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Indian Journal of Medical Sciences, Vol. 58, No. 8, Aug, 2004, pp. 327-333 Original Article Characteristics of acute bacterial meningitis in Southeast Turkey Celal Ayaz, Faruk Geyik Mehmet, Salih Hosoglu, Kemal Celen Mustafa, Serife Akalin, Faruk Kokoglu Omer Clinical Microbiology and Infectious Diseases, Dicle University Medical Faculty Code Number: ms04059 ABSTRACT BACKGROUND: Acute bacterial meningitis (ABM) remains a significant worldwide cause of death in adults. Even in the antibiotic era, the mortality rate in ABM remains significant and has been reported in the range of 8-40%. AIM: The aim of this study was to assess the characteristics of epidemiology, clinical manifestations, treatment modalities and outcome of patients with ABM in Southeast Turkey. SETTINGS AND DESIGN: This retrospective study included all cases of community-acquired ABM diagnosed and treated in Dicle University Hospital between June 1996 and December 2002. METHODS AND PATIENTS: The study group consisted of 186 adult patients (110 male, 76 female) with ABM, those patients who are older than 14 years, followed up at Dicle University Hospital from June 1996 to December 2002. Patients' charts were retrospectively reviewed, clinical characteristics were recorded and final data were analyzed. STATISTICAL ANALYSIS: In statistical analyses, the Chi-square test was used for binary variables and Student's t-test for continuous variables. RESULTS: The patients' mean age was 30.2 ± 15.3 years (range 14 to 90 years). On admission, typical symptoms of meningitis were found in most of the patients: headache in 92.5%, fever in 88.2%, and nuchal rigidity in 80.1%. The main predisposing factor for ABM was otitis media (40 patients, 21.5%) and closed head trauma (12 patients, 6.5%). Streptococcus pneumonia was the most common identified pathogen. Twenty-nine patients (15.6%) died during hospitalization period. In multivariate analyses, the significant mortality factor was found as initial level of consciousness, low cerebrospinal fluid/blood glucose ratio, high erythrocyte sedimentation rate and initial treatment by penicillin G. CONCLUSIONS: Although still remains as a serious infection, early diagnosis and effective treatment may reduce fatal outcome and improve the course of the disease in patients with ABM. Ceftriaxone should be considered as the drug of choice for initial empirical therapy, while waiting culture results and vancomycin must be withheld for patients having increased risk of penicillin resistant pneumococci strains. Keywords: Meningitis; epidemiology; mortality; risk factors; treatment INTRODUCTION Meningitis is an inflammation of the meninges, the membranes surrounding the brain and spinal cord. There is always some degree of concomitant encephalitis accompanying meningitis. The infection spreads throughout the subarachnoid space, involving the leptomeninges, brain and spinal cord.[1],[2] This spread may be exceedingly rapid in acute bacterial meningitis (ABM) and death may occur in a few hours. The three most common meningeal pathogens, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, accounted for more than 80% of cases. The disease remains a significant worldwide cause of death in adults[3]. Even in the antibiotic era, the mortality rate from ABM remains significant and has been reported in the range of 8-40%.[4],[5] The clinical course of patients suffering from ABM varies within a large range. Some factors determining the outcome of the patients are: the pathogen (bacterial specifications or increasing development of drug resistance), the patients′condition, and the occurrence of severe complications of the central nervous system such as brain edema, hydrocephalus, brain abscesses, and cerebrovascular alterations.[6] Present study aimed to assess the demographic characteristics, diagnostic difficulties, clinical manifestations, and treatment modalities of the patients with ABM in order to characterize risk factors for the morbidity and mortality. MATERIALS AND METHODS This retrospective study included all cases of community-acquired ABM diagnosed and treated in Dicle University Hospital (DUH) between June 1996 and December 2002. In the seven-year period, 186 adult patients were hospitalized and followed. The patients′ medical records were collected using a standardized data form, for adult patients with ABM patients upper than 14 years old. DUH is a 1050-bed, primary and tertiary referral hospital, which serves a population of almost 5.5 million in the Southeast region of Turkey. The University hospital has most types of medical and surgery units. The criteria for definite diagnosis of culture-proven bacterial meningitis included positive cultures of cerebrospinal fluid (CSF) in patients with clinical presentations of acute bacterial meningitis plus at least one of the following parameters of bacterial inflammation of CSF. They included 1) leukocyte counts >100/mm3 with predominant polymorphonuclear cells in immunocompetent host or >50/mm3 in immunocompromised host; 2) CSF lactate concentrations >3.5 mmol/L; 3) CSF glucose divided by blood sugar value in a ratio <0.4; or 4) CSF glucose <2.5 mmol/L if no simultaneous blood glucose was determined. Diphtheroids, coagulase-negative staphy-lococci, or propionibacteria isolated from CSF were considered etiologic agents only if found repeatedly or if cultured from the tip of an indwelling neurosurgical devices (1). The criteria for definite diagnosis of culture-negative bacterial meningitis included 1) clinical presentations of acute bacterial meningitis; 2) white blood cell count-concentration >500/mm3 and polymorphonuclear leukocyte ratio above 0.7; and 3) demonstrated more than one positive blood culture serving to establish the diagnosis of bacteremia but with no isolation of bacterial pathogens from CSF. The severity of the bacterial meningitis was assessed using the Glasgow Coma Scale (GCS) on admission. Stage I) normal consciousness (Glasgow coma scale score = 15); Stage II) inattention, confusion, and clouding of consciousness (Glasgow coma scale score = 10-14); and Stage III) comatose (Glasgow coma scale score = 3-9). Although, penicillin G was used in 35 cases, ceftriaxone was the first choice in most of the cases. Patients treated with ceftriaxone were intravenously given 50 mg/kg/day (maximum 4 gr/day in two equal doses). Penicillin G (20 million unites/day) was given by intravenous infusion. The duration of treatment was 14 days. Antibacterial agent was changed if there was prolonged fever (38.5 oC) for three days and no recovered parameters of CSF. Eligible patients were also excluded if they had fulminant meningitis that led to death within 48 hours and any cases use combination of more than two antimicrobial agents. The study protocol was approved by the Ethics committee of DUH. Statistical analysis RESULTS Totally 186 patients (110 male, 76 female) were included into this study. The patients′ mean age was 30.2 ±15.3 years (range 14 to 90 years). Forty patients with otitis media (21.5%) and 12 (6.5%) with closed head trauma were identified as the main predisposing factors for ABM. The patients were excluded if meningitis developed after a cranial surgery or acquired from hospital. The patients had a history of closed head trauma before admission was included into the study. On admission, typical symptoms of meningitis were predominant: 92.5% headache 88.2%, fever and 80.1% had nuchal rigidity. S. pneumonia was the most common identified pathogen. In 47 percent of the cases, no pathogen was identified [Table - 1]. Antibiotic treatment before to admission was started in 114 patients (61.6%). Twenty-nine patients (15.6%) died during hospitalization period. In univariate analyses, the significant risk factors for mortality were as follows: elderly age, comatose mental status, low CSF/blood glucose ratio, treatment with penicillin G, and higher erythrocyte sedimentation rate [Table - 2] and [Table - 3]. Variables used for the stepwise logistic regression included sex, headache, nuchal rigidity, brudzinski positivity, kerning positivity, consciousness and treatment. The results revealed that after analysis for all the above variables, only initial level of consciousness (p <0.001) was significant factor for mortality [Table - 4]. DISCUSSION Beside CSF and blood cultures, several rapid diagnostic tests have been developed to aid in the diagnosis of bacterial meningitis.[2] Kanungo and co-workers[7] suggests that the detection of pneumolysin in CSF by coagglutination is a promising new technique for rapid diagnosis of pneumococcal meningitis, and is affordable for routing use in the developing countries. Unfortunately, PCR and the other serological diagnostic methods have not been available in our hospital because of economic limitations. Unusual characteristic of this study is the high rate (47%) of cases with no identifiable pathogen. Unknown etiology varies from 5% to 70% in bacterial meningitis.[8] Despite improved diagnostic methods, the proportion of unknown etiology in ABM has remained constant during recent decades.