L-20 Cephalosporins Quiz

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Questions and Answers

What structural feature distinguishes cephalosporins from penicillins?

  • The presence of a beta-lactam ring
  • Resistance to penicillinases
  • A six-membered sulfur-containing ring adjoining the beta-lactam ring (correct)
  • Different R1 and R2 groups

Which of the following best describes the mechanism of resistance for bacteria against cephalosporins?

  • Inactivation by renal enzymes
  • Expression of a beta-lactamase called cephalosporinase (correct)
  • Reduced cell wall permeability
  • Altered penicillin-binding proteins

What characteristic is used to classify cephalosporins into different generations?

  • Method of administration
  • Toxicity profile
  • Renal excretion rate
  • Susceptibility to beta-lactamases and bacterial spectrum (correct)

Which of the following bacterial species is generally considered resistant to cephalosporins?

<p>Methicillin-resistant Staphylococcus aureus (MRSA) (D)</p> Signup and view all the answers

What effect does probenecid have on the pharmacokinetics of cephalosporins?

<p>Blocks tubular secretion, thus increasing plasma concentration (D)</p> Signup and view all the answers

Which of the following infections is NOT typically treated with cephalosporins?

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

Besides gram-positive cocci, which of the following additional group of bacteria exhibits sensitivity to cephalosporins, according to the content?

<p>Gram-negative bacilli (C)</p> Signup and view all the answers

Which of the following statements correctly describes the route of excretion for most cephalosporins?

<p>Excreted in the urine via renal tubular secretion (A)</p> Signup and view all the answers

Which of the following best describes the primary use of first-generation cephalosporins?

<p>Prophylaxis in perioperative infections and as penicillin G substitutes that are resistant to staphylococcal penicillinase. (C)</p> Signup and view all the answers

Which bacterial groups are generally NOT susceptible to first and second-generation cephalosporins?

<p>Enterococci and <em>Pseudomonas aeruginosa</em>. (A)</p> Signup and view all the answers

What is the main distinction of third-generation cephalosporins compared to first and second-generation drugs?

<p>They have broader gram-negative coverage and some can cross the blood-brain barrier. (D)</p> Signup and view all the answers

Which of the following second-generation cephalosporin has diminished use because of its high susceptibility to beta-lactamase?

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

What is a key consideration when selecting a second-generation cephalosporin for a specific infection?

<p>The specific activity of the drug may vary between different strains of bacteria. (B)</p> Signup and view all the answers

Which of the following organisms are classified as PEcK bacteria, targeted by first-generation cephalosporins?

<p><em>Proteus</em>, <em>E.coli</em>, and <em>Klebsiella pneumoniae</em>. (C)</p> Signup and view all the answers

Which cephalosporin is considered the drug of choice for surgical prophylaxis?

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

Why are second generation cephalosporins not recommended against Enterobacter?

<p>Enterobacter's resistance is due to chromosome-mediated beta-lactamase. (B)</p> Signup and view all the answers

Which of the following third generation cephalosporins is primarily excreted through the biliary tract, requiring no dosage adjustment in cases of renal insufficiency?

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

Which of the following best describes the mechanism of action for fosfomycin?

<p>Inhibition of enolpyruvate transferase, thus preventing formation of N-acetylmuramic acid. (A)</p> Signup and view all the answers

A patient presents with a severe cephalosporin allergy. According to the guidelines, which of these would be the recommended treatment for uncomplicated gonorrhea?

<p>A single 2-g dose of azithromycin orally. (D)</p> Signup and view all the answers

For which of the following infections is oral vancomycin the preferred treatment according to the text?

<p>Colitis caused by Clostridium difficile (A)</p> Signup and view all the answers

Which of the following is a characteristic of Cefditoren?

<p>It is a broad-spectrum oral beta-lactam antibiotic. (B)</p> Signup and view all the answers

Which of these third generation cephalosporins exhibits activity against Bacteroides fragilis?

