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Initial therapy and prognosis of bacterial meningitis in adults
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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: Nov 2016. | This topic last updated: Oct 07, 2015.

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 antimicrobial therapy 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

Pretreatment testing — 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 (algorithm 1) [5]. An important early decision relates to whether a head computed tomography (CT) should be performed prior to LP.

Although a screening CT scan is not necessary in the majority of patients, a head CT should be performed before LP in adults with suspected bacterial meningitis who have one or more of the following risk factors [5-7]:

Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic cell transplantation)

History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)

New-onset seizure (within one week of presentation)

Papilledema

Abnormal level of consciousness

Focal neurologic deficit

If a head CT is indicated, blood cultures should be obtained immediately, and dexamethasone (if indicated) and empiric antimicrobial therapy should be started once blood cultures have been obtained and prior to head CT. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

If the results of the CT reveal that LP is contraindicated, therapy for bacterial meningitis should be continued (if indicated) or evaluation and treatment for an alternative diagnosis should be undertaken (ie, if the CT suggests a different cause for the patient's clinical presentation).

In patients without any of the risk factors described above, blood cultures and LP may be performed without performing a head CT. Once CSF has been obtained (and before results are available), dexamethasone (if indicated) and empiric antimicrobial therapy should be initiated if bacterial meningitis is suspected.

CSF should be sent for:

Cell count and differential

Glucose concentration

Protein concentration

Gram stain and bacterial culture

Other appropriate tests, depending upon the level of concern for other etiologies of meningitis or meningoencephalitis

Characteristic findings in bacterial meningitis include a CSF glucose concentration <40 mg/dL, a CSF to serum glucose ratio of ≤0.4, a protein concentration >200 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 or 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 [8]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'CSF analysis'.)

The frequent absence of one or more of the expected CSF findings in patients with bacterial meningitis means that there is substantial overlap between bacterial meningitis, which is a life-threatening illness that requires hospital admission and urgent therapy, and viral meningitis, which is a less severe disease that is often monitored in the outpatient setting without antimicrobial therapy. Selected viruses that can cause meningitis are summarized in the Table (table 2). The diagnostic approach to aseptic meningitis is presented separately. (See "Aseptic meningitis in adults".)

Before CSF results are available, it can be difficult to know whether the patient has bacterial or viral meningitis. The decision of which tests to perform on the CSF will depend on patient-specific factors, such as those described above (see 'History' above). In addition to suggesting specific diagnostic tests, we often send an extra tube of CSF if possible to the laboratory to be held for further studies, as the CSF profile and the patient's clinical course may warrant additional testing.

The diagnosis of bacterial meningitis is discussed in greater detail separately. (See "Clinical features and diagnosis of acute bacterial meningitis in adults".)

GENERAL PRINCIPLES OF THERAPY — There are a number of general principles of antibiotic therapy in patients with bacterial meningitis [5,9]. The most important initial issues are avoidance of delay in administering therapy and the choice of drug regimen.

Avoidance of delay — Antimicrobial therapy, along with adjunctive dexamethasone when indicated, should be initiated as quickly as possible after the performance of the lumbar puncture (LP) or, if a computed tomography (CT) scan of the head is to be performed before LP, as quickly as possible after blood cultures are obtained (algorithm 1) [5,9,10]. (See 'Pretreatment testing' above and "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 antimicrobial agents can have adverse effects, as illustrated in the following studies [2,6,11,12]:

In a retrospective study that included 269 adults with bacterial meningitis, three baseline prognostic markers at the time of initiation of antimicrobial agents (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 antimicrobial therapy 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 antimicrobial treatment of more than three hours after hospital admission was a strong and independent risk factor for mortality (odds ratio [OR] 14.1; 95% CI 3.9-50.9). 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 antimicrobial 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 antimicrobial administration [11]. The adjusted odds ratio 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 (OR 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 CT scan of the head to exclude an occult mass lesion or other findings that could lead to cerebral herniation during subsequent cerebrospinal fluid (CSF) removal [5]. Should LP be delayed by the need for cranial imaging in patients suspected of having bacterial meningitis, blood cultures should be obtained and antimicrobial agents should be administered empirically along with adjunctive dexamethasone (if indicated) 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 [6,7]. 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 antimicrobial therapy until a CT scan and lumbar puncture were done was strongly associated with a delay of >6 hours to the first dose of antibiotic [11]. What cannot be measured as easily is the number of excess doses of glucocorticoids and antimicrobials administered in patients without meningitis but with clinical features suggestive of meningitis at the time of presentation. Some excess treatment may 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 antimicrobial agents, 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 antimicrobial therapy for bacterial meningitis [14]:

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 antimicrobial agents must achieve a bactericidal effect within CSF to result in optimal microbiologic cure [15]. In an animal model of bacterial meningitis, bactericidal antimicrobial therapy resulted in optimal microbiologic cure and survival in animals with pneumococcal meningitis [16]. This principle is also supported by clinical observations of poor outcomes in patients receiving bacteriostatic therapy [17].

Drug entry into CSF — Antimicrobial penetration into CSF depends to a large extent on the status of the blood-brain barrier [18]. 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, antimicrobial 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 [14]. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Blood-brain barrier'.)

There are specific dosing recommendations for the antimicrobial agents used to treat bacterial meningitis in order to attain maximal concentrations in the CSF. In some cases, higher doses of agents are used for bacterial meningitis than for other infections (table 3B).

Pharmacodynamics — For antimicrobial agents 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 [14]. 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 postantibiotic 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 — Antimicrobial selection must be empiric immediately after CSF is obtained or when lumbar puncture is delayed. In such patients, antimicrobial therapy needs to be directed at the most likely bacteria based upon patient age and underlying comorbid disease (table 3A-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 antimicrobial 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 antimicrobial therapy should be continued. (See 'Empiric therapy' below.)

The antimicrobial 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 antimicrobial penetration into the CSF, all patients should be treated with intravenous antimicrobial agents. Oral antimicrobial agents 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 Streptococcus pneumoniae or coagulase-negative Staphylococcus.

Duration — The duration of antimicrobial therapy for bacterial meningitis depends upon the causative pathogen. This is discussed in greater detail separately. (See "Treatment of bacterial meningitis caused by specific pathogens in adults".)

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 antimicrobial selection in patients with suspected bacterial meningitis is directed at the most likely bacteria based on the patient's age and host factors (table 3A-B) [5,19]. 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 L. monocytogenes rises with increasing age. For this reason, adults >50 years of age should receive an antimicrobial agent 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 meningitis' and "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Epidemiology'.)

Empiric regimens — The empiric approach to antimicrobial 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 3A-B) [5,19].

Selected third-generation cephalosporins (ie, cefotaxime and ceftriaxone) are the beta-lactams of choice in the empiric treatment of meningitis. These agents have been demonstrated to be superior to cefuroxime and chloramphenicol in randomized trials of bacterial meningitis in children [21-23]. These drugs have consistent cerebrospinal fluid (CSF) penetration and potent activity against the major pathogens of bacterial meningitis, with the notable exceptions of L. 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 [5,27]. (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 pneumococcus and gram-negative bacteria, such as P. aeruginosa, is necessary [29].

No known immune deficiency — S. pneumoniae, N. meningitidis, and, less often, H. 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 years [30]. Individuals over aged 50 years are also at increased risk of L. 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 3A-B) [5]:

Ceftriaxone – 2 g intravenously (IV) every 12 hours

or

Cefotaxime – 2 g IV every 4 to 6 hours

plus

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

In adults >50 years of age, ampicillin – 2 g IV every four hours

A third-generation cephalosporin (ceftriaxone, cefotaxime) should be continued even if in vitro tests demonstrate S. pneumoniae with reduced susceptibility to third-generation cephalosporins (minimum inhibitory concentration ≥1 mcg/mL), 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 [5], and there is some anecdotal evidence of efficacy in animal models and in humans [5,33]. One fluoroquinolone, trovafloxacin, was compared with ceftriaxone, with or without vancomycin, in a multicenter randomized trial of 311 children with bacterial meningitis; the overall efficacy (CSF sterilization and clinical success) of both treatment groups was similar [34]. Although trovafloxacin is no longer available because of its association with serious hepatotoxicity, these results suggest the potential usefulness of newer fluoroquinolones (eg, moxifloxacin) in the treatment of bacterial meningitis. 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. (See 'Beta-lactam allergy' below and "Treatment of bacterial meningitis caused by specific pathogens in adults", section on 'Alternative agents'.)

