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Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis

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Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis The new england journal of medicine original article Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis Diederik van de Beek, M.D., Ph.D., Jan de Gans, M.D., Ph.D., Lodewijk Spanjaard, M.D., Ph.D., Martijn Weisfelt, M.D., Johannes B. Reitsma, M.D., Ph.D., and Marinus Vermeulen, M.D., Ph.D. abstract background We conducted a nationwide study in the Netherlands to determine clinical features and From the Departments of Neurology prognostic factors in adults with community-acquired acute bacterial meningitis. (D.B., J.G., M.W., M.V.), Medical Microbi- ology (L.S.), and Clinical Epidemiology and Biostatistics (J.B.R.), Academic Medi- methods cal Center; and the Netherlands Reference From October 1998 to April 2002, all Dutch patients with community-acquired acute Laboratory for Bacterial Meningitis (L.S.) — both in Amsterdam. Address reprint re- bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively eval- quests to Dr. van de Beek at the Academic uated. All patients underwent a neurologic examination on admission and at discharge, Medical Center, University of Amsterdam, and outcomes were classified as unfavorable (defined by a Glasgow Outcome Scale score Department of Neurology H2, P.O. Box 22660, 1100 DD Amsterdam, the Nether- of 1 to 4 points at discharge) or favorable (a score of 5). Predictors of an unfavorable out- lands, or at [email protected]. come were identified through logistic-regression analysis. N Engl J Med 2004;351:1849-59. results Copyright © 2004 Massachusetts Medical Society. We evaluated 696 episodes of community-acquired acute bacterial meningitis. The most common pathogens were Streptococcus pneumoniae (51 percent of episodes) and Neisseria meningitidis (37 percent). The classic triad of fever, neck stiffness, and a change in men- tal status was present in only 44 percent of episodes; however, 95 percent had at least two of the four symptoms of headache, fever, neck stiffness, and altered mental status. On admission, 14 percent of patients were comatose and 33 percent had focal neuro- logic abnormalities. The overall mortality rate was 21 percent. The mortality rate was higher among patients with pneumococcal meningitis than among those with menin- gococcal meningitis (30 percent vs. 7 percent, P<0.001). The outcome was unfavorable in 34 percent of episodes. Risk factors for an unfavorable outcome were advanced age, presence of otitis or sinusitis, absence of rash, a low score on the Glasgow Coma Scale on admission, tachycardia, a positive blood culture, an elevated erythrocyte sedimenta- tion rate, thrombocytopenia, and a low cerebrospinal fluid white-cell count. conclusions In adults presenting with community-acquired acute bacterial meningitis, the sensi- tivity of the classic triad of fever, neck stiffness, and altered mental status is low, but almost all present with at least two of the four symptoms of headache, fever, neck stiff- ness, and altered mental status. The mortality associated with bacterial meningitis remains high, and the strongest risk factors for an unfavorable outcome are those that are indicative of systemic compromise, a low level of consciousness, and infection with S. pneumoniae. n engl j med 351;18 www.nejm.org october 28, 2004 1849 Downloaded from www.nejm.org by JUAN J. RONCO MD on October 27, 2004 . Copyright © 2004 Massachusetts Medical Society. All rights reserved. The new england journal of medicine he epidemiology of bacterial men- considered immunocompromised, as were patients t ingitis has changed. Meningitis due to infected with the human immunodeficiency virus. Haemophilus influenzae type b has been nearly At discharge, all patients underwent a neurologic eliminated in the Western world since vaccination examination performed by a neurologist, and the against H. influenzae type b was initiated,1 and the outcome was graded according to the Glasgow introduction of conjugate vaccines against Strepto- Outcome Scale. A score of 1 on this scale indicates coccus pneumoniae is expected to reduce the burden death; a score of 2, a vegetative state (the patient is of childhood pneumococcal meningitis significant- unable to interact with the environment); a score of ly.2 Although vaccination with a pneumococcal con- 3, severe disability (the patient is unable to live in- jugate vaccine is producing herd immunity among dependently but can follow commands); a score adults, the age distribution of meningitis has now of 4, moderate disability (the patient is capable of shifted to older age groups.2,3 Several studies of living independently but unable to return to work clinical features and prognostic factors in adults or school); and a score of 5, mild or