Aktuelle Entwicklungen im Bereich Antibiotic Stewardship

Was ist neu?

Antibiotikaverbrauch in Deutschland In Deutschland wurden in den letzten Jahren sowohl im Krankenhausbereich als auch im ambulanten Setting immer weniger Fluorchinolone verordnet. Auch der Verbrauch der Cephalosporine ging etwas zurück.

Renaissance von Aminoglykosiden? Die inzwischen relativ seltenen Substanzen können aufgrund einer recht guten Resistenzlage bei Harnwegsinfektionen als geeignete Alternative – allerdings nur parenteral – eingesetzt werden. Bei akuten schweren Infektionen ist eine einmalige Gabe, z. B. von Tobramycin, initial zusätzlich zu einem geeigneten Betalactam ebenfalls eine Option, aber keine klare Empfehlung.

Antibiotikaeinsatz in der Hämatologie/Onkologie Bei Fieber und Neutropenie gilt nach wie vor die initiale empirische Gabe von Piperacillin-Tazobactam oder einem pseudomonasaktiven Carbapenem als Standard. Diese Betalactame sollten mit verlängerter Infusionsdauer, z. B. über 4 h, verabreicht werden. Linezolid ist ein Reservemedikament und sollte auch bei hämatoonkologischen Patienten nicht empirisch, sondern nur in der gezielten Therapie verwendet werden.

Penicillinallergie Die anamnestische Angabe einer Penicillinallergie sollte durch genaues Hinterfragen differenziert werden. Patienten können so bezüglich ihres Risikos für allergische Reaktionen gruppiert werden – oft besteht kein oder ein sehr geringes Risiko bei einer (erneuten) Behandlung mit Penicillinderivaten. Niedrigrisikopatienten dürfen ohne weitergehende allergologische Untersuchungen reexponiert werden.

Abstract

Both in hospitals and outpatient settings, fewer fluoroquinolones have been prescribed in Germany in recent years. The consumption of cephalosporins also decreased somewhat in favor of penicillin derivatives. The aminoglycosides, which have only rarely been prescribed, can now be used again as a suitable alternative – but only parenterally – due to their relatively favorable activity and low resistance rates among typical urinary tract infection pathogens. In acute severe infection such as sepsis, addition, e. g. of tobramycin, to a suitable betalactam of a single dose has been discussed as a useful option, but the evidence for such a recommendation is weak. There is little news about the rational use of antibiotics in hematology-oncology patients. In the case of fever and neutropenia, the initial empirical regimens of choice remain piperacillin-tazobactam or a pseudomonas-active carbapenem as monotherapy. These betalactams should be given with extended infusion times, e. g. over 4 hours. Linezolid should be considered as a reserve drug and not be used empirically, but only in targeted therapy. With regard to an alleged penicillin allergy, the risk of true allergic reactions can be differentiated by careful taking of the history; on that ground patient subgroups can be defined that may be re-exposed without further allergological examinations.

Schlüsselwörter

Antiinfektiva - Antibiotikaverbrauch - Hämatologie-Onkologie - Penicillinallergie - Neutropenie

Key words

antiinfective agents - antibiotic consumption - hematology-oncology - penicillin allergy - neutropenia

