Teaching Plan
by
School of Basic Medicine
Peking Union Medical College
Department:
Pharmacology
Lesson:
Pharmacology
Name of Teacher: Dechang Zhang
Professional Title:
1
Professor
Teaching
topic：
Teaching
subjects：
Hours：
antibacterial drugs
Teaching
aims:
1.
Medical Students
3 hours
2.
3.
To master the principles of antibacterial drugs use; conceptions
such as chemotherapy, antimicrobial drugs, chemotheraputic index
(CI), antibiotics, antimicrobial spectrum, minimal inhibitory
concentration (MIC), minimal bactericidal concentration (MBC),
and drug resistance; the mechanisms of antimicrobial agents.
To be familiar with. the mechanisms that bacteria produce drug
resistance to agents
To understand the methods of avoiding drug resistance
Teaching
content:
Chapter 35
antibacterial drugs
Emphases:
1.
2.
the principles of antibacterial drugs use
drug resistance
Difficult
Points:
1.
2.
3.
the principles of antibacterial drugs use
Measurement Principle of MIC, MBC
drug resistance
Evaluation
methods
Evaluation from students
References
1..Rang and Dale’s Pharmacology 6th edition Rang HP, Dall MM,
Ritter JM, Flower RJ , Churchill Livingstong, Elsevier, 2007
2.Golan DE， et al. Principle of Pharmacology, The pathophysiologic
basis of drug therepy 2nd ed. 2008
3.Farrell SE, Priciples of Pharmacology, Workbook 2nd ed, 2008
Lippincott.
4.Finlel R.,et al. eds, Lippincott’s Illustrated Reviews: Pharmacology
4th ed. Lippincott 2009
5. 杨世杰主编《药理学》（8 年制规划教材），人民卫生出版社，2005
年
6. 张德昌主编《医学药理学》中国协和医科大学出版社 1998 年
2
Teaching
aims
Contents
Chapter
antibacterial drugs
Methods
TimeRemarks
assignment
35
Comprehend
Overview
5 min
Comprehend
ⅠHistory
of
antimicrobial therapy
5 min
Master
Media mix,
ⅡPrinciples
of explanation,
question-raising
antimicrobial use：
12 Factors to consider and discussion
when
selecting case study
antimicrobial agents for
therapy in patients
5 min
Master
1. Is an antimicrobial
agent necessary?
10 min
Master
2. Identification of the
pathogen
5 min
Master
3.
Empiric
versus
directed therapy
10 min
Master
4. Need for bactericidal
versus bacteriostatic
agent
5. Determination of
antimicrobial
susceptibility of
infective organisms
6. Pharmacokinetic and
pharmacodynamic
factors
10 min
7. Anatomical site of
infection
8. Cost
9. Toxicity
10. Host factors
11. Antimicrobial
combinations
10min
12. Antibiotic resistance
concerns
Classroom Q & A
The
summary
and
review
10 min
Master
Master
Master
Comprehend
Master
Master
Master
Master
15 min
15 min
5 min
10 min
10 min
10 min
10 min
5 min
3
Reflection
questions
References
1.
2.
The current challenges of drug resistance and Solutions
Can it do to compare the antibacterial activity of antimicrobial
agents only through MIC?
1..Rang and Dale’s Pharmacology 6th edition Rang HP, Dall MM,
Ritter JM, Flower RJ , Churchill Livingstong, Elsevier, 2007
2.Golan DE ，
et al. Principle of Pharmacology, The
pathophysiologic basis of drug therepy 2nd ed. 2008
3.Farrell SE, Priciples of Pharmacology, Workbook 2nd ed, 2008
Lippincott.
4.Finlel R.,et al. eds, Lippincott’s Illustrated Reviews:
Pharmacology 4th ed. Lippincott 2009
5. 杨世杰主编《药理学》（8 年制规划教材），人民卫生出版社，
2005 年
6. 张德昌主编《医学药理学》中国协和医科大学出版社 1998
年
4
Chapter 35
antibacterial drugs
ⅠHistory of antimicrobial therapy
ⅡPrinciples of antimicrobial use:
12 Factors to consider when selecting antimicrobial agents for therapy
in patients
1. Is an antimicrobial agent necessary?
2. Identification of the pathogen
3. Empiric versus directed therapy
4. Susceptibility of infecting microorganism
5. Need for bactericidal versus bacteriostatic agent
6. Pharmacokinetic and pharmacodynamic factors
7. Anatomical site of infection
8. Cost
9. Toxicity
10. Host factors:
Allergy history
Age
Renal function
Hepatic function
Pregnancy status
Genetic or metabolic abnormalities
Host defenses function
11. Need for combination therapy
12. Antibiotic resistance concerns
1. Is an antimicrobial agent necessary?
• viral infections that do not respond to antibiotics
• noninfectious processes mimicking a bacterial infection
• culture isolation of an organism that is colonizing an anatomical site and
not causing an infection
In general, the clinician should resist temptation to begin antimicrobial
therapy unless there is a reasonable probability that a bacterial infection is
present.
