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Antimicrobiële behandeling meningitis

Beoordeeld: 01-01-2012

Uitgangsvraag

Specific antimicrobial treatment.

Aanbeveling

Bacterial meningitis caused by penicillin susceptible (MIC≤0.06) S. pneumoniae should be treated with penicillin 200.000 IU/kg/day (4h – maximum 12 million units) in children and penicillin 12 million IU /day (4h or continuously) in adults, for a minimum of 10 days. Meningitis due to S. pneumoniae with intermediate resistance (0.06<MIC≤2.0) should be treated with ceftriaxone 100 mg/kg/day (24h – max 4g) in children and ceftriaxone 4 g/day (12h) or cefotaxime 8-12 g/day (4-6h) in adults, for a minimum of 10 days. Meningitis due to penicillin-resistant S. pneumoniae (MIC >2.0) should be treated with vancomycin 60 mg/kg/day (12h – max 2g)  plus ceftriaxone 100 mg/kg/day (24h – max 4g) in children and vancomycin 2 g/day (12h)  plus ceftriaxone 4 g/day (12h) or cefotaxime 8-12 g/day (4-6h) in adults.

 

Bacterial meningitis caused by penicillin susceptible N. meningitidis should be treated with penicillin 200.000 IU/kg/day (4h – maximum 12 million units) in children and penicillin 12 million IU /day (4h or continuously) in adults, for 7 days. Penicillin resistant strains (MIC >0.25) should be treated with ceftriaxone 100 mg/kg/day (24h – max 4g) in children and ceftriaxone 4 g/day (12h) or cefotaxime 8-12 g/day (4-6h) in adults, for 7 days.

 

Bacterial meningitis caused by L. monocytogenes should be treated with amoxicillin 200 mg/kg/day (6h – max 12g ) in children and amoxicillin 12 g/day (4h) in adults, for at least 21 days. 

 

Bacterial meningitis caused by H. influenzae, ß-lactamase positive or ß-lactamase unknown, should be treated with ceftriaxone 100 mg/kg/day (24h – max 4 g) in children and ceftriaxone 4 gr/day (12h) or cefotaxime 8-12 gr/day (4-6h) in adults, for 7 days. If the strain is susceptible to amoxicillin, it should be treated with amoxicillin 200 mg/kg/day (6h – max 12g) in children and amoxicillin 12g/day (4h) in adults, for 7 days.

 

Bacterial meningitis caused by Streptococcus agalactiae should be treated with penicillin 200.00 IU/kg/day (4h – maximum 12 million units) and penicillin 12 million units/day (4h or continuously) in adults, for at least 14 days. 

 

Bacterial meningitis caused by Escherichia coli should be treated with cefotaxime  plus gentamicin for 3 days in neonates (dose depends on gestational age and birth weight – SWAB website), ceftriaxone 100 mg/kg/day (24h – max 4g) for children and ceftriaxone 4g (12h) or cefotaxime 8-12g/day (4-6h) in adults, for 21 days. ESBL positive strains should be treated with meropenem 120mg/kg/day (8h - maximum 6 g) in children and 6g (8h) for adults.

 

Bacterial meningitis with negative CSF and blood cultures after 48 hours should be treated with ceftriaxone 100 mg/kg/day (24h – max 4g) in children and amoxicillin 12g/day (4h) in adults, for 14 days.

Overwegingen

For this module no considerations have been formulated. 

Onderbouwing

Level 1

No randomized controlled trials or adequate comparative studies have been performed to determine the optimal antibiotic treatment duration of bacterial meningitis caused by specific pathogens or in culture negative cases.

 

A1 Karageorgeopoulous (2007)25, vd Beek (2010)26

A summary of specific antimicrobial treatment for bacterial meningitis when a causative organism is identified is presented in Table 3. No randomized controlled trials or comparative studies have been performed to compare the efficacy of different antibiotics in bacterial meningitis due to specific bacteria. Therefore, the choice of specific antimicrobial therapy is based on bacterial susceptibility testing.

