Cell Wall Inhibitors in Antimicrobials
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Questions and Answers

What is the primary route of excretion for penicillin?

  • Biliary excretion
  • Cutaneous excretion
  • Oral secretion
  • Through the organic acid secretory system and glomerular filtration (correct)

Which β-lactam antibiotic primarily undergoes metabolism in the liver?

  • Penicillin G
  • Ceftriaxone
  • Nafcillin (correct)
  • Ampicillin

What may occur in patients receiving penicillins for more than 2 weeks?

  • Increased renal function
  • Decreased coagulation (correct)
  • Acute Gastrointestinal bleeding
  • Elevated liver enzymes

What is a common adverse reaction associated with penicillin use?

<p>Rashes and anaphylaxis (A)</p> Signup and view all the answers

Which side chains on cephalosporins modify their pharmacokinetic profile?

<p>At the 7-position (B)</p> Signup and view all the answers

What type of bacteria are cephalosporins generally more resistant to compared to penicillins?

<p>Certain β-lactamases (A)</p> Signup and view all the answers

What is a significant risk when penicillin is injected intrathecally or if high blood levels are reached?

<p>Seizures (B)</p> Signup and view all the answers

Which of the following statements about probenecid is correct?

<p>It increases blood levels of penicillins. (D)</p> Signup and view all the answers

Which semisynthetic penicillin is preferred for treating Listeria monocytogenes infections?

<p>Ampicillin (A)</p> Signup and view all the answers

What is the primary mechanism by which β-lactam antibiotics face bacterial resistance?

<p>β-Lactamase production (A)</p> Signup and view all the answers

What advantage do aminopenicillins have over regular penicillins?

<p>Extended spectrum of gram-negative bacteria activity (B)</p> Signup and view all the answers

Which of the following is a β-lactamase resistant penicillin?

<p>Nafcillin (D)</p> Signup and view all the answers

Which combination extends the antimicrobial spectrum of piperacillin?

<p>Piperacillin and tazobactam (D)</p> Signup and view all the answers

What is one common reason why methicillin is not used clinically in the US?

<p>Its associated toxicity (C)</p> Signup and view all the answers

Which of the following is NOT a mechanism of resistance to β-lactam antibiotics?

<p>Absorption of β-lactam antibiotics (C)</p> Signup and view all the answers

What type of infections are antistaphylococcal penicillins specifically indicated for?

<p>Infections caused by penicillinase-producing staphylococci (B)</p> Signup and view all the answers

What is the primary method of excretion for imipenem and other carbapenems?

<p>Glomerular filtration (C)</p> Signup and view all the answers

Which adverse effect is associated with high levels of imipenem?

<p>Seizures (C)</p> Signup and view all the answers

What is aztreonam's primary spectrum of activity?

<p>Gram-negative microorganisms, including Enterobacteriaceae (C)</p> Signup and view all the answers

What enables imipenem's prolonged activity in the body?

<p>Compounding with cilastatin (D)</p> Signup and view all the answers

Which of the following statements is true about beta-lactamase inhibitors?

<p>They protect antibiotics from being hydrolyzed by beta-lactamase enzymes. (A)</p> Signup and view all the answers

What effect do carbapenems have in terms of allergic reactions?

<p>They have a low immunogenic potential. (C)</p> Signup and view all the answers

Which β-lactam antibiotic does not require coadministration with a β-lactamase inhibitor?

<p>Ertapenem (C)</p> Signup and view all the answers

Which adverse effect is less common with carbapenems compared to other beta-lactams?

<p>Neutropenia (A), Eosinophilia (D)</p> Signup and view all the answers

Why are penicillin levels in the prostate ineffective against infections?

<p>Penicillin levels in the prostate are insufficient to be effective against infections due to inadequate penetration.</p> Signup and view all the answers

What mechanism does probenecid use to affect penicillin levels in the blood?

<p>Probenecid inhibits the secretion of penicillins by competing for the active tubular secretion via the organic acid transporter.</p> Signup and view all the answers

What type of hypersensitivity reactions can occur with penicillin administration?

<p>Reactions can range from rashes to anaphylaxis, with approximately 10% of patients reporting allergies.</p> Signup and view all the answers

How does the metabolism of penicillin G differ in patients with impaired renal function?

<p>In patients with impaired renal function, some metabolism of penicillin G may occur, requiring dosage adjustments.</p> Signup and view all the answers

What is a significant concern regarding prolonged therapy with penicillins?

<p>Cytopenias may develop in patients receiving penicillins for more than 2 weeks, necessitating regular blood count monitoring.</p> Signup and view all the answers

What structural component is fundamental to penicillins and contributes to their bactericidal function?

<p>The core four-membered β-lactam ring is fundamental to penicillins.</p> Signup and view all the answers

In what way are cephalosporins structurally altered to influence their antibacterial activity?

<p>Structural changes on the acyl side chain at the 7-position alter antibacterial activity.</p> Signup and view all the answers

How do penicillins interfere with bacterial growth?

<p>Penicillins interfere with bacterial growth by binding to penicillin-binding proteins (PBPs) and disrupting cell wall synthesis.</p> Signup and view all the answers

Why are gram-negative bacteria generally more resistant to penicillins compared to gram-positive bacteria?

<p>Gram-negative bacteria have an outer lipopolysaccharide membrane that acts as a barrier to penicillins.</p> Signup and view all the answers

What is the primary reason for the neurotoxicity seen with high doses of penicillins?

<p>Neurotoxicity, including seizures, can occur if penicillins are injected intrathecally or if very high blood levels are reached.</p> Signup and view all the answers

What is the clinical significance of natural penicillins like penicillin G and V?

