Treatment of bacterial meningitis caused by specific pathogens in adults

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

APPROACH TO THERAPY — There are a number of general principles of antimicrobial therapy in patients with bacterial meningitis. The most important initial issues are avoidance of delay in administering therapy and the choice of drug regimen. Intravenous antimicrobial therapy should be initiated immediately after the performance of the lumbar puncture (LP) or, if a computed tomography scan of the head is indicated to be performed before LP, immediately after blood cultures are obtained. Adjunctive dexamethasone should be given shortly before or at the same time as the first dose of antimicrobials, when indicated. General principles of initial therapy and selection of empiric antibiotic therapy are reviewed in detail separately. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'General principles of therapy'.)

THERAPY FOR SPECIFIC PATHOGENS — The prevalence of various pathogens in bacterial meningitis varies by region of the world. Among adults with bacterial meningitis in the United States, S. pneumoniae and Neisseria meningitidis are the most common infecting organisms [3,5,6]. (See "Epidemiology of community-acquired bacterial meningitis in adults", section on 'Incidence'.)

The following treatment recommendations are in agreement with the 2004 Infectious Diseases Society of America (IDSA) guidelines, with some updates, for the management of bacterial meningitis and the 2017 IDSA guidelines for health care-associated ventriculitis and meningitis [7,8]. Since there are limited randomized trials regarding the therapy of specific causes of bacterial meningitis, treatment recommendations are based upon in vitro susceptibility and pharmacodynamic data as well as accumulated clinical experience.

Directed therapy against a specific organism is recommended when the clinical presentation and results of the cerebrospinal fluid (CSF) Gram stain are unequivocal (table 1C) or the cultures are already positive (table 1A) [7-9]. If, on the other hand, empiric therapy is begun, the regimen should be adjusted, if necessary, once the culture results are available (table 1A). For the targeted regimen, agents should penetrate into the CSF to attain adequate concentrations to kill the meningeal pathogen rapidly, and the patient's isolate should demonstrate in vitro susceptibility [8]. Recommended dosages for use in patients with normal renal and hepatic function are shown in the table (table 1B).

The duration of therapy for meningitis in adults has not been subjected to rigorous trials in the United States or other developed countries. The recommendations in the following sections reflect general consensus and are fairly conservative. However, a longer course may be warranted when complicating features are present or the clinical response is unusually slow. On the other hand, shorter courses (eg, single doses of depot chloramphenicol or conventional ceftriaxone) have been successful in the management of epidemic meningococcal meningitis in resource-limited countries.

Streptococcus pneumoniae — S. pneumoniae is the most common cause of meningitis in adults, particularly in older adults [3,6]. (See "Epidemiology of community-acquired bacterial meningitis in adults", section on 'Incidence'.)

In the past, the conventional approach to the treatment of pneumococcal meningitis was the administration of penicillin alone for two weeks at a dose of four million units intravenously (IV) every four hours in patients with normal renal function. Good results were also obtained with a third-generation cephalosporin, such as ceftriaxone or cefotaxime [7].

However, the widespread emergence of penicillin-resistant pneumococcus has made penicillin an inappropriate empiric therapy without proof of in vitro susceptibility. Although many third-generation cephalosporins have good in vitro activity against strains of pneumococcus that have intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC] 0.12 to 1.0 mcg/mL) according to the cutoffs used prior to 2008, reports have raised the possibility of clinical failure when cephalosporin resistance coexists with penicillin resistance (table 2) [10]. In 2008, the Clinical and Laboratory Standards Institute removed the "intermediate" susceptibility category (MIC 0.12 to 1 mcg/mL) for the penicillin breakpoints of meningeal isolates of S. pneumoniae, such that all meningeal isolates with an MIC ≥0.12 are considered resistant. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics".)

