SAN DIEGO – Physicians often skipped out on using steroids when treating bacterial meningitis even though the benefits clearly outweigh the risks, Cinthia Gallegos, MD, reported during an oral presentation at an annual meeting on infectious diseases.
In a recent multicenter retrospective cohort study, only 40% of adults with bacterial meningitis received steroids within 4 hours of hospital admission, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and only 14% received steroids concomitantly or 10-20 minutes prior to antibiotic initiation, as recommended by the Infectious Diseases Society of America (IDSA), said Dr. Gallegos, an infectious disease fellow at University of Texas, Houston.
“Steroids are being underutilized in our patient population,” she said. “And when steroids are used, they are being used later than is recommended.”
To evaluate the prevalence of guideline-concordant steroid use, Dr. Gallegos and her associates analyzed the medical records of 120 adults with culture-confirmed, community-acquired bacterial meningitis treated at 10 Houston-area hospitals between 2008 and 2016.
Median duration of steroid therapy was 4 hours, which is consistent with IDSA guidelines, she noted.
Among the five patients (4%) who developed delayed cerebral thrombosis, three had Streptococcus pneumoniae meningitis, one had methicillin-resistant Staphylococcus aureus meningitis, and one had Listeria meningitis. All had received either dexamethasone monotherapy or dexamethasone and methylprednisolone within 4 hours of antibiotic initiation. They showed an initial improvement in clinical course, including normal CT and MRI, but their clinical condition deteriorated between 5 and 12 days later. “Repeat imaging showed thrombosis of different areas of the brain,” Dr. Gallegos said. Two patients died, two developed moderate or severe disability, and one fully recovered. The patients ranged in age from 26 to 69; three were male, and two were female.
The 4% rate closely resembles what is seen in the Netherlands, said Diederik van de Beek, MD, PhD, of the Academic Medical Center in Amsterdam, who comoderated the session at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. “We have some recent data where we did autopsies of cases and we saw a huge amount of bacterial fragments around the blood vessels,” he said. “We have seen this in previous autopsy studies, but here it was a massive amount of bacterial fragments.”
Researchers have suggested that delayed cerebral thrombosis in bacterial meningitis results from increases in C5a and C5b-9 levels in the cerebrospinal fluid and from an increase in the tissue factor VII pathway, Dr. Gallegos said.
Researchers think that these patients historically developed vasculitis, but that this complication “has disappeared somewhat in the dexamethasone era,” said Dr. van de Beek, lead author of the 2016 ESCMID guidelines on bacterial meningitis. “It appears that some patients are ‘pro-inflammatory’ and still react 7-9 days after treatment,” he said. “The difficult question is whether we give 4 days of steroids or longer. A clinical trial is not feasible, so we [recommend] 4 days.”
Left untreated, bacterial meningitis is fatal in up to 70% of cases, and about one in five survivors faces limb loss or neurologic disability, according to the Centers for Disease Control and Prevention. The advent of penicillin and other antibiotics dramatically improved survival, but death rates remained around 10% for meningitis associated with Neisseria meningitides and Haemophilus influenza infection, and often exceeded 30% for S. pneumoniae meningitis. “That’s important because besides antibiotics, the only treatment that decreases mortality has been shown to be steroids,” Dr. Gallegos said.
High-quality evidence supports their use. In a double-blind, randomized, multicenter trial of 301 adults with bacterial meningitis, adjunctive dexamethasone was associated with a 50% improvement in mortality, compared with adjunctive placebo (N Engl J Med. 2002 Nov 14;347:1549-56). Other data confirm that steroids do not prevent vancomycin from concentrating in CSF or increase the risk of hippocampal apoptosis. But although both IDSA and ESCMID endorse steroids as adjunctive therapy to help control intracranial pressure in patients with bacterial meningitis, studies have shown much higher rates of steroid use in the Netherlands, Sweden, and Denmark than in the United States.
The Grant A. Starr Foundation provided funding. The investigators had no conflicts of interest.