International Journal of Nutrition, Pharmacology, Neurological Diseases

ORIGINAL ARTICLE
Year
: 2011  |  Volume : 1  |  Issue : 2  |  Page : 194--200

Clinical and bacteriological spectrum of community-acquired acute bacterial meningitis in adults at a tertiary care hospital in northern India


P Madhumita, N Gupta 
 Department of Medicine, Maulana Azad Medical College and Associated Hospitals, Bahadur Shah Zafar Marg, New Delhi, India

Correspondence Address:
P Madhumita
Department of Medicine, Maulana Azad Medical College and Associated Hospitals, Bahadur Shah Zafar Marg, New Delhi - 110002
India

Abstract

Objective : To evaluate the clinical and bacteriological spectrum of community-acquired acute bacterial meningitis (ABM) in an adult population at Lok Nayak Hospital, New Delhi, a tertiary care hospital in northern India. Materials and Methods: Cerebrospinal fluid (CSF) samples from 120 clinically suspected cases of pyogenic meningitis were processed for cell counts, differential counts, bacterial stain and culture, antibiotic susceptibility test, and bacterial antigen detection by latex agglutination test (LAT) in CSF, serum and urine. Results : CSF LAT was positive in 56/120 cases of ABM. Streptococcus pneumoniae was the predominant pathogen in 41 of these 120 cases i.e. 34.0% of all cases. Neisseria meningitidis accounted for 24 cases i.e. 20% of all cases. Staphylococcus aureus was isolated in one case. Bacterial cultures were positive in 22 (18.3%) cases only. Conclusions: Evidence for presence of microbial activity could be detected in 44.1% cases by LAT, whereas a direct microbiological confirmation could be documented in only 22 cases i.e. 18.3%. Streptococcus pneumoniae remains the major etiological agent of ABM in our study. Penicillin resistance was detected in 50% of cases among the isolates which came positive by culture. Neisseria meningitidis was detected in 24 cases. But since none were cultured, sensitivity patterns could not be correlated. LAT is a convenient and rapid test to support bacterial etiology in ABM. In remote situations, their use in serum or urine needs to be considered after evaluation in longer studies. Further research should focus on the preventable aspects of ABM, especially pneumococcal and meningococcal vaccines, to potentially protect susceptible groups.



How to cite this article:
Madhumita P, Gupta N. Clinical and bacteriological spectrum of community-acquired acute bacterial meningitis in adults at a tertiary care hospital in northern India.Int J Nutr Pharmacol Neurol Dis 2011;1:194-200


How to cite this URL:
Madhumita P, Gupta N. Clinical and bacteriological spectrum of community-acquired acute bacterial meningitis in adults at a tertiary care hospital in northern India. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2019 Sep 15 ];1:194-200
Available from: http://www.ijnpnd.com/text.asp?2011/1/2/194/84214


Full Text

 Introduction



Acute bacterial meningitis (ABM) remains a major cause of mortality and long-term neurological sequelae worldwide. Despite the availability of potent newer antibiotics, the mortality rate due to ABM remains significantly high in India and other developing countries, ranging from 16-32%. [1] In India, meningococcal disease is endemic in Delhi and sporadic cases occurred in Haryana, Uttar Pradesh, Rajasthan, Sikkim, Gujarat, West Bengal and Orissa. The last outbreak of meningococcal meningitis in March 2005 in Delhi accounted for 214 cases including 16 deaths. [2]

Studies from various geographical regions reveal that meningitis is caused by various pathogens depending on the patient's age group. In neonates, Group B (49%) and non-Group B Streptococcus species, Escherichia coli (18%), and Listeria monocytogenes (7%) are the most common causative organisms. Children and infants acquire meningitis from infection with Haemophilus influenzae (40-60%), Neisseria meningitidis (25-40%), and Streptococcus pneumoniae (10-20%). The sources of adult meningitis include S. pneumoniae (30-50%), N. meningitidis (10-35%), Staphylococcus (5-15%), other Streptococcus species, H. influenzae (1-3%), Gram-negative bacilli (1-10%), and L. monocytogenes.[3],[4],[5]