<p>Natural penicillins are clinically significant for treating infections caused by various gram-positive organisms and certain gram-negative organisms.</p> Signup and view all the answers

How do cephalosporins compare to penicillins regarding resistance to β-lactamases?

<p>Cephalosporins are generally more resistant than penicillins to certain β-lactamases.</p> Signup and view all the answers

Which penicillin is preferred for treating syphilis and gas gangrene?

<p>Penicillin G is preferred for treating syphilis and gas gangrene.</p> Signup and view all the answers

What role does the R side chain play in determining the properties of penicillin?

<p>The R side chain affects the antimicrobial spectrum, stability to stomach acid, and susceptibility to β-lactamases.</p> Signup and view all the answers

Describe the difference in acid stability between penicillin G and penicillin V.

<p>Penicillin V is more acid stable than penicillin G, allowing it to be used in oral formulations.</p> Signup and view all the answers

What factors determine the susceptibility of PBPs to β-lactam antibiotics?

<p>The size, charge, and hydrophobicity of the specific β-lactam antibiotic determine the susceptibility of PBPs.</p> Signup and view all the answers

What is the primary resistance characteristic of first-generation cephalosporins?

<p>They are resistant to staphylococcal penicillinase.</p> Signup and view all the answers

What key activity differentiates second-generation cephalosporins from first-generation ones?

<p>Second-generation cephalosporins have greater activity against gram-negative organisms.</p> Signup and view all the answers

In what scenario are third-generation cephalosporins particularly important?

<p>They play a crucial role in the treatment of infectious diseases.</p> Signup and view all the answers

What is the significance of cefepime in fourth-generation cephalosporins?

<p>Cefepime has a wide antibacterial spectrum, effective against aerobic gram-negative organisms.</p> Signup and view all the answers

What makes ceftaroline unique among β-lactam antibiotics?

<p>Ceftaroline is the only β-lactam with activity against MRSA.</p> Signup and view all the answers

Why is caution advised when using ceftazidime?

<p>Resistance to ceftazidime is increasing; its use should be evaluated on a case-by-case basis.</p> Signup and view all the answers

Which generation of cephalosporins is associated with a risk of C. difficile infection?

<p>Third-generation cephalosporins are associated with the development of C. difficile infection.</p> Signup and view all the answers

What limitations are associated with the dosing of ceftaroline?

<p>Ceftaroline's twice-daily dosing regimen limits its use outside of institutional settings.</p> Signup and view all the answers

What causes resistance to cephalosporins?

<p>Resistance is mainly due to the hydrolysis of the β-lactam ring by β-lactamases or reduced affinity for penicillin-binding proteins (PBPs).</p> Signup and view all the answers

Why must many cephalosporins be administered intravenously or intramuscularly?

<p>Many cephalosporins have poor oral absorption, necessitating parenteral administration for effective treatment.</p> Signup and view all the answers

Which cephalosporins are effective against neonatal and childhood meningitis caused by H. influenzae?

<p>Ceftriaxone and cefotaxime are effective in treating neonatal and childhood meningitis caused by H. influenzae.</p> Signup and view all the answers

How is ceftriaxone uniquely excreted compared to other cephalosporins?

<p>Ceftriaxone is excreted primarily through the bile into the feces, allowing its use in patients with renal insufficiency.</p> Signup and view all the answers

What is the cross-reactivity percentage between penicillins and cephalosporins in allergic reactions?

<p>Cross-reactivity between penicillins and cephalosporins is approximately 3% to 5%.</p> Signup and view all the answers

What distinguishes carbapenems from penicillins in terms of structure?

<p>Carbapenems differ from penicillins by having a carbon atom replacing the sulfur atom in the thiazolidine ring.</p> Signup and view all the answers

Which carbapenem is known to resist hydrolysis by most β-lactamases?

<p>Imipenem is known to resist hydrolysis by most β-lactamases.</p> Signup and view all the answers

What specific coverage does ertapenem lack compared to other carbapenems?

<p>Ertapenem lacks coverage against P. aeruginosa, Enterococcus species, and Acinetobacter species.</p> Signup and view all the answers

What is the main benefit of compounding imipenem with cilastatin?

<p>It protects imipenem from renal dehydropeptidase, prolonging its activity in the body.</p> Signup and view all the answers

How does meropenem differ from imipenem regarding penetration in bacterial meningitis?

<p>Meropenem can reach therapeutic levels in bacterial meningitis even without inflammation.</p> Signup and view all the answers

What is a significant limitation of aztreonam's antimicrobial activity?

<p>Aztreonam lacks activity against gram-positive bacteria and anaerobes.</p> Signup and view all the answers

What adverse effect is commonly associated with high levels of imipenem?

<p>High levels of imipenem may provoke seizures.</p> Signup and view all the answers

Why might beta-lactamase inhibitors be administered in combination with beta-lactam antibiotics?

<p>They inactivate beta-lactamases, protecting the antibiotics from hydrolysis and preserving their antimicrobial activity.</p> Signup and view all the answers

What common side effects can be caused by imipenem/cilastatin?

<p>Nausea, vomiting, and diarrhea are common side effects.</p> Signup and view all the answers

How is aztreonam administered, and what special consideration is required for patients with renal failure?

<p>Aztreonam can be administered IV or IM, and it may accumulate in patients with renal failure.</p> Signup and view all the answers

What distinguishes monobactams, like aztreonam, from other β-lactams?

<p>Monobactams have a β-lactam ring that is not fused to another ring.</p> Signup and view all the answers

What drives the emergence of resistance in Enterococcus faecium infections?

