Epidemiology and Etiology
The rates of morbidity and mortality from bacterial meningitis remain unacceptably high despite the availability of effective antimicrobial therapy. In a surveillance study of all cases of bacterial meningitis in 27 states of the United States from 1978 to 1982, the overall annual attack rate of bacterial meningitis was approximately 3.0 cases per 100,000 population, although there was variability according to geographic area, sex, and race;1 incidences for the various meningeal pathogens are listed in Table 52-1. Bacterial meningitis is also a significant problem in hospitalized patients. In a review of 493 episodes of bacterial meningitis in adults 16 years or older from the Massachusetts General Hospital from 1962 through 1988, 40% of cases were nosocomial in origin, and these episodes carried a high mortality rate (35% for single episodes of nosocomial meningitis).2 With the introduction of Haemophilus influenzae type b conjugate vaccines in the United States and elsewhere, dramatic declines in the incidence of invasive H. influenzae type b disease have been reported; these conjugate vaccines have been licensed for routine use in all children beginning at age 2 months.3 In a study that evaluated the epidemiology of bacterial meningitis in the United States during 1995 in laboratories serving all the acute care hospitals in 22 counties in four states (Georgia, Tennessee, Maryland, and California),4 the incidence of bacterial meningitis decreased dramatically as a result of the vaccine-related decline in meningitis caused by H. influenzae type b (see Table 52-1).
Table 52–1. Etiology of Bacterial Meningitis in the United States ||Download (.pdf)
Table 52–1. Etiology of Bacterial Meningitis in the United States
|PERCENT OF TOTAL|
Before the development of effective vaccines against it, H. influenzae type b was isolated in almost half of all cases of bacterial meningitis in the United States, but this microorganism currently accounts for only 7% of cases. About 40% to 60% of cases were seen in children ages 2 months to 6 years; of these, 90% were due to capsular type b strains. Disease is most likely initiated after nasopharyngeal acquisition of a virulent organism with subsequent systemic invasion. Haemophilus influenzae is unusual after age 6
years; isolation of the organism in this older group should suggest the possible presence of certain predisposing factors, including sinusitis, otitis media, epiglottitis, pneumonia, head trauma with a cerebrospinal fluid (CSF) leak, diabetes mellitus, alcoholism, splenectomy or asplenic states, and immune deficiency (e.g., hypogammaglobulinemia).5
Meningitis due to Neisseria meningitidis is most often found in children and young adults and may occur in epidemics. Nasopharyngeal carriage of virulent organisms accounts for initiation of infection.6 The incidence of meningococcal serogroup C disease has been increasing in North America, with several recent outbreaks reported in the United States and Canada.7,8 Infection is more likely in persons who have deficiencies in the terminal complement components (C5, C6, C7, C8, and perhaps C9), the so-called membrane attack complex; the incidence of neisserial infections is more than 8000-fold greater in this group than among other persons.9
Pneumococcal meningitis is observed most frequently in adults (>30 years) and is often associated with distant foci of infection, such as pneumonia, otitis media, mastoiditis, sinusitis, and endocarditis; this organism currently accounts for 47% of cases of bacterial meningitis in the United States.4 Serious pneumococcal infections may be observed in persons with predisposing conditions, such as splenectomy or asplenic states, multiple myeloma, hypogammaglobulinemia, and alcoholism. Streptococcus pneumoniae is the most common meningeal isolate in head trauma patients who have basilar skull fracture with subsequent CSF leakage.10
Listeria monocytogenes accounts for only about 8% of all cases of bacterial meningitis but carries a high mortality rate.4 Infection with Listeria is more likely in neonates, the elderly, alcoholics, cancer patients, and immunosuppressed adults (e.g., renal transplant patients).11,12Listeria meningitis is found infrequently in patients with human immunodeficiency virus infection,13 despite its increased incidence in patients with deficiencies in cell-mediated immunity. However, up to 30% of adults and 54% of children and young adults with listeriosis have no apparent underlying condition. Listeriosis has been associated with several food-borne outbreaks involving contaminated cole slaw, milk, cheese, and processed meats.
Meningitis due to aerobic gram-negative bacilli is observed in specific clinical situations.14Escherichia coli is isolated in 30% to 50% of infants younger than 2 months with bacterial meningitis. Klebsiella species, E. coli, and Pseudomonas aeruginosa may be isolated in patients who have had head trauma or neurosurgical procedures, in the elderly, in immunosuppressed patients, and in patients with gram-negative septicemia. Despite the low frequency of meningitis due to this group of organisms, the mortality rates are very high (∼84% with P. aeruginosa, until recently).
