id000056 10.3205/id000056 urn:nbn:de:0183-id0000561 Leitlinie Guideline Calculated parenteral initial treatment of bacterial infections: Infections of the kidneys and the genito-urinary tract Fünfstück Fünfstück Reinhard R Prof. Dr.

Klinik für Innere Medizin, Sophien- und Hufeland-Klinikum gGmbH Weimar, Henry-van-de-Velde-Straße 2, 99425 Weimar, DeutschlandKlinik für Innere Medizin, Sophien- und Hufeland-Klinikum gGmbH Weimar, Deutschland

Klinik für Innere Medizin, Sophien- und Hufeland-Klinikum gGmbH Weimar, Henry-van-de-Velde-Straße 2, 99425 Weimar, GermanyKlinik für Innere Medizin, Sophien- und Hufeland-Klinikum gGmbH Weimar, Germany

r.fuenfstueck@klinikum-weimar.de author Hoyme Hoyme Udo U

Klinik für Gynäkologie und Geburtshilfe St. Georg Klinikum Eisenach, Deutschland

Klinik für Gynäkologie und Geburtshilfe St. Georg Klinikum Eisenach, Germany

author Naber Naber Kurt K

Urologische Klinik und Poliklinik, Technische Universität München, Deutschland

Urologische Klinik und Poliklinik, Technische Universität München, Munich, Germany

author Pilatz Pilatz Adrian A

Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Deutschland

Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Germany

author Schubert Schubert Sören S

Max von Pettenkofer-Institut, Medizinische Fakultät, Ludwig Maximilians-Universität München, Deutschland

Max von Pettenkofer-Institut, Medizinische Fakultät, Ludwig Maximilians-Universität München, Munich, Germany

author Wagenlehner Wagenlehner Florian F Prof. Dr.

Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Rudolf-Buchheim Str. 7, 35392 Giessen, DeutschlandKlinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Deutschland

Klinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Rudolf-Buchheim Str. 7, 35392 Giessen, GermanyKlinik für Urologie, Kinderurologie und Andrologie, Justus Liebig Universität Giessen, Germany