<p>Resistance is driven by alterations in binding affinity to peptidoglycan precursors.</p> Signup and view all the answers

Why is the use of oral vancomycin limited?

<p>Oral vancomycin has poor absorption, making it mainly effective for managing C. difficile infections in the colon.</p> Signup and view all the answers

What are the advantages of lipoglycopeptides compared to vancomycin?

<p>Lipoglycopeptides are more potent than vancomycin and may have activity against vancomycin-resistant isolates.</p> Signup and view all the answers

How do telavancin and oritavancin enhance their antibacterial activity?

<p>They inhibit bacterial cell wall synthesis and disrupt membrane potential, which minimizes resistance selection.</p> Signup and view all the answers

What is a significant risk associated with the use of telavancin?

<p>Telavancin has a risk of nephrotoxicity and interactions with certain medications known to prolong the QT interval.</p> Signup and view all the answers

What is daptomycin indicated for, and what should it not be used to treat?

<p>Daptomycin is indicated for complicated skin infections and bacteremia but should never be used to treat pneumonia.</p> Signup and view all the answers

How often is daptomycin administered and via what route?

<p>Daptomycin is administered IV once daily.</p> Signup and view all the answers

What is the mechanism of action of lipoglycopeptides?

<p>Lipoglycopeptides inhibit bacterial cell wall synthesis, similar to vancomycin.</p> Signup and view all the answers

What is the significance of the β-lactam ring structure in penicillins?

<p>The β-lactam ring structure is crucial as it allows penicillins to bind to penicillin-binding proteins (PBPs), disrupting bacterial cell wall synthesis and leading to cell death.</p> Signup and view all the answers

How do the side chains of penicillins influence their efficacy?

<p>The R side chains of penicillins affect their antimicrobial spectrum, stability to stomach acid, and susceptibility to β-lactamases, thus influencing their clinical use.</p> Signup and view all the answers

Why are gram-negative organisms generally more resistant to penicillins?

<p>Gram-negative organisms have an outer lipopolysaccharide membrane that acts as a barrier to penicillins, preventing their effective entry into the bacterial cell.</p> Signup and view all the answers

What is the mechanism by which penicillins exert their bactericidal effect?

<p>Penicillins disrupt bacterial cell wall synthesis by binding to PBPs and inhibiting transpeptidation, leading to a weakened cell wall and eventual cell lysis.</p> Signup and view all the answers

What clinical conditions are treated with penicillin G?

<p>Penicillin G is commonly used to treat infections such as gas gangrene (caused by Clostridium perfringens) and syphilis (caused by Treponema pallidum).</p> Signup and view all the answers

Explain the difference in acid stability between penicillin G and penicillin V.

<p>Penicillin V is more acid-stable than penicillin G, making it suitable for oral administration, while penicillin G requires injection due to its instability in stomach acid.</p> Signup and view all the answers

What is the role of porins in the resistance of gram-negative bacteria to penicillins?

<p>Porins are water-filled channels that allow certain substances to pass through the outer membrane of gram-negative bacteria, influencing the entry of penicillins and contributing to resistance.</p> Signup and view all the answers

Discuss the emerging resistance issues regarding penicillin and viridans streptococci.

<p>Some viridans streptococci have developed resistance to penicillin, which poses a challenge for treatment as these bacteria are typically sensitive to natural penicillins.</p> Signup and view all the answers

How do the mechanisms of β-lactam antibiotic resistance differ between gram-positive and gram-negative bacteria?

<p>Gram-positive bacteria secrete β-lactamases extracellularly, while gram-negative bacteria inactivate β-lactam drugs in the periplasmic space.</p> Signup and view all the answers

What is the primary mechanism of action of fosfomycin?

<p>Fosfomycin inhibits the enzyme enolpyruvyl transferase, blocking cell wall synthesis.</p> Signup and view all the answers

What role do modified penicillin-binding proteins (PBPs) play in antibiotic resistance?

<p>Modified PBPs have a lower affinity for β-lactam antibiotics, necessitating higher drug concentrations to inhibit bacterial growth.</p> Signup and view all the answers

What are the most common adverse effects associated with the use of fosfomycin?

<p>The most common adverse effects include diarrhea, vaginitis, nausea, and headache.</p> Signup and view all the answers

How does the unique structure of fosfomycin affect its resistance to other antimicrobials?

<p>Fosfomycin's unique structure and mechanism of action make cross-resistance with other antimicrobials unlikely.</p> Signup and view all the answers

Explain the impact of the cell wall structure on the effectiveness of β-lactam antibiotics in gram-negative bacteria.

<p>The complex cell wall of gram-negative bacteria, including porins and efflux pumps, limits the penetration and effectiveness of β-lactam antibiotics.</p> Signup and view all the answers

What factors influence the route of administration for β-lactam antibiotics?

<p>The route of administration is determined by the drug's stability to gastric acid and the severity of the infection.</p> Signup and view all the answers

What is a critical drawback of polymyxins in clinical use?

<p>The use of polymyxins is limited due to the increased risk of nephrotoxicity and neurotoxicity.</p> Signup and view all the answers

How does food intake affect the absorption of dicloxacillin?

<p>Food decreases the absorption of dicloxacillin as it increases gastric emptying time, which allows the drug to be destroyed by stomach acid.</p> Signup and view all the answers

What types of bacteria are polymyxins especially effective against?

<p>Polymyxins are effective against most clinically important gram-negative bacteria, including P.aeruginosa and E.coli.</p> Signup and view all the answers

Describe the concept of depot forms in relation to penicillin administration.