Specific clinical situations also predispose to the development of meningitis due to staphylococcal species.15 Staphylococcus epidermidis is the most common cause of meningitis in persons with CSF shunts. Meningitis due to Staphylococcus aureus is frequently found (when compared with other pathogens) soon after neurosurgery. Underlying diseases among persons with no prior CNS disease who develop S. aureus meningitis include diabetes mellitus, alcoholism, chronic renal failure requiring hemodialysis, and malignancies. Conditions that increase S. aureus nasal carriage rates (e.g., injection drug abuse, insulin-requiring diabetes, and hemodialysis) may also predispose to staphylococcal infection of the CNS.
Group B streptococcus (Streptococcus agalactiae) is a common cause of meningitis in neonates.16 The risk of transmission from the mother to her infant is increased when the inoculum of organisms and number of sites of maternal colonization are large; horizontal transmission has also been documented from the hands of nursery personnel to the infant. Risk factors for group B streptococcal meningitis in adults include age older than 60 years, diabetes mellitus, parturient status in women, cardiac disease, collagen vascular disease, malignancy, alcoholism, hepatic failure, renal failure, and corticosteroid therapy.17–19 No underlying illnesses were found in 43% of patients in one review.18
The classic clinical presentation in adults with bacterial meningitis includes fever, headache, meningismus, and signs of cerebral dysfunction;20 these symptoms and signs are found in more than 80% of cases. Also seen are nausea, vomiting, rigors, profuse sweating, weakness, and myalgias. The meningismus may be subtle or marked or accompanied (rarely) by the Kernig and/or Brudzinski sign. The Kernig sign is elicited by flexing the thigh on the abdomen with the knee flexed; the leg is then passively extended, and, if there is meningeal inflammation, the patient resists leg extension. The Brudzinski sign is present when passive flexion of the neck leads to flexion of the hips and knees. However, these signs are elicited in fewer than 20% of cases of bacterial meningitis in adults. Cerebral dysfunction is manifested by confusion, delirium, or a declining level of consciousness ranging from lethargy to coma. Cranial nerve palsies (especially involving cranial nerves III, IV, VI, and VII) and focal cerebral signs are uncommon (10% to 20% of cases). Seizures occur in about 30% of all cases. Papilledema is rare (<5%) and should suggest an alternate diagnosis, such as an intracranial mass lesion. Late in the disease, patients may develop signs of increased intracranial pressure, including coma, hypertension, bradycardia, and third-nerve palsy; these findings are ominous prognostic signs.
Certain symptoms and signs may suggest an etiologic diagnosis in patients with bacterial meningitis.20 Persons with meningococcemia present with a prominent rash, principally on the extremities (∼50% of cases). Early in the disease course, the rash may be erythematous and macular, but it quickly evolves into a petechial phase, with further coalescence into a purpuric form. The rash often matures rapidly, with new petechial lesions appearing during the physical examination. A petechial, purpuric, or ecchymotic rash may also be seen in other forms of meningitis (i.e., those due to echovirus type 9, Acinetobacter species, S. aureus, and, rarely, S. pneumoniae or H. influenzae), in Rocky Mountain spotted fever or S. aureus endocarditis, and in overwhelming sepsis (due to S. pneumoniae or H. influenzae) in splenectomized patients. An additional suppurative focus of infection (e.g., otitis media, sinusitis, or pneumonia) is present in 30% of patients with pneumococcal or H. influenzae meningitis but is rarely found in meningococcal meningitis. Meningitis due to S. pneumoniae is relatively likely after head trauma in persons who have basilar skull fractures in which a dural fistula is produced between the subarachnoid space and the nasal cavity, paranasal sinuses, or middle ear.10 These persons commonly present with rhinorrhea or otorrhea due to a CSF leak; a persistent defect is a common explanation for recurrent bacterial meningitis.