florian.wagenlehner@chiru.med.uni-giessen.de 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 12 Dies ist das achte 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.Es befasst sich mit der Behandlung schwererer Infektionen der Niere und des Urogenitaltrakts einschließlich der Urosepsis und enthält Empfehlungen für eine empirische und gezielte antibakterielle Behandlung. This is the eighth 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.The chapter deals with the treatment of more severe infections of the kidney and the urogenital tract, including urosepsis. Recommendations for empiric and targeted antibacterial treatment are given. Indikation zur initialen parenteralen Antibiotika-TherapieBei Infektionen der Nieren und des Urogenitaltraktes ist bei Erwachsenen in der Regel eine initiale (empirische) parenterale Antibiotika-Therapie nur bei schweren klinischen Verlaufsformen mit Allgemeinsymptomen, wie Übelkeit und Erbrechen, oder bei Verdacht auf Sepsis erforderlich . Im Wesentlichen handelt es sich dabei um schwere Verlaufsformen einer unkomplizierten oder komplizierten bzw. nosokomialen Pyelonephritis, einer akuten Prostatitis, selten einer akuten Epididymitis mit oder ohne Orchitis, einer akuten Salpingitis-Pelvioperitonitis oder um schwere abszedierende Infektionen im Bereich der Nieren und des Urogenitaltraktes. Gelegentlich muss auch eine parenterale Therapie empirisch initiiert werden, wenn in bestimmten klinischen Situationen mit multiresistenten Erregern gerechnet werden muss, für die keine oralen Antibiotika zur Verfügung stehen, und das mikrobiologische Testergebnis nicht abgewartet werden kann, da z.B. eine Operation sofort durchgeführt werden muss (z.B. akute Harnsteinobstruktion). Indication for initial parenteral antibiotic treatmentFor kidney and genito-urinary tract infections, initial (empirical) parenteral antibiotic treatment is usually only required in severe clinical cases with general symptoms, such as nausea and vomiting or suspected sepsis . These are mainly severe forms of uncomplicated or complicated or nosocomial pyelonephritis, acute prostatitis, rarely acute epididymitis with or without orchitis, acute salpingitis-pelvioperitonitis or severe abscessing infections in the kidney and genito-urinary tracts. Occasionally, parenteral treatment must also be initiated empirically if multidrug-resistant agents for which no oral antibiotics are available must be expected and waiting for microbiological test results is not an option, for example because surgery must be performed immediately (e.g. in acute urinary stone obstruction). Allgemeine Kriterien zur Antibiotika-AuswahlDie Antibiotika-Auswahl (Tabelle 1 ) erfolgt gemäß dem zu erwartenden Erregerspektrum unter Berücksichtigung pharmakokinetischer und pharmakodynamischer Gesichtspunkte, wobei zur Therapie von Infektionen des Harntraktes in jedem Fall auf eine ausreichende renale Elimination des Wirkstoffes zu achten ist , . Zusätzlich sollten auch die sogenannten Kollateralschäden von Antibiotika berücksichtigt werden, die über Nebenwirkungen beim individuellen Patienten hinausgehen und Resistenzentwicklungen bzw. die Selektion resistenter Erreger begünstigen (siehe Kapitel 2 , Abschnitt Kollateralschäden von Antibiotika). Neben der Antibiotika-Therapie sind auch entsprechende allgemeine, sowie fachspezifische Therapiemaßnahmen zu ergreifen, die jedoch nicht Gegenstand dieses Artikels sind , , . General criteria for antibiotic selectionThe choice of antibiotics (Table 1 ) is made in accordance with the expected pathogen spectrum, taking into account pharmacokinetic and pharmacodynamic aspects. In any case, ensuring sufficient renal elimination of the drug should be considered for the treatment of infections of the urinary tract , . In addition, the so-called collateral damage of antibiotics should be considered, which goes beyond the side effects in the individual patient and favors resistance development or the selection of resistant pathogens (see chapter 2 , paragraph collateral damage of antibiotics). In addition to antibiotic treatment, appropriate general as well as subject-specific therapeutic measures are to be taken but these are not the subject of this article , , . Akute unkomplizierte PyelonephritisHäufigster Erreger ist Escherichia coli, gefolgt von Proteus mirabilis und Klebsiella pneumoniae , , . Seltener werden andere Enterobacteriaceae im Harn nachgewiesen. Größere epidemiologische Studien zur Erregerempfindlichkeit fehlen. Ersatzweise können dafür Studien bei unkomplizierter Zystitis herangezogen werden, da mit einem etwa gleichen Erregerspektrum, jedoch weniger häufig Staphylococcus saprophyticus, und einer etwa gleichen Resistenzsituation gerechnet werden kann . Eine rechtzeitig eingeleitete wirksame Therapie kann möglicherweise einen Nierenparenchymschaden vermeiden. Eine initiale (empirische) parenterale Therapie mit einem Cephalosporin der Gruppe 3a, einem Aminopenicillin/Beta-Lactamase-Inhibitor (BLI), einem Aminoglykosid (aufgrund des Nebenwirkungsrisikos nicht zur ersten Wahl; immer in Kombination mit anderen Antibiotika) ist immer dann indiziert, wenn schwere Allgemeinsymptome mit Übelkeit und Erbrechen vorliegen , , , , , , . Fluorchinolone mit hoher renaler Ausscheidung, z.B. Ciprofloxacin oder Levofloxacin, können verabreicht werden, wenn eine Fluorchinolon-Resistenz nicht wahrscheinlich ist. Nach Besserung dieser Symptome sollte die parenterale Therapie so bald wie möglich in eine orale, testgerechte Therapie umgewandelt werden. Dazu eignet sich ein orales Fluorchinolon, z.B. Ciprofloxacin oder Levofloxacin, ein orales Cephalosporin der Gruppe 3</PlainText></TextGroup> (Cefpodoxim), ein Aminopenicillin in Kombination mit einem BLI oder Cotrimoxazol bzw. Trimethoprim, jedoch nur dann wenn der Erreger als empfindlich getestet wurde <TextLink reference="1"></TextLink>, <TextLink reference="18"></TextLink>, <TextLink reference="19"></TextLink>, <TextLink reference="20"></TextLink>. Die Dauer der Therapie orientiert sich am klinischen Verlauf, meist sind 7 Tage ausreichend <TextLink reference="21"></TextLink>. </Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Acute uncomplicated pyelonephritis"> <MainHeadline>Acute uncomplicated pyelonephritis</MainHeadline><Pgraph>The most common pathogen is <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2>, followed by <Mark2>Proteus</Mark2> <Mark2>mirabilis</Mark2> and <Mark2>Klebsiella</Mark2> <Mark2>pneumoniae</Mark2> <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>. Rarely, other Enterobacteriaceae are detected in the urine. Larger epidemiological studies on pathogen sensitivity are missing. However, studies on uncomplicated cystitis can be used because it has approximately the same pathogen spectrum although <Mark2>Staphylococcus</Mark2> <Mark2>saprophyticus</Mark2> occurs less frequently and the resistance situation is roughly the same <TextLink reference="11"></TextLink>. Renal parenchymal damage may possibly be prevented by initiating effective treatment in time. Initial (empirical) parenteral treatment with a group 3a cephalosporin, an aminopenicillin&#47;beta-lactamase inhibitor (BLI), an aminoglycoside (not a first choice due to the risk of side effects, always in combination with other antibiotics) is indicated whenever severe general symptoms with nausea and vomiting are present <TextLink reference="1"></TextLink>, <TextLink reference="12"></TextLink>, <TextLink reference="13"></TextLink>, <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>, <TextLink reference="16"></TextLink>, <TextLink reference="17"></TextLink>. Fluoroquinolones with high renal excretion, such as ciprofloxacin or levofloxacin may be given if fluoroquinolone resistance is unlikely. After the symptoms improve, oral treatment should replace parenteral treatment in line with the test results as soon as possible. This should be a suitable oral fluoroquinolone, for example ciprofloxacin or levofloxacin, an oral cephalosporin of group 3 (cefpodoxime), an aminopenicillin in combination with a BLI or cotrimoxazole or trimethoprim; but only if the pathogen has been tested as sensitive <TextLink reference="1"></TextLink>, <TextLink reference="18"></TextLink>, <TextLink reference="19"></TextLink>, <TextLink reference="20"></TextLink>. The duration of treatment is based on the clinical progression, usually 7 days are sufficient <TextLink reference="21"></TextLink>. </Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Komplizierte bzw. nosokomiale Harnwegsinfektion"> <MainHeadline>Komplizierte bzw. nosokomiale Harnwegsinfektion</MainHeadline><SubHeadline>Definition</SubHeadline><Pgraph>Eine komplizierte Harnwegsinfektion (HWI) ist definiert als eine Infektion der Harnwege, die assoziiert ist mit einer morphologischen, funktionellen oder metabolischen Anomalie, die zur St&#246;rung der Nierenfunktion, zur Beeintr&#228;chtigung des Harntransportes und zur St&#246;rung lokaler sowie systemischer Abwehrmechanismen f&#252;hrt <TextLink reference="5"></TextLink>, <TextLink reference="22"></TextLink>, <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>. Die Risikofaktoren werden in der sog. ORENUC-Klassifikation eingeteilt <TextLink reference="25"></TextLink>.