<p>Depot forms, like procaine penicillin G and benzathine penicillin G, are administered IM and release the drug slowly into circulation.</p> Signup and view all the answers

In what way does amoxicillin differ from penicillin V regarding acid stability and absorption?

<p>Amoxicillin is stable in acid and is readily absorbed, whereas only one-third of penicillin V's oral dose is absorbed due to the acidic environment.</p> Signup and view all the answers

What is the significance of β-lactam antibiotics crossing the placental barrier?

<p>β-lactam antibiotics, including penicillins, cross the placental barrier without teratogenic effects, ensuring treatment without harm to the fetus.</p> Signup and view all the answers

What is a primary characteristic of first-generation cephalosporins regarding their activity against specific bacteria?

<p>First-generation cephalosporins are resistant to staphylococcal penicillinase and provide modest activity against Proteus mirabilis, E. coli, and K. pneumoniae.</p> Signup and view all the answers

How do second-generation cephalosporins differ in their antimicrobial coverage compared to first-generation cephalosporins?

<p>Second-generation cephalosporins have greater activity against gram-negative organisms while having weaker activity against gram-positive organisms.</p> Signup and view all the answers

What is a key advantage of third-generation cephalosporins in treating infectious diseases?

<p>Third-generation cephalosporins provide enhanced activity against gram-negative bacilli, including strains producing beta-lactamase.</p> Signup and view all the answers

Why is cefepime classified as a fourth-generation cephalosporin?

<p>Cefepime exhibits a wide antibacterial spectrum, effective against both gram-positive and gram-negative organisms and must be administered parenterally.</p> Signup and view all the answers

What unique feature does ceftaroline possess that sets it apart from other beta-lactams?

<p>Ceftaroline is the only beta-lactam in the U.S. that is effective against MRSA.</p> Signup and view all the answers

What caution should be taken when using ceftazidime?

<p>Ceftazidime should be used with caution due to its association with increasing resistance and the development of C. difficile infections.</p> Signup and view all the answers

In what way does the dosing regimen of ceftaroline limit its use?

<p>Ceftaroline's twice-daily dosing limits its use outside of institutional settings.</p> Signup and view all the answers

Why are advanced-generation cephalosporins important in treating resistant bacterial infections?

<p>Advanced-generation cephalosporins, particularly ceftaroline, provide broad-spectrum coverage against both gram-positive and gram-negative bacteria, including resistant strains.</p> Signup and view all the answers

What is the primary use of ceftolozane-tazobactam?

<p>It is primarily used for treating infections caused by resistant Enterobacteriaceae and multidrug-resistant P.aeruginosa.</p> Signup and view all the answers

How does meropenem-vaborbactam function in treating infections?

<p>It combines a carbapenem with a β-lactamase inhibitor to treat complicated UTIs, including pyelonephritis.</p> Signup and view all the answers

What are the common adverse events associated with vancomycin use?

<p>Common adverse events include nephrotoxicity, infusion-related reactions like red man syndrome, and ototoxicity.</p> Signup and view all the answers

What is the role of tazobactam in the ceftolozane-tazobactam combination?

<p>Tazobactam acts as a β-lactamase inhibitor, enhancing the effectiveness of ceftolozane against resistant bacteria.</p> Signup and view all the answers

In which infections is ceftazidime-avibactam indicated?

<p>Ceftazidime-avibactam is indicated for intra-abdominal infections and complicated UTIs.</p> Signup and view all the answers

What types of bacteria does vancomycin target?

<p>Vancomycin is active against aerobic and anaerobic gram-positive bacteria, including MRSA and Enterococcus spp.</p> Signup and view all the answers

Why are ceftolozane-tazobactam and ceftazidime-avibactam reserved for specific infections?

<p>They are reserved for treating infections caused by multidrug-resistant pathogens due to their extensive antimicrobial activity.</p> Signup and view all the answers

What is a unique characteristic of meropenem-vaborbactam compared to other combinations?

<p>Meropenem-vaborbactam is effective against a broad spectrum of β-lactamases except metallo-β-lactamases.</p> Signup and view all the answers

What are semisynthetic penicillins and why are they important in treating gram-negative infections?

<p>Semisynthetic penicillins, such as ampicillin and amoxicillin, have extended antimicrobial activity against gram-negative bacteria due to their modified R groups, which allow them to target organisms like E.coli and H.influenzae.</p> Signup and view all the answers

Explain the significance of β-lactamase inhibitors when used with aminopenicillins.

<p>β-lactamase inhibitors, such as clavulanic acid, increase the effectiveness of aminopenicillins like ampicillin by preventing the hydrolysis of the β-lactam ring, which some bacteria produce to resist these antibiotics.</p> Signup and view all the answers

Identify the primary use of antistaphylococcal penicillins and their limitations.

<p>Antistaphylococcal penicillins, such as methicillin and nafcillin, are primarily used to treat infections caused by penicillinase-producing staphylococci, including MSSA, but have minimal activity against gram-negative infections.</p> Signup and view all the answers

What role does piperacillin play in treating infections, and how does its formulation with tazobactam enhance its activity?

<p>Piperacillin is an antipseudomonal penicillin effective against P.aeruginosa, and its combination with tazobactam extends its antimicrobial spectrum to include penicillinase-producing organisms.</p> Signup and view all the answers

Describe the mechanisms by which bacteria develop resistance to β-lactam antibiotics.

<p>Bacteria can develop resistance to β-lactam antibiotics through β-lactamase production, decreased drug permeability, and altered penicillin-binding proteins (PBPs).</p> Signup and view all the answers

How does the genetic transfer of β-lactamase production contribute to antibiotic resistance?

