A study on the clinical outcomes and management of meningitis at a tertiary care centre
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_785_15
Source of Support: None, Conflict of Interest: None
Background: Meningitis is a life threatening central nervous system infection that is prevalent worldwide. Many studies have been conducted on bacterial meningitis, but the information is inadequate on the other types of meningitis, especially prevalent in India. Regional information regarding trends, in terms of etiology and microbiological susceptibility, are essential for timely and adequate management of meningitis.
Keywords: Aseptic meningitis, meningitis, outcome, treatment, trends in management
Meningitis is a potentially fatal inflammation of the meninges, the thin, membranous coverings of the brain and the spinal cord. The causes of meningitis may be broadly classified as infectious (bacterial, viral, fungal) and noninfectious (cancer-related, systemic lupus erythematosus, drug induced, head trauma, and brain surgery). The most common types of meningitis are pyogenic (bacterial) meningitis and tuberculous meningitis (TBM). The most common bacterial pathogens are Streptococcus pneumoniae, Neisseria More Details meningitidis (meningococcus), Haemophilus influenzae, Listeria monocytogenes, and Staphylococcus aureus. Tuberculous meningitis is caused by Mycobacterium tuberculosis. Among the viral infections, the common causative organisms include the enterovirus (especially the Coxsackie virus), and the Herpes simplex virus. Cases where a bacterial or a viral organism have not been isolated are referred to as aseptic meningitis. Fungal meningitis is relatively uncommon and results in chronic meningitis. Cryptococcal meningitis is a common fungal form of the disease that affects people with immunodeficiencies, such as the acquired immunodeficiency syndrome.
Although meningitis is a notifiable disease in many countries, its exact incidence rate is unknown; however, in the decade from 1990 to 2010, an estimated global figure of approximately 420,000 deaths were associated with meningitis. Bacterial meningitis occurs in about 3 per 100,000 population annually in the Western countries. Population-wide studies have shown that viral meningitis is more common with an incidence of 10.9 per 100,000 population. In Brazil, the rate of bacterial meningitis is higher at 45.8 per 100,000 population annually. Sub-Saharan Africa has been plagued by large epidemics of meningococcal meningitis for over a century. The region, is therefore, labeled as the "meningitis belt." An incidence rate of between 100–800 cases per 100,000 population is encountered in this area, which is poorly served by medical care. These cases are predominantly caused by the meningococci group of organisms. The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing infection in approximately 250,000 cases and resulting in nearly 25,000 deaths. There are significant differences in the regional distribution of the etiological agents responsible for bacterial meningitis. For instance, while the N. meningitides groups B and C cause a significant proportion of the disease episodes in Europe, the group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for approximately 80 to 85% of the documented meningococcal meningitis cases.,
Most of the studies are mainly focused on the pediatric population, with studies on the adult population being scarce. Majority of the studies have been conducted on bacterial and tuberculous meningitis. Hence, it is of particular importance to study the various types of meningitis occurring in a tertiary care setting.
Several studies from India report a low cerebrospinal fluid (CSF) culture positivity in cases suffering from meningitis. A positive CSF culture has been found to have a wide range from 6–50% in the cases discovered to be suffering from meningitis. There is a need to distinguish between the type of meningitis based on the clinical features and the CSF biochemistry as there are varying grades of urgency as well as different treatment strategies involved in the management of each type of meningitis.
Therefore, we conducted this study with the main objectives of examining the specific clinical features with which our patients in a teritiary care setting presented, and also the abnormalities in the CSF biochemistry (proteins, glucose, white blood cells (WBCs), lymphocytes, and adenosine deaminase (ADA)). We also have tried to examine the characteristic features that distinguished the various types of meningitis, the incidence and patterns of the CSF culture obtained, and the probable reasons for obtaining a sterile culture, among the various types of meningitis prevalent in our study population.
