Antibiotic protocol for bacterial meningitis or suspected meningococcal disease

This topic will discuss the empirical antibiotic prescribing for bacterial meningitis or suspected meningococcal disease...

When to treat

Diagnosis of bacterial meningitis may be difficult as symptoms are similar in many other illnesses. A classic triad of fever, neck stiffness, and altered mental status is seen in about 40% of patients, although it is more common in the elderly and in those with pneumococcal meningitis. Rapidly evolving petechial or purpuric rash may indicate meningococcal disease.

Once there is clinical suspicion of acute bacterial meningitis, you are placed in an isolation room to protect staff and others from infection. Additionally, a mask may be placed over your nose and mouth to further prevent the spread of infection.

NPS-adv

When to investigate

Immediately obtain blood and CSF samples for culture and initiate empiric antimicrobial therapy. Delays in blood culture or lumbar puncture may result in delayed diagnosis. If diagnosis and initiation of therapy are delayed, risk of morbidity and mortality increases. Do not delay empiric therapy if lumbar puncture delayed.

Diagnosis of meningitis based on clinical suspicion and identification of causative bacteria from any of (1) CSF cultures (positive in up to 80% of patients not pretreated with antibiotics). (2) Blood culture (positive in 50%-90% in patients no pretreated with antibiotics and 30%-70% in patients receiving pretreatment).

Diagnosis

According to Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN); meningitis must meet at least 1 of the following criteria...

Organism identified from CSF by culture.
Patient has at least 1 of the following signs or symptoms with no other recognized cause: fever (> 38 degrees C), headache, stiff neck, meningeal signs, cranial nerve signs, or irritability. And at least 1 of the following...

Increased white cells, elevated protein, and/ or decreased glucose in CSF.
Organisms seen on Gram’s stain of CSF.
Organisms cultured from blood.
Positive antigen test of CSF, blood, or urine.
Diagnostic single antibody titer (IgM) or 4-fold increase in paired sera (IgG) for pathogen.

In patients ≤ 1 year old, has at least ≥ 2 of following signs or symptoms without other cause: fever (> 38 degrees C), headache, stiff neck, meningeal signs, cranial nerve signs, or irritability. And at least ≥ 1 of following...

Increased white cells, elevated protein, and decreased glucose in CSF.
Positive Gram’s stain of CSF.
Organism identified from blood by culture or nonculture-based testing method, performed for clinical diagnosis or treatment, not surveillance.
Diagnostic single antibody titer (IgM) or 4-fold increase in paired sera (IgG) for organism.

NPS-adv

How to treat

Empiric antibiotics

Delays in treatment are associated with an increased mortality. For community-acquired bacterial meningitis, empiric treatment in patients with normal renal function often includes...

For adults < 50 years old, ceftriaxone 2 g IV every 12 hours plus vancomycin 15-20 mg/kg IV every 8-12 hours.
For adults > 50 years old or immunocompromised patients, ceftriaxone 2 g IV every 12 hours plus vancomycin 15-20 mg/kg IV every 8-12 hours plus ampicillin 2 g IV every 4 hours.
Add acyclovir 10 mg/kg IV every 8 hours for all patients until herpes simplex meningoencephalitis is ruled out.

Add adjunctive dexamethasone for known or suspected Streptococcus pneumoniae meningitis by dose 0.15 mg/kg IV every 6 hours beginning 10-20 minutes before or during the antibiotic administration and continuing for 2-4 days. Dexamethasone may improve survival in adults with bacterial meningitis due to S. pneumoniae. Consider adding rifampin 600 mg every 24 hours when dexamethasone is given, even with vancomycin which may not adequately penetrate the central nervous system. Insufficient evidence to recommend adjunctive dexamethasone for meningitis caused by other bacteria.

For postsurgical bacterial meningitis, or meningitis associated with head trauma or shunt, empiric treatment often includes coverage for methicillin-resistant Staphylococcus aureus (MRSA) and aerobic gram-negative organisms, such as Pseudomonas spp. and Enterobacteriaceae. Infectious Diseases Society of America recommends vancomycin 15-20 mg/kg IV every 8-12 hours plus either ceftazidime 2 g IV every 8 hours or cefepime 2 g IV every 8 hours. A definitive therapy and the duration of therapy should be based on cerebrospinal fluid (CSF) culture results "see table 1".

