INTRODUCTION — Most cases of gram-negative bacillary meningitis occur in neonates or infants [1]. Gram-negative bacilli are the fifth most common cause of meningitis in infants, accounting for 3.6 percent of cases [2]. By contrast, gram-negative bacilli are an uncommon etiology of community-acquired meningitis in adults, but are a common cause of nosocomial meningitis, often occurring as a complication of head trauma and craniotomy [3].
The epidemiology, clinical features, and diagnosis of gram-negative bacillary meningitis will be reviewed here. Issues related to treatment are discussed separately. (See "Gram-negative bacillary meningitis: Treatment".)
BACKGROUND — Gram-negative meningitis was first recognized and reported in 1892. In the 1930s and 40s, cases were described resulting from abortion, genitourinary manipulation, and spinal anesthesia. In the following two decades, gram-negative bacillary meningitis was recognized as an occasional complication of injuries and neurosurgical procedures [4].
Subsequently, gram-negative bacillary meningitis has become an important cause of hospital-associated central nervous system (CNS) infection in adults, usually due to neurosurgery [5]. The likelihood of post-neurosurgery meningitis being due to gram-negative organisms is increased when antimicrobial prophylaxis, which predominantly provides gram-positive coverage, is given to prevent surgical site infection [6]. (See "Epidemiology of bacterial meningitis in adults", section on 'Health care-associated ventriculitis and meningitis' and "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery'.)
Although the incidence of gram-negative bacillary meningitis has increased as progressively more complex neurosurgical techniques and operations become more commonplace, this is still a rare infection. As an example, meningitis caused by Enterobacteriaceae accounted for 1.5 percent of all cases of acute bacterial meningitis in adults over a 20 year period in one Danish hospital [7]. In addition, of 1961 isolates of gram-negative bacilli from blood and/or cerebrospinal fluid (CSF) specimens over a two-year period at our institution, only 47 (2.4 percent) were from the CSF (unpublished data).
PATHOGENESIS — The major pathogenetic distinction in the development of meningitis due to gram-negative bacilli compared with organisms that more commonly produce meningitis, such as Streptococcus pneumoniae, is in the route of penetration into the CSF (see "Pathogenesis and pathophysiology of bacterial meningitis", section on 'Meningeal invasion'). The CSF is normally deficient in immunoglobulins and complement [8]. If bacterial contamination of the CSF occurs secondary to trauma, surgery or bacteremic seeding, there is an impairment in the ability of the CSF to effectively opsonize and phagocytose microorganisms [5,9]. The development of bacterial meningitis progresses through four interconnected phases [10]:
●Bacterial invasion of the host with subsequent infection of the CNS
●Bacterial multiplication and induction of inflammation in the subarachnoid and ventricular space
●Progression of inflammation with associated pathophysiologic alterations
●Development of neuronal damage.
Bacteria usually reach the CSF by bloodstream invasion, which follows nasopharyngeal colonization for organisms such as Neisseria meningitidis (see "Epidemiology of Neisseria meningitidis infection"). Nonhematogenous invasion of the CSF by bacteria occurs in situations of compromised integrity of the barriers surrounding the brain, such as neurosurgery, trauma, otitis media, mastoiditis, sinusitis and malformations [10].
EPIDEMIOLOGY — There are three patterns of meningitis caused by gram-negative bacilli [4]: neonatal meningitis, meningitis secondary to trauma or neurosurgery (usually nosocomial), and spontaneous gram-negative meningitis in adults. Among adults, approximately 60 percent of cases are spontaneous [4,11]. In a large, population-based observational study in the United States, the annual incidence of meningitis secondary to gram-negative bacilli remained remarkably stable (at 0.114 cases per 100,000 persons) from 1997 to 2010 [12]. This stable incidence was observed despite substantial declines in the rates of meningitis secondary to organisms such as Haemophilus influenzae, N. meningitidis, and S. pneumoniae as a result of vaccination.
