id000049 10.3205/id000049 urn:nbn:de:0183-id0000497 Leitlinie Guideline Calculated parenteral initial therapy of bacterial infections: Antibiotic treatment in the elderly Walger Walger Peter P Dr.

Hygiene, Infektionsmanagement und ABS, Bonn, DeutschlandHygiene, Infektionsmanagement und ABS, Bonn, DeutschlandJohanniter GmbH Berlin, DeutschlandVerbund Katholischer Kliniken Düsseldorf, Deutschland

Hygiene, Infektionsmanagement und ABS, Bonn, GermanyHygiene, Infektionsmanagement und ABS, Bonn, GermanyJohanniter GmbH Berlin, GermanyVerbund Katholischer Kliniken Düsseldorf, Germany

peter@walger.org author Heppner Heppner Hans Jürgen HJ

Geriatrische Klinik und Tagesklinik, Helios Klinikum Schwelm, Deutschland

Geriatrische Klinik und Tagesklinik, Helios Klinikum Schwelm, 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 05 Dies ist das fünfzehnte 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.Multimorbidität, eine atypische Symptomatik von Infektionen in Kombination mit Multimedikation, die damit verbundenen Interaktionsrisiken und die oft schwerwiegenden Folgen synergistischer Nebenwirkungen kennzeichnen die Bedingungen bei der Entscheidung über den Einsatz von Antibiotika im Alter. Strenge Indikationsentscheidung, Auswahl des besten Antibiotikums auch unter Berücksichtigung seltener, bei älteren Menschen gefährlicher Nebenwirkungen, Ermittlung der richtigen Dosis, des Dosierungsintervalls und der kürzestmöglichen Dauer entsprechend dem physiologischen Status des Patienten sowie Überwachung von Effektivität und Toxizität erkennen frühzeitig erwartete und unerwartete Nebenwirkungen. Empfehlungen müssen die Besonderheiten der Antibiotika-Behandlung bei älteren Patienten widerspiegeln. This is the fifteenth 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.Multimorbidity, an atypical symptomatology of infections in combination with multimedication, the associated interaction risks and serious consequences of synergistic side effects characterize the conditions when deciding on the use of antibiotics in old age. Strict decision regarding the indication itself, choice of the best antibiotic even considering rare side effects which may be dangerous in the elderly, determining the correct dose, dosing interval and the shortest possible duration according to the physiological status of the patient as well as monitoring effectiveness and toxicity detect expected and unexpected side effects early. Recommendations must reflect the peculiarities of antibiotic treatment in elderly patients. EinleitungAltern der Bevölkerung bedeutet, dass sich die Zusammensetzung der Bevölkerung immer mehr in Richtung älterer Menschen verschiebt. Im Jahr 2050 wird der Anteil der über 65-Jährigen auf 30–40% geschätzt, zugleich wird sich der Anteil der Hochbetagten (80 Jahre und älter) auf bis zu 15% erhöhen und sich damit fast verdreifachen . Dieser demographische Wandel führt zu einer Zunahme geriatrischer Patienten in allen Bereichen der medizinischen Versorgung. So ist es von großer Bedeutung, die grundlegende Definition des geriatrischen Patienten zu kennen (siehe Tabelle 1 ).Der Anteil der akut zu versorgenden 90-jährigen Patienten steigt ebenfalls, beispielsweise in der Herzchirurgie oder der Alterstraumatologie . Dies erfordert ein hohes Maß an geriatrischem Sachverstand bei der Betreuung, wenn bei dieser vulnerablen Patientengruppe begleitende oder verkomplizierende Infektionen behandelt werden müssen . Unter adäquater Therapie ist das Outcome bei erhaltener Funktionalität gut . Daher ist es wichtig, die grundlegenden Besonderheiten in der antiinfektiven Therapie beim alten Menschen zu kennen.Multimorbidität, also das gleichzeitige Vorliegen mehrerer chronischer behandlungsbedürftiger Erkrankungen, führt in der Konsequenz zur Multimedikation und damit zur Gefahr synergistischer Nebenwirkungen und unerwünschter Interaktionen bei der Antibiotika-Therapie.Neben den physiologischen körperlichen Alternsveränderungen führt auch die Immunseneszenz zu einer größeren Infektanfälligkeit in diesem Patientenkollektiv. Morbidität und Mortalität zahlreicher Infektionskrankheiten steigen mit zunehmendem Alter. Infektionen sind eine der Haupttodesursachen bei älteren Patienten . Die häufigste infektionsbedingte Todesursache bei Patienten >65 Jahre ist die ambulant erworbene Pneumonie (CAP), wobei Pflegebedürftigkeit und insbesondere Bettlägerigkeit das Letalitätsrisiko deutlich erhöhen . Zahlreiche weitere Infektionen wie Harnwegsinfektionen, Sepsis, Haut- und Weichgewebeinfektionen, bakterielle Endokarditis, Cholezystitis und Divertikulitis zeigen steigende Inzidenzen. Atypische klinische Manifestationen, z.B. durch Abschwächung der Fieberreaktion, unspezifische Allgemeinsymptome oder frühzeitige Beeinträchtigungen der Hirnfunktionen, erschweren die Diagnose und verzögern eine rechtzeitige und adäquate Therapie , , .