Page 926 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 71: Bacterial Infections of the Central Nervous System 657

The duration of therapy for bacterial meningitis should be 10 to 14 days disability in patients with proven bacterial meningitis. In contrast, two
for most causes of nonmeningococcal meningitis and 3 weeks for men- prospective, randomized, double-blind, placebo-controlled trials from
ingitis due to gram-negative enteric bacilli. 21,29 Seven days of therapy Malawi, one in children and one in adults, revealed no significant dif-
45
44
appear adequate for meningococcal meningitis; several reports have ferences in mortality in the patients treated with adjunctive dexametha-
suggested that 7 days of therapy is effective also for H influenzae men- sone. However, in these trials, many patients were infected with HIV
ingitis. Patients with S agalactiae meningitis should be treated for 14 to or had other associated comorbidities, and delayed presentation may
21 days, and patients with meningitis caused by L monocytogenes should have been associated with lack of benefit. In a recent meta-analysis that
be treated for at least 21 days. However, therapy must be individual- included 4041 individual patients entered into 24 randomized trials,
46
ized; on the basis of clinical response, some patients may require longer there were no significant differences in mortality between patients who
courses of treatment. received corticosteroids and those who did not, although there was a
trend in decreased mortality in adult patients who received corticoste-
Adjunctive Therapy: Despite the availability of effective antimicrobial roids and a subgroup analysis revealed a reduced mortality in patients
therapy, the morbidity and mortality rates of bacterial meningitis remain with pneumococcal meningitis. Corticosteroids were associated with
unacceptably high. Work in experimental animal models of meningitis lower rates of severe hearing loss, any hearing loss, and neurologic
has suggested a potentially useful role for anti-inflammatory agents (eg, sequelae, although there was no benefit of corticosteroid therapy in low-
corticosteroids and nonsteroidal anti-inflammatory agents) in decreas- income countries.
ing the inflammatory response in the subarachnoid space, which may Other adjunctive therapies may be useful in critically ill patients with
be responsible for the development of neurologic sequelae. Adjunctive bacterial meningitis. Patients who are stuporous or comatose (preclud-
21
dexamethasone therapy has been evaluated in a number of published ing assessment of worsening neurologic function) and who show signs of
trials. 21,29,32 A meta-analysis of clinical studies published from 1988 to increased intracranial pressure (eg, altered level of consciousness; dilated,
1996 confirmed the benefit of adjunctive dexamethasone (0.15 mg/kg poorly reactive, or nonreactive pupils; and ocular movement disorders)
every 6 hours for 2-4 days) in infants and children with H influenzae may benefit from the insertion of an intracranial pressure monitoring
type b meningitis and, if commenced with or before parenteral anti- device. Increased intracranial pressure can be lowered by elevating the
microbial therapy, suggested benefit for pneumococcal meningitis in head of the bed to 30° to maximize venous drainage with minimal com-
40
childhood. Administration of dexamethasone before or with initiation promise of cerebral perfusion, by the use of hyperosmolar agents, and
of antimicrobial therapy is recommended for optimal attenuation of by hyperventilation. However, the routine use of hyperventilation (to
the subarachnoid space inflammatory response; patients must be care- maintain the partial arterial pressure of CO between 27 and 30 mm Hg)
2
fully monitored for the possibility of gastrointestinal hemorrhage. In has been questioned in patients with bacterial meningitis. Infants and
a prospective, randomized, double-blind trial in adults with bacterial children with bacterial meningitis and normal initial CT scans can be
meningitis, adjunctive treatment with dexamethasone was associated treated with hyperventilation to decrease elevated intracranial pressure
with a reduction in the proportion of patients who had unfavorable because it is unlikely that cerebral blood flow will be decreased to ischemic
outcome and in the proportion of patients who died; the benefits were thresholds. However, in children in whom CT shows cerebral edema,
most striking in the subset of patients with pneumococcal meningitis. cerebral blood flow is likely to be normal or decreased, so hyperventila-
41
The use of adjunctive dexamethasone, however, is of particular concern tion might decrease intracranial pressure at the expense of cerebral blood
in patients with pneumococcal meningitis caused by highly penicil- flow, possibly reducing flow to ischemic thresholds. The use of hyperos-
lin- or cephalosporin-resistant strains who are treated with vancomycin molar agents (eg, mannitol, glycerol) may be useful in reducing increased
because a diminished inflammatory response may significantly decrease intracranial pressure in patients with bacterial meningitis. In one study in
CSF vancomycin penetration and delay CSF sterilization, perhaps lead- infants and children with bacterial meningitis, oral glycerol appeared to
ing to a worse outcome. In the study cited above, only 72% of the 108 help prevent neurologic sequelae. In a more recent study, oral glycerol
47
CSF cultures that were positive for S pneumoniae were submitted for prevented severe neurologic sequelae in children with bacterial meningi-
susceptibility testing, and all were susceptible to penicillin. However, tis, although methodological questions have been raised about this study.