Though the incidence of Listeria monocytogenes meningitis is low in most Indian studies, it should be considered especially in the elderly and immunocompromised patients. It is known to be resistant to third-generation cephalosporins used in the empirical treatment of bacterial meningitis. According to reports released by the World Health Organization (WHO), Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae Type b represent the triad responsible for over 80% of all cases of bacterial meningitis worldwide. Other bacteria causing the disease include Gram-negative rods (especially Escherichia coli), streptococci (other than S. pneumoniae), Listeria monocytogenes, and staphylococci. [6]

During non-epidemic conditions, meningococcal disease is most common in children under school age with 50-60% of cases occurring in children three months to five years of age. However, cases are also seen in teenagers and young adults under 25-30 years of age. Young people living in closed communities, such as boarding-school pupils and military recruits, are affected more than other individuals. The incidence among recruits is at least 4-10 times higher than in the general population. [7],[8]

Morbidity, mortality, and prognosis

This depends on the pathogen, the patient's age and condition, and the severity of acute illness. Mortality rates are highest in the first year of life, decrease in mid-life, and increase again in old age. Among bacterial pathogens, pneumococcal meningitis causes the highest mortality rate, which is 20-30% in adults and 10% in children, with a reported morbidity rate greater than 30% in those who are affected. Patients with meningococcal meningitis have a better prognosis, with a mortality rate of 4-5%; however, patients with meningococcemia have a poor prognosis, with a mortality rate of 20-30%.

The prognosis depends on both the severity and the cause of the meningitis. Prolonged or difficult-to-control seizures are predictors of a complication. Cerebral infarction and edema are predictors of poor outcome, as are the signs of disseminated intravascular coagulopathy and endotoxic shock. [7],[8],[9]

Epidemiology of infection

The annual incidence of meningitis caused by S. pneumoniae is 1-2 per 100,000 population in most developed countries. Developing countries have higher incidence rates, up to 20 per 100,000. In temperate climates, the incidence is higher in the cold season than in the warm season. The highest incidence is found in children under two years of age. Incidence decreases in the subsequent age groups to a low level in young adults but again increases in the elderly. The case-fatality rate in pneumococcal meningitis is several times higher than in meningococcal or Hib meningitis. [10],[11],[12] [Table 1]{Table 1}

 Materials and Methods



A prospective study of 120 cases of ABM admitted to the medical wards in Maulana Azad Medical College and Lok Nayak Hospital during the period from November 2007 to October 2008 was carried out. The cases were worked up clinically as per standard medical practice. The investigations included hematology, blood biochemistry and imaging studies as warranted. The cerebrospinal fluid (CSF) examination included cytology, biochemistry, latex agglutination test (LAT), and microbiological tests including the Gram/ acid-fast bacillus (AFB) staining and bacterial culture with sensitivity. Correlation with radiological tests such as magnetic resonance imaging (MRI) brain and computed tomography (CT) head was done. We also assessed the clinical outcome of these patients.

Specifically the following parameters were recorded as part of the study.



Clinical detailsCSF picture including cytology (cell count and type); biochemistry (sugar, protein), sediment staining for Gram stain, AFB staining and culturesPolymerase chain reaction (PCR) for tuberculosis (TB) herpes simplex virus (HSV) andcryptococcal antigen testing where relevantAppropriate imaging studiesLAT on CSF, serum and urine samples

Criteria used for inclusion of cases in the study were the presence of a clinical picture compatible with a diagnosis of bacterial meningitis with either a CSF neutrophilic pleocytosis of at least 50 neutrophils per cubic mm and/or a positive CSF culture for bacterial pathogens and/or a positive LAT for antigen detection. Cases of post-traumatic meningitis and meningitis developing after cranial surgery were excluded. Only one representative CSF sample from every patient was included, consecutive CSF samples from the same patient were ignored for the purpose of the study.

Cerebrospinal fluid

Cell counts, biochemistry smear, culture

The CSF samples were processed immediately. Along with the macroscopic appearance of CSF, a routine total and differential count was done using a standard hemocytometer. A biochemical analysis for protein and sugar was done as well. CSF sediment smears were Gram-stained and AFB-stained using Ziehl Neelsen's technique. Wherever warranted negative staining for capsulated pathogens was also done.

