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Initial therapy and prognosis of bacterial meningitis in adults
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2012. | This topic last updated: Aug 9, 2011.

INTRODUCTION — Bacterial meningitis is a medical emergency, and immediate steps must be taken to establish the specific cause and initiate effective therapy. The mortality rate of untreated disease approaches 100 percent and, even with optimal therapy, there is a high failure rate.

The possible presence of bacterial meningitis is suggested by the symptoms of fever, altered mental status, headache, and nuchal rigidity. Although one or more of these findings are absent in many patients with bacterial meningitis [1-4], virtually all patients (99 to 100 percent) have at least one of the classic triad of fever, neck stiffness, and altered mental status [4]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)

The initial therapy and prognosis of bacterial meningitis will be reviewed here. The epidemiology, pathogenesis, clinical features, diagnosis, treatment of specific pathogens, and use of dexamethasone in the management of bacterial meningitis are discussed separately. (See "Epidemiology of bacterial meningitis in adults" and "Pathogenesis and pathophysiology of bacterial meningitis" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults" and "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

PRETREATMENT EVALUATION

History — If possible, the following historical information should be obtained before antibiotic treatment of presumed bacterial meningitis is instituted. Has the patient had or does the patient have:

  • Serious drug allergies
  • Recent exposure to someone with meningitis
  • A recent infection (especially respiratory or ear infection)
  • Recent use of antibiotics
  • Recent travel, particularly to areas with endemic meningococcal disease such as sub-Saharan Africa
  • A history of injection drug use
  • A progressive petechial or ecchymotic rash, which would be most suggestive of meningococcal infection
  • A history of recent or remote head trauma
  • Otorrhea or rhinorrhea
  • HIV infection or risk factors
  • Any other immunocompromising conditions

Diagnostic tests — Initial blood tests should include a complete blood count with differential, and two sets of blood cultures, which are positive in 50 to 90 percent of adults with bacterial meningitis [1,2,5]. The rate of positive blood cultures is lowest with meningococcal infection [6], and cultures obtained after antimicrobials are much less likely to be positive [6-8]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Blood cultures for the detection of bacteremia".)

The initial approach to management in a patient with suspected bacterial meningitis includes performance of a lumbar puncture to determine whether the cerebrospinal fluid (CSF) findings are consistent with the diagnosis (figure 1) [9]. CSF should be sent for cell count and differential, glucose and protein concentrations, Gram stain, and culture. Characteristic findings in bacterial meningitis include a CSF glucose concentration <45 mg/dL, a CSF to serum glucose ratio of <0.4, a protein concentration of 100 to 500 mg/dL, and a white blood cell count above 1000/microL, usually composed primarily of neutrophils [1-3]. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states".)

However, the spectrum of CSF values in bacterial meningitis is so wide that the absence of one of more of these findings is of little value (table 1) [1-3]. This was illustrated in a review of 296 episodes of community-acquired bacterial meningitis: 50 percent had a CSF glucose above 40 mg/dL (2.2 mmol/L); 44 percent had a CSF protein below 200 mg/dL; and 13 percent had a CSF white cell count below 100/microL [3]. In another series of 696 episodes of community-acquired bacterial meningitis, 12 percent had none of the characteristic CSF findings [5]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'CSF analysis'.)

Another modality used during the evaluation for bacterial meningitis is polymerase chain reaction (PCR) of the CSF. Although PCR has high sensitivity and specificity for the detection of bacterial pathogens such as S. pneumoniae in the CSF, problems with false-positive results have been reported. Further refinements in this technique may make it useful for the diagnosis of bacterial meningitis, especially when results of CSF Gram stain and culture are negative. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Polymerase chain reaction'.)

GENERAL PRINCIPLES OF THERAPY — There are a number of general principles of antibiotic therapy in patients with bacterial meningitis. The most important initial issues are avoidance of delay in administering therapy and the choice of drug regimen.

Avoidance of delay — Antibiotic therapy, along with adjunctive dexamethasone when indicated, should be initiated immediately after the performance of the lumbar puncture (LP) or, if a computed tomography (CT) scan of the head is to be performed before LP, immediately after blood cultures are obtained (figure 1) [9]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Indications for CT scan before LP'.)