48
CSF concentrations of vancomycin were adequate (mean of 7.2 µg/mL) However, in another randomized, double-blind trial in 383 children with
in another study of 14 patients when vancomycin was administered bacterial meningitis, there was no significant relief in hearing impairment,
as a continuous infusion at a dosage of 60 mg/kg per day. Therefore, with use of adjunctive glycerol, intravenous dexamethasone, or their com-
34
routine use of adjunctive dexamethasone is warranted in most adults bination. Furthermore, in a randomized controlled trial of 265 Malawian
49
with suspected or proven pneumococcal meningitis. 21,29,42 In patients adults with bacterial meningitis, use of adjuvant glycerol was harmful
with meningitis caused by pneumococcal strains resistant to penicillin and increased mortality. Further studies are needed before adjunctive
50
and/or cephalosporins, careful observation and follow-up are critical to glycerol can be routinely recommended. A detailed discussion of the
determine whether dexamethasone therapy is associated with an adverse management of raised intracranial pressure is found in Chap. 86. Seizures
outcome. When dexamethasone is used, the timing of administration must be treated promptly to avoid status epilepticus, which might lead to
is crucial. Administration of dexamethasone before or concomitant anoxic brain injury (see Chap. 85). Another important adjunctive measure
with the first dose of antimicrobial therapy is recommended for opti- in patients with bacterial meningitis is fluid restriction to combat hypo-
mal attenuation of the subarachnoid space inflammatory response. natremia caused by excess secretion of antidiuretic hormone, although
Dexamethasone is not recommended in patients who have already this measure is not appropriate in the presence of shock or dehydration
received antimicrobial therapy. If the meningitis is found not to be because hypotension may predispose the patient to cerebral ischemia.
caused by S pneumoniae in adults, dexamethasone therapy may be dis- Many patients, particularly children, with bacterial meningitis are hypo-
continued. In patients receiving adjunctive dexamethasone who are not natremic (serum sodium level <135 mEq/L) at presentation; the degree
improving as expected or have a pneumococcal isolate with a cefotaxime and duration of hyponatremia may contribute to neurologic sequelae. The
or ceftriaxone MIC ≥2 µg/mL, a repeat lumbar puncture 36 to 48 hours management of hyponatremia is discussed in greater depth in Chap. 99.
after initiation of antimicrobial therapy is recommended to document
Despite these positive results, the routine use of adjunctive dexameth- ■
CSF sterility. PREVENTION
asone for patients with bacterial meningitis in the developing world A final point concerns chemoprophylaxis of contacts of meningitis
has been controversial. In one prospective, randomized, placebo- cases, which is indicated for close contacts of patients with N meningiti-
32
controlled, double-blind trial in adolescents and adults in Vietnam, dis or H influenzae type b meningitis. The definition of close contact
21
43
adjunctive dexamethasone was associated with a reduction in risk and generally refers to persons who have had prolonged (≥8 hours) contact

section05_c61-73.indd 657 1/23/2015 12:48:37 PM