Objective:
The aim of this study was to obtain data on predisposing factors, causative organisms and their associated mortality and complications related to acute bacterial meningitis.
Methods:
The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga Khan University Hospital from January 1995 through December 2001.
Results:
One hundred ninety-four patients were included in study. There were 146 males and 48 females. The mean age of our study population was 41±12.3 years. One hundred and ninety (97.9%) patients had community acquired meningitis; only 4 (2.0%) patients developed meningitis nosocomially. The two most common predisposing factors were diabetes mellitus (13.9%) and otitis media (7.7%) among all 194 patients. A significant proportion of patients with complications had diabetes mellitus (24.6%, p
Conclusion:
Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality. Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetes mellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictors of a poor outcome (JPMA 53:580;2003)

Ahmad, B.

Ali, S. S.

Beg, Mohammad Asim

Khan, A. A.

Khan, M. A.

Rabbani, M. A.

Wasay, Mohammad

English

eCommons@AKU

Original ArticlesSpectrum of Complications and Mortality of Bacterial Meningitis: an ExperienceM. A. Rabbani, A.A. Khan, S. S. Ali, B. Ahmad, S. M. Baig, M. A. Khan, M. WasayDepartment of Medicine, Aga Khan University, Karachi.Objective: The aim of this study was to obtain data on predisposing factors, causative organisms and theirassociated mortality and complications related to acute bacterial meningitis.Methods: The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga KhanUniversity Hospital from January 1995 through December 2001.Results: One hundred ninety-four patients were included in study. There were 146 males and 48 females. Themean age of our study population was 41±12.3 years. One hundred and ninety (97.9%) patients had community-acquired meningitis; only 4 (2.0%) patients developed meningitis nosocomially. The two most commonpredisposing factors were diabetes mellitus (13.9°/x) and otitis media (7.7%) among all 194 patients. A significantproportion of patients with complications had diabetes mellitus (24.6°/x, p<0.001). CSF and blood cultures werepositive in 53 (27.3%) and 42 (21.6%) patients respectively; there was no statistical difference found. The mostcommon organisms isolated were Streptococcus pneumoniae in 35 (36.8%) patients followed by Neisseriameningitides in 30 (31.5%) patients. Approximately 68% of positive cultures yielded S. pneumoniae and N.meningitides (p<0.0001). The overall mortality rate was 22.1 %. The mortality rate for Streptococcus pneumoniaewas 17.1 %. The highest mortality was observed in patients with Pseudomonal meningitis where all four patientsexpired followed by mortality rate of 85.7% in Escherichia coli afflicted patients (p<0.001). Complicationsoccurred in 73 (37.6%) patients with persistent complications in 31 (42.4%) patients. Complications resolved in34 (46.5%) patients. The most common complications were seizures (12.8%) and cranial nerve palsies (11.3%).Seizures were more likely to occur in older patients (p<0.05) whereas hydrocephalus was more common inyounger patients (p<0.05).Conclusion: Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality.Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetesmellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictorsof a poor outcome (JPMA 53:580;2003).IntroductionBefore the advent of antibiotics, bacterial meningitiswas almost exclusively a fatal disease, with a case fatalityrate of 95% to 100% for patients with pneumococcalmeningitis, 90% for those with Haetnophilus influenzaemeningitis and 70-90% for those with rneningococcalmeningitis1. The use of antibiotics has drastically reducedmortality. However, despite further progress inantimicrobial therapy, the fatality rate and sequelae ofmeningitis due to pneumococcus, which is the organismmost often responsible for bacterial meningitis in adults, hasremained unchanged (20% to 40%) during the lastdecades. 1 -3A major cause for mortality and sequelae of bacterialmeningitis are intracranial complications arising during theacute phase of the disease causing secondary braindamage.