Effects of delay — Delay in the administration of antibiotics can have adverse effects, as illustrated in the following studies [2,10-12]:

  • In a retrospective study that included 269 adults with bacterial meningitis, three baseline prognostic markers at the time of initiation of antibiotics - hypotension, altered mental status, and seizures - were predictive of an adverse outcome (defined as in-hospital mortality or a neurologic deficit at discharge) [2]. Delay in initial antibiotics in the emergency department (median delay of four hours) was associated with a worsening of these markers in about 15 percent of patients. Those patients whose delay in antibiotic therapy allowed their disease to advance from having zero or one to having two or three poor prognostic indicators had a significant increase in adverse outcomes.
  • In a prospective study of 156 patients with pneumococcal meningitis, a delay in antibiotic treatment of more than three hours after hospital admission was a strong and independent risk factor for mortality (OR 14.1; 95% CI: 3.9 to 50.9). Delayed therapy was a greater risk factor than the isolation of a penicillin-resistant strain (OR 6.83; 95% CI 2.94-20.8) or a higher disease severity (OR 1.12; 95% CI 1.07-1.15) [12].
  • In a retrospective cohort study of 286 patients with community-acquired bacterial meningitis, early and adequate administration of antibiotic therapy in relation to the onset of overt signs of meningitis was independently associated with a favorable outcome, defined as mild or no disability (OR 11.2, 95% CI 4.4-32.6) [13].
  • A retrospective study of 119 adults with bacterial meningitis examined the association between mortality and the time elapsed between emergency department presentation and antibiotic administration [11]. The adjusted odds ratio (OR) for mortality was 8.4 for a door-to-antibiotic time greater than six hours when the patient presented afebrile and 12.6 for patients with severely impaired mental status at presentation.

Causes of delay — Important causes of delay in the initiation of antimicrobial therapy include atypical clinical presentation and delay due to cranial imaging. It is important to note that antimicrobial therapy should NOT be delayed if imaging is performed prior to lumbar puncture.

  • Atypical presentation — In the retrospective study of 119 adults with bacterial meningitis described above, the most dramatic clinical predictor of death was the absence of fever at presentation (odds ratio 39.4, 95% CI 4.3-358.1) [11]. This finding, along with other "atypical features" (eg, lack of headache or neck stiffness), accounts for some of the delay in making the diagnosis and initiating therapy. While a deliberate delay of therapy is never warranted, the diagnosis can be quite challenging in cases with atypical features. Lowering the threshold for initiation of therapy may be prudent, but there is no clear guideline that will identify bacterial meningitis in patients with atypical features without some risk of over-treatment. (See 'Prediction of risk' below.)
  • Delay due to imaging — An important cause of delayed therapy in patients with suspected bacterial meningitis is performance of a computed tomography (CT) scan of the head to exclude an occult mass lesion that could lead to cerebral herniation during subsequent CSF removal [9]. Should LP be delayed by the need for cranial imaging in patients suspected of having bacterial meningitis, blood cultures should be obtained and antibiotics should be administered empirically along with adjunctive dexamethasone just prior to or concomitant with the first antibiotic dose. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

Although commonly performed, a screening CT scan of the head is NOT necessary in the majority of patients. In two large series, 3 to 5 percent of patients had a finding that was a contraindication to LP [10,14]. Risk factors included a suspicious history (eg, immunocompromised state, history of previous central nervous system disease, or a seizure within the previous week) as well as certain findings on neurologic examination (eg, reduced level of consciousness, focal motor or cranial abnormalities, and papilledema).

In the retrospective study of 119 adults with bacterial meningitis noted above, withholding antibiotics until a CT scan and lumbar puncture were done was strongly associated with a delay of >6 h to the first dose of antibiotic [11]. What cannot be measured as easily is the number of excess doses of glucocorticoids and antibiotics administered in patients without meningitis, but with clinical features suggestive of meningitis, at the time of presentation. Some excess treatment should be expected in order to optimize the outcome of patients with bacterial meningitis.

Although the use of antimicrobial therapy before LP has an adverse impact on the yield of CSF Gram stain and culture, a pathogen can still be identified in the CSF in the majority of patients up to several hours after the administration of antibiotics, with the possible exception of meningococcal infection. This issue is discussed in detail separately. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Lumbar puncture'.)

Antibiotic regimen — There are three general requirements of antibiotic therapy for bacterial meningitis [15]:

  • Use of bactericidal drugs effective against the infecting organism
  • Use of drugs that enter the CSF, since the blood-brain barrier prevents macromolecule entry into the CSF
  • Structuring the regimen to optimize bactericidal efficacy based on the pharmacodynamic characteristics of the antimicrobial agent(s)

Bactericidal drugs — Since the CSF is a site of impaired humoral immunity, a fundamental principle of therapy of bacterial meningitis is that antibiotics must achieve a bactericidal effect within CSF to result in optimal microbiologic cure [16]. In an animal model of bacterial meningitis, bactericidal antibiotic therapy resulted in optimal microbiologic cure and survival in animals with pneumococcal meningitis [17]. This principle is also supported by clinical observations of poor outcomes in patients receiving bacteriostatic therapy [18].

