principles of antimicrobial therapy

Question 1

what should we know before selecting the appropriate antimicrobial agents

Answer 1

1) The organism’s identity
2) The organism’s susceptibility to a particular agent
3) The site of the infection
4) Patient factors
5) The safety of the agent
6) The cost of therapy

Question 2

what is empiric therapy

Answer 2

immediate
administration of drug(s) prior to bacterial identification and
susceptibility testing

Question 3

when should we start the different therapies?

Answer 3

✓ Acutely ill patients with infections of unknown origin—for example, a
neutropenic patient or a patient with meningitis—require immediate
treatment.
✓ If possible, therapy should be initiated AFTER specimens for laboratory
analysis have been obtained but BEFORE the results of the culture and
sensitivity are available.

Question 4

Drug choice in the absence of susceptibility data is influenced by (in empiric therapy )

Answer 4

1. site if the infection
2. patient history (previous infections, age, recent travel history, recent antimicrobial therapy, immune
   status, whether the infection was hospital- or community-acquired)
   3.Local susceptibility data ( the use of an antibiogram)
3. Broad-spectrum therapy may be indicated initially when the organism is
   unknown or polymicrobial infections are likely.

Question 5

how do we determine the susceptibility of infective organisms?

Answer 5

After a pathogen is cultured, its susceptibility to specific antibiotics serves as a
guide in choosing antimicrobial therapy.
✓ The minimum inhibitory and bactericidal concentrations can are used in
determining of susceptibility a drug and can be experimentally determined

Question 6

Bacteriostatic versus bactericidal

Answer 6

Historically: Bacteriostatic drugs arrest the growth and replication of bacteria
at serum (or urine) levels achievable in the patient, thus limiting the spread
of infection until the immune system attacks, immobilizes, and eliminates the
pathogen

Bactericidal drugs effectively kill ≥99.9% bacteria within 18 to 24 hours of
incubation under specific laboratory conditions. Because of their more
aggressive antimicrobial action, bactericidal agents are often the drugs of
choice in seriously ill and immunocompromised patients

Question 7

why is the bacteriostatic\sididal classification is too simple?

Answer 7

most bacteriostatic agents are able to effectively kill organisms; however, they are
unable to meet the arbitrary cutoff value in the bactericidal definition.
✓ It is also possible for an antibiotic to be bacteriostatic for one organism and
bactericidal for another

Note that the rate of in vitro
killing is greater with
bactericidal agents,
but both agents are able to
effectively kill the organism

Question 8

what is the MIC and MBC

Answer 8

the minimum inhibitory concentration (MIC) :
✓ is the lowest antimicrobial concentration that prevents
visible growth of an organism after 24 hours of incubation.
✓ This serves as a quantitative measure of in vitro
susceptibility and is commonly used in practice to
streamline therapy

✓ The minimum bactericidal concentration:
✓ (MBC) is the lowest concentration of antimicrobial agent
that results in a 99.9% decline in colony count after
overnight broth dilution incubations

we use MIC and NOT MBC

Question 9

how does the site of infection affect therapy

Answer 9

Natural barriers to drug delivery are created by the structures of the
capillaries of some tissues such as:
✓ the prostate, testes, placenta, the vitreous body of the eye, and CNS,
like the BBB.

Question 10

The penetration and concentration of an antibacterial agent in the CSF
are particularly influenced by the following

Answer 10

1.
Lipid solubility of the drug
2.
Molecular weight of the drug
3.
Protein binding of the drug
4.
Susceptibility to transporters or efflux pumps

Question 11

what are the patient factors affecting choosing the antimicrobial agent

Answer 11

the status of the patient’s immune system?, kidneys, liver,
circulation( poor perfusion, e.g. DM), and age must be considered

In women, pregnancy or breast-feeding also affects selection of the
antimicrobial agent

Question 12

Cost of therapy
▪ is common for several drugs to show similar efficacy in treating an infection but vary
widely in cost
✓ Figure 37.5 illustrates the relative cost of commonly used drugs for
staphylococcal infections MRSA

Question 13

what are the different routes of administration and there uses

Answer 13

✓ The oral route of administration is appropriate for mild infections that
can be treated on an outpatient basis.
✓ In addition, economic pressures have prompted the use of oral
antibiotic therapy in all but the most serious infectious diseases.

✓ In hospitalized patients requiring intravenous therapy initially, the switch
to oral agents should occur as soon as possible.

✓ Parenteral administration is used for drugs that:
✓ are poorly absorbed from the GI tract ( e.g. aminoglycosides,
vancomycin)
✓ and for treatment of patients with serious infections, for whom it is
necessary to maintain higher serum concentrations of antimicrobial
agents.

Question 14

how do we determine the rational dose

Answer 14

Three important properties that have a significant influence on the
The frequency of dosing :
✓ concentration dependent killing (),
✓ time-dependent killing
✓ post antibiotic effect (PAE).