-1,7 Most of the clinical reports on suchcomplications during bacterial meningitis stem from casesi nvolving infants and children where H. influenzae is theVol 53, No. 12, December 2003from a Developing CountryAbstractmost frequent etiological agent, however only a few studieshave focused on the clinical and pathological features of theillness in adults.b , 7-10Knowledge of the entire clinical spectrum ofcomplications and their prompt detection are a prerequisitefor the improved management of the disease. Therefore, theaim of this study was to obtain data on predisposing factors,causative organisms and their associated mortality andcomplications.MethodsWe reviewed the charts of all patients in whom acutebacterial meningitis was diagnosed at The Aga KhanUniversity Hospital from January 1995 through December2001. Patients who were initially treated at other hospitalsbut were transferred to this hospital for further therapy,those with acute illness (less than seven days of symptoms)and a definite or probable bacterial cause were alsoi ncluded. A nosocomial infection was defined accordim , to580the 1988 guidelines of the Centers for Disease Control.„Although these guidelines do not specify a length ofhospitalization before the onset of meningitis, in our studynosocomial infection was defined as development ofmeningitis after 48 hours of hospitalization or within oneweek of discharge.The diagnosis of meningitis caused by a specificbacterial pathogen was based on a compatible clinicalpicture and one of the following: a positive cerebrospinalfluid culture; or a negative cerebrospinal fluid culture witha finding of neutrophilic pleocytosis and one of thefollowing: a positive blood culture, identification of gram-negative diplococci on Gram's staining of cerebrospinalfluid, or sputum or throat cultures positive for Neisseriameningitides in patients with a petechial or purpuric rashand a fulminant course. In addition, episodes of "culture-negative" bacterial meningitis were included in ouranalysis. These episodes were diagnosed on the basis of acompatible clinical picture and pleocytosis of at least 100neutrophils per cubic millimeter (0.1 x 109 per liter) despitenegative blood and cerebrospinal fluid cultures and resultsof cerebrospinal fluid Gram's staining that were negative,with any one of the following: a cerebrospinal fluid pressureof greater than 180 mm of Hg, a cerebrospinal fluid proteinconcentration greater than 45 mg /dl, or a cerebrospinal fluidglucose concentration less than 40 mg/dl or less than 40%of random blood glucose measured concomitantly, providedthat random blood glucose is greater than 250 mg/dl.Partially treated meningitis was defined as cases ofmeningitis, which were diagnosed at some other hospitaland received initial antibiotics there, were later shifted toAKUH. Stage I of bacterial meningitis was defined aspatients with classical triad of Bacterial Meningitis (fever,stiff neck, altered mentation). Stage 11 comprised of stage Itogether with complications secondary to bacterialmeningitis. Stage III represented patients with coma.Mortality was classified as meningitis-related ifdeath was due to meningitis or its complications, but not ifit was due to a preexisting serious illness after bacteriologiccure and clinical recovery from meningitis.The data was analyzed using SPSS version 10.0software. The chi-square and Fisher's exact tests were usedfor statistical analysis.We analyzed the medical charts of 194 patientsbetween the study period of January 1995 to July 2002.There were 146 males and 48 females. The mean age of ourstudy population was 41±12.3 years. One hundred andninety (97.9%) patients had community-acquiredmeningitis; only 4 (2.0%) patients developed meningitis58 1Resultsnosocomially. The underlying predisposing factors aresummarized in Table 1. The two most commonpredisposing factors were diabetes mellitus (13.9 0,%) andotitis media (7.7%) among all 194 patients. A significantproportion of patients with complications had diabetesmellitus (24.6%, p<0.001).Table 1. The underlying predisposing factors in 194 patients withacute bacterial meningitis.Piuurc. Swumary of s~'in~nuuu amts _	, u. I Iel ~Y.'li amThe most common presenting" symptoms were 1cver(90.7%) and headache (83.5`.'-0). The most common sign \vasneck stiffness (87.1%). An overview ol'symptoms and signsare shown in Figure.CSF and blood cu1turCS WCCC positive in 53 (27.')(0and 42 (21.6`%) patients respectively;_ there was nostatistical difference found. Tlie most common ort anis+nsi solated were Streptococcus pneumoniae in 35 (36.8"- )patients followed by Neisscria mcnjnl-iit9des ill 3() 139patients. Approximately 68% of positive cultures y'ieided S.pneumoniae and N. meningitides (1r==0.0001 ).J Pak Med AssocPredisposing Factor No. ofpatients PercentageNil 7 7, 39.6Diabetes 27 1 3.9Otitis Media 1 5 7.7Tuberculous meningitis 11 5.6CSF Leakage 9 4.6Upper Respiratory Tract Infection 8 4.1Pneumonia 7 3.6Upper respiratory tract infection 5 2.5Neurosurgery 4 2.0Pulmonary T13 4 2.oSinusitis 3 1.5Contact with patients 2 1.0Mastoiditis 2 I.0Conjunctivitis I 0.;>Table 2. Culture isolated pathogens vs mortality.Vol. 53. No. 12. Decembe 2003Table 3. Various. complications in 194 patients.The overall mortality rate was 22.1%. The mortalityrate for Streptococcus pneumoniae was 17.1%. The