id000054
10.3205/id000054
urn:nbn:de:0183-id0000540
Leitlinie
Guideline
Kalkulierte parenterale Initialtherapie bakterieller Infektionen: Knochen- und Gelenkinfektionen
Calculated parenteral initial treatment of bacterial infections: Bone and joint infections
Vossen
Vossen
Mathias G.
MG
Dr.
Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Infektionen & Tropenmedizin, Allgemeines Krankenhaus Wien, Währinger Gürtel 18–20, 1090 Wien, ÖsterreichMedizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Infektionen & Tropenmedizin, Allgemeines Krankenhaus Wien, Österreich
Medizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Infektionen & Tropenmedizin, Allgemeines Krankenhaus Wien, Währinger Gürtel 18–20, 1090 Wien, AustriaMedizinische Universität Wien, Universitätsklinik für Innere Medizin I, Klinische Abteilung für Infektionen & Tropenmedizin, Allgemeines Krankenhaus Wien, Vienna, Austria
matthias.vossen@meduniwien.ac.at
author
Gattringer
Gattringer
Rainer
R
Institut für Hygiene und Mikrobiologie, Klinikum Wels Grieskirchen, Wels, ÖsterreichInstitut für Hygiene und Mikrobiologie, Klinikum Wels Grieskirchen, Wels, Österreich
Institut für Hygiene und Mikrobiologie, Klinikum Wels Grieskirchen, Wels, AustriaInstitut für Hygiene und Mikrobiologie, Klinikum Wels Grieskirchen, Wels, Austria
author
Thalhammer
Thalhammer
Florian
F
Klinische Abteilung für Infektiologie und Tropenmedizin, Medizinische Universität Wien, ÖsterreichKlinische Abteilung für Infektiologie und Tropenmedizin, Medizinische Universität Wien, Österreich
Klinische Abteilung für Infektiologie und Tropenmedizin, Medizinische Universität Wien, Vienna, AustriaKlinische Abteilung für Infektiologie und Tropenmedizin, Medizinische Universität Wien, Vienna, Austria
author
Militz
Militz
Matthias
M
Abteilung für Septische und Rekonstruktive Chirurgie, BG-Unfallklinik Murnau, DeutschlandAbteilung für Septische und Rekonstruktive Chirurgie, BG-Unfallklinik Murnau, Deutschland
Abteilung für Septische und Rekonstruktive Chirurgie, BG-Unfallklinik Murnau, GermanyAbteilung für Septische und Rekonstruktive Chirurgie, BG-Unfallklinik Murnau, Germany
author
Hischebeth
Hischebeth
Gunnar
G
Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Universitätsklinikum Bonn, DeutschlandInstitut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Universitätsklinikum Bonn, Deutschland
Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Universitätsklinikum Bonn, GermanyInstitut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Universitätsklinikum Bonn, 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
10
Dies ist das zehnte 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.Diese Kapitel befasst sich mit bakteriellen Knochen- und Gelenks- sowie Implantatinfektionen. Dabei sollte nach einer kalkulierten Initialtherapie nach Möglichkeit immer auf eine keimgerichtete Therapie mit einem gut an den Infektionsort penetrierenden und über die üblicherweise lange Therapiedauer gut verträglichen Antibiotikum umgestellt werden.
This is the 10th 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.This chapter deals with bacterial Infections of bones, joints and prosthetic joints. One of the most pressing points is that after an initial empirical therapy a targeted antimicrobial which penetrates well to the point of infection and is tolerated well over the usually long duration of the therapy is chosen.