</Pgraph><SubHeadline>Indikation zur initialen parenteralen Antibiotika-Therapie</SubHeadline><Pgraph>Die Indikation f&#252;r eine initiale parenterale Antibiotika-Therapie richtet sich, wie oben erw&#228;hnt, nach dem Allgemeinbefinden und dem Risikoprofil des Patienten. CRP und Procalcitonin k&#246;nnen als Biomarker f&#252;r die Entscheidung mit verwendet werden <TextLink reference="26"></TextLink>. Die Antibiotika-Therapie einer komplizierten HWI kann immer nur dann kurativ sein, wenn die komplizierenden bzw. ausl&#246;senden Faktoren beseitigt oder verbessert werden <TextLink reference="1"></TextLink>.</Pgraph><SubHeadline>Erregerspektrum</SubHeadline><Pgraph>Das zu erwartende Erregerspektrum ist im Allgemeinen wesentlich breiter als bei unkomplizierten HWI und h&#228;ngt auch damit zusammen, unter welchen Umst&#228;nden eine komplizierte HWI erworben wurde <TextLink reference="22"></TextLink>, <TextLink reference="23"></TextLink>, <TextLink reference="27"></TextLink>. So ist z.B. das Erregerspektrum bei einer ambulant erworbenen erstmaligen komplizierten HWI, z.B. infolge akutem Calciumoxalat-Harnsteinleiden bei einem Patienten, bei dem keine Antibiotika-Vorbehandlung und keine Harnableitung vorliegen, relativ &#228;hnlich dem Spektrum einer unkomplizierten akuten Pyelonephritis <TextLink reference="6"></TextLink>. Dagegen muss bei nosokomial erworbenen komplizierten HWI auch mit Erregern gerechnet werden, die gew&#246;hnlich nicht Erreger von prim&#228;ren Harnwegsinfektionen sind, sondern meist erst sekund&#228;r als Folge einer Selektion oder Kolonisation in Erscheinung treten, wie z.B. <Mark2>Pseudomonas aeruginosa</Mark2> oder andere Enterobacteriaceae als <Mark2>Escherichia coli</Mark2> <TextLink reference="23"></TextLink>, <TextLink reference="27"></TextLink>. Bei Verdacht auf eine komplizierte HWI ist grunds&#228;tzlich eine Urinkultur vor Einleitung der Antibiotika-Therapie indiziert, da wegen des breiteren Erregerspektrums und der nicht immer vorhersehbaren Resistenzsituation immer die M&#246;glichkeit der Therapieanpassung an das mikrobiologische Testergebnis gegeben sein muss <TextLink reference="1"></TextLink>.</Pgraph><SubHeadline>Antibiotika-Auswahl</SubHeadline><Pgraph>Die empirische Antibiotika-Initialtherapie muss unter Ber&#252;cksichtigung der regionalen Resistenzsituation des zu erwartenden Erregerspektrums erfolgen <TextLink reference="23"></TextLink>. Dabei sind immer auch zuvor folgende klinische Umst&#228;nde anamnestisch zu kl&#228;ren, die einen Einfluss auf das zu erwartende Erregerspektrum und die Erregerempfindlichkeit haben <TextLink reference="23"></TextLink>:</Pgraph><Pgraph><OrderedList><ListItem level="1" levelPosition="1" numString="1.">Wo wurde die HWI erworben, z.B. ambulant, Pflegeheim, Krankenhaus, nach diagnostischen&#47;therapeutischen Eingriffen&#63;</ListItem><ListItem level="1" levelPosition="2" numString="2.">Erfolgte eine Antibiotika-Vorbehandlung (wie lange, welche Antibiotika)&#63;</ListItem><ListItem level="1" levelPosition="3" numString="3.">Erfolgte eine vorherige l&#228;ngere station&#228;re Behandlung&#63;</ListItem><ListItem level="1" levelPosition="4" numString="4.">Erfolgte eine vorherige Harnableitung (welche, wie lange, wie behandelt)&#63;</ListItem><ListItem level="1" levelPosition="5" numString="5.">Bei vorhandener Harnableitung Qualit&#228;t der Harndrainage &#252;berpr&#252;fen und ggf. Katheter wechseln (Entfernung des infekti&#246;sen Biofilms)</ListItem><ListItem level="1" levelPosition="6" numString="6.">Liegt ein Rezidiv bzw. ein Therapieversagen vor&#63;</ListItem><ListItem level="1" levelPosition="7" numString="7.">Aus Gr&#252;nden der &#8222;Antimicrobial Stewardship&#8220; sollte immer abgewogen werden, inwieweit die Anwendung von breit wirksamen Antibiotika (z.B. Cephalosporine&#47;BLI), Carbapeneme) notwendig ist.</ListItem></OrderedList></Pgraph><Pgraph>F&#252;r die parenterale Initialtherapie erstmals ambulant erworbener komplizierter HWI eignen sich Cephalosporine der Gruppe 3a, Fluorchinolone und Aminopenicilline&#47;BLI. Bei Risikofaktoren f&#252;r multiresistente Erreger (z.B. &#8222;Exten<TextGroup><PlainText>d</PlainText></TextGroup>ed-Spektrum&#8220;-Beta-Lactamase &#91;ESBL&#93; bildende Enterobacteriaceae) k&#246;nnen Antibiotika, wie Cephalosporine&#47;BLI (Ceftolozan&#47;Tazobactam; Ceftazidim&#47;Avibactam) oder ein Carbapenem der Gruppe 2 (Ertapenem) eingesetzt werden <TextLink reference="1"></TextLink>, <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="12"></TextLink>, <TextLink reference="13"></TextLink>, <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>. Bei Patienten mit nosokomial erworbenen bzw. Katheter-as<TextGroup><PlainText>s</PlainText></TextGroup>oziierten HWI treten ebenfalls vermehrt multiresistente Erreger auf <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>, <TextLink reference="27"></TextLink>, <TextLink reference="28"></TextLink>. Deshalb sollte zur empirischen Therapie ein Antibiotikum eingesetzt werden, das auch gegen seltenere und multiresistente gramnegative Erreger wirksam ist. Daf&#252;r kommen Cephalosporine der Grupp<TextGroup><PlainText>e 3b</PlainText></TextGroup>, einschlie&#223;lich der Cephalosporin&#47;BLI-Kombinationen Ceftolozan&#47;Tazobactam und Ceftazidim&#47;Avibactam, oder 4 (Cefepim), Fluorchinolone der Gruppe 2 oder 3 (lokale <Mark2>Escherichia-coli</Mark2>-Resistenz beachten) und Carbapeneme der Gruppe 1 (Imipenem, Meropenem) in Frage <TextLink reference="1"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>. Will man gleichzeitig die bei diesen Antibiotika vorhandene Enterokokken-L&#252;cke schlie&#223;en, da Mischin<TextGroup><PlainText>f</PlainText></TextGroup>ektionen mit Enterokokken h&#228;ufiger bei Katheter-assoziierten Harnwegsinfektionen anzutreffen sind, bietet sich ein Acylaminopenicillin&#47;BLI (z.B. Piperacillin&#47;Tazobactam) an <TextLink reference="1"></TextLink>, <TextLink reference="31"></TextLink>. Bei Verdacht auf multiresistente Erreger (im Rahmen von Ausbr&#252;chen bzw. bei hoher endemischer Resistenzrate) sollten entsprechend wirksame Substanzen in der empirischen Therapie eingesetzt werden. Da im deutschsprachigen Raum Carbapenemasen bisher selten auftreten, sind f&#252;r Enterobacteriaceae mit Expression einer ESBL ein Cephalosporin&#47;BLI (Ceftolozan&#47;Tazobactam, Ceftazidim&#47;Avibactam) <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, ein Carbapenem der Gruppe 2 (Ertapenem) bzw. bei gleichzeitigem Verdacht auf Pseudomonaden ein Cephalosporin&#47;BLI (Ceftolozan&#47;Tazobactam, Ceftazidim&#47;Avibactam), oder ein Carbapenem der Grupp<TextGroup><PlainText>e 1</PlainText></TextGroup> (Imipenem, Meropenem) geeignet <TextLink reference="1"></TextLink>, <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>. Um Carbapeneme einzusparen und damit der Selektion Carbapenem-re<TextGroup><PlainText>sis</PlainText></TextGroup>tenter Erreger entgegenzuwirken, kommen zur parenteralen Initialtherapie hier auch die neuen Cephalosporin&#47;BLI-Kombinationen, (Ceftolozan&#47;Tazobactam, Ceftazidim&#47;Avibactam) in Frage <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>. Bei ESBL-produzierenden Erregern k&#246;nnte auch Fosfomycin als parenterale Initialtherapie erwogen werden; es liegen aber nur wenige Daten &#252;ber die Monotherapie mit Fosfomycin bei komplizierten HWI vor <TextLink reference="32"></TextLink>, <TextLink reference="33"></TextLink>. F&#252;r die Therapie von Infektionen mit Methicillin-resistenten <Mark2>Staphylococcus aureus</Mark2> (MRSA) und Vancomycin-re<TextGroup><PlainText>s</PlainText></TextGroup>istenten Enterokokken (VRE) stehen mittlerweile mehrere gut wirksame Substanzen zur Verf&#252;gung, wie z.B. Ceftobiprol (nur gegen <Mark2>Staphylococcus aureus</Mark2> und einige St&#228;mme von <Mark2>Enterococcus faecalis</Mark2> wirksam), Daptomycin (gegen Enterokokken nur in hoher, nicht zugelassener Dosierung wirksam) oder Linezolid <TextLink reference="2"></TextLink>, <TextLink reference="34"></TextLink>, <TextLink reference="35"></TextLink>. F&#252;r Harnwegsinfektionen gibt es hierzu jedoch keine ausreichenden Studien, so dass individuelle Therapieent<TextGroup><PlainText>s</PlainText></TextGroup>cheidungen notwendig sind. </Pgraph><SubHeadline>Patienten mit Diabetes mellitus</SubHeadline><Pgraph>Harnwegsinfektionen bei Patienten mit Diabetes mellitus sind problematisch, da sie die pathogenetisch bedeutsame Insulin-Resistenz verst&#228;rken k&#246;nnen und durch die Aktivierung inflammatorischer Prozesse eine instabile Stoffwechselsituation verschlechtern. Dies gilt besonders f&#252;r Patienten mit einem HbA1c-Wert &#62;8,5&#37; (HbA1c &#8211; IDFF&#62;70 mmol&#47;l) mit Neigung zu Hypo- und Hyperglyk&#228;mien, f&#252;r Patienten mit einem BMI &#62;30 kg&#47;m<Superscript>2</Superscript> und f&#252;r F&#228;lle mit einer manifesten diabetischen Nephropathie (ab Stadium 2b, Albumin-Ausscheidung &#8805;200 mg&#47;l, Kreatinin-Clearance &#8804;60 ml&#47;min) <TextLink reference="36"></TextLink>. Eine Glukosurie f&#246;rdert die Kolonisation der Harnwege durch pathogene und fakultativ pathogene Mikroorganismen. </Pgraph><Pgraph>Bei einer asymptomatischen Bakteriurie ist bei einer stabilen diabetischen Stoffwechselsituation sowie bei Ausschluss obstruktiver St&#246;rungen und anderen anatomischen Ver&#228;nderungen keine antimikrobielle Therapie notwendig <TextLink reference="37"></TextLink>, <TextLink reference="38"></TextLink>. Bei unkomplizierten und komplizierten Infektionen sind prinzipiell die gleichen Therapieemp<TextGroup><PlainText>f</PlainText></TextGroup>ehlungen, sowohl f&#252;r die initiale parenterale als auch f&#252;r die orale Folgebehandlung, wie f&#252;r Patienten ohne Diabetes mellitus zutreffend. Zu beachten ist, dass antimikrobielle Chemotherapeutika die hypoglyk&#228;mische Wirkung oraler Antidiabetika verst&#228;rken k&#246;nnen; allerdings sind andere Wechselwirkungen zwischen Antibiotika und Antidiabetika selten.</Pgraph><SubHeadline>Patienten mit eingeschr&#228;nkter Nierenfunktion und nach Nierentransplantation</SubHeadline><Pgraph>Klinisch manifeste Harnwegsinfektionen beg&#252;nstigen die Progression eines akuten und chronischen Nierenversagens. Bei Patienten mit eingeschr&#228;nkter Nierenfunktion, dialysepflichtigen Patienten oder nach Nierentransplantation sollten keine potentiell nephrotoxischen Antibiotika, z.B. Aminoglykoside oder Vancomycin verwendet werden. Die Dosierung der Antibiotika richtet sich nach dem Grad der Nierenfunktionseinschr&#228;nkung. Dosierungsempfehlungen finden sich in Normogrammen oder differenzierten Tabellen <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>, <TextLink reference="41"></TextLink> und richtet sich u.a. nach dem Ausscheidungsmodus des Antibiotikums und der Nierenfunktion (siehe entsprechende Tabellen) <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>, <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>, <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink>, <TextLink reference="45"></TextLink>, <TextLink reference="46"></TextLink>, <TextLink reference="47"></TextLink>.</Pgraph><Pgraph>Unter den Bedingungen einer Nierenersatztherapie beeinflussen pharmakologische Eigenschaften wie die Molek&#252;lgr&#246;&#223;e des Antibiotikums, dessen Wasserl&#246;slichkeit und die Proteinbindung sowie die Dialyseprozedur Dosierungsempfehlungen. Sinnvoll ist es, Antibiotika erst nach dem Abschluss der Dialysebehandlung (HD, HDF, CVVHD, CVVHDF) zu applizieren.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Complicated or nosocomial urinary tract infection"> <MainHeadline>Complicated or nosocomial urinary tract infection</MainHeadline><SubHeadline>Definition</SubHeadline><Pgraph>A complicated urinary tract infection (UTI) is defined as an infection of the urinary tract that is associated with a morphological, functional or metabolic anomaly, which leads to disturbance of renal function, impaired urinary transport and disorder of local and systemic defense mechanisms <TextLink reference="5"></TextLink>, <TextLink reference="22"></TextLink>, <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>. The risk factors are classified in the so-called ORENUC classification <TextLink reference="25"></TextLink>.</Pgraph><SubHeadline>Indication for initial parenteral antibiotic treatment</SubHeadline><Pgraph>The indication for initial parenteral antibiotic treatment, as mentioned above, depends on the general condition and the risk profile of the patient. CRP and procalcitonin can be used as biomarkers in the decision making process <TextLink reference="26"></TextLink>. Antibiotic treatment of complicated UTIs can only achieve a cure if the complicating or triggering factors are eliminated or improved <TextLink reference="1"></TextLink>.</Pgraph><SubHeadline>Pathogen spectrum</SubHeadline><Pgraph>The expected pathogen spectrum is generally much broader than that of uncomplicated UTIs and is also related to the circumstances in which a complicated UTI was acquired <TextLink reference="22"></TextLink>, <TextLink reference="23"></TextLink>, <TextLink reference="27"></TextLink>. So, the pathogen spectrum in community-acquired first-time complicated UTIs, for instance as a result of acute calcium oxalate urinary stones in a patient with no prior antibiotic and no urinary diversion, is relatively similar to the spectrum of an uncomplicated acute pyelonephritis <TextLink reference="6"></TextLink>. But in cases of nosocomially acquired complicated UTIs, pathogens which are not usually pathogens of primary urinary tract infections but appear secondarily as a result of selection or colonization should also be expected. These may be <Mark2>Pseudomonas</Mark2> <Mark2>aeruginosa</Mark2> or Enterobacteriaceae like <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> <TextLink reference="23"></TextLink>, <TextLink reference="27"></TextLink>. If a complicated UTI is suspected, a urine culture prior to the initiation of antibiotic treatment is generally indicated because the pathogen spectrum is broad and the resistance situation not always predictable, so options for adapting treatment following the microbiological test result should be considered <TextLink reference="1"></TextLink>.</Pgraph><SubHeadline>Antibiotic selection</SubHeadline><Pgraph>The initial empirical antibiotic treatment must take into account the regional resistance situation of the expected pathogen spectrum <TextLink reference="23"></TextLink>. The following clinical conditions which have an impact on the expected pathogen spectrum and pathogen sensitivity must always be clarified in advance <TextLink reference="23"></TextLink>:</Pgraph><Pgraph><OrderedList><ListItem level="1" levelPosition="1" numString="1.">Where was the UTI acquired, for instance as an out-patient, in a nursing home, hospital, after diagnostic&#47;therapeutic interventions&#63;</ListItem><ListItem level="1" levelPosition="2" numString="2.">Was there prior antibiotic treatment (for how long, what antibiotics)&#63;</ListItem><ListItem level="1" levelPosition="3" numString="3.">Was there a previous longer hospital stay&#63;</ListItem><ListItem level="1" levelPosition="4" numString="4.">Was there a previous urinary diversion (what, how long, treated how)&#63;</ListItem><ListItem level="1" levelPosition="5" numString="5.">If urinary diversion is present, check the quality of the urinary drainage and, if necessary, change the catheter (removal of the infectious biofilm)</ListItem><ListItem level="1" levelPosition="6" numString="6.">Is it a case of recurrence or treatment failure&#63;</ListItem><ListItem level="1" levelPosition="7" numString="7.">For antimicrobial stewardship reasons, consideration should always be given to the extent to which the use of broad spectrum antibiotics is necessary (such as cephalosporins&#47;BLI, carbapenems).