highestmortality was observed in patients with Pseudomonalmeningitis where all four patients expired followed bymortality rate of 85.7% in Escherichia coli afflicted patients(p<0.00I ). Table 2 shows all the organisms and respectivet uortaliiv , rates.Complications occurred in 73 (37.6%) patients withpersistent complications in 31 (42.4%) patients.Complication resolved it. 34 (46.5%) patients: eight patientsTable 4. Predictors of mortality of bacterial meningitis in 194patients.were lost to follow-up. Table 3 summarizes all thecomplications observed in 194 patients. The most commoncomplications were seizures (12.8%) and cranial nervepalsies (11.3%). Seizures were more likely to occur in olderpatients (p< 0.05) whereas hydrocephalus was morecommon in younger patients (p<0.05). The difference inproportion of cranial nerve palsies between pediatric andadult population was, however, not significant. Table 4shows complications and mortality rates in various stages ofbacterial meningitis. A statistically significant differencewas observed among different stages of bacterial meningitiswith respect to complications and mortality (p<0.05).DiscussionAcute bacterial meningitis causes many deaths andsubstantial long-term morbidity throughout the world.! Incountries with few resources, the incidence of this disease isabout 10 times greater than that in well-resourced Countries.In developing countries, 12-15% of individuals with thisdisease die, compared with 5% in developed countries."Bacterial meningitis is more common in the veryyoung and the elderly. In the present series. more elderlypatients were affected by acute bacterial menitt-itis. Inbacterial meningitis there is a slight male predominance.Men outnumbered women by a ratio of 6:5 in a Germanstudy of bacterial meningitis in adults. 1 3 However, oneTaiwanese study of Gram-negative bacillary meningitis illadults found a ration of 6:1. 1 4 A male predominance of 3:1was also found in our study.58 2Pathogens No. of patients % No. expiredFatalityStrep. Pncumoniae 35 36.8 6 1 7.1N. Meningitides 30 31.5 3 1 0.0Staph. Aureus 8 8.4 3 37.5E. Coli - 7 7.3 6 85.7Pseudomonas 4 4.2 4 1 00Acinetobactor 4 4.2 3 75Klcbsiella 4 4.2 3 75Cryptococcal 2 2.1 0 0Multiple 1 1 . 0 0 0Complication No. of patients PercentageSeizures 25 1 2.8Cranial Nerve Palsies 22 11.38th Nerve Palsy 1 1 50.07th Nerve Palsy 7 31.86111 Nerve Palsy 2 9.03rd Nerve Palsy 2 9.0SIADII 1 4 7.21-lemiplegia 1 4 7.2Hydrocephalus 1 2 6.1Deafness 11 5.6DIC 9 4.6Monoplegia 8 4.1Aphasia 6 3.0Septic Arthritis" 4 2.0Paraplegia 2 1.0I -l opes labial is 2 1.0Acute renal failure 1 0.5Tinnifus / VCrll(-)o 1 0.5Variable Fatal cases Fatal Cases (%) P valueAge (years)< 60 26/146 17.8 < 0.05>60 1 7/48 35.4GenderMale 30/146 20.5 =0.21Female 1 3/48 27.0Diabetes mellitusYes 1 8/27 66.6 < 0.0001No 25/167 1 4.9CulturePositive 32/95 33.7 < 0.00•Negative 11/99 11.1SeizuresYes 1 3/25 52.0 < 0.005No 30/169 1 7.7The majority ifepisodes ofacute bacterial meningitis inour study were community-acquired (97.9%). In contrast,Durand et all y reported a nosocomial infection rate of 40%, thissignificant discrepancy is likely attributable to the inclusion ofneurosurgical patients in this Massachusetts review.More than 70% of our patients had at least oneunderlying disease or condition. Predisposing factors foracute bacterial meningitis include otitis media, sinusitis,pneumonia, endocarditis, head injury, neurosurgicalprocedures, immunodeficiency, diabetes mellitus,alcoholism and CSF leak. 1 5 Diabetes mellitus came out tobe the most important underlying condition in this study.The vast majority of patients presented with fever andnuchal rigidity, yet only 63% completed the classic triad byreporting headache. The incidence of seizures in our study was15.4%. This is comparable with earlier studies, which reportedrates of 5-23%. 1 3 , 15 , 1 6 Seizure activity was significantlyassociated with mortality (p<0.05). The frequency ofhydrocephalus in our study (6.1%) is comparable withobservations of other authors in childhood meningitis. 1 7-19Hearing impairment is a well-known sequela of acutebacterial meningitis in children.22 0, 21 In a prospective study, theincidence of hearing loss as determined by electric responseaudiometry and conventional tests was 31% with S.Pneumoniae.'-° Although out clinical experience leads us tobelieve that hearing abnormalities are more frequent in children,we have no scientific evidence to substantiate the observationsince long-term follow-up investigations were not performed.Streptococcus Pneumoniae species have been themajor cause of bacterial meningitis in many countries. 1 6,22As a whole it was the most common causativemicroorganism demonstrated in our patients followed byNeisseria Meningitides.Despite advances in anti-microbial therapy, anoverall mortality of 22.1% (43 patients) was observed,similar to rates seen in other studies. 