Duration of therapy

Infectious Diseases Society of America (IDSA) guideline for management of bacterial meningitis 2004 recommendations for duration of IV antibiotic therapy based on pathogen (IDSA Grade A-III). Examples...

H. influenzae - 7 days.
N. meningitidis - 7 days.
S. pneumoniae - 10-14 days.
S. agalactiae - 14-21 days.
Aerobic gram-negative bacilli - 21 days.
L. monocytogenes - at least 21 days.

While, European Federation of Neurological Societies (EFNS) recommendations for duration of IV antibiotic therapy based on pathogen. Examples...

Unspecified bacterial meningitis - 10-14 days.
H. influenzae meningitis - 7-14 days.
Pneumococcal meningitis - 10-14 days.
Meningococcal meningitis - 5-7 days.
Listeria meningitis - 21 days.
Gram-negative bacilli and Pseudomonas meningitis - 21-28 days.

Table (1). Empiric Therapy for Adults with Bacterial Meningitis (Infectious Diseases Society of America [IDSA] recommended first-line therapy for bacterial meningitis)
Patient Characteristics	Common Pathogens	Antibiotic Regimen	Total Daily Dosages and Dosing Intervals
Age < 50 years	Neisseria meningitis	Vancomycin plus either ceftriaxone or cefotaxime — Some experts would add rifampin if dexamethasone is also given	Vancomycin 30-45 mg/kg every 8-12 hours Ceftriaxone 4 g every 12-24 hours Cefotaxime 8-12 g every 4-6 hours
Age < 50 years	Streptococcus pneumoniae
Age > 50 years	S. pneumoniae	Vancomycin plus ampicillin plus either ceftriaxone or cefotaxime	Vancomycin 30-45 mg/kg every 8-12 hours Ampicillin 12 g every 4 hours Ceftriaxone 4 g every 12-24 hours Cefotaxime 8-12 g every 4-6 hours
	N. meningitidis
	Listeria monocytogenes
	Aerobic gram-negative bacilli
Post neurosurgery, penetrating head trauma, or if CSF shunt present	Coagulase-negative staphylococci (especially Staphylococcus epidermis)	Vancomycin plus any of cefepime, ceftazidime, or meropenem	Vancomycin 30-45 mg/kg every 8-12 hours Cefepime 6 g every 8 hours Ceftazidime 6 g every 8 hours Meropenem 6 g every 8 hours
	Aerobic gram-negative bacilli (including Pseudomonas aeruginosa)
	Propionibacterium acnes (for CSF shunt infections)
	Staphylococcus aureus

Prevention

Preventive measures recommended by the Centers for Disease Control and Prevention for meningococcal meningitis include droplet precautions for hospitalized patients as soon as diagnosis is suspected through the first 24 hours of antimicrobial therapy and chemoprophylaxis for close contacts of patients with confirmed meningococcal meningitis. Closer than 3 feet for > 8 hours or those exposed to oral secretions and exposed during the 7 days prior to and 1 day after the start of antibiotics. Ciprofloxacin 500 mg single dose is prescribed unless there is concern for quinolone-resistant Neisseria meningitidis (rare but has been reported).

References

Overview: Meningitis (bacterial) and meningococcal septicaemia in under 16s: recognition, diagnosis and management. NICE. www.nice.org.uk [online] Available at: https://www.nice.org.uk/guidance/cg102.
Smith L. (2019). Management of Bacterial Meningitis: New Guidelines from the IDSA. American Family Physician, [online] 71(10), p.2003. Available at: https://www.aafp.org/afp/2005/0515/p2003.html.
McGill, F., Heyderman, R.S., Panagiotou, S., Tunkel, A.R. and Solomon, T. (2016). Acute bacterial meningitis in adults. The Lancet, [online] 388(10063), pp.3036–3047. Available at: https://www.sciencedirect.com/science/article/pii/S0140673616306547.
Tunkel, A.R., Hasbun, R., Bhimraj, A., Byers, K., Kaplan, S.L., Scheld, W.M., van de Beek, D., Bleck, T.P., Garton, H.J.L. and Zunt, J.R. (2017). 2017 Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clinical Infectious Diseases, 64(6), pp.e34–e65. Available at: https://academic.oup.com/cid/article/64/6/e34/2996079.
Heckenberg, S.G.B., Brouwer, M.C. and van de Beek, D. (2014). Chapter 93 - Bacterial meningitis. [online] ScienceDirect. Available at: https://www.sciencedirect.com/science/article/pii/B9780702040887000936.