Antigen detection

Detection of soluble antigens of H. influenzae (Type b), S. pneumoniae and N. meningitidis A, C ,Y, W 135, B and E. coli K1 and Streptococcus B in CSF was performed by LAT, using commercial kits (Pastorex TM Meningitis, BIO- RAD , France). Antigen detection was done in serum and CSF samples simultaneously. The urine was also tested for these antigens in ten cases.

Polymerase chain reaction

CSF samples were also processed for polymerase chain reaction (PCR) for TB, HSV antigen detection and cryptococcal antigen testing where clinically indicated.

Statistics

The measurements obtained by the above-mentioned studies were used to calculate mean values for each patient and all cases as a whole. The Students' t test was used for both independent variables. The paired sample t test was performed to compare the difference of means between groups. P<0.05 was considered significant. Data was analyzed with SPSS software Version 13 (SPSS, Chicago, IL.)

 Results



One hundred and twenty consecutive patients with clinical acute meningitis admitted to the department of medicine constituted the study group. The patients had a mean age of 32.58 ± 13.32 years (range 15-70 years). Of these 67 (56%) were male and 53 (44%) were female.

All patients were symptomatic as described in [Table 2]. Fever (98.3%), headache (95.85%), neck stiffness (90.7%), nausea (94.9%) and vomiting (94%) were the common clinical findings. Ten patients (8.5%) had loss of consciousness (los) while four had seizures (3.4%). Six patients (5.15%) also presented with bleeding manifestations, mostly skin bleeding or subconjuctival hemorrhage. Hypotension was noted in 10 patients i.e. 8.1% cases. Skin rash was seen in 16 patients i.e. 13.6%, including the two patients with meningococcemia. Presence of rash in patients of meningitis correlated with a diagnosis of N. meningitidis (P< 0.01). No rash was present in any patient of Streptococcus pneumoniae infection.{Table 2}

It was observed that more serious symptoms occurred in patients with N. meningitides Type A infection or with no detectable pathogen. The latter poses a dilemma of an aggressive infection in the setting of an unconfirmed pathogen, and was associated with a much higher mortality rate.

Evidence for the presence of microbial activity could be detected in 44.1% cases by LAT, whereas a direct microbiological confirmation could be seen in only 22 cases i.e. 18.3%. Streptococcus pneumoniae was the predominant pathogen in 41 of these 120 cases i.e. 34% of all cases. Neisseria meningitides A was detected in 15 (12.4%) and N. meningitides B in six (4.9%). Both cases of meningococcemia tested positive on LAT.

The bacterial pathogen could be demonstrated by the Gram stain in the CSF samples in only three (2.5%) patients, while 22 (18.3%) samples yielded bacterial growth on culture. Streptococcus pneumoniae was the most common pathogen isolated on culture accounting for 14 cases (66.6% of culture-positive cases). Staphylococcus aureus was isolated in one case. An additional 27 cases of culture-negative pneumococcal meningitis could be identified by LAT and by typical morphology on Gram stain (one case). Of the 41 samples positive by LAT, one sample was also Gram-positive on sediment smear. Thus a total of 41 cases (34.16%) were attributed to pneumococcal meningitis in this study.Twenty-three cases were affected by a meningococcus comprising 15 (12.4%) cases with Neisseria meningitides A and six (4.9%) cases with N. meningitides B. There were two cases with meningococcemia. Gram stain demonstrated the characteristic Gram-negative diplococci in the rash smears of two cases. None of the samples yielded growth on CSF culture but LAT was positive in all the samples of meningococcal meningitis tested [Figure 1],[Figure 2],[Figure 3].{Figure 1}{Figure 2}{Figure 3}

Staphylococcus aureus was isolated in one case by Gram staining and culture. No case of E. coli, or Listeria monocytogenes was identified in this series [Table 3].{Table 3}

LAT for detection of capsular antigen of Streptococcus pneumoniae, N. meningitidis and H. influenzae (Type b) were performed on a total of 119 CSF samples. One patient with clinical meningitis and meningococcemia tested serum-positive on LAT but lumbar puncture could not be performed. The test had a positive result in 62 (53%) cases.