This descriptive, record-based study was conducted at the Apollo Group of Hospitals, Jubilee Hills, Hyderabad, India. The approval of the Ethics Committee of the hospital was obtained prior to the start of the study. The prospective data was collected for the period between February and August 2014; and, the retrospective data was obtained for the time duration from January 2012 to January 2014. The medical records of all patients suffering from meningitis were collected and reviewed. Details of demographic data, clinical presentation at admission, diagnosis, microbiological data, and other laboratory investigation reports of the patients were reviewed. The clinical course, treatment, and outcomes in these patients were also recorded.
The chi-square test was used to compare the risk of meningitis in the diabetic population versus the nondiabetic population; and, the association between the type of meningitis and the occurrence of seizures. Mantel–Haenszel chi-square test was used to determine the association between the type of meningitis and the adenosine deaminase levels (ADA) levels. Fisher's exact test was used to evaluate the difference in outcome in various types of meningitis. Statistical Analysis System (SAS) version 3 (SAS Institute, Cary, NC, USA) was used for the statistical analysis.
A total of 147 cases of meningitis were reviewed utilizing the records obtained by the medical records department and wards. A higher prevalence of meningitis was seen in the male patients compared to the female ones. The maximum number of cases suffering from meningitis were within the age range of 21–40 years. The mean (± standard deviation) age group of our study population was 50 ± 15 years [Table 1].
It was observed that the classic triad of headache with fever, neck stiffness, and altered mental status was present in 26% of the study population. Majority (83%) of the patients presented with at least 2 out of the 4 symptoms, namely, headache, neck stiffness, fever, and altered sensorium. Other common symptoms seen apart from headache (that was the intial presentation in nearly half of the recruited patients) included seizures, vomiting, and excessive drowsiness. The seasonal variations in the incidence of meningitis was also studied. The data is presented in [Figure 1]. No significant differences were obtained in this category between the patients suffering from various types of meningitis.
It was observed that patients with diabetes mellitus, and those who had undergone a neurosurgical procedure, especially a ventriculoperitoneal shunt, had a particularly higher propensity for the development of meningitis, compared to the other risk factors (P> 0.0001) [Table 2].
The incidence of various types of meningitis detected in our study is summaried in [Table 3]. Viral/aseptic meningitis was most common type of meningitis observed, followed by the occurrence of pyogenic and tuberculous meningitis (TBM). Fewer cases of fungal and other types of meningitis (including chemical meningitis or cancer-related meningitis) were observed [Table 3].
Among the signs and symptoms observed in meningitis, seizure was an important neurological manifestation that led the investigators to suspect the initial presence of meningitis. Seizures were more frequent among patients having an aseptic or a viral meningitis than in those suffering from other types of meningitis (P> 0.0004) [Table 4].
A higher incidence of abnormal CSF biochemical parameters were found in different types of meningitis. A higher incidence of CSF protein concentration was seen in TBM and pyogenic meningitis; a higher incidence of CSF glucose concentration was seen in TBM and in fungal meningitis. The total leucocytic count was elevated in TBM and in viral meningitis; in particular, a CSF lymphocytosis was observed in TBM, pyogenic meningits, and viral meningitis. ADA was significantly higher in TBM (P> 0.0001) as compared to the other groups of meningitis [Table 5].
The average total length of stay, and the average length of stay in the intensive care unit (ICU) among patients suffering from pyogenic meningitis were 15 and 9 days, respectively. The average total length of stay and the average length of the stay in ICU among patients suffering from TBM were 14 and 10 days, respectively. The average total length of stay and the average length of stay in the ICU among patients suffering from either viral/aseptic meningitis or fungal meningitis were 13 and 10, and 22 and 11 days, respectively.
It was found that it was a common practice to administer empiric antibiotics for at least 24 hours before the diagnostic lumbar puncture was performed in almost half of the studied cases; in nearly one-third of the cases, the empiric course of antibiotic administration was initiated on the day of the lumbar puncture; in 13% of the cases, the empiric antibiotics were started 24 hours after the lumbar puncture; and, in only 4% of the cases, no empiric treatment was administered [Table 6].