15,16,21 Previous studies,as well as our own, have shown that certain prognosticfactors correlate with a poor outcome in patients withbacterial meningitis. 1 5 , 1 6 In this study, a higher mortality wasobserved in the elderly, in patients with diabetes mellitus, inthose with seizures when occurring as a complication,positive cultures, and stage III of bacterial meningitis.ConclusionBacterial Meningitis remains a serious diseaseassociated with substantial morbidity and mortality in spite ofdevelopments in microbial diagnostic techniques and advancesi n antibiotics. Most cases are community acquired with S.Pneumoniae being the most common pathogen. Old age,diabetes mellitus, a positive culture, seizures as a complicationand late stage in the disease are the important predictors of a583poor outcome.Better management of the complications might be animportant factor in decreasing the mortality rate in bacterialmeningitis. The disease must be suspected on clinical grounds,and pursued with the prompt lumbar puncture and bloodcultures. Given the inherent urgency of bacterial meningitis,appropriate antibiotic therapy should be instituted promptlyand should not be delayed until brain imaging is completed.Since S. Pneumoniae is the major pathogen, the importance ofprevention of i nfection cannot be overemphasized.ReferencesSwartz MI•l. Bacterial Meningitis: snore involved than just die meninges. NFag] J Med 1984;311:912-14.2.	Geiseler PJ, Nelson KE, Levin S, et al. Community acquired purulentmeningitis: a review of 1,1316 cases during the antibiotic era 1954-1976 ReNInfec Dis 1980;2:725-45.Bruyn GAW, Kiemer HPH, deMaiie S, et al. Clinical evaluation ofpneumococcal meningitis in adults over a twelve-rear penod. Eyr 1 CamMicrobiol Infect Dis 1989;8:695-700.Smith JF, Landing BF{. Mechanisms of brain damage to H. uifluenzacmeningitis. J Neuropathol Exp New of 1 960:19.248-65Dodge PR, Swattz MN. Bacterial ineningitis-a review of selected aspect;. 1]'special neurological problems, postmeningitic complication; ;111(1chnieovathologic cotrelations. N Engi 'J Med 1965:272:954-606. Thomas VH, Hopkins IJ. Arieriographic demonstration of vasculai lesions inthe study of neurological deficit in advanced haenrophifus influenzaemeningitis. Dev Med Child Neuro. 1972,14:783-7.7. I garashi M, Gilmartin RC, Gerald B, et al. Cerebral arteinis and bacterialmeningitis. Arch Neurol 1984:41:531-58. Gado M. Axley J, Appleton DB, et aJ. Angiofraphy in in ,-, acute andpostireatment phases of Haemophi]us influenzae rnenin ,citis. Radmioic1 974;110:439-44.9. Lyons EL, Leeds NE. The angiographic demonstration of arterial vasculardisease in purulent meningitis- .Radiology 1967:88:935-8.1 0. Headings DL, Glasgow LA. Occlusion of the internal carotid airier`complicating Flaemophilus influenzae meningitis. Am J Dis Child1 977 1 1 31:854-6.Garner IS, Jarvis WR, Etnon 1G. e t a]- CDC definitions for nosocomiali nfections. Ain .1 I nfect Contio. 1988:16:128-40.1 2. Qazi SA, Khan MA, IV4ughal N, et al. Dexamethasone and bacterial meningitisi n Pakistan. Aicli Dis Child 1996:75.482-8,1 3. Pfister fi W, Feiden W, Einltaupl KM. The spectrum of ccmiplieations duringbacterial meningitis in adults: resu]ts of a prospective clinical stuck ArchNeurol 1993,50:576-80.1 4..tang TN, Wang FD, Wang LS. et al. Grain-negative bacifary mcnin4ltis inadults: a recent six-year experience. l 1= onnos Med Assoc 1 993:92:540-6-l 5. Dtuand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meuinp[tis i nadults: A review of 493 episodes. N Engl f Med 1993:328:2?-81 6. Sigurdardoltir B. Bjontsson OM, Jonsdouir KE, ei at Actue bacicrufmeningitis in adults: A 20-year oveivicw. Arch Intern Med 1997:157:4-5-301 7 Stoviing J, Snvder RD. Computed tomography in childhood buctenameningitis. J Pediatr 198Q96:820-31 8. Bodino .1, Lylyk P, Del Ville M, et al. Computed tomographv in puruhutmeningitis. Am.1 Dis Child 1982:136:495-5011 9. Snydei RD. Venuiculoniegaly in childhood bacte;-ial u;anu~nuNetuopcdiatrics 1984:15:136-8.20. Dodge PR, Davis H, Feigin RD, ct al: Prospective evaluation of hcarnngi mpairment as a sequela of acute bacterial meningitis- N EngI .1 Mcd1 984:311:869-74.21. Pomeroy SI„ Holntes S1, Dodge IT, et al. Seizmcs and other neuroloricsequelae of bacterial meningitis in children. New Engl J Med 1990_323:1651-Z22. Schuchat A, Robinson K, Wenger JD, et al. Bacterial Meningitis in the UnitedStates in 1995. 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Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country

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Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country

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