Neonatal meningitis — In neonates and infants, gram-negative bacillary meningitis is usually associated with neural tube defects and urinary tract anomalies [2]. The majority of neonates with Escherichia coli meningitis are infected with strains of E. coli that have the K1 capsular polysaccharide [13]. This bacterial capsule like those of S. pneumoniae, N. meningitidis, and H. influenzae can assist the organism in evading host defenses. (See "Epidemiology of bacterial meningitis in adults" and "Microbiology and pathobiology of Neisseria meningitidis".)
Neonatal E. coli meningitis typically occurs soon after birth, and epidemiologic data suggest that such infections are usually acquired during or soon after delivery. The source of these organisms may be the vaginal flora of the mother or the hands of hospital personnel [14]. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)
Nosocomial meningitis — In a review of 493 episodes of bacterial meningitis in adults seen in the Boston area between 1962 and 1988, gram-negative organisms accounted for 33 percent of nosocomial infections compared with only 3 percent of community-acquired infections [15]. The major risk factors for nosocomial meningitis were neurosurgery or head trauma within the past month, a neurosurgical device, and a CSF leak, which accounted for 75 percent of cases.
Anything that causes disruption of the dura mater, such as neurosurgery or trauma, can predispose to meningeal infection. In several series, 36 to 50 percent of cases of gram-negative bacillary meningitis occurred after neurosurgical procedures [4,11,15,16]. Although many such cases are due to gram-positive organisms, particularly Staphylococci, gram-negative bacilli account for an important percentage. The likelihood of post-neurosurgery meningitis being due to gram-negative organisms is increased when antimicrobial prophylaxis, which predominantly provides gram-positive coverage, is given to prevent surgical site infection [6]. (See "Epidemiology of bacterial meningitis in adults", section on 'Health care-associated ventriculitis and meningitis' and "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery'.)
Neurosurgical procedures most likely to be complicated by gram-negative infection include [4,11]:
●Ventriculoperitoneal shunt insertion
●Ventriculostomy
●Repair of CSF fistula
●Ommaya or Rickham reservoir insertion
●Craniofacial resection
●Hypophysectomy
●Myelography
●Transsphenoidal surgery.
One review of meningitis complicating ventriculoperitoneal shunt insertion in children, found the incidence of meningitis to be 6.3 percent per insertion [17]. The major responsible organisms in this series were coagulase-negative staphylococci (53 percent), Staphylococcus aureus (13 percent), and Pseudomonas aeruginosa (8 percent). Rates of meningitis following transsphenoidal surgery range from 0.4 to 2 percent, usually due to CSF leakage from a dural tear complicating the procedure [18]. In a review of meningitis due to P. aeruginosa from the United Kingdom, many cases were in patients with an external ventricular device in place [19].
Cranial fractures can secondarily tear the dural mater and cause dural fistulas. Such fistulae sometimes produce visible leakage of CSF through the nose or ear but may also be clinically inapparent. Subsequent CSF leakage through these fistulae may be continuous, intermittent, occult or overt. Post-traumatic meningitis associated with a dural fistula can occur within days, weeks, months, or rarely even years after head injury [20]. The majority of late infections occurring out of hospital in neurosurgical patients months to years after operation are due to S. pneumoniae [21].
Both temporary epidural catheters [22] and tunneled intraspinal catheter systems [23] can be complicated by meningitis. The vast majority of such infections do not involve the meninges and are due to skin flora or S. aureus [22,23]. However, gram-negative bacilli can also cause these infections. In two large surveys of the outcome of epidural catheters and tunneled intraspinal catheters, 14 infected patients were identified, only three of whom had meningitis [22,23]. Gram-negative bacilli (in both cases P. aeruginosa) were responsible for two of these 14 infections. Rarely, gram-negative meningitis can arise from direct extension from an infective focus such as mastoiditis or chronic sinusitis [20] or from cochlear implants in children [24]. In a study of meningitis secondary to P. aeruginosa, the majority of which were post-neurosurgery, over half of patients had the organism isolated from another site prior to their episode, indicative of likely hospital-acquired spread from a non CNS site of prior infection or colonization [19].
Spontaneous gram-negative meningitis — Gram-negative organisms are an infrequent cause of community-acquired meningitis, accounting for only 9 of 253 episodes (3.6 percent) in a report from the United States [15], and 5 of 696 episodes (0.7 percent) in a report from the Netherlands [25], and 40 of 544 (7 percent) in a report from Spain [26].