EinleitungEntscheidend für den Verlauf und die Prognose von Knochen- und Gelenkinfektionen sind eine frühe Diagnose und eine adäquate Therapie. Diese besteht in dem radikalen chirurgischen Débridement, der Sequestrektomie bzw. der Synovektomie bei Gelenken, der Stabilisierung einer Fraktur/Pseudarthrose und der Versorgung der Haut-Weichgewebe-Defekte. Eine Antibiotika-Behandlung ist indiziert (Tabelle 1 ). Wenn irgendwie möglich sollte versucht werden, Probenmaterial zur mikrobiologischen Aufarbeitung zu gewinnen. Dies gilt insbesondere im Fall der chronischen Osteomyelitis, bei der kein akuter Handlungsbedarf besteht und somit die Diagnostik oberste Priorität haben sollte. Die Entnahme von Probenmaterial aus dem Knochen, am besten vor Beginn einer antimikrobiellen Therapie oder nach einer mindestens 2-wöchigen Antibiotikapause, gilt als klinischer Standard. Sollte im Fall einer akuten Osteomyelitis eine kalkulierte Initialtherapie begonnen worden sein, sollte die Umstellung auf eine gezielte Therapie erfolgen sobald ein Erregernachweis und das Ergebnis der Empfindlichkeitsprüfung vorliegen , .Klassischerweise empfiehlt sich initial eine hochdosierte parenterale Therapie. Eine Sequenztherapie ist möglich, wenn mit der oralen Medikation adäquate Wirkstoffspiegel sichergestellt werden können. Die Studienlage erlaubt bei chronischen Osteomyelitiden, auch bereits initial eine hochdosierte orale Therapie mit Clindamycin oder Trimethoprim/Sulfamethoxazol durchzuführen . Doxycyclin und Tigecyclin weisen, je nach Art des infizierten Knochens, eine sehr unterschiedliche Penetration auf und sollten daher nur in speziellen Fällen eingesetzt werden. Eine Kombination von Rifampicin mit Fusidinsäure wurde lange Zeit problemlos eingesetzt, kann jedoch durch CYP3A4 Induktion zu niedrigen Fusidinsäure-Spiegeln führen und sollte aufgrund der Gefahr der Resistenzinduktion bis auf Weiteres eher zurückhaltend verwendet werden . Die zusätzliche Verabreichung von Fosfomycin in den ersten zwei Wochen kann, unabhängig von der Genese der Osteomyelitis, erwogen werden , , . Die Möglichkeiten und Vor- und Nachteile einer ambulanten parenteralen antimikrobiellen Therapie (APAT) sollten mit dem Patienten besprochen werden .Bezüglich der Wahl des Therapeutikums scheint aufgrund der ohnehin notwendigen langen Therapiedauer kein Unterschied bezüglich Therapieerfolg oder Rezidivrate zwischen bakteriostatischen und bakteriziden antimikrobiellen Wirkstoffen zu bestehen .
IntroductionEarly diagnosis and adequate treatment are critical for progression and prognosis of bone and joint infections. These include radical surgical debridement, sequestrectomy or joint synovectomy, stabilization of fracture/pseudarthrosis and skin-soft tissue defect repair. Antibiotic treatment is indicated (Table 1 ). If possible, attempts should be made to obtain sample material for microbiological processing. This is especially true in the case of chronic osteomyelitis, in which there is no acute need for action and thus diagnosis should be the top priority. The removal of sample material from the bone, preferably before the start of antimicrobial therapy or after an antibiotic break lasting at least 2 weeks, is considered standard clinical procedure. If, in the case of acute osteomyelitis, calculated initial treatment has been started, the change to targeted treatment should take place as soon as the pathogens have been identified and the results of sensitivity testing are available , .Traditionally, initial high-dose parenteral treatment is recommended. Sequential therapy is possible if adequate drug levels can be ensured with oral medication. Based on the available studies, initial high-dose oral treatment with clindamycin or trimethoprim/sulfamethoxazole can be carried out in cases of chronic osteomyelitis . Doxycycline and tigecycline have very different penetration depending on the type of infected bone and should therefore only be used in special cases. A combination of rifampicin with fusidic acid has been used for a long time without any issues but can lead to low levels of fusidic acid through induction of CYP3A4 and should be used with restraint until further notice due to the risk resistance induction . In the first two weeks, additional administration of fosfomycin may be considered, regardless of the origin of osteomyelitis , , . The possibilities, advantages and disadvantages of out-patient parenteral antimicrobial therapy (OPAT) should be discussed with the patient .With regard to the choice of therapeutic agent, there appears to be no difference regarding treatment success or recurrence rate between bacteriostatic and bactericidal antimicrobial agents due to the long duration of treatment which is necessary in any case .
