Klinische Bedeutung von Infektionen durch Carbapenem-resistente Enterobakterien bei Lebertransplantierten

Zusammenfassung

Infektionen durch Carbapenem-resistente Enterobakterien (CRE) stellen aufgrund ihrer hohen Morbidität und Mortalität weltweit eine wachsende Bedrohung für Lebertransplantatempfänger (LTR) dar, v. a. bei Nachweis von Klebsiella pneumoniae Carbapenemase (KPC)-bildenden Erregern. Nach der aktuellen Literatur entwickeln 3 bis 13 % der Organtransplantierten in Endemiegebieten Infektionen durch CRE, wobei der primäre Infektionsort eng mit dem transplantierten Organ im Zusammenhang steht. Die kumulative 30-Tage-Sterblichkeit von LTR mit Infektionen durch Carbapenem-resistente K. pneumoniae liegt bei 36 %, und die 180-Tage-Mortalitätsrate beträgt 58 %. Die hohe Anfälligkeit von LTR für potenziell tödlich verlaufende bakterielle Infektionen mit multiresistenten Erregern (MRE) führt in der Praxis zu einer häufigeren empirischen Anwendung von erweiterten Breitspektrum-Antibiotikatherapien, die wiederum die Selektion extremer Resistenzen fördert. Dennoch besteht eine relevante Gefahr des Scheiterns der herkömmlichen empirischen Behandlung, da kulturbasierte Techniken zur mikrobiologischen Identifikation von CRE eine 48- bis 72-stündige Verzögerung von der Abnahme der Blutkulturen bis zur mikrobiologischen Befunderstellung mit Resistenztestung beinhalten, sodass zielgerichtete Therapien nur verzögert begonnen werden können. Dieser Teufelskreis ist schwer zu durchbrechen und führt zu einer fortwährenden Einengung der antibiotischen Behandlungsmöglichkeiten. Da die derzeit verfügbaren therapeutischen Optionen äußerst begrenzt sind, kommt der Infektionsprävention eine herausragende Bedeutung zu, v. a. in der Frühphase nach Lebertransplantation mit intensiver Immunsuppression. Die Verbesserung klinischer Behandlungsergebnisse ist eine große Herausforderung und erfordert einen mehrgliedrigen Ansatz, bei dem stringent praktizierte Hygienemaßnahmen, Screening-Tests auf MRE, zeitsparende molekularbiologische Untersuchungstechniken und Antibiotic Stewardship (ABS) kombiniert werden. Dieser Artikel stellt die aktuelle Literatur in Bezug auf die Häufigkeit und das klinische Outcome von CRE-Infektionen bei LTR vor und fasst aktuelle präventive und therapeutische Empfehlungen zusammen, um die Bedrohung durch CRE im Real-Life-Setting der klinischen Transplantationsmedizin zu minimieren.

Abstract

Infections with carbapenem-resistant Enterobacteriaceae (CRE) are an emerging cause of morbidity and mortality among liver transplant recipients (LTR) worldwide, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Approximately 3 – 13 % of solid organ transplant recipients in CRE-endemic areas develop CRE infections, and the infection site correlates with the transplanted organ. The cumulative 30-day mortality rate of LTR infected with carbapenem-resistant K. pneumoniae is 36 %, and the 180-day mortality rate is 58 %. Awareness of the high vulnerability of LTR to fatal bacterial infection leads to the more frequent use of ultrabroad-spectrum empirical antibiotic therapy, which further contributes to the selection of extreme drug resistance. Moreover, it comprises a relevant risk of failure to initiate adequate empirical treatment due to the fact that culture-based techniques used to identify CRE imply a 48- to 72-hour delay from blood culture collection until administration of the targeted therapy. This vicious circle is difficult to avoid and leads to increased clinical intricacy and narrowed antimicrobial therapeutic options. Because available options are extremely limited, infection prevention measures have gained outstanding importance, particularly in the phase after liver transplant requiring intense immunosuppression early on. Improving clinical outcomes is a major challenge and involves a multi-targeted approach combining strictly applied hygiene measures, active surveillance tests, the use of modern, time-saving methods of molecular biology, and enforced antibiotic stewardship. This article reviews the current literature regarding the incidence and outcome of CRE infections in LTR, and it summarises current preventive and therapeutic recommendations to minimise the threat by CRE in real-life clinical transplant settings.

Schlüsselwörter

Carbapenem-resistente Enterobacteriaceae (CRE) - Klebsiella pneumoniae Carbapenemase (KPC) - Lebertransplantation - Kolonisierung - Infektion - Surveillance

Key words

carbapenem-resistant Enterobacteriaceae (CRE) - Klebsiella pneumoniae carbapenemase (KPC) - liver transplantation - colonisation - infection - surveillance

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