Achieving a conc. of antibiotics at the site of infection that is sufficient to inhibit bacterial growth is most important factor among several others that contribute towards therapeutic success.
If the dose or conc. of drug produces the desired necessary effects on microorganisms without being toxic to human cells, the microorganisms are said to be sensitive to drug. On the other hand, if the concentration of the drug required to inhibit or kill the microorganisms is greater than conc. that can be safely achieved, the microorganisms are considered to be resistant to antibiotics.
Most in vitro sensitivity tests are standardized on the basis of drug concentration that can be safely achieved in plasma. They don’t reflect conc. that can be achieved at the site of infection nor they take into account the local factors that might affect the activity of drug. Thus in vitro, sensitivity tests have their limitations e.g. Gram-negative bacilli (pseudomonas, aeruginosa) are inhibited by 2-4 micro Gram/ml conc. of Gentamycin or Tobramycin, so these are said to be sensitive to these 2 drugs. However, the sustained conc. in plasma above 6-10 micro Gram/ml may cause hyper toxicity. Also conc. of these drugs at certain sites of infection (such as cerebrospinal fluid or vitreous fluid) may be much lower than those in plasma.
Thus these drugs may be only marginally effective or ineffective in such cases even though standardized in vitro list would report the microorganism sensitive. Conversely, the concentration of the drug in urine may be much higher than plasma, the microorganism reported as resistant may respond to therapy when infection is restricted to urinary tract only.
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