Hämatogene OsteomyelitisIn osteomyelitis, there is an infection of the medullary cavity, with a distinction made between a post-traumatic/post-operative origin and a hematogenous origin. The pathogen spectrum in the hematogenous form varies according to age. In adulthood, monoinfections are dominated by Staphylococcus aureus, streptococci or enterobacteria.Depending on the expected pathogen and local resistance situation, calculated treatment is started with a group 2 or 3 cephalosporin in combination with clindamycin or an aminopenicillin/beta-lactamase inhibitor (BLI). For staphylococcal infections, monotherapy with flucloxacillin or a group 1 cephalosporin is preferable. In principle, for flucloxacillin, as with all beta-lactams, continuous or more frequent dosing is preferable; however, experience shows that splitting the daily dose into 3 equal single doses (“q8” dosing) also results in adequate treatment success. In enterobacteria with resistance mechanisms, such as the formation of AmpC or extended spectrum beta-lactamases (ESBL), even a group 4 cephalosporin (only effective in case of infections by AmpC-producing pathogens) or a carbapenem must even be considered. The additional use of fosfomycin can be beneficial, especially in the first two weeks of treatment. As an alternative to beta-lactams, moxifloxacin can be used as monotherapy or a group 2 or 3 fluoroquinolone in combination with clindamycin.Due to its high penetration into the bone, fusidic acid is also a good combination partner in the treatment of Staphylococcus aureus osteomyelitis. The combination of fosfomycin with a cephalosporin may be considered, especially in complicated cases (for instance severe spondylodiscitis) .
Hematogenous osteomyelitisIn osteomyelitis, there is an infection of the medullary cavity, with a distinction made between a post-traumatic/post-operative origin and a hematogenous origin. The pathogen spectrum in the hematogenous form varies according to age. In adulthood, monoinfections are dominated by Staphylococcus aureus, streptococci or enterobacteria.Depending on the expected pathogen and local resistance situation, calculated treatment is started with a group 2 or 3 cephalosporin in combination with clindamycin or an aminopenicillin/beta-lactamase inhibitor (BLI). For staphylococcal infections, monotherapy with flucloxacillin or a group 1 cephalosporin is preferable. In principle, for flucloxacillin, as with all beta-lactams, continuous or more frequent dosing is preferable; however, experience shows that splitting the daily dose into 3 equal single doses (“q8” dosing) also results in adequate treatment success. In enterobacteria with resistance mechanisms, such as the formation of AmpC or extended spectrum beta-lactamases (ESBL), even a group 4 cephalosporin (only effective in case of infections by AmpC-producing pathogens) or a carbapenem must even be considered. The additional use of fosfomycin can be beneficial, especially in the first two weeks of treatment. As an alternative to beta-lactams, moxifloxacin can be used as monotherapy or a group 2 or 3 fluoroquinolone in combination with clindamycin.Due to its high penetration into the bone, fusidic acid is also a good combination partner in the treatment of Staphylococcus aureus osteomyelitis. The combination of fosfomycin with a cephalosporin may be considered, especially in complicated cases (for instance severe spondylodiscitis) .
SpondylodiscitisEine besondere Form der hämatogenen Osteomyelitis ist die Spondylodiscitis. Hier ist – wie bereits der Name suggeriert – nicht nur der Wirbelkörper selbst, sondern auch der Discus infiziert. Auch hier dominieren grampositive Kokken, insbesondere Staphylococcus aureus (einschließlich MRSA), als Infektionserreger. In Fällen, wo nur der Knochen betroffen ist, handelt es sich oft um Mycobacterium-tuberculosis-assoziierte Erkrankungen. Im Normallfall ist eine Therapiedauer von 6 Wochen ausreichend , . Die Wahl der antimikrobiellen Wirkstoffe entspricht der für die hämatogene Osteomyelitis, da der Erreger vor Beginn der Behandlung meist nicht bekannt ist. Neben der Abnahme mehrerer Blutkulturen sollte auch mithilfe der CT-gestützten Punktion der Versuch einer Erregerisolierung unternommen werden. Bei unklarer Genese ist eine Fokussuche durchzuführen. Zu beachten ist die – wenn auch nur in einer retrospektiven Analyse aufgefallene – deutlich höhere Rezidivrate unter Vancomycin im Vergleich zu Daptomycin bei der MRSA-Spondylodiscitis . Zudem sollte immer ein orthopädisches bzw. wirbelsäulenchirurgisches Konsil beauftragt werden, um die Notwendigkeit einer zusätzlichen chirurgischen Sanierung oder/und Miederanpassung zur Prävention von Wirbelkörperkompressionen abschätzen zu können.