Certain subgroups of patients may not manifest the classic signs and symptoms of bacterial meningitis. Usually in a neonate there is no meningismus or fever, and the only clinical clues to meningitis are listlessness, high-pitched crying, fretfulness, refusal to feed, or irritability. Elderly patients, especially those with underlying conditions such as diabetes mellitus or cardiopulmonary disease, may present with insidious disease manifested only by lethargy or obtundation, variable signs of meningeal irritation, and no fever. In this subgroup, altered mental status should not be ascribed to other causes until bacterial meningitis has been excluded by CSF examination. A patient after neurosurgery or a patient who has undergone head trauma also presents a unique clinical situation because these patients already have many of the symptoms and signs of meningitis from their underlying disease processes.10 One must have a low threshold for CSF examination in these patients should they develop any clinical deterioration.
The diagnosis of bacterial meningitis rests on the CSF examination.20 The opening pressure is elevated in virtually all cases; values above 600 mm H2O suggest cerebral edema, the presence of intracranial suppurative foci, or communicating hydrocephalus. The fluid may be cloudy or turbid if the white blood cell count is elevated (>200/μL). If the lumbar puncture is traumatic, the CSF may appear bloody initially, but it should clear as flow continues. Xanthochromia, a pale-pink to yellow-orange color of the supernatant of centrifuged CSF, is found in patients with subarachnoid hemorrhage, usually within 2 hours after hemorrhage.
The CSF white cell count is usually elevated in untreated bacterial meningitis, ranging from 100 to at least 10,000 per microliter, with a predominance of neutrophils. About 10% of patients present with a lymphocytic predominance (>50%) in CSF. Some patients have a very low CSF white cell count (0 to 20/μL) despite high bacterial concentrations in CSF; these patients have a poor prognosis. Therefore, a Gram stain and culture should be performed on all CSF specimens, even those with a normal cell count. A CSF glucose concentration of less than 40 mg/dL is found in about 60% of patients with bacterial meningitis, and a CSF:serum glucose ratio of less than 0.31 is observed in 70% of cases. The CSF glucose level must always be compared with a simultaneous serum glucose concentration. The CSF protein concentration is elevated in virtually all cases of bacterial meningitis, presumably because of disruption of the blood-brain barrier.
CSF examination by Gram stain permits a rapid, accurate identification in 60% to 90% of cases of bacterial meningitis; the likelihood of detecting the organism by Gram stain correlates with the specific bacterial pathogen and the concentration of bacteria in CSF. False-positive findings may occur as a result of contamination in the collection of tubes or during staining. Cultures of CSF are positive in 70% to 80% of cases. These percentages may be lower in patients who have received prior antimicrobial therapy.
Several rapid diagnostic tests have been developed to aid in the diagnosis of bacterial meningitis.21 Tests using staphylococcal coagglutination or latex agglutination are rapid and sensitive, although many of the kits do not include tests for group B meningococcus, and other kits probably are poor detectors of this antigen because of the limited immunogenicity of group B meningococcal polysaccharide. Performance of one of these rapid diagnostic tests (preferably latex agglutination) should be considered on all CSF specimens from patients in whom bacterial meningitis is suspected when the Gram stain is negative. Recently, the routine use of CSF bacterial antigen tests for the etiologic diagnosis of bacterial meningitis has been questioned; positive results have not modified therapy and false-positive and false-negative results may occur. Measurement of serum C-reactive protein or pro-calcitonin may also be useful in discriminating between bacterial and viral meningitis because elevated serum concentrations of these proteins have been observed in patients with acute meningitis.22 In patients with acute meningitis in whom the CSF Gram stain is negative, serum concentrations of C-reactive protein or pro-calcitonin that are normal or below the limit of detection have a high negative predictive value in the diagnosis of bacterial meningitis. Polymerase chain reaction has been used to amplify DNA from patients with meningococcal meningitis; it showed a sensitivity and specificity of 91% in one study.23 Further refinements in polymerase chain reaction may render it useful in the diagnosis of bacterial meningitis when the CSF Gram stain and cultures are negative.
Neuroimaging techniques have little role in the diagnosis of acute bacterial meningitis, except to rule out the presence of other pathologic conditions or to identify a parameningeal source of infection. However, computed tomography (CT) or magnetic resonance imaging (MRI) may be useful in patients who have a persisting fever several days after initiation of antimicrobial therapy, prolonged obtundation or coma, new or recurrent seizure activity, signs of increased intracranial pressure, or focal neurologic deficits. MRI is better than CT for evaluation of subdural effusions, cortical infarctions, and cerebritis, although it is more difficult to obtain an MRI in a critically ill patient, which limits its usefulness in many patients with meningitis.
