Background and Methods To characterize acute bacterial meningitisin adults, we reviewed the charts of all persons 16 years ofage or older in whom acute bacterial meningitis was diagnosedat Massachusetts General Hospital from 1962 through 1988. Weincluded patients who were admitted after initial treatmentat other hospitals.
Results During the 27-year period, 445 adults were treated for493 episodes of acute bacterial meningitis, of which 197 (40percent) were nosocomial. Gram-negative bacilli (other thanHaemophilus influenzae) caused 33 percent of the nosocomialepisodes but only 3 percent of the community-acquired episodes.In the 296 episodes of community-acquired meningitis, the mostcommon pathogens were Streptococcus pneumoniae (37 percent),Neisseria meningitidis (13 percent), and Listeria monocytogenes(10 percent); these organisms accounted for only 8 percent ofthe nosocomial episodes. Only 19 of the 493 episodes of meningitis(4 percent) were due to H. influenzae. Nine percent of all patientshad recurrent meningitis; many had a cerebrospinal fluid leak.Seizures occurred in 23 percent of patients with community-acquiredmeningitis, and 28 percent had focal central nervous systemfindings. Risk factors for death among those with single episodesof community-acquired meningitis included older age ( 60 years),obtunded mental state on admission, and seizures within thefirst 24 hours. Among those with single episodes, the in-hospitalmortality rate was 25 percent for community-acquired and 35percent for nosocomial meningitis. The overall case fatalityrate was 25 percent and did not vary significantly over the27 years.
Conclusions In our large urban hospital, a major proportionof cases of acute bacterial meningitis in adults were nosocomial.Recurrent episodes of meningitis were frequent. The overallmortality rate remained high.
Few studies of bacterial meningitis have focused on the clinicaland pathologic features of the illness in adults1,2,3,4,5. Mostlarge series have included both children and adults, with childrenaccounting for 45 to 87 percent of cases6,7,8,9,10,11,12,13,14,15,16.Results have rarely been reported according to age group inthese studies. To characterize acute bacterial meningitis inadults, we reviewed our experience at Massachusetts GeneralHospital over a 27-year period, from 1962 through 1988. We focusedon several questions of particular current interest: What arethe differences between nosocomial and community-acquired meningitis,and has the relative frequency of each type changed? How dopatients with recurrent meningitis differ from other patientswith meningitis? What are the bacteriologic causes of meningitisin adults, and have these causes changed? What is the frequencyof seizures or focal neurologic findings, and what are theirneuroanatomical correlates? What has been the role of computedtomography (CT) in the evaluation of community-acquired meningitis?What are the risk factors for death in adults with meningitis?Has the mortality rate changed?
Methods
We reviewed the charts of all patients 16 years of age or olderin whom acute bacterial meningitis was diagnosed at MassachusettsGeneral Hospital from January 1962 through December 1988. Patientswho were initially treated at other hospitals but were transferredto this hospital for further therapy were also included. Onlythose with acute illness (less than seven days of symptoms)and a definite or probable bacterial cause were included. Anosocomial infection was defined according to the 1988 guidelinesof the Centers for Disease Control17. Although these guidelinesdo not specify a length of hospitalization before the onsetof meningitis, in our study meningitis developed in 97 percentof the patients with nosocomial episodes after more than 48hours of hospitalization or within one week of discharge.