Drug entry into CSF — Antibiotic penetration into CSF depends to a large extent on the status of the blood-brain barrier [19]. For example, when the blood-brain barrier is normal, most beta-lactam agents (eg, penicillin) penetrate poorly. However, in the presence of meningeal inflammation, CSF penetration is enhanced likely as a result of separation of intercellular tight junctions and increased numbers of pinocytotic vesicles in cerebral microvascular endothelial cells. As inflammation subsides, antibiotic entry decreases. Thus, maximal parenteral doses should be continued throughout the course of therapy to maintain adequate CSF concentrations. Antibiotic entry is also enhanced with drugs that have a high lipid solubility, low molecular weight, low protein binding, and low ionization at physiologic pH [15]. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Blood-brain barrier'.)

There are specific dosing recommendations for the antibiotics used to treat bacterial meningitis in order to attain maximal concentrations in the CSF. In some cases, higher doses of antibiotics are used for bacterial meningitis than for other infections (table 2B).

Pharmacodynamics — For antibiotics that exhibit time-dependent antimicrobial activity (eg, beta-lactams, vancomycin), the bactericidal activity depends upon the time that the agent is above the minimal inhibitory concentration (MIC) as a proportion of the dosing interval [15]. For agents that exhibit concentration-dependent antimicrobial activity (eg, aminoglycosides), killing occurs over a wide range of antimicrobial concentrations and there is a prolonged recovery period (ie, the post-antibiotic effect) after drug concentrations fall below the MIC during which regrowth of bacteria is delayed. The CSF pharmacodynamics of fluoroquinolones are more complicated, however, and features of both time-dependency and concentration-dependency have been described.

Choice of regimen — Antibiotic selection must be empiric immediately after CSF is obtained or when lumbar puncture is delayed. In such patients, antibiotic therapy needs to be directed at the most likely bacteria based upon patient age and underlying comorbid disease (table 2A-B) [3]. Knowledge of local susceptibility patterns also may be important. Empiric regimens are discussed in detail below. (See 'Empiric therapy' below.)

Once the CSF Gram stain results are available, the antibiotic regimen should be tailored to cover the most likely pathogen. (See 'Regimens based upon gram stain' below.)

If the CSF findings are consistent with the diagnosis of acute bacterial meningitis, but the Gram stain is negative, empiric antibiotic therapy should be continued. (See 'Empiric therapy' below.)

The antibiotic regimen should be modified further, when indicated, based on the CSF culture and susceptibility results. (See "Treatment of bacterial meningitis caused by specific pathogens in adults".)

Route of administration — Because of the general limitation in antibiotic penetration into the CSF, all patients should be treated with intravenous antibiotics. Oral antibiotics should be avoided since the dose and tissue concentrations tend to be considerably lower than with parenteral agents. An exception can be made for rifampin, which is useful as a synergistic agent for treatment of meningitis caused by beta-lactam-resistant S. pneumoniae or coagulase-negative staphylococcus.

Adjunctive dexamethasone — Permanent neurologic sequelae, such as hearing loss and focal neurologic deficits, are not uncommon in survivors of bacterial meningitis, particularly patients with pneumococcal meningitis. (See "Neurologic complications of bacterial meningitis in adults".)

Early intravenous administration of glucocorticoids (usually dexamethasone) has been evaluated as adjunctive therapy in an attempt to diminish the rate of hearing loss, other neurologic complications, and mortality. Based upon clinical trial data from Europe, the main indication for dexamethasone therapy in adults is known or suspected pneumococcal meningitis. Since the etiology of bacterial meningitis is not usually known at the time of treatment initiation, dexamethasone is administered to patients in the developed world with suspected bacterial meningitis in whom the organism is unknown. Dexamethasone should only be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S. pneumoniae. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

Since the entry of vancomycin into the CSF may be reduced by the decrease in inflammation with dexamethasone, rifampin is sometimes added in patients receiving dexamethasone. This is discussed in detail separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults", section on 'Antibiotic regimens'.)

The possible efficacy of dexamethasone therapy in the developing world varies with the patient population. These issues are discussed in detail elsewhere. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults", section on 'In developing regions'.)

EMPIRIC THERAPY — The empiric approach to antibiotic selection in patients with suspected bacterial meningitis is directed at the most likely bacteria based on the patient's age and host factors (table 2A-B) [9]. There have been no randomized trials in adults regarding the empiric therapy of bacterial meningitis. Treatment recommendations are based upon in vitro susceptibility and pharmacodynamic data, randomized trials in children, and accumulated clinical experience.