The initial approach to the patient with suspected bacterial meningitis is to perform a lumbar puncture to determine whether the CSF findings are consistent with that diagnosis.20,24 Patients should receive empirical antimicrobial therapy based on their age and underlying disease status, if no etiologic agent is identified by Gram stain or rapid diagnostic tests. In patients with a focal neurologic examination, CT should be performed immediately to exclude an intracranial mass lesion because lumbar puncture is relatively contraindicated in that setting. However, obtaining a CT scan generally entails some delay, so empirical antimicrobial therapy should be started immediately, before the CT scan and lumbar puncture are done and after obtaining blood cultures, because of the high mortality rate in patients with bacterial meningitis in whom antimicrobial therapy is delayed. Although many clinicians routinely perform CT before lumbar puncture, this is probably not necessary in most patients. In a recent retrospective study of 301 adults with suspected meningitis,25 the clinical features at baseline that were associated with an abnormal finding on CT of the head were an age of at least 60 years, immunocompromise, a history of CNS disease, a history of seizure within 1 week before presentation, and the following neurologic abnormalities: an abnormal level of consciousness, an inability to answer two consecutive questions correctly or to follow two consecutive commands, gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, and abnormal language. These results need to be validated but are a reasonable guide in determining which patients require CT before lumbar puncture.
Our choices for empirical antibiotic therapy in patients with presumed bacterial meningitis, based on age, are presented in Table 52-2.20,24 For neonates younger than 1 month, the most likely infecting organisms are E. coli, S. agalactiae, and L. monocytogenes; for those ages 1 to 23 months, infection may be due to S. pneumoniae, N. meningitidis, S. agalactiae, E. coli, or H. influenzae. From age 2 to 50 years, most cases of meningitis are due to N. meningitidis and S. pneumoniae. In older adults (≥50 years), the meningococcus and the pneumococcus are possible causes, as are L. monocytogenes and gram-negative bacilli. For all patients in whom S. pneumoniae is a possible causative pathogen, vancomycin should be added to empirical therapeutic regimens because highly penicillin- or cephalosporin-resistant strains of S. pneumoniae may be likely (see below). One other situation deserves comment: In patients after neurosurgery or patients with CSF shunts or foreign bodies, likely infecting organisms include staphylococci (S. epidermidis or S. aureus), diphtheroids, and gram-negative bacilli (including P. aeruginosa). Antimicrobial therapy in these situations should consist of vancomycin plus ceftazidime or cefepime pending culture results.
Table 52–2. Empirical Therapy of Purulent Meningitis
Once an infecting microorganism has been isolated, antimicrobial therapy can be modified for optimal treatment.20,24 Our antibiotics of choice are listed in Table 52-3. Dosages for adults are listed in Table 52-4. For bacterial meningitis due to S. pneumoniae or N. meningitidis,
penicillin G and ampicillin are equally efficacious. However, although in past years pneumococci remained uniformly susceptible to penicillin (minimal inhibitory concentration ≤0.06 μg/mL), worldwide reports have now documented relatively and highly resistant strains of pneumococci, with minimal inhibitory concentrations of 0.1 to 1.0 μg/mL and at least 2 μg/mL, respectively. In view of these recent trends, and because sufficient CSF concentrations of penicillin are difficult to achieve with standard high parenteral doses (initial CSF concentrations of ∼1 μg/mL), penicillin can never be recommended as empirical antimicrobial therapy when S. pneumoniae is considered a likely infecting pathogen. Further, susceptibility testing must be performed on all CSF isolates. For relatively resistant strains, a third-generation cephalosporin (e.g., cefotaxime or ceftriaxone) should be used; for highly resistant strains, vancomycin in combination with a third-generation cephalosporin is the antimicrobial regimen of choice. Vancomycin used alone may not be optimal therapy for patients with pneumococcal meningitis. In one report of 11 consecutive patients with culture-proven pneumococcal meningitis caused by relatively penicillin-resistant strains,26 four patients experienced a therapeutic failure with vancomycin, necessitating a change in therapy. These data indicate the need for careful monitoring, perhaps even including measurement of CSF vancomycin concentrations, in adult patients who are receiving vancomycin alone for pneumococcal meningitis. We recommend the combination of vancomycin plus a third-generation cephalosporin (cefotaxime or ceftriaxone) for documented pneumococcal meningitis pending results of susceptibility testing. Some investigators have recommended the addition of rifampin (if the organism is susceptible) to vancomycin for the treatment of meningitis caused by highly resistant pneumococcal strains,27 although there are no firm data to support this. Meropenem, a carbapenem antimicrobial agent, yields microbiologic and clinical outcomes similar to those of cefotaxime or ceftriaxone in the treatment of patients with bacterial meningitis.28 The newer fluoroquinolones (e.g., moxifloxacin, gatifloxacin) have in vitro activity against resistant pneumococci and have shown activity in experimental animal models of resistant pneumococcal meningitis but should not be used as first-line therapy in patients with bacterial meningitis, pending results of ongoing clinical trials. Trovafloxacin was recently shown to be therapeutically equivalent to ceftriaxone with or without vancomycin for the treatment of pediatric bacterial meningitis,29 although this agent is no longer used because of concerns of liver toxicity.
