Organic acids are particularly valuable as food
preservative.
• Lactic & acetic acid e.g. are important
preservatives in sour foods such as cheese &
pickled products.
• Propionic acid is added to bakery products to keep
microbial population low.

14. Hypertonic solutions –
• Sol Natrii chloride 10-20%
• A hypertonic salt solution - 10 % Sodium
chloridum sol.
• 30 % ureas sol.
• 40 % glucoses sol.
• Disadvantage of the hypertonic solutions
is the fast inactivation due to delution the
wound’s exudates.

15. Derivatives of nitrofuran. These agents are effective
against purulent cocci. Nitrofurazone is bactericidal against many
gram-negative and positive microorganisms in dilutions up to
1:75000. It is clinically useful as topical antiseptic on surgical
wounds and superficial skin lesions including burns, ulcers, but
systemic toxicity may result from absorption from large wound
areas.
• - Furacilin - Aqueous solution 1:5000 kills only gram-positive
bacteria. It is used for washing out purulent wounds during
dressing, washing out abscess cavities and empyemas through the
drainage tube (e.g. in purulent pleurisy and purulent fistula of
osteomyelitis).
• - Soluble Furagin (Furagin K- or Furagin-potassium,
Solafur). The indications of its 0,1% solution are similar to those of
furacilin. It can also be given intravenously in a dose of 300 ml.
Orally, furazolidon is taken as 50 mg tablets.
• Derivatives of nitrofuran may also be ingredients of the
membranous compound lifusol manufactured as an aerosol and
used to treat superficial wounds and burns. It forms a defensive
membrane that causes antimicrobial effect on the wound's surface.
Effect of this membrane lasts for 5—7 days.

16. Myramistinum
• «Miramistin» is Russian new generation antiseptic
drug. It has a wide scope of action and can be most
efficient in prevention and treatment of infections –
bacterial (profound antibacterial effect on gram-
positive and gram-negative, aerobic and anaerobic
bacteria in the form of monocultures and microbe
associations, including hospital strains with
multiresistance to antibiotics), mycotic and viral
infections.
• Method of issuance : 0.01% solution for local
applications in bottles of 100 ml and 500; 0.5%
ointment in the box on 15, 20 and 30 grams
and banks to 30, 100, 1000 and 2000.

• Biological antibacterial agents are used to combat
bacterial infection in the wound or inflammatory
foci. These are both effective for therapy and
prophylaxis and help achieve antibacterial effect
inside the human body.
• There are many biological antiseptics; they are
section into the following groups:
1. Antibiotics
2. Enzymes
3. Bacteriophages
4. Serums
5. Immunoglobulin

• 1. Antibiotics (AB) are known to be of
greatest importance as far as antibacterial
therapy is concerned. Currently, the use of
antibiotics has been facing a multitude of
problems associated with changes in biology
of target microorganisms, i.e. quite a number
of drug-resistant strains have emerged
1928: Fleming discovered
penicillin
1940: Howard Florey and Ernst
Chain performed first clinical
trials of penicillin.

1. Cyanobacteria
2. Bacteria
3. Actinomycetes
4. Fungi
5. Higher Organisms
• Mostly produce toxins that kill higher
organisms.
• Malingolide is an antibiotic produced by a
cyanobacteria.

• Out of the 19 different principal groups into which
bacterias can be divided (Bergey’s Classification )
the following groups mostly are source of
antibiotics
Bacterial group
number
Bacterial type
2 Gliding bacteria
7 Gram –ve aerobic rods & cocci
8 Gram –ve facultatively anaerobic rods
14 Gram +ve cocci
15 Bacillus
16 Gram +ve ,asporogenous rods
17 Actinomycetes & related organisms
12 Mycoplasmas

• It is the largest source of antibiotics.
• 90%-95% of which is produced by the genus
“Streptomyces”(soil bacteria).
• Another genus important for antibiotics
production is Micromonospora

• Richest source is the
genera “penicillium”
and “aspergillus”
• Such as algae, lichens,
higher plants , protozoa,
insects, molluscs,
sponges, worms and
vertebrates.