The diagnosis of meningitis caused by a specific bacterial pathogen,made in 421 episodes, was based on a compatible clinical pictureand one of the following: a positive cerebrospinal fluid culture(n = 367); confirmation at autopsy (n = 14); or a negative cerebrospinalfluid culture with a finding of neutrophilic pleocytosis andone of the following: a positive cerebrospinal fluid antigentest (n = 1) or quellung test (n = 2), a positive blood culture(n = 28), identification of gram-negative diplococci on Gram'sstaining of cerebrospinal fluid (n = 7), or sputum or throatcultures positive for Neisseria meningitidis in patients witha petechial or purpuric rash and a fulminant course (n = 2).In addition, 72 episodes of "culture-negative" bacterial meningitiswere included in our analysis. These episodes were diagnosedon the basis of a compatible clinical picture and pleocytosisof at least 100 neutrophils per cubic millimeter (0.1 x 109per liter) despite negative blood and cerebrospinal fluid culturesand results of cerebrospinal fluid Gram's staining that werenegative (n = 52), positive for organisms other than gram-negativediplococci (n = 10), or not available (n = 10). Most patients(97 percent) with culture-negative meningitis had more than300 leukocytes per cubic millimeter of cerebrospinal fluid (0.3x 109 per liter), and 96 percent had more than 50 percent neutrophils.Diphtheroids, coagulase-negative staphylococci, or propionibacteriaisolated from cerebrospinal fluid were considered etiologicagents only if found repeatedly or if cultured from the tipof an indwelling neurosurgical device. Almost one third of culture-negativeepisodes (22 of 72) occurred in patients with recurrent meningitis.
A second episode of meningitis was considered a recurrence ifit was due to a different organism from the first, or if itwas due to the same organism but occurred more than three weeksafter the completion of therapy for the initial episode. A relapseof meningitis due to the same organism within three weeks ofthe completion of therapy for the initial episode (as occurredin six patients) was not counted separately. A total of 404patients had single episodes of meningitis. Forty-one patients(9 percent) had more than 1 episode; all 89 episodes in thesepatients (including the 30 initial episodes) treated at MassachusettsGeneral Hospital between 1962 and 1988 are included in the category"recurrent meningitis." Of these 41 patients, 12 were knownto have had additional episodes, not included in this review,that were treated before 1962 or treated entirely at other hospitals.
Antibiotic therapy was considered inadequate if, of the antibioticsavailable in that era, those chosen were given at an insufficientdose, had poor central nervous system penetration, or were directedagainst a resistant organism. Mortality was classified as meningitis-relatedif death was due to meningitis or its complications, but notif it was due to a preexisting serious illness after bacteriologiccure and clinical recovery from meningitis.
The chi-square and Fisher's exact tests were used for statisticalanalysis.
Results
Classification of Case
Community-Acquired Meningitis
There were 296 episodes of community-acquired meningitis in275 patients; 253 patients had single episodes of meningitis,17 patients had more than 1 episode of community-acquired meningitis(38 episodes), and each of 5 patients had an episode of community-acquiredmeningitis and an episode of nosocomial meningitis. Of the 17patients with recurrent community-acquired meningitis, 10 hadthree or more episodes (not all of which were treated at MassachusettsGeneral Hospital); 1 patient had seven episodes over a periodof 11 years. The length of time between recurrences was usuallymonths or years.
In 56 percent of the episodes of community-acquired meningitis,the patients were 50 years of age or older (range, 16 to 88).
Nosocomial Meningitis
There were 197 episodes of nosocomial meningitis in 175 patients;5 of these patients also had an episode of community-acquiredmeningitis. A total of 151 patients had single episodes, and19 had recurrent meningitis (41 episodes); initial and recurrentepisodes usually occurred during the same hospitalization. Onlythree patients had more than one recurrence.
The relative frequency of nosocomial meningitis increased afterthe 1960s, from 28 percent in 1962 through 1970 to 45 percentfrom 1971 through 1979 and 48 percent from 1980 through 1988(P<0.01).
Predisposing Factors
The frequency of 13 predisposing factors for single episodesof meningitis is shown in Table 1. Of the 17 patients with recurrentcommunity-acquired meningitis, 8 had a remote history of headtrauma or neurosurgery (occurring more than one month beforethe onset of meningitis), 13 had a cerebrospinal fluid leak,and 7 had one or more episodes of meningitis even after repairof the leak. In recurrent nosocomial meningitis, a neurosurgicalprocedure preceded either the initial episode or a recurrentepisode in all 19 patients, and 9 patients had cerebrospinalfluid leaks. The frequency of cerebrospinal fluid leaks wassignificantly higher among patients with recurrent meningitis,either community-acquired or nosocomial, than among patientswith single episodes of meningitis (P<0.001).