<p>The gene responsible for β-lactamase production can be acquired through plasmid transfer between bacteria, leading to a rapid spread of resistance against β-lactam antibiotics.</p> Signup and view all the answers

What is the primary clinical application of amoxicillin in a dental context?

<p>Amoxicillin is employed prophylactically by dentists in high-risk patients to prevent bacterial endocarditis before dental procedures.</p> Signup and view all the answers

Why is methicillin primarily used in laboratory tests rather than clinically in the US?

<p>Methicillin is mainly utilized in laboratory settings to identify MRSA (methicillin-resistant Staphylococcus aureus) due to its toxicity and limited efficacy in clinical settings.</p> Signup and view all the answers

Flashcards

Penicillin metabolism

Usually insignificant, with some exceptions like penicillin G in patients with kidney problems.

Nafcillin/Oxacillin metabolism

Primarily metabolized in the liver, so renal function does not impact the dosage.

Penicillin excretion

Primarily through kidney's organic acid system (secretory) and glomerular filtration.

Penicillin dose adjustment

Necessary for patients with impaired kidney function; nafcillin and oxacillin do not need this adjustment.

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Probenecid effect on Penicillins

Increases penicillin blood levels by blocking its excretion through the kidney, competing for the same transporter.

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Penicillin hypersensitivity

About 10% of penicillin users experience allergies, ranging from rashes to serious reactions like anaphylaxis.

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Penicillin-related diarrhea

A common side effect, potentially caused by a bacteria (Clostridium difficile) infection called pseudomembranous colitis.

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Methicillin and Nephritis

Methicillin (though not used now) can cause a kidney inflammation (acute nephritis).

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Carbapenems administration

Imipenem, meropenem, and doripenem are intravenously administered and penetrate well into body tissues and fluids, including cerebrospinal fluid (CSF) when meningitis is inflamed. Meropenem can reach therapeutic levels even without inflammation.

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Carbapenem excretion

Carbapenems are primarily excreted through glomerular filtration, but imipenem requires cilastatin to protect it from renal dehydropeptidase, thus prolonging its activity.

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Cilastatin's role

Cilastatin protects imipenem from breakdown by the kidneys, extending imipenem's effectiveness in the body.

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Monobactams mechanism

Monobactams disrupt bacterial cell wall synthesis and primarily target gram-negative bacteria like Enterobacteriaceae and Pseudomonas aeruginosa.

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Aztreonam administration

Aztreonam, the only commercially available monobactam, can be administered intravenously or intramuscularly and can accumulate in patients with kidney failure.

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Beta-lactamase inhibitors mechanism

Beta-lactamase inhibitors (like clavulanate, sulbactam, tazobactam) inactivate beta-lactamases, protecting beta-lactam antibiotics from degradation.

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Beta-lactamase inhibitors structure

While some beta-lactamase inhibitors contain a beta-lactam ring, others, like avibactam and vaborbactam do not.

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Carbapenem adverse effects

Carbapenems can cause nausea, vomiting, diarrhea, eosinophilia, and neutropenia, but seizures are associated particularly with high imipenem levels. Cross-reactivity with penicillins may also occur.

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Semisynthetic penicillins

Chemically modified penicillin, like ampicillin and amoxicillin, increasing their effectiveness against specific bacteria.

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Aminopenicillins

A type of semisynthetic penicillin (like ampicillin and amoxicillin) effective against broader range of bacteria, including gram-negative.

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β-lactamase inhibitors

Substances that block enzymes (β-lactamases) produced by bacteria that break down penicillins thus increasing penicillin effectiveness.

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Antistaphylococcal penicillins

Penicillins that are resistant to bacterial enzymes (β-lactamases) produced by some types of Staphylococci.

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β-lactamase

Bacterial enzyme that breaks down some types of antibiotics (like penicillin).

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MRSA

Methicillin-resistant Staphylococcus aureus (bacteria).

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Anti-pseudomonal penicillin

Penicillin active against Pseudomonas aeruginosa, a type of gram-negative bacteria.

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Resistance to β-lactam antibiotics

Bacteria can develop resistance due to enzyme production (β-lactamases), decreased entry of drug or altered bacterial targets.

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Penicillin Structure

Penicillins have a core structure containing a β-lactam ring attached to a thiazolidine ring and an R side chain. The R side chain determines the penicillin's properties.

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Penicillins' Mechanism of Action

Penicillins block the final step of bacterial cell wall synthesis. They bind to enzymes called PBPs, which are essential for cross-linking the cell wall.

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Penicillin Susceptibility

Gram-positive bacteria are usually more susceptible to penicillins because they have a less complex cell wall. Gram-negative bacteria have an outer membrane that acts as a barrier.

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Natural Penicillins

Natural penicillins like Penicillin G and V are produced by the fungus Penicillium chrysogenum. They target gram-positive bacteria and some gram-negative organisms.

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Gram-positive and Penicillin

Gram-positive bacteria have a cell wall that's easily accessible to penicillins, making them highly susceptible.

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Gram-negative and Penicillin

Gram-negative bacteria have an outer membrane, called lipopolysaccharide, that acts as a barrier to penicillins.

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Penicillin V

Penicillin V is an oral penicillin that's more acid stable than Penicillin G and has similar spectrum of activity.

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Penicillin Resistance

Bacteria can develop resistance to penicillins by producing enzymes called β-lactamases that break down the penicillin.

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Penicillin Penetration

Penicillin can only effectively reach inflamed areas like bones or cerebrospinal fluid (CSF).

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Penicillin in Prostate

Penicillin levels in the prostate gland are too low to treat infections effectively.

