Podcast
Questions and Answers
What characterizes a bactericidal effect?
What characterizes a bactericidal effect?
- Kills bacteria above MIC (correct)
- Inhibits growth at all concentrations above MIC
- Requires lower concentration than MIC to be effective
- Only inhibits growth without killing
What type of killing does beta-lactams exhibit?
What type of killing does beta-lactams exhibit?
- Concentration Dependent Killing
- Time Above MIC Killing (correct)
- Peak to MIC Killing
- Dose Independent Killing
Which of the following classes of antibiotics is known for dose dependent killing?
Which of the following classes of antibiotics is known for dose dependent killing?
- Aminoglycosides (correct)
- Macrolides
- Beta-Lactams
- Tetracyclines
Above what concentration does a bacteriostatic agent inhibit bacterial growth?
Above what concentration does a bacteriostatic agent inhibit bacterial growth?
Which of the following statements is true regarding the action of antibiotics?
Which of the following statements is true regarding the action of antibiotics?
What type of antibiotics are known for time-dependent killing?
What type of antibiotics are known for time-dependent killing?
Which of the following changes facilitates the activity of penicillin against gram-negative aerobes?
Which of the following changes facilitates the activity of penicillin against gram-negative aerobes?
Nafcillin and Oxacillin are primarily eliminated through which route?
Nafcillin and Oxacillin are primarily eliminated through which route?
Which penicillin is recognized for high protein binding, typically greater than 90%?
Which penicillin is recognized for high protein binding, typically greater than 90%?
What major issue arises due to the presence of extended-spectrum β-lactamases (ESBL)?
What major issue arises due to the presence of extended-spectrum β-lactamases (ESBL)?
What limits the penetration of antibiotics into the prostate, eye, and bone?
What limits the penetration of antibiotics into the prostate, eye, and bone?
What is a common side effect associated with beta-lactam antibiotics?
What is a common side effect associated with beta-lactam antibiotics?
Which of the following penicillin derivatives is specifically designed to resist penicillinase?
Which of the following penicillin derivatives is specifically designed to resist penicillinase?
What is the effect of bacteriostatic agents on bacterial growth?
What is the effect of bacteriostatic agents on bacterial growth?
Which factor primarily determines clinical success in antibiotic treatment?
Which factor primarily determines clinical success in antibiotic treatment?
What is the area under the inhibitory concentration (AUIC) value associated with better outcomes for Vancomycin use?
What is the area under the inhibitory concentration (AUIC) value associated with better outcomes for Vancomycin use?
Which of the following is considered a dose-dependent killing antibiotic?
Which of the following is considered a dose-dependent killing antibiotic?
What is the recommended trough concentration of Vancomycin for serious infections?
What is the recommended trough concentration of Vancomycin for serious infections?
Which site of infection is known for poor penetration of aminoglycosides?
Which site of infection is known for poor penetration of aminoglycosides?
Which of the following antibiotics is associated with exposure-dependent killing?
Which of the following antibiotics is associated with exposure-dependent killing?
What does the acronym MIC stand for in pharmacodynamics?
What does the acronym MIC stand for in pharmacodynamics?
Which of the following describes the mechanism of action of Vancomycin?
Which of the following describes the mechanism of action of Vancomycin?
What is a notable characteristic of the pharmacokinetics of Oritavancin and Dalbavancin?
What is a notable characteristic of the pharmacokinetics of Oritavancin and Dalbavancin?
Which condition is most likely associated with the use of all antibiotic classes?
Which condition is most likely associated with the use of all antibiotic classes?
What describes a mechanism of resistance to Vancomycin?
What describes a mechanism of resistance to Vancomycin?
Which statement regarding Vancomycin's distribution is true?
Which statement regarding Vancomycin's distribution is true?
Which side effect is commonly associated with an allergic reaction to antibiotics?
Which side effect is commonly associated with an allergic reaction to antibiotics?
What is the typical half-life range of Vancomycin?
What is the typical half-life range of Vancomycin?
Which action describes the pharmacologic property of glycopeptides?
Which action describes the pharmacologic property of glycopeptides?
Which route of elimination is primarily associated with Nafcillin and Oxacillin?
Which route of elimination is primarily associated with Nafcillin and Oxacillin?
What is a common mechanism of resistance to beta-lactam antibiotics?
What is a common mechanism of resistance to beta-lactam antibiotics?
What factor does NOT determine the activity of beta-lactam cell wall agents?
What factor does NOT determine the activity of beta-lactam cell wall agents?
Which condition can result from the use of all antibiotic classes?
Which condition can result from the use of all antibiotic classes?
