Antibiotics in Surgery

Antibiotics (antimicrobials) have been in use for decades, first discovered in 1928 by Sir Alexander Fleming. They are either produced by microorganisms or synthesized and are designed to kill or slow down the growth of susceptible microbes. Commonly prescribed in health facilities, their misuse is prevalent, leading to resistance and opportunistic infections. While essential in surgical practice, antibiotics come with side effects.

Definition

Antibiotics are drugs used in the treatment and prevention of bacterial infections. They are substances produced by microorganisms like bacteria or synthesized by modifying existing antibiotic compounds. Some antibiotics also exhibit antiprotozoal activity. In sufficient quantity, antibiotics kill or inhibit the growth of other microbes.

Normal Body Flora

Different parts of the body harbor various organisms.

S. No.	Human body	Normal flora
1	Skin	Staphylococci, Micrococci, Diphtheroids
2	Oral and upper respiratory tract	Neisseria, Bordetella, Corynebacterium, Streptococcus
3	Conjunctiva	Haemophilus and Staphylococcus
4	Gastrointestinal tract	Enterococci, non-haemolytic Streptococcus, E.coli, Lactobacillus
5	Genital tract	Corynebacterium, Lactobacillus, non-pathogenic Neisseria

CLASSIFICATION

Several Classification Schemes

Natural / Synthetic

• Natural: Penicillin
• Synthetic: Cephalosporins

Broad / Narrow Spectrum

• Broad Spectrum: Tetracyclines
• Narrow Spectrum: Penicillin

Bactericidal / Bacteriostatic

• Bactericidal: Quinolones
• Bacteriostatic: Tetracyclines

Against Gram +ve / Gram –ve

• Gram-positive: Penicillins
• Gram-negative: Cephalosporins

By Chemical Structure Grouping

1. Penicillins:

   Examples include:

   • Penicillin G
   • Penicillin V
   • Ampicillin (Semi-synthetic)
   • Oxacillin (Semi-synthetic)

2. Tetracyclines:

   Examples include:

   • Doxycycline
   • Minocycline

3. Cephalosporins:

   Examples of first-generation cephalosporins include:

   • Cephalexin (Keflex)
   • Cefadroxil (Duricef)
   • Cephradine (Velosef)

4. Quinolones:

   Examples include:

   • Ciprofloxacin
   • Levofloxacin
   • Trovafloxacin

5. Lincomycins:

   An example is:

   • Lincomycin

6. Macrolides:

   Examples include:

   • Erythromycin
   • Azithromycin
   • Clarithromycin

7. Sulfonamides:

   Examples include:

   • Sulfamethoxazole (often combined with trimethoprim to form the antibiotic Bactrim)
   • Sulfasalazine (Azulfidine)
   • Sulfisoxazole (Truxazole)

8. Glycopeptides:

   Examples include:

   • Vancomycin
   • Teicoplanin
   • Telavancin

9. Aminoglycosides:

   Examples include:

   • Streptomycin
   • Kanamycin
   • Tobramycin
   • Gentamicin
   • Neomycin

10. Carbapenems:

    Examples include:

    • Ertapenem (Invanz)
    • Imipenem/cilastatin (Primaxin)
    • Meropenem (Merrem IV)
    • Doripenem (Doribax)

By Mechanism of Action

• Inhibition of cell wall synthesis: Penicillins
• Inhibition of protein synthesis: Tetracyclines
• Inhibition of DNA replication: Quinolones

Please note that some antibiotics can fall into multiple categories. For example, Penicillin is a natural antibiotic, has a narrow spectrum, is bactericidal, and works against Gram-positive bacteria by inhibiting cell wall synthesis.

More on Antibiotic Grouping by Mechanism of Action

Cell Wall Synthesis Inhibitors

• Penicillins
• Cephalosporins
• Vancomycin
• Carbapenems

Protein Synthesis Inhibitors

• Aminoglycosides
• Tetracyclines
• Chloramphenicol
• Clindamycin

DNA Synthesis Inhibitors

• Fluoroquinolones
• Metronidazole

RNA Synthesis Inhibitors

• Rifampicin

Folic Acid Synthesis Inhibitors

• Sulfonamides
• Trimethoprim

Mycolic Acid Synthesis Inhibitors

• Isoniazid

Cell Wall Inhibitors: Bactericidal

During cell division, interferes by inhibiting cell wall synthesis, blocking cross-linkages through competitive inhibition of transpeptidase and carboxypeptidase enzymes. This disrupts peptidoglycan cross-linkage. Not effective against bacteria without a cell wall.

Examples: Penicillins, Cephalosporins

Cell Membrane: Bactericidal

Bind to the phosphate in the membrane phospholipids, leading to disruption.