SpondylodiscitisSpondylodiscitis is a particular form of hematogenous osteomyelitis. As the name implies, in this form not only the vertebral body itself is infected but also the disc. Here, too, Gram-positive cocci dominate as infectious agents, in particular Staphylococcus aureus (including MRSA). In cases where only the bone is affected, the disease is often associated with Mycobacterium tuberculosis. In normal cases, treatment duration of 6 weeks is sufficient , . The choice of antimicrobial agents is the same as for hematogenous osteomyelitis, as the pathogen is usually unknown before treatment starts. In addition to multiple blood cultures, an attempt to isolate the pathogens should also be made using CT-assisted puncture. If the origin is unclear, a focus search should be carried out. It should be noted that – although this was only noted in a retrospective analysis – there is a significantly higher recurrence rate with vancomycin compared to daptomycin in MRSA spondylodiscitis . In addition, an orthopedic or spinal surgery consultation should always be requested to assess the need for additional surgical restoration and/or fitting of a corset to prevent vertebral body compression.
Posttraumatische/postoperative OsteomyelitisDiese entsteht posttraumatisch (durch direkte Kontamination während eines Traumas) oder postoperativ (intraoperativ). Hier ist ebenfalls in vielen Fällen Staphylococcus aureus das auslösende Pathogen, insbesondere bei der postoperativen Osteomyelitis. Häufig liegen jedoch auch Mischinfektionen mit Streptokokken, Enterobacteriaceae und Anaerobiern vor. Bei posttraumatischen Osteomyelitiden kann in einigen Fällen auch Pseudomonas aeruginosa als ursächlich erachtet werden.Die Therapie muss möglichst frühzeitig in einem chirurgischen Débridement, der Entfernung etwaiger Fremdkörper mit Stabilisierung des Knochens und einer kalkulierten initialen Antibiotika-Behandlung bestehen. Das beim Débridement gewonnene Material sollte auf jeden Fall zur mikrobiologischen Aufarbeitung geschickt werden. Zur antimikrobiellen Therapie werden ein Aminopenicillin/BLI (i.v.), ein Cephalosporin der Gruppe 2 oder 3 (i.v.) oder Clindamycin empfohlen. Bei hohem Risiko für multiresistente Staphylokokken können Daptomycin, Linezolid, Teicoplanin oder ein hochdosiertes Cephalosporin der Gruppe 5 eingesetzt werden. Für letztere gibt es bislang jedoch wenig Erfahrungen; insbesondere stellt sich die Frage nach einer möglichen Resistenzentwicklung aufgrund der notwendigen langen Therapiedauer , . Die Verwendung von Vancomycin kann wegen der geringen Knochenpenetration bei gleichzeitig limitierten maximalen Serumspiegeln aufgrund des nephrotoxischen Risikos nicht empfohlen werden. Rifampicin zeigt eine gute Penetration, sowohl in den Knochen als auch in Biofilme. Es ist somit grundsätzlich als zusätzliche Therapieoption geeignet. Der Einsatz sollte sich aber nach Möglichkeit auf die Behandlung von Fremdkörper-assoziierten Infektionen beschränken. Bei der Verwendung von Linezolid kann initial eine höhere Dosierung mit bis zu 3x 0,6 g oder eine „Frontloading“-Strategie mit 2x 1,2 g erwogen werden. Die zu erwartende höhere Wirksamkeit sollte jedoch streng gegen die möglichen Toxizitätseffekte abgewogen werden , , .Die Kombination mit Fosfomycin während der ersten zwei Wochen der Therapie kann einen zusätzlichen Nutzen bringen. Wenn mit hoher Wahrscheinlichkeit eine Infektion durch grampositive Erreger vermutet wird, kann auch eine ambulante intravenöse Therapie mit einem langwirksamen Glykopeptid wie Dalbavancin oder Teicoplanin erwogen werden. Liegt eine vermutete oder bestätigte Infektion mit P. aeruginosa vor, sollte ein Pseudomonas-wirksames Cephalosporin (z.B. Ceftazidim oder Cefepim) oder Piperacillin/Tazobactam verwendet werden.Bei der chronischen Osteomyelitis müssen der infizierte Knochen und etwaige vorhandene Implantate entfernt werden. Hier sollte eine gezielte Antibiotika-Therapie erfolgen , .
