CONTROLLING MICROBIAL

GROWTH IN VIVO USING

ANTIMICROBIAL AGENTS

• INTRODUCTION
• CHARACTERISTICS OF AN IDEAL
ANTIMICROBIAL ANGENT
• HOW ANTIMICROBIAL AGENTS
WORKS
• ANTIBACTERIAL AGENTS
• ANTIFUNGAL AGENTS
• ANTIPROTOZOAL AGENTS
• ANTIVIRAL AGENTS
CHAPTER 9 OUTLINE
• DRUG RESISTANCE
• SOME STRATEGIES IN THE WAR
AGAINST DRUG RESISTANCE
• EMPIRIC THERAPHY
• UNDESIRABLE EFFECTS OF
ANTIMICROBIAL AGENTS
 INTRODUCTION

• Chemotherapy is the use of any chemical to treat

any disease or condition.
• A chemotherapeutic agent is any drug used to
treat any condition or disease.
• An antimicrobial agent is any chemical used to treat
an infectious diseases, either by inhibiting or killing
pathogens in vivo. Some antimicrobial agents are
antibiotics.
 INTRODUCTION

• Antibacterial agent is a drug used to treat bacterial

disease .
• Antifungal agents are those to treat fungal disease.
• Antiprotozoal agents used to treat protozoal
disease.
• Antiviral agents used to treat viral disease.
 INTRODUCTION

• An antibiotic is a substance produced by a

microorganism that kills or inhibits growth of other
microorganisms.
• Semisynthetic antibiotics are antibiotics that have
been chemically modified to kill a wider variety of
pathogens or reduce side effects; examples includes
semisynthetic penicillin, such as ampicillin and
carbenicillin.
 THE DISCOVERY OF PENICILLIN BY
ALEXANDER FLEMING
• A. colonies of staphylococcus
aureus
• B. colonies are poorly develop in this
area of the plate because of the
antibiotic (penicillin) being produce
by a colony P. notatum (a mould)
shown at C. (This photograph
originally appeared in the British
Journal of Experimental Pathology in
1929.) (From Winn WC Jr., et al.
Koneman’s Color Atlas and
Textbook of Diagnostic
Microbiology, 6th ed. Philadelphia:
JB Lippincott, 2006.)
 CHARACTERISTICS OF AN IDEAL
ANTIMICROBIAL AGENT
• Kill or inhibit the growth of pathogens
• Cause no damage to the host
• Cause no allergic reaction in the host
• Be stable when stored in solid or liquid form
• Remain in specific tissues in the body long enough to be effective
• Kill the pathogens before they mutate and become resistant to it
 HOW ANTIMICROBIAL AGENTS
WORK
• The five most common mechanisms of action of antimicrobial agents are as
follows:
• Inhibition of cell wall synthesis
• Damage to cell membranes
• Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
• Inhibition of protein synthesis
• Inhibition of enzyme activity
 ANTIBACTERIAL AGENTS
• Bacteriostatic drugs inhibit growth of bacteria,
whereas
• bactericidal drugs kill bacteria.
• Penicillin
• Will inhibit cell wall synthesis by interfering with the
synthesis and cross linking of peptidoglycan. • Will kill
most gram positive bacteria. • It cannot effect
human cells because they don’t have cell walls.
 ANTIBACTERIAL AGENTS

• Narrow-spectrum Antibiotics
• Antibiotics that can destruct either Gram positive or
Gram negative bacteria.
• e.g. vancomycin work on Gram positive bacteria only.
colistin work on Gram negative bacteria only
• Broad-spectrum Antibiotics
• Antibiotics that can destruct Both Gram positive and Gram
negative bacteria.
• e.g. Ampicillin.
 MULTIDRUG THERAPY

• The simultaneous use of two or more drugs to

kill all the pathogens and prevent resistant
pathogens from growing.
• e.g. Treatment of Tuberculosis (Tb)- 4 drugs
are used.

