TAILIEUCHUNG - Chapter 127. Treatment and Prophylaxis of Bacterial Infections (Part 7)

Distribution To be effective, concentrations of an antibacterial agent must exceed the pathogen's MIC. Serum antibiotic concentrations usually exceed the MIC for susceptible bacteria, but since most infections are extravascular, the antibiotic must also distribute to the site of the infection. Concentrations of most antibacterial agents in interstitial fluid are similar to free-drug concentrations in serum. However, when the infection is located in a "protected" site where penetration is poor, such as cerebrospinal fluid (CSF), the eye, the prostate, or infected cardiac vegetations, high parenteral doses or local administration for prolonged periods may be required for cure. . | Chapter 127. Treatment and Prophylaxis of Bacterial Infections Part 7 Distribution To be effective concentrations of an antibacterial agent must exceed the pathogen s MIC. Serum antibiotic concentrations usually exceed the MIC for susceptible bacteria but since most infections are extravascular the antibiotic must also distribute to the site of the infection. Concentrations of most antibacterial agents in interstitial fluid are similar to free-drug concentrations in serum. However when the infection is located in a protected site where penetration is poor such as cerebrospinal fluid CSF the eye the prostate or infected cardiac vegetations high parenteral doses or local administration for prolonged periods may be required for cure. In addition even though an antibacterial agent may penetrate to the site of infection its activity may be antagonized by factors in the local environment such as an unfavorable pH or inactivation by cellular degradation products. For example since the activity of aminoglycosides is reduced at acidic pH the acidic environment in many infected tissues may be partly responsible for the relatively poor efficacy of aminoglycoside monotherapy. In addition the abscess milieu reduces the penetration and local activity of many antibacterial compounds so that surgical drainage may be required for cure. Most bacteria that cause human infections are located extracellularly. Intracellular pathogens such as Legionella Chlamydia Brucella and Salmonella may persist or cause relapse if the antibacterial agent does not enter the cell. In general 0-lactams vancomycin and aminoglycosides penetrate cells poorly whereas macrolides ketolides tetracyclines metronidazole chloramphenicol rifampin TMP-SMX and quinolones penetrate cells well. Metabolism and Elimination Like other drugs antibacterial agents are disposed of by hepatic elimination metabolism or biliary elimination by renal excretion of the unchanged or metabolized form or by a combination of the two .

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