Prevalence and Diagnosis of Acute Bacterial Meningitis in a Tertiary Care Centre.

Anuradha, N (2010) Prevalence and Diagnosis of Acute Bacterial Meningitis in a Tertiary Care Centre. Masters thesis, Madurai Medical College, Madurai.


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INTRODUCTION: Definition Bacterial meningitis is an acute purulent infection within the subarachnoid Space or throughout the leptomeninges. It is associated with the cns Inflammatory reaction that may result in decreased consciousness, seizures, raised Intracranial pressure (icp) and stroke. The meninges, the subarachnoid space, and The brain parenchyma are all frequently involved in the inflammatory reaction. Epidemiology Bacterial meningitis, an infection of the membranes (meninges) and Cerebrospinal fluid (csf) surrounding the brain and spinal cord, is a major cause Of death and disability worldwide. Beyond the perinatal period, three organisms Transmitted from person to person through the exchange of respiratory secretions Are responsible for most cases of bacterial meningitis: neisseria meningitidis, Haemophilus influenzae and streptococcus pneumoniae. The etiology of bacterial Meningitis varies with age and region of the world. Worldwide, without epidemics One million cases of bacterial meningitis are estimated to occur and 200,000 of These die annually. Case-fatality rates vary with age at the time of illness and the Species of bacterium causing infection, but typically range from 3 to 19% in Developed countries. Higher case-fatality rates (37-60%) have been reported in Developing countries. Up to 54% of survivors are left with disability due to Bacterial meningitis, including deafness, mental retardation, and neurological Sequelae. The epidemiology of bacterial meningitis has changed significantly in Recent years, reflecting a dramatic decline in the incidence of meningitis due to Haemophilus influenzae, and a smaller decline in that due to neisseria Meningitidis, following the introduction and increasingly widespread use of Vaccines for both these organisms. Currently, the organisms most commonly responsible for community Acquired bacterial meningitis are streptococcus pneumoniae (50%), n. Meningitidis (25%), group b streptococci (15%) and listeria monocytogenes (10%). H. Influenzae now accounts for <10% of cases of bacterial meningitis in Most series. Many other microbes and organisms, including mycobacterium Tuberculosis, bacteria, fungi, protozoa and worms, may also cause meningitis or Meningeal inflammation. In economically advanced countries, the mortality of Bacterial meningitis is less than 10 percent but it may be 30 percent or more in Developing countries (greenwood 1987; bryan et al. 1990; bijlmer 1991). The epidemiology is changing swiftly following the development of Conjugated polysaccharide vaccines for invasive hib disease, for meningococcal Meningitis caused by serogroups a, c, y, and w-135 and for pneumococcal Meningitis caused by a range of common serotypes. Bacterial meningitis carries a High mortality and morbidity if untreated or treated late. The success of parenteral Antibiotic therapy depends on early diagnosis. Bacterial profile of meningitis S. Pneumoniae is the most common cause of meningitis in adults >20 years Of age, accounting for nearly half the reported cases (1.1 per 100,000 persons per Year). S. Pneumoniae is acquired through the respiratory route. There are a number Of predisposing conditions that increase the risk of pneumococcal meningitis, the Most important of which is pneumococcal pneumonia. Additional risk factors Include coexisting acute or chronic pneumococcal sinusitis or otitis media, Alcoholism, diabetes, splenectomy, hypogammaglobulinemia, complement Deficiency, and head trauma with basilar skull fracture and csf rhinorrhea. Mortality remains ~20% despite antibiotic therapy. N. Meningitidis accounts for 25% of all cases of bacterial meningitis (0.6 Cases per 100,000 persons per year) and for up to 60% of cases in children and Young adults between the ages of 2 and 20. N. Meningitidis is classified into Serogroups based on the immunological reactivity of the capsular polysaccharide. Although 12 serogroups have been identified, the three serogroups a, b and c Account for over 90% of meningococcal disease. Meningococcal disease differs From other leading causes of bacterial meningitis because of its potential to cause Large-scale epidemics. A region of sub-saharan africa extending