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

What is the primary mechanism of bacitracin's antibacterial action?

<p>Inhibition of cell wall synthesis. (B)</p> Signup and view all the answers

Which of the following is NOT a typical route of administration for aztreonam?

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

For the treatment of uncomplicated gonorrhea in a patient who cannot be administered ceftriaxone, which of the following is recommended?

<p>Cefixime 400 mg orally plus azithromycin 1g orally single dose or doxycycline 100 mg orally twice daily for 7 days. (B)</p> Signup and view all the answers

Which of these statements best describes the use of third generation cephalosporins regarding meningitis?

<p>They are effective due to their CNS penetration. (D)</p> Signup and view all the answers

Which of the following best describes the role of clavulanic acid, sulbactam, and tazobactam?

<p>Inactivate beta-lactamases, protecting penicillins from degradation. (D)</p> Signup and view all the answers

Which bacterial species is targeted by vancomycin with an oral administration?

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

Which of the following third generation cephalosporins are recognized for their activity against P.aeruginosa?

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

What is the primary concern associated with combining vancomycin with aminoglycosides?

<p>Increased risk of ototoxicity and nephrotoxicity. (C)</p> Signup and view all the answers

Why might third generation cephalosporins not be effective against certain Enterobacter infections?

<p>They are hydrolyzed by Enterobacter chromosomal beta lactamases. (A)</p> Signup and view all the answers

What is the proposed mechanism of action for vancomycin according to the text?

<p>Inhibition of cell wall phospholipids and peptidoglycan polymerization by binding to D-alanyl-D-alanine. (A)</p> Signup and view all the answers

Which statement is NOT accurate regarding cycloserine?

<p>It exhibits limited distribution in bodily tissues. (D)</p> Signup and view all the answers

What is a key distinction in the mechanism of action between daptomycin and telavancin?

<p>Daptomycin relies solely on membrane disruption, whereas telavancin combines membrane disruption with vancomycin-like action. (B)</p> Signup and view all the answers

Why is daptomycin not suitable for the treatment of pneumonia?

<p>It is inactivated in pulmonary tissues. (C)</p> Signup and view all the answers

Which of the following is NOT a feature of telavancin?

<p>It shares a similar structure with daptomycin. (D)</p> Signup and view all the answers

What does the content imply regarding the effectiveness of the drugs against resistant gram-positive bacteria?

<p>Both daptomycin and telavancin are effective. (A)</p> Signup and view all the answers

Which of the following best explains why bacitracin is primarily used topically?

<p>It is poorly absorbed, resulting in local antibacterial activity with minimal systemic effects. (A)</p> Signup and view all the answers

What is the primary mechanism of action of polymyxins against bacteria?

<p>Disrupting bacterial cell membrane integrity by interacting with phospholipids. (C)</p> Signup and view all the answers

Why are polymyxins not a first-line treatment for systemic infections?

<p>They have a high risk of nephrotoxicity and neurotoxicity, and poor tissue distribution. (A)</p> Signup and view all the answers

Cycloserine's mechanism of action involves the inhibition of which process?

<p>The incorporation of D-alanine into peptidoglycans. (B)</p> Signup and view all the answers

Which of the following statements is true regarding the use of polymyxins?

<p>Polymyxins are used for topical applications and in the treatment of corneal ulcers caused by Pseudomonas. (D)</p> Signup and view all the answers

Which of the following is a key characteristic of Bacitracin?

<p>It can lead to proteinuria, hematuria, and nitrogen retention if systemically administered. (D)</p> Signup and view all the answers

How does Cycloserine exert its antibacterial effect?

<p>By blocking the conversion of L-alanine to D-alanine and incorporation into peptidoglycans. (B)</p> Signup and view all the answers

Which of the following is a typical combination for treating skin infections?

<p>Bacitracin, Polymyxins, and Neomycin (A)</p> Signup and view all the answers

Flashcards

First-generation cephalosporins: What are they effective against?