Publication History

Article published online:
30 November 2020

• Literatur

• 1 ADKA-if-DGI Antiinfektiva Surveillance. 10. Krankenhausvergleichsreport 2017/2018. http://www.antiinfektiva-surveillance.de/files/kvr_2017_2018_pub_080720_openaccess.pdf . Stand: 13.10.2020
• 2 Kern WV, Steib-Bauert M, Först G. et al Antibiotic prescribing in German acute care hospitals: current national estimates and trend of decreasing consumption of cephalosporins and fluoroquinolones between 2013 and 2017. Amsterdam: ECCMID; 2019 abstract P2040 (Stand: 13.10.2020). https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=68727
• 3 European Centre for Disease Prevention and Control. Antimicrobial consumption in the EU/EEA, annual epidemiological report for 2018. Stockholm: ECDC; 2019 https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-consumption-europe-2018 . Stand: 13.10.2020
• 4 Robert Koch-Institut. Antibiotika Resistenz Surveillance: Resistenzübersicht. https://ars.rki.de/Content/Database/ResistanceOverview.aspx . Stand: 13.10.2020
• 5 Goodlet KJ, Benhalima FZ, Nailor MD. A systematic review of single-dose aminoglycoside therapy for urinary tract infection: is it time to resurrect an old strategy?. Antimicrob Agents Chemother 2018; 63: e02165-18
• 6 Tamma PD, Aitken SL, Bonomo RA. et al Infectious Diseases Society of America guidance on the treatment of antimicrobial resistant Gram-negative infections. https://www.idsociety.org/globalassets/idsa/practice-guidelines/amr-guidance/idsa-amr-guidance.pdf . Stand: 13.10.2020
• 7 Prytz KL, Prag M, Fredlund H. et al. Antibiotic treatment with one single dose of gentamicin at admittance in addition to a β-lactam antibiotic in the treatment of community-acquired bloodstream infection with sepsis. PLoS One 2020; 15: e0236864
• 8 Ritchie ND, Irvine SC, Helps A. et al. Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection. QJM 2017; 110: 155-161
• 9 Ong DSY, Frencken JF, Klein Klouwenberg PMC. et al. Short-course adjunctive gentamicin as empirical therapy in patients with severe sepsis and septic shock: a prospective observational cohort study. Clin Infect Dis 2017; 64: 1731-1736
• 10 Deelen JWT, Rottier WC, Buiting AGM. et al. Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection, a cohort study. Clin Microbiol Infect 2020; S1198-743X(20)30269-X DOI: 10.1016/j.cmi.2020.04.041.
• 11 Heffernan AJ, Sime FB, Sun J. et al. β-lactam antibiotic versus combined β-lactam antibiotics and single daily dosing regimens of aminoglycosides for treating serious infections: a meta-analysis. Int J Antimicrob Agents 2020; 55: 105839
• 12 René L, Rello J, Silvio TF. et al. Aminoglycosides in immunocompromised critically ill patients with bacterial pneumonia and septic shock: a post-hoc analysis of a prospective multicenter multinational cohort. Shock 2020; DOI: 10.1097/SHK.0000000000001553.
• 13 Liljedahl Prytz K, Prag M, Fredlund H. et al. Antibiotic treatment with one single dose of gentamicin at admittance in addition to a β-lactam antibiotic in the treatment of community-acquired bloodstream infection with sepsis. PLoS One 2020; 15: e0236864
• 14 Heinz WJ, Buchheidt D, Christopeit M. et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol 2017; 96: 1775-1792
• 15 Aynioglu A, Mutlu B, Hacihanefioglu A. A comparison of the efficacy of piperacillin-tazobactam and cefoperazone-sulbactam therapies in the empirical treatment of patients with febrile neutropenia. Rev Esp Quimioter 2016; 29: 69-75
• 16 Ponraj M, Dubashi B, Harish BH. et al. Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia. Support Care Cancer 2018; 26: 3899-3908
• 17 Horita N, Shibata Y, Watanabe H. et al. Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: systematic review and network meta-analysis. Clin Microbiol Infect 2017; 23: 723-729
• 18 Torfoss D, Fladhagen T, Holte H. et al. Benzylpenicillin plus an aminoglycoside versus meropenem in neutropenic lymphoma and leukaemia patients with a suspected bacterial infection: a randomized, controlled trial. Clin Microbiol Infect 2017; 23: 179-187
• 19 Ram R, Halavy Y, Amit O. et al. Extended vs bolus infusion of broad-spectrum β-lactams for febrile neutropenia: an unblinded, randomized trial. Clin Infect Dis 2018; 67: 1153-1160
• 20 Lisboa LF, Miranda BG, Vieira MB. et al. Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant Enterococcus spp. Int J Infect Dis 2015; 33: 171-176
• 21 Kamboj M, Cohen N, Huang YT. et al. Impact of empiric treatment for vancomycin-resistant Enterococcus in colonized patients early after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2019; 25: 594-598
• 22 Wurpts G, Aberer W, Dickel H. et al. S2k-Leitlinie: Diagnostik bei Verdacht auf eine Betalaktamantibiotika-Überempfindlichkeit. Leitlinie der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) in Zusammenarbeit mit dem Ärzteverband Deutscher Allergologen (AeDA), der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), der Deutschen Kontaktallergiegruppe (DKG), der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI) und der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG). Allergo J Int 2019; 28: 121-151
• 23 Shenoy ES, Macy E, Rowe T. et al. Evaluation and management of penicillin allergy: a review. JAMA 2019; 321: 188-199
• 24 Stone CA, Trubiano J, Coleman DT. et al. The challenge of de-labeling penicillin allergy. Allergy 2020; 75: 273-289
• 25 Blumenthal KG, Kuper K, Schulz LT. et al. Association between penicillin allergy documentation and antibiotic use. JAMA Intern Med 2020; 180: 1120-1122
• 26 Blumenthal KG, Oreskovic NM, Fu X. et al. High-cost, high-need patients: the impact of reported penicillin allergy. Am J Manag Care 2020; 26: 154-161
• 27 Chua KYL, Vogrin S, Bury S. et al. The Penicillin Allergy Delabeling Program: a multicenter whole-of-hospital health services intervention and comparative effectiveness study. Clin Infect Dis 2020; DOI: 10.1093/cid/ciaa653.
• 28 Trubiano JA, Vogrin S, Chua KYL. et al. Development and validation of a penicillin allergy clinical decision rule. JAMA Intern Med 2020; 180: 1-9
• 29 Vyles D, Antoon JW, Norton A. et al. Children with reported penicillin allergy: Public health impact and safety of delabeling. Ann Allergy Asthma Immunol 2020; 124: 558-565