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Damage To Cell Membrane
Damage To Cell Membrane
The goal of the second mechanism of action is to disrupt the function of the cell
membrane by altering the cell membrane structure to make it more permeable in order
to increase the uptake of antibiotic leading to death of the bacteria
Specific antimicrobial agent
Polymyxin
Colistin and polymyxin B belong to the class of polymyxins, which is one of the primary
classes of antibiotics with activity against most Gram-negative bacteria. The target of
polymyxins is the outer membrane of Gram-negative bacteria. Because of an
electrostatic interaction occurring between the α,γ-diaminobutyric acid residue of the
positively charged polymyxin on one side and the phosphate groups of the negatively
charged lipid A membrane on the other side, divalent cations (Ca2+ and Mg2+) are
displaced from the negatively charged phosphate groups of membrane lipids. The
lipopolysaccharide (LPS) is therefore destabilized, consequently increasing the
permeability of the bacterial membrane, leading to leakage of the cytoplasmic content
and ultimately causing cell death
Finally, another mode of action of the polymyxins is the inhibition of vital respiratory
enzymes (inhibition of type II NADH-quinone oxidoreductases [NDH-2]) in the bacterial
inner membrane.
They are active against most members of the Enterobacteriaceae family, including:
Escherichia coli
Enterobacter spp.
Klebsiella spp.
Citrobacter spp.
Salmonella spp. and
Shigella spp.
Example of Brand Names
Colistin
It interacts with the bacterial cytoplasmic membrane, changing its
permeability.
Brand name:
Coly-Mycin S (colistin and neomycin)
Cortisporin-TC (colistin)
Polymyxin b sulphate
Polymyxin B incorporates and destabilization of the cytoplasmic outer
membrane of Gram-negative bacteria, altering membrane permeability
and causing cell death.
Brand name:
Polytrim (Polymyxin B sulfate/trimethoprim)
Stratol (Polymyxin b/ neomycin)
Colistimethate
Colistimethate is polycationic and has both hydrophobic and lipophilic
moieties. It interacts with the bacterial cytoplasmic membrane, changing
its permeability.
Brand name:
Colistimethate (Coly-Mycin M)
Colobreathe (Colistimethate Sodium)
Contraindications:
hypersensitivity to drug/class/components.
concurrent neurotoxic agent use
concurrent nephrotoxic agent use
caution if renal impairment
Nursing responsibilities
Perform baseline serum electrolytes and kidney function tests before parenteral
therapy. Frequent monitoring of kidney function and serum drug levels is advised
during therapy. Monitor electrolytes at regular intervals during prolonged therapy.
Review electrolyte results. Patients with low serum calcium and low intracellular
potassium are particularly prone to develop neuromuscular blockade.
Inspect tongue every day. Assess for signs and symptoms of superinfection
Polymyxin therapy supports growth of opportunistic organisms. Report symptoms
promptly.
Monitor input and output. Maintain fluid intake sufficient to maintain daily urinary
output of at least 1500 mL. Some degree of renal toxicity usually occurs within
first 3 or 4 d of therapy even with therapeutic doses. Consult physician.
Withhold drug and report findings to physician for any of the following: Decreases
in urine output (change in I&O ratio), proteinuria, cellular casts, rising BUN,
serum creatinine, or serum drug levels (not associated with dosage increase). All
can be interpreted as signs of nephrotoxicity.
Nephrotoxicity is generally reversible, but it may progress even after drug is
discontinued. Therefore, close monitoring of kidney function is essential, even
following termination of therapy.
Be alert for respiratory arrest after the first dose and also as long as 45 d after
initiation of therapy. It occurs most commonly in patients with kidney failure and
high plasma drug levels and is often preceded by dyspnea and restlessness.
Peptidoglycan
Cytoplasm
Strategies
• Education is crucial—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. The majority of sore
throats and many respiratory infections are caused by viruses, and viruses are
unaffected by antibiotics. Because viruses are not killed by antibiotics, patients and
parents should not expect antibiotics when they or their children have viral infections.
Instead of demanding antibiotics from clinicians, they should be asking why one is being
prescribed.
