Meningitis treatment

Before starting treatment for meningitis, patients with a suspected diagnosis should undergo a lumbar puncture (the main method for confirming the diagnosis).

Treatment of viral meningitis

Since viral meningitis is considered a non-life-threatening disease, antiviral therapy is used very sparingly. Indications for the use of antiviral drugs are severe complications or relapse of meningitis. For the treatment of meningitis caused by the herpes simplex virus, acyclovir is used at a dose of 10 mg / kg every 8 hours for adults and 20 mg / kg every 8 hours for children. For the treatment of meningitis caused by enteroviruses, pleconaril, a low-molecular inhibitor of piconaviruses, is used. It should be noted that its clinical trials are ongoing, since small clinical studies have noted its positive effect on the duration of headache compared with placebo.

Treatment of viral meningoencephalitis

Currently, there are antiviral drugs that are active against herpes viruses types 1 and 2, herpes zoster virus, cytomegalovirus and HIV. The use of acyclovir (10 mg/kg in adults and 20 mg/kg in children every 8 hours intravenously) for 21 days significantly reduced the mortality of patients with generalized herpes infection and herpes encephalitis from 70% to 40%. The degree of neurological disorders in surviving patients decreased from 90% to 50%. It was not possible to accurately estimate the ineffectiveness of acyclovir, but it is believed to be about 5%.

Combined use of acyclovir (10 mg/kg in adults and 20 mg/kg in children every 8 hours intravenously) for 21 days and specific immunoglobulin against the herpes zoster virus sharply reduced the incidence of complications in neonatal children and immunosuppressed patients. Despite the lack of reliable evidence of high efficacy of acyclovir in case of encephalitis, it is usually used in everyday practice.

Ganciclovir (5 mg/kg intravenously every 12 hours for 14 days, then 5 mg/kg intravenously every 24 hours) and foscarnet sodium (90 mg/kg intravenously every 12 hours for 14 days, then 90 mg/kg intravenously every 24 hours) are used to treat cytomegalovirus encephalitis in HIV-infected patients, although there is no reliable evidence of efficacy to date. In addition, it is unclear whether the possible positive effect of treatment is associated with suppression of the viral effect on the central nervous system, a positive effect on the function of the immune system (reduction of viral load), or a decrease in the negative impact of opportunistic infections.

There is no reliable data on the effectiveness of immunomodulatory therapy in patients with viral encephalitis. In practice, some doctors try to use immunomodulators to limit the destruction of the central nervous system by T cells with cytotoxic activity. As a rule, the authors point to the effectiveness of the method they have developed and, unfortunately, do not indicate the number of cases of ineffective use and iatrogenic complications that arise during treatment, which can also lead to an unfavorable outcome of the infection.

Treatment of bacterial meningitis and meningoencephalitis

Recommendations for the treatment of bacterial infections of the central nervous system have been repeatedly revised, which is associated with the changing epidemiological situation, changes in the etiological structure of pathogens and their sensitivity to antibiotics. Current recommendations for the treatment of bacterial infections of the central nervous system are presented in tables. The levels of evidence for antimicrobial therapy regimens are presented in parentheses.

Recommendations for antimicrobial therapy of purulent meningitis based on patient age and concomitant pathology

Predisposing factor	The most likely causative agent	Antimicrobial therapy
Age
<1 month	Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella spp.	Ampicillin + cefotaxime, Ampicillin + aminoglycosides
1-23 months	Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli	3rd generation cephalosporins ab
2-50 years	N. meningitidis, S. pneumoniae	Cephalosporins 3rd generation ab
>50 years	S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative rods	3rd generation cephalosporins + ampicillin ab
Type of pathology
Fracture of the base	S. pneumoniae H. influenzae, group A ß-hemolytic streptococci	3rd generation cephalosporins
Penetrating traumatic brain injury	Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacteria (including Pseudomonas aeruginosa)	Cefepime, ceftazidime, meropenem
After neurosurgical operations	Aerobic gram-negative bacteria (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)	Cefepime + vancomycin/linezolid, ceftazidime + vancomycin/linezolid meropenem + vancomycin/linezolid
CNS shunts	Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic gram-negative bacteria (including Pseudomonas aeruginosa) Propionibacterium acnes	Cefepime + vancomycin/linezolid B, ceftazidime + vancomycin/linezolid B meropenem + vancomycin/linezolid B

• a - ceftriaxone or cefotaxime,
• b - some experts recommend additional use of rifampicin,
• c - vancomycin monotherapy can be prescribed to newborns and children if Gram staining does not reveal gram-negative microbes

Role of vancomycin/linezolid

In the treatment regimens of primary community-acquired bacterial meningitis, drugs are used to suppress multidrug-resistant Streptococcus pneumoniae, since in the presence of resistance of S. pneumoniae to benzylpenicillin, 3rd generation cephalosporins are the most sufficient treatment regimen. Considering the fact that epidemiological data on the relevance of multidrug-resistant S. pneumoniae in the etiologic structure of bacterial meningitis have not been sufficiently studied, the advisability of including vancomycin in the regimens of initial therapy for this group of patients is justified by the extraordinary importance of adequate initial therapy. However, according to some domestic authors, the frequency of occurrence of multidrug-resistant S. pneumoniae in the etiologic structure of bacterial meningitis is less than 1%, which casts doubt on the advisability of using vancomycin in regions where there is information about the low incidence of such pneumococcal strains.