Table 1. Predisposing Factors in 404 Single Episodes of Bacterial Meningitis.
Bacteriologic Findings
Streptococcus pneumoniae was the most common pathogen overall(causing 24 percent of the 493 episodes); gram-negative bacilliother than Haemophilus influenzae caused 17 percent of the episodes,whereas N. meningitidis, streptococci, Staphylococcus aureus,and Listeria monocytogenes caused 7 to 8 percent each. H. influenzaecaused only 4 percent of the episodes. In 15 percent of thecases, no pathogen was identified. A higher percentage of patientswith culture-negative episodes had received antibiotics beforethe initial lumbar puncture than was the case for patients withculture-positive episodes (50 percent vs. 36 percent, P<0.05).
Significant changes in the frequency of cases caused by severalbacterial species (Figure 1) included peaks in the relativefrequency of meningitis caused by N. meningitidis in the 1960sand that caused by L. monocytogenes in the 1970s (P<0.05for the comparison of these peaks with the other periods shownin Figure 1). These peaks may have been due to unrecognizedoutbreaks in the Boston area. Our cluster of listeria meningitiscases occurred four years earlier than the previously reportedoutbreak in Boston18. The increase in the relative frequencyof gram-negative bacilli as a cause of meningitis (from 11 percentof cases in the 1960s to 24 percent in the 1980s, P<0.01)and the concomitant decline in pneumococcal meningitis (from36 percent to 21 percent, P<0.01) may be related to the increasein the relative frequency of nosocomial meningitis. Gram-negativebacillary meningitis made up 39 percent of all nosocomial episodesin our study, and this frequency did not vary significantlyover time.
Figure 1. Relative Frequency of Major Bacterial Pathogens in Cases of Meningitis in Adults.
The bars represent the percentage of episodes caused by each pathogen in each period. There were 172 episodes in 1962 through 1970, 186 episodes in 1971 through 1979, and 135 episodes in 1980 through 1988.
Strep. pneumoniae, N. meningitidis, and L. monocytogenes caused64 percent of all single episodes of community-acquired bacterialmeningitis but less than 10 percent of single episodes of nosocomialmeningitis (Table 2). Patients with recurrent community-acquiredmeningitis also had a high frequency of pneumococcal infection(Table 3). Gram-negative bacilli were the predominant organismsin single-episode and recurrent nosocomial meningitis (Table 2and Table 3) but caused only 3 percent of all community-acquiredcases (in nine patients). Eight of these nine patients had underlyingillnesses (e.g., acquired immunodeficiency syndrome, cirrhosis,leukemia, and diabetes); five also had urinary tract infections.Escherichia coli and klebsiella caused almost half of all episodesof nosocomial gram-negative bacillary meningitis and seven ofthe nine cases of community-acquired disease.
Table 3. Causative Organisms in Recurrent Meningitis, 1962 through 1988.
H. influenzae caused meningitis in 19 patients, ranging from21 to 79 years of age. In 6 patients H. influenzae meningitisdeveloped after neurosurgery, and 13 had community-acquiredepisodes. A cerebrospinal fluid leak was identified in ninepatients with H. influenzae meningitis.
Clinical Features
The clinical features of 279 episodes of community-acquiredmeningitis in 259 patients were reviewed (17 episodes treatedat other hospitals for more than 24 hours before transfer wereexcluded from this analysis).
Clinical Findings
On presentation, only two thirds of the patients had the classictriad of fever, nuchal rigidity, and change in mental status,but all had at least one of these findings.
Ninety-five percent of patients had fever (temperature, 37.7°C [100 °F]) at presentation; another 4 percent becamefebrile during the next 24 hours. Fever was the only presentingsign in six patients, but three of these had severe headache.Of the 227 patients who survived through defervescence for whomdata on the duration of fever were available, 19 percent hadprolonged fever (10 or more consecutive days), but most hadother possible causes of continued fever. Patients with no identifiablecause of fever other than meningitis had an average of 4 consecutivedays of fever (range, 0 to 14).