Ältere Patienten mit bakteriellen Infektionen weisen wegen eingeschränkter lokaler und systemischer Reaktionen auf die Infektion andere klinische Merkmale auf als junge Patienten. Die Symptome einer akuten Infektion beim älteren Patienten sind in der Regel „unspezifisch“ und „atypisch“. Das Kardinalsymptom einer bakteriellen Infektion, Fieber, ist in über 30% der Fälle nicht vorhanden . Die üblichen laborchemischen Marker für die Detektion einer Infektion, wie Leukozytenzahl oder C-reaktives Protein (CRP), können initial ebenfalls häufig normal oder nur minimal verändert sein . CRP und Leukozytenzahl sind daher bei geriatrischen Patienten unzuverlässige Parameter . IntroductionThe aging population means that the composition is shifting more and more towards older people. By 2050, it is estimated the proportion of over-65s will be at 30–40%, while at the same time the share of very elderly people (80 years and older) will rise to 15%, almost trebling . This demographic change is leading to an increase in geriatric patients in all areas of medical care. So it is very important to know the basic definition of what constitutes a geriatric patient (see Table 1 ).The proportion of 90-year-old patients requiring acute care is also increasing, for example in cardiac surgery or geriatric trauma . This requires a high level of geriatric expertise in care if it is necessary to treat concomitant or complicating infections in this vulnerable patient group . Under adequate treatment the outcome is good while maintaining the patient’s functional level . It is therefore important to have a basic understanding of the peculiarities of anti-infective treatment in the elderly.Multimorbidity, i.e. the simultaneous presence of several chronic diseases in need of treatment, consequently leads to multimedication and thus to the risk of synergistic side effects and undesirable interactions in antibiotic treatment.In addition to the physiological changes in the aging human body, immune senescence also leads to a greater susceptibility to infection in this patient group. Morbidity and mortality of many infectious diseases increase with age. Infections are a major cause of death in older patients . The most common cause of infection-related death in patients >65 years of age is community-acquired pneumonia (CAP), with long-term care and in particular being bed-ridden significantly increasing the risk of death . Numerous other infections such as urinary tract infections, sepsis, skin and soft tissue infections, bacterial endocarditis, cholecystitis and diverticulitis show increasing incidences. Atypical clinical manifestations, for example by weakening of the fever reaction, nonspecific general symptoms or early impairments of brain function make the diagnosis more difficult and delay timely and adequate treatment , , .Older patients with bacterial infections have different clinical characteristics compared to younger patients due to their limited local and systemic responses to an infection. Symptoms of acute infection in elderly patients are usually “nonspecific” and “atypical”. Fever, the cardinal symptom of a bacterial infection, is absent in over 30% of cases . The usual lab markers for the detection of an infection, such as leukocyte count or C-reactive protein (CRP), may initially also be normal or only minimally altered . CRP and white blood cell counts are therefore unreliable parameters in geriatric patients . Schwerpunkte Antibiotika-assoziierter Nebenwirkungen im AlterDurch physiologische Veränderungen ergeben sich im Alter Auswirkungen auf die Pharmakokinetik. Dies betrifft sowohl die Freisetzung und Resorption des Arzneistoffes als auch die Verteilung durch die Verschiebung von Fett- und Wassermasse im Alter und die (vornehmlich renale) Wirkstoffelimination. Eine Zusammenfassung der wichtigsten alternsbedingten Veränderungen mit Auswirkungen auf die Pharmakokinetik von Antiinfektiva zeigt Tabelle 2 .