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Questions and Answers
What is the main function of bacteriostatic antibiotics?
What is the main function of bacteriostatic antibiotics?
Which of the following best distinguishes between antibiotics and antimicrobials?
Which of the following best distinguishes between antibiotics and antimicrobials?
Which method describes how bactericidal antibiotics function?
Which method describes how bactericidal antibiotics function?
What is the significance of Minimum Inhibitory Concentration (MIC) in antibiotic therapy?
What is the significance of Minimum Inhibitory Concentration (MIC) in antibiotic therapy?
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What was the role of antibiotics like sulfonamides and penicillin in modern medicine?
What was the role of antibiotics like sulfonamides and penicillin in modern medicine?
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What is a common disadvantage of antibiotics regarding their effectiveness against certain bacteria?
What is a common disadvantage of antibiotics regarding their effectiveness against certain bacteria?
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What does the term 'chemotherapeutic agents' refer to?
What does the term 'chemotherapeutic agents' refer to?
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Which of the following best describes the risks associated with antibiotic use?
Which of the following best describes the risks associated with antibiotic use?
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What is the primary reason for using empiric therapy in antibiotic treatment?
What is the primary reason for using empiric therapy in antibiotic treatment?
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Which of the following statements about directed therapy is true?
Which of the following statements about directed therapy is true?
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Which factor should be avoided when choosing empirical therapy for antibiotic treatment?
Which factor should be avoided when choosing empirical therapy for antibiotic treatment?
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What is the recommended action if empiric therapy is initiated?
What is the recommended action if empiric therapy is initiated?
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What is the main disadvantage of using empiric therapy compared to directed therapy?
What is the main disadvantage of using empiric therapy compared to directed therapy?
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Which statement best describes the antibiotic classes mentioned?
Which statement best describes the antibiotic classes mentioned?
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What should be done before starting antibiotic therapy?
What should be done before starting antibiotic therapy?
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Which antibiotic class is known for its inhibition of cell wall synthesis?
Which antibiotic class is known for its inhibition of cell wall synthesis?
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What is a common misconception regarding the use of antibiotics based on prior patient responses?
What is a common misconception regarding the use of antibiotics based on prior patient responses?
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What mechanism allows bacteria to become unrecognizable to antibiotics through mutations?
What mechanism allows bacteria to become unrecognizable to antibiotics through mutations?
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What is a primary feature of plasmids in genetic origin of antibiotic resistance?
What is a primary feature of plasmids in genetic origin of antibiotic resistance?
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How do extrachromosomal elements contribute to antibiotic resistance?
How do extrachromosomal elements contribute to antibiotic resistance?
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What resistance mechanism do Salmonella species demonstrate against aminoglycosides?
What resistance mechanism do Salmonella species demonstrate against aminoglycosides?
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What type of mutation results in a permanent change in antibiotic susceptibility in bacteria?
What type of mutation results in a permanent change in antibiotic susceptibility in bacteria?
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What is a primary mechanism through which plasmids mediate drug resistance?
What is a primary mechanism through which plasmids mediate drug resistance?
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Which type of bacteria are typically resistant to penicillins due to their structural characteristics?
Which type of bacteria are typically resistant to penicillins due to their structural characteristics?
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Which process allows genetic material to be taken up by bacteria from their environment?
Which process allows genetic material to be taken up by bacteria from their environment?
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Which drug is specifically noted for its activity against MRSA and resistant streptococci?
Which drug is specifically noted for its activity against MRSA and resistant streptococci?
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Which beta-lactam is known for providing CNS coverage and is effective against Pseudomonas?
Which beta-lactam is known for providing CNS coverage and is effective against Pseudomonas?
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What is the primary use of Aztreonam?
What is the primary use of Aztreonam?
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Which combination is known as Co-amoxiclave?
Which combination is known as Co-amoxiclave?
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Which of the following is a side effect common to beta-lactam antibiotics?
Which of the following is a side effect common to beta-lactam antibiotics?
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Which non-ciprofloxacin quinolone is known to cover Pseudomonas?
Which non-ciprofloxacin quinolone is known to cover Pseudomonas?
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Which of the following antibiotics is contraindicated in patients with epilepsy or existing CNS lesions?
Which of the following antibiotics is contraindicated in patients with epilepsy or existing CNS lesions?
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What is a common caution associated with quinolone antibiotics?
What is a common caution associated with quinolone antibiotics?
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What is a potential disadvantage of using broad-spectrum antibiotics?
What is a potential disadvantage of using broad-spectrum antibiotics?
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When is the use of narrow-spectrum antibiotics considered dangerous?
