id000051
10.3205/id000051
urn:nbn:de:0183-id0000519
Leitlinie
Guideline
Kalkulierte parenterale Initialtherapie bakterieller Infektionen: Bakterielle Meningitis
Calculated parenteral initial therapy of bacterial infections: Bacterial meningitis
Shah
Shah
Pramod M.
PM
Prof. Dr.
Auf dem Mühlberg 30c, 60599 Frankfurt am Main, DeutschlandFrankfurt am Main, Deutschland
Auf dem Mühlberg 30c, 60599 Frankfurt am Main, GermanyFrankfurt am Main, Germany
infektiologie@posteo.de
author
Brodt
Brodt
Reinhard
R
Med. Klinik II / Infektiologie, Universitätsklinikum Frankfurt am Main, Deutschland
Med. Klinik II / Infektiologie, Universitätsklinikum Frankfurt am Main, Germany
author
Wichelhaus
Wichelhaus
Thomas A.
TA
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universitätsklinikum Frankfurt, Deutschland
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Universitätsklinikum Frankfurt, Germany
author
Nau
Nau
Roland
R
Geriatrisches Zentrum, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Deutschland
Geriatrisches Zentrum, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany
author
German Medical Science GMS Publishing House
Düsseldorf
610
Calculated parenteral initial therapy
Kalkulierte parenterale Initialtherapie
20200326
germ
engl
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung).
2195-8831
8
GMS Infectious Diseases
GMS Infect Dis
07
Dies ist das 13. Kapitel der von der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) herausgegebenen S2k Leitlinie „Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen – Update 2018“ in der 2. aktualisierten Fassung.Die bakterielle Meningitis ist eine lebensbedrohliche Infektionskrankheit mit hohen Mortalitäts- und Invaliditätsraten, die den sofortigen Beginn einer antimikrobiellen Behandlung erfordert, um diese Raten zu senken.
This is the thirteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Bacterial meningitis is a life-threatening infectious disease with high mortality and disability rates requiring prompt initiation of antimicrobial treatment to lower these rates.
EinleitungDie akute bakterielle Meningitis (Hirnhautentzündung) ist gekennzeichnet durch die klinischen Leitsymptome Fieber, Kopfschmerzen und meningitische Reizerscheinungen (Meningismus). Darüber hinaus können Verwirrtheitszustände, Vigilanzstörungen oder ein Koma das klinische Bild bestimmen , . Die akute bakterielle Meningitis ist von der Virusmeningitis abzugrenzen. Häufigste Erreger der akuten, außerhalb des Krankenhauses erworbenen bakteriellen Meningitis sind Meningokokken und Pneumokokken. Seltener sind Haemophilus influenzae, Listerien und Mycobacterium tuberculosis. Nach Infektionsepidemiologischem Jahrbuch meldepflichtiger Krankheiten für 2014 wurden 275 Fälle von Meningokokken-Meningitis in Deutschland (Inzidenz 0,3 pro 100.000) gemeldet . Davon gehörten 71,3% der Serogruppe B, 17,1% der Serogruppe C, 7,5% der Serogruppe Y und 4,2% der Serogruppe W an. Daten aus Deutschland zur Inzidenz der Meningitis durch Pneumokokken oder Listerien liegen nicht vor. Österreich meldete in 2013 für Pneumokokken eine Inzidenz von 0,42/100.000 und für Meningokokken eine Inzidenz von 0,71/100.000 (http://www.ages.at/). Das Erregerspektrum ist altersabhängig. In besonderen Situationen (post-operativ, Liquordrainage-assoziiert und bei Immunsupprimierten) können auch andere Erreger wie Staphylokokken, Enterobakterien und Pseudomonaden bakterielle Meningitiden verursachen. Die von kraniofazialen Infektionen fortgeleitete Meningitis wird vorwiegend von Pneumokokken und anderen Streptokokken verursacht. Auch kann es im Rahmen von anderen septisch verlaufenden Infektionskrankheiten zu einer fakultativen Organmanifestation im ZNS kommen, die vor allem bei einer Leptospirose oder Borrelia-burgdorferi-Infektion beobachtet wird. Das subakute bzw. chronische meningitische Syndrom wird insbesondere durch Mykobakterien, Candida-Arten, Cryptococcus neoformans, Coccidioides immitis und Treponema pallidum hervorgerufen. Unter schwerer Immunsuppression ist mit einem atypischen Verlauf der Meningitis zu rechnen.
IntroductionAcute bacterial meningitis is characterized by the clinical cardinal symptoms of fever, headaches and irritation of the meninges (meningism). In addition, confusion, epilepsies or coma may also feature in the clinical presentation , . Acute bacterial meningitis must be distinguished from viral meningitis. The most common causes of acute bacterial meningitis acquired outside of hospitals are meningococci and pneumococci. Less common are Haemophilus influenzae, Listeria and Mycobacterium tuberculosis. According to the Infectious Disease Yearbook of Notifiable Diseases 2014, 275 cases of meningococcal meningitis were reported in Germany (incidence 0.3 per 100,000) . Of these, 71.3% belonged to serogroup B, 17.1% to serogroup C, 7.5% to serogroup Y and 4.2% to serogroup W. Data from Germany on the incidence of meningitis caused by pneumococci or listeria are not available. Austria reported an incidence of 0.42/100,000 for pneumococci in 2013 and an incidence of 0.71/100,000 for meningococci (http://www.ages.at/). The pathogen spectrum is age-dependent. Under certain circumstances (post-operative, CSF-associated and immunosuppressed patients), other pathogens such as staphylococci, enterobacteria and pseudomonads can also cause bacterial meningitis.Meningitis associated with craniofacial infections is mainly caused by pneumococci and other streptococci. There may also be organic manifestations in the CNS in the context of other septic infectious diseases, especially in leptospirosis or Borrelia burgdorferi infections. Subacute or chronic meningitic syndrome is caused in particular by mycobacteria, Candida species, Cryptococcus neoformans, Coccidioides immitis and Treponema pallidum. An atypical progression of meningitis can be expected under severe immunosuppression.
DiagnostikBei allen Patienten sollen Blutkulturen entnommen werden. Je nach Lokalisation von Begleitinfektionen ist zusätzlich die Gewinnung eines Rachenabstrichs, von Bronchialsekret, Urin oder eines Wundabstrichs erforderlich. Die diagnostische Sicherung der bakteriellen Meningitis gelingt mit Hilfe der Lumbalpunktion und der Untersuchung des Liquor cerebrospinalis. Typisch ist eine granulozytäre Pleozytose über 1.000 Zellen/µl, ein Liquor-Eiweiß über 100 mg/dl, ein Liquor-Laktat über 3,5 mmol/l, sowie ein Liquor-Serum-Glucose-Quotient unter 0,3. Die Methylenblau-Färbung und die Gram-Färbung des Liquorsediments können orientierende Hinweise geben (gramnegative Stäbchen oder Kokken, grampositive Stäbchen oder Kokken). Zur ergänzenden Diagnostik haben sich Antigennachweisverfahren aus dem Liquor und Urin, die PCR aus dem Liquor (insbesondere bei Verdacht auf tuberkulöse Meningitis bzw. zum Nachweis/Ausschluss viraler ZNS-Infektionen), CRP/PCT-Bestimmung im Serum und Differential-Blutbild bewährt . Bei subakuten Meningitiden und Enzephalitiden, insbesondere bei der Neuroborreliose, ist der Nachweis der Erreger-spezifischen Antikörpersynthese im ZNS mittels Bestimmung des Liquor/Serum-Antikörperindex von großer Bedeutung .Bei schwer bewusstseinsgestörten Patienten, Patienten mit fokal-neurologischem Defizit (z.B. Hemiparese), Patienten mit epileptischen Anfällen innerhalb der letzten Tage oder immunsupprimierten Patienten, bei denen der dringende Verdacht auf eine bakterielle Meningitis besteht, soll sofort nach der Blutentnahme (für das Anlegen einer Blutkultur) die Initialtherapie mit parenteralen Antibiotika und Dexamethason eingeleitet werden. Anschließend werden ein Schädel-Computertomogramm und – wenn der CT-Befund nicht dagegen spricht – eine Liquorpunktion durchgeführt . Eine schwedische Studie deutet darauf hin, dass auch bei Patienten mit Bewusstseinsstörung ohne vorherige zerebrale Bildgebung Liquor zur Sicherung der Ätiologie entnommen werden kann. Die hierdurch erzielte Verkürzung des Intervalls zwischen Aufnahme und erster Antibiotika-Dosis scheint die Gefahr einer Herniation durch die Liquorentnahme mehr als aufzuwiegen .
DiagnosticsFor all patients blood cultures should be taken. Depending on the location of concomitant infections, it may be necessary to obtain a throat swab, bronchial secretions, urine or a wound swab. A diagnosis of bacterial meningitis can be proven through lumbar puncture and examination of the cerebrospinal fluid. Granulocytic pleocytosis in excess of 1,000 cells/µl, CSF protein above 100 mg/dl, CSF lactate greater than 3.5 mmol/l and a CSF/serum glucose ratio below 0.3 is typical. Methylene blue staining and Gram staining of the CSF sediment may provide general clues (Gram-negative rods or cocci, Gram-positive rods or cocci). For additional diagnostics, antigen detection methods from the CSF and urine, PCR from the CSF (especially in cases of suspected tuberculous meningitis or for the detection/exclusion of viral CNS infections), CRP/PCT measurement in serum and differential blood counts have proven useful . In subacute meningitis and encephalitis, in particular in neuroborreliosis, the detection of pathogen-specific antibody synthesis in the CNS through determining the CSF/serum antibody index is of great importance .Patients with severe disturbed consciousness, patients with a focal neurological deficit (for example hemiparesis), patients with epileptic seizures within the last few days or immunosuppressed patients who are strongly suspected of having bacterial meningitis should be referred to initial treatment with parenteral antibiotics and dexamethasone immediately after taking the blood sample (for blood culture). Subsequently, a cranial CT and, if the CT findings do not indicate otherwise, a lumbar puncture will be performed . A Swedish study indicates that even in patients with disturbed consciousness CSF can be taken without prior cerebral imaging to determine the etiology. Reducing the time gap between admittance and first dose of antibiotics this way seems to more than outweigh the risk of herniation due to CSF removal .
TherapieDer verzögerte Beginn der Antibiotika-Therapie ist mit einer ungünstigen Prognose vergesellschaftet , . Aufgrund des Erregerspektrums der ambulant erworbenen bakteriellen Meningitis soll eine kalkulierte Initialtherapie (Tabelle 1 ) mit einem Cephalosporin der Gruppe 3a in Kombination mit Ampicillin (Wirkung auf Listerien) eingeleitet werden . Bei nosokomialer bakterieller Meningitis und bei infizierten Liquordrainagen besteht die Initialtherapie aus Vancomycin plus Meropenem oder Vancomycin plus Ceftazidim. Kann ein Erreger nachgewiesen werden, wird gezielt nach dem Ergebnis der mikrobiologischen Untersuchung weiterbehandelt (Tabelle 2 ). Infizierte Liquordrainagen müssen in der Regel entfernt und durch eine externe Liquorableitung ersetzt werden. Die Behandlungsdauer bei unbekanntem Erreger und einer Meningitis durch Haemophilus influenzae oder Streptococcus pneumoniae soll nicht weniger als zehn Tage und bei der Meningokokken-Meningitis nicht weniger als sieben Tage betragen. Bei Patienten mit einer durch Listerien, Staphylococcus aureus, Pseudomonas aeruginosa oder Enterobakterien verursachten Meningitis dauert die Antibiotika-Therapie 3 Wochen.Fieber oder eine Zunahme der Pleozytose im sterilen Liquor allein sind kein Grund für eine Therapieverlängerung. Eine Abschlusspunktion am oder nach Ende der Behandlung ist bei komplikationslosem Verlauf nicht erforderlich.Bei Erregern mit verminderter Empfindlichkeit gegenüber Antibiotika kann eine intraventrikuläre Antibiotika-Therapie notwendig werden, um die Erreger aus dem ZNS zu eliminieren. Derzeit ist in Deutschland kein Präparat für die intraventrikuläre Applikation zugelassen und randomisierte Studien, die eine Verbesserung des Behandlungsergebnisses durch intraventrikuläre Therapie belegen könnten, fehlen. Bei der intraventrikulären Antibiotika-Gabe handelt es sich somit um einen Heilversuch. Antibiotika, bei denen die intraventrikuläre Anwendung aufgrund eines geringen Übertritts auch bei hoch entzündlichen Meningen in den Liquor und hoher systemischer Toxizität Sinn macht und für die Erfahrungsberichte publiziert wurden, sind in Tabelle 3 aufgeführt . Die Steuerung der intrathekalen Behandlung durch Messung der Liquorkonzentrationen erscheint sinnvoll .In einer Cochrane-Analyse von 25 Studien zum Einsatz von Kortikosteroiden bei bakterieller Meningitis fand sich in Ländern mit hohem medizinischen Standard (Diagnostik und Therapie) eine signifikante Reduktion der Letalität, wenn Pneumokokken die Erreger waren (RR 0,84, 95% KI 0,72–0,98), nicht aber bei der Haemophilus-influenzae- oder Neisseria-meningitidis-Meningitis . Die Behandlung mit Kortikosteroiden führte darüber hinaus zu einer signifikanten Reduktion von Hörschäden (<![CDATA[RR 0,74</PlainText></TextGroup>, 95% KI 0,63–0,8) und neurologischen Folgeschäden (RR 0,83, 95% KI 0,69–1,00). Dexamethason <TextGroup><PlainText>10 mg</PlainText></TextGroup> i.v. 4 mal pro Tag über 4 Tage plus empirische Antibiotika-Gabe ist das empfohlene Regime für die Initialtherapie bei erwachsenen Patienten mit Verdacht auf bakterielle Meningitis.</Pgraph><Pgraph>Für Patienten mit nosokomialen Meningitiden und für Immunsupprimierte mit bakterieller Meningitis liegen keine ausreichenden Daten vor, so dass die adjuvante Dexamethason-Gabe hier nicht empfohlen wird. Für weitere adjuvante, tierexperimentell wirksame Strategien liegen beim Erwachsenen keine ausreichenden Erfahrungen vor <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>. Aufgrund publizierter negativer Studien wird eine routinemäßige adjuvante Therapie mit Paracetamol, Glycerol oder Hypothermie bei bakterieller Meningitis nicht empfohlen <TextLink reference="16"></TextLink>, <TextLink reference="17"></TextLink>, <TextLink reference="18"></TextLink>.</Pgraph><Pgraph>Bei der tuberkulösen Meningitis verbessert die adjuvant<TextGroup><PlainText>e G</PlainText></TextGroup>abe von Dexamethason oder Prednisolon die Behandlungsergebnisse <TextLink reference="19"></TextLink>. Nach einem gebräuchliche<TextGroup><PlainText>n S</PlainText></TextGroup>chema erhalten Erwachsene und Jugendliche in den Stadien II und III intravenös Dexamethason <TextGroup><PlainText>0,4 m</PlainText></TextGroup>g/kg/Tag in Woche 1, 0,3 mg/kg/Tag in Woche 2, <TextGroup><PlainText>0,2 m</PlainText></TextGroup>g/kg/Tag in Woche 3 und 0,1 mg/kg/Tag in Woch<TextGroup><PlainText>e 4</PlainText></TextGroup>, gefolgt von oralem Dexamethason für 4 Wochen mit Verminderung der täglichen Dosis um 1 mg pro Woche. Im Stadium I wird intravenös 0,3 mg/kg/Tag Dexamethason in Woche 1, 0,2 mg/kg/Tag in Woche 2, gefolgt von Dexamethason 0,1 mg/kg/Tag oral in Woche 3, <TextGroup><PlainText>3 mg</PlainText></TextGroup>/Tag oral in Woche 4, 2 mg/Tag oral in Woche 5 und 1 mg/Tag in Woche 6 verabreicht <TextLink reference="20"></TextLink>. Alternativ kann ein Prednisolon-Regime beginnend mit 60–80 mg/Tag absteigend für 4–6 Wochen erwogen werden. Dosierungsempfehlungen bei Tuberkulose-Meningitis siehe <TextGroup><PlainText>Tabelle 4 </PlainText></TextGroup><ImgLink imgNo="4" imgType="table"/>.</Pgraph><Pgraph>Zur Thrombose-Prophylaxe wird eine „Low-dose-Heparinisierung“ und zur Magenprotektion die Applikation von Protonenpumpen-Inhibitoren empfohlen.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Treatment">