In the treatment of secondary meningitis associated with TBI or neurosurgical operations, vancomycin/linezolid is used against staphylococci that are resistant to oxacillin. Overcoming this type of resistance with ß-lactam antibiotics (penicillins, cephalosporins, carbapenems) is impossible, and the use of vancomycin should be considered as a forced measure. With respect to methicillin-sensitive strains of staphylococci, the clinical efficacy of ß-lactam antibiotics is significantly higher, therefore it is advisable to use this group, primarily oxacillin, and vancomycin should be discontinued.

Recommendations for antimicrobial therapy of bacterial meningitis based on microbiological data and antibiotic susceptibility testing

Exciter, sensitivity

Standard therapy

Alternative therapy

Streptococcus pneumoniae

MIC of benzylpenicillin <0.1 μg/ml	Benzylpenicillin or ampicillin	3rd generation cephalosporins and chloramphenicol
MIC of benzylpenicillin 0.1-1.0 μg/ml	3rd generation cephalosporins a	Cefepime, meropenem
MIC of benzylpenicillin >2.0 μg/ml	Vancomycin + 3rd generation cephalosporins av	Fluoroquinolones g
MIC of cefotaxime or ceftriaxone >1 mcg/ml	Vancomycin + 3rd generation cephalosporins	Fluoroquinolones g

Neisseria meningitidis

MIC of benzylpenicillin <0.1 μg/ml	Benzylpenicillin or ampicillin	3rd generation cephalosporins and chloramphenicol
MIC of benzylpenicillin 0.1-1.0 mcg/ml	3rd generation cephalosporins a	Chloramphenicol, fluoroquinolones meropenem
Listeria monocytogenes	Benzylpenicillin or ampicillin D	Co-trimoxazole meropenem
Streptococcus agalactiae	Benzylpenicillin or ampicillin D	3rd generation cephalosporins
Escherichia coh and other Enterobacteriaceae hedgehog	3rd generation cephalosporins (A-P)	Fluoroquinolones meropenem, co-trimoxazole, ampicillin
Pseudomonas aeruginosa f	Cefepimd or ceftazidime (A-P)	Ciprofloxacin d meropenem d

Haemophilus influenzae

Without ß-lactamase production	Ampicillin	3rd generation cephalosporins a cefepime chloramphenicol, fluoroquinolones
With ß-lactamase production	3rd generation cephalosporins (AI)	Cefepime chloramphenicol, fluoroquinolones

Staphylococcus aureus

Oxacillin sensitive	Oxacillin	Meropenem
Resistant to oxacillin or methicillin	Vancomycin e	Linezolid, rifampicin, Co-trimoxazole
Staphylococcus epidermidis	Vancomycin e	Linezolid

Enterococcus spp.

Ampicillin sensitive	Ampicillin + gentamicin
Ampicillin resistant	Vancomycin + gentamicin
Resistant to ampicillin and vancomycin	Linezolid

• a - ceftriaxone or cefotaxime,
• b - strains sensitive to ceftriaxone and cefotaxime,
• c - if the MIC of ceftriaxone is >2 mcg/ml, rifampicin may be additionally prescribed,
• g - moxifloxacin,
• d - aminoglycosides may be additionally prescribed,
• e - rifampicin may be additionally prescribed,
• f - selection of the drug only on the basis of in vitro strain susceptibility testing

Antibiotic Doses for Bacterial Meningitis

Antimicrobial drug	Daily dose, dosing interval
	Newborns, age, days		Children	Adults
	0-7	8-28
Amikacin b	15-20 mg/kg (12)	30 mg/kg (8)	20-30 mg/kg (8)	15 mg/kg (8)
Ampicillin	150 mg/kg (8)	200 mg/kg (6-8)	300 mg/kg (6)	12 g (4)
Vancomycin w	20-30 mg/kg (8-12)	30-45 mg/kg (6-8)	60 mg/kg (6)	30-45 mg/kg (8-12)
Gatifloxacin				400 mg (24) g
Gentamicin B	5 mg/kg (12)	7.5 mg/kg (8)	7 5 mg/kg (8)	5 mg/kg (8)
Chloramphenicol	25 mg/kg (24)	50 mg/kg (12-24)	75-100 mg/kg (6)	4-6 g (6)“
Linezolid	No data	10 mg/kg (8)	10 mg/kg (8)	600 mg (12)
Meropenem			120 mg/kg (8)	6 g (8)
Moxifloxacin				400 mg (24) g
Oxacillin	75 mg/kg (8-12)	150-200 mg/kg (6-8)	200 mg/kg (6)	9-12 g (4)
Benzylpenicillin	0.15 million units/kg (8-12)	0.2 million units/kg (6-8)	0.3 million units/kg (4-6)	24 million units (4)
Pefloxacin				400-800 mg (12)
Rifampicin		10-20 mg/kg (12)	10-20 mg/kg (12-24)d	600 mg (24)
Tobramycin b	5 mg/kg (12)	7.5 mg/kg (8)	7 5 mg/kg (8)	5 mg/kg (8)
Co trimoxazole e			10-20 mg/kg (6-12)	10-20 mg/kg (6-12)
Cefepime			150 mg/kg (8)	6 g (8)
Cefotaxime	100-150 mg/kg (8-12)	150-200 mg/kg (6-8)	225-300 mg/kg (6-8)	B-12 g (4-6)
Ceftazidime	100-150 mg/kg (8-12)	150 mg/kg (8)	150 mg/kg (8)	6 g (B)
Ceftriaxone			80-100 mg/kg (12-24)	4 g (12-24)
Ciprofloxacin				800-1200 mg (8-12)