When is the use of narrow-spectrum antibiotics considered dangerous?
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Which of the following factors is NOT associated with patient-specific considerations in antibiotic choice?
Which of the following factors is NOT associated with patient-specific considerations in antibiotic choice?
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What is the primary role of empirical therapy in antibiotic treatment?
What is the primary role of empirical therapy in antibiotic treatment?
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Which principle is recommended regarding microbiology specimens in antibiotic guidelines?
Which principle is recommended regarding microbiology specimens in antibiotic guidelines?
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What does the pharmacokinetic/pharmacodynamic (PK/PD) profile of an antibiotic include?
What does the pharmacokinetic/pharmacodynamic (PK/PD) profile of an antibiotic include?
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Why is it important to await microscopy or culture results when feasible?
Why is it important to await microscopy or culture results when feasible?
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What is a common misconception about laboratory diagnosis in antibiotic treatment?
What is a common misconception about laboratory diagnosis in antibiotic treatment?
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Which combination of drugs is used for treating Toxoplasmosis?
Which combination of drugs is used for treating Toxoplasmosis?
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What is a significant side effect of prolonged therapy with sulfonamides?
What is a significant side effect of prolonged therapy with sulfonamides?
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Which statement about sulfonamides in treating urinary tract infections is correct?
Which statement about sulfonamides in treating urinary tract infections is correct?
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What mechanism can lead to drug resistance in microorganisms regarding sulfonamides?
What mechanism can lead to drug resistance in microorganisms regarding sulfonamides?
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In the treatment and prophylaxis of resistant malaria, which combination is used?
In the treatment and prophylaxis of resistant malaria, which combination is used?
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Topical treatment for ocular infections typically involves which of the following agents?
Topical treatment for ocular infections typically involves which of the following agents?
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What precaution should be taken when using sulfonamides in patients with liver disease?
What precaution should be taken when using sulfonamides in patients with liver disease?
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Which of the following is a primary use of Silver sulfadiazine?
Which of the following is a primary use of Silver sulfadiazine?
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Study Notes
Clinical Uses of Antibiotics
- Antibiotics are a commonly used group of drugs, globally.
- In the USA, 23 million kg is used annually with half used for medical reasons.
- Antibiotic use can account for up to half of a hospital's drug expenditure.
- Research worldwide shows a high incidence of inappropriate antibiotic use.
Terminology
- Chemotherapy involves using drugs to treat infections and malignancies (antimicrobials and antineoplastics).
- Chemotherapeutic agents selectively target microbes or malignant cells, distinct from body cells.
- Antimicrobials are used to treat infectious illnesses.
- Antibiotics are derived from microbes and used to inhibit/kill other microbes. All antibiotics are antimicrobials, but not all antimicrobials are antibiotics.
Types of Antibiotic Action
- Bacteriostatic antibiotics prevent bacteria from multiplying, allowing the host's defence system to eliminate the remaining bacteria.
- Bactericidal antibiotics kill bacteria.
- Minimum Inhibitory Concentration (MIC) is the lowest concentration of an antibiotic that inhibits bacterial growth.
- Minimum Bactericidal Concentration (MBC) is the lowest antibiotic concentration that kills 99.99% of bacteria.
History of Antibiotics
- Sulfonamides were a key development in antibiotic therapies, starting in the 1930s.
- Penicillin, developed in the 1940s, revolutionized the field.
- These drugs markedly decreased morbidity and mortality from infectious diseases, leading to the modern antibiotic therapeutic era.
Sulfa Drugs
- Discovered by Gerhard Domagk, a German biochemist in 1932.
- Prontosil, a dye, initially tested, had a slight change in chemical structure yielding antibacterial properties against streptococci in mice.
- Development of various sulfonamide-based drugs followed, significantly advancing medical practice.
Nobel Prize 1945
- Alexander Fleming's discovery of penicillin's antimicrobial properties in 1928.
- Howard Florey and Ernst Chain's subsequent development of penicillin production processes in later years.
Choice of Antibiotics
- Aetiological agent (identifying the infectious agent), patient factors (age, physiological function, pregnancy), and antibiotic factors (PK/PD profile, toxicity) influence the selection of an appropriate antibiotic.
Empirical Therapy
- Diagnosis of the infection source and pathogens is crucial in choosing an empiric therapy.
- Universal and local data guide empiric therapy decisions.
- Resistance patterns vary from country to country, hospital to hospital, and even across different units within the same hospital.
- Identifying the isolated organism does not always equate to the true pathogen. Issues like contamination or miscollection of the sample need to be accounted for.