First-line regimens — Initial empiric therapy of S. pneumoniae in patients with normal renal function includes vancomycin (15 to 20 mg/kg IV every 8 to 12 hours) plus either ceftriaxone (2 g IV every 12 hours) or cefotaxime (2 g IV every 4 to 6 hours) [7]. In countries where the incidence of ceftriaxone-resistant pneumococcus (≥1.0 mcg/mL) is <1 percent, it is appropriate to use ceftriaxone monotherapy for empiric coverage, although some authorities would recommend continuation of dual therapy pending in vitro susceptibility testing [11].

In patients with isolates that are susceptible to penicillin (MIC ≤0.06 mcg/mL), penicillin G (4 million units IV every four hours) or ampicillin can be used instead of a third-generation cephalosporin, although it is also reasonable to continue therapy with a third-generation cephalosporin given the excellent efficacy, convenient dosing, and affordability of these agents.

If the isolate is resistant to penicillin (MIC ≥0.12 mcg/mL) but is susceptible to third-generation cephalosporins (MIC <1.0 mcg/mL), ceftriaxone (2 g IV every 12 hours) or cefotaxime (2 g IV every 4 to 6 hours) is the preferred drug. Although some retrospective studies have advocated cephalosporin monotherapy for organisms with MICs up to 1.0 mcg/mL for cefotaxime or ceftriaxone [12,13], it seems more prudent to use the lower breakpoint (ie, less than 1.0 mcg/mL) [7]. Vancomycin, in combination with a third-generation cephalosporin, should be continued if there is penicillin resistance (MIC ≥0.12 mcg/mL) and an MIC ≥1.0 mcg/mL to third-generation cephalosporins (table 1A)

Vancomycin is erratic in its penetration into the CSF and may be ineffective as monotherapy in pneumococcal meningitis. Nevertheless, it is recommended that vancomycin (15 to 20 mg/kg IV every 8 to 12 hours if renal function is normal) be given with ceftriaxone or cefotaxime in the initial treatment of pneumococcal meningitis until susceptibility results are available [7]. The vancomycin dose should not exceed 2 g per dose or a total daily dose of 60 mg/kg. Serum trough concentrations of vancomycin should range from 15 to 20 mcg/mL. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)

As noted above, early IV administration of glucocorticoids (usually dexamethasone) has been evaluated as adjunctive therapy in an attempt to diminish the rate of hearing loss and other neurologic complications as well as mortality in adults patients with pneumococcal meningitis in high-income countries. Specific recommendations regarding the use of dexamethasone as adjunctive therapy for bacterial meningitis are presented separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)

In patients receiving adjunctive dexamethasone, the diminished CSF inflammatory response after dexamethasone administration may reduce CSF vancomycin penetration and delay CSF sterilization. However, in a study of 14 patients, the administration of IV vancomycin (15 mg/kg loading dose, followed by a continuous infusion of 60 mg/kg per day) led to mean serum and CSF vancomycin concentrations of 25.5 and 7.9 mcg/mL, respectively, indicating that significant CSF concentrations can be attained with appropriate dosing [14]. If dexamethasone is given, some experts recommend empiric rifampin (600 mg orally or IV once daily) in addition to vancomycin, since its CSF penetration is unaffected by dexamethasone and it is synergistic with ceftriaxone against beta-lactam-resistant S. pneumoniae [15]. If susceptibility studies of the isolated pneumococcus show intermediate susceptibility or resistance (MIC ≥1 mcg/mL) to ceftriaxone and cefotaxime, rifampin may be continued or added if the organism is susceptible to rifampin [7].

The duration of antimicrobial therapy for pneumococcal meningitis is usually 10 to 14 days.

Alternative agents — Chloramphenicol (1.5 g IV every six hours) has been used in patients with pneumococcal meningitis who are allergic to penicillin and cephalosporins. However, many penicillin-resistant strains are also somewhat resistant to chloramphenicol killing (despite in vitro tests that show inhibition), and treatment failures of meningitis due to penicillin-resistant S. pneumoniae have occurred when chloramphenicol is used. One series evaluated 25 children with pneumococcal meningitis who had in vitro sensitivity to and were treated with chloramphenicol; 20 (80 percent) had an unsatisfactory outcome [16].