Post-traumatic/post-operative osteomyelitisThis develops post-traumatically (through direct contamination during trauma) or post-operatively (intra-operatively). Staphylococcus aureus is also the underlying pathogen in many cases, especially in post-operative osteomyelitis. However, mixed infections with streptococci, Enterobacteriaceae and anaerobes are also common. In some cases, Pseudomonas aeruginosa may also be considered the underlying cause in post-traumatic osteomyelitis.Treatment must commence as early as possible in surgical debridement, the removal of any foreign bodies with bone stabilization and calculated initial antibiotic treatment. In any case the material obtained during debridement should be sent for microbiological analysis. For antimicrobial treatment, aminopenicillin/BLI (i.v.), a cephalosporin of group 2 or 3 (i.v.) or clindamycin are recommended. Where there is high risk of multidrug-resistant staphylococci, daptomycin, linezolid, teicoplanin or a high-dose cephalosporin of group 5 can be used. For the latter, however, there is little experience so far; there is in particular a question of possible resistance development due to the necessarily long duration of treatment , . The use of vancomycin cannot be recommended because of its low bone penetration and simultaneously limited maximum serum levels due to the nephrotoxic risk. Rifampicin shows good penetration, both in the bones and in biofilms. It is therefore generally suitable as an additional treatment option. However, its use should be limited as far as possible to the treatment of foreign body-associated infections. When using linezolid, initially a higher dosage of up to 3x 0.6 g or a front-loading strategy of 2x 1.2 g can be considered. However, the expected higher efficacy should be weighed carefully against its potentially toxic effects , , .Combination with fosfomycin during the first two weeks of treatment can bring added benefits. If Gram-positive pathogens are strongly suspected, out-patient intravenous treatment with a long acting glycopeptide such as dalbavancin or teicoplanin may also be considered. If there is a suspected or confirmed infection with P. aeruginosa, a Pseudomonas-effective cephalosporin (for example ceftazidime or cefepime) or piperacillin/tazobactam should be used.In chronic osteomyelitis, the infected bone and any existing implants must be removed. Targeted antibiotic treatment should be carried out , .
SternumosteomyelitisDie Sternumosteomyelitis tritt im Allgemeinen postoperativ als Komplikation einer Sternotomie auf, sie kann jedoch selten auch hämatogen entstehen. Im Wesentlichen wird sie durch Staphylococcus aureus oder Koagulase-negative Staphylokokken, die nicht selten multiresistent sind, verursacht. Es gibt allerdings auch einzelne Berichte über pilzassoziierte sternale Infektionen , . Die Antibiotika-Therapie erfolgt initial hochdosiert mit einem Isoxazolylpenicillin oder einem Cephalosporin der Grupp<![CDATA[e 1</PlainText></TextGroup> oder 2 in Kombination mit Clindamycin oder Fosfomycin. Bei Infektionen durch MRSA oder Methicillin-resistenten Koagulase-negativen Staphylokokken, wie z.B. <Mark2>Staphylococcus</Mark2> <Mark2>epidermidis</Mark2>, wird der Einsatz von Daptomycin oder Linezolid empfohlen <TextLink reference="23"></TextLink>. Auch hier ist die Verwendung eines hochdosierten Cephalosporins der Gruppe 5 erwägenswert, jedoch bislang kaum erprobt <TextLink reference="14"></TextLink>.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Sternal osteomyelitis">
<MainHeadline>Sternal osteomyelitis</MainHeadline><Pgraph>Sternal osteomyelitis generally occurs post-operatively as a complication of a sternotomy but occasionally it can have a hematogenous origin. In essence, it is caused by <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> or coagulase-negative staphylococci, which are often multiresistant. However, there are also individual reports of fungal-associated sternal infections <TextLink reference="21"></TextLink>, <TextLink reference="22"></TextLink>. Antibiotic treatment is initially high-dose with an isoxazolylpenicillin or a cephalosporin of group 1 or 2 in combination with clindamycin or fosfomycin. For infections with MRSA or methicillin-resistant coagulase-negative staphylococci, such as <Mark2>Staphylococcus</Mark2> <Mark2>epidermidis</Mark2>, the use of daptomycin or linezolid is recommended <TextLink reference="23"></TextLink>. Again, the use of a high-dose cephalosporin of group 5 is worth considering but so far this has hardly been tested <TextLink reference="14"></TextLink>.</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Bakterielle Arthritis">