Spontaneous nontraumatic gram-negative bacillary meningitis is usually community-acquired (two-thirds of cases in one series) and most frequently occurs in patients who are elderly or have underlying conditions, such as alcohol-induced cirrhosis, diabetes, malignancy, splenectomy, and glucocorticoid therapy [4,5,11,26,27]. Instrumentation of the urinary tract and urinary tract infection has been identified as portals of entry in cases of spontaneous meningitis [4,26].
MICROBIOLOGY — Among the gram-negative bacilli that cause meningitis, the most frequently implicated organisms are E. coli, Klebsiella pneumoniae, P. aeruginosa, and Acinetobacter. E. coli and Klebsiella account for more than 50 percent of cases of gram-negative bacillary meningitis in adults [4,26,28]. Infrequent pathogens include Citrobacter species, Serratia marcescens, Enterobacter species, and Proteus mirabilis.
As noted above, E. coli is the most common cause of gram-negative meningitis in infants [28]. As an example, E. coli caused 53 percent of cases of gram-negative bacillary meningitis in one series [2]. E. coli is also a common cause in adults of both spontaneous gram-negative bacillary meningitis [4] and of meningitis complicating neurosurgical procedures. One study highlighted the connection between E. coli meningitis and bowel perforation in patients with ventriculoperitoneal shunts [29].
Klebsiella meningitis occurs more often in elderly patients [28], and has been reported in patients with alcoholic liver disease, diabetes [30], and transfusion-dependent thalassemia major [31]. Coinfection can occur with other pathogens such as Enterobacter [16]. (See "Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection", section on 'Meningitis/brain abscess'.)
Among cases of gram-negative meningitis in Taiwan, Klebsiella was the most common pathogen [11]. In two series from Taiwan, K. pneumoniae and Klebsiella oxytoca accounted for 13 and 2.3 percent of culture-proven cases, respectively [32,33]. In addition, particularly in Taiwan and other countries in Southeast Asia, K. pneumoniae meningitis can represent a metastatic infection from community-acquired primary liver abscess. This relationship is discussed in detail elsewhere. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection' and "Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection", section on 'Meningitis/brain abscess'.)
Enterobacter meningitis occurs predominantly among neurosurgical patients. In a matched case-control study, external CSF drainage devices and isolation of Enterobacter spp from a non-CSF culture, were independent risk factors for Enterobacter meningitis [34].
Pseudomonas meningitis can occur as a rare complication of chronic cranial osteomyelitis and mastoiditis [28] or following trauma. S. marcescens may also occur after trauma but in one review was recognized as an important pathogen following surgery involving the ear canal [1].
Acinetobacter spp are an infrequent of cause of nosocomial meningitis and a rare cause of community-acquired meningitis. Risk factors for nosocomial meningitis include neurosurgical procedures, cerebrospinal fluid (CSF) leak, prior antibiotic therapy, and intracranial hemorrhage. Multidrug resistance is an increasing problem. (See "Acinetobacter infection: Treatment and prevention" and "Acinetobacter infection: Treatment and prevention", section on 'Meningitis'.)
Salmonella is a prevalent cause of meningitis among infants in Taiwan, and infection carries with it a high risk of neurologic complications [35].
Citrobacter diversus is an occasional cause of meningitis in newborn infants but is associated with substantial morbidity and mortality. One-third of neonates with meningitis due to Citrobacter die, and the majority of survivors have significant neurologic sequelae [36]. Brain abscess also occurs in up to three-quarters of cases of neonatal C. diversus meningitis [36,37]. Citrobacter freundii and C. diversus very rarely cause meningitis in adults [38]. In the scattered cases reported to date, predisposing conditions included trauma, alcoholism, and diabetes [38].