Über 30% der Menschen >70 Jahre haben mindestens fünf chronische Erkrankungen . Ein extensiver Gebrauch von verschriebenen und rezeptfreien OTC (=over-the-counter)-Medikamenten sowie von pflanzlichen Präparationen ist typisch für alte Menschen. So nehmen 25% der Frauen über 65 Jahre (USA) fünf verordnete Medikamente und 12% zehn oder mehr Medikamente ein. Dies erhöht zwangsläufig das Komplikationsrisiko .Ähnliche Daten liegen für Deutschland vor. Über 70-Jährige nehmen durchschnittlich drei verschiedene Medikamente pro Tag ein, die 80- bis 85-Jährigen erhalten die höchste Anzahl pro Tag , 35% der >70-Jährigen erhalten 5 bis 8, 15% mehr als 13 verschiedene Medikamente . Zusätzliche pflanzliche oder sonstige Nahrungsergänzungsmittel nahmen 14% (1998) bzw. 26–27% (2002) , der untersuchten Älteren ein.Eine fiktive 79-jährige Patientin mit fünf der häufigsten Komorbiditäten (COPD, Diabetes mellitus Typ 2, Hypertonie, Osteoporose, Osteoarthritis) erhält entsprechend den Leitlinien (USA 2005) täglich 12 Medikamente, nach komplizierten Einnahmeregeln mit unvorhersehbaren Interaktionen zwischen Krankheiten und Medikamenten bzw. zwischen Medikamenten und mit zahlreichen unerwünschten Arzneimittelwirkungen .Nebenwirkungen von Medikamenten sind bei älteren Patienten generell bis zu 3-mal häufiger als bei 30-Jährigen . Bei der Einnahme von bis zu 5 Medikamenten besteht ein UAW-Risiko (Unerwünschte Arzneimittel-Wirkungen) von 4%, bei 6–10 Medikamenten von 10% und bei 11–15 Medikamenten von 28% . UAWs finden sich insgesamt bei 14,6–35% der alten Patienten. 20–25% der geriatrischen stationären Aufnahmen sind ursächlich Folge von UAWs. Antikoagulanzien, Nichtsteroidale Antiphlogistika (NSAID), Antidiabetika, Diuretika und Digitalisglykoside sind am häufigsten mit UAWs assoziiert, die zur stationären Aufnahme führen . Interaktionen spielen bei rund 40% der UAWs eine Rolle. Ein niedriges Körpergewicht ist besonders häufig mit UAWs assoziiert. Über 80% der UAW-assoziierten stationären Aufnahmen sind vermeidbar , . Key on antibiotic-associated side effects in old agePhysiological changes affect pharmacokinetics in old age. This concerns both the release and absorption of drugs as well as their distribution through the changes to fat and water mass in old age and the (mainly renal) drug elimination. A summary of the most important age-related changes affecting the pharmacokinetics of anti-infective agents is shown in Table 2 .Over 30% of people >70 years old have at least five chronic diseases . Extensive use of prescribed and over-the-counter (OTC) medication and herbal preparations is typical of the elderly. For example, 25% of women over the age of 65 (in the US) take five prescribed medications and 12% use ten or more medications. This inevitably increases the risk of complications .The data for Germany are similar. People over the age of 70 take an average of three different medicines per day; those aged 80 to 85 receive the highest number per day , 35% of those >70-year-olds receive 5 to 8 and 15% more than 13 different drugs . Of the elderly studied, 14% (in 1998) also took additional herbal or other dietary supplements ; in 2002 this figure was 26–27% , .A fictitious 79-year-old patient with five of the most common comorbidities (COPD, type 2 diabetes mellitus, hypertension, osteoporosis, osteoarthritis) receives 12 drugs a day according to guidelines (USA 2005), following complicated rules for administration with unpredictable interactions between diseases and medications and with numerous adverse drug reactions .Side effects of medications are generally up to 3 times more common in elderly patients compared to 30 year olds . When taking up to 5 medications, there is a 4% risk of ADR (adverse drug effects), with 6–10 medications this risk is 10% and with 11–15 medications 28% . Overall, ADRs are found in 14.6–35% of elderly patients. 