<MainHeadline>Bakterielle Arthritis</MainHeadline><Pgraph>Wesentliche Ursache der bakteriellen Arthritis ist die iatrogene Infektion. Dabei ist hinsichtlich der Prognose die Frühinfektion von der Spätinfektion zu differenzieren. Die Erreger sind meist Staphylokokken oder beta-hämolysierende Streptokokken der Gruppen A, B, C und G. Andere Erreger wie Enterobacteriaceae und Gonokokken sind selten. Neben der unverzüglichen chirurgischen Therapie, auch zur Sicherung der Diagnose, wird eine ähnliche kalkulierte Antibiotika-Initialtherapie wie bei der postoperativen Osteomyelitis empfohlen. Ist der Erreger durch vorherige Punktion gesichert, kann bei den seltenen Infektionen durch Salmonellen oder Gonokokken die alleinige Antibiotika-Therapie als ausreichend erachtet werden.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Bacterial arthritis">
<MainHeadline>Bacterial arthritis</MainHeadline><Pgraph>The main cause of bacterial arthritis is iatrogenic infection. With regard to the prognosis, early infection should be differentiated from late infection. The pathogens are usually staphylococci or beta-hemolytic streptococci of groups A, B, C and G. Other pathogens such as Enterobacteriaceae and gonococci are rare. In addition to immediate surgical treatment, also with confirmation of diagnosis, calculated initial antibiotic treatment similar to that of post-operative osteomyelitis is recommended. If the pathogen is confirmed through a preceding puncture, treatment with antibiotics only may be considered sufficient for rare infections caused by salmonella or gonococci.</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Endoprothesen-/Fremdkörper-assoziierte Infektionen">
<MainHeadline>Endoprothesen-/Fremdkörper-assoziierte Infektionen</MainHeadline><Pgraph>60–70% der Endoprothesen-Infektionen entwickeln sich innerhalb der ersten zwei Jahre nach der Implantation <TextLink reference="24"></TextLink>. Dabei sind <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> und Koagulase-negative Staphylokokken die häufigsten Verursacher. Polymikrobielle Infektionen kommen in etwa 15% der Fälle vor. Grundsätzlich besteht nicht nur bei Endoprothesen, sondern bei jedwedem Fremdkörper ein hohes Risiko der Biofilmbildung, besonders bei Koagulase-negativen Staphylokokken, welche zu einem hohen Prozentsatz Resistenzen gegen multiple Antibiotikaklassen aufweisen <TextLink reference="25"></TextLink>. <Mark2>Propionibacterium</Mark2> <Mark2>acnes</Mark2> wird vor allem in infizierten Schulterprothesen gefunden, dabei ist eine Kontamination der Kultur letztlich jedoch nur schwer auszuschließen <TextLink reference="24"></TextLink>.</Pgraph><Pgraph>Der Ausbau bzw. Wechsel nach radikalem chirurgischem Débridement und eine, idealerweise auf den Erreger abgestimmte, Antibiotika-Gabe in maximaler Dosierung sind die Therapie der Wahl <TextLink reference="26"></TextLink>. Explantierte Fremdkörper können zur Verbesserung der Sensitivität des Erregernachweises sonifiziert werden <TextLink reference="27"></TextLink>. Dies kann auch bei primär aseptisch interpretierten Prothesenlockerungen zu einer Erregerdiagnostik führen <TextLink reference="28"></TextLink>. Bei frühen Protheseninfektionen (innerhalb der ersten 2[–4] Wochen), können bereits der Austausch entfernbarer Oberflächen und chirurgisches Débridement gefolgt von einer drei- bis sechsmonatigen Therapie mit Biofilm-aktiven Substanzen (Rifampicin oder Hochdosis Daptomycin) zu einer Heilung führen („debridement, antibiotics, and implant retention [DAIR]“) <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>, <TextLink reference="32"></TextLink>, <TextLink reference="33"></TextLink>. Dabei zeigen Streptokokken-Infektionen eine größere Heilungstendenz als Infektionen mit <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> <TextLink reference="34"></TextLink>. Auch beim einzeitigen Implantataustausch sollte eine Biofilm-aktive Therapie über drei Monate verabreicht werden <TextLink