Meningitis antimicrobials

Antimicrobials also can be classified as possessing bactericidal or bacteriostatic activity in vitro. Bactericidal antibiotics generally kill at least 99.9% (3 log reduction) of a bacterial population, whereas bacteriostatic antibiotics possess antimicrobial activity but reduce bacterial load by less than 3 logs. Clinically, bactericidal antibiotics may be necessary to achieve success in infections such as endocarditis or meningitis. A full discussion of the application of antimicrobial pharmacodynamics is beyond the scope of this chapter, but excellent sources of information are available.15... 

Impact of Antimicrobial Resistance on Treatment Regimens for Meningitis... 

High-dose penicillin G traditionally has been the drug of choice for the treatment of pneumococcal meningitis. However, due to increases in pneumococcal resistance, the preferred empirical treatment now includes a third-generation cephalosporin in combination with vancomycin.13 All CSF isolates should be tested for penicillin and cephalosporin resistance by methods endorsed by the CLSI. Once in vitro sensitivity results are known, therapy may be tailored (Table 67-3). Patients with a history of type I penicillin allergy or cephalosporin allergy may be treated with vancomycin. Treatment should be continued for 10 to 14 days, after which no further maintenance therapy is required. Antimicrobial prophylaxis is not indicated for close contacts. 

Sinner SW, Tunkel AR. Antimicrobial agents in the treatment of bacterial meningitis. Infect Dis Clin North Am 2004 18 581-602. 

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. 

Empiric antimicrobial therapy should be instituted as soon as possible to eradicate the causative organism (Table 36-2). Antimicrobial therapy should last at least 48 to 72 hours or until the diagnosis of bacterial meningitis can be ruled out. Continued therapy should be based on the assessment of clinical improvement, cultures, and susceptibility testing results. Once a pathogen is identified, antibiotic therapy should be tailored to the specific pathogen. 

Antimicrobial Agents of First Choice and Alternative Choice for Treatment of Meningitis Caused by Gram-Positive and Gram-Negative Microorganisms]... 

Glucocorticoids are also used in the treatment of a number of HIV-related disorders, including Pneumocystis carinii pneumonia, demyelinating peripheral neuropathies, tuberculous meningitis, and nephropathy. Glucocorticoids are used as adjunctive therapy in Pneumo cystitis carinii pneumonia to decrease the inflammatory response and allow time for antimicrobial agents to exert their effects. In patients who are immunocompromised because of HIV infection, adjunctive steroids may be less beneficial in promoting survival. 

The intravenous route is preferred in the following situations (1) for critically ill patients (2) for patients with bacterial meningitis or endocarditis (3) for patients with nausea, vomiting, gastrectomy, or diseases that may impair oral absorption and (4) when giving antimicrobials that are poorly absorbed following oral administration. 

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). 

There are few clinically relevant examples of antimicrobial antagonism. The most striking example was reported in a study of patients with pneumococcal meningitis. Patients who were treated with the combination of penicillin and chlortetracycline had a mortality rate of 79% compared with a mortality rate of 21% in patients who received penicillin monotherapy (illustrating the first mechanism set forth below). 

Antimicrobial Agent CSF Concentration (Uninflamed Meninges) as Percent of Serum Concentration CSF Concentration (Inflamed Meninges) as Percent of Serum Concentration... 

When the greatest antimicrobial coverage is desirabie (for example, sepsis, meningitis) or in infections of unknown origin. 

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... 

---