</ListItem></OrderedList></Pgraph><Pgraph>For initial parenteral treatment of complicated complex UTI, cephalosporins of group 3a, fluoroquinolones and aminopenicillins&#47;BLI are suitable. In the case of risk factors for multidrug-resistant pathogens (such as extended spectrum beta-lactamase &#91;ESBL&#93;-producing Enterobac<TextGroup><PlainText>t</PlainText></TextGroup>eriaceae), antibiotics such as cephalosporins&#47;BLI (ceftolozane&#47;tazobactam, ceftazidime&#47;avibactam) or a carbapenem of group 2 (ertapenem) may be used <TextLink reference="1"></TextLink>, <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="12"></TextLink>, <TextLink reference="13"></TextLink>, <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>. Patients with nosocomially acquired or catheter-associated UTIs also show an increased incidence of multidrug-resistant pathogens <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>, <TextLink reference="27"></TextLink>, <TextLink reference="28"></TextLink>. An antibiotic which is also effective against more rare and multi-resistant Gram-negative pathogens should therefore be used for empirical treatment. These include cephalosporins of group 3b, the cephalosporin&#47;BLI combinations ceftolozane&#47;tazobactam and ceftazidime&#47;avibactam, or 4 (cefepime), fluoroquinolones of group 2 or 3 (observe local <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> resistances) and carbapenems of <TextGroup><PlainText>group 1 </PlainText></TextGroup>(imipenem, meropenem) <TextLink reference="1"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>. To close the enterococcal gap present in these antibiotics as mixed infections with enterococci are more common in catheter-associated urinary tract infections, acylaminopenicillin&#47;BLI (such as piperacillin&#47;Tazobatam) should be used <TextLink reference="1"></TextLink>, <TextLink reference="31"></TextLink>. If multidrug-resistant pathogens are suspected (in the context of outbreaks or high endemic resistance rates), appropriately effective substances should be used in empirical treatment. Since carbapenemases rarely occur in German-speaking countries, a cephalosporin&#47;BLI (ceftolozane&#47;tazobactam, ceftazidime&#47;avibactam) <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, a carbapenem of group 2 (ertapenem) or, in case of simultaneous suspected Pseudomonas, a cephalosporin&#47;BLI (ceftolozane&#47;tazobactam, ceftazidime&#47;avibactam) or a carbapenem of group 1 (imipenem, meropenem) <TextLink reference="1"></TextLink>, <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink> are suitable. In order to conserve carbapenems and thus counteract the selection of carbapenem-resistant pathogens, the new cephalosporin&#47;BLI combinations (ceftolozane&#47;tazobactam, ceftazidime&#47;avibactam) are also suitable for parenteral initial treatment <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>. For ESBL-producing pathogens, fosfomycin might also be considered for parenteral initial treatment; however, there is limited data on fosfomycin monotherapy in complicated UTIs <TextLink reference="32"></TextLink>, <TextLink reference="33"></TextLink>. For the treatment of infections with methicillin-resistant <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> (MRSA) and vancomycin-resistant enterococci (VRE) several highly-effective substances are now available, such as ceftobiprole (effective only against <Mark2>Staphylococcus</Mark2> <Mark2>aureus</Mark2> and some strains of <Mark2>Enterococcus</Mark2> <Mark2>faecalis)</Mark2>, daptomycin (effective only against enterococci in high, unauthorized doses) or linezolid <TextLink reference="2"></TextLink>, <TextLink reference="34"></TextLink>, <TextLink reference="35"></TextLink>. For urinary tract infections, however, there are insufficient studies, so that case-by-case decisions on treatment are necessary. </Pgraph><SubHeadline>Patients with diabetes mellitus</SubHeadline><Pgraph>Urinary tract infections in patients with diabetes mellitus are problematic because they can increase the pathogenetically significant insulin resistance and worsen an unstable metabolic situation by activating inflammatory processes. This is especially true for patients with a HbA1c value &#62;8.5&#37; (HbA1c &#8211; IDFF &#62;70 mmol&#47;l) with a tendency to hypo- and hyperglycaemia, for patients with a BMI &#62;30 kg&#47;m<Superscript>2</Superscript> and for cases with a manifest diabetic nephropathy (from stage 2b, albumin excretion <TextGroup><PlainText>&#8805;200 mg&#47;l</PlainText></TextGroup>, creatinine clearance &#8804;60 ml&#47;min) <TextLink reference="36"></TextLink>. Glucosuria promotes colonization of the urinary tract by pathogenic and facultative pathogenic microorganisms. </Pgraph><Pgraph>In case of asymptomatic bacteriuria, no antimicrobial treatment is necessary in a stable diabetic metabolic situation and if obstructive disorders and other anatomical changes have been excluded <TextLink reference="37"></TextLink>, <TextLink reference="38"></TextLink>. For both uncomplicated and complicated infections, the same treatment recommendations are applicable for patients with or withour diabetes mellitus. This is true for the initial parenteral as well as the oral follolw-up treatment. It should be noted that antimicrobial chemotherapeutic agents may increase the hypoglycemic effect of oral anti-diabetic drugs; however other interactions between antibiotics and anti-diabetic drugs are rare.</Pgraph><SubHeadline>Patients with impaired renal function and after kidney transplantation</SubHeadline><Pgraph>Urinary tract infections favor the progression of acute and chronic renal failure. In patients with renal impairment, dialysis or renal transplantation, no potentially nephrotoxic antibiotics should be used, such as aminoglycosides or vancomycin. The dosage of antibiotics depends on the degree of renal impairment. Dosage recommendations can be found in nomograms or tables with detailed breakdowns <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>, <TextLink reference="41"></TextLink> as pharmacokinetic parameters of the antimicrobial substances depend extensively on different excretion modes of each substance and the respective renal function (see corresponding tables) <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>, <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>, <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink>, <TextLink reference="45"></TextLink>, <TextLink reference="46"></TextLink>, <TextLink reference="47"></TextLink>.</Pgraph><Pgraph>Under the conditions of renal replacement therapy, pharmacological properties such as the molecular size of the antibiotic, its solubility in water and protein binding and the dialysis procedure influence dosage recommendations. It makes sense to only administer antibiotics after completion of the dialysis (HD, HDF, CVVHD, CVVHDF).