Antibiotics Mechanism of Action
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Antibiotics Mechanism of Action

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Questions and Answers

What is the primary purpose of antibiotic susceptibility testing?

  • To develop new antibiotics without testing against bacteria
  • To enhance bacterial growth in the laboratory
  • To identify the most effective antibiotic for a specific bacterial strain (correct)
  • To determine the cost of antibiotic treatment options

    • Which method is NOT commonly used for antibiotic susceptibility testing?

  • Broth microdilution
  • PCR amplification (correct)
  • Macrodilution
  • Kirby-Bauer disk diffusion

    • What does the Minimum Inhibitory Concentration (MIC) represent in antibiotic testing?

  • The concentration at which bacteria become resistant
  • The mean concentration across multiple species of bacteria
  • The lowest concentration necessary to inhibit bacterial growth (correct)
  • The highest concentration required for optimal bacterial growth

    • Why is it important to use cultures when determining the appropriate antibiotic for an infection?

    <p>Cultures help pinpoint the specific bacterial strain causing the infection</p> Signup and view all the answers

    What is the primary reason for performing antibiotic susceptibility testing after identifying a bacterial strain?

    <p>To determine which antibiotics the pathogen has not developed resistance against</p> Signup and view all the answers

    Which antibiotic is specifically a glycopeptide antibiotic used for serious infections and inhibits peptidoglycan synthesis?

    <p>Vancomycin</p> Signup and view all the answers

    Which of the following antibiotics is classified as a beta-lactam and used against penicillin-resistant bacteria?

    <p>Cefepime</p> Signup and view all the answers

    Which type of antibiotic primarily works by disrupting the bacterial cell membrane and creates efflux pumps leading to cell lysis?

    <p>Polymixins</p> Signup and view all the answers

    Which of the following options correctly identifies an aminopenicillin antibiotic?

    <p>Amoxicillin</p> Signup and view all the answers

    Which of these antibiotics is specifically known as a mono-bactam, particularly useful for penicillin-allergic patients?

    <p>Aztreonam</p> Signup and view all the answers

    What is the primary mechanism of action for sulfonamides in bacterial cells?

    <p>Inhibition of folic acid synthesis</p> Signup and view all the answers

    Which antibiotic is classified as an anti-pseudomonal penicillin and is commonly combined with tazobactam?

    <p>Piperacillin</p> Signup and view all the answers

    Which of the following beta-lactam antibiotics is characterized by broad-spectrum activity and is represented by the mnemonic 'DIME'?

    <p>Imipenem</p> Signup and view all the answers

    Which type of antibiotic is specifically indicated for treating infections caused by Neisseria meningitis?

    <p>Ceftazidime</p> Signup and view all the answers

    Which of the following combinations provides adequate coverage for community-acquired pneumonia (CAP)?

    <p>Fluoroquinolone Monotherapy</p> Signup and view all the answers

    Which antibiotic class is NOT effective against Pseudomonas aeruginosa?

    <p>First Generation Cephalosporins</p> Signup and view all the answers

    For treating Clostridium difficile infections, which choice is appropriate?

    <p>Metronidazole</p> Signup and view all the answers

    Which antibiotic is classified as a DNA integrity inhibitor that produces reactive oxygen species?

    <p>Metronidazole</p> Signup and view all the answers

    What is the mechanism of action for fluoroquinolones?

    <p>Inhibit DNA gyrase and topoisomerase IV</p> Signup and view all the answers

    Which of the following is NOT considered a treatment for anaerobic bacteria?

    <p>Ceftriaxone</p> Signup and view all the answers

    What is the primary treatment for tick-borne illnesses specifically caused by Borrelia burgdorferi?

    <p>Doxycycline</p> Signup and view all the answers

    Which antibiotic is recommended for treating infections caused by Extended Spectrum Beta-Lactamase (ESBL) bacteria?

    <p>Aminoglycosides</p> Signup and view all the answers

    Which of the following antibiotics is effective against Methicillin-resistant Staphylococcus aureus (MRSA)?

    <p>Vancomycin</p> Signup and view all the answers

    Which antibiotic combination would be considered inadequate for skin and soft tissue infections caused by MRSA?

    <p>Vancomycin + Ceftriaxone</p> Signup and view all the answers

    Which class of antibiotics is known to inhibit protein synthesis by binding to the 30S ribosomal subunit and is considered bactericidal?

    <p>Aminoglycosides</p> Signup and view all the answers

    What is the role of empiric therapy in antibiotic treatment?

    <p>To start treatment based on the most likely pathogen</p> Signup and view all the answers

    Which class of antibiotics provides good coverage for atypical bacteria but is ineffective against Legionella?

    <p>Chloramphenicol</p> Signup and view all the answers

    Which of the following antibiotics is primarily used for treating infections caused by Streptococcus pneumoniae?

    <p>Levofloxacin</p> Signup and view all the answers

    Which antibiotic is known as a bacteriostatic agent and inhibits protein synthesis by binding to the 50S ribosomal subunit?

    <p>Azithromycin</p> Signup and view all the answers

    Which of the following antibiotic classes is characterized by broad coverage against Gram-negative bacteria?

    <p>Carbapenems</p> Signup and view all the answers

    What type of bacterial coverage is provided by anti-pseudomonal penicillins?

    <p>Broad coverage excluding Enterobacter, Serratia, and Neisseria</p> Signup and view all the answers

    Which of the following antibiotics is effective against Enterococcus infections?

    <p>Vancomycin</p> Signup and view all the answers

    Which of the following agents is associated with causing nephrotoxicity due to direct effects?

    <p>Vancomycin</p> Signup and view all the answers

    What are the adverse effects linked to fluoroquinolones?

    <p>Hypoglycemia, hyperglycemia, and tendon rupture</p> Signup and view all the answers

    Which antibiotic is NOT known to interact with the CYP450 system as an inhibitor?

    <p>Aminoglycosides</p> Signup and view all the answers

    Which adverse reaction is specifically associated with Bactrim?

    <p>Kernicterus</p> Signup and view all the answers

    What is a primary mechanism by which bacteria develop resistance to antibiotics?

    <p>Enzyme inactivation and altered target sites</p> Signup and view all the answers

    Which antibiotic class is particularly noted for causing ototoxicity?

