Molecular Basis of Bacterial Infections Evelien Floor
Antibiotic resistance: clinical
point of view
A patients case
Male patient of 38 years old:
Kidney insufficiency
Dialysis
First kidney transplant
Hemodialysis
Arterial calcifications
Second kidney transplant
Hemodialysis
Transplantectomy (removal of the transplant after rejection)
Peritoneal dialysis
Third kidney transplant
A normal creatinine concentration in a healthy individual is about 60. This patient had a level of 1300.
After transplantation it took a couple of days until the kidney worked and levels dropped. However, it
never dropped to a normal concentration.
After several researches it was found that there was a fungus present in the kidney, causing
progressive kidney failure. This was a very aggressive kind of infection and therefore a
transplantectomy was required. Subsequently a PET-scan showed a lot of bright spots indicating
infection.
The patient was treated with antibiotics and in a couple of months the bacteria already obtained
resistance against multiple antibiotics. This is probably due to new efflux pumps, because they can
pump out all kinds of antibiotics.
PK/PD approach to antibiotic therapy
Bacteria can be divided into two groups based on Gram-staining: Gram-negative and Gram-positive.
An antibiotic target for cell wall synthesis are the -lactamases (penicillin’s, cephalosporins,
carbapenems). -lactam antibiotics all contain a -lactam ring, only the side chains of this ring differ.
Susceptibility for a certain antibiotic can be measured with a disk diffusion test or E-test. When
choosing antibiotics, we try to make the spectrum as narrow as possible. This means covering the
likely demonstrated pathogens and limiting selection pressure. Combination therapy is used to try to
limit overlap in spectrum.
Pharmacodynamics (PD) describes what a drug does to an organism (i.e. bacterium). The minimal
inhibitory concentration (MIC) is the main PD-parameter in microbiology. The MIC states how high
the concentration needs to be to inhibit growth. The higher the MIC, the more resistant the micro-
organism. The MIC is about inhibition and not about killing.
The MIC is a value of standardized lab-conditions:
Certain growth medium
Certain bacterial inoculum
Certain incubation temperature
Certain duration of incubation
Certain growth phase of bacteria
1
Antibiotic resistance: clinical
point of view
A patients case
Male patient of 38 years old:
Kidney insufficiency
Dialysis
First kidney transplant
Hemodialysis
Arterial calcifications
Second kidney transplant
Hemodialysis
Transplantectomy (removal of the transplant after rejection)
Peritoneal dialysis
Third kidney transplant
A normal creatinine concentration in a healthy individual is about 60. This patient had a level of 1300.
After transplantation it took a couple of days until the kidney worked and levels dropped. However, it
never dropped to a normal concentration.
After several researches it was found that there was a fungus present in the kidney, causing
progressive kidney failure. This was a very aggressive kind of infection and therefore a
transplantectomy was required. Subsequently a PET-scan showed a lot of bright spots indicating
infection.
The patient was treated with antibiotics and in a couple of months the bacteria already obtained
resistance against multiple antibiotics. This is probably due to new efflux pumps, because they can
pump out all kinds of antibiotics.
PK/PD approach to antibiotic therapy
Bacteria can be divided into two groups based on Gram-staining: Gram-negative and Gram-positive.
An antibiotic target for cell wall synthesis are the -lactamases (penicillin’s, cephalosporins,
carbapenems). -lactam antibiotics all contain a -lactam ring, only the side chains of this ring differ.
Susceptibility for a certain antibiotic can be measured with a disk diffusion test or E-test. When
choosing antibiotics, we try to make the spectrum as narrow as possible. This means covering the
likely demonstrated pathogens and limiting selection pressure. Combination therapy is used to try to
limit overlap in spectrum.
Pharmacodynamics (PD) describes what a drug does to an organism (i.e. bacterium). The minimal
inhibitory concentration (MIC) is the main PD-parameter in microbiology. The MIC states how high
the concentration needs to be to inhibit growth. The higher the MIC, the more resistant the micro-
organism. The MIC is about inhibition and not about killing.
The MIC is a value of standardized lab-conditions:
Certain growth medium
Certain bacterial inoculum
Certain incubation temperature
Certain duration of incubation
Certain growth phase of bacteria
1
