Antimicrobial Drugs: Combatting Infections

Antimicrobial drugs are the agents that kills microorganisms or prevent their growth in the body. There are different kinds of antibacterial medications which are grouped based on their structure and their mechanism of action.

1. Beta-lactam group
   • Penicillins
   • Cephalosporins
   • Carbapenems
   • Monobactams
   • Vancomycin

1. Penicillin- It includes penicillin G, penicillin V, Penicillinase-sensitive penicillins, penicillinase-resistant Penicillins, and anti-pseudomonal penicillins.
   • Penicillin G, penicillin V:
     • Mechanism of action- It is a D-Ala D-ALa structural analog, it binds the penicillin-binding protein called Transpeptidases. It blocks the transpeptidase cross-linking of peptidoglycan in the cell wall and activates the autolytic enzymes. 
   • Clinical use: To remember the bacteria on which penicillin reacts the mnemonic is- (SMART player GAYLE)
     • Syphilis
     • Meningitis
     • Actinomyces
     • Rat bite fever
     • Tetanus
     • Pasteurella multocida
     • Gas gangrene
     • Anthrax
     • Yaws
     • Leptospirosis
     • Every species: Streptococcus, Staphylococcus if sensitive.
   • Adverse effects- Hypersensitivity reactions, can cause direct Coombs-positive hemolytic anemia and drug-induced interstitial nephritis.

• Resistance- As these are beta-lactam antibiotics therefore some bacteria have developed beta-lactamase enzymes that can cleave the beta-lactam ring.
• The other source of resistance is mutation in penicillin-binding proteins.

2. Penicillin-sensitive Penicillins- These are amoxicillin and ampicillin.

• The mechanism of action is similar to penicillin but it has a wider spectrum. It can be combined with clavulanic acid to protect against destruction by beta-lactamase enzymes. 
• Clinical use- HHEELPSS
  • Hemophilus influenza
  • H pylori
  • E coli
  • Enterococci
  • Listeria monocytogenes
  • Proteus mirabilis
  • Salmonella 
  • Shigella
• Adverse effects- Hypersensitivity reactions, Rash, and Pseudomembrane colitis.
• Resistance- The bacteria develop penicillinase which cleaves the beta-lactam ring.

3. Penicillinase-resistant Penicillins

• These are dicloxacillin and Nafcillin.
• Mechanism of action:
  • It is similar to penicillin but it has a narrow spectrum. These are penicillinase-resistant because of the presence of bulky R group which blocks the beta-lactamase enzyme from reaching and damaging the beta-lactam ring.
• Clinical use- Staphylococcus aureus except MRSA.

4. Antipseudomonal Penicillins
   • Piperacillin and Ticarcillin
   • The mechanism of action is similar to penicillin.
   • Clinical use- It mainly acts against pseudomonas species and gram-negative rods.

1. Cephalosporins- It has five generations.
   • Mechanism of action- These are beta-lactam drugs that inhibit cell wall synthesis.
   • These are less susceptible to penicillinase.

Also Read: Arboviridae: Types, Symptoms, and Complications

1. 1^st generation- Cefazolin and Cephalexin
   • It is the best drug for gram-positive infection. The most important use of cefazolin is its application before surgery to prevent any Staph. aureus wound infection.
2. 2^nd generation- Cefaclor, Cefoxitin, Cefuroxime and Cefotetan.
   • These are better against gram-positive as compared to 1^st generation cephalosporins.
   • These are mainly used for anaerobic bacteria.
3. 3^rd Generation Cephalosporins-
   • These are ceftriaxone, Cefotaxime, Cefpodoxime, and Ceftazidime.
   • These are recommended against gram-negative bacteria and community-acquired gram-negative infection.
4. 4^th generation- Cefepime
   • These are mainly effective against nosocomial infections like pseudomonas.
5. 5^th generation- Ceftaroline
   • These broadly act against gram-positive and gram-negative Organisms. It covers MRSA, unlike 1^st to 4th-generation cephalosporins.
   • Adverse effects of Cephalosporins are:

• Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reactions, and vitamin K deficiency.
• Resistance- These are inactivated by the cephalosporinase enzyme which is a type of Beta lactams. 

2. Carbapenems

• These are Imipenem, meropenem, and ertapenem.
• It is a broad-spectrum, beta-lactamase-resistant carbapenem drug.
• Clinical use- These are used against gram-positive cocci, gram-negative rods, and anaerobes.
• It is a wide spectrum and has significant side effects that limit the use of life-threatening infections.
• Side effects- These are nephrotoxic, neurotoxic, and GI distress can occur.

3. Monobactams

• Mechanism of action- These are less susceptible to beta-lactamase enzyme and these are intravenous drugs that are given against gram-negative infections.
• The drug's name is Aztreonam.
• The mechanism of action is similar to penicillins.

4. Vancomycin

• Mechanism of action- It inhibits the cell wall peptidoglycan formation by binding the D-Ala D-Ala portion of cell wall precursors.
• It is bactericidal against most bacteria.
• Clinical use- It is mainly used against gram-positive bacteria and bacteria which are multidrug-resistant like MRSA. 
• Adverse effects- Nephrotoxicity, ototoxicity, and a very special syndrome called Redman syndrome. In Redman syndrome there is diffuse flushing and it can be prevented by pretreatment with antihistamines.
• The mechanism of resistance is by amino acid modification of D-ALA D-ALA to D-ALA D-Lac.

5. Aminoglycosides

• These include Gentamicin, Neomycin, Amikacin, Tobramycin, and Streptomycin.
• Mechanism- These are bactericidal and acts by irreversibly inhibiting the initiation complex through binding of the 30 S subunit. Hence it disrupts protein synthesis.
• The important point is these require oxygen for action and, therefore ineffective against anaerobic organisms.
• Clinical use- These are very effective against severe gram-negative Rods infections.
• Adverse effects- Nephrotoxicity, Neuromuscular blockage, Ototoxicity, and Teratogenicity.
• Resistance- There is an enzyme called transferase enzyme present in the bacteria that inactivates the drug by different mechanisms.

6. Macrolides

• These are azithromycin, clarithromycin, and erythromycin.
• These act by inhibiting the protein synthesis by blocking the translocation process.
• These bind to the 50 S ribosomal subunit and are bacteriostatic in nature.
• Clinical Use of macrolides is against atypical pneumonia bacteria like mycoplasma, chlamydia, and legionella. These are effective against gram-positive bacteria and chlamydia also.
• The adverse effects are gastrointestinal issues, arrhythmia (QT interval prolongation), rashes, and eosinophilia.

7. Fluoroquinolones

• These are ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, and moxifloxacin.
• The mechanism is by inhibiting the prokaryotic enzyme topoisomerase II and topoisomerase IV.
• These are effective against gram-negative rods of the urinary tract and GI tract.
• Adverse effects are gastrointestinal upset, skin rashes, headache, and dizziness. These are contraindicated during pregnancy or breastfeeding in children less than 18 years of age due to their destructive effect on cartilage.

8. Tetracyclines

• These are Doxycycline and Minocycline.
• These are bacteriostatic and bind to the 30S and Prevent attachment of aminoacyl-tRNA.
• These drugs should not be taken with milk and antacids because the calcium and magnesium ions present in these can inhibit their absorption by binding to them.
• Clinical use is against acne and doxycycline specifically against community-acquired MRSA.
• Adverse effects- GI distress, dislocation of teeth and inhibition of bone growth in children, photosensitivity and these are teratogenic.

Also Read: Measles: Causes, Clinical Presentation, Risk Factors, Complications, Diagnosis, Treatment And Vaccinations

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