    <p>Vancomycin</p> Signup and view all the answers

    Which of the following is a common adverse effect of clindamycin?

    <p>C. difficile infection</p> Signup and view all the answers

    Which among the following antibiotics is contraindicated in patients under 18 years of age due to potential joint issues?

    <p>Fluoroquinolones</p> Signup and view all the answers

    What is a notable adverse effect of carbapenems?

    <p>C. difficile infection</p> Signup and view all the answers

    Which mechanism of antibiotic resistance involves bacteria taking up DNA from dead bacteria?

    <p>Transformation</p> Signup and view all the answers

    Study Notes

    Antibiotics Mechanism of Action

    • Cell Wall Synthesis Inhibitors: Antibiotics that target the bacterial cell wall by inhibiting peptidoglycan synthesis or cross-linking.
      • Peptidoglycan Synthesis Inhibitors:
        • Vancomycin: Glycopeptide antibiotic used to treat serious infections, it inhibits peptidoglycan synthesis.
        • Fosfomycin: Used primarily to treat acute cystitis.
      • Peptidoglycan Cross-linking Inhibitors (Beta-Lactams):
        • Penicillins:
          • Natural Penicillins: Penicillin G (IV/IM) and Penicillin V (PO).
          • Anti-Staphylococcal Penicillins: Oxacillin (IV), Nafcillin (IV), and Dicloxacillin (PO).
          • Aminopenicillins: Amoxicillin and Ampicillin.
          • Anti-Pseudomonal Penicillins: Piperacillin (combined with tazobactam as Zosyn)
        • Cephalosporins: Five generations of cephalosporins with increasing gram-negative coverage as you move down the generations.
          • First Generation: Cefazolin (Ancef) and Cephalexin.
          • Second Generation: Cephaclor, Cefoxitin, and Cefotetan.
          • Third Generation: Ceftriaxone (Rocephin) and Ceftazidime (Fortaz)
          • Fourth Generation: Cefepime (Maxipime)
          • Fifth Generation: Ceftaroline (Teflaro)
        • Carbapenems: Broad-spectrum antibiotics (think "DIME" mnemonic): Doripenem, Imipenem, Meropenem, and Ertapenem.
        • Monobactins: Aztreonam (Azactam), a broad-spectrum antibiotic particularly useful for penicillin-allergic patients.
    • Beta-Lactamase Inhibitors: Some bacteria produce beta-lactamases, enzymes that can break down beta-lactam antibiotics rendering them ineffective. To overcome this, beta-lactamase inhibitors are used in combination with the beta-lactam antibiotic.
      • Clavulanate: Combined with amoxicillin (Augmentin).
      • Sulbactam: Combined with ampicillin (Unasyn)
      • Tazobactam: Combined with piperacillin (Zosyn)
      • Avibactam: Combined with ceftazidime
    • Cell Membrane Integrity Inhibitors:
      • Daptomycin: Creates efflux pumps in the cell membrane, leading to bacterial cell lysis.
      • Polymixins: Cationic detergents that disrupt the cell membrane and increase its permeability, leading to bacterial cell lysis.
    • Metabolic Pathway Inhibitors:
      • Folic Acid Synthesis Inhibitors (Bacteriostatic):
        • Sulfonamides: Sulfa methoxazole (SMX), inhibits the conversion from para-aminobenzoic acid to dihydrofolate.
        • Trimethoprim: Inhibits the conversion from dihydrofolate to tetrahydrofolate.
        • Trimethoprim-Sulfamethoxazole (Bactrim): Combination antibiotic often used together.
    • DNA Integrity Inhibitors:
      • Metronidazole: Produces reactive oxygen species, damaging DNA and leading to bacterial cell death.
      • Nitrofurantoin: Produces reactive oxygen species, damaging DNA and RNA; can also inhibit protein synthesis.
    • RNA Polymerase Inhibitors:
      • Rifampin: Inhibits bacterial RNA polymerase, used to treat tuberculosis.

    Antibiotic Mechanisms of Action

    • Fluoroquinolones inhibit DNA gyrase and topoisomerase IV, enzymes essential for DNA replication in bacteria. These drugs work by increasing the nicking activity of these enzymes, leading to DNA fragmentation and bacterial death.
      • Ciprofloxacin (first generation)
      • Levofloxacin, Gemifloxacin, Moxifloxacin (second generation)
    • Macrolides inhibit protein synthesis by binding to the 50S ribosomal subunit in bacteria. They do not kill bacteria but rather reduce their growth, considered bacteriostatic agents.
      • Azithromycin, Erythromycin, Clarithromycin
    • Clindamycin, Chloramphenicol, and Linezolid also inhibit the 50S ribosomal subunit and act as bacteriostatic agents.
    • Aminoglycosides also inhibit protein synthesis by binding to the 30S ribosomal subunit. Although they interfere with protein synthesis, they are considered bactericidal agents meaning they kill bacteria.
      • Tobramycin, Amikacin, Gentamicin
    • Tetracyclines inhibit protein synthesis by binding to the 30S ribosomal subunit, acting as bacteriostatic agents.
      • Doxycycline, Tetracycline

    Bacterial Coverage of Antibiotics

    • Gram-Positive Bacteria

      • Methicillin-sensitive Staphylococcus aureus (MSSA)
        • Anti-staphylococcal penicillins: (Nafcillin, Oxacillin, Dicloxacillin)
        • First-generation cephalosporins: (Cephalexin, Cefazolin)
        • Fluoroquinolones: (Ciprofloxacin, Levofloxacin)
      • Methicillin-resistant Staphylococcus aureus (MRSA)
        • Fifth-generation Cephalosporins: (Ceftaroline)
        • Vancomycin
        • Trimethoprim/Sulfamethoxazole (Bactrim)
        • Clindamycin
        • Linezolid
        • Doxycycline
        • Daptomycin (Skin and right-sided endocarditis only)
      • Streptococcus pneumoniae
        • Penicillin
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Third-generation cephalosporins: (Ceftriaxone)
        • Fluoroquinolones: (Moxifloxacin, Levofloxacin)
        • Macrolides: (Azithromycin, Erythromycin, Clarithromycin)
        • Clindamycin
      • Streptococcus groups A and B (Streptococcus pyogenes & Streptococcus agalactiae)
        • Penicillin
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • First-generation cephalosporins: (Cephalexin)
        • Trimethoprim/Sulfamethoxazole (Bactrim)
        • Macrolides
        • Clindamycin
      • Enterococcus
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Nitrofurantoin (for UTIs)
      • Listeria monocytogenes
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Trimethoprim/Sulfamethoxazole (Bactrim)
      • Vancomycin is used for penicillin-allergic patients and for patients with resistance to other gram-positive agents, including vancomycin-resistant strains.