1. Narrow spectrum antibiotics (NSAB)
Main effect : sensitive for gram positive bacteria
and bacil
e.g. : Pen. G, Pen. Resistent penicillinase
semisynthetics, bacitracin, macrolides, lincomycin,
vancomycin
2. Broad Spectrum Antibiotics (BSAB)
Main effect : sensitive for gram positive and gram
negative bacteriae
e.g. : Pen. (ampicillin and amoxycillin),
cefalosporins, tetracyclins, chloramphenicol,
trimetroprim and sulfonamides
Method of action – bactericidal/bacteriostatic

• The penicillins
• One of the first antibiotics was a natural antibiotic
• Bactericidal agents,
• Contain a β-lactam ring in structure.
• They inhibit synthesis of the bacterium cell wall by affecting synthesis of
peptidoglycan.
• Peptidoglycan cell wall surrounds certain bacteria and is essential for their
survival.
• benzylpenicillin still used nowadays in selected cases.
The main advantage of benzylpenicillin is low toxicity.
Semisynthetic penicillins fall into the next groups:
• I) stable penicillins (oxacillin, metycillin, dicloxacillin),
which are active against gram-positive bacteria. They are
indicated for staphylococcal infections of various
localization (pneumonia, lung abscess, pleural empyema,
osteomyelitis, abscess or phlegmon of soft tissues,
wounds)

• 2) broad-spectrum semisynthetic penicillins (ampicillin;
ampiox — a combination of ampicillin and oxacillin;
carbenicillin). These are effective in burns, peritonitis,
infected wounds caused by Pseudomonas and Proteus spp.
- Co-amoxiclav - Consists of amoxicillin combined with a beta-
lactamase inhibitor clavulanic acid
Spectrum: - Active against Gram-ve rods resistant to amoxicillin due to
beta-lactamases
– E.g. resistant strains of E.coli, S. aureus and H. influenzae.
– Clavulanic acid has no antibacterial activity
- Flucloxacillin - Bactericidal antibiotic, A beta-lactamase-resistant
penicillin, Used for penicillin-resistant staphylococci. IV dose: 0.25-
2g every 6 hours
Can be less effective against bacterium that does not produce beta-
lactamase
It is less active against Streptococcus pneumoniae and Str. pyogenes
than penicillin.

Fungi of genus
Cephalosporium
 4 Generations of
cephalosporins
1. First-generation: Narrow spectrum, gram-positive
(kefzol, cefazolin)
2. Second-generation: Extended spectrum includes
gram-negative (cephalothin, cephuroxim)
3. Third-generation: Includes pseudomonads; mostly
injected, some oral (cephalexin; cephataxime,
cefotaxim, ceftriaxon ).
4. Fourth-generation: Most extended spectrum

Aminoglycosides
• These include gentamicin, kanamycin,
streptomyocin, neomycin, tobramycin and
semisynthetic aminoglycoside (amikacin).
• They resemble each other in:
– Antibacterial activity
– Pharmacokinetic properties
– Toxicity
• Mechanism:
– Bactericidal activity
– Inhibit bacterial protein synthesis
– They do this by binding to the 30S ribosomal subunit.
– They stop the translation of mRNA into the proteins.

Aminoglycosides (cont..)
• Spectrum:
– Many Gram-ve (Including Pseudomonas)
– Some Gram+ve
– Inactive against anaerobes
– Used in serious Gram –ve infections in combination
with agents that disrupt cell wall synthesis (e.g.
penicillin)
– Synergistic effect with penicillin
– Not absorbed orally so only given IM or IV.
• Elimination:
– Renally by glomerular filtration
– In renal impairment accumulation occurs rapidly
– Result is an increase in toxicity (ototoxicity and
nephrotoxicity)
– Dose adjustment is essential in renal impairment

Macrolides
These include erythromycin, oleandomycin,
azithromycin, clarithromycin.
• Similar antibacterial spectrum to penicillins
• Mechanism: inhibit bacterial protein synthesis by binding
to bacterial ribosome.
• Bacteriostatic
• Can be effective against unusual organisms
• Generally safe drugs
• Erythromycin can cause gastrointestinal problems which
are less common with other agents.
• Azithromycin has a long half life
• Macrolides can inhibit cytochrome P450 leading to
accumulation of drugs.

• Fluorquinolones - Quinolones (bactericidal)
(ofloxacin, pefloxacin, cipro-floxacin, lomefloxacin
nalidixic acid, ciprofloxacin, ofloxacin, norfloxacin,
levofloxacin, lomefloxacin, sparfloxacin)
• Mode of action - These antimicrobials bind to the A
subunit of DNA gyrase (topoisomerase) and prevent
supercoiling of DNA, thereby inhibiting DNA
synthesis.
• Spectrum of activity - broad spectrum of activity
covers numerous gram-negative and gram-positive
microorganisms (e.g. E. coli, Enterobacteriaceae,
Klebsiella and Staphylococcus spp)
• Resistance - Common for nalidixic acid; developing
for ciprofloxacin.

Tetracyclines
• These include tetracycline, oxytetracycline and
semisynthetic tetracyclines (metacycline or rondo-
mycin), doxycycline (vibramycin).
• Mechanism inhibit protein synthesis
• Absorption of tetracyclines is affected by calcium and
magnesium ions, food and iron preparations.
• Broad spectrum antibiotics
• Bacteriostatic
• Should be avoided in pregnancy, breast feeding and
children under 12 years as they bind to calcium in growing
bones and teeth causing discoloration.