Ochrobactrum anthropi was found to be the cause of meningitis in three pediatric patients who had received pericardial dural grafts. Presumably these infections arose from contamination of the pericardial grafts during processing or freezing [39]. Other gram-negative bacilli which rarely cause meningitis include: Aeromonas, Moraxella, Flavobacterium, Bacteroides, Fusobacterium, Pasteurella [28], and Capnocytophaga [40]. Pasteurella multocida meningitis has been reported in infants who were licked by family pets [41,42].
CLINICAL FEATURES — Most cases of postoperative gram-negative meningitis occur 10 or more days after surgery (range 1 to 20 days) [4]. The time interval is similar in infants, with a mean of 5.5 days following surgery (range 1 to 15 days) [2]. However, meningitis following transsphenoidal surgery appears to develop more rapidly with a mean of 2.8 days (range, two to four days) [18]. Depending upon the etiologic organism, this interval may be quite variable. As an example, the period between neurosurgery and the onset of K. oxytoca meningitis ranged from as short as two days to 40 months in one study [33].
Fever and signs of CNS infection such as altered mental status, seizures, or nuchal rigidity are present in most patients with gram-negative meningitis and can be dramatic [5]. However, gram-negative meningitis following neurosurgical procedures may be subtle and insidious in onset [4,5]. Signs can be obscured by the use of corticosteroid therapy for the control of intracranial hypertension. The diagnosis can also be missed because other post-operative sources or complications may be deemed responsible for fever or neurologic abnormalities.
Furthermore, in elderly patients with underlying medical illness, such as diabetes mellitus and cardiac disease, confusional state may be the only presenting feature [43]. Fever is usually present in this group, but headache and meningeal signs may be absent. In a study from Barcelona, clinical characteristics associated with spontaneous gram-negative bacillary meningitis (compared with other etiologies) were atypical and included absence of rash and hypotension [26].
Fever, irritability, seizures, lethargy and poor feeding are the usual clinical clues to the presence of meningitis in infants, including infection caused by gram-negative bacilli [2]. Bulging of the fontanelle may suggest the diagnosis of meningitis in such children.
Septic shock is a serious complication of gram-negative meningitis and is associated with a high mortality [11]. Septic shock appears to be more common in cases of spontaneous meningitis [11] for reasons which are not clear.
Gram-negative meningitis commonly is accompanied by bacteremia.
●In one series of 30 adults with gram-negative meningitis following neurosurgery or arising spontaneously, 43 percent of patients were bacteremic [4]. The mortality rate was 53 percent in the bacteremic patients compared to 12 percent among those without accompanying bacteremia.
●In another study of gram-negative bacillary meningitis in neonates and infants over a 21-year period, bacteremia was present in 55 percent [2].
●A third survey of 77 adults, the majority of whom had spontaneous gram-negative meningitis, identified a bacteremia in 58 percent [11].
●Bacteremia was not associated with a higher mortality in these latter two studies [2,11].
Outcome of infection — The mortality due to gram-negative bacillary meningitis in adults and children has ranged from 40 to 80 percent [9,26,32]. Patients with spontaneous meningitis typically have a more fulminant course with a higher prevalence of bacteremia, shock, and death [4,32]. As an example, spontaneous meningitis due to gram-negative bacilli had an in-hospital mortality rate of 53 percent in a cohort of Spanish patients [26]. This mortality rate was twenty times higher than the mortality rate among patients infected with N. meningitidis.
In another study, 28 percent of patients died despite treatment with appropriate antibiotics, and the mortality rate was overall higher in patients with spontaneous gram-negative bacillary meningitis [11].
By contrast, in a large pediatric case series, the mortality rate was higher in gram-negative bacillary meningitis which followed surgery than in those cases which arose spontaneously [2]. The case fatality rate in the former group was 27 percent and almost 50 percent lower in the latter patients.
Important independent prognostic factors in predicting the outcome of gram-negative bacillary meningitis are use of appropriate antimicrobial therapy and the presence of septic shock [11]. In virtually all studies, one of the most important factors predicting survival is the state of consciousness at the time of admission [44]. In a large series from Massachusetts, patients who were unresponsive or responsive only to pain had a 49 percent mortality rate compared to 16 percent for those who were alert or only lethargic (P = 0.001) [15].
