Epidemiology of Meningitis and Encephalitis in the United States from 2011-2014.
Rodrigo Hasbun1 , Ning Rosenthal2 , JM Balada-Llasat3 , Jessica Chung2 , Steve Duff4 , Samuel Bozzette5,6 , Louise Zimmer5 , Christine C. Ginocchio5,7
1
UT Health McGovern Medical School; 2 Premier Research Services, Premier Inc., Charlotte, NC; 3 The Ohio State University; 4 Veritas Health Economics Consulting; 5 bioMérieux; 6 University of California, San Diego; 7 Hofstra Northwell School of Medicine.
Corresponding Author:
Rodrigo Hasbun, M.D. M.P.H. UT Health McGovern Medical School 6431 Fannin St. MSB 2.112, Houston, Texas 77030. Phone +1-713-500-7140 ; Fax +1-713-500-5495 ; Email :
[email protected]
Brief Summary: A study of 26,429 adults with meningitis or encephalitis in the US describing the management decisions and outcomes stratified by the most common etiologies.
Running Title: Epidemiology of Meningitis and Encephalitis in the US
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:
[email protected]
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Abstract Background Large epidemiological studies evaluating the etiologies, management decisions and outcomes of adults with meningitis and encephalitis in the United States (US) are lacking. Methods Adult patients (≥18 years) with meningitis or encephalitis by ICD-9 codes available in the Premier Healthcare Database during 2011-2014 were analyzed. Results A total of 26,429 patients with meningitis or encephalitis were identified. The median age was 43 years; 53% were female. The most common etiology was enterovirus (13463, 50.9%); followed by unknown (4944, 18.7%), bacterial meningitis (3692, 13.9%), Herpes Simplex Virus (2184, 8.3%), non- infectious (921, 3.4%), fungal (720, 2.7%) arboviruses (291, 1.1%), and other viruses (214, 0.8%). Empirical antibiotics, antivirals and antifungals were administered in 85.8%, 53.4%, and 7.8%, respectively and varied by etiologies. Adjunctive steroids were utilized in 15.9% of all patients and in 39.33% of patients with pneumococcal meningitis with an associated decrease in mortality (6.67% vs. 12.5%, P=0.0245). The median length of stay was 4 days; with the longest duration in those with fungal (13), arboviral (10), and bacterial meningitis (7). Overall inpatient mortality was 2.9% and was higher in those with bacterial (8.2%), fungal (8.2%), or arboviral (8.9%) disease. Overall readmission rate at 30 days was 3.2%; patients with arboviral (12.7%), bacterial (6.7%) and fungal (5.4%) etiologies had higher rates.
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Conclusion Viruses are the most common cause of meningitis and encephalitis in the US and are treated with antibiotic therapy in the majority of cases. Adjunctive steroids are underutilized in pneumococcal meningitis where it has shown to decrease mortality.
Keywords: meningitis, encephalitis, adjunctive corticosteroids, epidemiology, United States
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Introduction Meningitis and encephalitis are caused by a wide variety of infectious and non- infectious etiologies creating diagnostic and treatment challenges to clinicians [1-3]. Furthermore, the majority of patients continue to have unknown etiologies with some pathogens requiring urgent antimicrobial therapy for cure and survival [4,5]. Although autoimmune causes of encephalitis such as the anti N- methyl D-aspartate receptor antibody encephalitis have to be considered in the differential diagnosis, the majority of the identified etiologies in meningitis and encephalitis are infectious [3-5]. Some viral pathogens such as West Nile Virus (WNV), Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV) can cause either a meningitis or encephalitis presentation [5,6]. Three recent studies using the Nationwide Inpatient Sample (NIS) have evaluated the burden, costs and the etiologies of encephalitis and bacterial meningitis in the United States from 1997-2010 [7-9]. A major limitation with these studies is the lack of clinical information available through the NIS database. The purpose of our study was to utilize the Premier Healthcare Database (PHD) to evaluate the epidemiology, management and outcomes of adults with all types of meningitis and encephalitis in the United States from 2011 to 2014. Methods Study population Adult patients (age ≥18 years) with an admitting or discharge diagnosis (primary and/or secondary) of meningitis or encephalitis determined by ICD-9 diagnostic codes (see Appendix A) that were discharged between January 1, 2011 and December 31, 2014 were