Table 52–3. Antimicrobial Therapy of Bacterial Meningitis ||Download (.pdf)
Table 52–3. Antimicrobial Therapy of Bacterial Meningitis
|Organism||Antibiotic of Choice|
| Penicillin MIC <0.1 μg/mL||
Penicillin G or ampicillin|
| Penicillin MIC 0.1–1.0 μg/mL||Third-generation cephalosporina|
| Penicillin MIC ≥2.0 μg/mL||Vancomycin plus a third-generation cephalosporina|
Penicillin G or ampicillin; or a third-generation cephalosporina|
| β-Lactamase–positive||Third-generation cephalosporina|
|Pseudomonas aeruginosa||Ceftazidime or cefepimeb|
Penicillin G or ampicillinb|
|Listeria monocytogenes||Ampicillin or penicillin G
| Methicillin sensitive||Nafcillin or oxacillin|
| Methicillin resistant||Vancomycin|
Table 52–4. Recommended Doses of Antibiotics for Intracranial Infections in Adults with Normal Renal Function ||Download (.pdf)
Meningococcal strains that are relatively resistant to penicillin have also been reported from several areas (in particular Spain); however, most patients harboring these strains have recovered with standard penicillin therapy, so their clinical significance is unclear. In the United States, approximately 3% of meningococcal strains have shown intermediate resistance to penicillin.30 Some authorities would treat meningococcal meningitis with a third-generation cephalosporin (cefotaxime or ceftriaxone) pending results of in vitro susceptibility testing.
Treatment of H. influenzae type b meningitis has been hampered by the emergence of β-lactamase–producing strains of the organism, which accounted for approximately 25% to 33% of all isolates in the United States.1Chloramphenicol resistance also has been reported in the United States (<1% of isolates) and Spain (≥50% of isolates). In addition, a study found chloramphenicol to be bacteriologically and clinically inferior to certain β-lactam antibiotics (ampicillin, ceftriaxone, and cefotaxime) in childhood bacterial meningitis, and most of these cases were due to H. influenzae type b.20 From these findings and those of other studies, the third-generation cephalosporins (e.g., cefotaxime and ceftriaxone) seem to be at least as effective as ampicillin plus chloramphenicol for therapy of H. influenzae meningitis. Cefuroxime, a second-generation cephalosporin, has also been evaluated for therapy of H. influenzae meningitis. Although initial studies documented an efficacy for this drug similar to that of ampicillin plus chloramphenicol, recent case reports have documented delayed CSF sterilization and the development of epiglottitis in patients receiving cefuroxime for meningitis. In addition, a prospective randomized study of ceftriaxone versus cefuroxime for the treatment of childhood bacterial meningitis documented the superiority of ceftriaxone; patients receiving this drug had milder hearing impairment and more rapid CSF sterilization than did those receiving cefuroxime.31 We currently recommend a third-generation cephalosporin for empirical therapy when H. influenzae is considered a likely infecting pathogen.
The treatment of bacterial meningitis in adults that is caused by gram-negative enteric bacilli has been revolutionized by the third-generation cephalosporins,20 with cure rates of 78% to 94%. Ceftazidime or cefepime is also active against P. aeruginosa meningitis; ceftazidime, alone or in combination with an aminoglycoside, resulted in cure of 19 of 24 patients with Pseudomonas meningitis in one report. Intrathecal or intraventricular aminoglycoside therapy should be considered if there is no response to systemic therapy, although this therapy is now rarely needed. The fluoroquinolones (e.g., ciprofloxacin or pefloxacin) have been used in some patients with gram-negative bacillary meningitis, but at this time they can be considered only for patients with meningitis due to multidrug-resistant gram-negative bacilli or for patients in whom conventional therapy has failed.
