Question

w o most effective to heat this infections. • List three reasons why information regarding a particular microbial isolate's antibiotic susceptibility determined in vitro might not accurately predict how well the drug will perform in vivo. Explain why antimicrobial drugs that work against bacteria are not effective against fungi.

Answer 1

6. There are several reasons why in vitro antibiotic susceptibility is not predictive of in vivo antibiotic susceptibility.

a) Concentration of antibiotic in plasma is affected by the presence of plasma proteins. Hence, the concentration reached in plasma depends on these proteins. There may be degradation of the drug in plasma. Thus, there may be fluctuating levels of drug in plasma, which may affect its activity.

b) When the antibiotic reaches the different tissues, the conditions within the tissue may affect the physical properties of the drug and hence its effectiveness. For example, the pH of the site of infection or the tissue can affect the solubility of the drug in lipids. Further, it can affect the amount of drug absorbed by the tissue. Thus, the minimum inhibitory concentration of drug that is obtained from in vitro studies may therefore not be applicable in an in vivo setting. The pH at the infection site or within an organelle can dictate lipid solubility of the drug or its distribution in cells and tissues. Thus, in vivo properties at site of infection may differ from those in the culture medium.

c. The MIC (minimum inhibitory concentration) is calculated based on a standard bacterial inoculum. This standard bacterial inoculum may not be similar to the bacterial culture at site of infection. The infectious agent may have developed altered properties, which can make the antibiotic ineffective or the organism may be able to tolerate higher concentrations of the drug. Microbes at site of infections may be in a non-growing phase while the standard inoculum is in logarithmic phase.

7. Fungi are eukaryotes while bacteria are prokaryotes. Hence, their basic physiology differs. Antibacterial agents are designed to be effective against bacterial components. Fr example, penicillin acts on peptidoglycan layer in cell wall of bacteria. Fungi lack the peptidoglycan layer. Similarly, antibiotics are generated against the ribosomal subunit in bacteria are different in fungi, which have the eukaryotic ribosomes. Bacterial enzymes have very structure and functions that fungal enzymes. Most antibacterial antibiotics are products of fungal metabolism. Penicillin is produced by Aspergillus. Hence, antibacterial antibiotics do not work on fungi.