Neck stiffness was present in 88 percent of patients on initialphysical examination. This incidence was not significantly loweramong elderly patients ( 70 years of age), in contrast withother reports6. Neck stiffness persisted for more than sevendays in some patients, despite overall improvement.
A rash was noted on admission in 30 patients (11 percent), ofwhom 22 had meningococcal meningitis. Although a petechial rashwas characteristic of this infection (occurring in 16 patients),it was also seen in pneumococcal meningitis (2), staphylococcalmeningitis (2), and culture-negative meningitis (1). Purpurawas observed in meningococcal meningitis (six patients) andculture-negative cases (one). A maculopapular rash was seenin three patients with meningococcal meningitis and two patientswith pneumococcal meningitis.
Neurologic Findings
Most patients had an abnormal mental status on presentation:51 percent were confused or lethargic, 22 percent were responsiveonly to pain, and 6 percent were unresponsive to all stimuli.However, 22 percent were normally alert. On presentation orduring the first 24 hours, 29 percent of patients had focalseizures or focal neurologic findings (other than an isolatedBabinski reflex or hearing loss) that were not present beforethe onset of meningitis.
Findings on Funduscopic Examination at Admission
Although the results of a funduscopic examination were not recordedfor many patients, "blurred optic-disk margins," "early papilledema,"or "papilledema" was recorded for 12 patients (4 percent of279 episodes) and confirmed by a neurologist or ophthalmologistin 10. Only 3 of these 10 had very high cerebrospinal fluidopening pressures ( 440 mm of water); opening pressures for5 were near 300 mm of water and were not recorded for 2 others.One patient had cavernous-sinus thrombosis. All 10 patientssurvived.
Seizures
Seizures occurred in 23 percent of the episodes of meningitis;they were focal in 7 percent, generalized in 13 percent, andnot further characterized in 3 percent. In two thirds of thecases seizures occurred within 24 hours of admission; more thanone third of patients with such early-onset seizures had a historyof alcoholism. Strep. pneumoniae was the causal agent in a higherpercentage of patients who had seizures than of patients whodid not (58 percent vs. 30 percent, P<0.001), but alcoholismwas a confounding factor.
Cranial-nerve Palsies
Although cranial-nerve palsies accompanied focal central nervoussystem findings in several patients, they were the only focalneurologic findings in 12 patients (4 percent). Nine patientshad such findings on admission; they developed in three morethan 24 hours later. Two patients with cavernous-sinus thrombosishad involvement of cranial nerves III, IV, and VI. Three patientshad transient unilateral or bilateral sixth-nerve palsies alone,a finding associated with increased intracranial pressure thathas been observed in meningitis in children19. In other patients,including three with peripheral facial-nerve palsies, a neuropathologicbasis for the palsies could not be determined from the informationavailable.
Focal Central Nervous System Dysfunction
Seventy-seven patients (28 percent) had focal central nervoussystem findings other than focal seizures alone (Table 4). Inmost, these findings were apparent on admission. Of the 29 patientswith gaze preference, the most common early finding, 17 hadconcurrent evidence of a hemispheric defect (hemiparesis, aphasia,or visual-field defect). Hemiparesis occurred sometime duringhospitalization in 37 patients (13 percent), but it persisteduntil discharge in only 7 of the 25 survivors. Seizures heraldedthe onset of hemiparesis in three patients. In 13 patients withhemiparesis, intracranial abnormalities (cortical-vein or sagittal-sinusthrombosis, cerebral-artery spasm, subdural empyema, hydrocephalus,cerebral infarct, abscess, or edema) were eventually demonstratedby radiologic studies or at autopsy. The two patients with brainabscess (of the temporal lobe) had chronic otitis media, whichsuggests that the abscess predated the meningitis.
Table 4. Focal Central Nervous System Findings in 279 Episodes of Community-Acquired Meningitis.