The mortality rate for these infections, even for pathogens such as K. pneumoniae and P. aeruginosa, may be declining. The mortality rate for gram-negative meningitis due to these two pathogens was 91 and 84 percent, respectively, more than a decade ago [28] compared to 56 and 36 percent, respectively, in a more contemporary series [11]. Age over 60 years, diabetes mellitus and severe neurologic deficits have been identified as poor prognostic factors in K. pneumoniae meningitis [32]. E. coli is the gram-negative bacillus most associated with death in a few different series [4,11,28]. However, the introduction of third generation cephalosporins has been postulated to account for the decrease in mortality rate among adults with gram-negative bacillary meningitis [44].
A population-based observational study suggested that the fiscal ramifications of gram-negative meningitis are substantial [12]. The average length of stay for such infections ranged from 12.5 to 17.2 days.
Complications of meningitis — Possible complications and sequelae from gram-negative bacillary meningitis are numerous, especially in infants and children, just like for meningitis due to other organisms. Seizures occurring before or some time during hospitalization have been predictive of mortality or neurologic sequelae in several studies [44]. In addition, delayed sterilization of CSF cultures following commencement of therapy for meningitis has been associated with neurologic sequelae including hearing loss [44] (see "Neurologic complications of bacterial meningitis in adults" and "Bacterial meningitis in children: Neurologic complications"). Complications include [2,11,45]:
●Ventriculitis
●Subdural effusion
●Brain abscess
●Syndrome of inappropriate antidiuretic hormone secretion
●Hydrocephalus
●Seizure disorder
●Spastic paralysis
●Mental retardation
●Hearing deficit
●Metastatic septic abscesses
●Acute disseminated encephalomyelitis
DIAGNOSIS — The diagnosis of gram-negative meningitis predominantly relies upon examination of the cerebrospinal fluid (CSF). Although not always diagnostic, CSF analysis remains the mainstay of early diagnosis. However, in patients who have undergone neurosurgical procedures, CSF protein, glucose, leukocyte counts and Gram stain do not reliably distinguish bacterial meningitis from nonbacterial processes [46-48].
Gram-negative meningitis rarely causes nosocomial infection in patients who have no history of head trauma, neurosurgical procedures, or immunosuppression. Thus, lumbar puncture performed to exclude nosocomial meningitis as the cause of mental status changes in a hospitalized patient without the preceding conditions has a low yield and rarely changes management [49]. The rarity of nosocomial meningitis was documented in a study done in a university hospital in Turkey [50]. Nosocomial meningitis occurred in 0.3 percent of all admissions and accounted for 0.5 percent of all hospital-acquired infections during an eight year period.
Cerebrospinal fluid analysis — The appropriate CSF analysis for patients with suspected bacterial meningitis includes protein, glucose, and cell count determinations and a Gram stain. CSF lactate levels can also be measured.
●Protein — CSF protein levels in gram-negative bacillary meningitis are usually but not invariably high. As an example, CSF protein ranged from 17 to 1900 mg/dL in one series, but in 62 percent of patients, levels exceeded 200 mg/dL [2]. In another review, mean protein levels ranged from 171 to 1123 mg/dL [28].
●Glucose — The CSF glucose concentration is usually low in gram-negative bacillary meningitis. CSF glucose ranged from 0 to 4.3 mmol/L (77 mg/dL) in one study; in 88 percent of patients, the value was <2.8 mmol/L (<50 mg/dL) [2]. The glucose level in another case series ranged from 32 to 72 mg/dL [46]. Nearly three quarters of patients with gram-negative meningitis have CSF to blood glucose concentration ratios less than 0.5 [2].
It appears that the mean CSF glucose is lower in cases of spontaneous gram-negative bacillary meningitis than in those cases that follow neurosurgical procedures, despite similar CSF protein and leukocyte counts [4]. The reasons for this observation remain obscure. It is important to note that CSF to serum glucose ratios of less than 50 percent are infrequent after uncomplicated neurosurgical procedures [5].