The older fluoroquinolones have generally lacked sufficient activity against S. pneumoniae to warrant their use in the therapy of pneumococcal meningitis, but the newer fluoroquinolones, such as moxifloxacin, have shown excellent in vitro activity and efficacy in animal models of pneumococcal meningitis [17,18]. However, clinical data are sparse. One fluoroquinolone, trovafloxacin, was compared with ceftriaxone, with or without vancomycin, in a multicenter randomized trial of 311 children with bacterial meningitis in which 27 percent of cases had pneumococcal meningitis [19]. The overall efficacy (CSF sterilization and clinical success) of both treatment groups was similar. Trovafloxacin is no longer utilized because of its association with serious liver toxicity, although these results suggest the potential usefulness of newer fluoroquinolones in the treatment of bacterial meningitis.

Although there are not sufficient data to recommend fluoroquinolones as part of the routine treatment of pneumococcal meningitis, this class is sometimes used in patients with serious allergies to cephalosporins or vancomycin. If it is not possible to use cephalosporins or vancomycin, moxifloxacin is probably the best choice as a second agent given its excellent in vitro activity and CSF penetration. For example, in a patient with a serious cephalosporin allergy, moxifloxacin should be used in combination with vancomycin. Conversely, in a patient with a serious vancomycin allergy, moxifloxacin should be used in combination with ceftriaxone or cefotaxime, if the cefotaxime or ceftriaxone MIC is ≥1 mcg/mL.

Neisseria meningitidis — Third-generation cephalosporins, such as cefotaxime or ceftriaxone, should be used to treat suspected (eg, Gram stain with gram-negative diplococci) or culture-proven meningococcal infection prior to susceptibility results [7]. If the organism is proven to be penicillin susceptible, the treatment can then be switched to penicillin G or ampicillin. The treatment of meningococcal meningitis is discussed in detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Treatment of meningitis and sepsis'.)

A seven-day duration of therapy is adequate for meningococcal meningitis. However, there may still be nasopharyngeal colonization with the infecting strain. As a result, the index patient may need to take an agent that eradicates colonization (eg, rifampin or ciprofloxacin) to avoid transmission to others. This is discussed in detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Antimicrobial chemoprophylaxis'.)

Droplet precautions should be used for 24 hours after starting effective antimicrobial therapy in patients with suspected or confirmed N. meningitidis infection [7]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Droplet precautions'.)

Haemophilus influenzae — A third-generation cephalosporin (either cefotaxime or ceftriaxone) is the drug of choice for H. influenzae meningitis in adults. We recommend ceftriaxone (2 g IV twice daily) or cefotaxime (2 g IV every four to six hours) for at least seven days. If the organism does not produce beta-lactamase, ampicillin is also an effective therapy.

The best data supporting this recommendation come from randomized trials in children. One such trial compared ceftriaxone with cefuroxime (a second-generation cephalosporin with good CSF penetration) in children with bacterial meningitis, which was due to H. influenzae in the majority of cases [20]. Ceftriaxone was significantly more likely to sterilize the CSF at 24 hours (100 versus 90 percent) and was associated with a lesser likelihood of hearing impairment at the conclusion of therapy (11 versus 18 percent). Virtually identical findings were noted in a second randomized trial comparing these two drugs [21].

Pharyngeal colonization persists after curative therapy and may require a short course of rifampin if there are children in the household at risk for invasive Haemophilus infection. This is a rare situation because conjugate vaccines for H. influenzae type b are widely used and highly effective. (See 'Chemoprophylaxis' below.)

Listeria monocytogenes — Listeria, a gram-positive bacillus, is an important cause of bacteremia and meningitis, particularly in older adults (in whom it accounts for approximately 20 percent of cases [22]), pregnant women [23], and patients with impaired cell-mediated immunity [24]. When Listeria invades the bloodstream, it has a tropism for the CNS [25]. It is more likely than other causes of meningitis to cause small brain abscesses, especially in the midbrain and brainstem [26]. These lesions can account for many of the long-term sequelae of listerial meningitis. (See "Clinical manifestations and diagnosis of Listeria monocytogenes infection".)

