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Lecture 3

HSS 1101 Lecture Notes - Lecture 3: Antibiotic Misuse, Penicillin Binding Proteins, Antimicrobial Resistance


Department
Health Sciences
Course Code
HSS 1101
Professor
Kerry- Ann Hogan
Lecture
3

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Bacterial Infections and Host Defences
In human health the normal flora bacteria function as a balanced ecosystem with multiple species at a
site and no single organism predominating. Organisms do not invade the body outside their normal
territory. Infection with bacteria occurs when a single species becomes predominate at a site at which
there is normally many species or when a single organism invades a body site that is normally sterile.
When this occurs the outcome is determined by the bacterial pathogenicity factors and by the host
response to those aggressive bacterial mechanism(s). The more important of these are as follows, and
include mechanical barriers, adherence, phagocytosis, antibodies (humoural immunity), complement,
cell mediated immunity and endo/exo--‐toi produtio.
Mechanical Barriers
The skin is a barrier to the invasion of deep tissues by bacteria. The skin is extensively colonized by large
numbers of organisms that do not normally gain access to the deeper subcutaneous tissues. The
organisms on the surface of the skin may, however, initiate an infectious process if a break in the
integrity of the skin barrier allows them to gain access to the deeper layers.
Compromised Patients
Some patient may be deficient in some of the antimicrobial defences the body has. These deficiencies
may be due to a disease process (for instance leukemia may give rise to a deficiency in phagocytosis) or
to medical or surgical procedures, including the administration of medication. For instance,
administration of immunosuppressive drugs to transplant patients may depress their immune system to
the point where it is no longer effective as a defence.
Below are examples of circumstances in which deficiency in host defences may lead to infections. Some
host defence mechanisms are more important than others in the prevention of certain specific
infections, and hence it is possible to predict which infection will occur in which patient. This is
important in the management of infections.
PATHOGENESIS OF INFECTIOUS DISEASE AND THE IMMUNE RESPONSE
BACKGROUND OF MICROBIAL DISEASE
"Clinical infection" (microbial disease): occurs when changes result
in functional damage to the infected host. Such changes occur when the balance between host and
microorganisms is disturbed:
Large no. of microbes Versus Small no. of microbes
Increased virulence Versus Attenuated virulence
Susceptible host Versus Resistant host
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ANTIBIOTIC RESISTANCE:
1. History and significance of antibiotic resistance
First Antibiotic: Penicillin discovered by Sir Alexander Fleming 1929;
Antibiotics such as penicillin, when introduced into clinical use in the 1940s and 1950s, were hailed as
miracle drugs.
Antibiotics reduce morbidity & mortality associated with pathogenic bacterial infections;
Antibiotic resistance (overuse) caused by:
1) antibiotic mis/use in agriculture/aquaculture;
2) antibiotics mis/use in human pop. (develop. countries);
3) immunocompromised patients alive longer=transmit antibiotic resistant bacteria.
To add to the seriousness of the problem, the emergence of multiple antibiotic resistant (Mar) strains,
which develop simultaneous resistance to most of the commonly used antibiotics, has rendered some
infections untreatable. Therefore, there is an increased demand for the understanding of the
mechanisms of different antibiotic resistance and for the pharmaceutical industry to develop new
generations of antimicrobial agents.
Antibiotic Resistance:
Occurs to any antibiotic with sufficient time; he suseptile iroorgais is’t ihiited 
antibiotic agent; classified into 2 types: intrinsic resistance & acquired resistance.
Intrinsic: predictable form based on characteristics of microorganisms & antibiotics mechanism of action
(inherent or atural.
Acquired: previous susceptible organism becoming resistant to antibiotic; driven by 2 genetic processes
(mutation & selection; vertical evolution) & genetic material exchange (horizontal evolution); 3 major
mechanisms:
1) Alternation in drug target.
2) Production of inactivating enzymes.
3) Decreased antibiotic uptake.
2. Antibiotic Resistance Mechanisms:
Bacteria will develop resistance to virtually any antibiotic given sufficient time. Resistance develops
more often and more quickly in immunocompromised patients resulting in increased morbidity,
increased length of hospital stay and higher mortality.
Table 1 Major Resistance Mechanisms to Antibiotics
Resistance Type/Antibiotic Affected Mechanism of Resistance
Altered Target
Aminoblycosides (streptomycin) Altered ribosomal protein
$--‐latas Altered or new penicillin binding proteins
Clindamycin and Erythromycin Ribosomal RNA methylation
Fluoroquinolones Altered DNA gyrase
Rifampin Altered RNA polymerase
Sulfonamides New drug--‐resistat dihdropteroate synthase
Tetracycline Ribosomal protection
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