●Cell count — Patients with gram-negative bacillary meningitis typically have elevated leukocyte counts. CSF leukocyte counts range from 0 to 80,600 cells/mm3 in various reviews of gram-negative bacillary meningitis [2,33]; polymorphonuclear leukocytes (PMNs) account for more than 50 percent of these cells in 90 percent of cases. In one series, CSF white cell counts ranged from 3,174 to 12,495 cells/mm3 depending upon which species of gram-negative bacillus was isolated, and 57 to 80 percent of these cells consisted of PMNs [28].
In one pediatric case series, 6 percent of patients with gram-negative bacillary meningitis had normal CSF leukocyte counts [2]. Possible explanations for this infrequent and sometimes misleading finding include early timing of the lumbar puncture (LP) prior to the development of inflammation, failure of fluid obtained from the lumbar space to mirror the inflammatory changes present in ventricular fluid, or inability of young infants to mount an inflammatory response.
●Gram stain — The Gram stain of CSF is a crucial component of the diagnostic process. This test can be performed rapidly and may be a crucially important early clue to the diagnosis and appropriate early therapy. The Gram stain is positive for gram-negative bacilli in more than 50 percent of adult patients with a positive culture result [5]. In a large pediatric series, the CSF Gram stain was positive in 61 percent of patients with culture-proven gram-negative meningitis. The Gram stain was negative in all patients with a sterile CSF culture in this same case series [2]. However it is important to emphasize that false negative and false positive Gram stain results occasionally occur, and the properties and morphology of organisms seen on CSF Gram stain can be misinterpreted [5]. Thus, a negative or positive Gram stain should not be the sole basis for starting empiric therapy.
●Culture — CSF culture is essential to establish the etiology of meningitis and to determine the antimicrobial susceptibilities of the pathogen [5].
●Polymerase chain reaction — Polymerase chain reaction (PCR) amplification and sequencing of 16S ribosomal DNA can be performed on CSF for the diagnosis of meningitis. This method has shown a sensitivity of 86 percent and a specificity of 97 percent compared with culture. Importantly, this may be the diagnostic method of choice when antimicrobial therapy has already started or when cultures remain negative [51]. However, this technology is not available in most hospital laboratories and careful quality control measures are mandatory to prevent false positive results.
●Lactate — Measurement of the CSF lactate concentration is a rapid and inexpensive ancillary test, that occasionally may help support an early diagnosis of bacterial meningitis. Because lactate levels are not affected by the presence of red blood cells in the CSF, lactate testing can sometimes be helpful when the CSF is bloody or when routine tests give inconclusive results. In one study of CSF lactate levels in the diagnosis of bacterial meningitis following neurosurgery, lactate levels had a higher sensitivity and specificity compared with the CSF to blood glucose ratios (88 versus 77 percent and 98 versus 87 percent, respectively) [46]. Cases of proven bacterial meningitis in this study had mean CSF lactate levels of 7.8 mmol/L, while nonbacterial cases had mean lactate levels of 2.3 mmol/L.
Despite these data, testing for CSF lactate levels is not routinely ordered or performed in clinical practice because many clinicians perceive that this test does not offer substantially more information than standard CSF analysis for the diagnosis of bacterial meningitis. There have also been inconsistencies in the reported diagnostic power of the test [46].
Blood cultures — Blood cultures are also important for the isolation of a pathogen in patients with meningitis. Bacteremia is detectable in approximately 50 percent of adult patients with gram-negative bacillary meningitis, and bacteremic infection may precede clinical evidence of central nervous system (CNS) infection [5]. In fact, bacteremia is an important prognostic feature of gram-negative bacillary meningitis; patients with accompanying bloodstream infection have mortality rates up to five times higher than non-bacteremic patients in some studies [4].
Computed tomographic scanning — Performing cranial computed tomographic (CT) scanning has become almost routine practice prior to LP in many medical centers, despite the fact that cerebral herniation is a very rare complication of LP even in patients with purulent meningitis [52]. A study has identified clinical criteria which are associated with a high risk of abnormal findings on CT [53]. These criteria include:
●Age over 60 years
●The presence of an immunocompromising condition or therapy
●History of CNS lesion
●History of seizure within previous week
●Abnormal level of consciousness
●Inability to answer two consecutive questions correctly, or to follow two consecutive commands
●Abnormal neurologic signs: gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, abnormal language
We support the use of a focused approach, in which CT is performed only in patients who have one or more clinical features (as mentioned above) consistent with an intracranial mass lesion, or increased CSF pressure. Patients who have undergone neurosurgical procedures are one important exception to this recommendation; all such patients should have a CT scan prior to LP.