Drugs of choice — Listeria has traditionally been treated with ampicillin (2 g every four hours) or penicillin G (4 million units every four hours), since resistance to these drugs is rare [27]. Gentamicin is added for synergy, despite its poor penetration into the CSF [28]. The gentamicin dose (5 mg/kg per day in a person with normal renal function) is divided into three equal doses. Gentamicin has not been studied as a synergistic drug with any therapy other than the penicillin or ampicillin. Adjunctive dexamethasone should be avoided because it has been associated with higher mortality [29]. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults", section on 'Developed regions'.)

Ampicillin is given for at least 21 days in patients with Listeria meningitis; gentamicin is given until the patient improves (for at least the first week) or, in poor responders, for up to three weeks if there are no signs of nephrotoxicity or ototoxicity. Patients with cerebritis or rhombencephalitis should be treated for at least six weeks. (See "Treatment and prevention of Listeria monocytogenes infection".)

Alternative regimens — If a penicillin- or cephalosporin-allergic patient cannot be desensitized to ampicillin, an alternative therapy is trimethoprim-sulfamethoxazole (TMP-SMX) [7,30].

A more detailed discussion of alternative regimens for the treatment of CNS listeriosis is found in a separate topic review. (See "Treatment and prevention of Listeria monocytogenes infection", section on 'Alternatives to ampicillin or penicillin'.)

Gram-negative bacilli — Aerobic gram-negative bacilli, such as Escherichia coli and Klebsiella species, are rare causes of community-acquired meningitis in adults but are more commonly a cause of health care-associated infections, mostly following neurosurgical procedures. Gram negative bacillary meningitis can also be seen as part of the disseminated Strongyloides stercoralis infection in immunosuppressed individuals [31]. (See "Epidemiology of community-acquired bacterial meningitis in adults", section on 'Risk factors'.)

When culture results indicate a gram-negative bacillus, the regimen should be tailored to results of in vitro susceptibility testing, using agents that have good CNS penetration [8]. Antibiotic choices are outlined below based on susceptibility. The minimum duration of therapy is 10 to 14 days, although some experts prefer to treat for 21 days.

●For Enterobacterales (such as Escherichia coli, Klebsiella pneumoniae) or other gram-negative bacilli that are susceptible to third-generation cephalosporins – We suggest cefotaxime (2 g IV every four to six hours) or ceftriaxone (2 g IV every 12 hours).

●For Enterobacterales known to have inducible beta-lactamase production (eg, Enterobacter) – We suggest meropenem (2 g IV every eight hours). Trimethoprim-sulfamethoxazole (15 to 20 mg/kg per day divided every six to eight hours based upon the trimethoprim component) is another option.

●For susceptible P. aeruginosa isolates – We suggest a single active antipseudomonal agent, preferably ceftazidime (2 g IV every eight hours) or cefepime (2 g IV every eight hours). Other options include meropenem (2 g IV every eight hours), ciprofloxacin (400 mg IV every eight hours), or aztreonam (2 g IV every 6 hours). The addition of an aminoglycoside to any of these agents is not necessary.

●For organisms resistant to cephalosporins but susceptible to other agents (eg, if they produce an extended-spectrum beta-lactamase) – We suggest meropenem (2 g IV every eight hours) if the organism is susceptible. Other alternatives such as ciprofloxacin (400mg IV every eight hours), trimethoprim-sulfamethoxazole (15 to 20 mg/kg per day divided every six to eight hours based upon the trimethoprim component), or aztreonam (2 g IV every 6 hours) can be chosen based upon susceptibility testing [32].

●For carbapenem-resistant organisms – These organisms are typically resistant to multiple agents in addition to carbapenems, and consultation with an expert in infectious diseases is recommended.