    • Gram-Negative Bacteria

      • "HENS PECK" mnemonic: Haemophilus influenzae, Enterobacter, Neisseria gonorrhea & meningitidis, Serratia, Proteus mirabilis, Escherichia coli (E. coli), Klebsiella
        • Aminopenicillins: (Amoxicillin, Ampicillin) - Cover all except Enterobacter, Serratia, and Neisseria
        • Anti-pseudomonal penicillins: (Piperacillin/tazobactam) - Broad coverage
        • 1st Gen Cephalosporins: (PEcK)
        • Second to Fourth-generation Cephalosporins: (Cefuroxime, Ceftriaxone, Cefepime, etc.) - Broad coverage
        • Carbapenems: (Doripenem, Imipenem/cilastatin, Meropenem, Ertapenem) - Broad coverage
        • Monobactams: (Aztreonam) - Broad coverage
        • Polymyxins: (Colistin) - Broad coverage
        • Fluoroquinolones: (Ciprofloxacin, Levofloxacin) - Broad coverage

    • Pseudomonas + Acinetobacter

      • Amino-PCNS (Only Acinetobacter)
      • Antipseudomonal PCNs
      • 3rd Gen Cephalosporins (Ceftazidime)
      • 4th Gen Cephalosporins (Cefipime)
      • Carbapenems
      • Monobactams (no Acinobacter)
      • Fluoroqinolones (Ciprofloxacin, Levofloxacin)

    • ESBL

    • Stentrophomonas

    Empiric Therapy

    • Empiric therapy refers to starting treatment with antibiotics before the precise identification of the organism causing the infection.
    • The choice of antibiotic is based on the most likely pathogen for the specific infection.
    • Once a culture of the bacteria is obtained and identified, the antibiotic can be narrowed to target that specific bacterium.

    Antibiotics for Gram-Negative Bacteria

    • Hemophilus influenzae, Enterobacter, Nesseria, Serratia, Proteus, E. coli, Klebsiella (H.E.N.S.P.E.K):
      • Amino Penicillins: Cover all except Enterobacter, Serratia, Nesseria
      • Anti-pseudomonal Penicillins: Cover all except Enterobacter, Serratia, Nesseria.
      • First Generation Cephalosporins: Cover E. coli, Klebsiella (P.E.C)
      • Second to Fourth Generation Cephalosporins: Cover all
      • Carbapenems: Cover all
      • Monobactins: Cover all
      • Fluoroquinolones: Cover all except Nesseria
      • Aminoglycosides: Cover all except Nesseria
      • Doxycycline & Tetracyclines: Cover a limited amount, not the primary antibiotic
      • Ceftazidime (Third Generation Cephalosporin): Specifically covers Nesseria Meningitis

    Antibiotics for Pseudomonas aeruginosa and Acinetobacter

    • Pseudomonas aeruginosa: Considered a "nasty" nosocomial infection
    • Acinetobacter: Also considered a "nasty" nosocomial infection
    • Aminopenicillins: Only covers Acinetobacter
    • Anti-pseudomonal Penicillins: Cover both Pseudomonas aeruginosa and Acinetobacter
    • First & Second Generation cephalosporins: Do not cover either
    • Third Generation cephalosporins: Only Ceftazidime covers Pseudomonas aeruginosa
    • Fourth Generation cephalosporins (Cefepime): Cover Pseudomonas aeruginosa
    • Carbapenems: Cover both
    • Monobactins: Cover Pseudomonas aeruginosa, not Acinetobacter
    • Fluoroquinolones (Ciprofloxacin & Levofloxacin): May be considered as an add-on therapy, not enough evidence for monotherapy
    • Aminoglycosides: Cover Pseudomonas aeruginosa, not Acinetobacter
    • Polymixins: "Salvage therapy" for both Pseudomonas aeruginosa and Acinetobacter

    Antibiotics for Extended Spectrum Beta-Lactamase (ESBL) Bacteria

    • ESBL Bacteria: Have evolved resistance to many common antibiotics.
    • Examples: Enterobacter, E. coli, Klebsiella
    • Coverage: Carbapenems, Aminoglycosides, Polymixins
    • Ceftazidime + Avibactam: May have adequate coverage for ESBL bacteria

    Antibiotics for Stenotrophomonas

    • Antibiotics:
      • Anti-pseudomonal penicillins (Piperacillin/Tazobactam)
      • Polymixins
      • Trimethoprim/Sulfamethoxazole (Bactrim)

    Antibiotics for Anaerobic Bacteria

    • Anaerobic Bacteria: "Can't breathe perfectly fresh air"
    • Examples:
      • Clostridium species: C. perfringens, C. difficile, C. botulinum, C. tetani
      • Bacteroides
      • Peptostreptococcus
      • Fusobacterium
      • Actinomyces
    • Above the Diaphragm (Skin and Respiratory Infections): Clindamycin
    • Below the Diaphragm (GI & Pelvic Infections): Metronidazole
    • Broad Spectrum: Carbapenems, Anti-pseudomonal penicillins
    • Fluoroquinolones (Ciprofloxacin): May have coverage, but resistance is a concern

    Antibiotics for Clostridium difficile

    • C. difficile: Causes intestinal infection (colitis)
    • Antibiotics:
      • Metronidazole
      • Oral Vancomycin

    Antibiotics for Atypical Bacteria

    • Examples:
      • Mycoplasma
      • Chlamydia
      • Legionella
    • Fluoroquinolones: Preferred, especially for Legionella
    • Macrolides: Good coverage
    • Chloramphenicol: Good coverage, except for Legionella
    • Doxycycline: Preferred, covers all atypical bacteria

