Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking?

Gudina et al. BMC Neurology (2016) 16:153 DOI 10.1186/s12883-016-0678-0 RESEARCH ARTICLE Open Access Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking? Esayas Kebede Gudina1,2*, Markos Tesfaye2,3, Aynishet Adane4, Kinfe Lemma5, Tamiru Shibiru6, Andreas Wieser7,8,9, Hans-Walter Pfister10 and Matthias Klein10 Abstract Background: Bacterial meningitis is associated with significant morbidity and mortality despite advances in medical care. The main objective of this study was to assess the association of adjunctive dexamethasone treatment with discharge outcome of patients treated as bacterial meningitis in low income setting. Methods: A retrospective study was conducted at four teaching hospitals across Ethiopia. Patients of age 14 years and older treated as cases of bacterial meningitis between January 1, 2011 and April 30, 2015 were included in this study. Information regarding sociodemographic data, clinical presentations, laboratory data, treatments given and status at hospital discharge were retrieved from patients’ medical records using a structured questionnaire. Predefined outcome variables at discharge were analysed using descriptive statistics. Multivariable logistic regression was used to identify factors independently associated with poor outcome. Results: A total of 425 patients treated with the presumptive clinical diagnosis of bacterial meningitis were included in this study (lumbar puncture done in 56 %; only 19 % had CSF findings compatible with bacterial meningitis, and only 3 % had proven etiology). The overall in hospital mortality rate was 20.2 %. Impaired consciousness, aspiration pneumonia, and cranial nerve palsy at admission were independently associated with increased mortality. Adjuvant dexamethasone, which was used in 50.4 % of patients, was associated with increased in-hospital mortality (AOR = 3.38; 95 % CI 1.87–6.12, p < 0.001) and low Glasgow outcome scale (GOS) at discharge (AOR = 4.46 (95 % CI 1. 98–10.08). This association between dexamethasone and unfavorable outcome was found to be more pronounced in suspected but unproven cases and in those without CSF alterations compatible with bacterial meningitis. Conclusion: Most patients treated for suspected bacterial meningitis did not receive proper diagnostic workup. Adjuvant dexamethasone use in clinically suspected but unproven cases of bacterial meningitis was associated with an increased mortality and poor discharge GOS. These findings show that there are potential deleterious effects in unconfirmed cases in this setting. Physicians practising under such circumstances should thus abide with the current recommendation and defer the use of adjuvant corticosteroid in suspected cases of bacterial meningitis. Keywords: Bacterial meningitis, Outcome, Dexamethasone, Ethiopia, East-Africa (Continued on next page) * Correspondence: 1 Department of Internal Medicine, Jimma University, Jimma, Ethiopia 2 Centre for International Health, Ludwig-Maximilians-University, Munich, Germany Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Gudina et al. BMC Neurology (2016) 16:153 Page 2 of 8 (Continued from previous page) Abbreviations: ABM, Acute bacterial meningitis; AOR, Adjusted odds ratio; CI, Confidence interval; COR, Crude odds ratio; CSF, Cerebrospinal fluid; GCS, Glasgow coma scale; GOS, Glasgow outcome scale; HIV, Human immunodeficiency virus; LAMA, Left against medical advice; LOS, Length of (hospital) stay; OR, Odds ratio; SD, Standard deviation; TBM, Tuberculous meningitis; WHO, World health organization Background Bacterial meningitis is a serious infection of the central nervous system that can progress rapidly and result in death or permanent debilitation [1]. It is associated with a high fatality rate despite advances in medical care [2] and a significant proportion of survivors suffer from long term neurologic sequelae [3]. Most of the cases of acute bacterial meningitis (ABM) occur in low income countries [4] where case fatality rates are higher than in countries with a high standard of medical care [5, 6]. The duration of disease [7], age [8], and immune status of the patient [9–11], timing of antibiotic initiation [12, 13], and type of microorganism [14, 15] were found to be important factors in determining the outcome of ABM. Significant controllable factors known to improve survival and neurologic recovery are rapid diagnosis and an early treatment [12, 16], both of which are difficult to achieve when laboratory support and treatment options are limited [4]. Corticosteroid as adjunctive treatment of ABM is one of the most thoroughly studied and widely discussed controversial issues in recent years [17–21]. Yet, its benefit in mortality and morbidity reduction is far from being settled [20–23]. The existing evidences indicate that the efficacy of dexamethasone varies with etiologic agents [24, 25], clinical circumstances and regions of the world [19, 24–27]. The current adult recommendations limit its use to pneumococcal meningitis in high income countries [24, 25]. Furthermore, the few studies from the developing world did not find any benefits of corticosteroid on mortality and neurologic sequelae [28–30]. We recently analysed the characteristics of 425 patients who were treated and discharged with the presumed diagnosis of bacterial meningitis. One of the main findings was that CSF analysis was done in only 56 % of these patients and the diagnosis could be proven by detection of a causative pathogen in as little as 3.3 % of patients [31]. Now we aimed to assess treatment outcomes and factors associated with poor outcome in these patients. We especially aimed to investigate the effect of adjunctive dexamethasone treatment on the outcome of patients treated for suspected ABM in the four study centres in Ethiopia. Methods Settings Ethiopia is a country located in East Africa with an estimated population of 87,952, 000 as of July 2014 [32]. This study was conducted at four teaching hospitals in Ethiopia – Jimma University Specialized Hospital, Hawassa University Referral Teaching Hospital, University of Gondar Hospital and Arba Minch Hospital. The first three are full-fledged university hospitals serving as referral hospitals. Arba Minch hospital is a general hospital affiliated (...truncated)