</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Urosepsis"> <MainHeadline>Urosepsis</MainHeadline><Pgraph>Eine Urosepsis tritt nach h&#228;matogener Streuung aus dem infizierten Harntrakt ohne oder nach vorangegangener instrumenteller Intervention auf. Es werden vornehmlich <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> und andere Enterobacteriaceae nachgewiesen. Nach urologischen Eingriffen bzw. bei Patienten mit Harndauerableitung mittels Katheter m&#252;ssen auch multiresistente <Mark2>Pseudomonas</Mark2> spp., <Mark2>Proteus</Mark2> spp., <Mark2>Serratia</Mark2> spp., <Mark2>Enterobacter</Mark2> spp., Enterokokken und Staphylokokken ber&#252;cksichtigt werden (siehe komplizierte HWI) <TextLink reference="1"></TextLink>, <TextLink reference="23"></TextLink>. </Pgraph><Pgraph>Die initiale parenterale Antibiotika-Therapie muss bei Verdacht auf Urosepsis sofort (innerhalb der ersten Stunde) und nach vorheriger Abnahme entsprechender Proben f&#252;r Urin- und Blutkulturen initiiert werden <TextLink reference="48"></TextLink>, <TextLink reference="49"></TextLink>, <TextLink reference="50"></TextLink>, <TextLink reference="51"></TextLink>, <TextLink reference="52"></TextLink>. Daf&#252;r kommen u.a. Cephalosporine der Gruppen 3 oder 4 in Betracht <TextLink reference="13"></TextLink>, <TextLink reference="53"></TextLink>, <TextLink reference="54"></TextLink>. Alternativen sind ein Acylaminopenicillin&#47;BLI (z.B. Piperacillin&#47;Tazobactam) oder ein Cephalosporin&#47;BLI (Ceftolozan&#47;Tazobactam, Ceftazidim&#47;Avibactam) oder ein Carbapenem der Gruppe 2 (Ertapenem) oder der Gruppe 1 (Imipenem, Meropenem), je nachdem unter welchen Umst&#228;nden die Urosepsis aufgetreten ist (siehe komplizierte&#47;nosokomiale HWI) <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="13"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>. Eine Erweiterung des antibakteriellen Spektrums kann initial z.B. durch eine Kombination mit einem Aminoglykosid oder einem Fluorchinolon mit hoher Harnausscheidung erzielt werden <TextLink reference="1"></TextLink>. Generell sollte eine maximal hohe Dosierung der Antibiotika gew&#228;hlt werden <TextLink reference="3"></TextLink>, <TextLink reference="55"></TextLink>.</Pgraph><Pgraph>Da bei Urosepsis meist eine obstruktive Uropathie, z.B. bedingt durch Urolithiasis, Tumore, benigne Prostatahypertrophie, oder eine abszedierende Infektion vorliegt, muss nach Probenentnahme (Urin, Blut) und Einleitung einer entsprechenden Breitspektrum-Antibiotika-Therapie neben den bei einer Sepsis notwendigen intensivmedizinischen Ma&#223;nahmen, umgehend eine gezielte urologische Diagnostik zum Nachweis bzw. zur Lokalisation der obstruktiven Uropathie bzw. der abszedierenden Infektion mit dem Ziel erfolgen, den &#8222;Herd&#8220; so rasch wie m&#246;glich zu beseitigen oder die Obstruktion mit geeigneten Ma&#223;nahmen (z.B. transurethrale oder suprapubische Katheter, Ureterschiene, Nephrostomie) zu umgehen, damit der freie Urinabfluss wieder gew&#228;hrleistet ist <TextLink reference="48"></TextLink>, <TextLink reference="49"></TextLink>, <TextLink reference="56"></TextLink>, <TextLink reference="57"></TextLink>.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Urosepsis"> <MainHeadline>Urosepsis</MainHeadline><Pgraph>Urosepsis occurs after hematogenous spread from the infected urinary tract without or following instrumental intervention. Mainly <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> and other Enterobacteriaceae are found. After urological intervention or in patients with urinary diversion via a catheter, multidrug-resistant <Mark2>Pseudomonas</Mark2> spp., <Mark2>Proteus</Mark2> spp., <Mark2>Serratia</Mark2> spp., <Mark2>Enterobacter</Mark2> spp., enterococci and staphylococci must also be considered (see complicated UTI) <TextLink reference="1"></TextLink>, <TextLink reference="23"></TextLink>. </Pgraph><Pgraph>Initial parenteral antibiotic treatment must be initiated immediately (within the first hour) in cases of suspected urosepsis and after prior sampling of urine and blood cultures <TextLink reference="48"></TextLink>, <TextLink reference="49"></TextLink>, <TextLink reference="50"></TextLink>, <TextLink reference="51"></TextLink>, <TextLink reference="52"></TextLink> , group 3 or 4 cephalosporins are the most useful for this <TextLink reference="13"></TextLink>, <TextLink reference="53"></TextLink>, <TextLink reference="54"></TextLink>. Alternatives are acylaminopenicillin&#47;BLI (such as piperacillin&#47;tazobactam) or cephalosporin&#47;BLI (ceftolozan&#47;tazobactam, ceftazidime&#47;avibactam) or a carbapenem of group 2 (ertapenem) or group 1 (imipenem, meropenem), depending on the circumstances under which urosepsis has occurred (see complicated&#47;nosocomial UTI) <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="13"></TextLink>, <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>. An extension of the antibacterial spectrum can initially be achieved, for example through combination with an aminoglycoside or a fluoroquinolone with high urinary elimination <TextLink reference="1"></TextLink>. In general, the highest possible dosage of antibiotics should be chosen <TextLink reference="3"></TextLink>, <TextLink reference="55"></TextLink>.</Pgraph><Pgraph>Urosepsis usually involves an obstructive uropathy (for example due to urolithiasis, tumors, benign prostatic hypertrophy or where an abscess-forming infection is present). Therefore, after taking samples (urine, blood) and initiating an appropriate broad-spectrum antibiotic treatment, in addition to necessary intensive care measures in case of sepsis, targeted urological diagnostics must be performed immediately to detect or localize the obstructive uropathy or the abscessing infection. The aim is to eliminate the source as quickly as possible or to circumvent the obstruction with suitable measures (such as a transurethral or suprapubic catheter, ureteral splint or nephrostomy) to allow free urine drainage once more <TextLink reference="48"></TextLink>, <TextLink reference="49"></TextLink>, <TextLink reference="56"></TextLink>, <TextLink reference="57"></TextLink>.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Akute Prostatitis, Prostataabszess"> <MainHeadline>Akute Prostatitis, Prostataabszess</MainHeadline><Pgraph>Die empirische Therapie der akuten bakteriellen Prostatitis (ABP) richtet sich nach den gleichen Aspekten wie die der komplizierten Harnweginfektionen <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>. Bei der spontan auftretenden ABP finden sich &#252;berwiegend <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> und andere Enterobacteriaceae. Bei Patienten mit einer ABP nach einem urologischen Eingriff finden sich geh&#228;uft auch andere gramnegative Erreger, z.B. <Mark2>Pseudomonas</Mark2> spp. Bei diesen Patienten geht die ABP auch h&#228;ufiger mit einer abszedierenden Verlaufsform einher; dabei werden wiederum h&#228;ufiger auch <Mark2>Klebsiella</Mark2> <Mark2>pneumoniae</Mark2> gefunden <TextLink reference="59"></TextLink>.</Pgraph><Pgraph>Zur empirischen Therapie werden vorzugsweise Substanzen ausgew&#228;hlt, die neben hohen Antibiotika-Konzentrationen im Harn auch eine ausreichende Konzentration im Prostatagewebe, Prostatasekret und Ejakulat gew&#228;hrleisten <TextLink reference="1"></TextLink>. Die initiale parenterale Antibiotika-Therapie ist nur bei schweren Verlaufsformen der akuten bakteriellen Prostatitis mit und ohne Abszedierung notwendig. Mittel der Wahl sind Fluorchinolone der Gruppen 2 und 3 <TextLink reference="58"></TextLink>, <TextLink reference="59"></TextLink>, <TextLink reference="60"></TextLink>. Eine Antibiotika-Anamnese ist jedoch besonders wichtig, da viele Patienten bereits Fluorchinolone im Vorfeld erhalten haben und hierbei das Risiko Fluorchinolon-resistenter Erreger gro&#223; ist. Alternativ k&#246;nnen bei einer ABP dann auch Cephalosporine der Gruppen 3 und 4 oder Acylaminopenicilline&#47;BLI eingesetzt werden. Da die ABP keine h&#228;ufige Infektion ist, aber die Einleitung der Antibiotika-Therapie unverz&#252;glich notwendig ist, liegen keine prospektiv, kontrollierten und randomisierten Studien vor, so dass sich die Therapieempfehlungen im Wesentlichen auf Expertenmeinungen st&#252;tzen <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>, <TextLink reference="61"></TextLink>.</Pgraph><Pgraph>Nach dem kulturellen Erregernachweis aus dem Harn (Prostatamassage ist bei der ABP kontraindiziert) und dem Ergebnis der Resistenzbestimmung soll auf eine gezielte Antibiotika-Therapie umgestellt werden, die je nach Besserung der klinischen Situation als orale Therapie f&#252;r mindestens zwei (bis vier) Wochen fortgesetzt wird, um Komplikationen wie akuten Harnverhalt, Epididymitis, Prostataabszess oder chronische Prostatitis zu vermeiden <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>, <TextLink reference="61"></TextLink>.