 

Studies on optimal treatment duration are scarce. A 2010 meta-analysis on randomized trials comparing short (4-7 days) versus long duration (7-14 days) of antibiotic therapy for bacterial meningitis concluded that there was no difference in outcome between treatment durations.25 However, there were several biases in the included studies and the results can not be extrapolated to the unselected population of community-acquired bacterial meningitis.26 A recent study performed in Malawi compared the use of a 5 day regimen with a the standard 10 day regimen in children with uncomplicated bacterial meningitis due to H. influenzae, N. meningitidis or S. pneumoniae. The study showed equality of both regimens.27 However, the subgroup of children with pneumococcal meningitis was too small to conclude that there was no harm of early discontinuation, especially since the mortality was 8% in the 5 day regimen group vs. 5% in the 10 day group.27 Therefore, the results of this trial can not be extrapolated to the Netherlands.

 

Currently, the duration of antibiotic treatment is based on expert opinion. New studies on optimal treatment duration are needed. The level of evidence for treatment duration is therefore categorized as level 4.28

 

Table 3. Specific antimicrobial therapy for community-acquired bacterial meningitis based on causative microorganism

Micro-organism

Standard treatment

Alternative therapy

Duration

S. pneumoniae

        MIC ≤0.06 g/ml

 

penicillin G 

 

ceftriaxone or cefotaxime

 

10-14 days

0.06<MIC≤2.0μg/ml

ceftriaxone or cefotaxime

meropenem

10-14 days

MIC >2.0μg/ml

vancomycin plus either ceftriaxone or cefotaxime

vancomycin plus meropenem

 

N. meningitidis

        MIC ≤0.25μg/ml

 

penicillin G 

 

ceftriaxone or cefotaxime

 

7 days

        MIC >0.25μg/ml

ceftriaxone or cefotaxime

meropenem or chloramphenicol

7 days

H. influenzae

ceftriaxone or cefotaxime

meropenem or chloramphenicol

7/10 daysa

L. monocytogenes

amoxicillin or penicillin G

trimethoprim-sulfamethoxazole

≥21 days

S. agalactiae

 

penicillin G or amoxicillin 

 

ceftriaxone or cefotaxime

 

≥14 days

 

aDuration of treatment in children 10 days, adults 7 days.

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Streptococcus pneumoniae?

Resistance of S. pneumoniae to penicillin and third generation cephalosporins (cefotaxime or ceftriaxone) has been reported to cause treatment failure.6 The rate of pneumococcal resistance rates in the Netherlands is still very low, with only 0.5-1% strains showing intermediate resistance to penicillin (0.06<MIC≤2.0).10,11 So far, one strain resistant to third generation cephalosporins has been described (MIC>2.0).29 Therefore, in the overwhelming majority of patients with pneumococcal meningitis monotherapy with amoxicillin or penicillin suffices. When susceptibility testing shows intermediate resistance to penicillin, a third generation cephalosporin should be used. Patients at risk for infection with a resistant strain, such as inhabitants of countries with high pneumococcal resistance rates (e.g. South-European countries, or the US) or recent travelers from these countries should be treated with combination therapy consisting of vancomycin and a third generation cephalosporin until susceptibility testing is performed.6 When the isolate shows resistance to penicillin (MIC>2.0), combination therapy of vancomycin and a third generation cephalosporin should be used. The duration of therapy for S. pneumoniae meningitis is 10 days, unless persistent or recurrent fever or other complications occur that warrant prolonged treatment.28 

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Neisseria meningitidis?

Currently (2012), there is no consensus in Europe about the penicillin breakpoints of N.meningitidis. According to EUCAST the meningococcus has intermediate resistance (reduced susceptibility) when the penicillin MIC is >0.06 en ≤0.25 mg/l. Meningococcal strains with reduced susceptibility to penicillin have been described, but the clinical significance remains unclear. In the Netherlands, 17 of 392 (4%) meningococcal strains isolated from CSF between 2005-2009 showed intermediate resistance to penicillin. In 2010 the number increased to 10 out of 54 (19%). Penicillin-resistant strains are very rare. The majority of patients with N. meningitidis strains with intermediate resistance to penicillin reported in the literature have responded well to penicillin treatment.6 Treatment failures have been described in a few case reports, and none of these occurred in the Netherlands. Therefore, treatment with amoxicillin or penicillin for 7 days remains first choice.28 Infection with a penicillinresistant strain (MIC >0.25) should be treated with a third generation cephalosporin.6

 

All meningococcal meningitis cases have to be reported to the Public Health Service (GGD/GG&GD). Household contacts and others who have been in close contact with meningococcal meningitis patients in the week prior to disease onset should receive prophylaxis to minimize the risk of secondary cases. Health care workers are only at risk after intimate contact such as mouth-to mouth resuscitation or endotracheal intubation. Rifampicin and ciprofloxacin are both effective as prophylaxis for treating patient contacts.3 More information on this subject can be found in the bacterial meningitis guidelines of the Dutch Neurological Society.3 

 

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Listeria monocytogenes?