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Probenecid and Penicillin

Probenecid increases penicillin blood levels by preventing its kidney excretion.

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Penicillin Diarrhea

Diarrhea is a common side effect of penicillin, sometimes caused by a Clostridium difficile infection.

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Cephalosporin Resistance

Cephalosporins can be ineffective due to bacterial enzymes (beta-lactamases) breaking down the antibiotic, OR bacteria evolving to have lower affinity for the drug's target.

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Cephalosporin Administration

Many cephalosporins are given intravenously or intramuscularly because they aren't well absorbed from the gut.

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Cephalosporin Distribution

They spread well throughout the body fluids, including the spinal fluid for treating meningitis in some cases.

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Cephalosporin Elimination

They're primarily removed from the body through the kidneys, EXCEPT for ceftriaxone, which is excreted through bile.

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Carbapenem Structure

They are like penicillins, but instead of a sulfur atom, they have a carbon atom in the key structural ring.

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Carbapenem Spectrum

Effective against a wide range of bacteria including those resistant to other antibiotics, except for some resistant strains.

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Ertapenem's Limitation

Unlike most carbapenems, ertapenem doesn't work against Pseudomonas aeruginosa, certain types of Enterococcus, and Acinetobacter bacteria.

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Why Cilastatin?

Cilastatin is given with imipenem to protect it from breakdown in the kidneys, prolonging its effectiveness.

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First-generation Cephalosporins

These cephalosporins are similar to penicillin G but are resistant to staphylococcal penicillinase (the enzyme that breaks down penicillin). They are effective against many types of bacteria, including Streptococcus pneumoniae, but some strains are resistant. They are also effective against certain organisms like Peptostreptococcus but not Bacteroides fragilis.

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Second-generation Cephalosporins

These cephalosporins have increased activity against gram-negative bacteria compared to first-generation cephalosporins, but they are less effective against gram-positive bacteria. They are particularly helpful against some anaerobic bacteria like Bacteroides fragilis.

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Third-generation Cephalosporins

Third-generation cephalosporins are most powerful at fighting gram-negative bacteria, particularly those that produce beta-lactamases. They are less effective than first-generation cephalosporins against MSSA (methicillin-sensitive Staphylococcus aureus). Certain third-generation cephalosporins, like ceftriaxone and cefotaxime, are ideal for treating meningitis, but caution is needed as they can lead to C. difficile infections.

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Fourth-generation Cephalosporins

Fourth-generation cephalosporins, like cefepime, are administered intravenously and possess a wide spectrum of activity, including efficacy against streptococci and staphylococci (but only methicillin-susceptible strains). They are also effective against various aerobic gram-negative organisms like Enterobacter species, E. coli, and P. aeruginosa.

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Advanced-generation Cephalosporins

Ceftaroline is a broad-spectrum, advanced-generation cephalosporin. It is unique for its activity against MRSA (methicillin-resistant Staphylococcus aureus), making it valuable for treating complicated skin and skin structure infections and community-acquired pneumonia. It is available in the US and has a similar activity against gram-negative bacteria as third-generation ceftriaxone.

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What is the key difference between first and second-generation cephalosporins?

First-generation cephalosporins are more potent against gram-positive bacteria, while second-generation cephalosporins have greater activity against gram-negative bacteria.

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How are third-generation cephalosporins useful in treating meningitis?

Third-generation cephalosporins like ceftriaxone and cefotaxime are effective in treating meningitis because they can penetrate the cerebrospinal fluid (CSF), which is the fluid around the brain and spinal cord.

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What is unique about ceftaroline, an advanced-generation cephalosporin?

Ceftaroline is the only beta-lactam antibiotic approved in the US that is effective against MRSA (methicillin-resistant Staphylococcus aureus).

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β-Lactamase Inhibitors Mechanism

β-Lactamase inhibitors, like clavulanate, sulbactam, and tazobactam, work by inactivating the bacterial enzymes called β-lactamases. These enzymes would normally break down β-lactam antibiotics.

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Imipenem / Cilastatin

Imipenem, a carbapenem antibiotic, is always combined with cilastatin. Cilastatin protects imipenem from being broken down in the kidneys, allowing it to remain effective for a longer period.

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Meropenem's Unique Feature

Meropenem, another carbapenem antibiotic, can reach therapeutic levels in the cerebrospinal fluid (CSF) even without inflammation of the meninges. This makes it useful for treating bacterial meningitis.

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Vancomycin Resistance

Enterococcus faecium infections often exhibit resistance to vancomycin, unlike Streptococcus and Staphylococcus species. This resistance arises from modifications in the bacteria's ability to bind to peptidoglycan precursors, the building blocks of the bacterial cell wall.

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Vancomycin Oral Use

Vancomycin is poorly absorbed in the gut after oral administration. It's mainly used orally for treating Clostridium difficile infections in the colon.

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Lipoglycopeptides: Mechanism of Action

Lipoglycopeptides like telavancin, oritavancin, and dalbavancin are powerful antibiotics that fight gram-positive bacteria by interfering with cell wall synthesis. They achieve this by binding to peptidoglycan precursors, similar to vancomycin.

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Lipoglycopeptides: Advantages over Vancomycin

Lipoglycopeptides are more potent and effective against certain bacteria, even vancomycin-resistant strains, due to their unique chemical structure.

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Telavancin Use

Telavancin is an alternative to vancomycin for treating severe skin infections (ABSSSIs) and pneumonia caused by resistant gram-positive bacteria (including MRSA).

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Telavancin Side Effects

Telavancin can cause kidney problems (nephrotoxicity) and interact with other medications that prolong the QT interval, potentially leading to heart rhythm issues.