from ethiopia in The east to the gambia in the west and containing fifteen countries and over 260 Million people is known as the “meningitis belt” because of its high endemic rate Of disease with superimposed, periodic, large epidemics caused by serogroup a, And to a lesser extent, serogroup c. During epidemics, children and young adults are most commonly affected, With attack rates as high as 1,000/100,000 population, or 100 times the rate of Sporadic disease. The highest rates of endemic or sporadic disease occur in Children less than 2 years of age. In developed countries, endemic disease is Generally caused by serogroups b and c. Epidemics in developed countries are Typically caused by serogroup c although epidemics due to serogroup b have also Occurred in brazil, chile, cuba, norway and more recently in new zealand. The presence of petechial or purpuric skin lesions can provide an important Clue to the diagnosis of meningococcal infection. In some patients the disease is Fulminant, progressing to death within hours of symptom onset. Infection may be Initiated by nasopharyngeal colonization, which can result in either an Asymptomatic carrier state or invasive meningococcal disease. The risk of invasive Disease following nasopharyngeal colonization depends on both bacterial virulence Factors and host immune defense mechanisms, including the host's capacity to Produce antimeningococcal antibodies and to lyse meningococci by both classic And alternative complement pathways. Individuals with deficiencies of any of the Complement components, including properdin, are highly susceptible to Meningococcal infections. H. Influenzae causes meningitis in unvaccinated children and adults. Meningitis caused by h. Influenzae occurs mostly in children under the age of 5 Years and most cases are caused by organisms with the type b polysaccharide Capsule (h. Influenzae type b, hib).the frequency of h. Influenzae type b Meningitis in children has declined dramatically since the introduction of the hib Conjugate vaccine, although rare cases of hib meningitis in vaccinated children Have been reported. While most children are colonized with a species of h. Influenzae, only 2-15% harbour hib. H. Influenzae is acquired through the Respiratory route. An essential virulence factor which plays a major role in Determining the invasive potential of an organism is the polysaccharide capsule of Hib. Meningitis is the most severe form of hib disease. In most countries, However more cases and deaths are due to pneumonia than to meningitis. Escherichia coli k1 are an increasingly common cause of meningitis in Individuals with chronic and debilitating diseases such as diabetes, cirrhosis, or Alcoholism and in those with chronic urinary tract infections. Gram-negative Meningitis can also complicate neurosurgical procedures, particularly craniotomy. Group b streptococcus or s.agalactiae was previously responsible for Meningitis predominantly in neonates, but it has been reported with increasing Frequency in individuals >50 years of age, particularly those with underlying Diseases. Neonatal bacterial meningitis (bacterial meningitis in the first month of life) Is rare but serious, with a mortality up to 30–40 percent and permanent sequelae in Up to 30 percent of survivors. The causative organisms are different from those of Bacterial meningitis at other ages, since most bacterial meningitis in this age group Is due to organisms derived from ascending infection in utero or from the birth Canal during delivery (de louvois 1994). Occasionally outbreaks occur in hospital Nurseries. Neonatal bacterial meningitis is almost always preceded by bacteremia. In uk, the principal causative organisms are gram negative enteric bacilli and Group b streptococci. The latter can cause early onset or late onset disease as long As 3–4 months after birth. Other bacteria, including pneumococci, listeria Monocytogenes, meningococci, other streptococci, and staphylococcus aureus, Can also cause neonatal meningitis. L. Monocytogenes has become an increasingly important cause of Meningitis in neonates (<1 month of age), pregnant women, individuals >60 years, And immunocompromised individuals of all ages. Infection is acquired by Ingesting foods contaminated by listeria. Foodborne human listerial infection Has been reported from contaminated milk, soft cheeses, and several types of "ready-to-eat" foods, including delicatessen meat and uncooked hotdogs. Staphylococcus aureus and