Which of the following drugs would likely concentrate in the urine due to renal elimination?
Which of the following drugs would likely concentrate in the urine due to renal elimination?
What adverse effect is associated with the use of beta-lactam antibiotics, particularly with Nafcillin or Oxacillin?
What adverse effect is associated with the use of beta-lactam antibiotics, particularly with Nafcillin or Oxacillin?
Where in the body does beta-lactam absorption face significant challenges?
Where in the body does beta-lactam absorption face significant challenges?
Which factor can enhance the effectiveness of beta-lactam antibiotics against bacteria?
Which factor can enhance the effectiveness of beta-lactam antibiotics against bacteria?
Which class of antibiotics is known to penetrate poorly in the lungs?
Which class of antibiotics is known to penetrate poorly in the lungs?
What is a key factor in the activity of beta-lactam cell wall agents?
What is a key factor in the activity of beta-lactam cell wall agents?
Which condition is associated with all antibiotic classes, including beta-lactams?
Which condition is associated with all antibiotic classes, including beta-lactams?
Which route of elimination is NOT associated with Nafcillin and Oxacillin?
Which route of elimination is NOT associated with Nafcillin and Oxacillin?
What is the primary mechanism of resistance for beta-lactam antibiotics?
What is the primary mechanism of resistance for beta-lactam antibiotics?
What can interfere with the absorption of beta-lactam antibiotics?
What can interfere with the absorption of beta-lactam antibiotics?
Which of the following antibiotics offers significant renal elimination, concentrating in urine?
Which of the following antibiotics offers significant renal elimination, concentrating in urine?
Which beta-lactam antibiotic is specifically noted for its risk of cross-allergenicity?
Which beta-lactam antibiotic is specifically noted for its risk of cross-allergenicity?
Which of the following describes the factors determining the activity of beta-lactam antibiotics?
Which of the following describes the factors determining the activity of beta-lactam antibiotics?
Which antibiotics are known to concentrate in the urine due to renal elimination?
Which antibiotics are known to concentrate in the urine due to renal elimination?
What is a significant challenge for the absorption of beta-lactam antibiotics?
What is a significant challenge for the absorption of beta-lactam antibiotics?
Which statement is true about the penetration of aminoglycosides?
Which statement is true about the penetration of aminoglycosides?
What is a common side effect associated with Nafcillin and Oxacillin usage?
What is a common side effect associated with Nafcillin and Oxacillin usage?
What is the mechanism of resistance for gram-positive bacteria against beta-lactam antibiotics?
What is the mechanism of resistance for gram-positive bacteria against beta-lactam antibiotics?
Which condition is a precaution for all antibiotic classes, including beta-lactams?
Which condition is a precaution for all antibiotic classes, including beta-lactams?
What happens to aminoglycosides and vancomycin when administered for lung infections?
What happens to aminoglycosides and vancomycin when administered for lung infections?
Which antibiotics are known to poorly penetrate the lungs?
Which antibiotics are known to poorly penetrate the lungs?
What must be considered for drugs that penetrate the central nervous system (CNS) in terms of dosage?
What must be considered for drugs that penetrate the central nervous system (CNS) in terms of dosage?
Which factor does NOT determine the activity of beta-lactam cell wall agents?
Which factor does NOT determine the activity of beta-lactam cell wall agents?
What is the primary method of excretion for Nafcillin and Oxacillin?
What is the primary method of excretion for Nafcillin and Oxacillin?
Which condition is closely associated with all antibiotic classes, including beta-lactams?
Which condition is closely associated with all antibiotic classes, including beta-lactams?
What level of quinolone or fluconazole is typically found in urine compared to blood concentrations?
What level of quinolone or fluconazole is typically found in urine compared to blood concentrations?
What is one of the mechanisms of resistance for beta-lactam antibiotics?
What is one of the mechanisms of resistance for beta-lactam antibiotics?
Which of the following statements regarding absorption of beta-lactam agents is true?
Which of the following statements regarding absorption of beta-lactam agents is true?
Which antibiotics are known to exhibit poor penetration in the lungs?
Which antibiotics are known to exhibit poor penetration in the lungs?
What is the key factor affecting the activity of beta-lactam antibiotics?
What is the key factor affecting the activity of beta-lactam antibiotics?
Which of the following antibiotics must be given at higher doses due to the blood-brain barrier?
Which of the following antibiotics must be given at higher doses due to the blood-brain barrier?
Which antibiotics show significantly concentrated levels in the urine due to renal elimination?
Which antibiotics show significantly concentrated levels in the urine due to renal elimination?
What type of hypersensitivity reaction can occur with the use of penicillin antibiotics?