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Oritavancin and Dalbavancin: Advantages

Oritavancin and dalbavancin have much longer half-lives than telavancin, enabling a single-dose treatment for severe skin infections (ABSSSIs).

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Daptomycin: Mechanism of Action

Daptomycin is a powerful antibiotic that kills bacteria by disrupting their cell membrane. It's often used against resistant gram-positive bacteria like MRSA and VRE.

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Penicillin's Target

Penicillin blocks the last step in bacterial cell wall synthesis, a process called transpeptidation.

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Penicillin's Weakness

Some bacteria produce an enzyme called β-Lactamase that breaks down penicillin, rendering it ineffective.

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Gram-Positive Bacteria & Penicillin

Gram-positive bacteria have a cell wall easily penetrated by penicillin, making them generally susceptible.

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Gram-Negative Bacteria & Penicillin

Gram-negative bacteria have an outer membrane that blocks penicillin's entry, making them less susceptible.

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Why is Methicillin not used clinically in the US?

Methicillin is not used clinically in the US due to its toxicity, except in laboratory tests to identify MRSA.

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What is MRSA?

MRSA stands for Methicillin-Resistant Staphylococcus aureus. This strain is resistant to most commercially available β-lactam antibiotics.

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Antipseudomonal Penicillin: Piperacillin

Piperacillin has activity against Pseudomonas aeruginosa, a type of gram-negative bacteria.

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β-Lactamase Production

Bacteria produce β-lactamase, an enzyme that breaks down the β-lactam ring of penicillin, causing antibiotic resistance.

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Decreased Permeability to the Drug

Bacteria can develop resistance by decreasing their permeability to penicillin, preventing the drug from entering the cell.

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Altered PBPs

Bacteria can develop resistance by changing the target site of penicillin, altering the Penicillin-Binding Proteins (PBPs) that it needs to bind to.

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Gram-positive β-lactamases

Gram-positive bacteria secrete β-lactamases outside their cell walls, directly breaking down β-lactam antibiotics.

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Gram-negative β-lactamases

Gram-negative bacteria inactivate β-lactams within a special compartment called the periplasmic space, preventing antibiotic action.

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Decreased permeability to antibiotics

Bacteria can become resistant by preventing antibiotics from entering their cell walls.

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How do Gram-positive bacteria decrease permeability?

Gram-positive bacteria have a simpler cell wall, but they can make it tough for antibiotics to reach their target by altering their peptidoglycan.

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How do Gram-negative bacteria decrease permeability?

Gram-negative bacteria have a complex outer membrane with porins (gates) and efflux pumps (outward transporters) that can block antibiotic entry.

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What are PBPs?

Bacterial enzymes that are crucial for synthesizing the cell wall, the bacterial armor.

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How do bacteria become resistant by altering PBPs?

Bacteria can modify their PBPs, decreasing their affinity to β-lactam antibiotics, requiring higher doses to be effective.

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What is the MRSA resistance mechanism?

MRSA bacteria have modified PBPs that have a much lower affinity to β-lactam antibiotics, rendering most drugs ineffective.

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Fosfomycin: Mechanism

Fosfomycin blocks bacterial cell wall synthesis by inhibiting the enzyme enolpyruvyl transferase, crucial for peptidoglycan formation.

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Fosfomycin: Uses

First-line treatment for acute cystitis caused by E. coli or E. faecalis. It's well-absorbed, reaching high urinary concentrations, allowing for a single dose.

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Polymyxins: Mechanism

Polymyxins are cationic polypeptides that disrupt bacterial cell membranes by binding to phospholipids, leading to cell leakage and death.

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Polymyxins: Limitations

Their use is limited due to the risk of nephrotoxicity and neurotoxicity when used systemically. Gram-negative bacteria are increasingly resistant.

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Polymyxins: Forms

Two forms are used clinically: polymyxin B (parenteral, topical) and colistin (prodrug, IV or inhaled).

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Ceftriaxone & Meningitis

Ceftriaxone, a third-generation cephalosporin, is effective in treating meningitis because it can penetrate the cerebrospinal fluid (CSF), which is the fluid around the brain and spinal cord.

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Ceftaroline's Unique Feature

Ceftaroline, an advanced-generation cephalosporin, is the only beta-lactam antibiotic approved in the US that is effective against MRSA (methicillin-resistant Staphylococcus aureus).

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Ceftolozane-Tazobactam

A combination of a 3rd generation cephalosporin and a β-lactamase inhibitor. It is effective against some resistant Enterobacteriaceae and P. aeruginosa, but has limited activity against gram-positive bacteria and anaerobes.

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Ceftazidime-Avibactam

Another combination of a 3rd generation cephalosporin and a β-lactamase inhibitor. It has a broader spectrum of activity, including against Enterobacteriaceae and P. aeruginosa, but is less effective against Acinetobacter and anaerobes.

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Meropenem-Vaborbactam

A carbapenem antibiotic paired with a β-lactamase inhibitor. It is effective against Enterobacteriaceae producing a wide range of β-lactamases, except metallo β-lactamases.

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Vancomycin's Target

Vancomycin binds to peptidoglycan precursors, interfering with the polymerization and cross-linking of the bacterial cell wall. This disrupts cell wall integrity, leading to bacterial death.

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Vancomycin's Uses

Vancomycin effectively treats aerobic and anaerobic gram-positive bacteria, including MRSA, MRSE, Enterococcus spp., and C. difficile infections.

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Vancomycin's Side Effects

Vancomycin can cause nephrotoxicity, infusion-related reactions like red man syndrome, and ototoxicity.