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

An appropriate regimen in patients with normal renal function is (table 3A-B):

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Ampicillin – 2 g IV every 4 hours

plus either

Cefepime – 2 g IV every 8 hours

or

Meropenem – 2 g IV every 8 hours

Healthcare-associated infection — The distribution of causative organisms is appreciably different in patients with healthcare-associated meningitis (ie, following head trauma or neurosurgery, and in patients with internal or external ventricular drains) compared with community-acquired meningitis [36]. This was illustrated in a review of 197 episodes of healthcare-associated 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, S. 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 [37]. 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 Propionibacterium acnes), whereas, with prophylaxis, most cases were caused by noncutaneous organisms (Enterobacteriaceae > streptococci and P. aeruginosa > coagulase-negative staphylococci, S. aureus, and P. acnes). (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery'.)

Based upon such observations, empiric therapy must cover both gram-positive and gram-negative (such as Klebsiella pneumoniae and P. aeruginosa) pathogens (table 3A-B). Appropriate regimens in patients with normal renal function, pending culture results and susceptibility testing, are [5,36]:

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Ceftazidime – 2 g IV every 8 hours

or

Cefepime – 2 g IV every 8 hours

or

Meropenem – 2 g IV every 8 hours

An important clinical question is the safety of withdrawing antimicrobial therapy if the CSF culture results are negative and suggest aseptic rather than bacterial meningitis post-neurosurgery. A consensus conference recommended empiric antimicrobial 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 [38].

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 [39]. 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 antimicrobial therapy was discontinued on the third day if the meningitis was considered aseptic as defined by a negative CSF culture.

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 during 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 antimicrobial therapy is not recommended in patients who have received prior or are receiving concurrent antimicrobial therapy with a negative CSF culture and who are suspected of having bacterial meningitis based on clinical and laboratory findings (eg, CSF pleocytosis).

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

Beta-lactam allergy — The approach to therapy in patients with antimicrobial 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 immunoglobulin (Ig)E-mediated (anaphylactic) reaction to beta-lactams who require therapy with this antimicrobial 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 "Penicillin allergy: Immediate reactions" and "Rapid drug desensitization for immediate hypersensitivity reactions".)

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

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Moxifloxacin – 400 mg IV once daily

plus

If Listeria coverage is required (in patients >50 years of age and/or in those with defects in cell-mediated immunity or other risk factors), trimethoprim-sulfamethoxazole – 5 mg/kg (of the trimethoprim component) IV 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 antimicrobial therapy should be directed at the presumed pathogen if the Gram stain is diagnostic (table 3B-C) [5]. If indicated, antimicrobial therapy should then be modified once the cerebrospinal fluid (CSF) culture and in vitro susceptibility studies are available (table 3B, 3D). In addition, resistance patterns at a given hospital should be taken into account when choosing an empiric regimen.

If gram-positive cocci are seen on the Gram stain of a patient with community-acquired meningitis, S. 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, S. aureus and coagulase-negative staphylococci are more common, and therapy with vancomycin is warranted [3].

If gram-negative cocci are seen, N. meningitidis is the probable pathogen.

Gram-positive bacilli suggest L. 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 P. aeruginosa and Acinetobacter spp infection [36]; given issues of cephalosporin resistance with Acinetobacter spp, meropenem would be a more appropriate empiric choice when infection caused by this organism is suspected [40]. If the Acinetobacter isolate is later found to be resistant to carbapenems, intravenous colistin (usually formulated as colistimethate sodium) or polymyxin B should be substituted for meropenem and should also be administered by the intraventricular or intrathecal route. (See "Acinetobacter infection: Treatment and prevention", section on 'Meningitis'.)

THERAPY FOR SPECIFIC PATHOGENS — Directed therapy against a specific organism is recommended when the clinical presentation and results of the cerebrospinal fluid Gram stain are unequivocal (table 3C) or the cultures are already positive (table 3D) [28]. If, on the other hand, empiric therapy is begun, the regimen should be adjusted, if necessary, once the culture results are available (table 3D). Recommended dosages for use in patients with normal renal and hepatic function are shown in the Table (table 3B). 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 [41]. 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 neurologic sequelae. However, when neurologic 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 neurologic 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 when 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 [27,42]. Pressures exceeding 20 mmHg are abnormal and should be treated; there is also rationale for treating smaller pressure elevations (ie, above 15 mmHg) to avoid larger elevations that can lead to cerebral herniation and irreversible brainstem injury. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'ICP monitoring'.)

