3rd Generation Cephalosporins

Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

Introduction

Third-generation cephalosporins were developed as an improvement over the first and second generations to provide broader antibacterial coverage, especially against gram-negative bacteria, while retaining some activity against gram-positive bacteria. They are derived from the mold Acremonium and work by inhibiting bacterial cell wall synthesis through binding penicillin-binding proteins, leading to bacterial cell death.

These antibiotics have increased effectiveness against resistant strains of bacteria such as Enterobacteriaceae, Neisseria, Haemophilus, and others, making them useful for treating serious infections including bacteremia, central nervous system infections, intra-abdominal infections, bone and joint infections, urinary tract infections, and respiratory tract infections.

Common third-generation cephalosporins include ceftriaxone, cefotaxime, ceftazidime, cefdinir, and cefixime. They are administered via intravenous, intramuscular, or oral routes depending on the drug and infection type.

Illustrated mechanism of action

Third-generation cephalosporins are broad-spectrum beta-lactam antibiotics. Their primary action is to inhibit bacterial cell wall synthesis, which is essential for bacterial survival and integrity.

Step-by-Step Mechanism

- Third-generation cephalosporins penetrate the outer membrane of Gram-negative bacteria more effectively than previous generations, due to specific chemical modifications.

- They bind to penicillin-binding proteins (PBPs), which are enzymes (mainly transpeptidases) responsible for the final cross-linking step in peptidoglycan synthesis of the bacterial cell wall.

- By inhibiting PBPs, these antibiotics prevent the cross-linking of peptidoglycan strands, weakening the cell wall.

- The weakened cell wall cannot withstand osmotic pressure, leading to bacterial cell lysis and death.

Illustrated Mechanism (Text Description)

1. Drug Entry: The cephalosporin molecule enters the periplasmic space of the bacterium (especially Gram-negative) by passing through porin channels in the outer membrane.

2. Target Binding: The drug binds to PBPs located on the inner membrane.

3. Inhibition of Peptidoglycan Cross-Linking: PBPs are blocked from catalyzing cross-links between peptidoglycan chains.

4. Cell Wall Weakening: The bacterial cell wall becomes structurally compromised.

5. Cell Lysis: The bacterium bursts due to osmotic imbalance, resulting in cell death.

Examples of Medication Brand Names (with Images)

Ceftriaxone 250 mg

Ceftriaxone 1000 mg

(Ceftrexy) Ceftriaxone sodium 1g ,0.5g

Side Effects

-Abdominal pain

- Diarrhea.

- Injection site inflammation.

- Nausea and vomiting.

- Rash and itching.

- Decreased white blood cell count (leukopenia).

- Decreased platelet count (thrombocytopenia).

- Tongue and throat swelling, difficulty breathing (allergic reactions).

Serious side effects may include:

- Severe allergic reactions (anaphylaxis).

- Drug-induced immune hemolytic anemia.

- Pseudomembranous colitis due to overgrowth of Clostridium difficile.

- Suppression of normal gut flora leading to decreased vitamin K synthesis and bleeding.

- Disulfiram-like reaction with alcohol (alcohol intolerance).

- Bleeding, especially with compounds containing a methylthiotetrazole group (e.g., cefotetan, ceftriaxone).

- Rare seizures, especially in patients with renal impairment.

Additionally, ceftriaxone may cause biliary sludge or pseudolithiasis, presenting with nausea and abdominal pain, which usually resolves after discontinuation.

Overall, third-generation cephalosporins are considered safe with low toxicity, but patients at risk for bleeding or allergic reactions should be closely monitored.

Indication

Third-generation cephalosporins are broad-spectrum antibiotics primarily indicated for infections caused by susceptible Gram-negative and some Gram-positive bacteria. They are commonly used to treat:

- Bacteremia/septicemia.

- Bone and joint infections.

- Central nervous system infections (e.g., meningitis).

- Gynecological infections.

- Intra-abdominal infections.

- Lower respiratory tract infections (e.g., pneumonia).

- Skin and soft tissue infections.

- Urinary tract infections.

- Gonorrhea.

- Lyme disease.

- Sepsis.

Some specific agents like ceftriaxone are used for gonorrhea, pelvic inflammatory disease, and as alternatives in meningitis treatment. Ceftazidime is notable for its activity against Pseudomonas aeruginosa.

These antibiotics are favored for their enhanced efficacy against resistant Gram-negative bacteria compared to earlier generations, though they generally have reduced activity against Gram-positive cocci compared to first-generation cephalosporins. Most third-generation cephalosporins penetrate the cerebrospinal fluid, making them suitable for CNS infections.

In summary, third-generation cephalosporins are indicated for serious infections involving Gram-negative organisms, including respiratory, urinary, intra-abdominal, CNS infections, and certain sexually transmitted infections.

Precautions & Contraindications

Third-generation cephalosporins have several precautions and contraindications to consider:

*Precautions*

- Avoid alcohol during treatment to prevent disulfiram-like reactions (e.g., nausea, vomiting, dizziness).