First-generation cephalosporins are effective against a range of gram-positive bacteria, including Staphylococcus aureus, and some gram-negative bacteria like Proteus, E. coli, and Klebsiella pneumoniae.

What bacteria are first-generation cephalosporins NOT effective against?

First-generation cephalosporins are generally not effective against enterococci or Pseudomonas aeruginosa.

Which first-generation cephalosporin is often used for surgical prophylaxis?

Cefazolin is a first-generation cephalosporin that is often used for surgical prophylaxis due to its effectiveness against common surgical site infections.

How do second-generation cephalosporins differ from first-generation cephalosporins in terms of their activity?

Second-generation cephalosporins have a broader spectrum of activity compared to first-generation cephalosporins, being effective against more gram-negative bacteria, including Haemophilus influenzae, Enterobacter aerogenes, and Neisseria.

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What bacteria are second-generation cephalosporins NOT effective against?

Second-generation cephalosporins are generally not effective against enterococci or Pseudomonas aeruginosa.

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What are the key features of third-generation cephalosporins?

Third-generation cephalosporins have an even broader spectrum of activity than second-generation cephalosporins, with enhanced gram-negative coverage and some ability to cross the blood-brain barrier.

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Which second-generation cephalosporin is susceptible to beta-lactamase?

Cefaclor, a second-generation cephalosporin, is highly susceptible to beta-lactamase, an enzyme produced by some bacteria that can inactivate the drug.

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What factors should guide the choice of a cephalosporin?

The choice of cephalosporin depends on the specific type of infection, the patient's sensitivity, and the potential for resistance.

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What are cephalosporins?

Cephalosporins are a class of antibiotics with a similar structure and mechanism of action to penicillins. They contain a beta-lactam ring and a six-membered sulfur-containing ring, and their effectiveness against bacteria is determined by the presence of specific 'R' groups.

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How are cephalosporins classified?

Cephalosporins are classified into four generations, with each generation having increasing resistance to beta-lactamases, which are enzymes produced by bacteria to break down antibiotics.

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What kind of bacteria are cephalosporins ineffective against?

Cephalosporins are generally not effective against methicillin-resistant Staphylococcus aureus (MRSA), Listeria monocytogenes, Clostridium difficile, and Enterococci.

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How are cephalosporins administered?

Cephalosporins are typically administered intravenously or orally, but most do not penetrate the central nervous system (CNS).

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How are cephalosporins eliminated?

The half-lives of cephalosporins vary widely. They are mostly excreted in the urine through renal tubular secretion, and the process can be blocked by probenecid, leading to higher plasma concentrations.

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What kind of bacteria are cephalosporins effective against?

Cephalosporins are effective against many gram-positive cocci, including staphylococci and many strains of gram-positive bacilli. However, they are ineffective against enterococci.

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What are some specific infections that cephalosporins are used for?

Cephalosporins are drugs of choice for infections caused by S. pyogenes, Klebsiella pneumoniae, and Pneumococcal pneumonia.

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What is the expanded spectrum activity of cephalosporins?

Cephalosporins have an expanded spectrum of activity that includes effectiveness against Proteus, Bacteroides fragilis, Serratia, Enterobacter, and some activity against Pseudomonas.

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Cefixime (Suprax)

First line drug for N. gonorrhoeae infections. Its use is declining due to resistance.

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Ceftriaxone (Rocephin)

A third generation cephalosporin that's a good choice for N. gonorrhoeae treatment, especially when resistance is a concern.

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Third Generation Cephalosporins

Third generation cephalosporins are known for their broad spectrum of activity, including effectiveness against a variety of gram-negative bacteria.

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Ceftazidime and Cefoperazone

Ceftazidime (Fortaz) and Cefoperazone (Cefobid) are two examples that are particularly effective against P. aeruginosa, a challenging bacteria.

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Biliary Excretion of Ceftriaxone and Cefoperazone

Ceftriaxone and Cefoperazone are eliminated primarily through the biliary system, meaning they are excreted in bile. This makes them good choices for patients with kidney issues as they don't require dosage adjustments based on kidney function.