The third-generation cephalosporins are inactive against meningitis caused by L. monocytogenes, an important meningeal pathogen; this is a major drawback of these agents. Therapy in this situation should consist of ampicillin or penicillin G; addition of an aminoglycoside should be considered in documented infection, at least for the first several days of treatment.12,20 Alternatively, trimethoprim-sulfamethoxazole can be used. Patients with S. aureus meningitis should be treated with nafcillin or oxacillin; vancomycin should be reserved for patients allergic to penicillin and patients with disease caused by methicillin-resistant organisms.15 Infection with S. epidermidis, the most likely isolate in a patient with a CSF shunt, should be treated with vancomycin, with rifampin added if the patient fails to improve. Shunt removal is often essential to optimize therapy.
The durations of therapy for bacterial meningitis should be 10 to 14 days for most causes of non-meningococcal meningitis and 3 weeks for meningitis due to gram-negative enteric bacilli.20,32 Seven days of therapy appear adequate for meningococcal meningitis; several reports have suggested that 7 days of therapy is effective also for H. influenzae meningitis. Patients with S. agalactiae meningitis should be treated for 14 to 21 days, and patients with meningitis caused by L. monocytogenes should be treated for at least 21 days. However, therapy must be individualized; on the basis of clinical response, some patients may require longer courses of treatment.
Despite the availability of effective antimicrobial therapy, the morbidity and mortality rates of bacterial meningitis remain unacceptably high. Recent studies have focused on the pathogenesis and pathophysiology of bacterial meningitis, in the hope of developing innovative strategies for adjunctive treatment.20,24 Recent work in experimental animal models of meningitis has suggested a potentially useful role for anti-inflammatory agents (e.g., corticosteroids and nonsteroidal anti-inflammatory agents) in decreasing the inflammatory response in the subarachnoid space, which may be responsible for the development of neurologic sequelae. Adjunctive dexamethasone therapy has been evaluated over the past decade in a number of published trials, mostly in infants and children with H. influenzae type b meningitis.20,24 A meta-analysis of clinical studies published from 1988 to 1996 confirmed the benefit of adjunctive dexamethasone (0.15 mg/kg every 6 hours for 2 to 4 days) in infants and children with H. influenzae type b meningitis and, if commenced with or before parenteral antimicrobial therapy, suggested benefit for pneumococcal meningitis in childhood.33 Administration of dexamethasone before or with initiation of antimicrobial therapy is recommended for optimal attenuation of the subarachnoid space inflammatory response; patients must be carefully monitored for the possibility of gastrointestinal hemorrhage. In a recently published prospective, randomized, double-blind trial in adults with bacterial meningitis, adjunctive treatment with dexamethasone was associated with a reduction in the proportion of patients who had unfavorable outcome and in the proportion of patients who died; the benefits were most striking in the subset of patients with pneumococcal meningitis.34 The use of adjunctive dexamethasone, however, is of particular concern in patients with pneumococcal meningitis caused by highly penicillin- or cephalosporin-resistant strains who are treated with vancomycin because a diminished inflammatory response may significantly decrease CSF vancomycin penetration and delay CSF sterilization, perhaps leading to a worse outcome. In the study cited above, only 72% of the 108 CSF cultures that were positive for S. pneumoniae were submitted for susceptibility testing, and all were susceptible to penicillin. However, based on the results of this trial and the apparent absence of serious adverse outcomes in the patients who received dexamethasone, routine use of adjunctive dexamethasone is warranted in most adults with pneumococcal meningitis.35 In patients with meningitis caused by pneumococcal strains resistant to penicillin and/or cephalosporins, careful observation and follow-up are critical to determine whether dexamethasone therapy is associated with an adverse outcome. When dexamethasone is used, the timing of administration is crucial. Administration of dexamethasone before or concomitant with the first dose of antimicrobial therapy is recommended for optimal attenuation of the subarachnoid space inflammatory response. Dexamethasone is not recommended in patients who have already received antimicrobial therapy. If the meningitis is found not to be caused by S. pneumoniae in adults, dexamethasone therapy should be discontinued.