<MainHeadline>Treatment</MainHeadline><Pgraph>Delayed initiation of antibiotic treatment is associated with an unfavorable prognosis <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>. Based on the pathogen spectrum of community-acquired bacterial meningitis, calculated initial treatment (Table 1 <ImgLink imgNo="1" imgType="table"/>) with a Group 3a cephalosporin in combination with ampicillin (effect on Listeria) should be initiated <TextLink reference="10"></TextLink>. For nosocomial bacterial meningitis and infected CSF drainage, initial treatment consists of vancomycin plus meropenem or vancomycin plus ceftazidime. If a pathogen can be detected, further treatment will be based on the results of the microbiological testing (Table 2 <ImgLink imgNo="2" imgType="table"/>). Infected CSF drainage must usually be removed and replaced with external CSF drainage. The duration of treatment with unknown pathogens and meningitis caused by <Mark2>Haemophilus influenzae</Mark2> or <Mark2>Streptococcus pneumoniae</Mark2> should not be less than 10 days and in meningococcal meningitis not less than 7 days. In patients with meningitis caused by Listeria, <Mark2>Staphylococcus aureus</Mark2>, <Mark2>Pseudomonas aeruginosa</Mark2> or enterobacteria, antibiotic treatment lasts 3 weeks.</Pgraph><Pgraph>Fever or an increase in pleocytosis in sterile CSF alone is no reason for prolonging treatment. A final puncture on or after the end of the treatment is not required in cases of uncomplicated progression.</Pgraph><Pgraph>In pathogens with reduced sensitivity to antibiotics, intraventricular antibiotic treatment may be necessary to eliminate the CNS pathogens. At present, no drug is approved for intraventricular administration in Germany and randomized trials which could lead to an improvement of the treatment outcome through intraventricular treatment do not exist. Intraventricular administration of antibiotics thus constitutes an attempted cure. Antibiotics for which intraventricular use makes sense due to low crossover into the CSF even in cases of highly inflammatory meninges and high systemic toxicity and for which experience reports have been published are listed in Table 3 <ImgLink imgNo="3" imgType="table"/> <TextLink reference="11"></TextLink>. Managing intrathecal treatment by measuring CSF concentrations would appear to be sensible <TextLink reference="12"></TextLink>.</Pgraph><Pgraph>In a Cochrane analysis of 25 studies on the use of corticosteroids in bacterial meningitis, there was a significant reduction in mortality in countries with high medical standards (diagnosis and treatment) when pneumococci were the causative pathogens (RR 0.84, 95% CI 0,72– 0,98) but not in <Mark2>Haemophilus influenzae</Mark2> or <Mark2>Neisseria meningitidis</Mark2> meningitis <TextLink reference="13"></TextLink>. Treatment with corticosteroids also resulted in a significant reduction of damage to hearing (RR 0.74, 95% CI 0.63–0.8) and neurological consequential damage (RR 0.83, 95% CI 0.69–1.00). </Pgraph><Pgraph>Dexamethasone 10 mg i.v. 4 times a day over 4 days plus empirical antibiotic administration is the recommended initial treatment regimen for adult patients suspected of having bacterial meningitis.</Pgraph><Pgraph>Insufficient data are available for patients with nosocomial meningitis and immunosuppressed patients with bacterial meningitis, so adjuvant dexamethasone administration is not recommended. For further adjuvant strategies which have been proven effective in animal experiments, there is insufficient experience in human adults <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>. Due to published negative studies, routine adjuvant therapy with paracetamol, glycerol or hypothermia in bacterial meningitis is not recommended <TextLink reference="16"></TextLink>, <TextLink reference="17"></TextLink>, <TextLink reference="18"></TextLink>.</Pgraph><Pgraph>In tuberculous meningitis, adjuvant administration of dexamethasone or prednisolone improves outcomes <TextLink reference="19"></TextLink>. According to a common formula, adults and adolescents in stages II and III receive dexamethasone intravenously 0.4 mg/kg/day in week 1, 0.3 mg/kg/day in week 2, <TextGroup><PlainText>0.2 m</PlainText></TextGroup>g/kg/day in week 3 and 0.1 mg/kg/day in week 4, followed by oral dexamethasone for 4 weeks with a daily dose reduction of 1 mg per week. In stage I, intravenous administration of dexamethasone 0.3 mg/kg/day in <TextGroup><PlainText>week 1</PlainText></TextGroup>, 0.2 mg/kg/day in week 2, followed by dexamethasone 0.1 mg/kg/day orally in week 3, 3 mg/day orally in <TextGroup><PlainText>week 4</PlainText></TextGroup>, 2 mg/day orally in week 5 and 1 mg/day in <TextGroup><PlainText>week 6</PlainText></TextGroup> <TextLink reference="20"></TextLink>. Alternatively, a prednisolone regimen may be considered, starting at 60–80 mg/day decreasing for <TextGroup><PlainText>4–6 weeks</PlainText></TextGroup>. Dosage recommendations for tuberculous meningitis see Table 4 <ImgLink imgNo="4" imgType="table"/>.</Pgraph><Pgraph>For thrombosis prophylaxis, low-dose heparinization and for gastric protection, the application of proton pump inhibitors is recommended.</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Prophylaxe">
<MainHeadline>Prophylaxe</MainHeadline><Pgraph>Häufigster Erreger einer Meningitis nach Splenektomie ist <Mark2>Streptococcus pneumoniae</Mark2>, gefolgt von anderen bekapselten Bakterienarten. Es wird daher möglichst vor einer Milzentfernung (in Notfällen auch nach der OP) eine aktive Impfung durch eine Pneumokokken-, Hib- und Meningokokken-Vakzine empfohlen. Bezüglich der weiteren Indikationen zur <Mark2>Haemophilus</Mark2>-, Pneumokokken- und Meningokokken-Impfung wird auf die Homepage der Ständigen Impfkommission des Robert Koch-Instituts verwiesen (<Hyperlink href="http://www.rki.de/nn_199596/DE/Content/Infekt/Impfen/impfen.html">http://www.rki.de/nn_199596/DE/Content/Infekt/Impfen/impfen.html</Hyperlink>).</Pgraph><Pgraph>Auf Grundlage aktueller Resistenzdaten erhalten enge Kontaktpersonen von Patienten mit in Deutschland erworbener Meningokokken-Meningitis eine antimikrobielle Prophylaxe bis zu 10 Tage nach dem letzten Patientenkontakt mit Ciprofloxacin, Rifampicin oder Ceftriaxon <TextLink reference="21"></TextLink>. Erwachsene (außer Schwangere) erhalten Ciprofloxacin (Einmalgabe 500–750 mg, p.o.) oder alternativ Rifampicin (600 mg alle 12 Stunden für 2 Tage). Schwangere erhalten Ceftriaxon (Einmalgabe 250 mg, i.m.). Kinder erhalten Rifampicin (10 mg/kg KG alle 12 Stunden für 2 Tage, p.o.). Unter Rifampicin (auch als Prophylaxe) ist eine rasche Resistenzentwicklung beschrieben <TextLink reference="22"></TextLink>. Bei <Mark2>Neisseria-meningitidis</Mark2>-Stämmen aus Süd- und Westeuropa sowie aus Südost-Asien ist von einer zunehmenden Ciprofloxacin-Resistenz auszugehen <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>, <TextLink reference="25"></TextLink>.</Pgraph><Pgraph>Enge Kontaktpersonen von Patienten mit <Mark2>Haemophilus-influenzae</Mark2>-Meningitis erhalten eine antimikrobielle Prophylaxe bis zu 10 Tagen nach dem letzten Patientenkontakt <TextLink reference="26"></TextLink>: Erwachsene (außer Schwangere) erhalten Rifampicin (600 mg alle 24 Stunden für 4 Tage, p.o.); Kinder unter 12 Jahren erhalten Rifampicin (20 mg/kg KG alle 24 Stunden für 4 Tage, p.o.).</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Prophylaxis">
