Choice of Antimicrobial Agent:
- Choice of antimicrobial agent depend on the peculiarities of infecting organism, the drug and the patient.
- Aim of chemotherapy is to produce selective action on the infecting organism for a desirable period with least effect on host animal.
- Organism related factors:
a. Target organism
b. Sensitivity pattern
a. Target organism:
- Identification of target organism is first step in selection of antimicrobial agent.
- Identification can be made from historical data and experience or based on organism identified by culture at the site of infection.
- Culture, biochemical test, staining are important methods in determining target organism.
b. Sensitivity pattern:
- Important in selecting right antimicrobial drug.
- Most commonly used method to test susceptibility to antimicrobials has been disc-diffusion or Kirbey-Bauer technique.
- Useful when there is wide variation in susceptibility of organism of different strains to drugs.
- Drug-related factors:
a. Spectrum of activity:
- When causative agent has been identified and its sensitivity towards drugs is determined, a narrow spectrum antimicrobial drug is preferred.
- When bacteriological services are not available or treatment cant be delayed broad spectrum antimicrobials drug is preferred.
- Polymicrobial infection may require broad spectrum agent or combination of two or more agent.
b. Type of activity:
- Bactericidal drugs are preferred in life threatening conditions, endocarditis, infection at less accessible sites, impaired host defence and when carrier state is possible.
- Bacteriostatic drugs are preferred only when host immunity is strong and body system are functioning normally.
c. Pharmacokinetic profile:
- Determines effective concentration of drug at site of infection for adequate length of time.
- Antibacterials such as chloramphenicol and macrolides are extensively metabolised in liver so not utilized in UTI.
- Fluoroquinolones have excellent tissue penetration and attain high concentration in body tissues.
- Sulphonamides and chloramphenicol readily enter into CSF, whereas penicillins and aminoglycosides penetrate poorly into CSF.
d. Route of administration:
- all routes of administration are not possible for all drugs available.
- In critically ill patient, parenteral route, particularly IV is preferred.
- Oral administration of anti-microbial agent (AMA) is preferred for long-term administration for non-hospitalized animals.
e. Drug interactions:
- Antimicrobial are often used in combination with other drugs such as analgesic and anti-inflammatory drug.
- Some drug may enhance toxicity of antimicrobial agents or reduce efficacy.
- For ex; NSAID enhance CNS toxicity of fluoroquinolones.
f. Relative toxicity:
- Penicillin are least toxic among antimicrobials so preferred over aminoglycosides and chloramphenicol.
- Chloramphenicol and aminoglycosides are reserved for life-threatening conditions.
g. Antimicrobial policy:
- Selection of antimicrobial agent also depends on pre-determined policy so that bacterial resistance to drug may be minimised.
- Main aim of antimicrobial policy:
i. Morbidity & mortality due to antimicrobial resistant infection
ii. Preserve the effectiveness of antimicrobial agent in treatment
iii. Prevention of communicable disease.
- Certain AMA like fluoroquinolones are not recommended in food animals due to apprehension of developing bacterial resistance in humans.
- Host factors:
a. Host defence mechanism:
- Elimination of infecting organism depends on the integrity of host defence mechanism.
- Higher doses and longer therapy are required to eliminate organism in immunocompromised host.
b. Pathologic conditions:
- Conditions like renal insufficiency, hepatic dysfunction, and meningitis alter response of drug and toxic potential of some antimicrobial drug.
Renal disease: renal disease may cause accumulation of drug in kidney.
Hepatic dysfunction: antimicrobial which undergo hepatic metabolism are contraindicated in patients with liver disease.
Meningitis: penicillins should not be used in meningitis because they concentrate more in CNS and increases chances of CNS seizures.
c. Local factors:
i. Pus
Reduce efficacy of antimicrobial agents especially sulphonamid-es & aminoglycos-ides
ii. Haematomas
Favour bacterial growth and impair antimicrobial
iii. pH
Determine the efficacy of drugs. Ex; aminoglycosides are more active in alkaline urine. Penicillins are inactivated in acidic pH.
d. Age:
- Neonatal have low renal excretion & hepatic elimination of drug.
- Tetracyclines are contraindicated in young animals because they accumulate in developing bone and teeth and discolour & weaken them.
e. Species:
- Tetracyclines by any route are associated with enterocolitis in horses, subjected to stress.
- Cats are more susceptible to chloramphenicol toxicity due to deficient glucuronide conjugation.
f. Pregnancy:
- Antimicrobials should be avoided in pregnant animals because they crosses placenta.
- Aminoglycosides carry risk of hearing loss and tetracyclines can cause inhibition of bone growth in foetus.
g. Genetic factors:
- genetic abnormalities must be considered while choosing antimicrobial drugs.
- For ex: sulphonamides and chloramphenicol may produce acute hemolysis in patients with Glucose-6-phosphate dehydrogenase deficiency.