Causative organisms — In a United States surveillance study performed by the Centers for Disease Control and Prevention via the Emerging Infections Program Network, between 2003 and 2007, 1083 cases of bacterial meningitis were reported in adults; S. pneumoniae was responsible for 71 percent of cases, Neisseria meningitidis for 12 percent, group B streptococcus for 7 percent, Haemophilus influenzae for 6 percent, and Listeria monocytogenes for 4 percent [20]. Importantly, in adults, the incidence of bacterial meningitis caused by Listeria monocytogenes rises with increasing age. For this reason, adults ≥50 years of age should receive an antibiotic with activity against L. monocytogenes (eg, ampicillin) as part of the empiric regimen. (See 'No known immune deficiency' below.)

The epidemiology of bacterial meningitis and adults and children is discussed in detail separately. (See "Epidemiology of bacterial meningitis in adults", section on 'Community-acquired' and "Clinical features and diagnosis of acute bacterial meningitis in children older than one month of age", section on 'Epidemiology'.)

Empiric regimens — The empiric approach to antibiotic selection in patients with suspected bacterial meningitis is directed at the most likely bacteria based on the patient's age and underlying disease status (table 2A-B) [9].

Selected third-generation cephalosporins, such as cefotaxime and ceftriaxone, are the beta-lactams of choice in the empiric treatment of meningitis. These agents been demonstrated to be superior to cefuroxime and chloramphenicol in randomized trials of bacterial meningitis in children [21-23]. These drugs have consistent CSF penetration and potent activity against the major pathogens of bacterial meningitis, with the notable exceptions of Listeria monocytogenes and some penicillin-resistant strains of S. pneumoniae [24-26]. With the worldwide increase in the prevalence of penicillin-resistant pneumococci, vancomycin should be added to cefotaxime or ceftriaxone as empiric treatment until culture and susceptibility results are available [9,27]. (See "Treatment of bacterial meningitis caused by specific pathogens in adults".)

Ceftazidime, a third-generation cephalosporin with broad in vitro activity against gram-negative bacteria including Pseudomonas aeruginosa, is much less active against penicillin-resistant pneumococci than cefotaxime and ceftriaxone [28]. However, a fourth-generation cephalosporin, cefepime, has been shown to be safe and therapeutically equivalent to cefotaxime for the treatment of bacterial meningitis in infants and children, and can be considered a suitable alternative to cefotaxime or ceftriaxone when broad activity against both the pneumococcus and Gram negative bacteria, such as P. aeruginosa, is necessary [29].

No known immune deficiency — Streptococcus pneumoniae, Neisseria meningitidis, and, less often, Haemophilus influenzae and group B streptococcus are the most likely causes of community-acquired bacterial meningitis in otherwise healthy adults up to the age of 60 [30]. Individuals aged 50 years and older are also at increased risk of Listeria monocytogenes meningitis [31]. (See 'Causative organisms' above.)

Such patients, without evidence of renal insufficiency, should be treated empirically with the following regimen until culture and susceptibility data are available (table 2A-B) [9]:

  • Ceftriaxone — 2 g IV every 12 hours

    OR
  • Cefotaxime — 2 g IV every four to six hours

    PLUS
  • Vancomycin — 30 to 60 mg/kg IV per day in two or three divided doses

    PLUS
  • In adults ≥50 years of age, ampicillin — 2 g IV every four hours

A third-generation cephalosporin should be continued even if in vitro tests demonstrate intermediate susceptibility or resistance to cephalosporins, since they may provide synergy with vancomycin in this setting [32].

Fluoroquinolones have not been extensively studied for the treatment of bacterial meningitis. They achieve reasonably high CSF concentrations [9], and there is some anecdotal evidence of efficacy in animal models and in humans [9,33,34]. However, fluoroquinolones are not recommended as part of standard therapy unless unusual conditions, such as multiple severe drug allergies or highly resistant organisms, are present.

Impaired cellular immunity — Among patients with impaired cell-mediated immunity (due, for example, to lymphoma, cytotoxic chemotherapy, or high-dose glucocorticoids), coverage must be directed against Listeria monocytogenes and gram-negative bacilli (including Pseudomonas aeruginosa) as well as Streptococcus pneumoniae [35].

An appropriate regimen in patients with normal renal function is (table 2A-B):

  • Vancomycin — 30 to 60 mg/kg IV per day in two or three divided doses

    PLUS
  • Ampicillin — 2 g IV every four hours

    PLUS EITHER
  • Cefepime — 2 g IV every eight hours

    OR
  • Meropenem — 2 g IV every eight hours

Nosocomial infection — The distribution of causative organisms is appreciably different in patients with nosocomial meningitis (ie, following head trauma or after neurosurgery) compared with community-acquired meningitis. This was illustrated in a review of 197 episodes of nosocomial meningitis (most of which were related to recent neurosurgery or the presence of neurosurgical devices) seen between 1962 and 1988 in which gram-negative bacilli accounted for 33 percent of episodes, and streptococci, Staphylococcus aureus, and coagulase-negative staphylococci accounted for 9 percent each [3]. In contrast, S. pneumoniae, N. meningitidis, and L. monocytogenes accounted for only 8 percent.

Similar pathogens were involved in a later series of 6243 consecutive craniotomies performed between 1997 and 1999; patients with ventriculitis related to a device were excluded [36]. Meningitis occurred in 1.5 percent of procedures. When comparing patients from periods before and after antimicrobial prophylaxis was given (to prevent wound infection), prophylaxis had no effect on the rate of meningitis but did affect the cause of meningitis. Without prophylaxis most cases were caused by cutaneous organisms (S. aureus, coagulase-negative staphylococci, and P. acnes), whereas with prophylaxis most cases were caused by non-cutaneous organisms (Enterobacteriaceae > streptococci and Pseudomonas aeruginosa > coagulase-negative staphylococci, S. aureus, and P. acnes). (See "Overview of control measures to prevent surgical site infection", section on 'Neurosurgery'.)

Based upon such observations, empiric therapy must cover both gram-positive and gram-negative (such as Klebsiella pneumoniae and Pseudomonas aeruginosa) nosocomial pathogens (table 2A-B). Appropriate regimens in patients with normal renal function, pending culture results and susceptibility testing, are [9]:

  • Vancomycin — 30 to 60 mg/kg IV per day in two or three divided doses

    PLUS
  • Ceftazidime — 2 g IV every eight hours

    OR
  • Cefepime — 2 g IV every eight hours

    OR
  • Meropenem — 2 g IV every eight hours

An important clinical question is the safety of withdrawing antibiotic therapy if the CSF culture results are negative and suggest aseptic rather than bacterial meningitis post-neurosurgery. A consensus conference recommended empiric antibiotic therapy in all patients with clinical and laboratory features suggestive of postoperative meningitis; such therapy can be discontinued at 48 to 72 hours if the CSF culture is negative [37].

The safety of this approach has not been assessed in randomized trials but was evaluated in a cohort study of patients with meningitis at different time periods following neurosurgery or ear nose and throat surgery [38]. Between 1998 and most of 2003, the control period, guidelines were lacking or not implemented. From the end of 2003 through mid-2005, an interventional protocol was followed in which predefined intravenous antibiotic therapy was discontinued if the meningitis was considered aseptic as defined by a negative CSF culture on the third day.

There were 21 cases of bacterial meningitis and 54 of aseptic meningitis; no patient had an intracranial device. The duration of therapy was not different in the two time periods for bacterial meningitis but was significantly shorter with the interventional protocol in the later period for aseptic meningitis (3.5 versus 11.5 days). All episodes of meningitis were cured and complications were rare in both time periods.

An important limitation to this observational study is that it is unclear how many patients received perioperative antimicrobial therapy. This could have major implications for a negative CSF bacterial culture postoperatively, since the CSF may be infected but partially treated. For this reason, cessation of antibiotics is NOT recommended in patients who have received prior or are receiving concurrent antibiotic therapy with a negative CSF culture and who are suspected of having meningitis based on clinical and laboratory findings (eg, CSF pleocytosis).

Infections of CNS shunts are discussed separately. (See "Infections of central nervous system shunts and other devices".)

Beta-lactam allergy — The approach to therapy in patients with antibiotic allergies is challenging given the importance of early initiation of therapy and the crucial role of beta-lactam antibiotics in the therapy of bacterial meningitis. Although it is optimal to desensitize patients with a history of an IgE-mediated (anaphylactic) reaction to beta-lactams who require therapy with this antibiotic class, an alternative regimen must be used while the desensitization is being performed. Furthermore, the decision of whether to desensitize a patient should be based on the Gram stain and/or culture data, the latter of which can take several days to yield an organism. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams" and "Allergy to penicillins" and "Rapid drug desensitization for immediate hypersensitivity reactions".)

For empiric coverage in patients with severe beta-lactam allergies, the following regimen can be used:

  • Vancomycin — 30 to 60 mg/kg IV per day in two or three divided doses

    PLUS
  • Moxifloxacin — 400 mg IV once daily

    PLUS
  • If Listeria coverage is required (in patients ≥50 and/or in those with defects in cell-mediated immunity or other risk factors), trimethoprim-sulfamethoxazole - 10 to 20 mg/kg (of the trimethoprim component) IV per day divided every 6 to 12 hours

Empiric treatment during epidemics — Epidemics of meningitis due to N. meningitidis are reported almost every year from sub-Saharan Africa. The empiric therapy recommended by the World Health Organization for meningococcal meningitis during epidemics is one or two intramuscular injections of long-acting chloramphenicol (oily suspension), although intramuscular ceftriaxone is an acceptable alternative. This is discussed in detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Empiric treatment during epidemics'.)

REGIMENS BASED UPON GRAM STAIN — Rather than empiric therapy, intravenous antibiotics should be directed at the presumed pathogen if the Gram stain is diagnostic (table 2C, 2B) [9]. If indicated, antibiotic therapy should then be modified once the CSF culture and in vitro susceptibility studies are available (table 2D, 2B).

  • If gram-positive cocci are seen on the Gram stain of a patient with community-acquired meningitis, Streptococcus pneumoniae should be the suspected pathogen. Vancomycin plus a third-generation cephalosporin (either cefotaxime or ceftriaxone) should be administered. However, in the setting of neurosurgery or head trauma within the past month, a neurosurgical device, or a CSF leak, Staphylococcus aureus and coagulase-negative staphylococci are more common and therapy with vancomycin is warranted [3].
  • If gram-negative cocci are seen, Neisseria meningitidis is the probable pathogen.
  • Gram-positive bacilli suggest Listeria monocytogenes.
  • Gram-negative bacilli usually represent Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli) in cases of community-acquired meningitis. However, if there is a history of neurosurgery or head trauma within the past month, or if a neurosurgical device is present, ceftriaxone or cefotaxime should be replaced with ceftazidime, cefepime, or meropenem since such patients are at greater risk for Pseudomonas aeruginosa and Acinetobacter spp infection; given issues of cephalosporin resistance with Acinetobacter spp, meropenem would be a more appropriate empiric choice when infection caused by this organism is suspected [39]. In addition, resistance patterns at a given hospital should be taken into account when choosing an empiric regimen.

THERAPY FOR SPECIFIC PATHOGENS — Directed therapy against a specific organism is recommended when the clinical presentation and results of the CSF Gram stain are unequivocal (table 2C) or the cultures are already positive (table 2D) [28]. If, on the other hand, empiric therapy is begun, the regimen should be adjusted, if necessary, once the culture results are available (table 2D). Recommended dosages for use in patients with normal renal and hepatic function are shown in the Table (table 2B). The recommended treatment regimens for specific pathogens are discussed in detail separately. (See "Treatment of bacterial meningitis caused by specific pathogens in adults".)

SUPPORTIVE CARE

Fluid management — Careful management of fluid and electrolyte balance is important, since both over- and under-hydration are associated with adverse outcomes.

A meta-analysis evaluated three randomized controlled trials of treatment of differing volumes of fluid (maintenance versus restricted fluid) given in the initial management of bacterial meningitis [40]. The largest trial was conducted in a setting with a high mortality rate. There was no significant difference between the two groups in number of deaths, or acute severe or mild to moderate neurological sequelae. However, when neurological sequelae were defined further, there was a statistically significant difference in favor of the maintenance fluid group in regard to spasticity (relative risk [RR] 0.50, 95% CI 0.27-0.93), seizures at both 72 hours (RR 0.59, 95% CI 0.42-0.83) and 14 days (RR 0.19, 95% CI 0.04-0.88), and chronic severe neurological sequelae at three months follow up (RR 0.42, 95% CI 0.20-0.89). Thus, there is evidence that the use of intravenous maintenance fluids is preferred to restricted fluid intake in the first 48 hours in settings with high mortality rates and where patients present late. There is insufficient evidence to guide practice in other settings.

Reduction of intracranial pressure — Patients with bacterial meningitis who have elevations of intracranial pressure (ICP), and who are stuporous or comatose, may benefit from insertion of an ICP monitoring device [27,41]. Pressures exceeding 20 mm Hg are abnormal and should be treated; there is also rationale for treating smaller pressure elevations (ie, above 15 mm Hg) to avoid larger elevations that can lead to cerebral herniation and irreversible brainstem injury.

Methods to reduce ICP include elevating the head of the bed to 30º and hyperventilation to maintain PaCO2 between 27 and 30 mm Hg. . Another method that has been evaluated for reducing ICP is oral administration of the hyperosmolar agent, glycerol. However, a randomized trial in adults with bacterial meningitis in Malawi (a resource-poor country with high HIV prevalence) was stopped early because planned interim analysis demonstrated increased mortality by day 40 in the glycerol group (63 versus 49 percent) [42]. The reason for this finding is unclear, but might relate to an increased incidence of seizures in the patients who received glycerol. Another possible reason could be a rebound increase in ICP as the drug is eliminated, although ICP was not monitored in this trial. In contrast to this trial involving adults, some studies using glycerol have shown promising results in children with bacterial meningitis, although further data are needed before it can be recommended. (See "Dexamethasone and other measures to prevent neurologic complications of bacterial meningitis in children", section on 'Glycerol'.)

In a trial of 15 patients with bacterial meningitis in whom intracranial pressure was monitored, pressure was significantly lowered by a broad range of measures that utilized unconventional volume-targeted intracranial pressure management [43]. These included sedation, glucocorticoids, normal fluid and electrolyte homeostasis, blood transfusion, albumin infusion, decrease of mean arterial pressure, treatment with a prostacyclin analog, and eventually thiopental, ventriculostomy, and dihydroergotamine. In those not surviving their episode of bacterial meningitis, mean intracranial pressure was significantly higher. However, given that this was not a comparative trial, the results must be interpreted with caution.

REPEAT CSF ANALYSIS — There is limited utility to routine repeat LP to assess the response to therapy in adults with bacterial meningitis. This was illustrated in a review of 165 adults with meningitis who underwent an end of treatment LP [44]. Wide ranges of glucose and protein concentrations and cell counts were found at the end of treatment in patients who were ultimately shown to be cured without further therapy. In addition, repeat CSF examination failed to detect relapse in the two patients who relapsed following treatment, and the CSF test results led to unnecessary testing in 13 patients with abnormal CSF findings at the end of therapy. The authors concluded that clinical signs of improvement were a better indicator of response to therapy than the results of CSF analysis after treatment had been completed.

Although not routinely recommended, there are settings in which repeat LP should be performed in patients with bacterial meningitis [9]:

  • When there is no evidence of improvement by 48 hours after the initiation of appropriate therapy.
  • Two to three days after the initiation of therapy of meningitis due to microorganisms resistant to standard antimicrobial agents (eg, penicillin-resistant pneumococcal infection), especially for those who have also received adjunctive dexamethasone therapy and are not responding as expected, or for infection caused by a gram-negative bacillus, which is much more common with nosocomial infection [3].
  • Persistent fever for more than eight days without another explanation.

Repeat CSF cultures should be sterile. For patients in whom repeat cultures are positive despite appropriate therapy with parenteral antibiotic therapy, administration of intrathecal (or intraventricular) antibiotics may be considered [45].

PROGNOSIS — There is an appreciable mortality rate associated with bacterial meningitis even with the administration of appropriate antibiotics.

Mortality — The mortality rate increases linearly with increasing age. In a United States population-based surveillance study between 2003 and 2007, the case-fatality rate of bacterial meningitis in adults was 16.4 percent; among patients between 18 and 34 years of age, the case-fatality rate was 8.9 percent compared with 22.7 percent in patients ≥65 years of age [20]. The overall case-fatality rate did not change significantly between 1998-1999 and 2006-2007.

Outcomes also vary depending upon the organism. The following observations from different time periods illustrate the range of findings:

  • In a review of 493 episodes of bacterial meningitis in 445 adults seen at a single center in the United States from 1962 to 1988, the overall mortality rate was 25 percent and did not vary over the course of the study [3]. The mortality rate was higher with nosocomial compared to community-acquired infection (35 versus 25 percent), and was higher with infection due to S. pneumoniae and L. monocytogenes compared to N. meningitidis (28 and 32 versus 10 percent).
  • In a series of 248 patients seen in 1995 in acute care hospitals in 22 counties in four states in the United States, the mortality rate was highest with S. pneumoniae and L. monocytogenes (21 and 15 percent, respectively) and lowest with N. meningitidis (3 percent) [30].
  • A report from the Netherlands evaluated 696 cases of community-acquired acute bacterial meningitis seen between 1998 and 2002 [5]. The overall mortality rate was significantly higher with pneumococcal compared to meningococcal meningitis (30 versus 7 percent). In addition, an unfavorable outcome was six times more common with pneumococcal meningitis, even after adjustment for other clinical predictors.

Neurologic complications — Neurologic complications are not uncommon in adults with bacterial meningitis. In a review of 493 episodes of bacterial meningitis in adults, for example, 28 percent of community-acquired episodes resulted in one or more neurologic complications [3]. The neurologic complications of bacterial meningitis include:

  • Impaired mental status
  • Increased intracranial pressure and cerebral edema
  • Seizures
  • Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis)
  • Cerebrovascular abnormalities
  • Sensorineural hearing loss
  • Intellectual impairment

These are discussed in detail separately. (See "Neurologic complications of bacterial meningitis in adults".)

Prediction of risk — Baseline features can be used to estimate the individual patient's risk for an adverse outcome. A prognostic model was derived from a cohort of 176 adults and then validated in another cohort of 93 patients [2]. The in-hospital mortality was 27 percent, and 9 percent had a neurologic deficit at discharge. Three baseline clinical features - hypotension, altered mental status, and seizures - were independently associated with an adverse outcome (defined as in-hospital death or neurologic deficit at discharge) and stratified the patients into three risk groups:

  • Low risk (no clinical risk factors) — 9 percent adverse outcome
  • Intermediate risk (one clinical risk factor) — 33 percent adverse outcome
  • High risk (two or three risk factors) — 56 percent adverse outcome

An additional risk factor for an adverse outcome in this report was advancement from low or intermediate risk to high risk in the emergency department prior to the administration of antibiotics. Although this finding supports the recommendation to avoid delays in antimicrobial therapy in patients with suspected bacterial meningitis, it is also consistent with the hypothesis that severely ill patients at the start may have an adverse outcome regardless of the timing of initial therapy [46].