reference="35"></TextLink>. Nach der initialen vier- bis sechswöchigen intravenösen Therapie mit einem Aminopenicillin/BLI, einem Cephalosporin der Gruppe 1 oder 2 oder einem Glykopeptid, jeweils in Kombination mit Rifampicin, sollte die weitere orale Therapie mit Rifampicin in Kombination mit einem geeigneten Fluorchinolon (bevorzugt Levofloxacin oder Moxifloxacin) erfolgen, um eine Resistenzentwicklung gegen Rifampicin zu verhindern. Es gibt jedoch lediglich eine kleine randomisierte kontrollierte Studie zur Verwendung von Ciprofloxacin plus Rifampicin für Prothesenfrühinfektionen <TextLink reference="36"></TextLink>. Die Fluorchinolone der Gruppe 3 (Levofloxacin) und Gruppe 4 (Moxifloxacin) sind aber vermutlich als dem Ciprofloxacin (Gruppe 2) überlegen anzusehen <TextLink reference="36"></TextLink>, <TextLink reference="37"></TextLink>. Die korrekte Dosierung von Rifampicin ist nicht gänzlich unumstritten. Während vielfach eine Dosierung von 2x 0,3–0,45 g pro Tag empfohlen wird, gibt es auch pharmakokinetische Argumente für eine Dosierung von 1x 0,6 g <TextLink reference="36"></TextLink>, <TextLink reference="38"></TextLink>, <TextLink reference="39"></TextLink>. Die Kombination von Daptomycin plus Rifampicin zeigte im Rattenmodell eine sehr gute Effizienz <TextLink reference="40"></TextLink>. Fosfomycin hat im Tiermodell eine sehr gute Wirksamkeit in der Therapie von Implantat-assoziierten MRSA-Osteomyelitiden gezeigt, sollte jedoch aufgrund der raschen Resistenzentwicklung nicht als Monotherapie eingesetzt werden <TextLink reference="7"></TextLink>, <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>. Linezolid wurde als Alternativtherapie für späte Protheseninfektionen diskutiert <TextLink reference="43"></TextLink>. Heilungserfolge unter ausschließlicher konservativer Therapie sind sehr selten.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Endoprosthesis/foreign body-associated infections">
<MainHeadline>Endoprosthesis/foreign body-associated infections</MainHeadline><Pgraph>60–70% of endoprosthesis infections develop within the first two years following implantation <TextLink reference="24"></TextLink>. <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> and coagulase-negative staphylococci are the most common causes. Polymicrobial infections occur in about 15% of cases. Basically, there is a high risk of biofilm formation not only in endoprostheses but in any foreign body, especially of coagulase-negative staphylococci a high proportion of whom show resistance to multiple classes of antibiotics <TextLink reference="25"></TextLink>. <Mark2>Propionibacterium</Mark2> <Mark2>acnes</Mark2> is found mainly in infected shoulder prostheses but it is ultimately difficult to rule out culture contamination <TextLink reference="24"></TextLink>.</Pgraph><Pgraph>Expansion or changes after radical surgical debridement and, ideally targeting specific pathogens, treatment with maximally high doses of antibiotics are the treatment of choice <TextLink reference="26"></TextLink>. Extracted foreign bodies can be treated with ultrasound to improve the sensitivity of pathogen detection <TextLink reference="27"></TextLink>. This can lead to pathogen diagnosis even in prosthesis loosening primarily interpreted as aseptic <TextLink reference="28"></TextLink>. In early prosthesis infections (within the first 2[–4] weeks), even replacement of removable surfaces and surgical debridement followed by three to six months of biofilm-active drug treatment (rifampicin or high-dose daptomycin) may result in healing (“debridement, antibiotics, and implant retention [DAIR]”) <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>, <TextLink reference="32"></TextLink>, <TextLink reference="33"></TextLink>. Streptococcal infections show a greater tendency for healing than infections with <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> <TextLink reference="34"></TextLink>. Even in single-stage implant replacement, biofilm-active treatment should be administered over three months <TextLink reference="35"></TextLink>. Following initial four to six-week intravenous treatment with an aminopenicillin/BLI, a group 1 or 2 cephalosporin or a glycopeptide, each in combination with rifampicin, further oral treatment should carried out with rifampicin in combination with a suitable