Example: Polymixins

Protein Synthesis Inhibition: Bactericidal/Bacteriostatic

Interfere with translocation by inhibiting peptidyl transferase, disrupting amino acyl-tRNA complex:

• Bacteriostatic: Chloramphenicol, Erythromycin, Lincomycin

Block t-RNA for bacteriostatic action, for example:

• Tetracycline

Interfere with RNA attachment to Ribosomes for bactericidal effect.

Interfere with RNA replication for bactericidal action, e.g., Metronidazole, Rifampicin.

Inhibit DNA gyrase enzyme for bactericidal effect.

Irreversible binding results in bactericidal action, while reversible binding is bacteriostatic.

Cell Metabolism: Bacteriostatic

Inhibit Folic acid synthesis by competing with PABA needed for folic acid synthesis.

Inhibit dihydrofolate reductase enzyme required for metabolizing dihydrofolic acid to tetrahydrofolic acid.

Examples: Sulphonamides, Trimethoprim, Isoniazid, Ethambutol

Inhibit Mycolic acid synthesis.

• Antibiotics do not sterilize.
• They are not a replacement for good surgical technique.
• Should act at more than one site.
• Must reach the site of action in sufficient quantity.
• Avoid being inactivated by substances produced by host cells and bacteria.
• Ideally, interfere with an essential metabolic process in the infecting organism without deleterious effects on host cells.
• Have a selective action, killing or inhibiting sensitive bacteria at the site of infection.

Prophylaxis

The use of antibiotics to prevent infection

Has a scientific basis, though frequently abused

Rationale for Antibiotic Prophylaxis

• Presence of high concentration of antibiotics in the serum and tissue at the time of contamination with bacteria.
• Selected antibiotics should be bactericidal.
• Choice of antibiotics influenced by the organism likely to contaminate the wound, patient factors, physico-chemical properties, side effects, and cost-effectiveness of the chosen agent.
• Administration is by the intravenous route, often given at the time of induction of anesthesia and may be 2 or 3 doses for about 48 hours.
• Narrow-spectrum antibiotics are preferred.
• Combination agents used in some instances.

Common procedures that require prophylaxis

• Implant surgery: Orthopaedic, Cardiothoracic, Neurosurgery, General surgery
• Bowel surgery
• Elderly patients, especially with upper abdominal incisions
• Immunosuppressed patients

Therapeutic Use

Administration specifically for the treatment of an established infection.

Host defense mechanisms are necessary for the final elimination of the infecting pathogens.

Bactericidal agents are needed for conditions such as:

• Infective endocarditis
• Immunocompromised patients

Where a specific infection is established, a narrow-spectrum antibiotic will be more appropriate.

Compliance and correct dosing must be ensured to avoid the development of resistance.

Enteral: Oral, Rectal, NG Tube, Gastrostomy Tube

Parenteral: IV, IM, Subcutaneous

Topical: Aerosol, Powder, Ointment, Lotion, Drops (Surgical Wounds)

Clean Wounds: This class of wounds has minimal risk of infection (1-2% infection rate) and includes surgically incised wounds with complete adherence to all aseptic conditions without a breach of any hollow viscera. Examples include lipoma excision, thyroidectomy, simple herniorrhaphy, herniotomy, and lumpectomy. There is no need for antibiotic use in clean wounds except in immunosuppressed patients or patients having a prosthetic heart valve.

e.g. Herniorrhaphy, Thyroidectomy

Clean Contaminated Wounds: This type of wound has a low risk of infection (<10% infection rate). It includes wounds involving entry into a hollow organ that is not inflamed, entry into the abscess cavity, minor breaches in aseptic procedure, and mild spillage of intra-abdominal viscous. These wounds occur during uncomplicated appendectomy and interval cholecystectomy. Prophylactic treatment with antibiotics is required.

e.g. Appendicectomy, Elective GI, Cholecystectomy

Contaminated Wounds: These have a high rate of infection (15-20% infection rate). This occurs when there is a major breach in aseptic conditions even without entry into the abscess cavity or hollow viscus. Contaminated wounds are created de novo, such as in contamination of bile and feces, complicated appendectomy, colostomy, and cholecystectomy. Therapeutic antibiotics aimed at treatment and not prophylaxis are given.

e.g. Penetrating Abd. Injury, Large Tissue Injury

Dirty or Infected Wounds: These have a very high risk of infection (>40% infection rate). Dirty wounds appear grossly infected with pus with entry into an abscess cavity, such as in the gangrenous bowel.

e.g. Perforated Viscus, Necrotizing Soft Tissue Infection