Selecting a therapeutic regimen

1. Confirm presence of infection by: history, signs and symptoms; fever, pain, tenderness, inflammation, symptomps related to organ, WBC/ESR counts, Identifying predisposing factors

2. Selection of drug: Before selecting Empiric therapy get material for c/s or for microscopy

3. Consider the spectrum of activity; narrow versus broad spectrum

4. Special conditions like sepsis or meningitis

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I- Confirm the presence of an infection

1. Fever;

2. Increased WBC, elevated granulocyte in bacterials (neutrophils, basophils, eosinophils)

   • Bacterial; increased granulocytes (neutrophils, basophils, eosinophils)
   • Viral, TB, Fungal; Lymphocytes
   • Parasitic; Eosinophil

3. Swelling, eryhtema; at particular site

4. Purulent discharge; from visible site

5. Patient Complaints

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II- Selection of antimicrobial agents

1) Identification of the infecting organism:

Infected body materials (e.g., blood, sputum, urine, wound drainage, etc.) must be sampled and cultured before initiating treatment. Empirical therapy before identification of the organism is necessary in the following conditions: In all acutely ill patients with infections of unknown origin. oInfection in a neutropenic patient, or a patient with meningitis.

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2) Patient factors:

• Neonates: Chloramphenicol ⇒ Gray baby syndrome; Sulfonamides ⇒ Kernicterus (Brain damage)

• In growing children: Fluoiroquinolones ⇒ Arthropathy; tetracycline ⇒ abnormal teeth and bone formation

• In old age(>65years) The incidence of renal toxicity with aminoglycosides is greater than in younger patients.

• In immunocompromised patients The use of bactericidal agents is necessary , as the host’s immune system is not capable of final elimination of the bacteria.

• Pregnancy: Many antibiotics cross the placenta and cause adverse effects to the fetus e.g. aminoglycosides and tetracycline.

3) Tissue penetration:

• The capillary lining in some tissues e.g. brain form natural barriers to drug delivery due to presence of tight junctions of the capillary wall.

• Lipid soluble antibiotics e.g.
  Chloramphenicol and metronidazole can cross these barriers in normal conditions.

• Poor perfusion of some area e.g. diabetic foot, reduces the amount of antibiotic reaching this area, making treatment is difficult.

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III. Determinants of the rational dosing: May be : 

1. Concentration or dose dependent killing: Antibacterial effect directly depends on their concentrations in the locus of inflammation 

• Giving these antibiotics by a single large dose per day achieves high peak levels and cause rapid killing of bacteria. (high doses every 1-2 times/24h)

Examples: Aminoglycosides,  Fluoroquinolones, Metronidazol, Amphotericin

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2. Time-dependent killing:

• depends on the time of the drug concentration  to remain above the MIC.  So, preparations with long duration kill more bacteria.
• e.g. β-lactam antibiotics, macrolides, clindamycin, and linezolid

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3. Post-antibiotic effect (PAE):

• The Post-Antibiotic Effect (PAE) shows the capacity of an antimicrobial drug to inhibit the growth of bacteria after removal of the drug from the culture.(after levels of antibiotic fall below the MIC.) 

• The PAE provides additional time for the immune system to remove bacteria that might have survived antibiotic treatment before they can eventually regrow after removal of the drug. 

(e.g. Aminoglycosides and Fluoroquinolones) usually require one dose per day.