Potential options that may have activity against carbapenem-resistant organisms, depending on the organism, include ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, meropenem-vaborbactam, tigecycline, and (where the parenteral form is available) fosfomycin. Clinical data supporting use of these agents for meningitis or ventriculitis are limited to case series, and CSF levels achieved are not well studied, but they are generally the only active agents for such infections. Intrathecal or intraventricular antimicrobial therapy may be warranted as adjunctive therapy in cases of highly resistant gram-negative infection. In particular, if a polymyxin is warranted for a carbapenem-resistant meningitis or ventriculitis, we give colistin (usually formulated as colistimethate sodium) through the intrathecal or intraventricular route because it does not achieve sufficient CSF levels. (See "Health care-associated meningitis and ventriculitis in adults: Treatment and prognosis", section on 'Intrathecal and intraventricular therapy'.)

Antibiotic selection for specific carbapenem-resistant organisms is discussed elsewhere.

•(See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment'.)

•(See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Management of multidrug-resistant organisms'.)

•(See "Acinetobacter infection: Treatment and prevention", section on 'Meningitis'.)

Overall, clinical data supporting these choices are limited, particularly for health care-associated gram-negative infections. Since use of bacteriostatic antibiotics is associated with poor clinical outcome [33], agents with bactericidal activity are preferred. Bactericidal activity in the CSF is affected by the penetration, concentration, and intrinsic activity of the antibiotic, but the minimum concentration of an antibiotic in the CSF needed for bactericidal activity is controversial [34]. We agree with other experts that antibiotic regimens should achieve CSF levels 10 or more times above the minimum bactericidal concentration (MBC) of the organism [35].

Broad-spectrum cephalosporins, such as ceftriaxone, cefotaxime, ceftazidime, and cefepime, are the treatment of choice for susceptible gram-negative bacillary meningitis primarily because they have good activity against these organisms and penetrate well into the CSF [34,36]. Small clinical series, mainly in children, have described clinical cure rates of 70 to 90 percent for treatment of susceptible gram-negative bacilli with these cephalosporins [37-39]. Cefpirome is a broad-spectrum cephalosporin that is not available in the United States or Australia but may be used in other countries; it reaches CSF levels sufficient to treat susceptible gram-negative pathogens, and its spectrum of activity includes Pseudomonas aeruginosa [40,41].

Carbapenems also penetrate well into the CSF [42,43] but because of antimicrobial stewardship concerns, are generally reserved for infections when cephalosporins cannot be used. The carbapenems have overall good efficacy, comparable to that of the cephalosporins, in the treatment of meningitis in both children and adults [42,44]. Of the carbapenems, we generally prefer meropenem. Use of imipenem-cilastatin is limited by potential for seizures; in one study of pediatric patients with meningitis, 33 percent developed seizure activity following imipenem-cilastatin administration [45]. Seizures have also been reported with ertapenem when used in the setting of CNS disorders [46]. Moreover, ertapenem has a narrower spectrum than either meropenem or imipenem and is not active against P. aeruginosa or Acinetobacter spp.

As above, alternative options for susceptible isolates in patients who cannot use cephalosporins or carbapenems include aztreonam, ciprofloxacin, and TMP-SMX. Aztreonam has excellent CSF penetration into either inflamed or uninflamed meninges and reaches CSF levels adequate for treatment of meningitis caused by most gram-negative bacilli [47-50]. Small clinical series have described good outcomes with aztreonam used for various gram-negative pathogens. Ciprofloxacin is highly active in vitro against most susceptible gram-negative organisms that cause meningitis and high cure rates (80 to 90 percent) have been reported in small series and case reports [51-54]. However, because it has variable penetration into the CSF [51], we reserve it for when first-line agents cannot be used. Moxifloxacin reportedly achieves high CSF concentrations based on data on tuberculous meningitis; however, there is limited clinical evidence on moxifloxacin use for gram-negative bacillary meningitis [55-57]. TMP-SMX penetrates well into the CSF and has bactericidal activity in vitro against numerous gram-negative bacilli that cause meningitis [36,58]. However, consistent bactericidal activity has not been shown for some organisms, including Klebsiella and Providencia, and treatment failures have been reported [58].