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CNS Penetration of Third Generation Cephalosporins

Their ability to penetrate the central nervous system (CNS) makes them suitable for treating serious infections like meningitis.

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Cefditoren (Spectracef)

Cefditoren is especially good at combating beta-lactamase producing strains of Haemophilus influenzae, a common cause of ear infections.

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Meningitis Caused by Resistant Pneumococci

Highly penicillin-resistant strains of pneumococci may not be effectively treated by third generation cephalosporins alone. Adding rifampin or vancomycin might be necessary.

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Cycloserine

Cycloserine is an antibiotic that inhibits the growth of mycobacteria, often used to treat tuberculosis. It's taken orally and mainly excreted in its active form in urine.

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Daptomycin

Daptomycin is a bactericidal antibiotic that disrupts bacterial cell membranes, also interfering with protein and DNA synthesis. It's effective against resistant gram-positive bacteria such as MRSA and VRE, but not used for pneumonia.

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Telavancin

Telavancin is a bactericidal antibiotic similar to vancomycin in structure, but with a broader spectrum of activity. It's effective against resistant bacteria like MRSA and is used for complicated skin infections and pneumonia.

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What are the side effects of Cycloserine?

Cycloserine can cause side effects on the central nervous system, including headaches, tremors, psychosis, and even convulsions.

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Why is Daptomycin not used for treating pneumonia?

Daptomycin is inactivated by pulmonary tissue and is therefore not used for treating pneumonia. It's effective for complicated skin infections and bacteremia.

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Vancomycin

A type of antibiotic that works by inhibiting the synthesis of cell wall phospholipids and peptidoglycan polymerization. It is particularly effective against methicillin-resistant staphylococcal infections.

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Aztreonam

A group of antibiotics often used for urinary tract and respiratory tract infections.

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Beta- Lactamase Inhibitors

Antibiotics such as clavulanic acid, sulbactam, and tazobactam that enhance the effectiveness of penicillins by deactivating bacterial beta-lactamases.

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Vancomycin's Mechanism of Action

A type of antibiotic that works by binding to D-alanyl-D-alanine cell wall precursors, thereby inhibiting cell wall synthesis. Effective against gram-positive bacteria.

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Red Man Syndrome

A rare side effect of vancomycin treatment characterized by flushing, redness, and itching, typically affecting the face and neck. This is caused by the release of histamine.

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Fosfomycin

An antibiotic that works by inhibiting the early stages of cell wall synthesis. It is effective against both gram-positive and gram-negative bacteria.

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Bacitracin

A mixture of polypeptides that inhibits bacterial cell wall synthesis (particularly effective against gram-positive bacteria).

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Indications for Vancomycin

Situations in which vancomycin is clinically indicated. This includes infections by resistant Staphylococcus species, such as sepsis or endocarditis.

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Polymyxins

Polymyxins are a group of antibiotics active against gram-negative bacteria. They are cationic detergents that disrupt bacterial cell membranes, effectively killing the bacteria. Despite their effectiveness, their nephrotoxicity and neurotoxicity limit their use to topical applications.

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Polymyxin B

Polymyxin B is a specific type of polymyxin used in the USA. It is a cationic peptide that disrupts bacterial cell membranes, killing gram-negative bacteria like Pseudomonas. Its use is primarily restricted to topical applications due to its toxicity.

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Colistin (Polymyxin E)

Colistin, also known as Polymyxin E, is another type of polymyxin that is used outside of the USA. Like other polymyxins, it is effective against gram-negative bacteria and is used primarily in topical applications due to its toxicity.

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Cycloserine's Mechanism of Action

Cycloserine is a structural analogue of D-alanine, a molecule crucial for building bacterial cell walls. It works by inhibiting the formation of D-alanine, which is necessary for cell wall synthesis. This disruption prevents the bacteria from multiplying and causing infection.

