E Sanya, S Taiwo, O Azeez, R Oluyombo
bacteria, empirical, meningitis, therapy, tropics
E Sanya, S Taiwo, O Azeez, R Oluyombo. Bacteria Meningitis: Problems Of Empirical Treatment In A Teaching Hospital In The Tropics. The Internet Journal of Infectious Diseases. 2006 Volume 6 Number 1.
Bacteria meningitis (BM) is commonly associated with high fatality. This study was conducted in Ladoke Akintola University Teaching Hospital, Osogbo, Nigeria, with the view to assessing the outcome and usefulness of empirical therapy of BM. Medical records of patients with BM managed in the year 2004 and 2005 were retrieved and demographic, clinical and laboratory data obtained analyzed using GraphPad computer software. Records of 172 patients were available for analysis; age range was 1day - 80 years, M: F ratio 1.7: 1. Mortality rate was 45.6%; 38.3% had favourable outcome, 8.1% had varying neurological sequelae and 11.5% discharged self against medical advice. Cerebrospinal fluid (CSF) analysis was done in only 68 patients; 30 had CSF parameters suggestive of BM; Gram stain was positive for bacteria in only 18 (26.5%) and culture in 6 (8.9%). Outcome was poorer in dehydrated patients (P=0.032), cases without CSF investigations (P=0.0001), and those who did not receive antibiotics (P=0008). The only empiric antibiotic combination with significant favourable outcome was penicillinG and chloramphenicol (P=0.021). This result shows that empirical treatment of BM is associated with high case fatality.
Since the first recognition of bacteria meningitis (BM) in 18051, mortality from this infection has remained unacceptably high and developmental disabilities and neurologic sequelae following neonatal and infantile meningitis still occur in significant number of survivals. Specific aetiological diagnosis of BM in developing countries is often difficult. Although Gram staining of CSF sediment is a very useful cheap and fairly rapid method of identification of organism, the sensitivity in developing countries is only 25-40%2 when compared to 80-85% in developed countries3. Cultures of CSF are also infrequently performed in many health institutions in developing countries and sensitivity does not exceed 40% with results available only after 2-3days2,4. Other methods such as latex antigen tests (LAT)5 and polymerase chain reaction (PCR)6 that are highly sensitive and specific are expensive and not available for routine use in developing countries.
In Nigeria, epidemics of meningitis due to
In many tertiary health institutions in Nigeria, financial constraints have compelled many clinicians to employ empiric therapy for patients with meningitis without CSF analysis or culture. In this study, we assess the use of empiric therapy for suspected BM in our institution in order to determine its suitability in a resource poor country.
Materials And Method
Medical records of 172 patients clinically diagnosed and managed as BM in Ladoke Akintola University Teaching Hospital, Osogbo, between 2004 and 2005 were retrieved for analysis. Information retrieved included demographic data, height, weight, presenting complaints, results of physical examination, predisposing factors, complications, outcome and problems encountered during management. In those investigated, results of microbiological and other laboratory investigations were also retrieved.
Data entry and management were done with Microsoft Excel on IBM ThinkPad computer. All analyses and calculations were performed using GraphPad software (GraphPad Software Inc, San Diego, USA). Relationship between categorical variables was done using Chi square or Fisher's exact test and for continuous variables using Student's t-test or Mann Whitney test as appropriate and P < 0.05 was taken as significant value.
Of the 172 patients with suspected BM reviewed over the study period, 108 were males and 64 were females giving a male to female ratio of 1.7 to 1. The age of the patients ranged from 1 month to 80 years. The age group 16-50 years constituted the majority (36.2%) followed by age group above 50 years (18.6%), 6-15 years (17.4%), 1-5 years (12.8%), infants (8.1%) and neonates (8.1%) (Table 1).
The common symptoms at presentation were fever in 75.6% of cases, impaired consciousness (50.0%), headache (32.6%), convulsion (27.9%), neck stiffness/pain (18.6%) and others (45.9%). Signs of meningeal irritation such as neck stiffness, Kernig's, Brudzinski and Babinski were found in only 62.8%, 43.0%, 33.7% and 6.2% respectively (Table 2).
Only 68 (42.0%) patients were investigated by CSF microscopy and culture. CSF cell morphology (protein > 45mg/dL, WBC > 50cells/ml and sugar < 2.2mmol/L) was suggestive of BM in 30 (41.1%) patients, 18 (26.5%) of these were positive for bacteria on Gram stain and 6 (8.8%) of these 18 had positive culture,
Sixty two (38.3%) patients recovered completely before being discharged home, while 10 (8.1%) had varied neurological deficits (such as cranial nerve deficit, exaggerated deep tendon reflexes, quadriparesis and quadrilplegia) and 20 (10.5%) discharged self against medical advice (Table 4).
A total of 80 patients died giving a mortality rate of 45.5%. Mortality was significantly associated with severe dehydration (P=0.0319), those who did not have CSF microscopy or culture performed (P<0.0001) and those who did not receive antibiotic therapy (P=0.0008). (Table 4). The antibiotic combination that was significantly associated with favourable outcome was penicillin and chloramphenicol (P=0.021). Ampicillin/gentamicin (P=0.54), ampicillin/chloramphenicol/cephalosporins (P=0.41) and ampicillin/gentamicin/cephalosporin (P=0.46) combinations did not significantly influenced outcome. The presence of clinical symptoms such as convulsion, impaired consciousness and jaundice also did not significantly influenced outcome (P > 0.05). The greatest problem encountered during the course of patients care in this series was financial constraint as many patients were unable to pay for investigations and medications.
The result of this study showed that mortality from BM in Osogbo, Southwestern Nigeria is unacceptably high. The 45.6% mortality rate in this series is far higher than reports of previous studies in other parts of the country13,14,15,16,17,18 and elsewhere.22 This underscores the fact that BM still remains a fatal disease with high mortality, and morbidity in those who recovers.22,23 The outcome of this infectious neurological disease has been shown to largely depend on age, type of organisms, time of initiation and appropriateness of antibiotic therapy, other intercurrent illnesses and immunological status of patient affected.19,20,21 The high mortality in this report might not be unconnected with the fact that more than half (60%) of the patients were treated empirically without any recourse to CSF investigation. The likelihood of using inappropriate antimicrobial agents is high with empirical therapy.
Mortality from BM in our study was significantly higher in cases with dehydration and in cases where basic CSF investigations and antibiotic therapy could not be administered due to financial constraints. Especially in those who did not receive antibiotics, mortality was 100% indicating the grave consequence of BM in those who are not financially empowered in the society and also lend credence to the fact that BM is invariably fatal. Mortality was also high (60%) in cases of BM due to
Apart from the combination of crystalline penicillin and chloramphenicol therapy, which gave a statistically significant favorable outcome, other combination regimen such as ampicillin/gentamicin, ampicillin/chloramphenicol/cephalosporin and ampicillin/gentamicin/cephalosporin gave comparable but poorer outcome. Our observation of a favorable outcome with penicillin/chloramphenicol combination corroborates the findings of Ozumba18 who used the same combination in Enugu, a centre in the same meningitis belt as our centre. However, some recent studies have shown an increase in the incidence and dissemination of strains of
Aside from fever which was present in about 75% of patients, symptoms such as convulsion, altered consciousness, headache and neck pain/stiffness were found in less than 50% of our patients, and these symptoms were notably absent in the neonates. The classical signs of meningitis such as Kernig's and Brudzinski signs were elicited in less than 40% of patients, although when present were associated with poor prognosis. The implication is that clinical diagnosis alone is inadequate as a diagnostic modality for BM, especially in our environment where antibiotic abuse/misuse tends to modify the classical symptoms of BM and therefore creates diagnostic difficulties to unsuspecting physicians. Also, the presence of convulsion and impaired consciousness, which were associated with high mortality in some series25, did not significantly influenced outcome in this study. Their presence should therefore not be seen as a discouraging sign but rather as a challenge to proper investigation and management.
The CSF parameters (sugar, protein and white cell counts) were suggestive of BM in 41% of those investigated by CSF analysis while the 26.5% sensitivity of CSF Gram stain in the study is comparable to what is normally obtained in developing countries4 but culture is correspondingly less sensitive. Factors that may be responsible for this include frequent inappropriate use of antibiotics before presentation, delay in processing of CSF specimens and lack of laboratory facilities to isolate fastidious organisms. For mortality from BM to appreciably decrease, these factors must be addressed.
Our study shows that empiric antibiotic therapy of BM without CSF investigations is associated with extremely high case fatality. We suggest that in a resource poor country like Nigeria with widespread abject poverty, the initial management of BM especially the cost of performance of basic CSF investigation and antibiotic therapy should be borne by the government through the hospital management while the choice of empiric therapy should be guided by research findings.
Dr. Taiwo Samuel S Department of Medical Microbiology, Ladoke Akintola University Teaching Hospital, PMB 5000, Osogbo, Nigeria E-mail: firstname.lastname@example.org Tel: 234 0 80 3343 6344