Staphylococcus aureus — Staphylococcus aureus meningitis is typically associated with penetrating head trauma or neurosurgery [7]. Given substantial rates of methicillin-resistant S. aureus (MRSA), vancomycin (table 3) should be used as initial therapy when S. aureus is suspected or proven (table 4) [7,59]. If susceptibility testing reveals methicillin-susceptible S. aureus (MSSA), therapy should be changed to nafcillin (2 g IV every four hours) or oxacillin (2 g IV every four hours) (table 1B). Cefazolin should not be used for MSSA meningitis because it does not adequately penetrate into the CNS. If the organism is methicillin resistant, vancomycin should be continued.(See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)

The duration of therapy for S. aureus meningitis is 10 to 14 days; the precise duration is based on clinical response [59]. We treat for 14 days if vancomycin is administered. Removal of any CSF device, if present, is advised as retention is associated with higher mortality [60,61].

A significant drawback to vancomycin is its poor penetration into the CSF of approximately 1 and 5 percent with uninflamed and inflamed meninges, respectively [59,60,62,63]. Rifampin can be added to vancomycin at a dose of 600 mg orally or IV once daily or 300 to 450 mg twice daily because it achieves bactericidal concentrations in the cerebrospinal fluid regardless of meningeal inflammation [7,59,64], although there are few data to support this [65-67].

Although there are insufficient data regarding the efficacy of alternative agents for the treatment of meningitis caused by MRSA, linezolid, daptomycin (usually combined with rifampin), and TMP-SMX are reasonable options when vancomycin cannot be used or is ineffective. If the patient's MRSA isolate has a vancomycin MIC ≥1 mcg/mL and the patient has not had an appropriate clinical or microbiologic response, one of the alternative regimens can be used [8]. Linezolid has good CSF penetration of approximately 66 percent [59,68-70], and TMP-SMX has moderately good CSF penetration (13 to 53 percent for TMP and 17 to 63 percent for SMX) [58,59,71]. In a rabbit meningitis model, CSF daptomycin penetration was 5 to 6 percent and achieved adequate concentrations [59,72,73]. Based upon case reports and case series of patients with CNS infections caused by MRSA, alternatives to vancomycin include linezolid (600 mg IV twice daily) [74-77], TMP-SMX (5 mg/kg of the trimethoprim component IV every 8 to 12 hours) [58,59,78], and daptomycin (6 to 10 mg/kg IV once daily) usually combined with rifampin [79]. Ceftaroline has also been successfully used in two patients with MRSA meningitis, one with a ventriculoperitoneal shunt infection and the other with MRSA bacteremia and meningitis who was also treated with rifampicin during the initial two weeks of therapy [80-82]. Further studies are needed to establish the benefit of these agents for the treatment of meningitis.

Streptococcus agalactiae — S. agalactiae (group B streptococcus) is an uncommon cause of meningitis in adults. (See "Group B streptococcal infections in nonpregnant adults", section on 'Meningitis'.)

Initial therapy in patients with normal renal function includes ampicillin (2 g IV every four hours) or penicillin G (4 million units IV every four hours). A third-generation cephalosporin (eg, ceftriaxone or cefotaxime) is an alternative agent. For patients who cannot take penicillin or cephalosporins, vancomycin is suggested.

The duration of therapy is usually 14 to 21 days depending on clinical response.

REGIMENS IN PATIENTS WITH DRUG ALLERGIES — The approach to therapy in patients with antimicrobial allergies is challenging, given the importance of early initiation of therapy and the role of beta-lactam antimicrobial regimens in the therapy of bacterial meningitis. Although it is optimal to desensitize patients with a history of anaphylaxis 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 a beta-lactam is a necessary part of the regimen is based on the Gram stain and/or culture data, the latter of which can take several days to yield an organism.

For some bacteria, regimens that do not include a beta-lactam are sufficient but, for others, a beta-lactam is the optimal therapy. (See 'Alternative agents' above and 'Listeria monocytogenes' above.)