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Study Notes

Cell Wall Synthesis Inhibitors II

  • Telavancin and daptomycin are included in this category.

Cephalosporins

  • Structurally and functionally similar to penicillins, with variable R1 and R2 groups.
  • Contain a 6-membered sulfur ring attached to a beta-lactam ring.
  • Show high resistance to penicillinases (e.g., cephalosporinase).
  • Classified into generations (first, second, third, fourth) based on bacterial susceptibility and resistance to beta-lactamases.
  • Commonly ineffective against methicillin-resistant Staphylococcus aureus (MRSA), Listeria monocytogenes, Clostridium difficile, and Enterococci.

First-Generation Cephalosporins

  • Examples include Cefazolin (Ancef, Kefzol), Cefadroxil (Duricef), Cephalexin (Keflex), Cephradine (Anspor, Velosef), Cephalothin (Keflin), and Cephapirin (Cefadyl).
  • Substitute for penicillin G, resistant to staphylococcal penicillinase.
  • Active against Proteus, E. coli, and Klebsiella pneumoniae (PEcK drugs).
  • Not active against enterococci or Pseudomonas aeruginosa.
  • Primarily excreted via glomerular filtration and tubular secretion.
  • Cefazolin is the common parenteral first-generation cephalosporin in use.
  • Alternative option for penicillin-allergic patients.

Second-Generation Cephalosporins

  • Examples include Cefaclor (oral av. Ceclor), Cefamandole (Mandol), Cefmetazole (Zefazone), Cefprozil (oral av. Cefzil), Cefoxitin (Mefoxin), Cefonicid (Monocid), Cefotetan (Cefotan), Cefuroxime (oral av. Ceftin, Kefurox, Zinacef), and Loracarbef (oral av. Lorabid).
  • Greater activity against gram-negative organisms (e.g., Haemophilus influenzae, Enterobacter aerogenes, Neisseria) as well as PEcK drugs.
  • Not recommended for Enterobacter due to chromosome-mediated beta-lactamase.
  • Not effective against Gram-positive organisms.
  • Cefaclor's use is diminished due to high beta-lactamase susceptibility.
  • IM injections may be painful.

Third-Generation Cephalosporins (Broad Spectrum)

  • Examples include Cefdinir (Omnicef), Cefixime (Suprax), Cefoperazone (Cefobid), Cefotaxime (Claforan), Ceftazidime (Fortaz, Tazidime), Ceftizoxime (Cefizox), Ceftriaxone (Rocephin), Ceftibuten (Cedax), Cefditoren (Spectracef), and Cefpodoxime (Banan, Vantin).
  • Increased gram-negative coverage and some ability to cross the blood-brain barrier.
  • Ceftriaxone and Cefixime are first-line drugs against Neisseria gonorrhoeae.
  • Cefoperazone and Ceftriaxone are excreted through the biliary tract, thus dosage adjustment isn't needed for renal insufficiency.
  • These are helpful in treating meningitis as they have good CNS penetration.

Fourth-Generation Cephalosporins

  • Cefepime (Maxipime) is a fourth-generation cephalosporin.
  • Similar to third-generation drugs, but with more resistance to hydrolysis by chromosomal beta-lactamases produced by Enterobacter.
  • High activity against Pseudomonas aeruginosa, Enterobacteriaceae, S. aureus, S. pneumoniae, and Hemophilus and Neisseria.
  • Primarily renally eliminated, 100%.

Fifth or Advanced Generation Cephalosporins: Ceftaroline

  • Ceftaroline (Teflaro) is a fifth-generation cephalosporin approved for treating complicated skin and skin structure infections and community-acquired pneumonia.
  • Has extended activity against Gram-positive organisms and activity against Gram-negative organisms.
  • Intravenous drug
  • Effective against methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA), vancomycin-insensitive S. aureus (VISA), and hetero-resistant vancomycin-insensitive S. aureus (hVISA).