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eligible for the study. If patients had multiple admissions for the same diagnosis, only the first hospitalization was included for analysis. Patients were excluded from the study if the lumbar puncture was done 2 days before or after admission to the hospital, or patients were electively admitted or had a trauma related admission, or patients with chronic meningitis (ICD-9 diagnosis code: 322.2), or patients with possible nosocomial meningitis (cerebrospinal fluid (CSF) shunt, craniotomies, spinal procedures, or head trauma with CSF leaks during the 30 days prior to admission and at time of admission). All data was de-identified and no individual data was reported in accordance to the health insurance portability and accountability act. Data Source Data for the study were derived from the de-identified Premier Healthcare Database (PHD), the largest hospital discharge database in the United States. It currently contains data from more than 619 million patient encounters, or one in every five hospital discharges in the United States since January of 2000 through June of 2016. The PHD is a complete census of inpatient and hospital-based outpatient encounters from nearly 700 hospitals in all fifty states in the nation. Hospitals of all sizes from large tertiary hospitals to small community hospitals in both rural and urban areas are included in the database. PHD data includes patient’s demographics, admission and discharge diagnoses and dates, etiologies of meningitis and encephalitis, inpatient mortality, and discharge status. PHD also contains a date-stamped log of billed items, including procedures, medications, laboratory test results, and diagnostic and therapeutic services at the individual patient level. All procedures and diagnoses are captured for each patient, as well as all drugs and
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devices received. Drug utilization information is available by day of stay and includes quantity, dosing, strength used, and cost. Role of the funding source bioMérieux paid for the Premier database analysis and paid SD, RH and JB as consultants on the project. Data analysis Descriptive data was summarized using frequencies and percentages for categorical variables and using mean, standard deviation, median, interquartile range for each subgroup. Chi-square or Fisher’s exact tests were used to compare the differences between subgroups for categorical variables. Two sample paired T-tests was used for comparing differences in continuous variables. All analyses were performed using SAS (v9.4). Results Cohort assembly A total of 46,828 adults with an admitting or discharge diagnosis of meningitis or encephalitis were identified. We excluded 4,291 patients with repeated admission for the same diagnosis. Amongst the 42,537 unique adult patients, 31,495 (74%) had a lumbar puncture performed. A total of 26,429 adult patients were included in the study after we excluded patients that had the lumbar punctures done 2 days before or after admission (n=4620), who had nosocomial meningitis (n=336), or had chronic meningitis (n=110).
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Baseline demographics, comorbidities and site of care As seen in Table 1, there was a slight female predominance (53.3%) and the median age of the cohort was 43 years (range 18-101). Non-Hispanic white (49.9%) was the most common race and ethnicity group. A Charlson comorbidity score >1 was seen in 16.4% of the patients. The most common comorbidities seen in the study population included diabetes mellitus (15.4%), chronic pulmonary disease (12.8%), renal disease (6.0%) and cerebrovascular
diseases
(5.8%).
Human
immunodeficiency
virus
(HIV)
infection/Acquired Immunodeficiency Syndrome (AIDS) was seen in 1120 (4.2%). A total of 24,091 (91.2%) of the patients were admitted to the hospital either through t he emergency department (21,013; 87.2%), outpatient clinics (2,210; 9.2%), or as a transfer from another facility (868; 3.6%). Frequency and duration of antimicrobial therapies A total of 22,684 (85.8%) of patients were treated with intravenous antibiotics, 14,109 (53.4%) with intravenous antivirals and 2,055 (7.8%) received intravenous antifungal therapies. (see Table 2).
Antibiotics were universally administered in bacterial
meningitis (99%), but were also given to the majority of patients with viral (enterovirus [EV], herpes viruses [including CMV, EBV, HHV6, VZV], arboviruses, other viruses), fungal, and unknown etiologies. The median duration of antibiotic therapy ranged from 3 days in EV meningitis to 8 days in bacterial meningitis. Antiviral therapy (mainly intravenous acyclovir) was frequently administered in viral etiologies (HSV/VZV, 94.4%; arboviruses, 74.2%; EV, 51%) and also given in a significant proportion of unknown cases (52.3%), and in patients with bacterial (41.6%) and fungal etiologies
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(32.4%). Lastly, antifungal was given in 81.7% of patients with fungal meningitis and infrequently (