• Similar mode of action to other -lactams
• Greater affinity for PBP-2
– Faster bacterial death
– Extremely broad spectrum
• E.g. imipenem / meropenem
• Used for severe hospital acquired infections
• carbopinems (imipenem, pleropenem,
tienam (a combination of imipenem + sodium
celastatin).

• Prevent bacterial cell wall synthesis
– Bind to amino acids in cell wall
• Active against Gram positive bacteria.
– Don’t penetrate outer membrane of Gram neg bacteria (polar
molecules)
• E.g. Teicoplanin, vancomycin Used in severe Gram pos
infection
• Vancomycin
– Needs levels monitoring (after 3-4 doses in normal
renal function)
– “red man syndrome”
– Glycopeptide from Streptomyces
– Inhibition of cell wall synthesis
– Used to kill MRSA
– Emerging Vancomycin
resistance: VRE and VRSA

• Mode of action - These antimicrobials bind to the
50S ribosome and inhibit peptidyl transferase
activity.
• Spectrum of activity - Chloramphenicol - Broad
range;Lincomycin and clindamycin - Restricted range
• Resistance - Common
• Adverse effects - Chloramphenicol is toxic (bone
marrow suppression) but is used in the treatment
of bacterial meningitis.

• Mode of action - Fusidic acid binds to elongation
factor G (EF-G) and inhibits release of EF-G from the
EF-G/GDP complex.
• Spectrum of activity - Gram-positive cocci

• Mode of action - These antimicrobials bind to DNA-
dependent RNA polymerase and inhibit initiation
of mRNA synthesis.
• Spectrum of activity - Wide spectrum but is used
most commonly in the treatment of tuberculosis
• Resistance - Common
• Combination therapy - Since resistance is common,
rifampin is usually used in combination therapy.

Agar Disk Diffusion Method determines
susceptibility of an organism to a series of
antibiotics: Kirby-Bauer test
More sophisticated methods available for clinical
labs

• Fungi are plant-like, eukaryotic organisms. Most fungi live
as saprophytes in soil or on dead plant materials and are
important in the mineralization of organic matter.
• There are 300,000 kinds of fungi, but only 270 of which
cause disease in humans and animals. These fungi are
divided into two classes according to mycotic illnesses in
humans they caused.
• Mucocutaneous Fungi : cause skin and hair infections
(shallow infections)
• Systemic Fungi : cause visceral infections (deep infections)

Fungal
Infections
intensive uses of antibiotics
for bacterial infections
surgery operation and
organ transplant
immune systems diseses
such as AIDS
chemotherapy of cancers
Fungal infections
In recent year, the incidence of fungal infections has reached
alarming proportions. This duo to a number of factors .

The classification of antifungal agents
Antimycotic antibiotics:
Synthetic
antifungal
Agents:
Polyenes ( Amphotericin B)
Others (Griseofulvin)
Fluorinated pyrimidines
(Fluorocytosine)
Azoles
Imidazoles
(ketoconazole)
Triazoles
(Fluoconazole)
Allyamines (Terbinafine)
Thioureas (Tolnafate)
Others (Ciclopirox)

• Polyenes, such as nystatin and amphotericin
B, for systemic fungal infections. Inhibition
of ergosterol synthesis  fungicidal.
Nephrotoxic
• Griseofulvin from Penicillium. Systemic/oral.
Binds to tubulin 
For Tineae

Nucleoside analogs inhibit DNA synthesis
Acyclovir and newer derivatives: Selective
inhibition of herpes virus replication.
Acyclovir conversion to nucleotide analog
only in virus infected cells  very little
harm to uninfected cells!
Fig 20.16

• Enzymes
– Antimicrobial enzymes act against microorganisms
– Human tears contain lysozyme
• Digests peptidoglycan cell wall of bacteria
– Enzymes to control microbes in the environment
• Lysozyme used to reduce the number of bacteria in
cheese
• Prionzyme can remove prions on medical
instruments
As anti-inflammatory agents proteolytic enzymes
(trypsin, chemotrypsin) are given intramuscularly or
intravenously in doses of 0,07 mg/kg.
© 2012 Pearson Education Inc.

• Bacteriophages are viruses that can infect and
destroy bacteria.
• They have been referred to as bacterial parasites,
with each phage type depending on a single strain
of bacteria to act as host.
• Two basic types of bacterial viruses
Lytic viruses – infect cells,
multiply rapidly,lyse cells
Lysogenic viruses – infect
cells, can integrate into
genome and go dormant
(a prophage). - at some point,
can excise,
multiply and lyse cells.