Fifth or Advanced Generation Cephalosporins: Ceftobiprole

  • Ceftobiprole medocaril (ZEVTERA) is a fifth-generation cephalosporin effective against Gram-positives and Gram-negatives.
  • Administered by infusion.
  • Useful in community-acquired pneumonia and nosocomial pneumonia, excluding ventilator-associated pneumonia.

Other Facts

  • Available oral formulations: Cefadroxil, Cephalexin, Cephradine, Cefaclor, Cefprozil, Cefuroxime axetil, Cefdinir, Cefixime, Cefpodoxime, and Ceftibuten.
  • Similar resistance mechanisms as penicillins.
  • Similar elimination mechanisms as penicillins (with two exceptions).

Cephalosporin Adverse Effects

  • Hypersensitivity (5% of patients)
  • Cross-reactivity with penicillin allergies.
  • Disulfiram-like reactions with methyl-thiotetrazole group cephalosporins and alcohol.
  • Superinfections, renal damage, and local reactions (e.g., thrombophlebitis).

Carbapenems

  • Synthesized from thienamycin.
  • Imipenem is metabolized to potentially nephrotoxic compounds in the kidneys.
  • Often combined with cilastatin to inhibit the dehydropeptidase enzyme.
  • Imipenem/cilastatin (Primaxin) is a broad-spectrum antibiotic effective against gram-positive and gram-negative cocci (except methicillin-resistant S. aureus).
  • Other carbapenems include meropenem, ertapenem, and doripenem.

Monobactams

  • Aztreonam (Azactam) is a monobactam.
  • Specifically targets gram-negative rods, such as Pseudomonas and Serratia.
  • Little/no activity against Gram-positive cocci or anaerobic bacteria.
  • Administered intravenously or intramuscularly.

Beta-Lactamase Inhibitors

  • Clavulanic acid, Sulbactam, and Tazobactam inhibit beta-lactamases protecting penicillins.

Vancomycin

  • Tricyclic glycopeptide used orally and parenterally.
  • Effective against methicillin-resistant Staphylococcus aureus (MRSA) infections.
  • Inhibits cell wall synthesis.
  • Used to treat enterococcal and Clostridium difficile colitis.
  • Possible side effects include "red man" syndrome, kidney damage, and allergy.

Fosfomycin

  • Inhibits early stages of cell wall synthesis.
  • Analogue of N-acetyl muramic acid.
  • Effective against gram-positive and gram-negative organisms.
  • Oral administration, 3g dose suitable in uncomplicated UTI's in women.
  • Safe for use during pregnancy.

Bacitracin

  • Mixture of polypeptides that inhibit cell wall synthesis.
  • Active against Gram-positive cocci and bacilli, but typically used topically due to nephrotoxicity.
  • Can be combined with other antibiotics like neomycin and polymyxin.

Polymyxins

  • Peptides primarily used against gram-negative bacteria.
  • Nephrotoxic and limited to topical or ophthalmic use.
  • Effective against Pseudomonas and other gram-negative bacteria.

Cycloserine

  • Water-soluble antibiotic useful for treating tuberculosis resistant to first-line drugs.
  • Inhibits the enzymes involved in D-alanine synthesis which is essential in cell wall synthesis.
  • Has adverse effects, such as neurotoxicity (headaches, tremors, psychosis, convulsions).

Daptomycin

  • Bactericidal lipopeptide antibiotic.
  • Disrupts cell membranes.
  • Effective in complicated skin infections and bacteremia caused by S. aureus, including infective endocarditis.
  • Inactivates in pulmonary tissue and not suitable for pneumonia.

Telavancin

  • Lipoglycopeptide antibiotic similar in structure to vancomycin.
  • Dual mechanism of action similar to daptomycin.
  • Effective in complicated skin and skin-structure infections caused by MRSA, and in nosocomial and ventilator-associated bacterial pneumonia.
  • Contraindicated in pregnancy due to renal impairment and anticoagulation test interference. Cardiac abnormalities may occur.

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