Amoxicillin and penicillin are highly effective against L. monocytogenes, and one of these should be used in patients with proven or suspected L. monocytogenes meningitis. Third generation cephalosporins are ineffective against this pathogen and therefore empirical monotherapy with these agents in patients at higher risk for L. monocytogenes meningitis, e.g. elderly (>50 years) and immunocompromised patients, should be avoided.24 As it is difficult to define patients that have an increased risk of L. monocytogenes, the empirical treatment for all adults includes amoxicillin to cover L. monocytogenes. Patients allergic to penicillin can be treated with trimethoprimsulfamethoxazole.6 

The addition of aminoglycosides is debated. Synergistic activity of gentamicin with other antibiotics has been shown in in vitro experiments. However, a cohort of 118 Spanish adults with L. monocytogenes disease showed increased mortality and renal failure in the aminoglycoside-treated patients.30 Therefore, aminoglycosides are not advised in adults with L. monocytogenes meningitis. Minimal duration of treatment of L. monocytogenes meningitis is 21 days for children and adults.28,31,32 

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Haemophilus influenzae?

The rate of beta-lactamase producing H. influenzae strains in the Netherlands has fluctuated in the last 25 years from 0.9% to 12.5%, with an average around 5% (data NRLBM). Therefore, third generation cephalosporins have become standard for H. influenzae meningitis, until susceptibility testing is performed. If the strain is susceptible to amoxicillin, amoxicillin should be used. The standard duration of therapy for adults is 7 days and for children 10 days.28,32

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Streptococcus agalactiae?

S. agalactiae is invariably susceptible to penicillin, amoxicillin, and cephalosporins. Treatment of S. agalactiae meningitis consists of penicillin or amoxicillin, and alternatively third generation cephalosporins can be used. The minimal advised treatment duration is 14 days, but courses up to 21 days should be considered in patients with a complicated disease course. In neonates with S. agalactiae meningitis gentamicin is added for 3 days.

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by Escherichia coli?

E. coli strains are mostly susceptible to third generation cephalosporins and 30-40% is susceptible to amoxicillin. Strains producing extended spectrum beta-lactamases (ESBL) are increasing in frequency but have not been described in meningitis patients in the Netherlands so far. Treatment of E. coli meningitis consists of third generation cephalosporins combined with gentamicin during the first three days of treatment in neonates. In children beyond the neonatal age and adults third generation cephalosporins are advised, or amoxicillin if the strain is sensitive to amoxicillin. When ESBL producing E. coli are suspected or proven, meropenem is the treatment of choice. The minimal advised treatment duration is 21 days.

 

What is the optimal antibiotic therapy and duration for community-acquired bacterial meningitis caused by unidentified pathogens (culture-negative cases)?

In 10 to 20% of bacterial meningitis cases, defined by elevated CSF markers of inflammation, CSF and blood cultures remain negative.6 No studies have been performed to determine the treatment regimen for these patients and the optimal duration of therapy is therefore also unclear. The given recommendations are based on the duration of therapy advised for the most common causative microorganisms. For children empirical therapy with a third generation cephalosporin should be continued for 14 days in culture-negative cases. In adults the empirical therapy can be changed, from amoxicillin combined with a third generation cephalosporin to monotherapy with amoxicillin for 14 days if after 48 hours cultures remain negative. Monotherapy amoxicillin is the antimicrobial therapy of choice in adults because infection with β-lactamase producing H. influenzae is virtually excluded if cultures remain negative after 48 hours. L. monocytogenes should still be covered after 48 hours as it is a slow growing microorganism. As L. monocytogenes is extremely rare in children beyond the neonatal age, monotherapy with a third generation cephalosporin suffices for children.

