Community-Acquired Bacterial Meningitis in Adults: Antibiotic Timing in Disease Course and Outcome

Abstract

Word count of the abstract: 296 Word count of the text: 2695Key words: bacterial meningitis, adults, risk factors, antibiotic timing, clinical outcome Conflict of interestNone. Authors' contributionsBoth authors planned, wrote, reviewed and revised the article and approved the final version of the manuscript. Dr Lepur was primarily responsible for data collection and basic statistics. Prof Baršić performed advanced statistical tests. 2 ABSTRACT ObjectivesDespite improvements in diagnostic and therapeutic approach to adult patients with bacterial meningitis, the overall mortality rate is still high. The aim of this study was to evaluate antibiotic timing in the course and outcome of bacterial meningitis.. MethodsTwo hundred and eighty six patients with community-acquired bacterial meningitis aged 14 years and more were included in this retrospective cohort study. Observational period was between 1 January 1990 and 31 December 2004. To assess the association of antibiotic timing and disease outcome we analyzed three timing periods (according to the onset of disease, onset of consciousness disturbance and the time of admission to hospital). Analysis was also performed in a subgroup of culture positive meningitis in 176 patients with altered mental status. ResultsUnfavorable outcome was found in 125 (43,7%) patients. In this group, the start of appropriate antibiotic treatment in relation to the onset of first symptoms and particularly to the onset of consciousness disturbance was significantly delayed (p=0,018 and p<0,001 respectively) compared to the favorable group. Logistic regression analysis in a subgroup of culture positive meningitis in patients with altered mental status revealed that early adequate antibiotic treatment related to the onset of overt signs of meningitis was independently associated with favorable outcome (OR= 11,19; 95% CI 4,57; p<0,001). Advanced age, lower GCS and seizures (OR=1.05,OR=1,45 and OR= 3.65, respectively ) were other risk factors of poor outcome. The presence of chronic diseases, pneumococcal etiology and clinical and laboratory variables which are indicators of disease severity (renal and/or liver 3 dysfunction, hypotension and low cerebrospinal fluid glucose) were not confirmed as independent risk factors of poor outcome. ConclusionsOur study emphasizes the importance of early and adequate antibiotic treatment in the management of bacterial meningitis which significantly enhances the chances for favorable outcome.

Bacterial meningitis after tooth extraction

“…16,21 Furthermore, unexpected serious complications may be indicative of an underlying undiagnosed condition. …”

“…16 The typical clinical signs of meningitis are severe headaches, neck stiffness and fever. However, especially at the beginning, not all components of this pathognomonic trias have to be present.…”

Dexamethasone for adult community-acquired bacterial meningitis: 20 years of experience in daily practice

“…The following further independent variables were considered in multivariate analysis: age; sex; time (days) elapsed since first symptoms (any) to admission; use of antibiotics (any) before the diagnosis of meningitis; presence of serious comorbidity [includes malignancy, immunodeficiency (immunosuppressants, human immunodeficiency virus infection or splenectomy), diabetes mellitus (DM), other endocrinological diseases, alcohol abuse and liver cirrhosis, other chronic organ diseases (lungs, heart, kidney, liver)]; presence of focal neurological symptoms on admission (includes aphasia, cranial nerve palsy, monoparesis or hemiparesis); leukocyte count on admission; pathophysiological mechanism of the disease (e.g., meningitis following septicemia, or following middle ear infection or trauma; dichotomized as "following septicemia" and "other"); microbiologically verified BM (considered as yes/no, and also as pneumococcal/other bacterial/probable); worst Glasgow Coma Score (GCS) within 24 hours since admission as a continuous variable and also categorized into levels of consciousness disturbance as: none (GCS ≥15), mild (GCS [13][14], moderate (GCS 10-12 ) or severe (GCS ≤9); and timing of the appropriate antibiotic treatment (empirical as per in-house guidelines, or bacteriologically targeted, see above) commencement specifically in relation to the onset of consciousness disturbance and/or overt meningitis symptoms (e.g., fever, headache, vomiting, malaise) (16). Namely, although the "door-to-antibiotic" delay negatively affects the outcomes in community-acquired adult BM (particularly if > 2hours), timing of the appropriate antibiotic treatment relative to the onset of consciousness disturbance and/or other specific meningitis symptoms appears to be a particularly relevant predictor of the disease outcome (17,18). Therefore, considering that the database included anamnestic/heteroanamnestic data on disease course before hospital admission, appropriate antibiotic timing relative to the onset of meningitis symptoms was assessed as "within 24 hours" or "later", based on agreement between two investigators unaware of the patients outcome and dexamethasone treatment.…”

“…A delay in antibiotic treatment has a considerable unfavourable effect in adult BM and timing relative to the onset of more specific (and not "any") meningitis symptoms seems to be particularly important (17,18,22). In the European trial, no adjustments were made for "timing of antibiotic treatment" and no data on this variable were provided (6).…”

Prospective observational cohort study of cerebrovascular CO2 reactivity in patients with inflammatory CNS diseases

“…This is particularly true with pneumococcal meningitis [1][2][3][4]. The most common factors associated with poor outcome in bacterial meningitis are seizures, advanced age, disturbed consciousness, the presence of multiple organ dysfunction, hypotension, APACHE II score > 13, pneumococcal etiology and delay in antimicrobial treatment [3][4][5][6][7][8].…”