<MainHeadline>Prophylaxis</MainHeadline><Pgraph>The most common cause of meningitis after splenectomy is <Mark2>Streptococcus pneumoniae</Mark2>, followed by other encapsulated bacterial species. It is therefore recommended that active vaccination using a pneumococcal, hib- and meningococcal vaccine is carried out prior to removal of the spleen (in emergencies also after surgery). Concerning the further indications for <Mark2>Haemophilus</Mark2>-, pneumococcal and meningococcal vaccination, refer to the homepage of the Standing Vaccination Commission of the Robert Koch-Institute (<Hyperlink href="http://www.rki.de/nn_199596/DE/Content/Infekt/Impfen/impfen.html">http://www.rki.de/nn_199596/DE/Content/Infekt/Impfen/impfen.html</Hyperlink>).</Pgraph><Pgraph>Based on current resistance data, people in close contact with patients with meningococcal meningitis acquired in Germany receive antimicrobial prophylaxis up to 10 days after the last patient contact using ciprofloxacin, rifampicin or ceftriaxone <TextLink reference="21"></TextLink>. Adults (except pregnant women) receive ciprofloxacin (single dose 500–750 mg p.o.) or alternatively rifampicin (600 mg every 12 hours for <TextGroup><PlainText>2 days</PlainText></TextGroup>). Pregnant women receive ceftriaxone (single dose 250 mg, i.m.). Children receive rifampicin (10 mg/kg bodyweight every 12 hours for 2 days, p.o.). There have been reports of rifampicin (including as prophylaxis) leading to rapid development of resistance <TextLink reference="22"></TextLink>. An increase in ciprofloxacin resistance is to be expected in Neisseria meningitidis strains from southern and western Europe as well as from southeast Asia <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>, <TextLink reference="25"></TextLink>.</Pgraph><Pgraph>People in close contact with patients with Haemophilus influenzae meningitis receive antimicrobial prophylaxis up to 10 days after the last patient contact <TextLink reference="26"></TextLink>: Adults (except pregnant women) receive rifampicin (600 mg every 24 hours for 4 days, p.o.); children under the age of 12 receive rifampicin (20 mg/kg body weight every <TextGroup><PlainText>24 hours</PlainText></TextGroup> for 4 days, p.o.).</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Anmerkung">
<MainHeadline>Anmerkung</MainHeadline><Pgraph>Dies ist das 13. Kapitel der von der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) herausgegebenen S2k Leitlinie „Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen – Update 2018“ in der 2. aktualisierten Fassung.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Note">
<MainHeadline>Note</MainHeadline><Pgraph>This is the thirteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2<Superscript>nd</Superscript> updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemothe<TextGroup><PlainText>ra</PlainText></TextGroup>pie e.V. (PEG) has been translated to address an international audience.</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Interessenkonflikte">
<MainHeadline>Interessenkonflikte</MainHeadline><Pgraph>Die Autoren erklären, dass sie keine Interessenkonflikte in Zusammenhang mit diesem Artikel haben.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Competing interests">
<MainHeadline>Competing interests</MainHeadline><Pgraph>The authors declare that they have no competing interests.</Pgraph></TextBlock>
<References linked="yes">
<Reference refNo="1">
<RefAuthor>Bohr V</RefAuthor>
<RefAuthor>Hansen B</RefAuthor>
<RefAuthor>Jessen O</RefAuthor>
<RefAuthor>Johnsen N</RefAuthor>
<RefAuthor>Kjersem H</RefAuthor>
<RefAuthor>Kristensen HS</RefAuthor>
<RefAuthor>Nyboe J</RefAuthor>
<RefAuthor>Rasmussen N</RefAuthor>
<RefTitle>Eight hundred and seventy-five cases of bacterial meningitis. Part I of a three-part series: clinical data, prognosis, and the role of specialised hospital departments</RefTitle>
<RefYear>1983</RefYear>
<RefJournal>J Infect</RefJournal>
<RefPage>21-30</RefPage>
<RefTotal>Bohr V, Hansen B, Jessen O, Johnsen N, Kjersem H, Kristensen HS, Nyboe J, Rasmussen N. Eight hundred and seventy-five cases of bacterial meningitis. Part I of a three-part series: clinical data, prognosis, and the role of specialised hospital departments. J Infect. 1983 Jul;7(1):21-30. DOI: 10.1016/S0163-4453(83)90894-0</RefTotal>
<RefLink>https://doi.org/10.1016/S0163-4453(83)90894-0</RefLink>
</Reference>
<Reference refNo="2">
<RefAuthor>Durand ML</RefAuthor>
<RefAuthor>Calderwood SB</RefAuthor>
<RefAuthor>Weber DJ</RefAuthor>
<RefAuthor>Miller SI</RefAuthor>
<RefAuthor>Southwick FS</RefAuthor>
<RefAuthor>Caviness VS Jr</RefAuthor>
<RefAuthor>Swartz MN</RefAuthor>
<RefTitle>Acute bacterial meningitis in adults. A review of 493 episodes</RefTitle>
<RefYear>1993</RefYear>
<RefJournal>N Engl J Med</RefJournal>
<RefPage>21-8</RefPage>
<RefTotal>Durand ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS Jr, Swartz MN. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med. 1993 Jan;328(1):21-8. DOI: 10.1056/NEJM199301073280104</RefTotal>
<RefLink>https://doi.org/10.1056/NEJM199301073280104</RefLink>
</Reference>
<Reference refNo="3">
<RefAuthor>Robert Koch Institut</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2015</RefYear>
<RefBookTitle>Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2014</RefBookTitle>
<RefPage></RefPage>
<RefTotal>Robert Koch Institut. Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2014. Berlin: RKI; 2015. DOI: 10.25646/3224</RefTotal>
<RefLink>https://doi.org/10.25646/3224</RefLink>
</Reference>
<Reference refNo="4">
<RefAuthor>Marcos MA</RefAuthor>
<RefAuthor>Martínez E</RefAuthor>
<RefAuthor>Almela M</RefAuthor>
<RefAuthor>Mensa J</RefAuthor>
<RefAuthor>Jiménez de Anta MT</RefAuthor>
<RefTitle>New rapid antigen test for diagnosis of pneumococcal meningitis</RefTitle>
<RefYear>2001</RefYear>
<RefJournal>Lancet</RefJournal>
<RefPage>1499-500</RefPage>
<RefTotal>Marcos MA, Martínez E, Almela M, Mensa J, Jiménez de Anta MT. New rapid antigen test for diagnosis of pneumococcal meningitis. Lancet. 2001 May 12;357(9267):1499-500. DOI: 10.1016/S0140-6736(00)04658-4</RefTotal>
<RefLink>https://doi.org/10.1016/S0140-6736(00)04658-4</RefLink>
</Reference>
<Reference refNo="5">
<RefAuthor>Reiber H</RefAuthor>
<RefAuthor>Lange P</RefAuthor>
<RefTitle>Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain</RefTitle>
<RefYear>1991</RefYear>
<RefJournal>Clin Chem</RefJournal>
<RefPage>1153-60</RefPage>
<RefTotal>Reiber H, Lange P. Quantification of virus-specific antibodies in cerebrospinal fluid and serum: sensitive and specific detection of antibody synthesis in brain. Clin Chem. 1991 Jul;37(7):1153-60.</RefTotal>
</Reference>
<Reference refNo="6">
<RefAuthor>Deutsche Gesellschaft für Neurologie</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2015</RefYear>