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Acute prostatitis, prostate abscess"> <MainHeadline>Acute prostatitis, prostate abscess</MainHeadline><Pgraph>Empirical treatment of acute bacterial prostatitis (ABP) is based on the same aspects as those for complicated urinary tract infections <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>. In spontaneously occurring ABP, mainly <Mark2>Escherichia</Mark2> <Mark2>coli</Mark2> and other Enterobacteriaceae are found. In patients with ABP following urological intervention, other Gram-negative pathogens, for example <Mark2>Pseudomonas</Mark2> spp. are commonly found. In these patients, ABP is more often associated with abscess-forming progression; here <Mark2>Klebsiella</Mark2> <Mark2>pneumoniae</Mark2> are again found more frequently <TextLink reference="59"></TextLink>.</Pgraph><Pgraph>For empirical treatment, the preference is for substances which, in addition to high antibiotic concentrations in the urine, also ensure sufficient concentration in the prostate tissue, prostatic fluid and ejaculate <TextLink reference="1"></TextLink>. Initial parenteral antibiotic treatment is only necessary in severe forms of acute bacterial prostatitis with or without abscess formation. The drugs of choice are fluoroquinolones of groups 2 and 3 <TextLink reference="58"></TextLink>, <TextLink reference="59"></TextLink>, <TextLink reference="60"></TextLink>. However, an antibiotic history is especially important as many patients have previously received fluoroquinolones and the risk of fluoroquinolone-resistant pathogens is high. Alternatively, it is also possible to use groups 3 and 4 cephalosporins or acylaminopenicillins&#47;BLI in an ABP. Since ABP is not a common infection but antibiotic treatment has to be initiated immediately, there are no prospective, controlled or randomized studies, so the treatment recommendations are essentially based on expert opinions <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>, <TextLink reference="61"></TextLink>.</Pgraph><Pgraph>Following in-culture pathogen identification from the urine (prostate massage is contraindicated in ABP) and the results of resistance testing, treatment should be switched to targeted therapy, depending on the improvement of the clinical situation and continued orally for at least two (up to four) weeks, to avoid complications such as acute urinary retention, epididymitis, prostate abscess or chronic prostatitis <TextLink reference="1"></TextLink>, <TextLink reference="58"></TextLink>, <TextLink reference="61"></TextLink>.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Akute Epididymitis, Epididymoorchitis ggf. mit Abszess"> <MainHeadline>Akute Epididymitis, Epididymoorchitis ggf. mit Abszess</MainHeadline><Pgraph>W&#228;hrend traditionell eine &#228;tiologische Altersgrenze bei 35 Jahren gesetzt wurde (&#60;35 Jahre: sexuelle &#252;bertragbare Erreger; &#62;35 Jahre klassische Uropathogene) <TextLink reference="1"></TextLink>, <TextLink reference="62"></TextLink>, konnte k&#252;rzlich gezeigt werden, dass auch bei jungen Patienten klassische Uropathogene h&#228;ufig vorkommen und entsprechend antimikrobiell ad&#228;quat erfasst werden m&#252;ssen <TextLink reference="63"></TextLink>, <TextLink reference="64"></TextLink>.</Pgraph><Pgraph>Dies bedeutet, dass mit Ausnahme einer Gonokokken-Epididymitis, Fluorchinolone mit Aktivit&#228;t gegen Chlamydien (z.B. Levofloxacin), bevorzugt bei jungen M&#228;nnern, Anwendung finden sollten. Die Kombination von Ceftriaxon i.m. mit Doxycyclin p.o. ist bei sexuell &#252;bertragbaren Erregern weiterhin akzeptiert. Bei &#228;lteren M&#228;nnern kommen ebenfalls Fluorchinolone der Gruppen 2 und 3 in Frage, wenn eine ambulante F&#252;hrung m&#246;glich ist <TextLink reference="64"></TextLink>. </Pgraph><Pgraph>Generell ist eine parenterale und station&#228;re Therapie nur bei schweren Verlaufsformen (z.B. Abszessbildung), ausgepr&#228;gten Komorbidit&#228;ten (z.B. Dauerkatheter), oder Therapieversagern notwendig. Zu beachten ist insbesondere bei Kathetertr&#228;gern eine zunehmende Resistenzbildung gegen&#252;ber Fluorchinolonen, so dass eine Kombinationstherapie, z.B. mit einem Cephalosporin der Gruppe 3a, sinnvoll ist. Die parenterale Therapie sollte nach Erhalt des Antibiogramms m&#246;glichst rasch auf eine orale Sequenztherapie umgestellt werden <TextLink reference="63"></TextLink>.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Acute epididymitis, epididymoorchitis possibly with abscess"> <MainHeadline>Acute epididymitis, epididymoorchitis possibly with abscess</MainHeadline><Pgraph>While an etiological age limit of 35 years has traditionally been set (&#60;35 years: sexually transmitted pathogens, &#62;35 years for classical uropathogens) <TextLink reference="1"></TextLink>, <TextLink reference="62"></TextLink>, it has recently been shown that classical uropathogens are also common in young patients, and the antimicrobial makeup must therefore be adequately assessed <TextLink reference="63"></TextLink>, <TextLink reference="64"></TextLink>.</Pgraph><Pgraph>This means that, with the exception of gonococcal epididymitis, in young men preferably fluoroquinolones with activity against chlamydia (for example levofloxacin), should be used. The combination of ceftriaxone i.m. with doxycycline p.o. is still accepted for sexually transmitted pathogens. In older men, group 2 and 3 fluoroquinolones are also options if out-patient treatment is possible <TextLink reference="64"></TextLink>. </Pgraph><Pgraph>Generally, parenteral and in-patient treatment is necessary only for severe forms (for example abscess formation), severe comorbidities (for example indwelling catheters) or treatment failures. Note there is an increasing resistance to fluoroquinolones, especially amongst catheter carriers, so that combination therapy makes sense, for example with a group 3a cephalosporin. Once the antibiogram has been created, parenteral treatment should be switched to oral sequential therapy as soon as possible <TextLink reference="63"></TextLink>.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Endometritis, Salpingitis, Tuboovarialabszess, Pelveoperitonitis"> <MainHeadline>Endometritis, Salpingitis, Tuboovarialabszess, Pelveoperitonitis</MainHeadline><Pgraph>Bei Infektionen des weiblichen Genitale sexuell aktiver pr&#228;menopausaler Frauen muss mit einem breiten Spektrum potenzieller Erreger gerechnet werden. Neben den sexuell &#252;bertragbaren Erregern <Mark2>Neisseria</Mark2> <Mark2>gonorrhoeae</Mark2> und <Mark2>Chlamydia</Mark2> <Mark2>trachomatis</Mark2> kommen &#228;tiologisch die Vaginalflora und die Erreger der bakteriellen Vaginose in Frage, in seltenen F&#228;llen auch Mykoplasmen und Ureaplasmen <TextLink reference="65"></TextLink>, <TextLink reference="66"></TextLink>, <TextLink reference="67"></TextLink>. Hinsichtlich der &#196;tiologie aufgestiegener Infektionen sind, von Ausnahmen abgesehen, nur laparoskopisch gewonnene Proben, diagnostisch relevant <TextLink reference="68"></TextLink>. Da kein einzelnes Antibiotikum gegen das gesamte Spektrum der infrage kommenden Erreger wirksam ist, konnte bislang kein Konsens zur Therapie der Wahl gefunden werden, zumal eine Vielzahl von Untersuchungen mit Kombinationen verschiedener Substanzgruppen positive Resultate gezeigt hat. Eine zweifelsfreie Wertung parenteraler und oraler Therapieregime sowie Gegen&#252;berstellungen der ambulanten und station&#228;ren Behandlung stehen aus, sodass die Entscheidung f&#252;r eines der Regime individuell je nach Schweregrad der Erkrankung, Patientenakzeptanz und regionaler Resistenzlage potenzieller Erreger getroffen werden muss. Eine parenterale Initialtherapie kann nach klinischer Besserung auf eine orale Sequenztherapie mit einem der Kombinationspartner, meist Doxycyclin, Clindamycin oder auch einem Fluorchinolon umgestellt werden <TextLink reference="62"></TextLink>, <TextLink reference="69"></TextLink>. Cephalosporine sollten zur Erfassung von Anaerobiern prim&#228;r mit Metronidazol kombiniert werden. Alternativ k&#246;nnen auch Fluorchinolone oder Aminopenicilline&#47;BLI verwendet werden. Zur Anwendung kommen Fluorchinolone der Gruppen 2 und 3, jeweils in Kombination mit Metronidazol, Aminopenicilline&#47;BLI plus Doxycyclin oder das Carbapenem der Gruppe 2 (Ertapenem) <TextLink reference="69"></TextLink>. Stets erforderlich ist eine Verlaufskontrolle binnen 72 Stunden auch bei prim&#228;r unkompliziert erscheinenden Infektionen <TextLink reference="62"></TextLink>. Bei Therapieversagen sollte die antimikrobielle Behandlung rechtzeitig entsprechend den zwischenzeitlich zur Verf&#252;gung stehenden mikrobiologischen Befunden adaptiert werden und falls notwendig eine chirurgische Intervention eingeleitet werden <TextLink reference="65"></TextLink>, <TextLink reference="66"></TextLink>. </Pgraph><Pgraph>In der Gravidit&#228;t muss das embryotoxische bzw. teratogene Potenzial verschiedener Antibiotika-Gruppen bei Einsatz vor der 14. SSW ber&#252;cksichtigt werden.