What type of hypersensitivity reaction can occur with the use of penicillin antibiotics?
What is the mechanism by which beta-lactam antibiotics become ineffective against certain bacteria?
What is the mechanism by which beta-lactam antibiotics become ineffective against certain bacteria?
Which class of antibiotics is associated with the risk of causing interstitial nephritis?
Which class of antibiotics is associated with the risk of causing interstitial nephritis?
Which factor is NOT involved in the action of beta-lactam cell wall agents?
Which factor is NOT involved in the action of beta-lactam cell wall agents?
What primarily affects the clinical success of beta-lactam antibiotics?
What primarily affects the clinical success of beta-lactam antibiotics?
Which of the following antibiotics is notable for penetrating poorly in the lungs?
Which of the following antibiotics is notable for penetrating poorly in the lungs?
What is a significant factor determining the activity of beta-lactam cell wall agents?
What is a significant factor determining the activity of beta-lactam cell wall agents?
What are the effects of beta-lactam antibiotics on the human immune system?
What are the effects of beta-lactam antibiotics on the human immune system?
Which condition may arise as a precaution for all antibiotic classes including beta-lactams?
Which condition may arise as a precaution for all antibiotic classes including beta-lactams?
What is a common route of elimination for beta-lactam antibiotics?
What is a common route of elimination for beta-lactam antibiotics?
What can inhibit the effectiveness of beta-lactam antibiotics?
What can inhibit the effectiveness of beta-lactam antibiotics?
Where do aminoglycosides exhibit poor penetration?
Where do aminoglycosides exhibit poor penetration?
Study Notes
Bactericidal Agents
- Bacteriostatic agents inhibit bacterial growth at all concentrations above the Minimum Inhibitory Concentration (MIC).
- Bactericidal agents inhibit growth above MIC and kill bacteria when concentrations exceed the Minimum Bactericidal Concentration (MBC).
Mechanisms of Killing
-
: Dose Dependent Killing: This type of killing is characterized by the relationship between drug concentration and its effect on bacteria.
- Agents such as aminoglycosides, quinolones, and daptomycin demonstrate concentration-dependent killing, where efficacy correlates with the peak concentration relative to the MIC.
-
Exposure (Time) Dependent Killing: Efficacy relies on the duration that the drug concentration remains above the MIC.
- Beta-lactams exemplify time-dependent killing, with effectiveness primarily determined by the time the drug remains active above the MIC.
Pharmacodynamics
- Pharmacodynamics examines the drug's effect on organisms, particularly on bacteria.
Drug Activity
- Bacteriostatic drugs inhibit bacterial growth at all concentrations above the minimum inhibitory concentration (MIC).
- Bactericidal drugs kill bacteria above the minimum bactericidal concentration (MBC) and inhibit growth above the MIC.
- Killing characteristics can be:
- Dose-Dependent (Peak: MIC) - efficacy related to drug concentration at peak levels.
- Exposure-Dependent (Time Above MIC) - efficacy relates to the duration the drug concentration exceeds the MIC.
Bactericidal Agents
- Aminoglycosides and quinolones exhibit dose-dependent killing.
- Beta-lactams demonstrate exposure-dependent killing.
- Composite measures like AUIC (Area Under Inhibitory Concentration) predict outcomes, with Vancomycin having an AUIC > 400 associated with improved clinical results.
Site of Infection
- Drug concentration at the infection site relative to the MIC is crucial for clinical success.
- Blood is the primary distribution route for antibiotics, regardless of administration method.
- Blood levels can be easily measured, unlike concentrations in other sites.
Specific Drug Concentrations
- Vancomycin:
- AUIC of 400-600 is optimal.
- Trough levels for serious infections: 15-20 mcg/mL; for mild infections: 10-15 mcg/mL.
- Aminoglycosides:
- Peak concentration varies by infection site (3-13 mcg/mL).
- Trough levels should be < 2 mcg/mL to minimize nephrotoxicity.
Historical Context
- 1929: Alexander Fleming discovered Penicillium notatum inhibits Staphylococcus aureus.
- 1941: Howard W Florey treated first patients with penicillin for streptococcal and gonococcal infections.
- Emergence of penicillinase-producing staphylococci led to modifications in penicillin structure, resulting in:
- Aminopenicillins
- Carboxypenicillins
- Ureidopenicillins
- β-lactamase inhibitors
Structure and Mechanism of Action
- Bacterial cell wall structures are primary targets for beta-lactam antibiotics.
- Key factors influencing activity include:
- Affinity, type, and concentration of penicillin-binding proteins.
- Activation of autolysins, enzymes crucial for cell wall remodeling.