As is clear from [Table 4], LAT was positive in all the cases which were picked up by the gold standard, CSF culture, except for one case which was S. aureus meningitis. The S. aureus antigen was not part of the LAT kit we used. This makes LAT a very sensitive test.{Table 4}

[Table 5] shows that CSF LAT was more sensitive than serum LAT in concurrently drawn serum samples. This may also reflect on the degree of septicemia of these patients.{Table 5}

Cerebrospinal fluid polymerase chain reaction

PCR for TB was done in 12 cases in view of a subacute history. It was positive in two patients who were LAT-negative. These patients were started on anti tubercular therapyATT . PCR for cryptococcal antigen and herpes simplex virus was done in two HIV-positive patients. Both samples were negative. Interestingly, in our series, two patients of clinically suspected tubercular meningitis TBM were positive by CSF LAT for N. meningitidis Type b. PCR for TB in the CSF was positive and magnetic resonance imaging (MRI) of the brain showed meningeal enhancement with basal exudates confirming the diagnosis of TB in both these cases. The false positive CSF LAT in these cases may be due to cross reactive antigens.

Bacterial culture

CSF samples from 21 (18.3%) patients were positive on culture in our study. Forty-four of the culture-negative cases were detectable by antigen detection tests. Several studies from India report culture-negative cases of meningitis or a low CSF culture positivity, ranging from 6-50%. [1],[3],[4],[5]

In vitro sensitivity patterns

S. pneumoniae were sensitive to penicillin in 50% (7/14cases), ceftriaxone in 57.14% (8/14) and vancomycin in 90% (11/14) cases. However, in view of the low yield by culture these results need to be interpreted carefully [Table 6].{Table 6}

All of the 120 cases had an elevated cell count in CSF, with a mean of 372 cells /mm 3. Interestingly, the cell count in CSF was relatively higher in cases of S. pneumoniae meningitis (mean 600 cells/mm 3 ) whereas a relatively higher value of CSF protein was seen in meningococcal meningitis with a mean value of 413.6 ± 689.1 mg/dL as compared to a lower 112±47.5 mg/dL in those with pneumococcal meningitis. A higher cell count correlated with a lower CSF sugar. In addition we found that the group with the undetected pathogen had a relatively lower degree of lymphocytosis in CSF (P =0.01).

Clinical outcome

Fourteen out of the 120 patients expired in this study (11.6%). N. meningitidis accounted for five (35.7%) while S. pneumoniae was the agent in one (7.1%) of these deaths in this case series. In eight (57.1%) of the deaths, the pathogen could not be identified. All these 14 cases were culture-negative.

 Discussion



Meningitis is an inflammation of the membranes of the brain, spinal cord and ventricles often from an infective etiology. Broadly it can be divided into three general categories: pyogenic, granulomatous, and lymphocytic. Pyogenic (bacterial) meningitis is a potentially life-threatening disease that consists of inflammation of the meninges and the underlying subarachnoid CSF.Gram-stained smear can immediately diagnose pyogenic meningitis. Some studies have reported a CSF Gram stain sensitivity of 60-90% and a high specificity of >97%, stressing its importance in the rapid and accurate diagnosis of the causative bacteria. [15],[16] In our study, Gram stain on CSF provided an evidence of the causative bacteria in three (2.3%) patients.. The yield of bacteria on a Gram stain depends on several factors like the number of organisms present, prior use of antibiotics, technique used for smear preparation (centrifuged deposit, direct smear etc.), staining techniques and the observer's skill and experience.

CSF samples from only 21 (18.3%) patients were positive on culture in our study. Several studies from India report culture-negative cases of meningitis or a low CSF culture positivity, ranging from 6-50%. In these cases, the use of a CSF bacterial antigen assay based on a LAT that can detect the antigens of H. influenze B, S. pneumoniae, N. meningitidis, E. coli K1, etc. has a theoretical advantage. It is complementary to the Gram stain.

