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What defines the principle of selective toxicity in antimicrobial therapy?
What defines the principle of selective toxicity in antimicrobial therapy?
Which of the following accurately distinguishes narrow-spectrum antibiotics from broad-spectrum antibiotics?
Which of the following accurately distinguishes narrow-spectrum antibiotics from broad-spectrum antibiotics?
Which mechanism is NOT associated with microbial acquisition of antibiotic resistance?
Which mechanism is NOT associated with microbial acquisition of antibiotic resistance?
Patients in which of the following categories are more likely to have resistant microbes?
Patients in which of the following categories are more likely to have resistant microbes?
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What is one recognized disadvantage of using combinations of antibiotics?
What is one recognized disadvantage of using combinations of antibiotics?
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Which of the following factors is NOT typically considered in the selection of the best antimicrobial?
Which of the following factors is NOT typically considered in the selection of the best antimicrobial?
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What is the main purpose of antimicrobial stewardship?
What is the main purpose of antimicrobial stewardship?
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What common adverse effect is associated with penicillins?
What common adverse effect is associated with penicillins?
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Which of the following medications require laboratory monitoring for liver function?
Which of the following medications require laboratory monitoring for liver function?
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What is a major consideration when prescribing macrolides?
What is a major consideration when prescribing macrolides?
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Which class of antivirals is particularly significant for travelers at risk of malaria?
Which class of antivirals is particularly significant for travelers at risk of malaria?
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Which of the following antibiotics is associated with serious drug-to-drug interactions?
Which of the following antibiotics is associated with serious drug-to-drug interactions?
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What is a recommended lab test for patients on PrEP?
What is a recommended lab test for patients on PrEP?
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Which of the following antifungals has known concerns in pregnancy and lactation?
Which of the following antifungals has known concerns in pregnancy and lactation?
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Which medication is primarily used to treat anaerobic bacterial infections?
Which medication is primarily used to treat anaerobic bacterial infections?
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Which of the following drugs should be monitored for potential renal adverse effects?
Which of the following drugs should be monitored for potential renal adverse effects?
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Study Notes
Selective Toxicity
- Drugs that target essential metabolic pathways or structures in microbes that are not present or differ in humans
- The goal is to selectively kill or inhibit the microbe without causing significant harm to the host
Narrow-spectrum Antibiotics vs. Broad-spectrum Antibiotics
- Narrow-spectrum antibiotics are effective against a limited range of microbes, typically targeting specific bacterial species.
- Broad-spectrum antibiotics are effective against a wider variety of microbes, including both gram-positive and gram-negative bacteria.
Acquired Resistance. Four mechanisms microbes have for resisting drugs.
- Inactivation of the drug: The microbe may produce enzymes that break down or inactivate the antibiotic.
- Alteration of the drug target: The microbe may mutate the target site of the antibiotic, making it ineffective.
- Decreased drug accumulation: The microbe may develop ways to reduce the amount of antibiotic that enters the cell or to increase the rate at which it is pumped out.
- Development of alternative metabolic pathways: The microbe may evolve a new way to perform an essential metabolic function, bypassing the pathway targeted by the antibiotic.
Promotion of Antibiotic Resistance
- Overprescribing antibiotics
- Improper use of antibiotics
Patients more likely to have a resistant microbe:
- Patients with previous exposure to antibiotics
- Patients with prolonged hospital stays
- Patients in long-term care facilities
- Patients with compromised immune systems
Superinfection
- Occurs when the normal flora of the body is disrupted, allowing opportunistic pathogens to thrive.
- This can happen due to antibiotic use, which can eliminate sensitive bacteria, leaving resistant ones to proliferate.
Importance of Antimicrobial Stewardship
- Antibiotic stewardship programs aim to optimize antimicrobial use to minimize the development of resistance.
- They involve promoting appropriate antibiotic selection, dosage, duration of therapy, and monitoring of patient responses.
First rule of antimicrobial therapy
- "Culture and Sensitivity (C&S) before prescribing"
Drug Susceptibility and the Antibiogram
- An antibiogram is a laboratory test that helps determine which antibiotics are most likely to be effective against a specific microbe.
- It is used to guide antibiotic selection and treatment decisions.
Indications for Using Antibiotic Combinations:
- To achieve synergy (where the combination of drugs is more effective than either drug alone).
- To cover a broader range of potential pathogens
- To prevent resistance
- To treat polymicrobial infections (infections caused by multiple microbes)
- To treat infections in immunocompromised patients
- To treat severe infections
Disadvantages of Using Antibiotic Combinations:
- Increased risk of adverse effects
- Higher cost
- Enhanced potential for drug interactions
- Increased risk of superinfection
Prophylactic Use of Antimicrobials
- Prophylactic antibiotics are used to prevent infections, such as:
- Before surgery
- After dental procedures
- For specific infections (ie. travelers' diarrhea)
- For specific patient populations (ie. immunocompromised individuals)
- In cases of known exposure to a specific pathogen
Five Misuses of Antimicrobial Drugs
- Treating viral infections
- Treating non-bacterial infections
- Using antibiotics for the wrong duration
- Using antibiotics for the wrong indication
- Using antibiotics without a proper culture and sensitivity test
Factors in the Selection of the Best Antimicrobial
- The patient's age
- The patient's immune status
- The site of infection
- The severity of the infection
- The susceptibility pattern of the microbe
Review adverse antibiotic effects versus allergy. Two drug classes in this unit have a high rate of allergic reactions. Complete the table below:
| Class of Drug | Type of Reaction |
|---|---|
| Penicillin | Allergy: Minor rash to life-threatening anaphylaxis; Adverse effects: Pain at IM site, sensory and motor dysfunction, intra-arterial injection can cause gangrene, IV can cause hyperkalemia. |
| Sulfonamide | Adverse effects: Hypersensitivity (e.g., Steven-Johnson syndrome), blood dyscrasias (e.g., hemolytic anemia), kernicterus in newborns (bilirubin deposition in the brain). |
Term Review
- Bactericidal: Kills bacteria
- Bacteriostatic: Inhibits bacterial growth
- Selective Toxicity: The ability of a drug to harm a pathogen without harming the host
- Antimicrobial Stewardship: A program of actions to promote the appropriate use of antimicrobials to preserve their effectiveness.