    Antibiotics for Tick-Borne Illnesses

    • Examples:
      • Borrelia burgdorferi (Lyme disease)
      • Rickettsia rickettsii (Rocky Mountain Spotted Fever)
      • Ehrlichia
      • Anaplasma
    • Doxycycline: Preferred for all, except Babesiosis
    • Chloramphenicol: Alternative for low-income countries
      • Ceftriaxone: Preferred for disseminated Borrelia burgdorferi (CNS infections)

    Antibiotics for Treponema pallidum (Syphilis)

    • Penicillin G: Preferred
    • Doxycycline: Alternative for penicillin allergy

    Empiric Antibiotic Therapy for Common Infections

    • Community-Acquired Pneumonia (CAP):
      • Monotherapy Options: Fluoroquinolones
      • Combination Options: Ceftriaxone + Doxycycline or Macrolide
    • Hospital-Acquired Pneumonia (HAP):
      • Coverage: MRSA and Pseudomonas
      • Vancomycin: For MRSA
      • Anti-pseudomonal Penicillins (Piperacillin/Tazobactam), Ceftazidime, Cefepime, or Aminoglycosides: For Pseudomonas
    • Gastrointestinal Infections:
      • Coverage: Gram-negative rods, especially Enterobacteriaceae (E. coli, Klebsiella)

    Antibiotic Coverage and Considerations

    • Anaerobic Infections: Carbapenems, anti-pseudomonal penicillins, metronidazole + fluoroquinolone (e.g., cipro), metronidazole + ceftriaxone, metronidazole + ceftazidime can be used for coverage.
    • Skin and Soft Tissue Infections:
      • MSSA (Methicillin-Susceptible Staphylococcus Aureus) & Strep A: Dicloxacillin, cephalexin (PO); nafcillin, oxacillin, cefazolin (IV).
      • MRSA (Methicillin-Resistant Staphylococcus Aureus): Bactrim, doxycycline, clindamycin (PO); vancomycin (IV), ceftaroline (IV - if budget allows).
    • Urinary Tract Infections (UTIs):
      • Pyelonephritis (Kidney Infection): Ceftriaxone, ciprofloxacin, ampicillin can be considered.
      • Acute Cystitis (Bladder Infection): Trimethoprim-sulfamethoxazole, nitrofurantoin, fosfomycin, ciprofloxacin (second-line due to resistance).
      • Complicated UTIs: Anti-pseudomonal drugs (piperacillin-tazobactam, cefepime, ceftazidime) for Pseudomonas coverage; vancomycin for MRSA and Enterococcus; amino penicillins for Enterococcus.
    • Bone and Joint Infections (Septic Arthritis and Osteomyelitis): Vancomycin for MRSA; ceftriaxone for Neisseria gonorrhoeae; anti-pseudomonal drugs for Pseudomonas coverage (cefepime, ceftazidime).
    • Meningitis:
      • Community-Acquired: Vancomycin, ceftriaxone are primary choices. Ampicillin can be added for suspected Listeria infection (patients >60 years, immunocompromised, infants).
      • Hospital-Acquired: Vancomycin, cefepime are preferred for MRSA and Pseudomonas coverage. Carbapenems could be used, but caution due to potential for neurotoxicity.
    • Bloodstream Infections (Bacteremia):
      • Central Line-Associated: Vancomycin for MRSA coverage. Piperacillin-tazobactam for gram-negative and Pseudomonas coverage, especially with femoral lines due to proximity to the gut.
      • Sepsis (Unknown Etiology): Vancomycin (gram-positive) and piperacillin-tazobactam or carbapenems (gram-negative, anaerobes).

    Adverse Effects

    • Neurotoxicity: Penicillins, cephalosporins, carbapenems, polymixins, linezolid.
    • Pancytopenia: Penicillins, cephalosporins, bactrim, chloramphenicol, linezolid.
    • Respiratory Failure: Polymixins, nitrofurantoin (pulmonary fibrosis).

    ### Nephrotoxic Agents

    • Acute interstitial nephritis (AIN) due to hypersensitivity reaction:

      • Penicillins
      • Cephalosporins
      • Bactrim (trimethoprim sulfamethoxazole)

    • Direct nephrotoxic effects:

      • Aminoglycosides
      • Vancomycin

    ### Ototoxic Agents

    • Aminoglycosides
    • Vancomycin (especially when combined with aminoglycosides)

    ### Myasthenia Gravis-Worsening Agents

    • Fluoroquinolones
    • Aminoglycosides
    • Macrolides
    • Clindamycin

    ### Teratogenic Agents

    • Bactrim: can cause kernicterus
    • Fluoroquinolones: contraindicated under 18 years of age
    • Chloramphenicol: can cause "gray baby syndrome"
    • Tetracyclines (e.g., doxycycline)

    ### Disulfiram Reactions

    • Metronidazole
    • Third-generation cephalosporin ceftriaxone

    ### QT Prolongation

    • Fluoroquinolones
    • Macrolides

    ### CYP450 Inhibitors

    • Fluoroquinolones
    • Macrolides
    • Trimethoprim sulfamethoxazole

    Hemolytic Anemia

    • Penicillins and cephalosporins: cause hypersensitivity reactions leading to a positive Coombs test
    • Trimethoprim sulfamethoxazole, fluoroquinolones, and nitrofurantoin: can exacerbate or worsen G6PD deficiency

    Phototoxicity

    • Doxycycline
    • Trimethoprim sulfamethoxazole

    ### Additional Adverse Effects

    • Penicillins: anaphylactic shock
    • Cephalosporins: vitamin K deficiency, increased risk of biliary sludge (especially ceftriaxone), and increased risk of acute kidney injury when combined with aminoglycosides
    • Vancomycin: phlebitis, Red Man Syndrome, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
    • Daptomycin: rhabdomyolysis
    • Doxycycline: pill-induced esophagitis, teeth discoloration in children
    • Macrolides: MACRO mnemonic for adverse effects:
      • Motility dysfunction
      • Arrhythmias (QT prolongation)
      • Cholestasis
      • Rash
      • Eosinophilia
    • Clindamycin: C. difficile infection
    • Linzolid: lactic acidosis
    • Fluoroquinolones: hypoglycemia or hyperglycemia, arthropathy (especially under 18 years of age), Achilles tendon rupture (increased risk in patients over 60 years of age or on steroids)
    • Bactrim: can cause kernicterus

    ### Drugs Known to Cause C. difficile Infections

    • Clindamycin
    • Carbapenems
    • Trimethoprim sulfamethoxazole
    • Third- and fourth-generation cephalosporins
    • Fluoroquinolones

    Adverse Effects of Fluoroquinolones

    • Fluoroquinolones can cause hyperglycemia or hypoglycemia.
    • Fluoroquinolones can cause arthropathy, especially in children under 18 years old.
    • Fluoroquinolones can cause tendon rupture, particularly in patients older than 60 years old or those taking steroids.

