Adjunctive therapy

Because of the unacceptable morbidity and mortality rates in patients with bacterial meningitis, even in the antibiotic era, investigators have been studying the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis in the hopes of improving outcome from this disorder. Initial experimental studies focused on the subarachnoid space inflammatory response that occurs during bacterial meningitis to determine whether attenuation of this response would improve outcome. Through the use of experimental animal models of infection, it was determined that one corticosteroid agent, dexamethasone, was effective in reducing the CSF white blood cell response and CSF tumor necrosis factor concentrations, with a trend toward earlier improvement in CSF concentrations of glucose, protein, and lactate; these parameters improved without any apparent decrease in the rate of CSF bacterial killing.

Based on these and other studies in experimental animal models, numerous clinical trials were undertaken to determine the effects of adjunctive dexamethasone on the outcome in patients with bacterial meningitis. A meta-analysis of these clinical studies confirmed the benefit of adjunctive dexamethasone (0.15 mg/kg every 6 hours for 2 to 4 days) for H. influenzae type b meningitis and, if commenced with or before parenteral antimicrobial therapy, suggested benefit for pneumococcal meningitis in childhood. Evidence of clinical benefit was strongest for hearing outcomes. In adults with acute bacterial meningitis, a prospective, randomized, placebo-controlled, double-blind multicenter trial in 301 patients demonstrated that patients randomized to receive adjunctive dexamethasone were less likely to have unfavorable outcome and death; benefit was most evident among the subgroup of patients with pneumococcal meningitis. Based on the available evidence, adjunctive dexamethasone (0.15 mg/kg every 6 hours for 4 days with the first dose administered 10 to 20 minutes before, or at least concomitant with, the first dose of an antimicrobial agent) should be utilized in adults with suspected or proven pneumococcal meningitis. Adjunctive dexamethasone should not be given to adults who have already received antimicrobial therapy, because administration in this setting is unlikely to improve patient outcome. The data are inadequate to recommend adjunctive dexamethasone in adults with meningitis caused by other meningeal pathogens; continuing dexamethasone in patients with culture-proven meningococcal meningitis did not lead to improvement in rates of unfavorable outcome, although its use was not associated with harm. Some authorities would initiate dexamethasone in all adults because the etiology of meningitis is not always ascertained at initial evaluation.

Despite the positive benefits of adjunctive dexamethasone in adults with bacterial meningitis, its routine use in patients in the developing world has been controversial. In one randomized, double-blind, placebo-controlled trial from Malawi in adults, there were no significant differences in mortality, although almost 90% of the patients in this trial were infected with HIV and likely had advanced disease. In a Cochrane meta-analysis of 24 studies involving 4041 participants, adjunctive dexamethasone did not reduce overall mortality, but there was a trend to lower mortality rates in adults; corticosteroids were associated with lower rates of severe hearing loss, any hearing loss, and neurologic sequelae, but these benefits were only seen in studies from high-income countries.

In addition, the use of adjunctive dexamethasone is of concern in those with pneumococcal meningitis caused by highly penicillin- and cephalosporin-resistant strains, in which patients may require antimicrobial therapy with vancomycin. In this instance, a diminished CSF inflammatory response after dexamethasone administration might significantly reduce vancomycin penetration into CSF and delay CSF sterilization. The published trials have not examined outcome in patients with these resistant isolates who have received adjunctive dexamethasone, and it is unlikely that this question will be definitively answered in the near future, given the difficulty in enrolling adequate numbers of patients with these resistant strains into clinical trials. However, CSF vancomycin penetration was not reduced by dexamethasone in a study in which a continuous infusion of vancomycin (at a dose of 60 mg/kg/day) was utilized. For any patient receiving adjunctive dexamethasone who is not improving as expected, a repeat lumbar puncture 36 to 48 hours after initiation of antimicrobial therapy is recommended to document sterility of CSF.

Antimicrobial therapy

Once the infecting meningeal pathogen is isolated and susceptibility testing known, antimicrobial therapy can be modified for optimal treatment (Table 74.3). Recommended antimicrobial dosages for meningitis in adults with normal renal and hepatic function are shown in Table 74.4. The following sections review recommendations for use of antimicrobial therapy in patients with bacterial meningitis based on the isolated meningeal pathogen.

Table 74.3 Specific antimicrobial therapy for acute bacterial meningitis

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Microorganism	Standard therapy	Duration of therapy
Streptococcus pneumoniae Penicillin MIC ≤0.06 μg/mL Penicillin MIC ≥0.12 μg/mL Cefotaxime or ceftriaxone MIC <1.0 μg/mL Cefotaxime or ceftriaxone MIC ≥1.0 μg/mL	Penicillin G or ampicillin Third-generation cephalosporina Vancomycin plus a third-generation cephalosporina, b	10–14 d
Neisseria meningitidis Penicillin MIC <0.1 μg/mL Penicillin MIC 0.1–1.0 μg/mL	Penicillin G or ampicillin Third-generation cephalosporina	7 d
Listeria monocytogenes	Ampicillin or penicillin Gc	≥21 d
Streptococcus agalactiae	Ampicillin or penicillin Gc	14–21 d
Haemophilus influenzae β-lactamase – negative β-lactamase – positive	Ampicillin Third-generation cephalosporina	7 d
Escherichia coli and other Enterobacteriaceaed	Third-generation cephalosporina	21 d
Pseudomonas aeruginosa	Cefepimec Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: Peritonitis Diverticulitis Bordetella Syphilis and other treponematoses Hantavirus cardiopulmonary syndrome in the Americas Esophageal infections Stay updated, free articles. Join our Telegram channel Join Tags: Clinical Infectious Disease Jun 18, 2016 | Posted by admin in INFECTIOUS DISEASE | Comments Off on Bacterial meningitis Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access