<RefBookTitle>Ambulant erworbene bakterielle (eitrige) Meningoenzephalitis im Erwachsenenalter. S2k-Leitlinie. AWMF-Registernummer: 030/089</RefBookTitle>
<RefPage></RefPage>
<RefTotal>Deutsche Gesellschaft für Neurologie. Ambulant erworbene bakterielle (eitrige) Meningoenzephalitis im Erwachsenenalter. S2k-Leitlinie. AWMF-Registernummer: 030/089. AWMF; 2015. (Leitlinien für Diagnostik und Therapie in der Neurologie). Available from: https://www.awmf.org/uploads/tx_szleitlinien/030-089l_S2k_Ambulant_erworbene_Meningoenzephalitis_2016-08-verlaengert_01.pdf</RefTotal>
<RefLink>https://www.awmf.org/uploads/tx_szleitlinien/030-089l_S2k_Ambulant_erworbene_Meningoenzephalitis_2016-08-verlaengert_01.pdf</RefLink>
</Reference>
<Reference refNo="7">
<RefAuthor>Glimåker M</RefAuthor>
<RefAuthor>Johansson B</RefAuthor>
<RefAuthor>Grindborg Ö</RefAuthor>
<RefAuthor>Bottai M</RefAuthor>
<RefAuthor>Lindquist L</RefAuthor>
<RefAuthor>Sjölin J</RefAuthor>
<RefTitle>Adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture</RefTitle>
<RefYear>2015</RefYear>
<RefJournal>Clin Infect Dis</RefJournal>
<RefPage>1162-9</RefPage>
<RefTotal>Glimåker M, Johansson B, Grindborg Ö, Bottai M, Lindquist L, Sjölin J. Adult bacterial meningitis: earlier treatment and improved outcome following guideline revision promoting prompt lumbar puncture. Clin Infect Dis. 2015 Apr;60(8):1162-9. DOI: 10.1093/cid/civ011</RefTotal>
<RefLink>https://doi.org/10.1093/cid/civ011</RefLink>
</Reference>
<Reference refNo="8">
<RefAuthor>Aronin SI</RefAuthor>
<RefAuthor>Peduzzi P</RefAuthor>
<RefAuthor>Quagliarello VJ</RefAuthor>
<RefTitle>Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing</RefTitle>
<RefYear>1998</RefYear>
<RefJournal>Ann Intern Med</RefJournal>
<RefPage>862-9</RefPage>
<RefTotal>Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998 Dec;129(11):862-9. DOI: 10.7326/0003-4819-129-11_Part_1-199812010-00004</RefTotal>
<RefLink>https://doi.org/10.7326/0003-4819-129-11_Part_1-199812010-00004</RefLink>
</Reference>
<Reference refNo="9">
<RefAuthor>Auburtin M</RefAuthor>
<RefAuthor>Wolff M</RefAuthor>
<RefAuthor>Charpentier J</RefAuthor>
<RefAuthor>Varon E</RefAuthor>
<RefAuthor>Le Tulzo Y</RefAuthor>
<RefAuthor>Girault C</RefAuthor>
<RefAuthor>Mohammedi I</RefAuthor>
<RefAuthor>Renard B</RefAuthor>
<RefAuthor>Mourvillier B</RefAuthor>
<RefAuthor>Bruneel F</RefAuthor>
<RefAuthor>Ricard JD</RefAuthor>
<RefAuthor>Timsit JF</RefAuthor>
<RefTitle>Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study</RefTitle>
<RefYear>2006</RefYear>
<RefJournal>Crit Care Med</RefJournal>
<RefPage>2758-65</RefPage>
<RefTotal>Auburtin M, Wolff M, Charpentier J, Varon E, Le Tulzo Y, Girault C, Mohammedi I, Renard B, Mourvillier B, Bruneel F, Ricard JD, Timsit JF. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med. 2006 Nov;34(11):2758-65. DOI: 10.1097/01.CCM.0000239434.26669.65</RefTotal>
<RefLink>https://doi.org/10.1097/01.CCM.0000239434.26669.65</RefLink>
</Reference>
<Reference refNo="10">
<RefAuthor>Peltola H</RefAuthor>
<RefAuthor>Anttila M</RefAuthor>
<RefAuthor>Renkonen OV</RefAuthor>
<RefTitle>Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group</RefTitle>
<RefYear>1989</RefYear>
<RefJournal>Lancet</RefJournal>
<RefPage>1281-7</RefPage>
<RefTotal>Peltola H, Anttila M, Renkonen OV. Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group. Lancet. 1989 Jun 10;1(8650):1281-7. DOI: 10.1016/S0140-6736(89)92685-8</RefTotal>
<RefLink>https://doi.org/10.1016/S0140-6736(89)92685-8</RefLink>
</Reference>
<Reference refNo="11">
<RefAuthor>Nau R</RefAuthor>
<RefAuthor>Sörgel F</RefAuthor>
<RefAuthor>Eiffert H</RefAuthor>
<RefTitle>Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections</RefTitle>
<RefYear>2010</RefYear>
<RefJournal>Clin Microbiol Rev</RefJournal>
<RefPage>858-83</RefPage>
<RefTotal>Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 2010 Oct;23(4):858-83. DOI: 10.1128/CMR.00007-10</RefTotal>
<RefLink>https://doi.org/10.1128/CMR.00007-10</RefLink>
</Reference>
<Reference refNo="12">
<RefAuthor>Ziai WC</RefAuthor>
<RefAuthor>Lewin JJ 3rd</RefAuthor>
<RefTitle>Improving the role of intraventricular antimicrobial agents in the management of meningitis</RefTitle>
<RefYear>2009</RefYear>
<RefJournal>Curr Opin Neurol</RefJournal>
<RefPage>277-82</RefPage>
<RefTotal>Ziai WC, Lewin JJ 3rd. Improving the role of intraventricular antimicrobial agents in the management of meningitis. Curr Opin Neurol. 2009 Jun;22(3):277-82. DOI: 10.1097/WCO.0b013e32832c1396</RefTotal>
<RefLink>https://doi.org/10.1097/WCO.0b013e32832c1396</RefLink>
</Reference>
<Reference refNo="13">
<RefAuthor>Brouwer MC</RefAuthor>
<RefAuthor>van de Beek D</RefAuthor>
<RefTitle>Earlier Treatment and Improved Outcome in Adult Bacterial Meningitis Following Guideline Revision Promoting Prompt Lumbar Puncture</RefTitle>
<RefYear>2015</RefYear>
<RefJournal>Clin Infect Dis</RefJournal>
<RefPage>664-5</RefPage>
<RefTotal>Brouwer MC, van de Beek D. Earlier Treatment and Improved Outcome in Adult Bacterial Meningitis Following Guideline Revision Promoting Prompt Lumbar Puncture. Clin Infect Dis. 2015 Aug;61(4):664-5. DOI: 10.1093/cid/civ328</RefTotal>
<RefLink>https://doi.org/10.1093/cid/civ328</RefLink>
</Reference>
<Reference refNo="14">
<RefAuthor>Nau R</RefAuthor>
<RefAuthor>Brück W</RefAuthor>
<RefTitle>Neuronal injury in bacterial meningitis: mechanisms and implications for therapy</RefTitle>
<RefYear>2002</RefYear>
<RefJournal>Trends Neurosci</RefJournal>
<RefPage>38-45</RefPage>
<RefTotal>Nau R, Brück W. Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci. 2002 Jan;25(1):38-45. DOI: 10.1016/S0166-2236(00)02024-5</RefTotal>
<RefLink>https://doi.org/10.1016/S0166-2236(00)02024-5</RefLink>
</Reference>
<Reference refNo="15">
<RefAuthor>Nau R</RefAuthor>
<RefAuthor>Djukic M</RefAuthor>
<RefAuthor>Spreer A</RefAuthor>
<RefAuthor>Ribes S</RefAuthor>
<RefAuthor>Eiffert H</RefAuthor>
<RefTitle>Bacterial meningitis: an update of new treatment options</RefTitle>
<RefYear>2015</RefYear>
<RefJournal>Expert Rev Anti Infect Ther</RefJournal>
<RefPage>1401-23</RefPage>
<RefTotal>Nau R, Djukic M, Spreer A, Ribes S, Eiffert H. Bacterial meningitis: an update of new treatment options. Expert Rev Anti Infect Ther. 2015;13(11):1401-23. DOI: 10.1586/14787210.2015.1077700</RefTotal>
<RefLink>https://doi.org/10.1586/14787210.2015.1077700</RefLink>
</Reference>
<Reference refNo="16">
<RefAuthor>Ajdukiewicz KM</RefAuthor>
<RefAuthor>Cartwright KE</RefAuthor>
<RefAuthor>Scarborough M</RefAuthor>
<RefAuthor>Mwambene JB</RefAuthor>
<RefAuthor>Goodson P</RefAuthor>
<RefAuthor>Molyneux ME</RefAuthor>
<RefAuthor>Zijlstra EE</RefAuthor>
<RefAuthor>French N</RefAuthor>
<RefAuthor>Whitty CJ</RefAuthor>
<RefAuthor>Lalloo DG</RefAuthor>
<RefTitle>Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial</RefTitle>
<RefYear>2011</RefYear>
<RefJournal>Lancet Infect Dis</RefJournal>
<RefPage>293-300</RefPage>
<RefTotal>Ajdukiewicz KM, Cartwright KE, Scarborough M, Mwambene JB, Goodson P, Molyneux ME, Zijlstra EE, French N, Whitty CJ, Lalloo DG. Glycerol adjuvant therapy in adults with bacterial meningitis in a high HIV seroprevalence setting in Malawi: a double-blind, randomised controlled trial. Lancet Infect Dis. 2011 Apr;11(4):293-300. DOI: 10.1016/S1473-3099(10)70317-0</RefTotal>