Clostridium Difficile (C. diff) As An Adverse Effect
- C. diff is a bacterium that can cause severe diarrhea, colitis, and even death.
- It commonly occurs as an adverse effect of antibiotic use, particularly broad-spectrum antibiotics, as it can disrupt the normal gut flora, allowing C. diff to overgrow and cause disease.
Generations of Antibiotics
- Generations of antibiotics generally refer to newer versions of drugs that are more effective, have a broader spectrum of activity, and have a longer duration of action.
QT interval Prolongation
- QT interval prolongation: is a heart rhythm abnormality that can lead to a potentially life-threatening condition called torsades de pointes. QT prolongation can happen due to certain medications, including some antibiotics, antifungals, and anti-arrhythmics.
Beta-Lactam. Beta-Lactamase. Beta-Lactamase Inhibitors
- Beta-lactam antibiotics (e.g., penicillin, cephalosporins) have a beta-lactam ring structure in their chemical makeup.
- Beta-lactamase is an enzyme produced by some bacteria that breaks down the beta-lactam ring, rendering the antibiotic ineffective.
- Beta-lactamase inhibitors (e.g., clavulanate, sulbactam, tazobactam) are a class of drugs that can bind to beta-lactamase and prevent it from inactivating beta-lactam antibiotics. They are often combined with certain beta-lactam antibiotics to improve their effectiveness.
Antivirals
- Antivirals are drugs that target specific stages in the viral life cycle to inhibit viral replication and spread.
- Antivirals are often used to treat viral infections such as influenza, herpes viruses, and HIV.
Relationship Between Onset of Viral Illness and Antivirals
- Antiviral medications are most effective when started early in the course of viral illness.
- For some viral infections, such as influenza, antiviral medications are most effective when started within 48 hours of the onset of symptoms.
Classes of Selected Antivirals
- Neuraminidase inhibitors (e.g., oseltamivir, zanamivir) - prevent influenza from spreading and infecting other cells.
- Acyclovir, Valacyclovir, and Famciclovir are antiviral drugs that are effective against specific herpes viruses, including herpes simplex virus (HSV) and varicella-zoster virus (VZV).
PrEP
- Pre-exposure prophylaxis (PrEP) is a medication that is taken daily to prevent HIV infection.
- PrEP is shown to be highly effective in reducing the risk of HIV infection, especially in individuals at high risk for exposure to HIV.
Major Concerns with Oral Antifungals
- Hepatotoxicity: Some oral antifungals can be toxic to the liver, particularly those in the azole class.
- Drug interactions: Oral antifungals can have a variety of drug interactions, particularly with medications that are metabolized by the liver.
Oral Antifungals in Pregnancy and Lactation
- Generally, oral antifungals are not recommended during pregnancy, especially in the first trimester.
- Some oral antifungals may be used during pregnancy, but only when the potential benefit to the mother outweighs the potential risks to the fetus.
- Some oral antifungals may be safe to use during lactation, but it is important to consult with a health care professional before using any medication during lactation.
Immunization Basics
- Vaccines are biological preparations that contain weakened or inactive pathogens or parts of pathogens.
- They work by stimulating the immune system to produce antibodies against the pathogen, providing immunity to future infections.
- Vaccination is the process of administering a vaccine to an individual to provide immunity.
Tdap in Pregnancy
- Tdap (tetanus, diphtheria, and acellular pertussis) vaccine is recommended for pregnant women to protect both themselves and their infants.
- Tdap is typically administered between 27 and 36 weeks of pregnancy.
QT Drugs Mentioned in the Unit
- Macrolides: a class of antibiotics that can prolong the QT interval.
- Fluoroquinolones: a class of antibiotics that can prolong the QT interval.
- Antimalarial (chloroquine): an antimalarial drug that can prolong the QT interval.
- Anti-protozoal, Ant-parasitic, Anti-fungal: These drug classes may also cause QT prolongation depending on the specific drug.
Drugs Used in the Treatment of Tuberculosis (TB)
- Isoniazid (INH): Most frequently prescribed TB drug.
- Rifampin (RIF): Powerful antibiotic used to kill TB bacteria.
- Pyrazinamide (PZA): Used during the initial phase of TB treatment. Important to monitor for hepatotoxicity.
- Ethambutol (EMB): Used for multidrug-resistant TB.
- Streptomycin (SM): Reserved for drug-resistant TB.
Metronidazole (Flagyl) in Treating Anaerobic Bacterial Infections
- Metronidazole is an antibiotic that is effective against anaerobic bacteria, which are bacteria that can survive without oxygen.
- It is commonly used to treat infections caused by anaerobic bacteria, such as C. diff colitis, giardiasis, and some types of vaginal infections.
Summary of Use in Pregnancy and Lactation
- Antibiotics:
- Antivirals:
- Antifungals:
- Antiprotozoals:
Module 2 Forum Questions:
- What antibiotics did you find that had significant drug-to-drug interactions?
- What drugs from this module required laboratory monitoring?
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Description
This quiz covers the concept of selective toxicity, focusing on how certain drugs specifically target microbes without harming human cells. It explores the differences between narrow-spectrum and broad-spectrum antibiotics, as well as the mechanisms of acquired resistance that microbes use against these drugs.