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SUMMARY AND RECOMMENDATIONS

General approach

  • Bacterial meningitis is a medical emergency, and immediate steps must be taken to establish the specific cause and initiate effective therapy. The mortality rate of untreated disease approaches 100 percent and, even with optimal therapy, there is a high failure rate. (See 'Introduction' above.)
  • If possible, crucial historical information (eg, serious drug allergies, recent exposure to an individual with meningitis), should be obtained before antibiotic treatment of presumed bacterial meningitis is instituted. (See 'History' above.)
  • Initial blood tests should include a complete blood count with differential, and two sets of blood cultures. The initial approach to management in a patient with suspected bacterial meningitis includes performance of a lumbar puncture (LP) to determine whether the cerebrospinal fluid (CSF) findings are consistent with the diagnosis. (See 'Diagnostic tests' above.)
  • There are three general requirements of antibiotic therapy for bacterial meningitis: use of bactericidal drugs effective against the infecting organism, use of drugs that enter the CSF, and use of drugs with optimal pharmacodynamics. (See 'Antibiotic regimen' above.)
  • We recommend that antibiotic therapy be initiated immediately after the performance of the lumbar puncture (LP) or, if a computed tomography scan is to be performed before LP, immediately after blood cultures are obtained (Grade 1B). Adjunctive dexamethasone should be given shortly before or at the same time as the first dose of antibiotics, when indicated. (See 'Avoidance of delay' above.)
  • For adults in the developed world with suspected bacterial meningitis in whom the organism is unknown or Streptococcus pneumoniae is confirmed, we recommend administration of dexamethasone (Grade 1B). Dexamethasone should be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S. pneumoniae. The indications for dexamethasone in patients in the developing world with suspected or confirmed bacterial meningitis depend upon the prevalence of HIV in the population. Rifampin is added to the regimen in patients receiving dexamethasone under certain circumstances. This is discussed in detail separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
  • Once the CSF Gram stain results are available, the antibiotic regimen should be tailored to cover the most likely pathogen. If the CSF findings are consistent with the diagnosis of acute bacterial meningitis, but the Gram stain is negative, empiric antibiotic therapy should be continued. (See 'Regimens based upon gram stain' above.)
  • The antibiotic regimen should be modified further, when indicated, based on the CSF culture and susceptibility results. (See "Treatment of bacterial meningitis caused by specific pathogens in adults".)

Empiric antibiotics

  • Antibiotic selection must be empiric immediately after CSF is obtained or when lumbar puncture is delayed. The empiric approach to antibiotic selection in patients with suspected bacterial meningitis is directed at the most likely bacteria based on the patient's age and underlying disease status (table 2A-B). (See 'Empiric regimens' above.)

No known immunodeficiency

  • Streptococcus pneumoniae, Neisseria meningitidis, and, less often, Haemophilus influenzae and group B streptococcus are the most likely causes of community-acquired bacterial meningitis in otherwise healthy adults up to the age of 60. Individuals aged 50 years and older are also at substantial risk of Listeria monocytogenes meningitis. Patients without known immune deficiency and with normal renal function should be treated empirically with the following regimen until culture and susceptibility data are available (table 2A-B):

Impaired cell-mediated immunity

  • Among patients with impaired cell-mediated immunity (due, for example, to lymphoma, cytotoxic chemotherapy, or high-dose glucocorticoids), coverage must be directed against Listeria monocytogenes and gram-negative bacilli (including Pseudomonas aeruginosa) as well as Streptococcus pneumoniae. An appropriate regimen in patients with normal renal function is (table 2A-B):

Nosocomial meningitis

  • Empiric therapy for nosocomial meningitis must cover both gram-positive and gram-negative (such as Klebsiella pneumoniae and Pseudomonas aeruginosa) nosocomial pathogens (table 2A-B). An appropriate regimen in patients with normal renal function is:

Allergy to beta-lactams

  • For empiric coverage in patients with severe beta-lactam allergies, we suggest (Grade 2C):

  • Vancomycin — 30 to 60 mg/kg IV per day in two or three divided doses

    PLUS
  • Moxifloxacin — 400 mg IV once daily

    PLUS
  • If Listeria coverage is required (in patients ≥50 and/or in those with defects in cell-mediated immunity), trimethoprim-sulfamethoxazole — 10 to 20 mg/kg (of the trimethoprim component) IV per day divided every 6 to 12 hours

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