Antimicrobial tissue penetration

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. Apart from the bloodstream, other body fluids where drug concentration data are clinically relevant include urine, synovial fluid, and peritoneal fluid. Pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration can be predictive of treatment outcome when specific ratios of AUC or maximal plasma concentration to the minimum inhibitory concentration (MIC) are achieved. For... 

Bergeron MG, Beauchamp D, Poirier A, et al. Continuous vs intermittent administration of antimicrobial agents Tissue penetration and efficacy in vivo. Rev Infect Dis 1985 3 84-97. 

Animal and human studies support the use of antibiotics for the prevention of infectious morbidity and mortality in severe ANP. The most effective antimicrobial agents are the fluoroquinolones, imipenem-cilastatin, and metronidazole, which achieve adequate penetration into pancreatic juice and necrotic tissue and inhibit the growth of enteric bacteria. Although a recent meta-analysis [185] suggested that prophylactic antibiotic administration reduces sepsis and mortality and this approach has been recommended by recent guidelines and consensus state-... 

Most antimicrobial agents are well distributed to most body tissues and fluids. Penetration into the cerebrospinal fluid is an exception. Most do not penetrate uninflamed meninges to an appreciable extent. In the presence of meningitis, however, the cerebrospinal fluid concentrations of many antimicrobials increase (Table 51-6). 

Available studies suggest that penetration of the newer quinolones into all extravascular sites (large-volume spaces i.e., ascites, pleural fluid, etc.), secretory fluids (urine, prostatic secretions, sputum, etc.), barrier fluids (CSFL), and whole tissues is high relative to the penetration reported for most other categories of antimicrobial agents, particularly, the penicillins, cephalosporins, and aminoglycosides... 

Caution must be excercised when selecting an antimicrobial agent for clinical use on the basis of tissue or fluid penetration. Body fluids where drug concentration data are clinically relevant include CSF, urine, synovial fluid, and peritoneal fluid. Apart from these areas, more attention should be paid to clinical efficacy, antimicrobial spectrum, toxicity, and cost than to comparative data on penetration into a given body site. 

The external surfaces of the normal, fit, healthy human being have evolved to be effective barriers against penetration by opportunistic microorganisms to internal tissues that might provide them with nourishment at the expense of the host. Sometimes the external physical barriers fail, and then other antimicrobial defense mechanisms come into play, the immune system for instance. These internal mechanisms are combating infection. The various symptoms of infectious disease are the result of the interaction between the attempts by the infecting agent to colonize the internal tissues of the body and the attempts by the body s defense mechanisms to overcome this invasion. 

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