Various reasons cited in the literature for a low yield of bacteria on culture are:



Improper technique of lumbar punctureDelay in transport of specimens to the laboratoryNon-availability of special media for specific pathogens in the emergency settingAutolysis enzymes in CSFFastidious nature of pathogenAntibiotic treatment prior to lumbar puncture.

The false-negative LAT in our study could be possibly because of low antigen titers in the CSF. The clinical usefulness of the convenient latex antigen detection tests is limited as a negative test does not rule out infection and a false-positive test results in a prolonged course of antibiotics. A recent immunization with Hib conjugate vaccine, meningococcal and pneumococcal vaccine may give a false-positive LAT. Nevertheless, several studies advocate the usefulness of LAT, especially in pretreated cases and to differentiate partially treated pyogenic meningitis from tuberculous meningitis. We found LAT to be a simple, rapid procedure suitable to be used as an adjunct laboratory test, though it needs to be interpreted cautiously in the context of the patient's clinical condition.

S. pneumoniae, a Gram-positive coccus, is a common colonizer of the human nasopharynx affecting 5-10% of healthy adults and 20-40% of healthy children. It causes meningitis by escaping the local host defenses and phagocytic mechanisms, either through choroid plexus seeding from bacteremia or through direct extension from sinusitis or otitis media. Presently, it is the most common bacterial cause of meningitis, accounting for up to half of cases. It is also associated with one of the highest mortality rates among the bacterial agents that cause meningitis (19-26%). [10],[11],[17] Risk factors identified for pneumococcal meningitis are Asplenia, hypogammaglobulinemia, multiple myeloma, glucocorticoid therapy, diabetes mellitus, alcoholism and chronic liver disease, renal insufficiency and malnutrition. In our case series, S. pneumoniae accounted for 34% of all cases of ABM in adults and about 60% of the culture-positive patients. Of the 38 patients positive by LAT, 70% were in the age group of 20-40 years with 20% having one or more of the above-mentioned predisposing factors.

N. meningitidis

N. meningitidis is a Gram-negative diplococcus that is carried in the nasopharynx of otherwise healthy individuals. It initiates invasion by penetrating the nasal epithelium and traveling along the perineural spaces causing central nervous system (CNS) infection. In case of meningococcal meningitis, most sporadic cases are caused by serogroups B, C, and Y, while the A and C strains are observed in epidemics (<3% of cases). [18],[19]

Presently, it is the leading cause of bacterial meningitis in children and young adults, accounting for 59% of cases. In our case series it was identified in 16.5% of ABM patients and accounted for 3/14 deaths. The serovars identified were Serovar A in 12/14 patients and Serovar B in 2/14 patients. Over 80% of the patients were in the age group 20-40 years. Serovar A was the most commonly identified pathogen. In view of the availability of an efficacious vaccine against Serovar A, C, Y and W-135, immunization may help curb the mortality and morbidity due to this illness especially in high-risk groups. [20] This may also lead to the development of targeted drug delivery systems. [21]

Staphylococcus species (S. aureus and coagulase-negative staphylococci): Meningitis caused by staphylococci is associated with the following risk factors: (1) status postneurosurgery and posttrauma, (2) presence of CSF shunts (3) infective endocarditis and paraspinal infection and (4) diabetes mellitus. We detected one case of S. aureus by both blood and CSF culture in a diabetic patient.

L. monocytogenes is a small Gram-positive bacillus that causes 8% of bacterial meningitis cases, especially affecting the elderly, neonates and pregnant or immunocompromised patients. It is associated with one of the highest mortality rates (22%). However, this antigen was not part of the control reagent in our LAT kits and it was also not isolated on culture in any of the 120 cases of ABM in our series. No case of H. influenzae, Group B streptococcus or E. coli meningitis was detected in this series. [13],[18]

 Conclusion



In our study, we could identify some proof of the infecting agent (culture and/or smear and/or LAT) in 66 of the total 120 cases. In many cases the etiological agent was identified by LAT alone while all the patients detected by microbiological techniques were picked up by LAT. Though all these CSF samples showed a neutrophilic pleocytosis and were clinically compatible with a diagnosis of pyogenic meningitis, in such cases the final diagnosis can be established only after analyzing other biochemical parameters and tests to rule out the initial stages of tuberculous or viral meningitis.