- Monitor kidney function, especially in older adults or those with renal impairment, as these drugs are primarily renally excreted.

- Use caution in patients with bleeding disorders or those on anticoagulants (e.g., warfarin) due to risk of hypoprothrombinemia and bleeding, particularly with agents containing N-methyl-thio-tetrazole (NMTT) side chains.

- Be aware of the risk of superinfection, including Clostridium difficile-associated diarrhea.

- Monitor for allergic reactions, especially in patients with penicillin allergy due to possible cross-reactivity (about 10% cross-sensitivity).

- Use cautiously in patients with a history of seizures or neurological disorders, as seizures have been reported rarely.

- Ceftriaxone is contraindicated in some newborns because it can increase the risk of jaundice.

*Contraindications*

- Known allergy to cephalosporins or severe penicillin allergy (especially anaphylaxis to beta-lactams).

- Newborns with hyperbilirubinemia (for ceftriaxone).

In summary, third-generation cephalosporins should be used with caution in patients with allergies to beta-lactams, renal impairment, bleeding risk, or seizure history. Alcohol should be avoided during treatment, and newborns should not receive ceftriaxone due to jaundice risk.

Monographs

DOC-20250323-WA0503.docx

Rana sabry-1.pdf

Drug monograph (Recovered) (1).pdf

Drug monograph.docx

Drug monograph.docx_20250423_220841_0000.pdf

Drug monograph.docx_20250323_064213_٠٠٠٠ (1).pdf

4_5976582730530428794.pdf

Reference

Citations:

[1] Third-Generation Cephalosporins - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK549881/

[2] Cephalosporins, 3rd Generation: Drug Class, Uses, Side ... - RxList https://www.rxlist.com/how_do_third-generation_cephalosporins_work/drug-class.htm

[3] Third generation cephalosporins: safety profiles after 10 ... - PubMed https://pubmed.ncbi.nlm.nih.gov/2189900/

[4] Third generation cephalosporins: Uses, common brands, and safety ... https://www.singlecare.com/drug-classes/third-generation-cephalosporins

[5] List of Third Generation Cephalosporins + Uses, Types & Side Effects https://www.drugs.com/drug-class/third-generation-cephalosporins.html

[6] What are Cephalosporins? Uses, Warnings, Side Effects, and More https://www.everydayhealth.com/cephalosporins/

[7] Distinguishing Second vs. Third-Generation Cephalosporins https://anesthesiaexperts.com/distinguishing-vs-third-generation-cephalosporins-understanding-clinical-differences-2023/

[8] Cephalosporins - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK551517/

Citations:

[1] Third-Generation Cephalosporins | DrugBank Online https://go.drugbank.com/categories/DBCAT002268

[2] Third-Generation Cephalosporins - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK549881/

[3] List of Third Generation Cephalosporins + Uses, Types & Side Effects https://www.drugs.com/drug-class/third-generation-cephalosporins.html

[4] Cephalosporins - StatPearls - NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK551517/

[5] Cephalosporins: Uses, List of Generations, Side Effects, and More https://www.healthline.com/health/cephalosporins

[6] Cephalosporins, 3rd Generation: Drug Class, Uses, Side ... - RxList https://www.rxlist.com/how_do_third-generation_cephalosporins_work/drug-class.htm

[7] Cephalosporins - Infectious Diseases - MSD Manuals https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-medications/cephalosporins

[8] Third Generation Cephalosporins - ScienceDirect.com https://www.sciencedirect.com/science/article/pii/S0891552020302919

Citations:

[1] Third-Generation Cephalosporins: Structure, Action, and Clinical Uses https://biologyinsights.com/third-generation-cephalosporins-structure-action-and-clinical-uses/

[2] Third-Generation Cephalosporins: A Comprehensive Guide to Usage, Mechanism of Action, and Considerations - DoveMed https://www.dovemed.com/health-topics/focused-health-topics/third-generation-cephalosporins-comprehensive-guide-usage-mechanism-action-and-considerations

[3] Third-generation cephalosporins: a critical evaluation - PubMed https://pubmed.ncbi.nlm.nih.gov/6432420/

[4] Third-Generation Cephalosporins https://europepmc.org/books/n/statpearls/article-30061/?extid=28846260&src=med

[5] Cephalosporins: Structure, SAR, Mechanism of action and Classifications / Infectious Disease https://www.youtube.com/watch?v=rJTi5ILFneU

[6] Third-Generation Cephalosporins - PubMed https://pubmed.ncbi.nlm.nih.gov/31751071/

[7] CE Activity | Third-Generation Cephalosporins https://www.statpearls.com/nursepractitioner/ce/activity/97547

[8] Third-Generation and Investigational Cephalosporins: I. Structure-Activity Relationships and Pharmacokinetic Review - Pamela Garzone, James Lyon, Victor L. Yu, 1983 https://journals.sagepub.com/doi/10.1177/106002808301700703

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