General Pharmacologic Properties of Beta-Lactam Antibiotics
- Absorption varies, with excellent penetration in some tissues and poor in others (e.g., prostate, eye, bone).
- CNS penetration is significant only when the meninges are inflamed; can cross placenta and breast milk.
- Metabolism/Excretion:
- Biliary excretion for Nafcillin, Oxacillin, and Piperacillin, while Ceftriaxone is both renal and biliary.
Resistance Mechanisms
- Inactivation by β-lactamases:
- Occurs outside the cell wall for gram-positives and in the periplasmic space for gram-negatives.
- Extended-spectrum β-lactamases (ESBLs) found in K. pneumoniae and E. coli.
- Decreased cell wall permeability and development of new penicillin-binding proteins enhance bacterial resistance, notably in Streptococcus pneumoniae and MRSA.
Side Effects
- Common side effects: nausea, vomiting, diarrhea, and risk of Pseudomembranous colitis (CDAD).
- Allergic reactions can range from mild rashes to severe anaphylaxis; interstitial nephritis particularly with Nafcillin/Oxacillin.
Mechanism of Glycopeptide and Lipoglycopeptide Action
- Vancomycin and analogous agents inhibit cell wall synthesis by binding to the D-Ala-D-Ala termini.
- Resistance mechanisms include substituting D-Ala with D-lactate (VanH and VanA resistance).
Agents
- Vancomycin (Vancocin®): MOA 1,2 (IV, PO, glycopeptide).
- Telavancin (Vibativ®): MOA 1,2,4 (IV, lipoglycopeptide).
- Oritavancin (Orbactiv®): Compatible in D5W only; MOA 1,2,3,4 (IV, lipoglycopeptide).
- Dalbavancin (Dalvance®): Compatible in D5W only; MOA 1,2,4 (IV, lipoglycopeptide).
General Pharmacologic Properties
- Absorption: Poor oral absorption; used orally or rectally predominantly for C. diff colitis.
- Distribution: Vancomycin has poor CNS penetration and lung penetration; trough targeted to achieve systemic effectiveness.
- Metabolism/Excretion:
- Vancomycin and Telavancin have a half-life of 6-10 hours; renal adjusting is necessary.
- Oritavancin and Dalbavancin have a long half-life of 14-16 days, allowing for weekly dosing.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
Lungs
- Quinolones and macrolides exhibit high concentration in lung tissue.
- Aminoglycosides and vancomycin, along with daptomycin, have poor penetration in the lungs.
Central Nervous System (CNS)
- The blood-brain barrier (BBB) protects the CNS; higher doses and possibly intrathecal (IT) administration are necessary.
Urine
- Drugs eliminated through the kidneys concentrate in urine.
- Quinolones and fluconazole can reach urine levels that are 100 times higher than blood levels.
Action of Beta-Lactam Cell Wall Agents
- Beta-lactams are bactericidal and exhibit time-dependent killing.
- Factors influencing activity include:
- Cell wall penetration and permeability.
- Affinity for penicillin-binding proteins (PBPs).
- Specific type and concentration of PBPs.
- Activation of autolysins, enzymes that break down cell wall components.
Absorption and Distribution
- Most beta-lactam agents are destroyed by gastric acid.
- CNS penetration occurs only through inflamed meninges.
- Commonly excreted renally, including via tubular secretion.
- Biliary excretion occurs for agents like Nafcillin, Oxacillin, Piperacillin, and Ceftriaxone.
Resistance
- Resistance can occur through inactivation by beta-lactamases:
- Beta-lactamases can be found outside the cell wall for gram-positive bacteria.
- For gram-negative bacteria, they are typically present in the periplasmic space.
- Hydrolysis of the beta-lactam ring leads to resistance.
- Development of new penicillin-binding proteins can emerge, notably in:
- Streptococcus pneumoniae.
- Methicillin-resistant Staphylococcus aureus (MRSA).
Adverse Effects
- Pseudomembranous colitis (CDAD) poses a risk with all antibiotic classes.
- Hemolytic anemia may occur, evidenced by a positive direct Coombs test, due to penicillin binding to human proteins, forming a hapten that is recognized as foreign.
- Cross-reactivity can occur among various penicillins and other beta-lactams.
- Interstitial nephritis is particularly associated with Nafcillin and Oxacillin use.
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Description
Explore the concepts of bacteriostatic and bactericidal activities of antibiotics in this quiz. Learn about dose-dependent and time-dependent killing mechanisms, focusing on aminoglycosides, quinolones, daptomycin, and beta-lactams. Test your understanding of these critical pharmacological principles.
