Treatment of meningitis

Before the treatment of meningitis, patients with a presumptive diagnosis should undergo spinal puncture (the main method of confirming the diagnosis).

Treatment of viral meningitis

Due to the fact that viral meningitis is considered to be life-threatening diseases, antiviral therapy is very limited. Indications for the use of antiviral drugs are severe complications or recurrence of meningitis. For the treatment of meningitis caused by the herpes simplex virus, aciclovir is used at a dose of 10 mg / kg at 8 hours for adults and 20 mg / kg at 8 hours for children. For the treatment of meningitis caused by enteroviruses, change plexonil - a low-molecular inhibitor of piconaviruses. It should be noted that his clinical trials continue, since in small clinical studies, his positive effect on the duration of the headache compared to placebo was noted.

Treatment of viral meningoencephalitis

Currently, there are antiviral drugs that are active against herpesviruses type 1 and type 2, herpes zoster virus, cytomegalovirus and HIV. The use of acyclovir (10 mg / kg in adults and 20 mg / kg in children at 8 h intravenously) for 21 days significantly reduced the lethality of patients with generalized herpetic infection and herpetic encephalitis from 70% to 40%. The degree of neurologic damage in surviving patients decreased from 90% to 50%. It was not possible to accurately assess the inefficiency of acyclovir, it is estimated that it is about 5%.

The combined use of acyclovir (10 mg / kg in adults and 20 mg / kg in children at 8 h intravenously) for 21 days and a specific immunoglobulin against the herpes zoster virus dramatically reduced the incidence of complications in neonatal children and patients with immunosuppression. Despite the lack of reliable evidence of high efficacy of acyclovir in the case of encephalitis, it is usually used in everyday practice.

For the treatment of cytomegalovirus encephalitis in HIV-infected patients, ganciclovir is used (5 mg / kg intravenously after 12 hours for 14 days, then 5 mg / kg intravenously after 24 hours) and sodium foscarnet (90 mg / kg intravenously after 12 hours for 14 days , then 90 mg / kg intravenously after 24 hours), although there is no reliable evidence of efficacy to date. In addition, it is not clear what is the possible positive effect of treatment with the suppression of viral action on the central nervous system, a positive effect on the function of the immune system (reducing the viral load) or a decrease in the negative impact of opportunistic infections.

There are no reliable data on the effectiveness of immunomodulatory therapy in patients with viral encephalitis. In practice, some physicians try to use immunomodulators to limit the destruction of the CNS by T cells with cytotoxic activity. As a rule, the authors point out the effectiveness of the method developed by them and, unfortunately, do not indicate the number of cases of ineffective use and iatrogenic complications arising in the course of treatment, which can also lead to an unfavorable outcome of the infection.

Treatment of bacterial meningitis and meningoencephalitis

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

Recommendations for the antimicrobial therapy of purulent meningitis based on the age of patients 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	Cephalosporins of the 3rd generation ab
2-50 years	N. Meningitidis, S. Pneumoniae	Cephalosporins of the 3rd generation ab
> 50 years	S. Pneumoniae, N. Meningitidis, L. Monocytogenes, aerobic gram-negative rods	Third-generation cephalosporins + ampicillin ab
Type of pathology
Fracture of the base	S. Pneumoniae H. Influenzae, ß-hemolytic streptococci of the group A	Third-generation cephalosporins
Penetrating craniocerebral 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 in, ceftazidime, vancomycin + / linezolid in meropenem + vancomycin / linezolid in

• a - ceftriaxone or cefotaxime,
• b - some experts recommend the addition of rifampicin,
• in - newborns and children, monotherapy with vancomycin can be prescribed, if Gram staining does not reveal gram-negative microbes

The role of vancomycin / linezolid

In the treatment of primary community-acquired bacterial meningitis, drugs are used to suppress multiresistant Streptococcus pneumoniae, since in the presence of S. Pneumoniae resistance to benzylpenicillin, third-generation cephalosporins are the most appropriate treatment regimen. Considering the fact that epidemiological data on the relevance of multidrug-resistant S. Pneumoniae in the etiological structure of bacterial meningitis have not been sufficiently studied, the advisability of including vancomycin in the regimens of starting therapy of this group of patients is justified by the extraordinary importance of adequate starting therapy. However, according to some domestic authors, the incidence of multidrug-resistant S. Pneumoniae in the etiologic structure of bacterial meningitis is less than 1%, which calls into question the advisability of using vancomycin in regions where there is evidence of a low occurrence of such strains of pneumococci.

In regimens for the treatment of secondary meningitis associated with CCT or neurosurgical operations, vancomycin / linezolid is used against staphylococci with resistance 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-susceptible strains of staphylococci, the clinical efficacy of β-lactam antibiotics is substantially higher, so it is advisable to use this group, primarily oxacillin, and vancomycin should be discontinued.

