Download Treatment of Infections

Treatment of Infections
1. Outline the defence mechanisms in the lung which are impaired by CF
As CF is a deficit of the epithelial chloride channels due to abnormal functioning of the cystic fibrosis
transmembrane conductance regulator (CFTR), the epithelial cells of the lungs will be affected.
The defence mechanisms in the lung which are impaired are:

Innate Defences
o Surface barrier
Mucous membrane impaired due to mutation of CFTR gene
Cl⁻ secretion into the lumen
Epithelial sodium channel (ENaC) action is also ↑
↑ Na⁺ into cell
↑water into the cell
Mucous membrane is dehydrated
Less effective barrier

Less effective barrier means
o Defective mucociliary clearance
o Accumulation of hyperconcentrated viscid secretions leading to obstruction and an
inability to clear bacteria (especially pseudomonas aeruginosa species)
o Static mucous creates hypoxic microenvironment which favours alginate production
that allows bacteria to form a protective biofilm that protects them, allowing them
to evade host defences. This leads to chronic lung disease and pulmonary
destruction
o Bronchioles distended with mucous which leads to hyperplasia (increase in number
of cells) and hypertrophy (increase in size of cells) of mucous secreting cells.
o Prone to bronchitis and bronchiestasis (irreversible dilatation and destruction of the
bronchial walls, often as a result of infection or obstruction).
o Lung abscesses can occur
2. List the major groups of antibiotics a nd outline their mechanisms of
action
Antibiotics can be classified according to



Chemical structure
Spectrum of activity
Mechanism of action
Bacteriocidal effect – kills all bacteria
Bacteriostatic effect – stops growth (bacteria survive but don’t multiply)
Narrow spectrum – affects some bacteria only
Broad spectrum – affects numerous types of bacteria
Group
Inhibitors of cell
wall
Protein synthesis
inhibitors
Action
 Bacteriocidal
 Inhibits cell wall
production that
protects bacteria
 Inhibits production
of murein
(peptidoglycan)
lattice of cell wall


Can be
bacteriocidal or
bacteriostatic
Selectively inhibits
bacterial protein
Class
β-lactam
Chloramphernical
(broad spectrum,
bacteriostatic, inhibits
enzyme that links AA
together, side effect is
aplastic anaemia 1:50
Examples
Penicillin (βlactamase resistant –
methicillin, broad
spectrum – ampicillin
and amoxicillin,
extended spectrum –
antipseudomonal.
These are more
expensive)
Cephalosporin
(structurally similar
to pencillin)
synthesis
000, not to be given
to babies because
they cannot
metabolise the drug)
Tetracyclines (broad
spectrum,
bacteriostatic, bulky
structure of drug
blocks aminoacyltRNA binding
therefore peptide
bond synthesis is
inhibited)
Aminoglycosides
(bacteriocidal, but not
absorbed orally, has a
narrow therapeutic
window and requires
monitoring.
Penetration through
the cell wall and
requires oxygen
dependent active
transport, used for
serious gram –ve
infections)
Folate synthesis
inhibitors

Microorganisms
synthesise folate
from paminobenzoic acid
(PABA) so these
antibiotics interfere
with this synthesis
process
Macrolides
(bacteriostatic or –
cidal, wide spectrum,
gram +ve, suppresses
ribosome
advancement, widely
used as alternative to
penicillin allergic
patients)
Trimethoprim
(bacteriostatic,
resembles folic acid,
selective inhibitor of
dihydrofolate
reductase)
Tetracycline,
doxycycline
Gentamicin,
streptomycin,
amikacin
Erythromycin,
clarithromycin,
roxirithromycin
Sulphonamides
Sulfamethoxazole
(bacteriostatic, wide
range of gram +ve and
–ve)
Usually
Nucleic acid
synthesis inhibitors

Narrow spectrum
sulfamethoxazole
used in combination
with trimethoprim
(co-trimoxazole) for
complicated
infections
Quinolones (gram –
ve, urinary and GIT
infections only)
Antimycobacterial
agents (bacteriostatic,
used for leprosy and
TB, resistance
developed rapidly)
Nalidixic acid,
norfloxacin
Rifampicin
3. Describe the common mechanisms of resistance to antibiotics
1. Metabolic characteristics that confer a natural insensitivity to the drug on a particular strain
of the bacteria (natural resistance) Lullman et al (2005)
http://www.thieme.com.ipacez.nd.edu.au/SID2483990066258/ebooklibrary/flexibook/pubi
d1005568195/show_pdf.html?/pdf/pubid1005568195_1000.pdf
2. Acquired resistance – random genetic mutation gives rise to resistance (susceptible bacteria
die off, the resistant ones free to multiply)
3. Non susceptible DNA (resistant plasmid) is passed on from one resistant bacteria to another
via conjugation (temporary fusion so genetic material can be transferred) or transduction
(DNA transferred from one cell to another via a viral vector - bacteriophages – virus that
causes lysis of host bacteria). This is also acquired resistance.
E.g. some bacteria produce β-lactamase which breaks down the bonds in β-lactam (present in βlactam antibiotics). Therefore this renders the antibiotic ineffective against the bacteria which are
resistant to it.
The more frequently a drug is given the more probable resistance will develop.