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What is the primary difference between acquired resistance and intrinsic resistance?
What is the primary difference between acquired resistance and intrinsic resistance?
Which mechanism is primarily responsible for the transfer of antibiotic resistance between bacteria?
Which mechanism is primarily responsible for the transfer of antibiotic resistance between bacteria?
Which of the following mechanisms does NOT contribute to antibiotic resistance?
Which of the following mechanisms does NOT contribute to antibiotic resistance?
What type of genetic element carries antibiotic resistance genes and replicates independently?
What type of genetic element carries antibiotic resistance genes and replicates independently?
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What is the significance of conjugation in the context of antibiotic resistance?
What is the significance of conjugation in the context of antibiotic resistance?
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Which option best describes transposons?
Which option best describes transposons?
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Which mechanism allows bacteria to prevent drug accumulation effectively?
Which mechanism allows bacteria to prevent drug accumulation effectively?
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How can a single antibiotic resistance be exhibited by a microorganism?
How can a single antibiotic resistance be exhibited by a microorganism?
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What is antimicrobial resistance?
What is antimicrobial resistance?
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Why is antimicrobial resistance a significant concern?
Why is antimicrobial resistance a significant concern?
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Which of the following is a factor promoting antimicrobial resistance?
Which of the following is a factor promoting antimicrobial resistance?
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What is a proposed strategy to overcome bacterial resistance?
What is a proposed strategy to overcome bacterial resistance?
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Which type of infections might valuable antimicrobials be restricted to?
Which type of infections might valuable antimicrobials be restricted to?
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What is a secondary infection also referred to as?
What is a secondary infection also referred to as?
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Which of the following practices might contribute to the development of antimicrobial resistance?
Which of the following practices might contribute to the development of antimicrobial resistance?
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What is intrinsic resistance?
What is intrinsic resistance?
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What type of resistance occurs in bacteria that have never been susceptible to a particular antibiotic?
What type of resistance occurs in bacteria that have never been susceptible to a particular antibiotic?
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Which of the following methods is primarily responsible for acquired bacterial resistance?
Which of the following methods is primarily responsible for acquired bacterial resistance?
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Which bacteria are intrinsically resistant to vancomycin due to their inability to allow the drug passage?
Which bacteria are intrinsically resistant to vancomycin due to their inability to allow the drug passage?
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How can bacteria acquire resistance through horizontal gene transfer?
How can bacteria acquire resistance through horizontal gene transfer?
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What mechanism describes a bacteria's intrinsic resistance to aminoglycosides as observed in obligate anaerobes?
What mechanism describes a bacteria's intrinsic resistance to aminoglycosides as observed in obligate anaerobes?
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Which type of bacteria is known for intrinsic resistance to all β-lactams?
Which type of bacteria is known for intrinsic resistance to all β-lactams?
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What is a common factor leading to acquired resistance in bacteria?
What is a common factor leading to acquired resistance in bacteria?
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What is the primary difference between intrinsic and acquired resistance in bacteria?
What is the primary difference between intrinsic and acquired resistance in bacteria?
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What mechanism allows bacteria to resist beta-lactam antibiotics by rendering them ineffective?
What mechanism allows bacteria to resist beta-lactam antibiotics by rendering them ineffective?
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How can superinfection occur following the use of broad-spectrum antibiotics?
How can superinfection occur following the use of broad-spectrum antibiotics?
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Which of the following conditions is caused by the overgrowth of Clostridium difficile following antibiotic use?
Which of the following conditions is caused by the overgrowth of Clostridium difficile following antibiotic use?
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What effect do probiotics have on gut microbiota?
What effect do probiotics have on gut microbiota?
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Which of the following can be a consequence of the destruction of lactobacilli in the vagina due to antibiotics?
Which of the following can be a consequence of the destruction of lactobacilli in the vagina due to antibiotics?
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What characterizes normal microflora in the human body?
What characterizes normal microflora in the human body?
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What is a primary cause of increased susceptibility to pathogenic bacteria after antibiotic therapy?
What is a primary cause of increased susceptibility to pathogenic bacteria after antibiotic therapy?
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What is the role of lactobacilli normally found in the vagina?
What is the role of lactobacilli normally found in the vagina?
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What mechanism allows bacteria to prevent antibiotic accumulation?
What mechanism allows bacteria to prevent antibiotic accumulation?
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Which enzyme is responsible for the deactivation of the β-lactam ring in penicillins?
Which enzyme is responsible for the deactivation of the β-lactam ring in penicillins?
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What alteration occurs to decrease the affinity of β-lactam antibiotics for their target?
What alteration occurs to decrease the affinity of β-lactam antibiotics for their target?
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What is one of the ways bacteria may develop resistance against sulfonamide?
What is one of the ways bacteria may develop resistance against sulfonamide?
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Which antibiotic is modified by acetylation in certain Gram-negative bacteria?
Which antibiotic is modified by acetylation in certain Gram-negative bacteria?
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Which alterations cause resistance to fluoroquinolones in some Gram-negative bacteria?
Which alterations cause resistance to fluoroquinolones in some Gram-negative bacteria?
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What is a consequence of bacteria altering RNA polymerase?
What is a consequence of bacteria altering RNA polymerase?
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What characteristic defines the new active form of tetracycline known as Tigicycline?
What characteristic defines the new active form of tetracycline known as Tigicycline?
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Study Notes
Pharmaceutical Microbiology PM 502, Lecture 5
- Bacterial resistance is a significant concern in the field of pharmaceutical microbiology.