• Staphylococcal anatoxins are given
subcutaneosly in doses of 0,1 ml at the
scapular area, and repeated each 2—3 days,
with an increase in the dose by 0,1 ml each
time up to a maximum of 1 ml. In emergency,
0,5 ml can be given preoperatively.
• Tetanus antitoxin is used for both scheduled
and emergent prophylaxis against tetanus.
Injection of the drug in emergency is
combined with prophylactic doses of
antitetanus serum.

• Antibodies are substances made by the
body's immune system in response to
bacteria, viruses, fungus, animal dander, or
cancer cells. Antibodies attach to the foreign
substances so the immune system can
destroy them.
• Antistaphylococcal gamma globulin
• Antitetanus gamma globulin

immune serum is a serum containing naturally or
artificially produced antibodies to a given antigen,
obtained from human or animal sources.
• Antitetanus serum
• Antigangrene serum
• polyvalent serum - antiserum containing antibody to
more than one kind of antigen.
• antilymphocyte serum (ALS) antiserum derived from
animals immunized against human lymphocytes; a
powerful nonspecific immunosuppressive agent that
causes destruction of circulating lymphocytes.
• antirabies serum antiserum obtained from the blood
serum or plasma of animals immunized with rabies
vaccine; used for postexposure prophylaxis against
rabies if rabies immune globulin is unavailable.

• A prebiotic is a nondigestible component which
beneficially affects the host by selectively
stimulating the growth and/or activity of one or a
limited number of colonic bacteria, thereby
improving the health of the host
***In other words, prebiotics are nutrients that the bacteria use as a
fuel source; these include dietary fiber and carbohydrates
Not absorbed or degraded
• Alter the balance of intestinal flora and by acting
as substrates stimulate the growth of beneficial
bacteria (i.e., Lactobacillus and Bifidobacteria)

• Must not be hydrolyzed nor absorbed in the upper
gastrointestinal tract
• Must be a substrate for growth or activity of one or a
limited number of beneficial colonic bacteria
• Must therefore be able to alter the colonic microflora
towards a healthier composition and to induce luminal or
systemic effects which are beneficial to the health of the
host
• Fructooligosaccharide (aka oligofructose)
• Isomaltooligosaccharide
• Xylooligosaccharide
• Inulin
• Fiber
• Oligomate
• Palatinose
• Pyrodextrin
• Raftiline

• Inulin
• Garlic
• Onions
• Chicory root
• Asparagus
• Whole wheat
• Rye
• Barley

• Probiotics defined as microorganisms that
have a beneficial effect on the host
intestinal microbial balance
• Probiotics, which means “for life” was
meant to contrast “antibiotics”, popularly
prescribed and known to also destroy
beneficial organisms and impact the
immune system.

• Non-pathogenic live microbial food
supplements
• Organisms that, when administered in adequate
amounts, exert a positive influence on the
health of the host animal
• Live organisms that benefit the host animal by
improving intestinal microbial balance
• Usually administered in yogurt or capsules

• Metchnikoff – 1907 – ingesting yogurt with
Lactobacilli reduces toxic bacteria of the gut
and prolongs life
• Kipeloff – 1926 – stressed importance of
Lactobacillus acidophilus for good health
• Rettger – 1930’s – early clinical application of
Lactobacillus
• Parker – 1974 – 1st to use the term probiotics
• Fuller – 1989 – defined probiotics

• Lactobacilli – anerobic, gram (+) rods
– casei
– plantarum
– acidophilus
– reuteri
• Bifidobacteria – anerobic, gram (+) rods
• VSL #3 (8 separate organisms: 3 Bifidobacteria, 1
Streptococcus, 4 Lactobacilli)
• Enterococcus
• Streptococcus salivarius
• Saccharomyces

• GI secretions (saliva, acid, bile)
• Mucus
• Normal peristalsis (presence of MMC)
• Barrier function (tight junctions)
• Intestinal proteolysis
• Intestinal immune cells
• IgA production and secretion

• Human GI tract contains 10x more bacteria
(1014) than eukaryotic cells in the body
• Protects the host
– Stimulates immune function
– Produces antimicrobial substances
• Trophic effect on intestinal epithelium
• Maintains the enterohepatic circulation of bile
acids
• Involved in metabolic processes (i.e.,
fermentation) in the colon

• Competitive inhibition
• Barrier protection
• Immune effects
• Anti-inflammatory effects
• Production of various substances (enzymes,
SCFA, bacteriocidal agents)
• Ability to alter local pH and physiology
• Provides nutrition to colonocytes

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