Another indication for antimicrobials is prophylactic therapy, which is
intended to prevent illness in someone at risk of infection.
2.
Identification of the pathogen
Characterization of the organism is central to selection of the proper
drug.
3.
Empiric versus directed therapy
The acutely ill patient with infections of unknown origin a neutropenic
patient
a patient with severe headache, a rigid neck, and sensitivity to bright
lights(meeningitis)
Therapy is initiated after specimens for laboratory analysis have been
obtained but before the results of the culture are available.
The choice of drug in the absence of susceptibility data
5
the site of infection
the patient's history
Broad-spectrum therapy may be needed initially for serious infections
when the identity of the organism is unknown or the site makes a
polymicrobial infection likely.
4.Need for bactericidal versus bacteriostatic agent
Bacteristatic drugs arrest the growth and replication of bacteria at serum
levels achievable in the patient, thus limiting the spread of infection while the
body’s immune system attachs, immoblilizes, and eliminates the pathogens.
Bactericidal drugs kill bacteria at drug serum levels achievable in the
patient. They are more aggressive compare with bicteriostatic antimicrobial
drugs .
5. Determination of antimicrobial susceptibility of infective organisms
In the laboratory, susceptibility is most often measured using a disk
diffusion test
Stokes controlled sensitivity test
An alternative measure of susceptibility is to determine the Minimum
Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration
(MBC) of a drug.
A series of broths are mixed with serially diluted antibiotic solutions and
a standard inoculum is applied. After incubation, the MIC is the first broth in
which growth of the organism has been inhibited.
The more resistant an organism is, then the higher will be the MIC.
The MBC is measured by inoculating the broths used for MIC
determinations onto drug-free medium. The MBC is the first dilution at which
no growth is observed.
6. Pharmacokinetic and pharmacodynamic factors
Oral: peak concentrations :
1 to 2 hours may be delayed by food or delayed intestinal transit vary
widely in their oral bioavailability
Most life-threatening infections are treated, at least initially, with IV agents.
Parenteral therapy ensures adequate serum levels, and, for many agents,
higher drug levels can be achieved when administered IV.
Post-antibiotic effect (PAE)
These agents also continue to inhibit growth of bacteria for several hours
after the concentrations of the drug fall below the MIC in the serum.
The Post-Antibiotic Effect (PAE) shows the capacity of an antimicrobial
6
drug to inhibit the growth of bacteria after removal of the drug from the
culture.
A longer PAE can therefore influence the clinical outcome of antimicrobial
therapy.
Most β-lactam agents do not exhibit concentration-dependent killing nor
do they have a prolonged post-antibiotic effect.
7. Anatomical site of infection
The site of infection often influences not only the agent used but also the
dose, route, and duration of administration.
The desired peak concentration of drug at the site of infection should be at
least 4 times the MIC.
Blood-Brain Barrier
8. Cost
9. Toxicity
Because of nephrotoxicity and ototoxicity, aminoglycoside use has
decreased with the development of β-lactams and fluoroquinolones with
broad gram-negative activity.
10. Host factors
Allergy history, Age, Renal function, Hepatic function, Pregnancy status,
Genetic or metabolic abnormalities, Host defenses function
11. Antimicrobial combinations
Synergism is present if the activity of the combined antimicrobial agents is
greater than the sum of the independent activities.
12. Antibiotic resistance concerns
Prevalence of antibiotic resistant bacteria
Resistance in nosocomial infections
Resistance in community acquired infections
Antibiotic resistance can be intrinsic or acquired. Pseudomonas
aeruginosa outer membrane
Acquired resistance can be due to mutation of existing genetic information
or acquisition of new genes.
Mechanisms of bacterial resistance to antibiotics
Combating Antibiotic Resistance
Defining the Problem
Solving the problem
References
7