Methods to reduce ICP include elevating the head of the bed to 30º and hyperventilation to maintain PaCO2 between 27 and 30 mmHg. 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) [43]. 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 with 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 "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Glycerol'.)

In a study 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 [44]. 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.

In a prospective intervention-control comparison study of adult patients with acute bacterial meningitis, 53 patients were treated with conventional intensive care and 52 patients were given ICP-targeted treatment in the neuro-intensive care unit [45]. ICP-targeted treatment included CSF drainage using external ventricular catheters (48 patients), osmotherapy (21 patients), hyperventilation (13 patients), external cooling (9 patients), high doses of methylprednisolone (3 patients), and deep barbiturate sedation (2 patients), aiming to keep the ICP <20 mmHg and cerebral perfusion pressure of >50 mmHg. Mortality was significantly lower in the intervention group (10 versus 30 percent). However, this was not a randomized controlled trial and controls were identified retrospectively. Additional data are therefore needed.

Induced hypothermia — There has been interest in evaluating induced hypothermia in patients with severe meningitis since there is evidence that it is beneficial in patients with global cerebral hypoxemia following cardiac arrest (see "Post-cardiac arrest management in adults", section on 'Temperature management and therapeutic hypothermia (TH)'). However, more data are needed before therapeutic hypothermia can be recommended in patients with severe bacterial meningitis.

In an open-label multicenter randomized trial in 49 intensive care units in France, 98 comatose patients were randomly assigned to undergo induced hypothermia with a loading dose of 4°C cold saline and cooling to 32 to 34°C for 48 hours or standard care [46]. The trial was stopped early because of concerns about excess mortality in the induced hypothermia group compared with the control group (51 versus 31 percent; RR 1.99, 95% CI 1.05-3.77). At three months, 86 percent of patients in the hypothermia group had an unfavorable outcome (defined as a Glasgow Coma Scale score of 1 to 4) compared with 74 percent of those in the control group (RR 2.17, 95% CI 0.78-6.01). After adjustment for age, Glasgow Coma Scale score at inclusion, and the presence of septic shock at inclusion, mortality remained higher in the induced-hypothermia group, although the difference was not statistically significant (hazard ratio 1.76; 95% CI 0.89-3.45). The authors concluded that moderate hypothermia did not improve outcomes in patients with severe bacterial meningitis and that it may be harmful.

In a study of therapeutic hypothermia in adults with community-acquired bacterial meningitis, the incidence of hospital mortality (20 versus 49 percent) and adverse neurologic outcome (ie, a Glasgow outcome score 1 to 3; 44 versus 66 percent) were significantly lower in patients treated with therapeutic hypothermia [47]. However, the number of enrolled patients was small, and outcomes in this study of the 41 enrolled patients were compared with historical controls.

REPEAT CSF ANALYSIS — There is limited utility to routine repeat lumbar puncture (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 [48]. 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 cerebrospinal fluid (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 [5]:

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 healthcare-associated infection [3,36]

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 [49].

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

Mortality — The mortality rate of bacterial meningitis increases linearly with increasing age. In a United States population-based surveillance study between 2003 and 2007, the case-fatality rate 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 to 1999 and 2006 to 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 healthcare-associated compared with community-acquired infection (35 versus 25 percent) and was higher with infection due to S. pneumoniae and L. monocytogenes compared with 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 [8]. The overall mortality rate was significantly higher with pneumococcal compared with 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.

The use of adjunctive dexamethasone is associated with a reduction in mortality in selected patients with bacterial meningitis. This is discussed in detail separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

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]. 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 [50].

In a retrospective study of 65 patients admitted to the intensive care unit for acute bacterial meningitis, adverse clinical outcomes were noted in 46 patients; these patients were older, had a higher Acute Physiology and Chronic Health Evaluation II score, and a lower Glasgow Coma Scale score [51].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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Basics topic (see "Patient education: Bacterial meningitis (The Basics)")

Beyond the Basics topics (see "Patient education: Adult vaccines (Beyond the Basics)" and "Patient education: Vaccines for children age 7 to 18 years (Beyond the Basics)")

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 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 (algorithm 1). (See 'Pretreatment testing' above.)

