Cerebrospinal fluid antimicrobials

Many areas of the human body are colonized with bacteria— this is known as normal flora. Infections often arise from one s own normal flora (also called an endogenous infection). Endogenous infection may occur when there are alterations in the normal flora (e.g., recent antimicrobial use may allow for overgrowth of other normal flora) or disruption of host defenses (e.g., a break or entry in the skin). Knowing what organisms reside where can help to guide empirical antimicrobial therapy (Fig. 66-1). In addition, it is beneficial to know what anatomic sites are normally sterile. These include the cerebrospinal fluid, blood, and urine. 

Ideally, lumbar puncture to obtain cerebrospinal fluid (CSF) for direct examination and laboratory analysis, as well as blood cultures and other relevant cultures, should be obtained before initiation of antimicrobial therapy. However, initiation of antimicrobial therapy should not be delayed if a pretreatment lumbar puncture cannot be performed. 

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. 

Penetration of Antimicrobial Agents into the Cerebrospinal Fluid (CSF)... 

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). 

Table 51-6 Cerebrospinal Fluid (CSF) Penetration of Selected Antimicrobials.

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... 

The general rule is that selection of antimicrobials should be based on identification of the microbe and sensitivity tests. All appropriate specimens (blood, pus, urine, sputum, cerebrospinal fluid) must therefore be taken for examination before administering any antimicrobial. 

Some antimicrobials are both static and cidal. For example, chloramphenicol is bacteriostatic, inhibiting most bacteria from growing. In higher concentrations it is bacteriocidal and kills S. pneumoniae and II. influenza in cerebrospinal fluid. Tetracycline is also bacteriostatic and bacteriocidal. 

Langley JM, Leblanc JC, Drake J, Milner R. Efficacy of antimicrobial prophylaxis in placement of cerebrospinal fluid shunts Meta-analysis. Clin Infect Dis 1993 17 98-103. 

The unbound drug in the systemic circulation is available to distribute extravascularly. The extent of distribution is mainly determined by lipid solubility and, for weak organic acids and bases, is influenced by the pK3/pH-dependent degree of ionization because only the more lipid-soluble non-ionized form can passively diffuse through cell membranes and penetrate cellular barriers such as those which separate blood from transcellular fluids (cerebrospinal and synovial fluids and aqueous humour). The milk-to-plasma equilibrium concentration ratio of an antimicrobial agent provides a reasonably... 

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