<RefLink>https://doi.org/10.1016/S1473-3099(10)70317-0</RefLink>
</Reference>
<Reference refNo="17">
<RefAuthor>Molyneux EM</RefAuthor>
<RefAuthor>Kawaza K</RefAuthor>
<RefAuthor>Phiri A</RefAuthor>
<RefAuthor>Chimalizeni Y</RefAuthor>
<RefAuthor>Mankhambo L</RefAuthor>
<RefAuthor>Schwalbe E</RefAuthor>
<RefAuthor>Kataja M</RefAuthor>
<RefAuthor>Pensulo P</RefAuthor>
<RefAuthor>Chilton L</RefAuthor>
<RefAuthor>Peltola H</RefAuthor>
<RefTitle>Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children</RefTitle>
<RefYear>2014</RefYear>
<RefJournal>Pediatr Infect Dis J</RefJournal>
<RefPage>214-6</RefPage>
<RefTotal>Molyneux EM, Kawaza K, Phiri A, Chimalizeni Y, Mankhambo L, Schwalbe E, Kataja M, Pensulo P, Chilton L, Peltola H. Glycerol and acetaminophen as adjuvant therapy did not affect the outcome of bacterial meningitis in Malawian children. Pediatr Infect Dis J. 2014 Feb;33(2):214-6. DOI: 10.1097/INF.0000000000000122</RefTotal>
<RefLink>https://doi.org/10.1097/INF.0000000000000122</RefLink>
</Reference>
<Reference refNo="18">
<RefAuthor>Mourvillier B</RefAuthor>
<RefAuthor>Tubach F</RefAuthor>
<RefAuthor>van de Beek D</RefAuthor>
<RefAuthor>Garot D</RefAuthor>
<RefAuthor>Pichon N</RefAuthor>
<RefAuthor>Georges H</RefAuthor>
<RefAuthor>Lefevre LM</RefAuthor>
<RefAuthor>Bollaert PE</RefAuthor>
<RefAuthor>Boulain T</RefAuthor>
<RefAuthor>Luis D</RefAuthor>
<RefAuthor>Cariou A</RefAuthor>
<RefAuthor>Girardie P</RefAuthor>
<RefAuthor>Chelha R</RefAuthor>
<RefAuthor>Megarbane B</RefAuthor>
<RefAuthor>Delahaye A</RefAuthor>
<RefAuthor>Chalumeau-Lemoine L</RefAuthor>
<RefAuthor>Legriel S</RefAuthor>
<RefAuthor>Beuret P</RefAuthor>
<RefAuthor>Brivet F</RefAuthor>
<RefAuthor>Bruel C</RefAuthor>
<RefAuthor>Camou F</RefAuthor>
<RefAuthor>Chatellier D</RefAuthor>
<RefAuthor>Chillet P</RefAuthor>
<RefAuthor>Clair B</RefAuthor>
<RefAuthor>Constantin JM</RefAuthor>
<RefAuthor>Duguet A</RefAuthor>
<RefAuthor>Galliot R</RefAuthor>
<RefAuthor>Bayle F</RefAuthor>
<RefAuthor>Hyvernat H</RefAuthor>
<RefAuthor>Ouchenir K</RefAuthor>
<RefAuthor>Plantefeve G</RefAuthor>
<RefAuthor>Quenot JP</RefAuthor>
<RefAuthor>Richecoeur J</RefAuthor>
<RefAuthor>Schwebel C</RefAuthor>
<RefAuthor>Sirodot M</RefAuthor>
<RefAuthor>Esposito-Farèse M</RefAuthor>
<RefAuthor>Le Tulzo Y</RefAuthor>
<RefAuthor>Wolff M</RefAuthor>
<RefTitle>Induced hypothermia in severe bacterial meningitis: a randomized clinical trial</RefTitle>
<RefYear>2013</RefYear>
<RefJournal>JAMA</RefJournal>
<RefPage>2174-83</RefPage>
<RefTotal>Mourvillier B, Tubach F, van de Beek D, Garot D, Pichon N, Georges H, Lefevre LM, Bollaert PE, Boulain T, Luis D, Cariou A, Girardie P, Chelha R, Megarbane B, Delahaye A, Chalumeau-Lemoine L, Legriel S, Beuret P, Brivet F, Bruel C, Camou F, Chatellier D, Chillet P, Clair B, Constantin JM, Duguet A, Galliot R, Bayle F, Hyvernat H, Ouchenir K, Plantefeve G, Quenot JP, Richecoeur J, Schwebel C, Sirodot M, Esposito-Farèse M, Le Tulzo Y, Wolff M. Induced hypothermia in severe bacterial meningitis: a randomized clinical trial. JAMA. 2013 Nov;310(20):2174-83. DOI: 10.1001/jama.2013.280506</RefTotal>
<RefLink>https://doi.org/10.1001/jama.2013.280506</RefLink>
</Reference>
<Reference refNo="19">
<RefAuthor>Prasad K</RefAuthor>
<RefAuthor>Singh MB</RefAuthor>
<RefTitle>Corticosteroids for managing tuberculous meningitis</RefTitle>
<RefYear>2008</RefYear>
<RefJournal>Cochrane Database Syst Rev</RefJournal>
<RefPage>CD002244</RefPage>
<RefTotal>Prasad K, Singh MB. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD002244. DOI: 10.1002/14651858.CD002244.pub3</RefTotal>
<RefLink>https://doi.org/10.1002/14651858.CD002244.pub3</RefLink>
</Reference>
<Reference refNo="20">
<RefAuthor>Thwaites GE</RefAuthor>
<RefAuthor>Nguyen DB</RefAuthor>
<RefAuthor>Nguyen HD</RefAuthor>
<RefAuthor>Hoang TQ</RefAuthor>
<RefAuthor>Do TT</RefAuthor>
<RefAuthor>Nguyen TC</RefAuthor>
<RefAuthor>Nguyen QH</RefAuthor>
<RefAuthor>Nguyen TT</RefAuthor>
<RefAuthor>Nguyen NH</RefAuthor>
<RefAuthor>Nguyen TN</RefAuthor>
<RefAuthor>Nguyen NL</RefAuthor>
<RefAuthor>Nguyen HD</RefAuthor>
<RefAuthor>Vu NT</RefAuthor>
<RefAuthor>Cao HH</RefAuthor>
<RefAuthor>Tran TH</RefAuthor>
<RefAuthor>Pham PM</RefAuthor>
<RefAuthor>Nguyen TD</RefAuthor>
<RefAuthor>Stepniewska K</RefAuthor>
<RefAuthor>White NJ</RefAuthor>
<RefAuthor>Tran TH</RefAuthor>
<RefAuthor>Farrar JJ</RefAuthor>
<RefTitle>Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults</RefTitle>
<RefYear>2004</RefYear>
<RefJournal>N Engl J Med</RefJournal>
<RefPage>1741-51</RefPage>
<RefTotal>Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, Nguyen QH, Nguyen TT, Nguyen NH, Nguyen TN, Nguyen NL, Nguyen HD, Vu NT, Cao HH, Tran TH, Pham PM, Nguyen TD, Stepniewska K, White NJ, Tran TH, Farrar JJ. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004 Oct;351(17):1741-51. DOI: 10.1056/NEJMoa040573</RefTotal>
<RefLink>https://doi.org/10.1056/NEJMoa040573</RefLink>
</Reference>
<Reference refNo="21">
<RefAuthor>Nationales Referenzzentrum für Meningokokken und Haemophilus influenza am Institut für Hygiene und Mikrobiologie der Universität Würzburg</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2015</RefYear>
<RefBookTitle>Daten zur Laborüberwachung von Meningokokken, 2014. Version 0.2</RefBookTitle>
<RefPage></RefPage>
<RefTotal>Nationales Referenzzentrum für Meningokokken und Haemophilus influenza am Institut für Hygiene und Mikrobiologie der Universität Würzburg. Daten zur Laborüberwachung von Meningokokken, 2014. Version 0.2. NRZMHi; 2015. Available from: http://www.meningococcus.uni-wuerzburg.de/startseite/berichte/berichte-meningokokken/daten-2014/</RefTotal>
<RefLink>http://www.meningococcus.uni-wuerzburg.de/startseite/berichte/berichte-meningokokken/daten-2014/</RefLink>
</Reference>
<Reference refNo="22">
<RefAuthor>Fraser A</RefAuthor>
<RefAuthor>Gafter-Gvili A</RefAuthor>
<RefAuthor>Paul M</RefAuthor>
<RefAuthor>Leibovici L</RefAuthor>
<RefTitle>Antibiotics for preventing meningococcal infections</RefTitle>
<RefYear>2006</RefYear>
<RefJournal>Cochrane Database Syst Rev</RefJournal>
<RefPage>CD004785</RefPage>
<RefTotal>Fraser A, Gafter-Gvili A, Paul M, Leibovici L. Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004785. DOI: 10.1002/14651858.CD004785.pub3</RefTotal>
<RefLink>https://doi.org/10.1002/14651858.CD004785.pub3</RefLink>
</Reference>
<Reference refNo="23">
<RefAuthor>Alcalá B</RefAuthor>
<RefAuthor>Salcedo C</RefAuthor>
<RefAuthor>de la Fuente L</RefAuthor>
<RefAuthor>Arreaza L</RefAuthor>
<RefAuthor>Uría MJ</RefAuthor>
<RefAuthor>Abad R</RefAuthor>
<RefAuthor>Enríquez R</RefAuthor>
<RefAuthor>Vázquez JA</RefAuthor>
<RefAuthor>Motgé M</RefAuthor>
<RefAuthor>de Batlle J</RefAuthor>
<RefTitle>Neisseria meningitidis showing decreased susceptibility to ciprofloxacin: first report in Spain</RefTitle>
<RefYear>2004</RefYear>
<RefJournal>J Antimicrob Chemother</RefJournal>
<RefPage>409</RefPage>
<RefTotal>Alcalá B, Salcedo C, de la Fuente L, Arreaza L, Uría MJ, Abad R, Enríquez R, Vázquez JA, Motgé M, de Batlle J. Neisseria meningitidis showing decreased susceptibility to ciprofloxacin: first report in Spain. J Antimicrob Chemother. 2004 Feb;53(2):409. DOI: 10.1093/jac/dkh075</RefTotal>