</Pgraph><Pgraph>Das in Deutschland etablierte Screening auf asymptoma<TextGroup><PlainText>t</PlainText></TextGroup>ische Bakteriurie in der Gravidit&#228;t ist erneut in der Diskussion. Eine Cochrane-Analyse auf der Basis von <TextGroup><PlainText>14 S</PlainText></TextGroup>tudien ergab hinsichtlich Pyelonephritis eine Reduktion von 21&#37; auf 5&#37; (RR 0,23; 95&#37; KI: 0,13&#8211;0,41), Geburtsgewicht &#60;2.500 g von 13&#37; auf 8,5&#37; (RR 0,66; <TextGroup><PlainText>95&#37; KI</PlainText></TextGroup>: 0,49&#8211;0,89) sowie nicht signifikant Fr&#252;hgeburt &#60;38 SSW von 21&#37; auf 13&#37; (RR 0,37; 95&#37; KI: 0,10&#8211;1,36) bei Antibiotika-Therapie <TextLink reference="70"></TextLink>. In einer k&#252;rzlich publizierte<TextGroup><PlainText>n p</PlainText></TextGroup>rospektiv-randomisierten Multicenter-Untersuchung wurde dagegen kein Unterschied zu der Pr&#228;valenz von niedrigerem Geburtsgewicht und -zeitpunkt gefunden, wohl aber in Bezug auf eine Pyelonephritis <TextLink reference="71"></TextLink>. Mit 16&#8211;22 SSW setzten Screening und ggf. Nitrofurantoin-Therapie allerdings recht sp&#228;t ein. Eine detailliertere Analyse der Neugeborenen fand nicht statt. Prinzipiell herrscht geburtshilflich die Auffassung vor, dass derartige Studien &#252;ber den Aspekt der Harnweginfektion hinaus schwer zu bewerten und ethisch ausgesprochen problematisch bzw. kaum durchf&#252;hrbar sind.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis"> <MainHeadline>Endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis</MainHeadline><Pgraph>A broad spectrum of potential pathogens must be expected for infections of the genitalia of sexually active pre-menopausal women. In addition to sexually transmitted pathogens <Mark2>Neisseria</Mark2> <Mark2>gonorrhoeae</Mark2> and <Mark2>Chlamydia</Mark2> <Mark2>trachomatis</Mark2>, etiologically the vaginal flora and pathogens of bacterial vaginosis must be considered, in rare cases also mycoplasmas and ureaplasmas <TextLink reference="65"></TextLink>, <TextLink reference="66"></TextLink>, <TextLink reference="67"></TextLink>. With regard to the etiology of ascended infections, with exceptions only laparoscopic samples are diagnostically relevant <TextLink reference="68"></TextLink>. Since no single antibiotic is effective against the full spectrum of possible pathogens, no consensus on the treatment of choice has yet been found, especially as a variety of studies with combinations of different substance groups have shown positive results. Unequivocal evaluation of parenteral and oral treatment regimes as well as comparisons of out-patient and in-patient treatment has not been carried out to date, so choosing a treatment must be made on a case-by-case basis according to the severity of the disease, patient acceptance and regional resistance of potential pathogens. After clinical improvement, initial parenteral therapy can be switched to oral sequential therapy with one of the combination partners, usually doxycycline, clindamycin or even a fluoroquinolone <TextLink reference="62"></TextLink>, <TextLink reference="69"></TextLink>. Cephalosporins should be combined primarily with metronidazole to cover anaerobes. Alternatively, fluoroquinolones or aminopenicillins&#47;BLI can be used. Fluoroquinolones of groups 2 and 3 are used, in each case in combination with metronidazole, aminopenicillins&#47;BLI plus doxycycline or a carbapenem of group 2 (ertapenem) <TextLink reference="69"></TextLink>. Progress monitoring is always required within 72 hours, even in cases of seemingly uncomplicated infections <TextLink reference="62"></TextLink>. In the event of treatment failure, antimicrobial treatment should be adapted quickly in line with the microbiological findings available and, if necessary, surgical intervention should be initiated <TextLink reference="65"></TextLink>, <TextLink reference="66"></TextLink>. </Pgraph><Pgraph>In pregnancy, embryotoxic or teratogenic potential of various antibiotic groups should be taken into account if used before the 14<Superscript>th</Superscript> week.</Pgraph><Pgraph>The screening established in Germany for asymptomatic bacteriuria in pregnancy is under discussion once more. A Cochrane analysis based on 14 studies showed a reduction from 21&#37; to 5&#37; for pyelonephritis (RR 0.23, <TextGroup><PlainText>95&#37; CI</PlainText></TextGroup>: 0.13&#8211;0.41), birth weight &#60;2,500 g from 13&#37; to 8.5&#37; (RR 0.66, 95&#37; CI: 0.49&#8211;0.89) and not significant premature birth &#60;38 weeks of age from 21&#37; to 13&#37; (RR 0.37, 95&#37; CI: 0.10&#8211;1.36) with antibiotic treatment <TextLink reference="70"></TextLink>. In contrast, a recently published prospective randomized multi-center study found no difference in the prevalence of lower birth weight and earlier time of birth but did find a difference in relation to pyelonephritis <TextLink reference="71"></TextLink>. At 16&#8211;2<TextGroup><PlainText>2 w</PlainText></TextGroup>eeks, however, screening and possibly nitrofurantoin treatment start rather late. A more detailed analysis of newborns did not take place. In principle, as far as obstetrics are concerned, the assumption is that studies looking beyond urinary tract infections are difficult to assess and ethically very problematic or hardly feasible.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Anmerkung"> <MainHeadline>Anmerkung</MainHeadline><Pgraph>Dies ist das achte Kapitel der von der Paul-Ehrlich-Gesellschaft f&#252;r Chemotherapie e.V. (PEG) herausgegebenen S2k Leitlinie &#8222;Kalkulierte parenterale Initialtherapie bakterieller Erkrankungen bei Erwachsenen &#8211; Update 2018&#8220; in der 2. aktualisierten Fassung.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Note"> <MainHeadline>Note</MainHeadline><Pgraph>This is the eighth chapter of the guideline &#8220;Calculated initial parenteral treatment of bacterial infections in adults &#8211; update 2018&#8221; in the 2<Superscript>nd</Superscript> updated version. The German guideline by the Paul-Ehrlich-Gesellschaft f&#252;r 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 erkl&#228;ren, 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>Grabe M</RefAuthor> <RefAuthor>Bjerklund-Johansen TE</RefAuthor> <RefAuthor>Bonkat G</RefAuthor> <RefAuthor>Cek M</RefAuthor> <RefAuthor>Naber KG</RefAuthor> <RefAuthor>Pickard R</RefAuthor> <RefAuthor>Tenke P</RefAuthor> <RefAuthor>Wagenlehner F</RefAuthor> <RefAuthor>Wullt B</RefAuthor> <RefTitle></RefTitle> <RefYear>2015</RefYear> <RefBookTitle>Guidelines on urological infections</RefBookTitle> <RefPage></RefPage> <RefTotal>Grabe M, Bjerklund-Johansen TE, Bonkat G, Cek M, Naber KG, Pickard R, Tenke P, Wagenlehner F, Wullt B. 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DOI: 10.3205&#47;id000062</RefTotal> <RefLink>https:&#47;&#47;doi.org&#47;10.3205&#47;id000062</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: Empfehlungen zur empirischen parenteralen Antibiotika-Initialtherapie bei Infektionen der Nieren und des Urogenitaltraktes (Antibiotika nach Gruppen)</Mark1></Pgraph></Caption> <Caption language="en"><Pgraph><Mark1>Table 1: Recommendations for empirical initial parenteral antibiotic treatment for kidney and genito-urinary tract infections (antibiotics by groups)</Mark1></Pgraph></Caption> </Table> <NoOfTables>1</NoOfTables> </Tables> <Figures> <NoOfPictures>0</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>