Patient Factors
- Age, physiological functions, genetic factors, pregnancy status, location and severity of infection, and allergies are patient-specific factors crucial in antibiotic use.
Antibiotic Factors
- Pharmacokinetic/pharmacodynamic (PK/PD) profile, absorption, excretion, tissue levels (peak levels/time above MIC), toxicity, drug-drug interactions, and cost are relevant factors to consider.
Antibiotic Guidelines
- Employ empiric antibiotic use in treatment before definitive results from lab tests become available.
- Avoid unnecessary antibiotic use when possible. Antibiotic treatment should follow tests results to ensure the best treatment outcome for the patient.
- Follow hospital guidelines during antibiotic treatment protocols.
- Ensure that allergies are documented before starting treatment.
- Justification of treatment protocol decisions should be well-documented.
Empiric vs. Directed Therapy
- Empiric therapy (85% of cases) is employed when an infection is poorly defined, using broad-spectrum antibiotics and multiple drug treatments.
- Directed therapy (15% of cases) is used when the infection is well-defined with a known pathogen, using a narrow-spectrum antibiotic for a better, targeted treatment approach.
Reasons for Empiric Therapy
- The need for rapid treatment of potentially life-threatening infections.
- The difficulty in obtaining definitive cultures to identify the infection, in cases of critical illness.
Reasons for Antibiotic Misuse Beliefs
- Fear of missing something, if culture data is not available, but the patient's condition is critical.
- Belief that patients who are very ill need more antibiotics
- "Double coverage" to account for gram-negative bacteria when culture results are negative.
Increasing Directed Therapy
- Precise identification of the infection through anatomical, microbiological, and pathophysiological methods to narrow down the treatment.
- Obtain cultures before initiating antibiotics.
- Utilize imaging, rapid diagnostics, and specific procedures for early intervention.
- Follow established guidelines and don't rely on solely on response to therapy for treatment decisions.
- Reassess patient response after 48-72 hours to adjust treatment if needed.
General Principles of Therapy
- Adherence to hospital-specific antibiotic use guidelines.
- Empiric use of appropriate antibiotics before results are available.
- Transitioning to directed therapy once results of culture and sensitivity tests are available.
- Speciment collection (e.g., culture, PCR) before treatment, especially in serious cases (e.g., meningitis or sepsis).
- Use of parenteral antibiotics to ensure drug delivery in severe conditions like sepsis.
- Consider pharmacodynamic/pharmacokinetic parameters that might require adjusting doses or choosing alternative drugs.
- Limit the use of topical antibiotics unless necessary.
- Consult microbiologists or infectious disease specialists for expert guidance.
- Define the use of antibiotics for both treatment and prophylaxis clearly.
Antibiotic Classes
- Beta-lactam, Lipopeptides, Tetracyclines, Chloramphenicol, Polymyxins, Sulfonamides, Trimethoprim, Rifamycins, Nitrofurantoin, Aminoglycosides, Quinolones, Macrolides, Lincosamides, Metronidazole, Glycopeptides, Oxazolidinones.
Mechanisms of Action
- Inhibition of cell wall synthesis (e.g., penicillin, vancomycin).
- Inhibition of cell membrane function (e.g., polymyxin).
- Inhibition of protein synthesis (e.g., chloramphenicol, aminoglycosides).
- Inhibition of nucleic acid synthesis (e.g., quinolones, rifampin).
B-Lactams: Penicillins
- Penicillin binds to bacterial cell wall proteins, disrupting cell wall formation.
- Bacteria produce β-lactamases, which deactivate penicillin.
- Natural penicillins (e.g., penicillin G) are primarily administered parentally.
- Penicillin V is an orally administered penicillin, mainly effective against Gram-positive bacteria.
- Aminopenicillins (e.g., ampicillin) have expanded activity against gram-negative bacteria.
- Clavulanate and sulbactam increase the effectiveness of penicillin against bacteria that produce β-lactamases.
- Penicillinase-resistant penicillins (e.g., methicillin) are resistant to β-lactamases, targeting staphylococci, but not MRSA.
B-Lactams: Cephalosporins
- Well-tolerated with fewer hypersensitivity reactions than penicillins.
- First-generation cephalosporins (e.g., cefazolin) are effective against Gram-positive cocci (e.g., staphylococci and streptococci), used prophylactically for clean surgeries.
- Second-generation cephalosporins (e.g., cefuroxime) treat respiratory infections (covering gram-negatives like Haemophilus influenzae and Streptococcus pneumoniae ) and meningitis.