<RefLink>https://doi.org/10.1093/jac/dkh075</RefLink>
</Reference>
<Reference refNo="24">
<RefAuthor>Singhal S</RefAuthor>
<RefAuthor>Purnapatre KP</RefAuthor>
<RefAuthor>Kalia V</RefAuthor>
<RefAuthor>Dube S</RefAuthor>
<RefAuthor>Nair D</RefAuthor>
<RefAuthor>Deb M</RefAuthor>
<RefAuthor>Aggarwal P</RefAuthor>
<RefAuthor>Gupta S</RefAuthor>
<RefAuthor>Upadhyay DJ</RefAuthor>
<RefAuthor>Rattan A</RefAuthor>
<RefAuthor>Raj VS</RefAuthor>
<RefTitle>Ciprofloxacin-resistant Neisseria meningitidis, Delhi, India</RefTitle>
<RefYear>2007</RefYear>
<RefJournal>Emerging Infect Dis</RefJournal>
<RefPage>1614-6</RefPage>
<RefTotal>Singhal S, Purnapatre KP, Kalia V, Dube S, Nair D, Deb M, Aggarwal P, Gupta S, Upadhyay DJ, Rattan A, Raj VS. Ciprofloxacin-resistant Neisseria meningitidis, Delhi, India. Emerging Infect Dis. 2007 Oct;13(10):1614-6. DOI: 10.3201/eid1310.060820</RefTotal>
<RefLink>https://doi.org/10.3201/eid1310.060820</RefLink>
</Reference>
<Reference refNo="25">
<RefAuthor>Skoczynska A</RefAuthor>
<RefAuthor>Alonso JM</RefAuthor>
<RefAuthor>Taha MK</RefAuthor>
<RefTitle>Ciprofloxacin resistance in Neisseria meningitidis, France</RefTitle>
<RefYear>2008</RefYear>
<RefJournal>Emerging Infect Dis</RefJournal>
<RefPage>1322-3</RefPage>
<RefTotal>Skoczynska A, Alonso JM, Taha MK. Ciprofloxacin resistance in Neisseria meningitidis, France. Emerging Infect Dis. 2008 Aug;14(8):1322-3. DOI: 10.3201/eid1408.080040</RefTotal>
<RefLink>https://doi.org/10.3201/eid1408.080040</RefLink>
</Reference>
<Reference refNo="26">
<RefAuthor>Robert Koch Institut</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2002</RefYear>
<RefJournal>Epidemiologisches Bulletin</RefJournal>
<RefPage></RefPage>
<RefTotal>Robert Koch Institut, editor. Epidemiologisches Bulletin. 2002;30. Available from: https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2002/Ausgabenlinks/30_02.html?nn=237558</RefTotal>
<RefLink>https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2002/Ausgabenlinks/30_02.html?nn=237558</RefLink>
</Reference>
<Reference refNo="27">
<RefAuthor>Rupprecht TA</RefAuthor>
<RefAuthor>Pfister HW</RefAuthor>
<RefTitle>Clinical experience with linezolid for the treatment of central nervous system infections</RefTitle>
<RefYear>2005</RefYear>
<RefJournal>Eur J Neurol</RefJournal>
<RefPage>536-42</RefPage>
<RefTotal>Rupprecht TA, Pfister HW. Clinical experience with linezolid for the treatment of central nervous system infections. Eur J Neurol. 2005 Jul;12(7):536-42. DOI: 10.1111/j.1468-1331.2005.01001.x</RefTotal>
<RefLink>https://doi.org/10.1111/j.1468-1331.2005.01001.x</RefLink>
</Reference>
<Reference refNo="28">
<RefAuthor>Sousa D</RefAuthor>
<RefAuthor>Llinares P</RefAuthor>
<RefAuthor>Meijide H</RefAuthor>
<RefAuthor>Gutiérrez JM</RefAuthor>
<RefAuthor>Miguez E</RefAuthor>
<RefAuthor>Sánchez E</RefAuthor>
<RefAuthor>Castelo L</RefAuthor>
<RefAuthor>Mena A</RefAuthor>
<RefTitle>Clinical experience with linezolid for the treatment of neurosurgical infections</RefTitle>
<RefYear>2011</RefYear>
<RefJournal>Rev Esp Quimioter</RefJournal>
<RefPage>42-7</RefPage>
<RefTotal>Sousa D, Llinares P, Meijide H, Gutiérrez JM, Miguez E, Sánchez E, Castelo L, Mena A. Clinical experience with linezolid for the treatment of neurosurgical infections. Rev Esp Quimioter. 2011 Mar;24(1):42-7.</RefTotal>
</Reference>
<Reference refNo="29">
<RefAuthor>Global Tuberculosis Community Advisory Board</RefAuthor>
<RefTitle></RefTitle>
<RefYear></RefYear>
<RefBookTitle>TB online. TB Guidelines. Overview</RefBookTitle>
<RefPage></RefPage>
<RefTotal>Global Tuberculosis Community Advisory Board. TB online. TB Guidelines. Overview. Available from: http://www.tbonline.info/guidelines/</RefTotal>
<RefLink>http://www.tbonline.info/guidelines/</RefLink>
</Reference>
<Reference refNo="30">
<RefAuthor>Schaberg T</RefAuthor>
<RefAuthor>Bauer T</RefAuthor>
<RefAuthor>Brinkmann F</RefAuthor>
<RefAuthor>Diel R</RefAuthor>
<RefAuthor>Feiterna-Sperling C</RefAuthor>
<RefAuthor>Haas W</RefAuthor>
<RefAuthor>Hartmann P</RefAuthor>
<RefAuthor>Hauer B</RefAuthor>
<RefAuthor>Heyckendorf J</RefAuthor>
<RefAuthor>Lange C</RefAuthor>
<RefAuthor>Nienhaus A</RefAuthor>
<RefAuthor>Otto-Knapp R</RefAuthor>
<RefAuthor>Priwitzer M</RefAuthor>
<RefAuthor>Richter E</RefAuthor>
<RefAuthor>Rumetshofer R</RefAuthor>
<RefAuthor>Schenkel K</RefAuthor>
<RefAuthor>Schoch OD</RefAuthor>
<RefAuthor>Schönfeld N</RefAuthor>
<RefAuthor>Stahlmann R</RefAuthor>
<RefTitle>S2k-Leitlinie: Tuberkulose im Erwachsenenalter. Eine Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose e.V. im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V.</RefTitle>
<RefYear>2017</RefYear>
<RefJournal>Pneumologie</RefJournal>
<RefPage>325-97</RefPage>
<RefTotal>Schaberg T, Bauer T, Brinkmann F, Diel R, Feiterna-Sperling C, Haas W, Hartmann P, Hauer B, Heyckendorf J, Lange C, Nienhaus A, Otto-Knapp R, Priwitzer M, Richter E, Rumetshofer R, Schenkel K, Schoch OD, Schönfeld N, Stahlmann R. S2k-Leitlinie: Tuberkulose im Erwachsenenalter. Eine Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose e.V. im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. [Tuberculosis Guideline for Adults – Guideline for Diagnosis and Treatment of Tuberculosis including LTBI Testing and Treatment of the German Central Committee (DZK) and the German Respiratory Society (DGP)]. Pneumologie. 2017 Jun;71(6):325-97. DOI: 10.1055/s-0043-105954</RefTotal>
<RefLink>https://doi.org/10.1055/s-0043-105954</RefLink>
</Reference>
<Reference refNo="31">
<RefAuthor>Schaberg T</RefAuthor>
<RefAuthor>Bauer T</RefAuthor>
<RefAuthor>Castell S</RefAuthor>
<RefAuthor>Dalhoff K</RefAuthor>
<RefAuthor>Detjen A</RefAuthor>
<RefAuthor>Diel R</RefAuthor>
<RefAuthor>Greinert U</RefAuthor>
<RefAuthor>Hauer B</RefAuthor>
<RefAuthor>Lange C</RefAuthor>
<RefAuthor>Magdorf K</RefAuthor>
<RefAuthor>Loddenkemper R</RefAuthor>
<RefTitle>Empfehlungen zur Therapie, Chemoprevention und Chemoprophylaxe der TB im Erwachsenen- und Kindesalter (DZK und DGP)</RefTitle>
<RefYear>2012</RefYear>
<RefJournal>Pneumologie</RefJournal>
<RefPage>133-71</RefPage>
<RefTotal>Schaberg T, Bauer T, Castell S, Dalhoff K, Detjen A, Diel R, Greinert U, Hauer B, Lange C, Magdorf K, Loddenkemper R. Empfehlungen zur Therapie, Chemoprevention und Chemoprophylaxe der TB im Erwachsenen- und Kindesalter (DZK und DGP) [Recommendations for therapy, chemoprevention and chemoprophylaxis of tuberculosis in adults and children. German Central Committee against Tuberculosis (DZK), German Respiratory Society (DGP)]. Pneumologie. 2012 Mar;66(3):133-71. DOI: 10.1055/s-0031-1291619</RefTotal>
<RefLink>https://doi.org/10.1055/s-0031-1291619</RefLink>
</Reference>
<Reference refNo="32">
<RefAuthor>Caminero JA</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2013</RefYear>
<RefBookTitle>Guidelines for Clinical and Operational Management of Drug-Resistant Tuberculosis</RefBookTitle>
<RefPage></RefPage>