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Metronidazole's Role

Metronidazole is an antibiotic that is often used in combination with other antibiotics, such as ceftolozane-tazobactam and ceftazidime-avibactam, to treat intra-abdominal infections.

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Multidrug-Resistant Pathogens

These are bacteria that have developed resistance to multiple antibiotics, making treatment challenging. Ceftolozane-tazobactam and ceftazidime-avibactam are reserved for infections caused by these resistant pathogens.

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Study Notes

Cell Wall Inhibitors

  • Cell wall inhibitors are antimicrobial agents that target the cell wall synthesis of bacteria.

  • Penicillins

    • Basic structure: a four-membered β-lactam ring attached to a thiazolidine ring and an R side chain.
    • Differ in the R substituent attached to the 6-aminopenicillanic acid residue.
    • Side chain nature impacts antimicrobial spectrum, stability to stomach acid, cross-hypersensitivity, and susceptibility to β-lactamases.
    • Natural penicillins include penicillin G and penicillin V, derived from Penicillium chrysogenum fermentations.
    • Penicillin G is more potent against Neisseria spp. and anaerobes.
    • Most streptococci are sensitive to penicillin G, but penicillin-resistant strains are emerging.
    • The majority of S. aureus are now penicillinase-producing and resistant to penicillin G.
    • Penicillin V is more acid-stable and used orally.

  • Cephalosporins

    • Structurally related to penicillins, with a core β-lactam ring and different side chains attached to 7-aminocephalosporanic acid.
    • Structural variations alter antibacterial activity; pharmacokinetic profiles.
    • Cephalosporins have a similar mode of action and resistance mechanisms to penicillins.
    • More resistant to some β-lactamases.
    • Classified based on bacterial susceptibility and resistance to β-lactamases into generations.
      • First generation
      • Second generation
      • Third generation
      • Fourth generation
      • Advanced generation.

  • Carbapenems

    • Synthetic β-lactam antibiotics with a different structure than penicillins.
    • The sulfur atom in the thiazolidine ring is replaced by a carbon atom.
    • Imipenem, meropenem, doripenem, and ertapenem are examples.
    • Imipenem resists hydrolysis by most β-lactamases, but not metallo-β-lactamases.
    • Meropenem and doripenem are similar to imipenem in antibacterial activity.
    • Ertapenem lacks coverage against P. aeruginosa, Enterococcus species, and Acinetobacter species.

  • Monobactams

    • Unique structure: the β-lactam ring is not fused to another ring.
    • Aztreonam is the only commercially available monobactam.
    • Primarily active against gram-negative pathogens, including Enterobacteriaceae and P. aeruginosa.
    • Lacks activity against gram-positive bacteria and anaerobes.
    • It can accumulate in patients with renal failure
    • Relatively nontoxic and has minimal cross-reactivity with antibodies.

  • β-Lactamase Inhibitors

    • Inhibit β-lactamases, preventing the hydrolysis of the β-lactam ring.
    • Examples include clavulanic acid, sulbactam, and tazobactam
    • Co-formulated with other β-lactam antibiotics to overcome resistance.

  • Vancomycin

    • Tricyclic glycopeptide antibiotic active against aerobic and anaerobic gram-positive bacteria, including MRSA, MRSE, Enterococcus spp., and C. difficile.
    • Binds to peptidoglycan precursors, disrupting polymerization, and cross-linking.
    • Bactericidal; commonly used in skin and soft tissue infections, endocarditis, and nosocomial pneumonia.
    • Renal function monitoring is crucial. -Resistance is uncommon but can be seen in Enterococci spp.

  • Lipoglycopeptides

    • Similar spectrum of activity than vancomycin.
    • More potent than vancomycin and effective against vancomycin-resistant isolates.
    • Inhibit bacterial cell wall synthesis and disrupt membrane potential.

  • Daptomycin

    • Bactericidal cyclic lipopeptide antibiotic.
    • Alternative to vancomycin or linezolid for treating infections caused by resistant gram-positive organisms, including MRSA and VRE.
    • Indicated for complicated skin and skin structure infections and bacteremia caused by S. aureus, but should not be used for the treatment of pneumonia.

  • Fosfomycin

    • Bactericidal synthetic derivative of phosphonic acid that blocks essential steps in peptidoglycan synthesis.
    • Indicated for UTIs caused by E. coli or E. faecalis; first-line therapy for acute cystitis.

  • Polymyxins

    • Cationic polypeptides that bind to bacterial cell membranes and disrupt cell membrane integrity.
    • Concentration-dependent bactericidal agents.
    • Active against gram-negative bacteria.
    • Clinical use is limited due to nephrotoxicity and neurotoxicity when used systemically.

Mechanisms of Action

  • These drugs interfere with the final stage of bacterial cell wall synthesis, causing a weakened cell wall.
  • Penicillins and cephalosporins structurally resemble portions of peptidoglycan, competing and binding to enzymes involved in cross-linking the cell wall.

Antibacterial Spectrum

  • Factors impacting PBP susceptibility, such as size, charge, and hydrophobicity of the β-lactam antibiotic, influence the spectrum. Gram-positive organisms are more susceptible. The outer layer of gram-negative organisms hinders water-soluble penicillins.

Resistance

  • Resistance mechanisms include β-lactamase production; reduced drug permeability, and altered PBPs.

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Cell Wall Inhibitors PDF

Description

This quiz focuses on cell wall inhibitors, specifically antimicrobial agents like penicillins and cephalosporins. Understanding their structure, mechanism of action, and differences in effectiveness against various bacterial strains is crucial. Test your knowledge on the intricacies of these vital components in microbiology and pharmacology.

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