    Adverse Effects of Bactrim

    • Bactrim can lead to hyperkalemia.

    Mechanisms of Antibiotic Resistance

    • Antibiotic resistance occurs when bacteria evolve mechanisms to evade the effects of antibiotics.

    Resistance Mechanisms: Reduced Permeability

    • Bacteria can reduce their permeability to antibiotics, hindering the entry of antibiotics into the cell.
    • Common antibiotics affected by reduced bacterial permeability include:
      • Vancomycin
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Beta-lactams

    Resistance Mechanisms: Increased Efflux

    • Bacteria can also increase the efflux of antibiotics, effectively pumping antibiotics out of the cell.
    • Common antibiotics affected by increased efflux include:
      • Fluoroquinolones
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Macrolides

    Resistance Mechanisms: Altered Target Sites

    • Bacteria can alter the target sites for antibiotics, preventing the antibiotics from binding and exerting their effects.
    • This can involve changes in amino acid sequences or structural morphology of target proteins.
    • Common antibiotics affected by altered target sites:
      • Fluoroquinolones
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Beta-lactams
      • Vancomycin
      • Macrolides
      • Linezolid
      • Trimethoprim-sulfamethoxazole

    Resistance Mechanisms: Enzyme Inactivation

    • Bacteria can produce enzymes that inactivate antibiotics.
    • Certain enzymes, like beta-lactamases, can break down beta-lactam antibiotics.
    • Aminoglycosides can be inactivated through phosphorylation, acetylation, or methylation.
    • Macrolides can also be inactivated by bacterial enzymes.
    • Common antibiotics affected by enzymatic inactivation:
      • Beta-lactams
      • Aminoglycosides
      • Macrolides

    Transmission of Antibiotic Resistance

    • Antibiotic resistance can spread through vertical gene transfer or horizontal gene transfer.
    • Vertical gene transfer: Bacteria pass on resistance genes to their offspring during binary fission.
    • Horizontal gene transfer: Bacteria transfer resistance genes to other bacteria through three mechanisms:
      • Transformation: Bacteria take up DNA from dead bacteria.
      • Conjugation: Bacteria transfer DNA through a sex pilus.
      • Transduction: Bacteriophages transfer DNA between bacteria.

    Risk Factors for Antibiotic Resistance

    • Exposure in hospital settings: Hospitals are a major breeding ground for multi-drug-resistant pathogens.
    • Over-prescription of antibiotics: Unnecessary use of antibiotics contributes to the development of resistance.
    • Antibiotics in food production: Antibiotic use in livestock can lead to antibiotic-resistant bacteria in food products.

    Determining Antibiotic Susceptibility

    • Antibiotic susceptibility testing is used to identify the most effective antibiotic for a specific bacterial strain.
    • Common methods include:
      • Broth microdilution and macrodilution
      • Kirby-Bauer disk diffusion
    • These tests determine the Minimum Inhibitory Concentration (MIC), which is the minimum concentration of antibiotic necessary to inhibit bacterial growth.
    • These tests help clinicians select antibiotics that are effective against the specific pathogen and to which the pathogen has not developed resistance.

    Culture and Sensitivity

    • To determine the most appropriate antibiotic for a specific infection, it is crucial to obtain cultures (e.g., sputum, skin, urine, blood).
    • The cultures are analyzed to identify the infecting bacterial strain.
    • Once the bacterial strain is identified, antibiotic susceptibility testing is performed to determine the best antibiotic choice.

    Antibiotics Mechanisms of Action

    • Antibiotics target different aspects of bacterial biology to inhibit growth or kill bacteria.
    • Cell Wall Synthesis Inhibitors: Interfere with the formation of the bacterial cell wall, leading to cell lysis.
      • Peptidoglycan Synthesis Inhibitors:
        • Vancomycin: Inhibits the synthesis of peptidoglycan, a major component of the bacterial cell wall.
        • Phosphomycin: Inhibits the synthesis of peptidoglycan, used primarily for urinary tract infections.
      • Peptidoglycan Cross-linking Inhibitors (Beta-Lactams):
        • Penicillins: Include multiple types with varying spectra of activity, including natural penicillins (Penicillin G & V), anti-staphylococcal penicillins (Oxacillin, Nafcillin, Dicloxacillin), aminopenicillins (Amoxicillin, Ampicillin), and anti-pseudomonal penicillins (Piperacillin).
        • Cephalosporins: Divided into five generations with increasing gram-negative coverage. First generation includes Cefazolin and Cephalexin, while third generation includes Ceftriaxone and Ceftazidime. Ceftaroline is a fifth generation cephalosporin with activity against MRSA.
        • Carbapenems: Broad-spectrum antibiotics, with "DIME" mnemonic for Doripenem, Imipenem, Meropenem, and Ertapenem.
        • Monobactins: Aztreonam is a broad-spectrum antibiotic for penicillin-allergic patients.
        • Beta-Lactamase Inhibitors: Clavulanate, sulbactam, tazobactam, and avibactam are used in combination with beta-lactam antibiotics to overcome bacterial beta-lactamases
    • Cell Membrane Integrity Inhibitors: Disrupt the bacterial cell membrane, leading to cell lysis.
      • Daptomycin: Creates efflux pumps in the cell membrane, leading to bacterial cell lysis.
      • Polymixins: Cationic detergents that disrupt the bacterial cell membrane.
    • Metabolic Pathway Inhibitors: Target essential metabolic pathways in bacteria.
      • Folic Acid Synthesis Inhibitors (Bacteriostatic): Inhibit the synthesis of folic acid, a vital component of bacterial metabolism.
        • Sulfonamides: Sulfa methoxazole (SMX) inhibits the conversion from para-aminobenzoic acid to dihydrofolate.
        • Trimethoprim: Inhibits the conversion from dihydrofolate to tetrahydrofolate.
        • Trimethoprim-Sulfamethoxazole (Bactrim): Combination antibiotic often used together.
    • DNA Integrity Inhibitors: Damage bacterial DNA, leading to cell death.
      • Metronidazole: Produces reactive oxygen species that damage bacterial DNA.
      • Nitrofurantoin: Produces reactive oxygen species that damage bacterial DNA and RNA.
    • RNA Polymerase Inhibitors: Inhibit the synthesis of bacterial RNA.
      • Rifampin: Inhibits bacterial RNA polymerase, used to treat tuberculosis.