3rd Generation Cephalosporins
- Wider spectrum than 1st and 2nd generation, cover many gram-negative bacteria, CNS infections, less activity against gram-positives.
4th Generation Cephalosporins
- Wider spectrum than 3rd generation cephalosporins with increased gram-negative coverage, including many enteric bacteria, gram positives, and Pseudomonas. Cefepime, cefpirome.
5th Generation Cephalosporins
- High activity against staphylococcoi, including MRSA, and streptococci resistant to penicillin.
Cephalosporins: Uses and Limitations
Carbapenems
- Activity against both Gram-positive and Gram-negative bacteria.
- Excellent activity against various gram-negative bacteria but limited to severe infections.
- Important in cases of bacterial resistance and sepsis.
Monobactams
- Effective against some gram-negative bacteria (eg. Pseudomonas aeruginosa)
- Often preferred for cases that are resistant to other drugs, especially against gram-negatives.
Side Effects of Antibiotic Classes
- Many antibiotics can cause side effects such as diarrhea, nausea, rash, and occasionally more serious reactions (e.g., liver damage).
Combination Treatments
- Combination therapy (e.g., penicillin + β-lactamase inhibitor) often needed for specific types of infections.
Glycopeptides
- Effective against MRSA, Clostridium difficile, and some streptococci.
Quinolones
- Excellent activity against many gram-negative bacteria (including Pseudomonas sp).
- Used for respiratory, urinary tract and skin infections.
Macrolides
- Effective against gram-positive bacteria and some atypical bacteria.
- Useful in treating various respiratory infections, especially pneumonia.
Aminoglycosides
- Effective against a spectrum of gram-negative bacteria, including Pseudomonas.
- Used for severe infections, often combined with other antibiotics.
Metronidazole
- Effective against anaerobic bacteria, parasites, and protozoa.
- A useful therapy for various anaerobic infections, such as infections of the abdomen and vagina.
Mechanisms of Antibiotic Resistance
- Enzymatic inactivation: Bacteria produce enzymes (like β-lactamases) to break down the antibiotic.
- Altered permeability: Cells alter bacterial membrane permeability to prevent entry of the antibiotics.
- Altered target molecule: Genetic mutation leads to changes in the target proteins for antibiotics, reducing effectiveness.
- Metabolic bypass: Microorganisms modify metabolic pathways to avoid the point of blockage by antibiotics.
- Efflux pumps: Cells expel antibiotics from inside the cell, preventing antibiotics from working.
Origins of Resistance
- Non-genetic reasons (e.g., slow bacterial replication) limit effectiveness.
- Genetic origins of resistance can occur via chromosomal mutation or via extrachromosomal factors such as plasmids.
Types of Genetic Transfer
- Transformation is the uptake of extracellular DNA from another bacterium into other bacteria.
- Transduction is the transfer of genetic material from one bacterium to another by a virus (Bacteriophage).
- Conjugation is the transfer of genetic material (usually via plasmids) from one bacterial cell to another through direct contact.
- Transposition is considered a means of moving genetic material from one position in a cell's DNA (eg. from a plasmid to the bacterial chromosome), or from one region of the genome to another.
Cross-Resistance
- Microorganisms that are resistant to one antibiotic may also be resistant to other closely related antibiotics which share a mechanism of action.
Factors Favoring Antibiotic Resistance
- Overuse of antibiotics.
- Early discontinuation of antibiotics.
- Insufficient dosing or duration of antibiotic treatment.
- Livestock/animal treatment with antibiotics and exposure to antibiotics in general, which can lead to antibiotic resistance in general bacterial populations.
Limitation of Drug Resistance
- High antibiotic drug levels in tissues to address both original bacteria and first-step mutations.
- Simultaneous (combined) use of antibiotics that avoid cross-resistance.
- Limiting antibiotic use to minimize resistance development, especially in hospitals.
- Enhancing public and provider awareness about appropriate antibiotic use and misuse prevention.
- Antibiotic sensitivity testing (MIC/MBC) to direct targeted treatment
Resistance mechanisms in specific antibiotic classes
- Different types of resistance develop in specific antibiotic classes.
References
- Goodman & Gilman's pharmacological basis of therapeutics.
- Jawetz Medical Microbiology.
- Essentials of Microbiology by Welsby A. Volk.
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Test your knowledge on the functions and mechanisms of bacteriostatic and bactericidal antibiotics. This quiz covers the significance of Minimum Inhibitory Concentration (MIC), the role of antibiotics in modern medicine, and the principles of empirical versus directed therapy. It's essential for anyone studying pharmacology or microbiology.