When cranial imaging is indicated, it is prudent to obtain blood cultures and commence empiric antibiotic therapy before sending the patient for the CT since delay in administering antibiotics may have a deleterious effect on the outcome [54]. The LP should be immediately performed after the imaging, if no intracranial mass lesion is visualized [55]. A single dose of antibiotic administered before lumbar puncture is unlikely to influence the outcome of CSF culture results [56]. (See "Initial therapy and prognosis of bacterial meningitis in adults".)
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" and "Society guideline links: Bacterial meningitis in infants and children".)
SUMMARY
●Gram-negative bacilli are important pathogens in neonatal or infant meningitis and in nosocomial meningitis, often as a complication of trauma or neurosurgery. Despite the increasing use of complex neurosurgical techniques, nosocomial gram-negative bacillary meningitis remains a relatively uncommon infection. Spontaneous nontraumatic gram-negative bacillary meningitis in adults is rare, most frequently occurs in patients who are elderly or have other comorbidities, and is associated with urinary tract instrumentation. (See 'Introduction' above and 'Epidemiology' above.)
●Gram-negative bacilli can seed the cerebrospinal fluid secondary to bacteremia, trauma, and surgery. Subsequent meningitis can develop as a result of bacterial multiplication and induction of inflammation in the subarachnoid and ventricular space, followed by progression of inflammation and development of neuronal damage. (See 'Pathogenesis' above.)
●Escherichia coli and Klebsiella pneumoniae account for the majority of cases of gram-negative bacillary meningitis in adults. Other important, less frequent pathogens include Pseudomonas aeruginosa, Acinetobacter, Enterobacter, and Serratia. E. coli is the most common cause of gram-negative meningitis in infants. (See 'Microbiology' above.)
●Signs of meningitis, such as fever, altered mental status, seizures, and nuchal rigidity, are often dramatic in cases of spontaneous gram-negative bacillary meningitis, but may be insidious in onset or obscured by corticosteroid therapy in nosocomial cases. Confusional state may be the only presenting feature in elderly patients with underlying medical illness. Fever is usually present in this group, but headache and meningeal signs may be absent. In infants, fever, irritability, seizures, lethargy, poor feeding, and a bulging fontanelle are often clinical clues of meningitis. Gram-negative bacillary meningitis is commonly accompanied by bacteremia. (See 'Clinical features' above.)
●Mortality due to gram-negative bacillary meningitis in adults and children has ranged from 40 to 80 percent. Important negative prognostic factors include an altered state of consciousness at presentation (unresponsive or responsive to pain only), failure of timely administration of appropriate antimicrobial therapy, and the presence of septic shock. (See 'Outcome of infection' above.)
●Complications are similar to those of meningitis of any bacterial etiology and include ventriculitis, brain or metastatic abscesses, seizures, and hearing, cognitive, or motor deficits. (See 'Complications of meningitis' above.)
●As with meningitis in general, the diagnosis of gram-negative bacillary meningitis predominantly relies upon examination of the CSF for protein, glucose, cell count determinations, Gram stain, and culture. (See 'Cerebrospinal fluid analysis' above and "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Cerebrospinal fluid analysis'.)
●The Gram stain is positive for gram-negative bacilli in more than 50 percent of adult patients with a positive culture result. CSF culture is essential to establish the etiology of meningitis and to determine the antimicrobial susceptibilities of the pathogen. (See 'Cerebrospinal fluid analysis' above.)
●Indications for performing computed tomographic (CT) scanning of the head prior to lumbar puncture are similar to those for patients with suspected acute bacterial meningitis in general. However, patients who have undergone prior neurosurgical procedures should undergo CT scan prior to lumbar puncture. (See 'Computed tomographic scanning' above and "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'Indications for CT scan before LP'.)