Cerebrospinal Fluid Findings
Community-Acquired Meningitis
In almost one fifth of the 296 episodes, patients with community-acquiredmeningitis had opening pressures of 400 mm of water or more(Table 5); 55 percent of these patients were alert or lethargicon presentation. Only half of all patients had hypoglycorrhachia,although 96 percent had elevated protein levels (>45 mg perdeciliter). Ten percent of positive cerebrospinal fluid smearswere misinterpreted. The most frequent error (occurring in 7of 17 cases) was misidentification of listeria as Strep. pneumoniae.
Table 5. Initial Cerebrospinal Fluid Values in 493 Episodes of Bacterial Meningitis.
CT Scanning
A cranial CT scan was performed in 87 of the 122 adults treatedfor community-acquired bacterial meningitis after 1975. Of these87 patients, 13 percent had findings on CT scanning that wereconsistent with a disruption of the dural barrier (eroding retrobulbarmass, pneumocephalus, or mastoid or sinus-wall defect), and31 percent had abnormalities related to meningitis or its complications:ventriculomegaly or hydrocephalus (13 patients), cerebral edema(5), meningeal enhancement (4), cerebral infarct (4), subduraleffusion (2), abscess (2), lesions consistent with septic emboli(2), cavernous-sinus thrombosis (1), and subdural empyema (1).Only two patients with hydrocephalus required a shunting procedure.Infarcts that were not apparent on the admission CT scan wereseen on later CT scans (>72 hours after admission) in fourpatients. All had persistent focal deficits (hemiparesis inthree and triplegia in one). Nineteen of the 39 patients withfocal neurologic findings or focal seizures had evidence onCT scanning of an intracranial abnormality related to meningitis,whereas only 8 of the 48 patients with nonfocal findings hadsuch evidence (P<0.01).
Treatment
Once the results of cultures were known, appropriate antibioticagents were used in nearly all 223 episodes of community-acquiredmeningitis with an identifiable cause that were treated initiallyat Massachusetts General Hospital (and in which the patientssurvived for at least 24 hours). However, in 17 episodes patientsreceived inadequate parenteral antibiotic therapy during thefirst 24 hours. The mortality rate among these patients washigher than that among the other patients (41 percent vs. 19percent), but the difference was not significant (P>0.05).
Adrenocorticosteroids were given within 24 hours of presentationin 8 percent of the 279 episodes of community-acquired meningitisthat were treated initially at Massachusetts General Hospital,and this percentage did not vary significantly between the threenine-year study periods.
Cerebral Herniation
Autopsy records, available for 27 of the 40 patients with community-acquiredmeningitis who died within seven days of presentation, containedevidence of herniation in 8 cases. All had temporal-lobe herniation;four also had cerebellar herniation. All had cerebral edema;two also had dural-sinus or cortical-vein thrombosis, and onehad an infarct from a septic embolus. In five, clinical signsof herniation developed within a period ranging from severalminutes to several hours after a lumbar puncture (includingtwo patients given intrathecal penicillin in 1962); openingpressures were recorded for four patients and were greater than500 mm of water.
Mortality
We found no significant difference in mortality rates betweenperiods for any given bacterial pathogen (Table 6), althoughmeningitis-related mortality in episodes of gram-negative bacillarymeningitis decreased from 21 percent in 1962 through 1970 and34 percent in 1971 through 1979 to 13 percent in 1980 through1988. Overall mortality rates (computed per patient, ratherthan per episode) were 25 percent for single episodes of community-acquiredmeningitis, 6 percent for recurrent community-acquired meningitis,35 percent for single episodes of nosocomial meningitis, and16 percent for recurrent nosocomial meningitis. None of the17 patients with recurrent community-acquired meningitis diedof meningitis, even though several had four or more episodes.
Table 6. In-Hospital Mortality Rates According to Pathogen.