Recommendations for the antimicrobial therapy of bacterial meningitis, based on microbiological data and the definition of sensitivity to antibiotics

Causative agent, sensitivity

Standard Therapy

Alternative Therapy

Streptococcus pneumoniae

IPC of benzylpenicillin <0 1 μg / ml	Benzylpenicillin or ampicillin	Cephalosporins third generation and chloramphenicol
IPC of benzylpenicillin 0 1-1 0 μg / ml	Cephalosporins third generation and	Cefepime, meropenem
IPC of benzylpenicillin> 2.0 μg / ml	Vancomycin + cephalosporins of 3rd generation av	Fluoroquinolones g
MIC of cefotaxime or ceftriaxone> 1 μg / ml	Vancomycin + cephalosporins of the 3rd generation av	Fluoroquinolones g

Neisseria meningitidis

IPC of benzylpenicillin <0.1 μg / ml	Benzylpenicillin or ampicillin	Cephalosporins third generation and chloramphenicol
IPC of benzylpenicillin 0.1-1.0 μg / ml	Cephalosporins third generation and	Chloramphenicol, fluoroquinolones meropenem
Listeria monocytogenes	Ampicillin benzylpenicillin or d	Co-trimoxazole meropenem
Streptococcus agalactiae	Ampicillin benzylpenicillin or d	Third-generation cephalosporins
Escherichia coh and other Enterobacteriaceae hedgehog	Third-generation cephalosporins (A-P)	Fluoroquinolones meropenem, co-trimoxazole, ampicillin
Pseudomonas aeruginosa f	Cephepimid or ceftazidime (A-P)	Ciprofloxacin d meropenem d

Haemophilus influenzae

Without production of ß-lactamases	Ampicillin	Third-generation cephalosporins and cefepime chloramphenicol, fluoroquinolones
With the production of ß-lactamases	Third-generation cephalosporins (AI)	Cefepime chloramphenicol, fluoroquinolones

Staphylococcus aureus

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

 Enterococcus spp.

Sensitive to ampicillin	Ampicillin + gentamicin
Resistant to ampicillin	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> 2 μg / ml, rifampicin may additionally be prescribed,
• g - moxifloxacin,
• d - aminoglycosides may additionally be prescribed,
• e - Rifampicin may additionally be prescribed,
• g - drug selection only based on the in vitro sensitivity test of the strain

Doses of antibiotics for the treatment of bacterial meningitis

Antimicrobial preparation	Daily dose, dosing interval
	Newborns, age, days		Children	Adults
	0-7	8-28
Amicacin 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 f	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) g	600 mg (24)
Tobramycin b	5 mg / kg (12)	7.5 mg / kg (8)	7 5 mg / kg (8)	5 mg / kg (8)
To trimoxazole e			10-20 mg / kg (6-12)	10-20 mg / kg (6-12)
Cefepim			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 intervals of administration can be used in newborns with low weight (<2000 g),
• b - it is necessary to monitor the peak and residual concentrations in the plasma,
• c - the maximum dose is recommended for patients with pneumococcal meningitis,
• g - there is no data on optimal dosages in patients with bacterial meningitis,
• d is the maximum daily dose of 600 mg,
• The e - dose is based on the amount of trimethoprim,
• g - maintain a residual concentration of 15-20 μg / ml 

The duration of antibiotic treatment of meningitis

The optimal duration is unknown and, apparently, is related to the characteristics of the micro- and macroorganism. Usually, meningococcal meningitis treatment duration is 5-7 days, with meningitis caused by H. Influenzae, 7-10 days, with pneumococcal - 10 days. In patients without immune disorders and listeriosis etiology of meningitis - 14 days, with immunosuppression - 21 days, the same duration is recommended for meningitis caused by gram-negative flora. The general rule for a justified cessation of antibacterial therapy is the sanation of CSF, a decrease in cytosis below 100 cells per 1 μl and its lymphocytic character. These recommendations on the duration of antibiotic therapy are rational to use only in those cases when immediately after diagnosis of the infection an antibiotic, active against the subsequently isolated pathogen, was assigned, and there was a stable positive clinical dynamics of the disease. In the case of complications of cerebral edema and dislocation, ventriculitis, intracerebral hemorrhages and ischemic lesions that limit the effectiveness of antibiotic delivery to the focus of infectious inflammation, the duration of antibiotic therapy determines on the basis of a combination of clinical and laboratory data a consultation of specialists having sufficient experience for making a responsible decision.

Delayed prescription of antibacterial drugs

Special studies were not conducted for ethical reasons. However, when studying outcomes of treatment of patients with atypical clinical manifestations of bacterial meningitis, it was shown that the delay in diagnosis and treatment led to weight gain and increased mortality. The frequency of complications and the level of mortality were also related to age, the presence of immunological disorders and the level of impaired consciousness in the moment of diagnosis. Separately it is necessary to specify that the appointment in the mode of empirical therapy of drugs inactive against the pathogen of infection should be considered as one of the options for delaying the appointment of antibacterial drugs.

Use of original and generic antibacterial drugs for the treatment of bacterial meningitis. Meningitis is a life-threatening condition, and antibiotic therapy is considered the basis of effective treatment. All the above antibiotic 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. The determination of the sensitivity of flora to the active substance of antibacterial drugs in vitro creates the illusion of equal effectiveness of all drugs that have it in its composition. However, studies on the comparative efficacy of the original and generic drugs have not been conducted. Therefore, preparations with non-proprietary trade names can be used only in the absence of original products for various reasons on the market.

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

International Nonproprietary Name	Original trade name	Alternative for lack of an original drug on the market
Amikacin	Amikin
Vancomycin	Vancocin	Edicine
Gentamicin		Domestic analogue
Linezolid	Zivox
Meropenem	Meronem
Moxifloxacin	Avelox
Cefepim	Maksipim
Cefotaxime	Claforan
Ceftazidime	Fortum
Ceftriaxone	Rocefine

[1], [2], [3], [4], [5], [6], [7], [8]

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 a reduction in mortality in adults with meningitis caused by S. Pneumoniae. It is recommended to use dexamethasone in a dose of 0.15 mg / kg after 6 hours for 4 days. It should be remembered that dexamethasone reduces the increased penetration of antibiotics into the subarachnoid space as a result of inflammation.

[9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23]