coagulase negative staphylococci are Important causes of meningitis that occurs following invasive neurosurgical Procedures, particularly shunting procedures for hydrocephalus, or as a Complication of the use of subcutaneous ommaya reservoirs for administration of Intrathecal chemotherapy. Pathophysiology The most common bacteria that cause meningitis, s. Pneumoniae and n. Meningitidis, initially colonize the nasopharynx by attaching to nasopharyngeal Epithelial cells. Bacteria are transported across epithelial cells in membrane bound Vacuoles to the intravascular space or invade the intravascular space by creating Separations in the apical tight junctions of columnar epithelial cells. Once in the Bloodstream, bacteria are able to avoid phagocytosis by neutrophils and classic Complement–mediated bactericidal activity because of the presence of a Polysaccharide capsule. Bloodborne bacteria can reach the intraventricular choroid Plexus, directly infect choroid plexus epithelial cells, and gain access to the csf. Some bacteria such as s. Pneumoniae can adhere to cerebral capillary endothelial Cells and subsequently migrate through or between these cells to reach the csf. Bacteria are able to multiply rapidly within csf because of the absence of Effective host immune defenses. Normal csf contains few white blood cells (wbcs) and relatively small Amounts of complement proteins and immunoglobulins. The paucity of the latter Two prevents effective opsonization of bacteria, an essential prerequisite for Bacterial phagocytosis by neutrophils. Phagocytosis of bacteria is further impaired By the fluid nature of csf, which is less conducive to phagocytosis than a solid Tissue substrate. A critical event in the pathogenesis of bacterial meningitis is the Inflammatory reaction induced by the invading bacteria. Many of the neurologic Manifestations and complications of bacterial meningitis result from the immune Response to the invading pathogen rather than from direct bacteria induced tissue Injury. As a result, neurologic injury can progress even after the csf has been Sterilized by antibiotic therapy. The lysis of bacteria with the subsequent release of cell-wall components Into the subarachnoid space is the initial step in the induction of the inflammatory Response and the formation of a purulent exudate in the subarachnoid space. Bacterial cell-wall components, such as the lipopolysaccharide (lps) Molecules of gram negative bacteria and teichoic acid and peptidoglycans of s. Pneumoniae, induce meningeal inflammation by stimulating the production of Inflammatory cytokines and chemokines by microglia, astrocytes, monocytes, Microvascular endothelial cells, and csf leukocytes. In experimental models of meningitis, cytokines including tumor necrosis Factor (tnf) and interleukin 1 (il-1) are present in csf within 1–2 h of Intracisternal inoculation of lps. This cytokine response is quickly followed by an Increase in csf protein concentration and leukocytosis. Chemokines (cytokines That induce chemotactic migration in leukocytes) and a variety of other Proinflammatory cytokines are also produced and secreted by leukocytes and Tissue cells that are stimulated by il-1 and tnf. In addition, bacteremia and the Inflammatory cytokines induce the production of excitatory amino acids, reactive Oxygen and nitrogen species (free oxygen radicals, nitric oxide, and peroxynitrite), And other mediators that can induce death of brain cells. Diagnosis Examination of csf still offers the best chance of observing, isolating, and Identifying the causative organism in bacterial meningitis (kaplan et al. 1986b; British society for the study of infection research committee 1995). Lumbar Puncture is particularly valuable if a dose of a parenteral antibiotic has not been Given either before or on hospital admission. The clearance of organisms in csf after antibiotic use was estimated as 2 Hrs for meningococci and 4 hrs for pneumococci (kanegaye et al. 2001). Even if Bacteria cannot be recovered on culture, microscopy is likely to confirm the Diagnosis of bacterial meningitis and may indicate the likely causative organism. Lumbar puncture should never be used as a reason to defer commencing antibiotic Treatment and other resuscitation measures. The ‘door-to-needle’ time for patients Hospitalized for suspected bacterial meningitis should be less than 1 h. Direct microscopy Direct microscopy of uncentrifuged or centrifuged csf may reveal the Presence of