According to the univariate analysis, three factors were associatedwith a significantly higher overall mortality rate among patientswith single episodes of community-acquired meningitis: an ageof 60 years or more (mortality rate, 37 percent vs. 17 percentfor patients <60 years of age; P<0.001); obtunded mentalstate on admission (49 percent among patients who were unresponsiveor responsive only to pain vs. 16 percent among those normallyalert or lethargic, P<0.001); and onset of seizures within24 hours of admission (72 percent vs. 18 percent among thosewithout early-onset seizures, P<0.001). The relative riskof death among patients with single episodes of community-acquiredmeningitis was 2.1 (95 percent confidence interval, 1.4 to 3.3)for patients 60 years of age or older, 3.0 (2.0 to 4.5) forthose with obtunded mental status on admission, and 4.0 (2.8to 5.8) for those in whom seizures began within 24 hours ofadmission. Ninety-eight percent of the 63 patients who diedhad at least one of these three risk factors. Risk factors thatdid not reach statistical significance in this analysis includedan absence of nuchal rigidity, focal central nervous systemfindings, late-onset seizures (>24 hours after admission),and highly abnormal cerebrospinal fluid values (opening pressure, 450 mm of water; glucose level, <40 mg per deciliter; orprotein level, 300 mg per deciliter).
Discussion
The most striking finding in this study of acute bacterial meningitisin adults was the high frequency of recurrent and nosocomialmeningitis (which occurred in 9 percent and 39 percent of patients,respectively). It is difficult to compare these numbers withthe results of other studies. The frequency of recurrent meningitisis unknown20. Two studies reported a lower frequency,6,21 butthese studies included a substantial proportion of cases inchildren and reviewed an earlier period. The frequency of nosocomialmeningitis among adults is also unknown, although it has beenreported as 28 percent among those 50 years of age or older22.We would expect the frequency of nosocomial and recurrent meningitisto be lower at community hospitals than at tertiary care centerssuch as ours.
In studies that include all age groups, typically with a majorityof the cases occurring among children, H. influenzae, N. meningitidis,and Strep. pneumoniae cause 70 to 87 percent of all cases6,7,8,9,10,11,23,24.In our study, in contrast, these pathogens caused fewer than40 percent of cases. At our hospital, pneumococcal meningitisdecreased and gram-negative bacillary meningitis nearly doubledin frequency over the 27 years we reviewed, reflecting the increasein the incidence of nosocomial episodes. The number of inpatientneurosurgical procedures at our hospital also increased by 25percent after the 1960s, a fact that may partly explain thesechanges. The importance of gram-negative bacillary meningitisin adults has been noted in other studies,3,25 although the17 percent frequency that we found was comparatively high. Analysisof data from a population-based study of bacterial meningitis24showed that gram-negative bacillary meningitis accounted for11 percent of 426 culture-positive cases in patients 16 yearsof age or older (Wenger JD: unpublished data).
When Gram's staining of the cerebrospinal fluid is negative,the choice of empirical therapy must be guided by knowledgeof the frequency of pathogens within each category of meningitis(community-acquired, nosocomial, single-episode, and recurrent).In community-acquired meningitis, Strep. pneumoniae, N. meningitidis,listeria, and streptococci are the most likely pathogens. Gram-negativebacilli should also be considered in patients with underlyingillnesses (particularly those with concurrent urinary tractinfections); H. influenzae becomes more likely if there is otorhinorrhea.In recurrent community-acquired meningitis, Strep. pneumoniaepredominates,13,26 but other streptococci and H. influenzaeare important causal agents as well. If little information isavailable, previously healthy patients with acute pyogenic community-acquiredmeningitis may be treated empirically with ampicillin (or chloramphenicolif the patient is highly allergic to penicillin). It is appropriateto add a third-generation cephalosporin initially in patientswho may have an underlying illness or a cerebrospinal fluidleak or who live in geographic areas where penicillin-resistantStrep. pneumoniae has been isolated. Other proposed empiricalregimens are also reasonable27,28,29. Modifications of theseregimens may be required depending on the specific clinicalsituation.