    Antibiotic Mechanisms of Action

    • Fluoroquinolones: Inhibit DNA gyrase and topoisomerase IV, enzymes essential for DNA replication in bacteria.
      • Ciprofloxacin (first generation)
      • Levofloxacin, Gemifloxacin, Moxifloxacin (second generation)
    • Macrolides: Inhibit protein synthesis by binding to the 50S ribosomal subunit in bacteria.
      • Azithromycin, Erythromycin, Clarithromycin
    • Clindamycin, Chloramphenicol, and Linezolid also inhibit the 50S ribosomal subunit.
    • Aminoglycosides: Bind to the 30S ribosomal subunit and prevent protein synthesis.
      • Tobramycin, Amikacin, Gentamicin
    • Tetracyclines: Inhibit protein synthesis by binding to the 30S ribosomal subunit.
      • Doxycycline, Tetracycline

    Bacterial Coverage of Antibiotics

    • Gram-Positive Bacteria
      • Methicillin-sensitive Staphylococcus aureus (MSSA)
        • Anti-staphylococcal penicillins: (Nafcillin, Oxacillin, Dicloxacillin)
        • First-generation cephalosporins: (Cephalexin, Cefazolin)
        • Fluoroquinolones: (Ciprofloxacin, Levofloxacin)
      • Methicillin-resistant Staphylococcus aureus (MRSA)
        • Fifth-generation Cephalosporins: (Ceftaroline)
        • Vancomycin
        • Trimethoprim/Sulfamethoxazole (Bactrim)
        • Clindamycin
        • Linezolid
        • Daptomycin (Skin and right-sided endocarditis only)
      • Streptococcus pneumoniae
        • Penicillin
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Third-generation cephalosporins: (Ceftriaxone)
        • Fluoroquinolones: (Moxifloxacin, Levofloxacin)
        • Macrolides: (Azithromycin, Erythromycin, Clarithromycin)
        • Clindamycin
      • Streptococcus groups A and B (Streptococcus pyogenes & Streptococcus agalactiae)
        • Penicillin
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • First-generation cephalosporins: (Cephalexin)
        • Trimethoprim/Sulfamethoxazole (Bactrim)
        • Macrolides
        • Clindamycin
      • Enterococcus
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Nitrofurantoin (for UTIs)
      • Listeria monocytogenes
        • Aminopenicillins: (Amoxicillin, Ampicillin)
        • Trimethoprim/Sulfamethoxazole (Bactrim)
      • Vancomycin is used for penicillin-allergic patients and for patients with resistance to other gram-positive agents, including vancomycin-resistant strains.
    • Gram-Negative Bacteria
      • "HENS PECK" mnemonic: Haemophilus influenzae, Enterobacter, Neisseria gonorrhea & meningitidis, Serratia, Proteus mirabilis, Escherichia coli (E.coli), Klebsiella
        • Aminopenicillins: (Amoxicillin, Ampicillin) - Cover all except Enterobacter, Serratia, and Neisseria
        • Anti-pseudomonal penicillins: (Piperacillin/tazobactam) - Broad coverage
        • Second to Fourth-generation Cephalosporins: (Cefuroxime, Ceftriaxone, Cefepime, etc.) - Broad coverage
        • Carbapenems: (Doripenem, Imipenem/cilastatin, Meropenem, Ertapenem) - Broad coverage
        • Monobactams: (Aztreonam) - Broad coverage
        • Polymyxins: (Colistin) - Broad coverage
        • Fluoroquinolones: (Ciprofloxacin, Levofloxacin) - Broad coverage

    Empiric Therapy

    • Empiric antibiotic therapy - Starting treatment with antibiotics without knowing the specific pathogen.
    • Choice of antibiotic is based on the likely organism for the specific infection.
    • Once the pathogen is identified, antibiotic therapy is narrowed to target the specific bacterium.

    Antibiotics for Gram-Negative Bacteria

    • Hemophilus influenzae, Enterobacter, Nesseria, Serratia, Proteus, E.coli, Klebsiella (H.E.N.S.P.E.K):
      • Amino Penicillins: Cover all except Enterobacter, Serratia, Nesseria
      • Anti-pseudomonal Penicillins: Cover all except Enterobacter, Serratia, Nesseria
      • First Generation Cephalosporins: Cover E.coli, Klebsiella (P.E.C)
      • Second to Fourth Generation Cephalosporins: Cover all
      • Carbapenems: Cover all
      • Monobactins: Cover all
      • Fluoroquinolones: Cover all except Nesseria
      • Aminoglycosides: Cover all except Nesseria
      • Doxycycline & Tetracyclines: Limited coverage, not the primary antibiotic
      • Ceftazidime (Third Generation Cephalosporin): Specifically covers Nesseria Meningitis

    Antibiotics for Pseudomonas aeruginosa and Acinetobacter

    • Pseudomonas aeruginosa: Common nosocomial (hospital-acquired) pathogen
    • Acinetobacter: Also a common nosocomial pathogen
    • Aminopenicillins: Only covers Acinetobacter
    • Anti-pseudomonal Penicillins: Cover both Pseudomonas aeruginosa and Acinetobacter
    • First & Second Generation cephalosporins: Do not cover either
    • Third Generation cephalosporins: Only Ceftazidime covers Pseudomonas aeruginosa
    • Fourth Generation cephalosporins (Cefepime): Cover Pseudomonas aeruginosa
    • Carbapenems: Cover both
    • Monobactins: Cover Pseudomonas aeruginosa, not Acinetobacter
    • Fluoroquinolones (Ciprofloxacin & Levofloxacin): May be considered as an add-on therapy, limited evidence for monotherapy.
    • Aminoglycosides: Cover Pseudomonas aeruginosa, not Acinetobacter
    • Polymixins: "Salvage therapy" for both Pseudomonas aeruginosa and Acinetobacter

    Antibiotics for Extended Spectrum Beta-Lactamase (ESBL) Bacteria

    • ESBL Bacteria: Resistant to many common antibiotics.
    • Examples: Enterobacter, E.coli, Klebsiella.
    • Coverage: Carbapenems, Aminoglycosides, Polymyxins
    • Ceftazidime + Avibactam: May have adequate coverage for ESBL bacteria.