bacteria or fungi and can provide immediate confirmation of the Diagnosis. Staining with acridine orange is more sensitive than the gram stain (kleinman et al. 1984). The organisms seen on microscopy in antibiotic-treated Patients may fail to grow on culture, but the morphology and gram reaction of the Organism, the age of the patient, and the clinical features often permit an educated Guess at the identity of the causative organism. Bacterial antigen detection test Tests for bacterial antigen in csf can provide a quick diagnosis, but they Are less sensitive than the gram stain and do not often alter clinical management (maxson et al. 1994). Many tests are based on the agglutination of antibody-coated Latex particles and work quite well for pneumococci, meningococci of serogroups And for group b streptococci. They are less successful for the detection of Serogroup b meningococci. The limulus lysate test is a sensitive test for endotoxin from gram negative Organisms but has not found wide acceptance till date. Rapid identification of the Offending organism by gram's stain characteristics or bacterial antigen detection Testing (badt) allows chemoprophylaxis of contacts whenever indicated Csf culture Csf should be inoculated on to good-quality culture media, always Including at least columbia blood agar and a heated blood agar. Plates should be Incubated in five percent co2 for a minimum of 48 h. If a ruptured cerebral Abscess is suspected, or if meningitis has followed neurosurgery or a history of Previous meningeal trauma, a second blood agar plate should be incubated Anaerobically for 5–7 days. If delay in processing of specimens was anticipated, Csf can be inoculated in trans isolate medium. T-i medium is a biphasic medium That is useful for the primary culture of etiological agents of bacterial meningitis From csf samples. It was used as a growth medium as well as a holding and Transport medium. The possibility of parameningeal infection especially subdural empyema And brain abscess must be considered and pursued actively, if csf shows an Inflammatory response, but no bacteria is seen or cultured or detected by pcr Tests and the patient’s condition is not improving. Ct scans may sometimes fail to Detect intracranial collections of pus. Subdural empyema (or brain abscess) should Be suspected if ‘meningitis’ is diagnosed in a child or young adult in whom there Is a recent history of sinusitis or middle ear infection. The importance of not Missing these conditions lies in the need for urgent neurosurgical and ear, nose, And throat (ent) assessment as part of the management protocol. Most cases of Subdural empyema are initially misdiagnosed as bacterial meningitis. Blood culture For the diagnosis of bacterial meningitis, blood should be collected when a Spinal tap is contraindicated or cannot be performed for technical reasons. Blood Should be cultured in trypticase soy broth (tsb) or brain heart infusion with a Growth supplement and chemical inhibitors such as 0.025% sodium polyanethol Sulfonate(sps). Polymerase chain reaction Pcr tests for the detection of meningococcal and pneumococcal Dna in csf are now used routinely in the uk. Meningococcal pcr is specific And sensitive for the diagnosis of meningococcal meningitis (borrow et al. 1997) And provides serogroup information in the majority of cases. Amplification of Sections of 16s ribosomal rna, common to most species of pathogenic bacteria, May also prove to be of value (greisen et al. 1994). Treatment Bacterial meningitis is a medical emergency. The goal is to begin antibiotic Therapy within 60 min of a patient's arrival in the emergency room. Empirical Antimicrobial therapy is initiated in patients with suspected bacterial meningitis Before the results of csf gram's stain and culture are known. S. Pneumoniae and N. Meningitidis are the most common etiologic organisms of community-acquired Bacterial meningitis. Due to the emergence of penicillin and cephalosporin Resistant s. Pneumoniae, empirical therapy of community acquired suspected Bacterial meningitis in children and adults should include a combination of Dexamethasone, a third-generation cephalosporin (e.g., ceftriaxone or cefotaxime) And vancomycin plus acyclovir, as hsv encephalitis is the leading disease in the Differential diagnosis. Ceftriaxone or cefotaxime provide good coverage for Susceptible s. Pneumoniae, group b streptococci, and h. Influenzae and adequate Coverage for n. Meningitidis. Cefepime is a