20–25% of geriatric in-patient admissions are the result of ADRs. Anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), antidiabetics, diuretics and digitalis glycosides are most commonly associated with ADRs that lead to hospital admission . Interactions play a role in around 40% of ADRs. Low body weight is associated with ADRs especially often. Over 80% of ADR-associated in-patient admissions are preventable , . Prävalenz von inadäquaten VerordnungenDaten aus den USA, Kanada und Europa belegen einen hohen Anteil „Potentiell Inadäquater Medikationen“ (PIM) bei alten Patienten, z.B. in den USA 1994: 23,5%, USA 1996: 20% (davon 3% aus der Beers-Liste (historisch die erste publizierte PIM-Liste) der 11 „always avoid“-Präparate mit erhöhtem Risiko für Hospitalisation und Tod), USA 2002: 19%, Europa 2005: ~20%. Der typische Patient für Polypharmazie mit erhöhtem Anteil inadäquater Medikamente ist weiblich, >85 Jahre alt, alleinlebend und hat einen geringen Gesundheitsstatus sowie niedrigen sozialen Status , .Die Beers Criteria umfassen eine Liste inadäquater Medikationen bestehend aus drei Gruppen: „always avoid“ (11 Medikamente), „rarely appropriate“ (8 Medikamente) und „some indication, but often misused“ (14 M</PlainText></TextGroup>edikamente). In Anlehnung an diese Kriterien sind revidierte PIM-Listen in den USA, Frankreich, den Niederlanden und Kanada publiziert worden <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>, <TextLink reference="32"></TextLink>. Das Risiko f&#252;r UAW, die zur station&#228;ren Aufnahme von &#228;lteren Patienten f&#252;hren, ist demnach dann besonders erh&#246;ht, wenn mehrere Arzneimittel gleichzeitig eingenommen werden (Interaktionsrisiko). Multimedikation, Verordnung von Neuroleptika oder Antidementiva sind signifikante Risikofaktoren f&#252;r UAWs bei Menschen aus Altenheimen <TextLink reference="33"></TextLink>. Eine auf die Verh&#228;ltnisse in Deutschland zugeschnittene Aufstellung stellt die PRISCUS-Liste dar. Sie umfasst 83 Wirkstoffe, die als potenziell ungeeignet f&#252;r Senioren gelten, und aus 18 verschiedenen Arzneistoffklassen eines breiten Spektrums an Behandlungsgebieten entstammen <TextLink reference="34"></TextLink>, <TextLink reference="35"></TextLink>. Allerdings wird hier zu Antibiotika mit Ausnahme von Nitrofurantoin keine dezidierte Stellung bezogen.</Pgraph><Pgraph>Durch die Polypharmazie kommt es generell zu einer Risikoerh&#246;hung f&#252;r unerw&#252;nschte Wirkungen, und die Gefahr von klinisch relevanten Arzneimittelinteraktionen steigt. Dies ist auch f&#252;r einige Antiinfektiva, die zu einer bestehenden Multimedikation hinzugef&#252;gt werden, beschrieben. Um diese potentiellen Risiken zu minimieren, sollte hierauf bei Entscheidungen zur antiinfektiven Arzneimitteltherapie mit einer erh&#246;hten Aufmerksamkeit geachtet werden.</Pgraph><Pgraph>Die Behandlung alter Patienten mit einer bakteriellen Infektionskrankheit bedeutet deshalb typischerweise, einer langen Liste von verschiedenen Medikamenten mit zum Teil un&#252;bersichtlichem Interaktionspotenzial und verschiedenen UAWs eine weitere Substanz, ein Antibiotikum, hinzuzuf&#252;gen, welches m&#246;glicherweise selbst &#252;ber eigene Nebenwirkungen sowie ein eigenes Interaktionspotenzial verf&#252;gt.</Pgraph><Pgraph>Dies kann dann schnell zu behandlungsbed&#252;rftigen und zum Teil lebensbedrohlichen Situationen f&#252;hren <TextLink reference="36"></TextLink>.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Prevalence of inadequate regulations"> <MainHeadline>Prevalence of inadequate regulations</MainHeadline><Pgraph>Data from the US, Canada and Europe show a high proportion of &#8220;potentially inadequate me<TextGroup><PlainText>d</PlainText></TextGroup>ications&#8221; (PIM) in elderly patients, for example in the USA 1994: 23.5&#37; USA 1996 20&#37; &#8211; of which 3&#37; from the Beers list, historically the first published PIM list &#8211; of the 11 &#8220;always avoid&#8221; drugs with increased risk of hospitalization and death), USA 2002: 19&#37; Europe 2005: &#126;20&#37;. The typical polypharmacy patient with an increased incidence of inadequate medication is female, &#62;85 years old, living alone and has low health and social status <TextLink reference="26"></TextLink>, <TextLink reference="27"></TextLink>.