Based upon their Glasgow Coma Scale (GCS) scores, the patients were categorized as having a mild (13–15), moderate (9–12), or severe (≤8) form of meningitis. An improved GCS score was usually observed in patients suffering from a moderate-to-mild form of viral meningitis, whereas the GCS score often worsened from mild-to-severe in fungal meningitis [Table 7].
In our study, the adult population was more often affected; this, however, may have been a selection bias, as our institution is a preferred centre for the tertiary care of adult patients. There is a dearth of available literature regarding the incidence of various types of meningitis present in adult patients when compared to the pediatric population. In the study conducted by Borade et al., contrary to the findings of the present study, the most commonly affected age group was the pediatric one. The classical triad of meningitis, or even the presence of two of the four common symptoms were observed to a lesser extent in our study when compared to the study conducted by Van de Beek et al.
Diabetes mellitus is a major risk factor for the development of various infections including meningitis. Approximately one-third of our study population had diabetes mellitus. Several aspects of the immunity are altered in patients with diabetes. Joshi et al., reported that the functions of polymorphonuclear leukocytes is suppressed in the presence of diabetes mellitus, particularly when acidosis is also present. Moreover, leukocytic adherence, chemotaxis, and phagocytosis are also affected. Antioxidant systems involved in the bactericidal activity may also be impaired in patients with diabetes mellitus. Viral/aseptic meningitis was commonly seen in our study. This was at variance with the study conducted by Borade et al., where TBM was the most common type of meningitis found in all the age groups, followed by the occurrence of viral and pyogenic meningitis.
Previous studies have shown that even though cultures were negative, CSF parameters were diagnostic for different forms of meningitis. We found that antibiotic pretreatment did not significantly affect the CSF WBC count or the total CSF protein levels. WBC was elevated with a lymphocyte predominance. Even if the treatment for meningitis has already been started, these CSF parameters were helpful for the diagnosis of meningitis. Adenosine deaminase (ADA) is considered to be an indicator of cell-mediated immunity and is found mainly in T lymphocytes. The chief function of ADA is related to lymphocytic proliferation and differentiation, and its activity is found to be elevated in diseases where there is a cell-mediated immune response. As the cell mediated immune response is seen in TBM, ADA levels are also elevated. A study conducted by Kumar et al., showed similar findings.
It was observed that, in our series, the most commonly prescribed empirical antibiotic was ceftriaxone, followed by a combination of cefoperazone and sulbactam. Vancomycin, meropenem, and amikacin were also often used in the treatment of pyogenic meningitis.
TBM was treated mainly utilizing a combination of rifampicin, pyrazinamide, ethambutol, and isoniazid. Dexamethasone, a corticosteroid, was also given as an adjunctive treatment in approximately half of the patients with TBM. The average total length of stay and the average length of stay in the ICU of patients suffering from TBM was 14 and 10 days, respectively. The European Dexamethasone Study showed that the adjunctive treatment with dexamethasone was found to be beneficial in adult patients with meningitis due to their role in reducing inflammation and in decreasing the frequency of development of neurological sequelae. Acyclovir was the antiviral drug used, whereas fluconazole, amphotericin B, and caspofungin were used to treat fungal meningitis.
Antiepileptic drugs such as levitiracetam, phenytoin, quetiapine, and divalproate sodium to treat the associated seizures; ondansetron to relieve the recurrent episodes of vomiting; and, paracetamol to decrease the fever and headache that were often associated with meningitis, were the symptomatic medications administered.