broad spectrum fourth generation Cephalosporin with in vitro activity similar to that of cefotaxime or ceftriaxone Against s. Pneumoniae and n. Meningitidis. Ampicillin should be added to the empirical regimen for coverage of l. Monocytogenes in individuals <3 months of age, those >55 or those with suspected Impaired cell-mediated immunity because of chronic illness, organ transplantation, Pregnancy, malignancy or immunosuppressive therapy. In hospital acquired Meningitis, and particularly meningitis following neurosurgical procedures, Staphylococci and gram negative organisms including p. Aeruginosa are the most Common etiologic organisms. In these patients, empirical therapy should include a Combination of vancomycin, ceftazidime, cefepime or meropenem. Ceftazidime, Cefepime or meropenem should be substituted for ceftriaxone or cefotaxime in Neurosurgical patients and in neutropenic patients, as ceftriaxone and cefotaxime Do not provide adequate activity against cns infection with p. Aeruginosa. Meropenem is a carbapenem antibiotic that is highly active in vitro against l. Monocytogenes, has been demonstrated to be effective in cases of meningitis Caused by p. Aeruginosa, and shows good activity against penicillin-resistant Pneumococci. Prevention The risk of secondary cases of meningococcal disease among close contacts (i.e. Household members, day-care centre contacts, or anyone directly exposed to The patient’s oral secretions) is high. Antimicrobial chemoprophylaxis with a short Course of oral rifampin or a single oral dose of ciprofloxacin, or a single injection Of ceftriaxone is effective in eradicating nasopharyngeal carriage of n. Meningitidis. Although very effective in preventing secondary cases, antimicrobial Chemoprophylaxis is not an effective intervention for altering the course of an Outbreak. In epidemics, mass chemoprophylaxis is not recommended. Vaccines have an important role in the control and prevention of bacterial Meningitis. Vaccines against n. Meningitidis, h. Influenzae, and s. Pneumoniae Are currently available, but the protection afforded by each vaccine is specific to Each bacterium and restricted to some of the serogroups or serotypes of each Bacterium. In industrialized countries, routine use of polysaccharide-protein hib Conjugate vaccines for immunization of infants has almost eliminated hib Meningitis and other forms of severe hib disease. Pneumococcal polysaccharide Vaccines have been used to prevent disease in the elderly and in persons with Chronic illnesses that may impair their natural immunity to pneumococcal disease. Meningococcal polysaccharide vaccines are generally used in response to Epidemics and for the prevention of disease in travellers although other uses are Currently under investigation. In addition to the existing armamentarium of vaccines, new generation Vaccines against meningococcal and pneumococcal disease are under development And evaluation. These vaccines may provide a high degree of protection and broad Coverage in all age groups. Until these vaccines become widely available, the Current vaccines should be used appropriately and efficiently. Use of any of these Vaccines will require laboratory identification of the agents causing disease in Addition to epidemiological information about the age and risk groups that are Most affected. Though various indian studies on epidemiology and comparison of various Diagnostic techniques for acute bacterial meningitis are available, no such study Has been carried out in madurai. Since government rajaji hospital, madurai (grh) is the largest tertiary care hospital attached to madurai medical college Catering the needs of lakhs of people from southern districts of tamilnadu, the Present study was carried out among patients admitted at medicine & paediatric Wards at grh and the data were analysed with reference to objectives. Efforts Have been made to diagnose acute bacterial meningitis by collecting the csf from Patients satisfying the inclusion criteria and processing them by various Microbiological techniques like gram stain, culture (direct and after trans isolate Medium inoculation) and latex agglutination test.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Prevalence ; Diagnosis ; Acute Bacterial Meningitis ; Tertiary Care Centre.
Subjects: MEDICAL > Microbiology
Depositing User: Subramani R
Date Deposited: 19 Aug 2017 02:21
Last Modified: 19 Aug 2017 02:21

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