Antibiotic treatment delay and outcome in acute bacterial meningitis
Introduction
The mortality in community acquired acute bacterial meningitis has been described as 13–27% in countries comparable to Northern Europe1, 2, 3, 4, 5, 6 and severe sequelae were found in 6–26% of the survivors depending on bacterial aetiology and patient age.3, 7 Early steroid treatment has shown a beneficial correlation to outcome,8 whereas co-morbidities and coma have been associated to an adverse clinical outcome.1, 4, 9
In-hospital delay of antibiotic therapy may influence outcome5, 6, 10, 11 and there seems to be a consensus that the prognosis worsens, if initiation of treatment is delayed until a late stage of the disease.1, 6, 10, 12, 13 Recognized textbooks of infectious disease and internal medicine recommend administration of antibiotics within 60 min of arrival to hospital7 or no later than 90–120 min,12 despite the fact that no clinical studies exist to support these specified recommendations. The recent IDSA guidelines recommend administration of antibiotics as soon as possible.13 Aronin et al found that delay of antibiotic therapy was associated with adverse clinical outcome, if the patient's condition had progressed to the highest stage of severity,1 but a general correlation between delayed therapy and clinical outcome was not demonstrated.1, 14 Miner et al suggested such a possible correlation, but the groups compared had a difference in median treatment delay of 5 h.10 In ICU patients with community acquired pneumococcal meningitis, in-hospital antibiotic delay exceeding 3 h was identified as an independent risk factor for mortality.11 In adult meningitis, one study demonstrated a sharp rise in the case-fatality rate after 6 h of antibiotic therapy delay, where treatment delay correlated to the absence of the meningitis symptom triad and to the need of further patient transferral for head CT scan.6
Studies have demonstrated a large variation in antibiotic delay in bacterial meningitis with a lower treatment delay among children.10, 15, 16, 17, 18, 19 The median treatment delay in various publications was found to be between 1 h and 5.5 h.6, 10, 15, 16, 17, 18, 19 Talan et al described in an analysis of an emergency room department that 90% of the total delay of antibiotics occurred after the initial physician encounter,16 and that prompt administration of antibiotics was associated with general clinical signs of severe disease rather than more specific symptoms of meningitis.17
The intention of the present study was to do an outcome analysis focusing on in-hospital antibiotic delay and the mentioned hypothesised factors of importance in a complete population of patients with community acquired bacterial meningitis.
Section snippets
Patients and setting
Patients with bacterial meningitis were identified through the seven regional departments of clinical microbiology in eastern Denmark. All culture-positive cerebrospinal fluids (CSF) and culture-negative CSF with matching culture-positive blood samples or positive microscopy in Denmark between January 1st 2002 and January 1st 2004 were reported to the Danish Bacterial Meningitis Group. Cases included in this study were admitted to the 24 hospitals in the eastern part of Denmark covering a
Results
A total of 187 cases were included, as the medical records from three cases were not obtainable. Thus, case completeness was 98.4%. Median age was 62 years among the 125 adult cases (≥18 years). Median age among the 62 children was 2 years, and nine cases were younger than 3 months. Aetiology and outcome are described in Table 1.
In 178 cases, the exact delay of antibiotic therapy was established (Fig. 1). The median delay to the first dose of adequate antibiotics was 1 h and 39 min (1 h and 14 min
Discussion
This retrospective study demonstrated an independent correlation between increasing in-hospital delay of antibiotic therapy and unfavourable outcome in adult community acquired bacterial meningitis. In the first 12 h from admission, the odds for an unfavourable outcome increased 30% with every hour, and these clinically most relevant cases accounted for 87% of the patients. Thus, our results not only confirmed but also quantified the effect of in-hospital antibiotic delay suggested by Aronin and
Conflicts of interest
None declared.
Acknowledgements
We received economic contribution from Lily Bentine Lunds Foundation and Director Jacob Madsen and Olga Madsen Foundation, which had no influence on the design of the study.
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