• a - lower doses or longer administration intervals may be used in low birth weight infants (<2000 g),
• b - it is necessary to monitor peak and residual concentrations in plasma,
• in - the maximum dose is recommended for patients with pneumococcal meningitis,
• g - there is no data on optimal dosages in patients with bacterial meningitis,
• d - maximum daily dose 600 mg,
• e - the dose is based on the amount of trimethoprim,
• g - maintain a residual concentration of 15-20 mcg/ml 

Duration of antibacterial treatment for meningitis

The optimal duration is unknown and is probably related to the characteristics of the micro- and macroorganism. Usually, the duration of treatment for meningococcal meningitis is 5-7 days, for meningitis caused by H. influenzae - 7-10 days, for pneumococcal meningitis - 10 days. In patients without immune disorders and listeriosis etiology of meningitis - 14 days, in the presence of immunosuppression - 21 days, the same duration is recommended for meningitis caused by gram-negative flora. The general rule for justified cessation of antibacterial therapy is considered to be CSF sanitization, a decrease in cytosis below 100 cells per 1 μl and its lymphocytic nature. The above recommendations on the duration of antibacterial therapy are rational to use only in cases where an antibiotic active against the subsequently isolated pathogen was prescribed immediately after the infection was diagnosed, and there was a stable positive clinical dynamics of the disease. In case of complications of edema and dislocation of the brain, ventriculitis, intracerebral hemorrhages and ischemic damage that limit the effectiveness of antibiotic delivery to the site of infectious inflammation, the duration of antibacterial therapy is determined on the basis of a combination of clinical and laboratory data by a council of specialists with sufficient experience to make a responsible decision.

Delay in prescribing antibacterial drugs

Special studies were not conducted for ethical reasons. However, when studying the treatment outcomes of patients with atypical clinical manifestations of bacterial meningitis, it was shown that delayed diagnosis and treatment led to a worsening of the condition and an increase in mortality. The incidence of complications and the mortality rate were also associated with age, the presence of immunological disorders and the level of impaired consciousness at the time of diagnosis. It should be noted separately that the prescription of drugs inactive against the infectious agent in the empirical therapy regimen should be considered as one of the options for delaying the prescription of antibacterial drugs.

Use of original and generic antibacterial drugs for the treatment of bacterial meningitis. Meningitis is a life-threatening condition, and antibacterial therapy is considered the basis of effective treatment. All the above-mentioned antibacterial therapy regimens have been studied using original drugs. The emergence of the possibility of using generic drugs can significantly reduce the costs associated with the use of antibiotics. Determining the sensitivity of flora to the active substance of antibacterial drugs in vitro creates the illusion of equal effectiveness of all drugs that contain it. However, no studies have been conducted on the comparative effectiveness of original and generic drugs. Therefore, drugs with non-proprietary trade names can only be used in the absence of original drugs on the market for various reasons.

List of trade (proprietary) names and corresponding international non-proprietary names

International Nonproprietary Name	Original trade name	Alternative due to the lack of the original drug on the market
Amikacin	Amikin
Vancomycin	Vancocin	Editsin
Gentamicin		Domestic analogue
Linezolid	Zyvox
Meropenem	Meronem
Moxifloxacin	Avelox
Cefepime	Maxipim
Cefotaxime	Claforan
Ceftazidime	Fortum
Ceftriaxone	Rocephin

[ 1 ], [ 2 ], [ 3 ]

Dexamethasone in the treatment of bacterial meningitis

The effectiveness of glucocorticoids has been proven in terms of reducing neurological complications (hearing loss) in children with meningitis caused by H. influenzae and reducing mortality in adults with meningitis caused by S. pneumoniae. It is recommended to use dexamethasone at a dose of 0.15 mg/kg every 6 hours for 4 days. It should be remembered that dexamethasone helps to reduce increased penetration of antibiotics into the subarachnoid space as a result of inflammation.

[ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ]