Cephalosporins Overview

3rd Generation Cephalosporins

• Are less effective against staphylococcus bacteria, but have increased activity against streptococcus bacteria.
• Ceftazidime and Cefixime have minimal or no useful activity against Gram-positive bacteria, but are more effective against Gram-negative bacteria.
• Ceftazidime is active against Pseudomonas aeruginosa.
• Ceftriaxone and Cefoperazone are eliminated by the kidneys.
• Ceftriaxone is eliminated through both renal and biliary pathways; it can contribute to biliary sludging in newborns.
• These drugs are used to treat conditions such as meningitis and Lyme disease.

4th Generation Cephalosporin

• Cefepime is eliminated by kidneys.
• It is useful for treating Methicillin-susceptible Staphylococcus aureus (MSSA), streptococci, and hospital-acquired infections.

Anti-MRSA Cephalosporins

• These medications target MRSA and MSSA, streptococci, and Gram-negative rods.
• They are not effective against Pseudomonas bacteria.
• They are susceptible to beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• It combines a cephalosporin structure with a siderophore, which binds to iron and is actively transported into bacteria.
• This medication kills Gram-negative rods (GNR) and Pseudomonas aeruginosa.
• It is an effective treatment for highly resistant bacterial infections.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• These combinations eliminate highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Cephalosporin Groups

• Cefazolin (1st generation) is effective against most Gram-positive cocci (GPCs).
• Ceftolaroline is primarily useful against resistant Gram-negative rods (GNRS).
• Anti-MRSA cephalosporins are used specifically against MRSA.

Monobactam

• Aztreonam is only effective against Gram-negative rods (GNR), including Pseudomonas bacteria.
• It is eliminated by the kidneys.
• It does not cross-react with other beta-lactams, except for ceftazidime and cefiderocol.
• It is useful in patients allergic to other beta-lactams for treating Gram-negative infections.

Cephalosporin Activity and Combinations

• 3rd Generation Cephalosporins:
  • Have reduced activity against Staphylococcus but improved activity against Streptococcus.
  • Ceftazidime and Cefixime have limited Gram-positive coverage.
  • Ceftazidime is active against Pseudomonas aeruginosa.
  • Ceftriaxone and Cefoperazone are primarily eliminated through the kidneys.
  • Ceftriaxone can be eliminated both renally and hepatically, and may cause biliary sludging in newborns.
  • Used to treat conditions like meningitis and Lyme disease.

4th Generation Cephalosporin

• Cefepime is eliminated by the kidneys.
• Effective against MSSA, Streptococci, and Gram-negative rods, commonly utilized in hospital settings.

Anti-MRSA Cephalosporins

• Effective against both MRSA and MSSA, also against Streptococci and Gram-negative rods.
• Not effective against Pseudomonas.
• Susceptible to beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• Combines the cephalosporin structure with a siderophore to enhance bacterial uptake.
• Kills Gram-negative rods (GNR) and Pseudomonas aeruginosa, even highly resistant strains.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Effective against highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Cephalosporin Groups

• 1st Generation:
  • Cefazolin: Most effective against Gram-positive cocci.
• 2nd Generation:
  • Cefuroxime: Wider spectrum than first generation.
• 3rd Generation:
  • Ceftriaxone: Broad spectrum, including some Gram-negative organisms.
  • Ceftazidime: Excellent activity against Pseudomonas aeruginosa.
• 4th Generation:
  • Cefepime: Broadest spectrum, including Pseudomonas aeruginosa.
  • Ceftolaroline: Highly effective against resistant Gram-negative rods.
• Anti-MRSA:
  • Used specifically against MRSA.

Monobactam

• Aztreonam: Only active against Gram-negative rods, including Pseudomonas.
• Eliminated through the kidneys.
• Not cross-reactive with other beta-lactams, except for ceftazidime and cefiderocol.
• Useful as a treatment option for Gram-negative infections in patients with allergies to other beta-lactams.

3rd Generation Cephalosporins

• Have decreased anti-staphylococcal activity
• Have better anti-streptococcal activity
• Ceftazidime and Cefixime have little to no useful Gram-positive coverage, but better coverage against Gram-negative bacteria
• Ceftazidime is active against Pseudomonas aeruginosa
• Ceftriaxone and Cefoperazone are eliminated renally
• Ceftriaxone is eliminated through both pathways (renally and hepatically) and may cause biliary sludging in neonates
• Uses include treating meningitis and Lyme disease

4th Generation Cephalosporin

• Cefepime is eliminated renally
• Useful for treating methicillin-susceptible Staphylococcus aureus (MSSA), streptococci in hospital settings

Anti-MRSA Cephalosporins

• Useful for treating MRSA and MSSA, streptococci, and Gram-negative rods
• Not useful for treating Pseudomonas
• Susceptible to beta-lactamases

Cefiderocol Siderophore Cephalosporin

• Combines cephalosporin structure with a siderophore that binds to iron and is transported into bacteria actively
• Kills Gram-negative rods (GNR) and Pseudomonas aeruginosa
• Kills bacteria that are resistant to other antibiotics

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Kill really resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae

Cephalosporin Groups

• 1st generation cephalosporins like Cefazolin are most useful against Gram-positive cocci (GPCs)
• 2nd generation cephalosporins like Cefuroxime have limited Gram-positive activity
• 3rd generation cephalosporins like Ceftriaxone are most useful against Gram-negative bacteria
• 4th generation cephalosporins like Cefepime are most useful against Gram-negative bacteria
• Ceftolaroline is useful against resistant Gram-negative rods (GNRS)
• Anti-MRSA cephalosporins are used against MRSA
• Monobactams like Aztreonam are only active against Gram-negative rods (GNR), including Pseudomonas
• Aztreonam is renally eliminated
• Aztreonam is not cross-reactive with other beta-lactams except for ceftazidime and cefiderocol
• Aztreonam is useful in treating Gram-negative infections in patients with allergies to other beta-lactams

Cephalosporins - Activity and Combinations

• 3rd Generation Cephalosporins:
  • Less effective against staphylococcus bacteria.
  • Better at fighting streptococcus bacteria.
  • Ceftazidime and Cefixime: Limited or no gram-positive coverage, better against gram-negative bacteria.
    • Ceftazidime: Effective against Pseudomonas aeruginosa.
  • Elimination: Ceftriaxone and Cefoperazone are primarily removed by the kidneys.
  • Ceftriaxone: Also eliminated through the bile which can cause blockage in newborns (biliary sludging).
  • Uses: Treatment for meningitis and Lyme disease.

4th Generation Cephalosporin

• Cefepime: Eliminated by the kidneys.
  • Usefulness: Effective against methicillin-sensitive Staphylococcus aureus (MSSA), streptococcus, and hospital-acquired infections.

Anti-MRSA Cephalosporins

• Usefulness: Effective against MRSA and MSSA, streptococcus bacteria, and gram-negative rods.
  • Pseudomonas: Not effective against Pseudomonas.
  • Beta-lactamase: Susceptible to breakdown by beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• Mechanism: Combines the cephalosporin structure with a siderophore, which binds iron for entry into bacteria.
  • Activity: Kills gram-negative bacteria (GNR) and Pseudomonas aeruginosa.
  • Resistance: Effective against highly resistant bacteria as well.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Activity: Effective against highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Monobactam

• Aztreonam: Effective only against gram-negative bacteria (GNR), including Pseudomonas.
  • Elimination: Primarily removed by the kidneys.
  • Cross-reactivity: Does not cross-react with other beta-lactams, except for ceftazidime and cefiderocol.
  • Gram-negative infections: Valuable for treating gram-negative infections in patients allergic to other beta-lactams.

Cephalosporin Activity and Combinations

• 3rd generation cephalosporins have decreased anti-staphylococcal activity but better anti-streptococcal activity.
• Ceftazidime and Cefixime have little to no gram-positive coverage but better gram-negative coverage.
• Ceftazidime is active against Pseudomonas aeruginosa.
• Ceftriaxone and Cefoperazone are eliminated renally.
• Ceftriaxone has dual elimination pathways and can cause biliary sludging in neonates.
• 3rd generation cephalosporins are used for meningitis, Lyme disease

4th Generation Cephalosporin

• Cefepime is eliminated renally and is useful for MSSA, streptococci in hospital settings.

Anti-MRSA Cephalosporins

• Useful for both MRSA and MSSA, streptococci, and Gram-negative rods.
• Not useful for Pseudomonas
• Susceptible to beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• Drug that combines the cephalosporin structure with a siderophore, which binds to iron and is transported into bacteria actively
• Kills Gram-negative rods (GNR) and Pseudomonas aeruginosa
• Kills really resistant bacteria.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Kill really resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Monobactam

• Aztreonam is only active against Gram-negative rods (GNR), including Pseudomonas.
• Renally eliminated.
• Not cross-reactive with other beta-lactams, except for ceftazidime and cefiderocol.
• Useful in Gram-negative infections in patients with allergies to other beta-lactams.

3rd Generation Cephalosporins

• 3rd generation drugs have decreased anti-staphylococcal activity, but better anti-streptococcal activity.
• Ceftazidime and Cefixime have little or no useful Gram-positive coverage, but better Gram-negative coverage.
• Ceftazidime is active against Pseudomonas aeruginosa.
• Ceftriaxone and Cefoperazone are eliminated renally, while Ceftriaxone has dual elimination pathways and can cause biliary sludging in neonates.
• 3rd generation cephalosporins are used for conditions like meningitis and Lyme disease.

4th Generation Cephalosporin

• Cefepime is eliminated renally and is useful for MSSA, streptococci, and other hospital-acquired infections.

Anti-MRSA Cephalosporins

• Useful for MRSA and MSSA, streptococci, and Gram-negative rods.
• Not useful for Pseudomonas
• Susceptible to beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• Combines the cephalosporin structure with a siderophore, which binds to iron and is actively transported into bacteria.
• Kills Gram-negative rods (GNR) and Pseudomonas aeruginosa.
• Even kills very resistant bacteria.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Effective against highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Monobactam

• Aztreonam is only active against Gram-negative rods (GNR), including Pseudomonas.
• It's Renally eliminated.
• Not cross-reactive with other beta-lactams, except for ceftazidime and cefiderocol.
• Useful for Gram-negative infections in patients with allergies to other beta-lactams.

3rd Generation Cephalosporins

• Offer better protection against streptococcal infections compared to first and second generation cephalosporins
• Have limited to no effectiveness against Gram-positive bacteria
• Ceftazidime and Cefixime are known for their strong activity against Gram-negative bacteria
• Ceftazidime is particularly effective against Pseudomonas aeruginosa
• Ceftriaxone and Cefoperazone are primarily eliminated through the kidneys
• Ceftriaxone can be eliminated through the kidneys and the liver, and it may cause biliary sludging in newborns
• Common uses include treatment of meningitis and Lyme disease

4th Generation Cephalosporin

• Cefepime is primarily eliminated through the kidneys
• Proven efficacy against MSSA, streptococci, and hospital-acquired infections

Anti-MRSA Cephalosporins

• Demonstrate good efficacy against MRSA, MSSA, streptococci, and Gram-negative rods
• Not effective against Pseudomonas
• Susceptible to inactivation by beta-lactamases

Cefiderocol Siderophore Cephalosporin

• Combines a cephalosporin structure with a siderophore, which binds to iron and gets actively transported into bacteria
• Effectively kills Gram-negative rods (GNR) and Pseudomonas aeruginosa
• Notably effective against highly resistant bacteria

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Demonstrate potent activity against highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae

Cephalosporin Groups

• 1st Generation: Cefazolin is most effective against Gram-positive cocci
• 2nd Generation: Cefuroxime has a broader spectrum of activity than first generation cephalosporins
• 3rd Generation: Ceftriaxone and Ceftazidime have strong activity against Gram-negative bacteria
• 4th Generation: Cefepime shows good efficacy against Gram-positive and Gram-negative bacteria, and Ceftolaroline specifically targets resistant Gram-negative rods
• Anti-MRSA: Primarily used to treat Methicillin-resistant Staphylococcus aureus infections

Monobactam

• Aztreonam exhibits specific activity against Gram-negative rods (GNR), including Pseudomonas
• Eliminated primarily by the kidneys
• Does not cross-react with common beta-lactams (except ceftazidime and cefiderocol)
• Offers a useful treatment option for Gram-negative infections in patients allergic to other beta-lactam antibiotics

Cephalosporin Activity and Combinations

• 3rd Generation Cephalosporins:
  • Increased activity against Gram-negative bacteria, but decreased activity against Gram-positive bacteria.
  • Ceftazidime and Cefixime: Have limited or no coverage against Gram-positive bacteria.
  • Ceftazidime: Effective against Pseudomonas aeruginosa.
  • Ceftriaxone and Cefoperazone: Excreted via the kidneys.
  • Ceftriaxone: Can be eliminated through the kidneys and the liver, potentially causing biliary complications in newborns.
  • Uses: Treatment of meningitis and Lyme disease.

4th Generation Cephalosporin

• Cefepime: Excreted by the kidneys.
• Effectiveness: Effective against MSSA, streptococci, and hospital-acquired infections.

Anti-MRSA Cephalosporins

• Effectiveness: Useful for treating MRSA, MSSA, streptococci, and Gram-negative rods.
• Ineffectiveness: Not active against Pseudomonas.
• Susceptibility: Vulnerable to beta-lactamases.

Cefiderocol Siderophore Cephalosporin

• Mechanism: Combines a cephalosporin structure with a siderophore, which binds to iron and is actively transported into bacterial cells.
• Activity: Eliminates Gram-negative rods (GNR) and Pseudomonas aeruginosa, including highly resistant bacteria.

Cephalosporin/Beta-lactamase Inhibitor Combinations

• Activity: Effective against highly resistant bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

Cephalosporin Groups

• First-generation: Cefazolin: Primarily active against Gram-positive cocci (GPCs).
• Second-generation: Cefuroxime: Have broader activity than first-generation cephalosporins.
• Third-generation: Ceftriaxone: Primarily active against Gram-negative bacteria.
  • Ceftazidime: Primarily active against Gram-negative bacteria, including Pseudomonas aeruginosa.
• Fourth-generation: Cefepime: Broad-spectrum activity including Gram-positive and Gram-negative bacteria.
  • Ceftolaroline: Primarily active against resistant Gram-negative rods (GNRs).
• Anti-MRSA: Used against MRSA.

Monobactam

• Aztreonam: Only active against Gram-negative rods (GNR), including Pseudomonas.
• Elimination: Excreted by the kidneys.
• Cross-reactivity: Does not cross-react with other beta-lactams, except for ceftazidime and cefiderocol.
• Usefulness: Treatment of Gram-negative infections in patients with allergies to other beta-lactams.