Most clinical features of community-acquired meningitis in adultsare similar to those in children. Twenty-seven percent of adultshave initial cranial-nerve palsies or focal central nervoussystem findings (beginning <24 hours after admission), and23 percent have seizures during hospitalization. In one study,16.5 percent of 235 children presented with focal neurologicsigns and about 30 percent had seizures during the course ofthe meningitis30. As in several studies of childhood meningitis,31,32,33ventriculomegaly was the most common abnormality identifiedon CT scanning in our study (in 15 percent), but it rarely requireda shunting procedure. Subdural effusions, common among infantswith meningitis,31,32,34,35 occurred in only 2 percent in thisstudy. Cerebral infarcts were a late finding in 5 percent andwere associated with hemiparesis, as in pediatric studies34,36.
The role of CT scanning in meningitis continues to be debated.A CT scan is indicated before the performance of a lumbar puncturein patients with suspected meningitis and signs of increasedintracranial pressure or focal findings on neurologic examination.Patients with meningitis rarely have major abnormalities onCT scanning in the absence of focal neurologic findings34. Inour study, nearly half the patients with community-acquiredmeningitis and focal findings who underwent CT scanning hadevidence of an intracranial abnormality related to meningitis.It is important to emphasize that antimicrobial therapy shouldbe initiated before any patient with suspected meningitis issent for a CT scan; to do otherwise risks an average delay ofmore than an hour in starting therapy,37 a delay that couldbe of consequence in such patients.
Though it has been described in children38,39,40 and in generalstudies7,8,41 of bacterial meningitis, few reports describecerebral herniation as a complication in adults42. In our study,all eight adults with evidence of herniation at autopsy hadcerebral edema. There are many causes of cerebral edema andincreased intracranial pressure in meningitis,27 and the roleof lumbar puncture in causing herniation is still controversial43,44,45,46,47.Herniation has occurred in some patients who have not receiveda lumbar puncture41.
In many studies, as in ours, older age and an obtunded mentalstate correlate with a poor outcome in patients with meningitis.Other risk factors for death observed in some studies -- notably,the absence of nuchal rigidity,48 elevated cerebrospinal fluidprotein levels,48 and hypoglycorrhachia6 -- were not significantin ours.
Over the past three decades, progress has been made in identifyingthe bacterial causes of meningitis (by, for instance, the developmentof antigen detection), identifying complications (such as cerebraledema, infarction, and hydrocephalus) by CT scanning, and localizingcerebrospinal fluid fistulas. Despite the introduction of newerantimicrobial agents, the mortality rate among adults with acutebacterial meningitis has not decreased; the exception may bethe rate of mortality among adults with gram-negative bacillarymeningitis since the advent of third-generation cephalosporins.Even in the 1980s, almost one quarter of adults with meningitisin our study died. Further progress in improving the outcomeof meningitis may stem as much from newer developments in themanagement of the pathophysiologic consequences of meningealinfection49 as from the introduction of new generations of antimicrobialagents.
We are indebted to Gregory P. Samsa, Ph.D., for assistance incomputer programming and statistical analysis.
Source Information
From the Infectious Disease Unit (M.L.D., S.B.C., D.J.W., S.I.M., F.S.S., M.N.S.) and the Neurology Department (V.S.C.), Massachusetts General Hospital, Boston.
Address reprint requests to Dr. Durand at the Infectious Disease Unit, Massachusetts General Hospital, Fruit St., Boston, MA 02114.
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Acute Bacterial Meningitis in Adults
Martinez E., Marcos A., Brivet F. G., Guibert M., Dormont J., Durand M. L., Calderwood S. B., Swartz M. N.
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N Engl J Med 1993;
328:1712-1713, Jun 10, 1993.
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A correction has been published: N Engl J Med 1993;328(23):1712.
60 years), obtunded mental state on admission, and seizures within the first 24 hours. Among those with single episodes, the in-hospital mortality rate was 25 percent for community-acquired and 35 percent for nosocomial meningitis. The overall case fatality rate was 25 percent and did not vary significantly over the 27 years. 
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