    Antibiotics for Stenotrophomonas

    • Antibiotics:
      • Anti-pseudomonal penicillins (Piperacillin/Tazobactam)
      • Polymixins
      • Trimethoprim/Sulfamethoxazole (Bactrim)

    Antibiotics for Anaerobic Bacteria

    • Anaerobic Bacteria: "Can't breathe perfectly fresh air"
    • Examples:
      • Clostridium species: C.perfringens, C.difficile, C.botulinum, C.tetani
      • Bacteroides
      • Peptostreptococcus
      • Fusobacterium
      • Actinomyces
    • Above the Diaphragm (Skin and Respiratory Infections): Clindamycin
    • Below the Diaphragm (GI & Pelvic Infections): Metronidazole
    • Broad Spectrum: Carbapenems, Anti-pseudomonal penicillins
    • Fluoroquinolones (Ciprofloxacin): May have coverage, resistance is a concern.

    Antibiotics for Clostridium difficile

    • C.difficile: Causes intestinal infection (colitis)
    • Antibiotics:
      • Metronidazole
      • Oral Vancomycin

    Antibiotics for Atypical Bacteria

    • Examples:
      • Mycoplasma
      • Chlamydia
      • Legionella
    • Fluoroquinolones: Preferred, especially for Legionella
    • Macrolides: Good coverage
    • Chloramphenicol: Good coverage, except for Legionella
    • Doxycycline: Preferred, covers all atypical bacteria.

    Antibiotics for Tick-Borne Illnesses

    • Examples:
      • Borrelia burgdorferi (Lyme disease)
      • Rickettsia rickettsii (Rocky Mountain Spotted Fever)
      • Ehrlichia
      • Anaplasma
    • Doxycycline: Preferred for all, except Babesiosis
    • Chloramphenicol: Alternative for low-income countries
      • Ceftriaxone: Preferred for disseminated Borrelia burgdorferi (CNS infections)

    Antibiotics for Treponema pallidum (Syphilis)

    • Penicillin G: Preferred
    • Doxycycline: Alternative for penicillin allergy

    Empiric Antibiotic Therapy for Common Infections

    • Community-Acquired Pneumonia (CAP):
      • Monotherapy Options: Fluoroquinolones
      • Combination Options: Ceftriaxone + Doxycycline or Macrolide
    • Hospital-Acquired Pneumonia (HAP):
      • Coverage: MRSA and Pseudomonas
      • Vancomycin: For MRSA
      • Anti-pseudomonal Penicillins (Piperacillin/Tazobactam), Ceftazidime, Cefepime, or Aminoglycosides: For Pseudomonas.
    • Gastrointestinal Infections:
      • Coverage: Gram-negative rods, especially Enterobacteriaceae (E.coli, Klebsiella)

    Antibiotic Coverage and Considerations

    • Anaerobic Infections: Carbapenems, anti-pseudomonal penicillins, metronidazole + fluoroquinolone (e.g., cipro), metronidazole + ceftriaxone, metronidazole + ceftazidime can be used for coverage.
    • Skin and Soft Tissue Infections:
      • MSSA (Methicillin-Susceptible Staphylococcus Aureus) & Strep A: Dicloxacillin, cephalexin (PO); nafcillin, oxacillin, cefazolin (IV).
      • MRSA (Methicillin-Resistant Staphylococcus Aureus): Bactrim, doxycycline, clindamycin (PO); vancomycin (IV), ceftaroline (IV).
    • Urinary Tract Infections (UTIs):
      • Pyelonephritis (Kidney Infection): Ceftriaxone, ciprofloxacin, ampicillin can be considered.
      • Acute Cystitis (Bladder Infection): Trimethoprim-sulfamethoxazole, nitrofurantoin, fosfomycin, ciprofloxacin (second-line due to resistance).
      • Complicated UTIs: Anti-pseudomonal drugs (piperacillin-tazobactam, cefepime, ceftazidime) for Pseudomonas coverage; vancomycin for MRSA and Enterococcus; amino penicillins for Enterococcus.
    • Bone and Joint Infections (Septic Arthritis and Osteomyelitis): Vancomycin for MRSA; ceftriaxone for Neisseria gonorrhoeae; anti-pseudomonal drugs for Pseudomonas coverage.
    • Meningitis:
      • Community-Acquired: Vancomycin, ceftriaxone are primary choices. Ampicillin can be added for suspected Listeria infection.
      • Hospital-Acquired: Vancomycin, cefepime are preferred for MRSA and Pseudomonas coverage. Carbapenems could be used, but caution due to potential for neurotoxicity.
    • Bloodstream Infections (Bacteremia):
      • Central Line-Associated: Vancomycin for MRSA coverage. Piperacillin-tazobactam for gram-negative and Pseudomonas coverage, especially with femoral lines.
      • Sepsis (Unknown Etiology): Vancomycin (gram-positive) and piperacillin-tazobactam or carbapenems (gram-negative, anaerobes).

    Adverse Effects

    • Neurotoxicity: Penicillins, cephalosporins, carbapenems, polymixins, linezolid.
    • Pancytopenia: Penicillins, cephalosporins, bactrim, chloramphenicol, linezolid.
    • Respiratory Failure: Polymixins, nitrofurantoin (pulmonary fibrosis).