OUTPATIENT THERAPY — Continuing antimicrobial therapy as an outpatient may be appropriate for selected patients with bacterial meningitis. When complications occur, they usually happen within the first two to three days of therapy, although delayed cerebral injury (characterized by neurologic deterioration several days after presentation) has been reported in up to 4 percent of patients with bacterial meningitis [83]. Treatment outside of the hospital leads to decreased costs of hospitalization, decreased risk of development of nosocomial infections, and improved quality of life. Patients who are candidates for outpatient therapy should continue to receive intravenous antimicrobials for the entire course.

Caution is advised when determining appropriate candidates for outpatient therapy. The following criteria have been suggested as a guide for outpatient antimicrobial therapy in patients with bacterial meningitis [7,84]:

●Inpatient therapy for >6 days

●Absence of fever for at least 24 to 48 hours prior to initiation of outpatient therapy

●No significant neurologic dysfunction, focal findings, or seizure activity

●Clinical stability or improving infection

●Ability to take fluids by mouth

●Access to home health nursing for antimicrobial administration

●Reliable intravenous line and infusion device (if needed)

●Daily availability of a physician

●Established plan for physician visits, nurse visits, laboratory monitoring, and emergencies

●Patient and/or family compliance

●Safe environment with access to a telephone, utilities, food, and refrigerator

PREVENTION — Some forms of bacterial meningitis can be prevented by successful vaccination, and temporary protection can be provided in certain cases with chemoprophylaxis.

Vaccines — Among the major causes of bacterial meningitis in adults, vaccines are available for S. pneumoniae, N. meningitidis, and H. influenzae. Vaccines against S. pneumoniae and N. meningitidis are recommended for adults with a variety of risk factors for infection. Routine immunization of adults against H. influenzae type b is not recommended, except for those with prior splenectomy. The indications for vaccination are discussed separately. (See "Pneumococcal vaccination in adults" and "Meningococcal vaccination in children and adults".)

Chemoprophylaxis

Specific organisms — There is a role for postexposure chemoprophylaxis to prevent spread of meningococcal and Haemophilus meningitis under certain circumstances but not for pneumococcal disease. Indications for chemoprophylaxis are discussed in detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Antimicrobial chemoprophylaxis' and "Prevention of Haemophilus influenzae type b infection", section on 'Postexposure chemoprophylaxis'.)

Basilar skull fracture and cerebrospinal fluid leak — We recommend against using prophylactic antimicrobials in those with a basilar skull fracture and CSF leak because there is no evidence of benefit [8].

Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid (CSF) leaks and predispose patients to meningitis because of the potential for direct communication of bacteria in the upper respiratory tract with the central nervous system. In a large prospective study, CSF leak was seen in 65 (3 percent) of 2022 episodes of community-acquired bacterial meningitis [85]. CSF leak was most commonly due to ear-nose-throat surgery or remote head trauma, and it recurred despite surgical correction of the leak and vaccination efforts. However, most CSF leaks resolve spontaneously within one week of injury and without complications; in addition, most CSF leaks following trauma are not recognized [8,86]. A meta-analysis of five randomized trials and 17 other studies (involving over 2000 patients) of antibiotic prophylaxis following basilar skull fracture concluded that routine prophylaxis is not supported by the available evidence but noted that this evidence contains methodologic shortcomings and is therefore not conclusive [87].

Among patients with a basilar skull fracture and a CSF leak who develop meningitis, the median time between the injury and the onset of meningitis is 11 days [86,88]. In patients with a basilar skull fracture and a prolonged CSF leak (>7 days), an attempt should therefore be made to repair the leak [8]. (See "Skull fractures in adults", section on 'Basilar skull fracture'.)

Patients with a CSF leak (due to either basilar skull fracture or another cause) should receive pneumococcal vaccination [8,89]. The approach to vaccination in this setting is discussed in detail separately. (See "Pneumococcal vaccination in adults" and "Pneumococcal vaccination in adults", section on 'Approach to individuals at highest risk of pneumococcal disease'.)

Neurosurgery — Perioperative antimicrobial prophylaxis is indicated for patients undergoing neurosurgery, including procedures to place CSF shunts or other hardware [90]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery' and "Infections of cerebrospinal fluid shunts", section on 'Antibiotic prophylaxis'.)