[9],[10] In previous series, most of the episodes of bacterial meningitis had no identified pathogen in the CSF culture.[3] A recent Singapore study reported an even lower rate of pathogen detection (42%) probably explained by the administration of antibiotics prior to hospitalization.[11] Many large studies on ABM show far lower rates of unknown etiology at 11-15%.[1],[4],[12],[13] Bacteriologic identification ratio of our patients was very low in comparison with other series. The main reason for low bacteriological identification was probably antibiotic treatment before admission. There are three factors affecting antibiotic activity in ABM 1) ability to penetrate the CSF, 2) plasma drug concentration, and 3) intrinsic antibacterial activity of infected fluids.[14],[15] ABM is of special concern because consequences are potentially destructive and isolates with reduced susceptibility to penicillin are found to be increasing. In the previous studies from Turkey, ratio of penicillin resistance in S. pneumoniae and Neisseria meningitidis were lower than those of many other countries.[10],[16],[17],[18],[19] But, there is no recent study on drug resistance in Southeast Turkey of Turkey. Penicillin therapy for ABM has not been preferable in recent years because of the resistance to penicillin found against S. pneumoniae in some countries. However, in many countries the ratio of resistance to penicillin and particularly to ceftriaxone is very low. If the organism is relatively resistant to penicillin, then ceftriaxone or cefotaxime should be used.[20],[21],[22],[23] Many authors recommend vancomycin, usually combined with a third-generation cephalosporin, for treating presumptive or proven pneumococcal meningitis pending penicillin-susceptibility results.[24] Since penicillin resistance remains at very low levels in the majority of infectious diseases centers in Turkey, we recommend that empirical use of vancomycin is not necessary. In present study, penicillin G was not as effective as ceftriaxone for treatment of bacterial meningitis in adults. We suggest that ceftriaxone may be used for initial empirical therapy in adults. Closed head trauma is also one of the main reasons for CSF rhinorrhea and ABM. CSF rhinorrhea occurs in approximately 1%-2% of all cases. Posttraumatic CSF rhinorrhea usually presents acutely, but its appearance may be delayed from several hours to years.[25],[26],[27] High falls from flat-roofed houses and road-traffic accidents are a common cause of death and disability in the southeast Turkey.[28] Closed head injury, chronic otitis media caused to parameningeal infections, mastoiditis and sinusitis are the other important predisposing conditions for ABM in our country. Perhaps, these sorts of infections are related to low socio-economic status and can persist long years. In many studies, different factors were reported as significant factors on mortality in ABM cases.[3],[8],[25] Andersen et al[29] have found transferring from another hospital, old age, mechanical ventilation requirement and marked change in mental status as risk factors for poor outcome. The level of consciousness was reported as a striking factor for prognosis in the other reports and this result was similar to our study[3],[8]. The prognosis of the patients who remained normal consciousness is known to be better, and their influence on prognosis is of statistical significance. Despite the introduction of new antibiotics and diagnostic approaches, no significant changes were found in outcomes of ABM cases during two study periods in our hospital[3]. Mortality is also partially high in the presence of intracranial complications. In conclusion, this study demonstrates that ABM still remains a serious infection. In the Southeast Turkey, low socio-economical conditions and insufficient healthcare system contribute to the problem. Under light of this study, we hope to improve diagnosis and therapeutic strategies for ABM cases. Early diagnosis and treatment may reduce fatal outcome and improve the course of the disease. We suggest that ceftriaxone can be considered as the drug of choice for initial empirical therapy for adults. Future researches should concern improvement of rapid diagnostic test methods and adjunctive therapy to decrease morbidity and mortality from ABM of adults. REFERENCES
Copyright 2004 - Indian Journal of Medical Sciences The following images related to this document are available:Photo images[ms04059t2.jpg] [ms04059t3.jpg] [ms04059t1.jpg] [ms04059t4.jpg] |
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