Question 15

what are
✓ concentration dependent killing (),
✓ time-dependent killing
✓ post antibiotic effect (PAE).

Answer 15

Concentration-dependent killing:
– A significant increase in the rate of bacterial killing as the concentration of antibiotic
increases (from 4- to 64-fold the MIC of the drug)
– Figure 28.6A
– Giving these drugs by a once-a-day bolus infusion achieves high peak levels, favoring
rapid killing of the infecting pathogen.
– E.g. aminoglycosides &daptomycin
•
Time-dependent (concentration-independent) killing:
– The efficacy of these drugs is best predicted by the time that blood concentrations of
a drug remain above the MIC.
– (Figure 28.6B)
– For example, dosing schedules for the penicillins and cephalosporins that ensure
blood levels greater than the MIC for 50% of the time provide the most clinical
efficacy.
• Therefore, extended (generally 3 hours) or continuous (24 hours) infusions can be
utilized instead of intermittent dosing (30 minutes).
•
Postantibiotic effect (PAE)
– The PAE is a persistent suppression of microbial growth that occurs after levels of
antibiotic have fallen below the MIC.
– For example, aminoglycosides and fluoroquinolones (Antimicrobial drugs exhibiting a
long PAE ) often require only one dose per day against gram -ve bacteria.

Question 16

what are the different spectrums

Answer 16

A. Narrow-spectrum antibiotics
✓ Chemotherapeutic agents acting only on a single or a limited group of
microorganisms are said to have a narrow spectrum.
For example, isoniazid is active only against Mycobacterium tuberculosis
(Figure 28.7B).
B. Extended-spectrum antibiotics
✓ Extended spectrum is the term applied to antibiotics that are modified
to be effective against gram-positive organisms and also against a
significant number of gram-negative bacteria.
✓ For example, ampicillin is considered to have an extended spectrum
because it acts against gram-positive and some gram-negative bacteria
(Figure 28.7C).
C. Broad-spectrum antibiotics
✓ Drugs such as tetracycline, fluoroquinolones and carbapenems affect a
wide variety of microbial species and are referred to as broad-spectrum
antibiotics

Question 17

what are the advantages of combination therapy

Answer 17

✓ This strategy:
✓ reduces the possibility of superinfections,
✓ decreases the emergence of resistant organisms,
✓ and minimizes toxicity.
✓ Combination therapy may be used empirically while culture results are
pending
✓ Some situations require combinations of antimicrobial drugs.
✓ For example, the treatment of tuberculosis benefits from drug
combinations, since the microorganisms show variable sensitivity
✓ Or when synergistic effect is required in special conditions ( enterococcal
endocarditis), e.g. Beta-lactams with aminoglycosides

Question 18

what are the disadvantages of combination therapy

Answer 18

Giving unnecessary combination therapy may lead to development of
antibiotic resistance
✓ Some antimicrobials act only when the microbe is multiplying, and
coadministration of a bacteriostatic agent with a second agent that
bactericidal may result in the interference of the first drug with the
action of the second .
✓ E.g. tetracycline with penicillins or cephalosporins
✓ Development of antimicrobial resistance by using unnecessary
combination therapy

Question 19

what is drug resistance in bacteria

Answer 19

Bacteria are considered resistant to an antibiotic if the maximal level of
that antibiotic that can be tolerated by the host does not halt their
growth.
✓ Some organisms are inherently resistant to an antibiotic. For example,
most gram-negative organisms are inherently resistant to vancomycin.
✓ However, microbial species that are normally responsive to a particular
drug may develop more virulent or resistant strains through
spontaneous mutation or acquired resistance and selection.
✓ Some of these strains may even become resistant to more than one
antibiotic.
A. Genetic alterations leading to drug resistance, due to a
spontaneous mutation on DNA
B. Altered expression of proteins in drug-resistant organisms leading to:
modification of target sites, decreased accumulation & enzymatic
inactivation.

Question 20

when can we use antibiotics prophylactically

Answer 20

Certain clinical situations, such as dental procedures and surgeries,
require the use of antibiotics for the prevention rather than for the
treatment of infections (Figure 28.9).
✓ Because the indiscriminate use of antimicrobial agents can result in
bacterial resistance and superinfection, prophylactic use is restricted to
clinical situations in which the benefits outweigh the potential risks.
✓ The duration of prophylaxis should be closely observed to prevent the
unnecessary development of antibiotic resistance.

Question 21

what are the complications of using antibiotics

Answer 21

A. Hypersensitivity: eg. penicillins

B. Direct
toxicity:
e.g.
aminoglycosides,
chloramphenicol,
tetracycline,
fluoroquinolones

C.
Superinfections:
use
of
broad
spectrum
antimicrobials
or
combinations of agents