- Antimicrobial resistance is defined as the ability of a microorganism to survive and multiply in the presence of an antimicrobial agent that was intended to inhibit or kill it.
- Resistance leads to treatment failure and increased mortality.
- Resistant bacteria, including Pseudomonas, Streptococci, Staphylococci, Enterococci, and Klebsiella pneumoniae can spread in communities and healthcare facilities (nosocomial infections).
Lecture Outline
- What is antimicrobial resistance?
- Why is antimicrobial resistance a concern?
- Factors that promote antimicrobial resistance
- Strategies to contain or overcome bacterial resistance
- Genetic basis of bacterial resistance (intrinsic and acquired)
- Mechanisms of resistance to antimicrobials
- What is a secondary infection (superinfection)?
Introduction
- Throughout history, humans have battled microorganisms causing infections and diseases.
- Antimicrobial resistance is a significant issue.
Evolution of Bacterial Resistance
- The observation of Staphylococcus spp. growing in the presence of penicillin marked the beginning of the antimicrobial resistance era.
- The timeline shows the development of antibiotic resistance observed over time.
What is Antimicrobial Resistance?
- Antimicrobial resistance is the ability of a microorganism to survive and multiply in the presence of an antimicrobial agent designed to inhibit or kill it.
- Resistant organisms result in treatment failure and heightened mortality rates.
- Resistant bacteria such as Pseudomonas, streptococci, staphylococci, enterococci, and Klebsiella pneumoniae can spread in the community and healthcare settings (nosocomial infections).
Factors Promoting Antimicrobial Resistance
- Antibiotics sold without proper medical supervision.
- Failure to take prescribed antibiotics correctly.
- Exposure to suboptimal levels of antimicrobial agents.
- Taking antibiotics for viral infections.
- Use of antibiotics in animal feed and agriculture to prevent infection and promote growth.
Strategies to Overcome Bacterial Resistance
- Educational programs for healthcare workers.
- Requiring justification for prescribing antibiotics.
- Physicians taking responsibility for accurate diagnoses and correct therapies.
- Ensuring patients take the correct dosage of antibiotics by the appropriate route and for the correct duration.
- Restricting the use of valuable antimicrobials to only one or two types of infections.
- Reducing the addition of antimicrobials to animal feeds globally.
Bacterial Resistance to Antibiotics
- Resistance can be intrinsic (innate) or acquired.
- Intrinsic resistance occurs in organisms that have never been susceptible to a particular drug. It's usually due to inherent properties of the organism.
- Acquired resistance occurs when a microorganism becomes resistant after exposure to an antibiotic. This can be due to mutations or horizontal gene transfer.
Examples of Intrinsic Resistance
- Obligate anaerobes lack the electron transport system, making them resistant to aminoglycosides because this system is required for drug uptake.
- Mycoplasma lacks a cell wall, making them inherently resistant to beta-lactams and other cell wall-targeting antibiotics.
- Gram-negative bacteria are resistant to vancomycin due to its size; it cannot pass through the porin channels in their outer membrane.
- Many Gram-negative organisms are resistant to macrolides and certain beta-lactams because of their hydrophobic nature.
Acquired Resistance
- Acquired resistance is the ability of a microorganism to resist the activity of a particular antimicrobial agent after being previously susceptible..
- Unlike intrinsic resistance, the traits associated with acquired resistance only appear in some strains or subpopulations within a bacterial species.
Mechanisms of Acquired Resistance (a) Chromosomal Mutations
- Changes in a single base pair can alter the amino acid sequence of an enzyme or cellular structure.
- This, in turn, changes the affinity of the microorganism for the antibiotic, affecting its activity.
Mechanisms of Acquired Resistance (b) Horizontal Gene Transfer
- Resistance genes can be acquired from plasmids or transposons transferred through conjugation, transformation, or transduction.
- Plasmids are extra-chromosomal DNA elements that replicate independently in the cytoplasm.
- R-plasmids carry resistance genes.
- Transposons are "jumping" genes capable of moving between different DNA molecules (chromosomes or plasmids).
Biochemical Mechanisms of Antibiotic Resistance
- Decreased membrane permeability: Alteration in membrane structure decreases antibiotic uptake.
- Efflux pumps: Proteins actively pump antibiotics out of the cell.
- Enzyme inactivation: Enzymes (e.g., beta-lactamases) modify or inactivate antibiotics.
- Target site alteration: Modification of target sites (e.g., ribosomes, DNA gyrase) reduces the efficacy of antibiotics.
- Alternative metabolic pathways: Microorganisms use alternative pathways to satisfy metabolic requirements, unaffected by the antibiotic.
Superinfections
- Broad-spectrum antimicrobials can destroy beneficial microbes, allowing resistant microbes to overgrow and cause a secondary infection.
- Certain infections (e.g., pseudomembranous colitis, vaginal candidiasis, oral candidiasis) are examples of superinfections that may occur after antibiotic use.
Clinical Situations with Prophylactic Antibiotics
- Pretreatment for preventing streptococcal infections in patients with a history of rheumatic heart disease.
- Pretreatment for patients undergoing dental extractions or having implanted prosthetic devices.
- Pretreatment before most surgical procedures can reduce post-operative infections.
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Test your knowledge on antibiotic resistance with this quiz that covers fundamental concepts like intrinsic vs acquired resistance, mechanisms of gene transfer, and the significance of antimicrobial resistance. Explore factors promoting resistance and potential strategies to overcome these challenges in microbial infections.