    Nephrotoxic Agents

    • Acute interstitial nephritis (AIN) due to hypersensitivity reaction:
      • Penicillins
      • Cephalosporins
      • Bactrim (trimethoprim sulfamethoxazole)
    • Direct nephrotoxic effects:
      • Aminoglycosides
      • Vancomycin

    Ototoxic Agents

    • Aminoglycosides
    • Vancomycin (especially when combined with aminoglycosides)

    Myasthenia Gravis-Worsening Agents

    • Fluoroquinolones
    • Aminoglycosides
    • Macrolides
    • Clindamycin

    Teratogenic Agents

    • Bactrim: can cause kernicterus.
    • Fluoroquinolones: contraindicated under 18 years of age.
    • Chloramphenicol: can cause "gray baby syndrome."
    • Tetracyclines (e.g., doxycycline): can cause teeth discoloration.

    Disulfiram Reactions

    • Metronidazole
    • Third-generation cephalosporin ceftriaxone

    QT Prolongation

    • Fluoroquinolones
    • Macrolides

    CYP450 Inhibitors

    • Fluoroquinolones
    • Macrolides
    • Trimethoprim sulfamethoxazole

    Hemolytic Anemia

    • Penicillins and cephalosporins: cause hypersensitivity reactions leading to a positive Coombs test.
    • Trimethoprim sulfamethoxazole, fluoroquinolones, and nitrofurantoin: can exacerbate or worsen G6PD deficiency.

    Phototoxicity

    • Doxycycline
    • Trimethoprim sulfamethoxazole

    Additional Adverse Effects

    • Penicillins: anaphylactic shock.
    • Cephalosporins: vitamin K deficiency, increased risk of biliary sludge (especially ceftriaxone), and increased risk of acute kidney injury when combined with aminoglycosides.
    • Vancomycin: phlebitis, Red Man Syndrome, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS).
    • Daptomycin: rhabdomyolysis.
    • Doxycycline: pill-induced esophagitis, teeth discoloration in children.
    • Macrolides: MACRO mnemonic for adverse effects:
      • Motility dysfunction
      • Arrhythmias (QT prolongation)
      • Cholestasis
      • Rash
      • Eosinophilia
    • Clindamycin: C.difficile infection
    • Linezolid: lactic acidosis.
    • Fluoroquinolones: hypoglycemia or hyperglycemia, arthropathy (especially under 18 years of age), Achilles tendon rupture (increased risk in patients over 60 years of age or on steroids).
    • Bactrim: can cause hyperkalemia.

    Drugs Known to Cause C.difficile Infections

    • Clindamycin
    • Carbapenems
    • Trimethoprim sulfamethoxazole
    • Third- and fourth-generation cephalosporins
    • Fluoroquinolones

    ### Adverse Effects of Fluoroquinolones

    • Fluoroquinolones can cause hyperglycemia or hypoglycemia.
    • Fluoroquinolones can cause arthropathy, especially in children under 18 years old.
    • Fluoroquinolones can cause tendon rupture, particularly in patients older than 60 years old or those taking steroids.

    ### Adverse Effects of Bactrim

    • Bactrim can lead to hyperkalemia.

    Mechanisms of Antibiotic Resistance

    • Antibiotic resistance occurs when bacteria evolve mechanisms to evade the effects of antibiotics.

    Resistance Mechanisms: Reduced Permeability

    • Bacteria can reduce their permeability to antibiotics, hindering the entry of antibiotics into the cell.
    • Common antibiotics affected by reduced bacterial permeability include:
      • Vancomycin
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Beta-lactams

    Resistance Mechanisms: Increased Efflux

    • Bacteria can increase the efflux of antibiotics, effectively pumping antibiotics out of the cell.
    • Common antibiotics affected by increased efflux include:
      • Fluoroquinolones
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Macrolides

    Resistance Mechanisms: Altered Target Sites

    • Bacteria can alter the target sites for antibiotics, preventing the antibiotics from binding and exerting their effects.
    • This can involve changes in amino acid sequences or structural morphology of target proteins.
    • Common antibiotics affected by altered target sites:
      • Fluoroquinolones
      • Aminoglycosides
      • Tetracyclines (like doxycycline)
      • Beta-lactams
      • Vancomycin
      • Macrolides
      • Linezolid
      • Trimethoprim-sulfamethoxazole

    Resistance Mechanisms: Enzyme Inactivation

    • Bacteria can produce enzymes that inactivate antibiotics.
      • Certain enzymes, like beta-lactamases, can break down beta-lactam antibiotics.
      • Aminoglycosides can be inactivated through phosphorylation, acetylation, or methylation.
      • Macrolides can also be inactivated by bacterial enzymes.
    • Common antibiotics affected by enzymatic inactivation:
      • Beta-lactams
      • Aminoglycosides
      • Macrolides

    Transmission of Antibiotic Resistance

    • Antibiotic resistance can spread through vertical gene transfer or horizontal gene transfer.
      • Vertical gene transfer: Bacteria pass on resistance genes to their offspring.
      • Horizontal gene transfer: Bacteria transfer resistance genes through:
        • Transformation: Bacteria take up DNA from dead bacteria.
        • Conjugation: Bacteria transfer DNA through a sex pilus.
        • Transduction: Bacteriophages transfer DNA between bacteria.

    Risk Factors for Antibiotic Resistance

    • Exposure in hospital settings: Hospitals are a major breeding ground for multi-drug-resistant pathogens.
    • Over-prescription of antibiotics: Unnecessary use of antibiotics contributes to resistance.
    • Antibiotics in food production: Antibiotic use in livestock can lead to resistant bacteria in food products.

    Determining Antibiotic Susceptibility

    • Antibiotic susceptibility testing is used to identify the most effective antibiotic for a specific bacterial strain.
      • Common methods:
        • Broth microdilution and macrodilution
        • Kirby-Bauer disk diffusion
    • These tests determine the Minimum Inhibitory Concentration (MIC) - the minimum concentration of antibiotic necessary to inhibit bacterial growth--

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    Description

    This quiz explores the various mechanisms by which antibiotics act, specifically focusing on cell wall synthesis inhibitors. Understand the roles of different categories like glycopeptides, penicillins, and cephalosporins in bacterial infection treatment. Test your knowledge on the specific antibiotics and their clinical applications.

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