Other adjunctive therapies may be useful in critically ill patients with bacterial meningitis.20 Patients who are stuporous or comatose (precluding assessment of worsening neurologic function) and who show signs of increased intracranial pressure (e.g., altered level of consciousness; dilated, poorly reactive or nonreactive pupils; and ocular movement disorders) may benefit from the insertion of an intracranial pressure monitoring device. Increased intracranial pressure can be lowered by elevating the head of the bed to 30 degrees to maximize venous drainage with minimal compromise of cerebral perfusion, by the use of hyperosmolar agents, and by hyperventilation. However, the routine use of hyperventilation (to maintain the partial arterial pressure of CO2 between 27 and 30 mm Hg) has been questioned in patients with bacterial meningitis. Infants and children with bacterial meningitis and normal initial CT scans can be treated with hyperventilation to decrease elevated intracranial pressure because it is unlikely that cerebral blood flow will be decreased to ischemic thresholds. However, in children in whom CT shows cerebral edema, cerebral blood flow is likely to be normal or decreased, so hyperventilation might decrease intracranial pressure at the expense of cerebral blood flow, possibly reducing flow to ischemic thresholds. The use of hyperosmolar agents (e.g., mannitol, glycerol) may be useful in reducing increased intracranial pressure in patients with bacterial meningitis. In one recent study in infants and children with bacterial meningitis, oral glycerol appeared to help prevent neurologic sequelae,36 although further studies are needed before adjunctive glycerol can be routinely recommended. A detailed discussion of the management of raised intracranial pressure is found in Chap. 65. Seizures must be treated promptly to avoid status epilepticus, which might lead to anoxic brain injury (see Chap. 64). Another important adjunctive measure in patients with bacterial meningitis is fluid restriction to combat hyponatremia caused by excess secretion of antidiuretic hormone, although this measure is not appropriate in the presence of shock or dehydration because hypotension may predispose the patient to cerebral ischemia. Many patients, particularly children, with bacterial meningitis are hyponatremic (serum sodium level <135 mEq/L) at presentation; the degree and duration of hyponatremia may contribute to neurologic sequelae. The management of hyponatremia is discussed in greater depth in Chap. 76.
A final point concerns chemoprophylaxis of contacts of meningitis cases, which is indicated for contacts of patients with N. meningitidis or H. influenzae type b meningitis.20 For meningococcal meningitis, chemoprophylaxis usually is administered only to intimate contacts (e.g., household contacts, day-care contacts, nursery school contacts, contacts who eat or sleep in the same dwelling, and close contacts such as in a military barracks or boarding school); it is not indicated for other groups (e.g., office coworkers or classmates) unless there has been intimate contact. However, one study has suggested that school-aged children may be at increased risk of secondary infection when classrooms are crowded and/or when contact during lunch or recess is frequent. Prophylaxis is not necessary for medical personnel caring for cases unless there has been intimate contact (e.g., mouth-to-mouth resuscitation, or those who perform endotracheal intubation or endotracheal tube management). All contacts (children and adults) of a patient with H. influenzae meningitis should receive chemoprophylaxis if exposure has occurred in a household or day-care center containing children 4 years or younger (other than the index case), provided that the exposure to H. influenzae type b was in the week before presentation. The recommended drug of choice for chemoprophylaxis, for contacts of patients with either type of meningitis, is rifampin. For contacts of patients with H. influenzae meningitis, rifampin at a daily dose of 20 mg/kg (not exceeding 600 mg) for 4 consecutive days is most effective. For contacts of meningococcal cases, one rifampin dose of 10 mg/kg (not exceeding 600 mg) twice a day for 2 days is effective. One dose of ciprofloxacin (500 or 750 mg) may also be effective for eradicating nasopharyngeal carriage of meningococci; ciprofloxacin is not recommended in pregnant women or in persons younger than 18 years because of concerns of cartilage damage. Ciprofloxacin may well supplant rifampin for chemoprophylaxis in adults. On one study, ceftriaxone (250 mg intramuscularly in adults or 125 mg in children) was shown to eliminate the meningococcal serogroup A carrier state in 97% of patients for up to 2 weeks and is probably the safest alternative for meningococcal chemoprophylaxis in pregnant women. Azithromycin (500 mg orally once) was also shown to be as effective as a four-dose regimen of rifampin in the eradication of meningococci from the nasopharynx.37