In our study, lumbar puncture done to collect CSF for a biochemical analysis was done only once in a majority of cases and was repeated only in a few patients. Antibiotics were initiated prior to the performance of the lumbar puncture in nearly half of the patients [Table 6]. On the other hand, in the study conducted by Adhikari et al., antibiotics were initiated in a very few patients prior to obtaining the CSF culture and sensitivity results via a lumbar puncture. In other studies, in an experience similar to ours, a definite microbiological data could not be obtained due to the initiation of empirical antibiotics prior to obtaining the CSF culture and sensitivity results. Therefore, in an experience similar to ours, the CSF samples and blood cultures were found to be positive for the representative organisms in a very few patients.
CSF sterilization may occur more rapidly after the initiation of empirical parenteral antibiotics. Lack of inadequate culture may result in an unnecessarily prolonged treatment if the clinical presentation and laboratory data cannot establish the presence of bacterial meningitis. The yield of bacteria on a gram stain depends on several factors such as the number of organisms present, the prior use of antibiotics, the technique used for smear preparation, the staining techniques utilized, and the observer's skill and experience.
While comparing outcomes based on the type of meningitis observed, it was found that a significant clinical improvement was seen in a majority of patients suffering from viral/aseptic meningitis (P> 0.0182) when compared to those with tuberculous, pyogenic, fungal, and other forms of meningitis. In our study, the case fatality rate was 6%. The cause of mortality was often not attributable to meningitis; in fact, the maximum fatality rate was seen in TBM due to the presence of multiple associated comorbidities and a low GCS score at admission. In the study conducted by Borade et al., in the state of Maharashtra, however, a high case fatality rate was attributable to meningitis. The probable reasons mentioned were the severity of the clinical symptoms in the included cases, and the delay in the timing of initiation of appropriate treatment.
In our study, the normalization of CSF biochemistry (protein, glucose, white blood cells, lymphocytes and ADA) as well as the improvement in the symptomatology of meninigits at discharge, were taken as predictors of outcome. We observed a clinical improvement in the majority of patients; CSF biochemistry, however, improved completely in only a few patients at discharge [Table 8]. There was no improvement observed in either of these parameters in some cases, especially when multiple comorbidities were also present in them. Our data regarding the overall management of meningitis in a tertiary care institution was compared with the available data from other Indian studies, and has been presented in [Table 9].,,,,,
In our study, some unusual causes of meningitis were also found. These included 4 cases of scrub typhus meningitis, where the Weil Felix test was positive; and, 2 patients, where the Leptospira IgM antibodies were positive. Doxycycline in a daily oral dosage of 100 mg was the treatment initiated in all these patients.
The study had its limitations. The retrospective inclusion of the patients precluded the study of a long term follow-up outcome in them. It was often difficult to determine the type of meningitis present as treatment had often been started empirically prior to the determination of etiology utilizing the microbiological culture and sensitivity of organisms. An enzyme-linked immunosorbent assay, an automated immunoassay analyzer (AIA), and a latex fixation agglutination test, that would have led to an increased sensitivity in the determination of the organisms, were not conducted for a majority of the cases. Since a standardized treatment was not administered in the initial phase of the treatment (though most of the patients were initially started on ceftriaxone), prior to the obtaining of a positive culture and sensitivity, it was difficult to evaluate the appropriateness of various treatment regimens.
CSF cultures were negative in the maximum number of cases in our study because of the use of empirical antibiotics prior to the hospitalization of the patient; as well as, due to the presence of patients suffering from partially treated meningitis. For establishing the etiology of meningitis, sensitive alternative strategies for the diagnosis of various organisms need to be explored. Elevated ADA level forms a sensitive marker in differentiating TBM from other types of meningitis. The management of meningitis in the adult population is complex and the outcome is often influenced by their advanced age, as well as by the presence of various comorbid conditions and of multiple infections in them.
We acknowledge the kind cooperation and support of Dr. Ratna Rao from the Department of Microbiology, Dr. Suneetha Narreddy from the Department of Infectious Diseases, and Dr. Sanjeev Sharma from the Medical Records Department of Apollo hospitals; and, the Principal and Management of Sri Venkateshwara College of Pharmacy, Hyderabad, during the course of the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]