</Pgraph><Pgraph>The Beers Criteria <TextLink reference="28"></TextLink> include a list of inadequate medications consisting of three groups: &#8220;always avoid&#8221; (<TextGroup><PlainText>11 drugs</PlainText></TextGroup>), &#8220;rarely appropriate&#8221; (8 drugs) and &#8220;some indication but often misused&#8221; (14 drugs). Based on these criteria, revised PIM lists have been published in the US, France, the Netherlands and Canada <TextLink reference="29"></TextLink>, <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>, <TextLink reference="32"></TextLink>. The risk of ADR leading to in-patient admission of elderly patients is therefore particularly high if several medicines are taken at the same time (risk of interaction). Multimedication, prescription of neuroleptics or anti-dementia drugs are significant risk factors for ADRs in nursing home residents <TextLink reference="33"></TextLink>. The PRISCUS list has been tailored to the conditions in Germany. It comprises <TextGroup><PlainText>83 drugs</PlainText></TextGroup> from 18 different drug classes, hailing from a wide range of treatment areas, that are considered potentially unsuitable for senior citizens <TextLink reference="34"></TextLink>, <TextLink reference="35"></TextLink>. However, there is no definite position on antibiotics with the exception of nitrofurantoin.</Pgraph><Pgraph>Polypharmacy generally increases the risk of adverse events and increases the risk of clinically relevant drug interactions. This is also described for some anti-infective drugs which are added to existing multi-medication. To minimize these potential risks, this issue should receive increased attention in making decisions about anti-inf<TextGroup><PlainText>ec</PlainText></TextGroup>tive drug treatment.</Pgraph><Pgraph>The treatment of elderly patients with a bacterial infectious disease therefore typically means adding a further substance, an antibiotic, to a long list of different medications with a partially unclear potential for interactions and various ADRs, which may themselves have their own side effects as well as their own potential for interactions.</Pgraph><Pgraph>This can then quickly lead to situations requiring treatment and that are sometimes life-threatening <TextLink reference="36"></TextLink>.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Antibiotika-Verordnungen f&#252;r alte Patienten"> <MainHeadline>Antibiotika-Verordnungen f&#252;r alte Patienten</MainHeadline><Pgraph>Die Bewertung der verschiedenen Antibiotika-Klassen (bzw. einzelner Substanzen daraus) erfolgt nach spezifischen dem Alter des Patienten angepassten Aspekten und Risiken (siehe Tabelle 3 <ImgLink imgNo="3" imgType="table"/>).</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Antibiotic prescriptions for elderly patients"> <MainHeadline>Antibiotic prescriptions for elderly patients</MainHeadline><Pgraph>The assessment of the different classes of antibiotics (or individual substances thereof) is based on specific aspects and risks adapted to the age of the patient (see Table 3 <ImgLink imgNo="3" imgType="table"/>).</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Beurteilung der Nierenfunktion im Alter"> <MainHeadline>Beurteilung der Nierenfunktion im Alter</MainHeadline><Pgraph>Die Ver&#228;nderung der renalen Eliminationsfunktion stellt die klinisch bedeutsamste Ver&#228;nderung einer K&#246;rperfunktion im Hinblick auf die Auswirkungen auf die Pharmakokinetik von Arzneistoffen dar und tritt mit h&#246;herem Alter zwangsl&#228;ufig auf <TextLink reference="37"></TextLink>. Der durchschnittliche renale Blutfluss verringert sich um etwa 10&#37; pro Alters-Dekade von 600 ml&#47;min pro 1,73 m<Superscript>2</Superscript> in der 4. Dekade auf etwa <TextGroup><PlainText>300 ml</PlainText></TextGroup>&#47;min pro 1,73 m<Superscript>2</Superscript> in der 9. Dekade. Parallel dazu verringert sich die glomerul&#228;re Filtrationsrate um rund 10&#37; pro Dekade. Da gleichzeitig die Kreatinin-Produktion in Abh&#228;ngigkeit vom progredienten Verlust an Muskelmasse im Alter sinkt, bleibt der Serum-Kreatinin-Spiegel konstant. Kreatinin-Spiegel im oberen Normbereich weisen daher auf eine bereits bestehende Nierenfunktionseinschr&#228;nkung hin. Ein Anstieg des Serum-Kreatinin ist bei der Entscheidung &#252;ber Antibiotika-Dosierungen besonders kritisch zu ber&#252;cksichtigen. Viele Labore geben die glomerul&#228;re Filtrationsrate (GFR) auf der Basis einer Berechnung nach der MDRD-Formel (MDRD&#61;Modification of Diet in Renal Disease Study) an. Diese Formel wurde im Rahmen der MDRD-Studie allerdings nicht bei Personen &#252;ber 70 Jahre validiert. Auch die alternative Formel nach Cockcroft-Gault zeigt erhebliche Limitationen der GFR-Berechnung in Abh&#228;ngigkeit vom Alter und bei gro&#223;en Abweichungen des K&#246;rpergewichtes auf. In