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Autorisatiedatum en geldigheid

Laatst beoordeeld  : 01-01-2012

Laatst geautoriseerd  : 01-01-2012

Geplande herbeoordeling  :

Initiatief en autorisatie

Initiatief:
  • Stichting Werkgroep Antibioticabeleid
Geautoriseerd door:
  • Nederlandse Vereniging voor Kindergeneeskunde
  • Nederlandse Vereniging voor Medische Microbiologie
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Neurologie
  • Stichting Werkgroep Antibioticabeleid

Algemene gegevens

The Dutch Working Party on Antibiotic Policy (SWAB; Stichting Werkgroep Antibiotica Beleid), established by the Dutch Society for Infectious Diseases (VIZ), the Dutch Society of Medical Microbiology (NVMM) and the Dutch Society for Hospital Pharmacists (NVZA), develops evidence-based guidelines for the use of antibiotics in hospitalized patients in order to optimize the quality of prescribing, thus, contributing to the containment of antimicrobial drug costs and resistance. By means of the development of national guidelines, SWAB offers local antibiotic and formulary committees a guideline for the development of their own, local antibiotic policy.  These are the first SWAB guidelines on bacterial central nervous system infections. It is developed according to the Evidence Based Guideline Development method (EBRO; www.cbo.nl). The AGREE criteria

(www.agreecollaboration.org) provided a structured framework both for the development and the assessment of the draft guideline. 

 

Relationship between the SWAB Guidelines and the 2012 Guidelines on Meningitis by the Dutch Society for Neurology (Nederlandse Vereniging voor Neurologie)

The SWAB guidelines cover the antimicrobial therapy in children and adults with bacterial meningitis, brain abscesses and tuberculous meningitis. They do not cover other treatment components of bacterial meningitis, such as corticosteroids, osmotic agents and anticoagulants.2 This is discussed extensively in the 2012 guidelines by the Dutch Society for Neurology (Nederlandse Vereniging voor Neurologie). The Nederlandse Vereniging voor Neurologie guidelines adopted the SWAB guidelines on meningitis to be the treatment part of their meningitis guidelines.

Doel en doelgroep

Core issues on cryptococcal meningitis are extensively discussed in the 2008 SWAB guidelines on fungal infections. Diagnostics for bacterial meningitis are briefly discussed in the introduction, but not systematically reviewed in these guidelines. Encephalitis falls outside the scope of these guidelines.

For this guideline we made a distinction based on the setting in which bacterial meningitis was acquired: community-acquired versus nosocomial. Further, we provide recommendations for empirical antimicrobial therapy for clinical subgroups of bacterial meningitis patients. The choice of initial antimicrobial therapy for these subgroups is based on the bacteria most commonly causing the disease, taking into account the patient’s age and clinical setting, and patterns of antimicrobial susceptibility. After the results of culture and susceptibility testing have become available, antimicrobial therapy can be modified for optimal treatment. 

Samenstelling werkgroep

Preparatory Committee: Dr. M.C. Brouwer, Drs. S.G.B. Heckenberg, Dr. G.T.J. van Well (Nederlandse Vereniging voor Kindergeneeskunde), Dr. A. Brouwer (Vereniging voor Infectieziekten), Dr. E.J. Delwel (Nederlandse Vereniging voor Neurochirurgie), Dr. L. Spanjaard (Nederlandse Vereniging voor Medisch Microbiologie), Prof. dr. D. van de Beek (Nederlandse Vereniging voor Neurologie), Prof. dr. J.M. Prins (SWAB).

Methode ontwikkeling

Evidence based

Werkwijze

Twelve key questions were formulated concerning the antibiotic treatment of bacterial central nervous system infections. Using several data sources (see data sources) conclusions were drawn, with their specific level of evidence, according to the CBO grading system adopted by SWAB (Table 1).1

Subsequently, specific recommendations were formulated. Each key question will be answered in a separate chapter. 

 

Table 1a

Methodological quality of individual studies.1

 

 

Intervention

Etiology, prognosis

A1 

Systematic review of at least two independent A2-level studies 

A2 

Randomised Controlled Trial (RCT) of sufficient methodological quality and power 

Prospective cohort study with sufficient power and with adequate confounding corrections 

B 

Comparative Study lacking the same quality

as mentioned at A2 (including patientcontrol and cohort studies) 

Prospective cohort study lacking the same quality as mentioned at A2, retrospective cohort study or patient-control study 

C 

Non-comparative study 

D 

Expert opinion 

 

Table 1b

Level of evidence of conclusions

 

 

Conclusions based on 

1 

Study of level A1 or at least two independent studies of level A2 

2 

One study of level A2 or at least two independent studies of level B 

3 

One study of level B or C 

4 

Expert opinion 

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Nosocomiale bacteriële meningitis