There are three general requirements of antimicrobial 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 antimicrobial therapy be initiated immediately after the performance of the lumbar puncture or, if a computed tomography (CT) 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. 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 antimicrobial 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 antimicrobial therapy

Antimicrobial selection must be empiric immediately after CSF is obtained or when lumbar puncture is delayed. The empiric approach to antimicrobial 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 3A-B). (See 'Empiric regimens' above.)

No known immunodeficiency

S. 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 over 50 years 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 3A-B):

Ceftriaxone – 2 g intravenously (IV) every 12 hours

or

Cefotaxime – 2 g IV every 4 to 6 hours

plus

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

In adults >50 years of age, ampicillin – 2 g IV every four hours (see 'No known immune deficiency' above)

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 L. monocytogenes and gram-negative bacilli (including Pseudomonas aeruginosa) as well as S. pneumoniae. An appropriate regimen in patients with normal renal function is (table 3A-B):

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Ampicillin – 2 g IV every 4 hours

plus either

Cefepime – 2 g IV every 8 hours

or

Meropenem – 2 g IV every 8 hours (see 'Impaired cellular immunity' above)

Healthcare-associated meningitis

Empiric therapy for healthcare-associated meningitis must cover both gram-positive and gram-negative (such as Klebsiella pneumoniae and P. aeruginosa) pathogens (table 3A-B). An appropriate regimen in patients with normal renal function is:

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Ceftazidime – 2 g IV every 8 hours

or

Cefepime – 2 g IV every 8 hours

or

Meropenem – 2 g IV every 8 hours (see 'Healthcare-associated infection' above)

Allergy to beta-lactams

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

Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20 mcg/mL)

plus

Moxifloxacin – 400 mg IV once daily

plus

If Listeria coverage is required (in patients >50 years of age and/or in those with defects in cell-mediated immunity), trimethoprim-sulfamethoxazole – 5 mg/kg (of the trimethoprim component) IV every 6 to 12 hours