vergleichenden Untersuchungen zeigten die GFR-Absch&#228;tzungen auf der Basis eines 24-Stunden-Sammelurins die besten Resultate, wenn auch mit einer Tendenz zur &#220;bersch&#228;tzung. In der Praxis bestehen jedoch erhebliche Einschr&#228;nkungen der Methode durch Sammelfehler. Eine weitere Alternative ist die Cystatin-C-Bestimmung, die sich durch Unabh&#228;ngigkeit von Alter und Muskelmasse auszeichnet <TextLink reference="38"></TextLink>, wobei auch dieser Parameter kontrovers diskutiert wird <TextLink reference="39"></TextLink>. Am zuverl&#228;ssigsten scheint diese Methode im Bereich einer beginnenden Nierenfunktionseinschr&#228;nkung zu sein, bei der sich noch keine Erh&#246;hungen des Kreatinins zeigen. Insgesamt weisen s&#228;mtliche Bestimmungsmethoden der Nierenfunktion bei alten Menschen deutliche Limitationen auf. Eine &#220;bersch&#228;tzung der glomerul&#228;ren Filtrationsrate sollte deshalb durch einen zur&#252;ckhaltenden Gebrauch potenziell nephrotoxischer Substanzen kompensiert werden <TextLink reference="40"></TextLink>.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Assessment of renal function in old age"> <MainHeadline>Assessment of renal function in old age</MainHeadline><Pgraph>Changes to renal elimination represent the most clinically significant change in body function in terms of pharmacokinetic effects on drugs and is inevitably associated with increasing age <TextLink reference="37"></TextLink>. The average renal blood flow decreases by about 10&#37; per decade of age from <TextGroup><PlainText>600 m</PlainText></TextGroup>l&#47;min per 1.73 m<Superscript>2</Superscript> in the 4th decade to about <TextGroup><PlainText>300 m</PlainText></TextGroup>l&#47;min per 1.73 m<Superscript>2</Superscript> in the 9<Superscript>th</Superscript> decade. At the same time, the glomerular filtration rate decreases by about 10&#37; per decade. At the same time, as creatinine production decreases with age as a result of the progressive loss of muscle mass, the serum creatinine level remains constant. Creatinine levels in the upper normal range therefore indicate an already existing restriction of kidney function. An increase in serum creatinine should be given special consideration when determining antibiotic dosages. Many labs report the Glomerular Filtration Rate (GFR) based on calculation using the MDRD (Modification of Diet in Renal Disease Study) formula. However, this formula was not validated in the MDRD study regarding people over the age of 70. The alternative formula according to Cockcroft-Gault shows significant limitations of the GFR calculation depending on the age and large variances of the body weight. In comparative studies, GFR estimates based on a 24-hour composite urine sample showed the best results, albeit with a tendency to overestimate. In practice, however, there are significant limitations of the method due to collection errors. Another alternative is the determination of cystatin C, which is characterized by independence from age and muscle mass <TextLink reference="38"></TextLink>, although discussion of this parameter is also controversial <TextLink reference="39"></TextLink>. This method seems to be most reliable in cases of incipient kidney function restriction where there is still no increase in creatinine. Overall, all methods of determining renal function in the elderly have clear limitations. An overestimation of the glomerular filtration rate should therefore be compensated for by a cautious use of potentially nephrotoxic substances <TextLink reference="40"></TextLink>.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Antibiotika-Resistenzen im Alter"> <MainHeadline>Antibiotika-Resistenzen im Alter</MainHeadline><Pgraph>S&#228;mtliche Faktoren, die mit dem Risiko von Besiedlung oder Infektion durch multiresistente Erreger assoziiert sind, gewinnen im Alter eine zunehmende Bedeutung. Multimorbidit&#228;t und spezifische Komorbidit&#228;ten wie Diabetes mellitus oder COPD, antimikrobielle Vortherapien, vorbestehende Krankenhausaufenthalte, Versorgung in Pflegeheimen, Rehabilitationseinrichtungen und sonstige<TextGroup><PlainText>n t</PlainText></TextGroup>erti&#228;ren Versorgungsstrukturen, Tr&#228;ger invasiver <TextGroup><PlainText>&#8222;devices&#8220;</PlainText></TextGroup> wie enterale Ern&#228;hrungssonden, zentrale