• It is important that clinicians not allow themselves to be pressured by patients. They
should prescribe antibiotics only when warranted (i.e., only when there is a
demonstrated need for them). Whenever possible, clinicians should collect a specimen
for culture and have the Clinical Microbiology Laboratory perform susceptibility testing
(Chapter 13) to determine which antimicrobial agents are likely to be effective.
• Clinicians should prescribe an inexpensive, narrowspectrum drug whenever the
laboratory results demonstrate that such a drug effectively kills the pathogen. According
to Dr. Stuart B. Levy,e by some estimates, at least half of current antibiotic use in the
United States is inappropriate—antibiotics are either not indicated at all or they are
incorrectly prescribed as the wrong drug, the wrong dosage, or the wrong duration.
Another studyf demonstrated that colds, other upper respiratory infections, and
bronchitis accounted for 21% of all antibiotic prescriptions in 1992, although these
conditions typically do not benefit from antibiotics.
• Patients must take their antibiotics in the exact manner in which they are prescribed.
Healthcare professionals should emphasize this to patients and do a better job
explaining exactly how medications should be taken. • It is critical that clinicians
prescribe the appropriate amount of antibiotic necessary to cure the infection. Then,
unless instructed otherwise, patients must take alltheir pills—even after they are feeling
better. Again, this must be explained and emphasized. If treatments are cut short, there
is selective killing of only the most susceptible members of a bacterial population. The
more resistant variants are left behind to multiply and cause a new infection.
• Patients should always destroy any excess medications and should never keep
antibiotics in their medicine cabinet. Antimicrobial agents, including antibiotics,should be
taken only when prescribed and only under a clinician’s supervision.
• Unless prescribed by a clinician, antibiotics should never be used in a prophylactic
manner—such as to avoid “traveler’s diarrhea” when traveling to a foreign country.
Taking antibiotics in that manner actually increases the chances of developing traveler’s
diarrhea. The antibiotics kill some of the beneficial indigenous intestinal flora,
eliminating the competition for food and space, making it easier for pathogens to gain a
foothold.
• Healthcare professionals must practice good infection prevention and control
procedures (Chapter 12). Frequent and proper handwashing is essential to prevent the
transmission of pathogens from one patient to another. Healthcare professionals should
monitor for important pathogens (such as MRSA) within healthcare settings and always
isolate patients infected with multidrug-resistant pathogens.
Undesirable effects
Listed below are some of the many reasons why antimicrobial agents should not be
used indiscriminately.
• Whenever an antimicrobial agent is administered to a patient, organisms within that
patient that are susceptible to the agent will die, but resistant ones will survive. This is
referred to as selecting for resistant organisms (Fig. 9-6). The resistant organisms then
multiply, become dominant, and can be transmitted to other people. To prevent the
overgrowth of resistant organisms, sometimes several drugs, each with a different mode
of action, are administered simultaneously.
• The patient may become allergic to the agent. For example, penicillin G in low doses
often sensitizes those who are prone to allergies; when these persons receive a second
dose of penicillin at some later date, they may have a severe reaction known as
anaphylactic shock, or they may break out in hives.
• Many antimicrobial agents are toxic to humans, and some are so toxic that they are
administered only for serious diseases for which no other agents are available. One
such drug is chloramphenicol, which, if given in high doses for a long period, may cause
a very severe type of anemia called aplastic anemia. Another is streptomycin, which can
damage the auditory nerve and cause deafness. Other drugs are hepatotoxic or
nephrotoxic, causing liver or kidney damage, respectively.
• With prolonged use, broadspectrum antibiotics may destroy the normal flora of the
mouth, intestine, or vagina. The person no longer has the protection of the indigenous
microflora and thus becomes much more susceptible to infections caused by
opportunists or secondary invaders. The resultant overgrowth by such organisms is
referred to as a superinfection. A superinfection can be thought of as a “population
explosion” of organisms that are usually present only in small numbers. For example,
the prolonged use of oral antibiotics can result in a superinfection of Clostridium
difficilein the colon, which can lead to such diseases as antibiotic-associated diarrhea
(AAD) and pseudomembranous colitis (PMC). Yeast vaginitis often follows antibacterial
therapy because many bacteria