Cephalosporins: Fungus-Derived Antibiotics for Bacterial Infections

Cephalosporins are used to manage a wide range of infections such as from gram-positive and gram negative bacteria. The five generations of cephalosporins are extremely effective against skin infection, resistant bacteria and other infections. 

Cephalosporins are an vital topic in Pharmacology. Read this blog post thoroughly to understand everything you need to know about this topic and ace your NEET PG preparation. 

• Cephalosporins are derived from fungus. It is an antibiotic, there are five generations of cephalosporins. It is similar to β lactam, they bind to penicillin-binding protein. They inhibit the enzyme transpeptidase, cross-linking, and cell wall synthesis. These are bactericidal drugs.

Mechanism of action of cephalosporins

• They inhibit the enzyme transpeptidase. They inhibit cell wall synthesis. They are bactericidal drugs.

Spectrum of action of cephalosporins

There are five generations of cephalosporins:

1^st Generation

• Cover more gram-positive and less gram-negative bacteria.

2nd Generation

• They little cover gram +ve and gram -ve bacteria.
• Majorly they cover anaerobes.

3rd Generation

• They cover gram +ve. But their major activity is on gram -ve and anaerobes.

4th Generation

• They also cover gram-positive, major activity is on gram-negative. These are used for resistant cases.

5th Generation

• It has anti-MRSA properties. It is the only β lactam having MRS activity. It also covers gram-positive and gram-negative infections. It is also used to treat CAP (community acquired bacterial pneumonia)

Cephalosporins are ineffective

• M- MRSA (methicillin-resistant staphylococcus aureus) except 5^th generation cephalosporins.
• A- Atypical bacteria (Chlamydia pneumonia, Mycoplasma pneumonia, and Legionella pneumonia).
• L- Listeria monocytogenes
• E- Enterococci.
• A-Acinetobacter 
• C- C. jejuni, Clostridium difficile.

1st Generation

• Oral Drug:
  • Cefadroxil 
    • Uses- Upper respiratory tract infection, Lower respiratory tract infection.
• IV Drug:
  • Cefazolin
    • Uses- Used in surgical prophylaxis (before surgery if there is a chance of infection, it can be reduced by cefazolin)
  • Cephaloridine (it is a nephrotoxic drug, so it is not in use).

2nd Generation

• Oral Drug:
  • Cefuroxime oxetil, Cefaclor
• Parenteral:  
  • Cefuroxime,
  • Cefamycins (cefoxitin, cefotetan, cefmetazole)
    • Uses- Cefamycins are active on anaerobe B.fragilis.
  • Cefomandole.

3rd Generation

• Oral drugs:
  • Cefixime
  • Cefpodoxime proxetil
  • Cefdinir.

• Parenteral:
  • Ceftriaxone 
  • Cefoperazone 
  • Cefotaxime
  • Ceftazidine 
  • Ceftizoxime
  • Moxalactam
  • Ceftizoxime.

Ceftriaxone:

• It is long-acting 
• Drug of choice for gram-negative infections (serious).
• Drug of choice for STDs (gonorrhoea, chancroid)
• Drug of choice for typhoid.
• Empirical drug of choice for meningitis
• Drug of choice for HACEK organisms.

Pharmacokinetics of Ceftriaxone

• It undergoes bile elimination.
• Safe in renal failure. (No need for dose reduction in renal failure)

Drug displaces bilirubin from plasma protein, so the problem can occur in neonates (less than 28 days child) kernicterus may occur.

• For neonates preferred drug is cefotaxime.
• It can form biliary sludge in the gall bladder (Pseudolithiasis) if it is undergoing bile elimination.
• They don’t have any effect on pseudomonas.

Cefoperazone

• Anti-pseudomonas properties like Ceftazidine, Moxalactam, and Ceftolozane. It also undergoes bile elimination. Safe in renal failure.
• Adverse effects: 
  • It can cause severe diarrhoea. It can produce a disulfiram-like reaction because they have a metabolite called N- methyl thiotetrazole, it may also be responsible for decreasing prothrombin (patient may lead to bleeding because prothrombin is required for clotting)
• Cefomandole, Cefotetan, and Moxalactam all have N- methyl thiotetrazole in their structure and responsible for the disulfiram-like reaction. If cefoperazone is used with Warfarin, it can increase prothrombin time.

Ceftazidime

• Drug of choice for melioidosis.
• Drug of choice for Pseudomonas, combined with Ceftazidime and Gentamicin to avoid resistance.

4^th Generation Drugs

• All are parenteral drugs. Examples are Cefepime and Cefpirome. Used for Resistant gram-negative infections. Can be used for Pseudomonas.

5th Generation Drugs

• They are also parenteral drugs only. Examples are Ceftobiprole and Ceftaroline. Ceftobiprole has the same activity as Ceftazidime for gram-negative. These drugs are pro-drugs, they metabolize and become active in the body. They have anti-MRSA properties. Given in resistant gram-negative infections. Ceftobiprole can be used for Pseudomonas, but Ceftaroline can’t be used. Adverse effects are hypersensitivity can be there, cross allergy, and they can produce pseudomembranous colitis.

New Drug

Cefiderocol

• It enters periplasmic space through a siderophore transporter.
• It has increase stability for β lactamase. It does not have any generation, but its chemical structure is similar to 3^rd generation Ceftazidime and 4^th generation Cefepime. Uses: complicated UTI, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia.

Other β Lactum Drugs

Carbapenems

• Spectrum of activity: they cover Gram-positive, Gram-negative Anaerobes. They are reserve drugs. 
• MOA: inhibit transpeptidase enzyme and inhibit cell wall synthesis.

Imipenem

• In nephron they have the dehydropeptidase enzyme. When imipenam is metabolized by dehydropeptidase they cant be reabsorbed back, therefore it is short acting and the metabolite is nephrotoxic. Cilastatin inhibits dehydropeptidase enzyme.
• Advantage of combining imipenem + cilastatin
  • Long acting – increase in duration of action
  • Less nephrotoxicity
• Among carbapenems: imipenem causes maximum seizures. 

Other Carbapenems

• Doripenem
• Meropenem
• Ertapenem is less effective on psuedomonas 
• Oral carbapenem - Faropenem 

Carbapenems are DOC in 

• Serratia
• Enterobacter 
• ESBL producing bacteria 
• Acinetobacter  

Monobactam

• It has only one ring i.e β lactum ring. Drug is Aztreonam. Acts on gram -ve bacteria only. No cross allergy with other beta lactam except ceftazidime.

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