Venenver<TextGroup><PlainText>w</PlainText></TextGroup>eilkatheter, Trachealkan&#252;len und Harnwegska<TextGroup><PlainText>t</PlainText></TextGroup>heter, andere ambulante nosokomiale Risiken wie Dialyse, Versorgung chronischer Ulzera oder sonstige Pflegebe<TextGroup><PlainText>d</PlainText></TextGroup>&#252;rftigkeit und vorbestehende Kolonisation kumulieren mit steigendem Alter. Erwartungsgem&#228;&#223; treten bei Bewohnern von Pflegeheimen in Abh&#228;ngigkeit ihrer Funktionseinschr&#228;nkungen vermehrt resistente Erreger auf <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>. Das Risiko f&#252;r Multiresistenz stellt im Falle einer Infektion besondere Anforderungen an die Verordnung einer ad&#228;quaten Antibiotika-Therapie, sei es durch die Wahl eines geeigneten Breitspektrum-Antibiotikums oder durch eine geeignete Kombinationsstrategie. Bei einer inad&#228;quate<TextGroup><PlainText>n T</PlainText></TextGroup>herapie besteht die Gefahr eines verl&#228;ngerten Krankenhausaufenthaltes, von erh&#246;hten Kosten und im schlimmsten Fall einer erh&#246;hten Krankenhausletalit&#228;t <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink>. Das Multiresistenzrisiko muss individuell erfasst werden, eine pauschale Annahme eines altersbe<TextGroup><PlainText>d</PlainText></TextGroup>ingt erh&#246;hten MRE-Risikos ohne W&#252;rdigung der individuellen Risikofaktoren f&#252;hrt zu inad&#228;quater &#220;bertherapie mit Breitspektrum-Antibiotika.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Antibiotic resistance in old age"> <MainHeadline>Antibiotic resistance in old age</MainHeadline><Pgraph>All factors associated with the risk of colonization or infection by multidrug-resistant agents are becoming increasingly important in old age. Multimorbidity and specific comorbidities such as diabetes mellitus or COPD, previous antimicrobial treatment, prior hospital stays, being cared for in nursing homes, rehabilitation facilities and other tertiary care structures, carriers of invasive devices such as enteral feeding tubes, central venous indwelling catheters, tracheostomy and urinary catheters, other out-patient nosocomial risks such as dialysis, chronic ulcers or other long-term care and pre-existing colonization accumulate with increasing age. As expected, residents of nursing homes show an increased incidence of resistant pathogens, depending on their functional limitations <TextLink reference="41"></TextLink>, <TextLink reference="42"></TextLink>. The risk of multidrug resistance in the case of an infection poses special requirements for the prescription of adequate antibiotic treatment, be it through the selection of a suitable broad-spectrum antibiotic or through a suitable combination strategy. With inadequate treatment, there is a risk of prolonged hospitalization, increased costs and, in the worst case, increased hospital mortality <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink>. The risk of multidrug resistance has to be assessed individually, a general assumption of an age-related increased risk of MRE without appreciation of the individual risk factors leads to inadequate over-treatment with broad-spectrum antibiotics.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Schlussfolgerung"> <MainHeadline>Schlussfolgerung</MainHeadline><Pgraph>Grunds&#228;tzlich kann der Einsatz von Antibiotika bei &#228;lteren Patienten nach den gleichen Prinzipien wie bei j&#252;ngeren erfolgen. Es gibt kein Antibiotikum, welches grunds&#228;tzlich als inad&#228;quat f&#252;r &#228;ltere Menschen angesehen werden muss.</Pgraph><Pgraph>Die Auswahl und die Dosierung von Antibiotika m&#252;ssen allerdings den generellen medizinischen Problemen des hohen Alters in Verbindung mit den physiologischen Ver&#228;nderungen angepasst werden. Dabei spielt das in den letzten Jahren gestiegene Risiko durch resistente und multiresistente Infektionserreger im Kontext multipler Krankenhausaufenthalte und antibiotischer Vortherapien eine zunehmende Rolle.