In developing countries like India where many laboratories lack facilities for culture and other elaborate investigations, LAT can help establish the crucial diagnosis. However, the high costs of LAT kits remain a prohibitive factor for its routine use in most laboratories.

References

1Mani R, Pradhan S, Nagarathna S, Wasiulla R, Chandramuki A. Bacteriological profile of community acquired acute bacterial meningitis: A ten-year retrospective study in a tertiary neurocare centre in South India. Indian J Med Microbiol 2007;25:108-14.
2Kumar Snone , Kashyap Bnone , Bhalla Pnone . The rise and fall of epidemic Neisseria meningitidis from a tertiary care hospital in Delhi, January 2005-June 2007. Trop Doctnone 2008;38:222-4.
3Chandramukhi A. Neuromicrobiology. In: Neurosciences in India: Retrospect and Prospect . The Neurological Society of India, Trivandrum. New Delhi: CSIR; 1989. p. 361-95.
4Chinchankar N, Mane M, Bhave S, Bapat S, Bavdekar A, Pandit A,et al. Diagnosis and outcome of acute bacterial meningitis in childhood. Indian Pediatr 2002;39:914-21.
5Sonavane A, Baradkar VP, Mathur M. Bacteriological profile of pyogenic meningitis in adults. Bombay Hosp J 2008;50:452-5.
6World Health Organization. Meningococcal disease in India 2005. WHO Meningococcal disease in India Peltola H. Spectrum and burden of severe haemophilus influenzae type b diseases in Asia. Bull World Health Organ 1999; 7 :878-87.
7van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical Features and Prognostic Factors in Adults with Bacterial Meningitis. N Engl J Med 2004;351:1849-59.
8Kabra SK, Kumar P, Verma IC, Mukherjee D, Chowdhary BH, Sengupta S, et al. Bacterial meningitis in India: An IJP survey. Indian J Pediatr 1991;58:505-11.
9Rosenstein NE, Perkins BA, Stephens DS, Lefkowitz L, Cartter ML, Danila R, et al. The changing epidemiology of meningococcal disease in the United States, 1992-1996. J Infect Dis 1999;180:1894-901.
10Invasive Bacterial Infection Surveillance (IBIS) group, International Clinical Epidemiology Network (INCLEN). Prospective multicentric hospital surveillance of Streptococcus pneumoniae disease in India. Lancet 1999;353:1216-21.
11Vashishtha VM. Emergence of multidrug resistant pneumococci in India. BMJ 2000;321:1022-3.
12Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Eng J Med 1997;337:970-6.
13Wenger JDnone , Hightower AWnone , Facklam RRnone , Gaventa Snone , Broome CVnone . Bacterial meningitis in the United States, 1986: Report of a multistate surveillance study. The Bacterial Meningitis Study Group. J Infect Disnone 1990;162:1316-23.
14Centers for Disease Control and Prevention (CDC)none . Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae--United States, 2006-2007. MMWR Morb Mortal Wkly Repnone 2008;57:1353-5.
15Elmore JG, Horwitz RI, Quagliarello VJ. Acute meningitis with a negative Gram′s stain: Clinical and management outcomes in 171 episodes. Am J Med 1996;100:78-84.
16Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med 1993;328:21-8.
17Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, LynÞ eld R, et al. Decline in invasive pneumococcal disease after the introduction of protein polysaccharide conjugate vaccine. N Engl J Med 2003;348:1737-46.
18Suri Mnone , Kabra Mnone , Singh Snone , Rattan Anone , Verma ICnone . Group B meningococcal meningitis in India. Scand J Infect Disnone 1994;26:771-319
19Centers for Disease Control and Prevention. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2000;49:1-10.
20Updated Recommendations for use of Meningococcal Conjugate vaccines- Advisory Committee on Immunization Practices (ACIP), 2010. MMRW 2011/60(03);72-76 available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a3.htmnone
21Saini R, Saini S, Sugandha RS. Biotechnology: The novel drug delivery system. Int J Nutr Pharmacol Neurol Dis 2011;1:82-3.