<RefTotal>Caminero JA, editor. Guidelines for Clinical and Operational Management of Drug-Resistant Tuberculosis. Paris: International Union Against Tuberculosis and Lung Disease; 2013. Available from: http://www.theunion.org/what-we-do/publications/technical/english/mdr-tbguide_6-19-13_web.pdf</RefTotal>
<RefLink>http://www.theunion.org/what-we-do/publications/technical/english/mdr-tbguide_6-19-13_web.pdf</RefLink>
</Reference>
<Reference refNo="33">
<RefAuthor>World Health Organization</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2013</RefYear>
<RefBookTitle>The use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Interim policy guidance. WHO/HTM/TB/2013.6</RefBookTitle>
<RefPage></RefPage>
<RefTotal>World Health Organization. The use of bedaquiline in the treatment of multidrug-resistant tuberculosis. Interim policy guidance. WHO/HTM/TB/2013.6. Geneva: WHO; 2013. Available from: http://www.who.int/tb/publications/mdrtb-treatment-guideline/en/</RefTotal>
<RefLink>http://www.who.int/tb/publications/mdrtb-treatment-guideline/en/</RefLink>
</Reference>
<Reference refNo="34">
<RefAuthor>World Health Organization</RefAuthor>
<RefTitle></RefTitle>
<RefYear>2014</RefYear>
<RefBookTitle>Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. WHO/HTM/TB/2014.11</RefBookTitle>
<RefPage></RefPage>
<RefTotal>World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. WHO/HTM/TB/2014.11. Geneva: WHO; 2014. Available from: http://www.who.int/tb/publications/pmdt_companionhandbook/en/</RefTotal>
<RefLink>http://www.who.int/tb/publications/pmdt_companionhandbook/en/</RefLink>
</Reference>
<Reference refNo="35">
<RefAuthor>Lange C</RefAuthor>
<RefAuthor>Abubakar I</RefAuthor>
<RefAuthor>Alffenaar JW</RefAuthor>
<RefAuthor>Bothamley G</RefAuthor>
<RefAuthor>Caminero JA</RefAuthor>
<RefAuthor>Carvalho AC</RefAuthor>
<RefAuthor>Chang KC</RefAuthor>
<RefAuthor>Codecasa L</RefAuthor>
<RefAuthor>Correia A</RefAuthor>
<RefAuthor>Crudu V</RefAuthor>
<RefAuthor>Davies P</RefAuthor>
<RefAuthor>Dedicoat M</RefAuthor>
<RefAuthor>Drobniewski F</RefAuthor>
<RefAuthor>Duarte R</RefAuthor>
<RefAuthor>Ehlers C</RefAuthor>
<RefAuthor>Erkens C</RefAuthor>
<RefAuthor>Goletti D</RefAuthor>
<RefAuthor>Günther G</RefAuthor>
<RefAuthor>Ibraim E</RefAuthor>
<RefAuthor>Kampmann B</RefAuthor>
<RefAuthor>Kuksa L</RefAuthor>
<RefAuthor>de Lange W</RefAuthor>
<RefAuthor>van Leth F</RefAuthor>
<RefAuthor>van Lunzen J</RefAuthor>
<RefAuthor>Matteelli A</RefAuthor>
<RefAuthor>Menzies D</RefAuthor>
<RefAuthor>Monedero I</RefAuthor>
<RefAuthor>Richter E</RefAuthor>
<RefAuthor>Rüsch-Gerdes S</RefAuthor>
<RefAuthor>Sandgren A</RefAuthor>
<RefAuthor>Scardigli A</RefAuthor>
<RefAuthor>Skrahina A</RefAuthor>
<RefAuthor>Tortoli E</RefAuthor>
<RefAuthor>Volchenkov G</RefAuthor>
<RefAuthor>Wagner D</RefAuthor>
<RefAuthor>van der Werf MJ</RefAuthor>
<RefAuthor>Williams B</RefAuthor>
<RefAuthor>Yew WW</RefAuthor>
<RefAuthor>Zellweger JP</RefAuthor>
<RefAuthor>Cirillo DM</RefAuthor>
<RefAuthor> TBNET</RefAuthor>
<RefTitle>Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement</RefTitle>
<RefYear>2014</RefYear>
<RefJournal>Eur Respir J</RefJournal>
<RefPage>23-63</RefPage>
<RefTotal>Lange C, Abubakar I, Alffenaar JW, Bothamley G, Caminero JA, Carvalho AC, Chang KC, Codecasa L, Correia A, Crudu V, Davies P, Dedicoat M, Drobniewski F, Duarte R, Ehlers C, Erkens C, Goletti D, Günther G, Ibraim E, Kampmann B, Kuksa L, de Lange W, van Leth F, van Lunzen J, Matteelli A, Menzies D, Monedero I, Richter E, Rüsch-Gerdes S, Sandgren A, Scardigli A, Skrahina A, Tortoli E, Volchenkov G, Wagner D, van der Werf MJ, Williams B, Yew WW, Zellweger JP, Cirillo DM; TBNET. Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement. Eur Respir J. 2014 Jul;44(1):23-63. DOI: 10.1183/09031936.00188313</RefTotal>
<RefLink>https://doi.org/10.1183/09031936.00188313</RefLink>
</Reference>
</References>
<Media>
<Tables>
<Table format="png">
<MediaNo>1</MediaNo>
<MediaID language="de">1de</MediaID>
<MediaID language="en">1en</MediaID>
<Caption language="de"><Pgraph><Mark1>Tabelle 1: Kalkulierte Antibiotika-Therapie der bakteriellen Meningitis bei Erwachsenen.Die Empfehlungen der S2k-Leitlinie zur Therapie der Tuberkulose durch das Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e.V. im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. sind zu beachten.</Mark1></Pgraph></Caption>
<Caption language="en"><Pgraph><Mark1>Table 1: Calculated antibiotic treatment of bacterial meningitis in adults. The recommendations of the S2k guideline on the treatment of tuberculosis by the German Central Committee for the Control of Tuberculosis e.V. on behalf of the German Society of Pneumology and Respiratory Medicine e.V.</Mark1></Pgraph></Caption>
</Table>
<Table format="png">
<MediaNo>2</MediaNo>
<MediaID language="de">2de</MediaID>
<MediaID language="en">2en</MediaID>
<Caption language="de"><Pgraph><Mark1>Tabelle 2: Gezielte Antibiotika-Therapie der bakteriellen Meningitis bei Erwachsenen [nach Leitlinien der Deutschen Gesellschaft für Neurologie (http://www.dgn.org)]</Mark1></Pgraph></Caption>
<Caption language="en"><Pgraph><Mark1>Table 2: Targeted antibiotic treatment of bacterial meningitis in adults [according to guidelines of the German Society of Neurology (http://www.dgn.org)]</Mark1></Pgraph></Caption>
</Table>
<Table format="png">
<MediaNo>3</MediaNo>
<MediaID language="de">3de</MediaID>
<MediaID language="en">3en</MediaID>
<Caption language="de"><Pgraph><Mark1>Tabelle 3: Intraventrikuläre Antibiotika-Therapie (in der Regel gleichzeitige systemische Therapie erforderlich)</Mark1></Pgraph></Caption>
<Caption language="en"><Pgraph><Mark1>Table 3: Intraventricular antibiotic treatment (usually simultaneous systemic treatment is required)</Mark1></Pgraph></Caption>
</Table>
<Table format="png">
<MediaNo>4</MediaNo>
<MediaID language="de">4de</MediaID>
<MediaID language="en">4en</MediaID>
<Caption language="de"><Pgraph><Mark1>Tabelle 4: Tuberkulose-Meningitis: Dosierungsempfehlungen nach nationalen und internationalen Leitlinien. Da bei Unverträglichkeit oder Resistenz von Standardsubstanzen der Tuberkulosetherapie jeweils eine Kombinationstherapie mit 4 wirksamen Tuberkulosemittel durchgeführt werden sollte, müssen ggf. neben einer parenteralen Gabe auch ausschließlich oral verfügbare Mittel wie (PZA, PAS, Bedaquilin, Delamanid) mit appliziert werden. Diese sind deshalb in der Tabelle mit aufgeführt.</Mark1></Pgraph></Caption>
<Caption language="en"><Pgraph><Mark1>Table 4: Tuberculous meningitis: Dosage recommendations according to national and international guidelines. Due to intolerance or resistance to standard substances of tuberculosis treatment in each case combination treatment with 4 effective tuberculosis drugs should be performed. If necessary, in addition to parenteral administration, only orally available agents (such as PZA, PAS, bedaquiline, delamanid) should be administered. These are therefore also listed in the table.</Mark1></Pgraph></Caption>
</Table>
<NoOfTables>4</NoOfTables>
</Tables>
<Figures>
<NoOfPictures>0</NoOfPictures>
</Figures>
<InlineFigures>
<NoOfPictures>0</NoOfPictures>
</InlineFigures>
<Attachments>
<NoOfAttachments>0</NoOfAttachments>
</Attachments>
</Media>
</OrigData>
</GmsArticle>]]></plaintext></textgroup></pgraph></textblock></origdata></gmsarticle>