</Pgraph><Pgraph>Aufgrund des h&#228;ufigeren Auftretens und der potenziell gravierenden Konsequenzen von Antibiotika-Nebenwirkungen (unerw&#252;nschte Arzneimittelwirkungen, UAW) bei &#228;lteren im Vergleich zu j&#252;ngeren Patienten sind folgende Schritte zur Optimierung essentiell: Strenge Entscheidung &#252;ber die Indikation an sich, Wahl des besten Antibiotikums auch unter Ber&#252;cksichtigung seltener, daf&#252;r aber im Alter bedrohlicher Nebenwirkungen, Festlegung der richtigen Dosis, des Dosierungsintervalls und der k&#252;rzest m&#246;glichen Dauer entsprechend dem physiologischen Status des Patienten sowie Monitoring von Effektivit&#228;t und Toxizit&#228;t zur fr&#252;hen Erkennung erwarteter und unerwarteter Nebenwirkungen. Geriatrische Patienten sind durch die ihnen eigene Frailty, also das Syndrom der Gebrechlichkeit, in hohem Ma&#223;e gef&#228;hrdet, einen komplikationsreichen Verlauf mit einer erschwerten Rekonvaleszenz und einer h&#246;heren Mortalit&#228;t zu erleiden <TextLink reference="45"></TextLink>. Daher m&#252;ssen Empfehlungen die besonderen Bedingungen der antibiotischen Therapie bei alten Patienten reflektieren.</Pgraph></TextBlock> <TextBlock language="en" linked="yes" name="Summary"> <MainHeadline>Summary</MainHeadline><Pgraph>In principle, the use of antibiotics in elderly patients can be based on the same principles as for younger people. There is no antibiotic which in principle must be regarded as inadequate for older people.</Pgraph><Pgraph>However, the choice and dosage of antibiotics must be adjusted to the general medical problems of old age in conjunction with the physiological changes. The increased risk of resistant and multi-drug resistant infectious pathogens as a result of multiple hospital stays and prior antibiotic treatment has become an increasingly prominent issue in recent years.</Pgraph><Pgraph>Due to the more frequent and potentially serious consequences of antibiotic side effects (adverse drug reactions, ADRs) in older compared to younger patients, the following steps for optimization are essential: Strict decision regarding the indication itself, choice of the best antibiotic even considering rare side effects which may be dangerous in the elderly, determining the correct dose, dosing interval and the shortest possible duration according to the physiological status of the patient as well as monitoring effectiveness and toxicity detect expected and unexpected side effects early. In geriatric patients their frailty carries a great risk of developing a complicated progression with more difficult convalescence and higher mortality <TextLink reference="45"></TextLink>. Therefore, recommendations must reflect the peculiarities of antibiotic treatment in elderly patients.</Pgraph></TextBlock> <TextBlock language="de" linked="yes" name="Anmerkung"> <MainHeadline>Anmerkung</MainHeadline><Pgraph>Dies ist das f&#252;nfzehnte 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 fifteenth 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>Tesch-R&#246;mer C</RefAuthor> <RefAuthor>Engstler H</RefAuthor> <RefAuthor>Wurm S</RefAuthor> <RefTitle></RefTitle> <RefYear>2006</RefYear> <RefBookTitle>Altwerden in Deutschland</RefBookTitle> <RefPage></RefPage> <RefTotal>Tesch-R&#246;mer C, Engstler H, Wurm S. Altwerden in Deutschland. Wiesbaden: VS Verlag f&#252;r Sozialwissenschaften; 2006. 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Dtsch Med Wochenschr. 2007;112(2):1-4.</RefTotal> </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: Definition des geriatrischen Patienten &#91;46&#93;</Mark1></Pgraph></Caption> <Caption language="en"><Pgraph><Mark1>Table 1: Definition of the geriatric patient &#91;46&#93;</Mark1></Pgraph></Caption> </Table> <Table format="png"> <MediaNo>2</MediaNo> <MediaID language="de">2de</MediaID> <MediaID language="en">2en</MediaID> <Caption language="de"><Pgraph><Mark1>Tabelle 2: Pharmakokinetik und physiologisches Altern</Mark1></Pgraph></Caption> <Caption language="en"><Pgraph><Mark1>Table 2: Pharmacokinetics and physiological aging</Mark1></Pgraph></Caption> </Table> <Table format="png"> <MediaNo>3</MediaNo> <MediaID language="de">3de</MediaID> <MediaID language="en">3en</MediaID> <Caption language="de"><Pgraph><Mark1>Tabelle 3: Bewertung der einzelnen Antibiotikaklassen bzw. einzelner Substanzen daraus nach Nebenwirkungen und Interaktionsrisiken im Alter</Mark1></Pgraph></Caption> <Caption language="en"><Pgraph><Mark1>Table 3: Evaluation of the individual antibiotic classes or individual substances according to side effects and risk of interactions in elderly patients</Mark1></Pgraph></Caption> </Table> <NoOfTables>3</NoOfTables> </Tables> <Figures> <NoOfPictures>0</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>