no disability with bacterial meningitis have been performed; (the patient is able to return to work or school). A however, all were retrospective and relatively small favorable outcome was defined as a score of 5, and in size.4-23 We performed a nationwide prospective an unfavorable outcome as a score of 1 to 4. The study of clinical features and prognostic factors in Glasgow Outcome Scale is a well-validated instru- adults with community-acquired bacterial menin- ment with good interobserver agreement.25 gitis in the Netherlands. The susceptibility of meningococci to penicil- lin was determined by inoculating strains onto choc- methods olate agar containing 0.1 mg of penicillin per liter. A 1-µg oxacillin disk was used to identify penicil- We identified adults (defined as patients older than lin-resistant strains of pneumococci. Whenever 16 years of age) who had bacterial meningitis and a strain showed antibiotic resistance, the E rosette were listed in the database of the Netherlands Ref- assay was used to determine the minimal inhibi- erence Laboratory for Bacterial Meningitis from tory concentration of the antibiotic. The inocula- October 1998 to April 2002. This laboratory re- tion procedure and susceptibility testing were per- ceives cerebrospinal fluid and blood isolates from formed as described elsewhere.26 Parts of this approximately 85 percent of all patients with bacte- cohort study have been reported previously.7,26-28 rial meningitis in the Netherlands (population, This observational study used patient data that 16.2 million).3,24 The laboratory provides daily up- had been rendered anonymous and was carried out dates of the names of hospitals where patients with in accordance with Dutch privacy legislation. The bacterial meningitis have been admitted in the study was announced in the journal of the Dutch preceding two to six days and the names of phy- Neurologic Society, followed by periodic remind- sicians, usually neurologists. Physicians were in- ers. Before the study, all Dutch neurologists re- formed about the study by telephone. Subsequent- ceived information about the study, including a ly, patients or their legal representatives received case-record form. written information concerning the study and were Parametric and nonparametric tests were used asked to give written informed consent for partic- to identify differences between groups in continu- ipation; only patients for whom consent was ob- ous outcomes, and chi-square tests were used to tained were enrolled. Case-record forms were used compare categorical outcomes. We used logistic to collect data on patients’ history, symptoms and regression to examine the association between po- signs on admission, laboratory findings at admis- tential predictors and the likelihood of an unfavor- sion, clinical course, outcome and neurologic find- able outcome. Odds ratios and 95 percent confi- ings at discharge, and treatment. dence intervals were used to quantify the strength Patients were categorized as having either com- of these associations. On the basis of previous re- munity-acquired or hospital-acquired meningitis search and pathophysiologic interest, 20 potential- (the latter was defined as meningitis that occurred ly relevant predictors were chosen. during hospitalization or within one week after dis- Despite the low median percentage of missing charge). Patients with an altered immune status values for individual variables (2 percent), only owing to the use of immunosuppressive drugs or 320 of the 696 patients had complete data on all splenectomy, diabetes mellitus, or alcoholism were predictors — which presented a considerable 1850 n engl j med 351;18 www.nejm.org october 28, 2004 Downloaded from www.nejm.org by JUAN J. RONCO MD on October 27, 2004 . Copyright © 2004 Massachusetts Medical Society. All rights reserved. clinical features and prognostic factors of bacterial meningitis limitation for multivariate models. Therefore, we used multiple imputation techniques to reduce this 29 1108 Patients with bacterial loss. All predictors together were used to impute meningitis identified missing values on the basis of multivariate normal distributions. The coefficients of five rounds of im- putation were combined to obtain the final esti- 81 Patients were untraceable mates for the multivariate model. The low rate of 33 Physicians declined to missing values per variable, the large number of participate predictors, and the large sample size maximized the benefits of the multiple imputation methods.30 All statistical tests were two-tailed, and P values of 994 Case-record forms less than 0.05 were considered to indicate statisti- sent out cal significance. Statistical analyses were performed with use of SAS software, version 8.02 (SAS Institute). The study 754 Case-record forms returned was designed,
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