fluoroquinolone (preferably levofloxacin or moxifloxacin) to prevent development of resistance to rifampicin. However, there is only one study about a small randomized controlled trial on the use of ciprofloxacin plus rifampicin for early prosthesis infections <TextLink reference="36"></TextLink>. Nonetheless, <TextGroup><PlainText>group 3</PlainText></TextGroup> fluoroquinolones (levofloxacin) and group 4 (moxifloxacin) should probably be considered superior to ciprofloxacin (group 2) <TextLink reference="36"></TextLink>, <TextLink reference="37"></TextLink>. The correct dosage of rifampicin is uncontroversial. While often a dosage of <TextGroup><PlainText>2x 0.3–0.45 g</PlainText></TextGroup> per day is recommended, there are also pharmacokinetic arguments for a dosage of 1x 0.6 g <TextLink reference="36"></TextLink>, <TextLink reference="38"></TextLink>, <TextLink reference="39"></TextLink>. The combination of daptomycin plus rifampicin showed very good efficiency in tests with rats <TextLink reference="40"></TextLink>. Fosfomycin has shown very good efficacy in the treatment of implant-associated MRSA osteomyelitis in animal tests but should not be used as monotherapy due to the rapid development of resistance <TextLink reference="7"></TextLink>, <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>. Linezolid was discussed as an alternative treatment for late prosthesis infections <TextLink reference="43"></TextLink>. Healing rates under exclusively conservative treatment are very low.</Pgraph></TextBlock>
<TextBlock language="de" linked="yes" name="Anmerkungen">
<MainHeadline>Anmerkungen</MainHeadline><Pgraph>Dies ist das zehnte 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><Pgraph>Nach Veröffentlichung der 1. Version der Leitlinie wurden von der Arbeitsgruppe folgende Dosierungsvorschläge aktualisiert (Tabelle 1: Empfehlungen zur kalkulierten Antibiotika-Therapie von Knochen- und Gelenkinfektionen): Dalbavancin 1,5 g an Tag 1 und Tag 8, ausreichend für 8 Wochen ANSTATT Dalbavancin 1 g als erste Dosis, dann 1x/Woche 0,5 g als Erhaltungsdosis oder 1,5 g jeden 15. Tag.</Pgraph></TextBlock>
<TextBlock language="en" linked="yes" name="Notes">
<MainHeadline>Notes</MainHeadline><Pgraph>This is the tenth 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 Chemotherapie e.V. (PEG) has been translated to address an international audience.</Pgraph><Pgraph>Following the publication of the 1<Superscript>st</Superscript> version of the guideline in German, these dosage suggestions were updated by the working group (Table 1: Recommendations for the calculated antibiotic therapy of bone and joint infections): dalbavancin 1.5 g on day 1 and day 8, sufficient for <TextGroup><PlainText>8 weeks</PlainText></TextGroup> INSTEAD OF dalbavancin 1 g as first dose, then 0.5 g once per week as a maintenance dose or 1.5 g every 15 days.</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>
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<RefLink>https://doi.org/10.1128/JCM.03484-13</RefLink>
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<RefAuthor>Cobo J</RefAuthor>
<RefAuthor>Lora-Tamayo J</RefAuthor>
<RefAuthor>Euba G</RefAuthor>
<RefAuthor>Jover-Sáenz A</RefAuthor>
<RefAuthor>Palomino J</RefAuthor>
<RefAuthor>del Toro MD</RefAuthor>
<RefAuthor>Rodríguez-Pardo D</RefAuthor>
<RefAuthor>Riera M</RefAuthor>
<RefAuthor>Ariza J</RefAuthor>
<RefAuthor> Red Española para la Investigación en Patología Infecciosa (REIPI)</RefAuthor>
<RefTitle>Linezolid in late-chronic prosthetic joint infection caused by gram-positive bacteria</RefTitle>
<RefYear>2013</RefYear>
<RefJournal>Diagn Microbiol Infect Dis</RefJournal>
<RefPage>93-8</RefPage>
<RefTotal>Cobo J, Lora-Tamayo J, Euba G, Jover-Sáenz A, Palomino J, del Toro MD, Rodríguez-Pardo D, Riera M, Ariza J; Red Española para la Investigación en Patología Infecciosa (REIPI). Linezolid in late-chronic prosthetic joint infection caused by gram-positive bacteria. Diagn Microbiol Infect Dis. 2013 May;76(1):93-8. DOI: 10.1016/j.diagmicrobio.2013.02.019</RefTotal>
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<Caption language="de"><Pgraph><Mark1>Tabelle 1: Empfehlungen zur kalkulierten Antibiotika-Therapie von Knochen- und Gelenkinfektionen</Mark1></Pgraph></Caption>
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