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 5^th to 6^th 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 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

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

SUMMARY AND RECOMMENDATIONS

●General principles – There are a number of general principles of antimicrobial therapy in patients with bacterial meningitis. The most important initial issues are avoidance of delay in administering therapy and the choice of drug regimen. Antimicrobial therapy, along with adjunctive dexamethasone when indicated, should be initiated immediately after the performance of the lumbar puncture (LP) or, if a computed tomography scan of the head is indicated to be performed before LP, immediately after blood cultures are obtained. Adjunctive dexamethasone should be given shortly before or at the same time as the first dose of antimicrobials, when indicated. General principles of initial therapy and selection of empiric antibiotics are reviewed in detail separately. (See "Initial therapy and prognosis of community-acquired bacterial meningitis in adults", section on 'General principles of therapy'.)

●Treatment of meningitis due to Streptococcus pneumoniae – For the initial therapy of S. pneumoniae, we recommend vancomycin plus either ceftriaxone or cefotaxime rather than a third-generation cephalosporin alone (Grade 1B). In countries where the incidence of ceftriaxone-resistant pneumococcus is <1 percent, it is appropriate to use ceftriaxone monotherapy for empiric coverage although some authorities would recommend continuation of dual therapy until the results of in vitro susceptibility testing are available. (See 'First-line regimens' above.)

•If the isolate is proven to be susceptible to penicillin (minimum inhibitory concentration [MIC] ≤0.06 mcg/mL), monotherapy with penicillin G or ampicillin can be used. It is also reasonable to continue therapy with a third-generation cephalosporin alone instead of changing to penicillin or ampicillin, given the excellent efficacy, convenient dosing, and affordability of these agents.

•If the isolate is resistant to penicillin (MIC ≥0.12 mcg/mL), but susceptible to third-generation cephalosporins (MIC <1.0 mcg/mL), either cefotaxime or ceftriaxone should be used. However, if the isolate is resistant to both penicillin and third-generation cephalosporins, vancomycin plus a third-generation cephalosporin should be continued for the total duration of therapy (table 1A-B).

●Treatment of meningitis due N. meningitidis – For the initial therapy of N. meningitidis, we recommend a third-generation cephalosporin, such as cefotaxime or ceftriaxone, rather than penicillin, while awaiting susceptibility data (table 1B-C) (Grade 1C). If the isolate is susceptible to penicillin, either a third-generation cephalosporin or penicillin may be used to complete the course of therapy (table 1A-B). (See 'Neisseria meningitidis' above.)

●Treatment of other pathogens – The preferred regimens for other causes of bacterial meningitis are discussed above (table 1B-C and table 1A-B). (See 'Haemophilus influenzae' above and 'Listeria monocytogenes' above and 'Gram-negative bacilli' above and 'Staphylococcus aureus' above.)

●Considerations in patients with drug allergies – The optimal regimens for patients with severe drug allergies depends upon the organism. (See 'Alternative agents' above and 'Listeria monocytogenes' above.)

●Prevention of meningitis due to certain pathogens

•Certain interventions may reduce the risk of developing meningitis. As examples, vaccines against N. meningitidis and S. pneumoniae are recommended for adults at increased risk of these infections. In addition, there is a role for postexposure chemoprophylaxis to prevent spread of meningococcal and Haemophilus meningitis under certain circumstances. (See 'Chemoprophylaxis' above.)

•By contrast, for patients with a basilar skull fracture and a CSF leak, we recommend against using prophylactic antimicrobials (Grade 1B). If the CSF leak persists for >7 days, an attempt should be made to repair it. (See 'Basilar skull fracture and cerebrospinal fluid leak' above.)

Patients with a CSF leak (due to either basilar skull fracture or another cause) should receive pneumococcal vaccination. The approach to vaccination in this setting is discussed in detail separately. (See "Pneumococcal vaccination in adults" and "Pneumococcal vaccination in adults", section on 'Approach to individuals at highest risk of pneumococcal disease'.)