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REFERENCES

  1. de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549.
  2. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med 1998; 129:862.
  3. Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993; 328:21.
  4. Attia J, Hatala R, Cook DJ, Wong JG. The rational clinical examination. Does this adult patient have acute meningitis? JAMA 1999; 282:175.
  5. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
  6. Gopal AK, Whitehouse JD, Simel DL, Corey GR. Cranial computed tomography before lumbar puncture: a prospective clinical evaluation. Arch Intern Med 1999; 159:2681.
  7. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001; 345:1727.
  8. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004; 351:1849.
  9. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment of bacterial meningitis. Lancet 2012; 380:1693.
  10. Brouwer MC, Thwaites GE, Tunkel AR, van de Beek D. Dilemmas in the diagnosis of acute community-acquired bacterial meningitis. Lancet 2012; 380:1684.
  11. Proulx N, Fréchette D, Toye B, et al. Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis. QJM 2005; 98:291.
  12. Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 2006; 34:2758.
  13. Lepur D, Barsić B. Community-acquired bacterial meningitis in adults: antibiotic timing in disease course and outcome. Infection 2007; 35:225.
  14. Sinner SW, Tunkel AR. Antimicrobial agents in the treatment of bacterial meningitis. Infect Dis Clin North Am 2004; 18:581.
  15. Finberg RW, Moellering RC, Tally FP, et al. The importance of bactericidal drugs: future directions in infectious disease. Clin Infect Dis 2004; 39:1314.
  16. Scheld WM, Sande MA. Bactericidal versus bacteriostatic antibiotic therapy of experimental pneumococcal meningitis in rabbits. J Clin Invest 1983; 71:411.
  17. Cherubin CE, Marr JS, Sierra MF, Becker S. Listeria and gram-negative bacillary meningitis in New York City, 1972-1979. Frequent causes of meningitis in adults. Am J Med 1981; 71:199.
  18. Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 2010; 23:858.
  19. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010; 23:467.
  20. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011; 364:2016.
  21. Schaad UB, Suter S, Gianella-Borradori A, et al. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med 1990; 322:141.
  22. Lebel MH, Hoyt MJ, McCracken GH Jr. Comparative efficacy of ceftriaxone and cefuroxime for treatment of bacterial meningitis. J Pediatr 1989; 114:1049.
  23. Peltola H, Anttila M, Renkonen OV. Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group. Lancet 1989; 1:1281.
  24. Cherubin CE, Appleman MD, Heseltine PN, et al. Epidemiological spectrum and current treatment of listeriosis. Rev Infect Dis 1991; 13:1108.
  25. París MM, Ramilo O, McCracken GH Jr. Management of meningitis caused by penicillin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 1995; 39:2171.
  26. Cherubin CE, Eng RH, Norrby R, et al. Penetration of newer cephalosporins into cerebrospinal fluid. Rev Infect Dis 1989; 11:526.
  27. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. N Engl J Med 2006; 354:44.
  28. Spangler SK, Jacobs MR, Appelbaum PC. Susceptibilities of 177 penicillin-susceptible and -resistant pneumococci to FK 037, cefpirome, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, biapenem, meropenem, and vancomycin. Antimicrob Agents Chemother 1994; 38:898.
  29. Sáez-Llorens X, O'Ryan M. Cefepime in the empiric treatment of meningitis in children. Pediatr Infect Dis J 2001; 20:356.
  30. Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 1997; 337:970.
  31. Clauss HE, Lorber B. Central nervous system infection with Listeria monocytogenes. Curr Infect Dis Rep 2008; 10:300.
  32. Friedland IR, Paris M, Ehrett S, et al. Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1993; 37:1630.
  33. Cottagnoud P, Acosta F, Cottagnoud M, Täuber MG. Gemifloxacin is efficacious against penicillin-resistant and quinolone-resistant pneumococci in experimental meningitis. Antimicrob Agents Chemother 2002; 46:1607.
  34. Sáez-Llorens X, McCoig C, Feris JM, et al. Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin. Pediatr Infect Dis J 2002; 21:14.
  35. Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med 1997; 336:708.
  36. van de Beek D, Drake JM, Tunkel AR. Nosocomial bacterial meningitis. N Engl J Med 2010; 362:146.
  37. Korinek AM, Baugnon T, Golmard JL, et al. Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis. Neurosurgery 2006; 59:126.
  38. The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy. Br J Neurosurg 2000; 14:7.
  39. Zarrouk V, Vassor I, Bert F, et al. Evaluation of the management of postoperative aseptic meningitis. Clin Infect Dis 2007; 44:1555.
  40. Kim BN, Peleg AY, Lodise TP, et al. Management of meningitis due to antibiotic-resistant Acinetobacter species. Lancet Infect Dis 2009; 9:245.
  41. Oates-Whitehead RM, Maconochie I, Baumer H, Stewart ME. Fluid therapy for acute bacterial meningitis. Cochrane Database Syst Rev 2005; :CD004786.
  42. Kramer AH, Bleck TP. Neurocritical care of patients with central nervous system infections. Curr Infect Dis Rep 2007; 9:308.
  43. Ajdukiewicz KM, Cartwright KE, Scarborough M, et al. Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial. Lancet Infect Dis 2011; 11:293.
  44. Lindvall P, Ahlm C, Ericsson M, et al. Reducing intracranial pressure may increase survival among patients with bacterial meningitis. Clin Infect Dis 2004; 38:384.
  45. Glimåker M, Johansson B, Halldorsdottir H, et al. Neuro-intensive treatment targeting intracranial hypertension improves outcome in severe bacterial meningitis: an intervention-control study. PLoS One 2014; 9:e91976.
  46. Mourvillier B, Tubach F, van de Beek D, et al. Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA 2013; 310:2174.
  47. Kutleša M, Lepur D, Baršić B. Therapeutic hypothermia for adult community-acquired bacterial meningitis-historical control study. Clin Neurol Neurosurg 2014; 123:181.
  48. Durack DT, Spanos A. End-of-treatment spinal tap in bacterial meningitis. Is it worthwhile? JAMA 1982; 248:75.
  49. Ziai WC, Lewin JJ 3rd. Improving the role of intraventricular antimicrobial agents in the management of meningitis. Curr Opin Neurol 2009; 22:277.
  50. Kilpi T, Anttila M, Kallio MJ, Peltola H. Length of prediagnostic history related to the course and sequelae of childhood bacterial meningitis. Pediatr Infect Dis J 1993; 12:184.
  51. Fernandes D, Gonçalves-Pereira J, Janeiro S, et al. Acute bacterial meningitis in the intensive care unit and risk factors for adverse clinical outcomes: retrospective study. J Crit Care 2014; 29:347.
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