Synergism
• Is when 2 antimicrobial agent are
used together to produce a degree
of pathogen killing that is greater
than that achieved by either drug
alone.
MULTIDRUG THERAPY
Antagonism
• Is when 2 drugs actually work
against each other. The extent of
pathogens killing less than that
achieved by either drug alone.
 ANTIFUNGAL AGENT
• Most antifungal agents work in one of 3 ways:
• By binding with cell membrane sterols (e.g., nystatin and amphotericin
B)
• By interfering with sterol synthesis (e.g., clotrimazole and miconazole)
• By blocking mitosis or nucleic acid synthesis (e.g., griseofulvin and 5-
flucytosine).
 ANTIPROTOZOAL AGENT
• Antiprotozoal drugs are usually quite toxic to the host.
• Anti protozoal agent works by:
• (a) interfering with DNA and RNA synthesis (e.g.,
chloroquine, pentamidine, and quinacrine),
• (b) interfering with protozoal metabolism (e.g.,
metronidazole; brand name Flagyl).
 ANTIVIRAL AGENTS
• Antiviral agents are the newest weapons in antimicrobial
methodology.
• difficult to develop and use because viruses are produced within host
cells.
• Some drugs have been developed that are effective in certain viral
infection, but not others; they work by inhibiting viral replication cell.
• e.g. Acyclovir for the treatment of HSV.
• “cocktail” of drugs including lamivudine for HIV.
 DRUG RESISTANCE
(SUPERBUGS)
• Superbugs are microbes(bacteria) that have
become resistant to one or more antimicrobial
agent.
• Infections caused by superbugs are much
more difficult to treat.
 DRUG RESISTANT
• Bacterial superbugs include:
• Methicillin-resistant S. aureus (MRSA)
• Vancomycin-resistant Enterococcus spp. (VRE)
• Multidrug-resistant M. tuberculosis (MDR-TB)
• Multidrug-resistant strains of Acinetobacter baumannii, Burkholderia
cepacia, E. coli, Klebsiella pneumoniae, N. gonorrhoeae,
• • β-Lactamase–producing strains of S. pneumoniae and Haemophilus
influenza
 DRUG RESISTANCE
(HOW BACTERIA BECOME RESISTANT
TO DRUGS)
Intrinsic Resistance
• Some bacteria are naturally resistant to a particular
antimicrobial agent because they lack the specific
target site for that drug or the drug is unable to cross
the organism’s cell wall or cell membrane and, thus,
cannot reach its site of action.
• Acquired Resistance
• Bacteria can acquire resistance by one of these
methods:
 DRUG RESISTANCE
• Before a drug can enter a bacterial cell, molecules of the
drug must first bind (attach) to proteins on the surface of the
cell; these protein molecules are called drug binding sites.
• A chromosomal mutation can result in an alteration in the
structure of the drug-binding site, so that the drug is no
longer able to bind to the cell. If the drug cannot bind to
the cell, it cannot enter the cell, and the organism is,
therefore, resistant to the drug.
 DRUG RESISTANCE

• In summary: Bacteria can acquire resistance to antimicrobial agents

• By chromosomal mutation or
• By the acquisition of new genes by
• Transduction(bacteriophage carry DNA from on bacteria to another.)
• Transformation(naked DNA from environment)
• Most common in, by Conjugation(plasmid containing such genes)
 SOME STRATEGIES IN THE WAR
AGAINST DRUG RESISTANCE
• Education of healthcare professionals and, in turn, education of patients.
• Patients should never pressure clinicians to prescribe antimicrobial agents.
Parents must stop demanding antibiotics every time they have a sick child.
• Clinicians not allow themselves to be pressured by patients. They should
prescribe antibiotics only when warranted.
• Clinicians should prescribe an inexpensive, narrow spectrum drug whenever
the laboratory results demonstrate that such a drug effectively kills the
pathogen
 SOME STRATEGIES IN THE WAR
AGAINST DRUG RESISTANCE
• Patients must take their antibiotics in the exact manner in
which they are prescribed.
• Healthcare professionals must practice good infection
prevention and control procedures
 EMPIRIC THERAPY

• Empiric therapy is when drug therapy is initiated

before laboratory results are available.
• Empiric therapy is sometimes necessary to save
patients life.
 EMPIRIC THERAPY
• If pathogen is identity known use • Site of infection
the “pocket chart” of antimicrobial • What other medications is the
susceptibility test data from past patient taking
year.
• What other medical problems does
• Is the patient allergy to any the patient have.
microbial agents
• What is the cost of the drug
• What is the age of patient
• Is the patient pregnant
• Inpatient or outpatient
 UNDESIRABLE EFFECTS OF
ANTIMICROBIAL AGENTS

reasons why antimicrobial agents should not be used indiscriminately.

• Organisms susceptible to the agent will die, but resistant ones will survive; this
is known as selecting for resistant organism
• Patient may become allergic to the agent
• Many agent are toxic to human and some are very toxic
• Prolonged antibiotic use can lead to population explosions of
microorganisms that are resistant to the antibiotic(s) being used. Such
overgrowths are known as “superinfections.