Anwendung von Antibiotika in deutschen Krankenhäusern. Qualität der Verschreibungen und Ansatzpunkte zur rationaleren Verwendung

Die Relevanz von Infektionen mit antibiotikaresistenten Bakterien stellt weltweit ein zunehmendes Problem für Patient:innen und die Humanmedizin insgesamt dar. Auch wenn in Deutschland Infektionen mit multiresistenten Erregern weiterhin eine untergeordnete Rolle im klinischen Alltag spielen, schränken Resistenzen gegen spezielle Antibiotikagruppen kalkulierte als auch gezielte Therapieregime ein. Eine effektive Strategie, um die weitere Entstehung und Ausbreitung von Resistenzen zu verlangsamen, stellt das Antimicrobial Stewardship dar. Hierbei kommen Strategien zum Einsatz, welche die rationale Anwendung antiinfektiver Therapeutika unterstützen. Die Vermeidung nicht nützlicher antimikrobieller Therapien und die bevorzugte Verschreibung von Antibiotika mit einem optimalen Wirksamkeitsspektrum führen zu einem reduzierten Selektionsdruck auf Bakterien. Darüber hinaus ergeben sich auf Ebene der individuellen Patient:innen Vorteile hinsichtlich eines höheren Therapieerfolgs sowie seltener auftretenden unerwünschten Nebenwirkungen. In der stationären Versorgung in Deutschland kann ein relevanter Anteil der Antibiotikaanwendung verbessert werden. Neben fehlender Indikation oder Notwendigkeit für eine antibiotische Anwendung kommen einer Vielzahl weiterer Faktoren eine Bedeutung bei. Die Dauer der Anwendung von Antibiotika spielt hierbei eine große Rolle. Inbesondere bei den häufig unnötig langen Therapien unkomplizierter Infektionen und Anwendungen zur Prophylaxe bei operativen Eingriffen liegen deutliche Einsparpotenziale. Auch in Bezug auf die Wahl des Wirkstoffs sind Maßnahmen notwendig, um den Stand des medizinischen Wissens besser in die klinische Anwendung einfließen zu lassen. Bestimmte Wirkstoffgruppen sind mit erhöhten Raten an unerwünschten Arzneimittelwirkungen assoziiert und sollten daher nur bei absoluter Notwendigkeit Verwendung finden. In Bezug auf Spektrum und Resistenzsituation der zu erwartenden Bakterien finden bei kalkulierten Therapieregimen breiteste Spektren Anwendung, die teilweise bei Kombinationstherapien eine doppelte Abdeckung von z.B. anaerob wachsenden Bakterien erreichen, die aus klinischer Sicht nicht notwendig ist. Infolge der limitierten Anzahl neuer antibiotischer Wirkstoffe sollte deren Anwendung indikationsspezifisch erfolgen. Hohe Kosten neuer Substanzen limitieren deren irrationale Anwendung. Reduzierte Kosten eines neuen Wirkstoffs gehen in aller Regel mit einer breiteren Verfügbarkeit einher. Dies führt zu einer vermehrten und häufig unkritischen Anwendung. Die Surveillance des Verbrauchs und der Anwendung von Antiinfektiva spielt bei der Verbesserung der Verschreibungsqualitiät und -menge eine übergeordnete Rolle. Insbesondere in speziellen Bereichen, wie der neonatologischen Intensivmedizin, die über eine langjährige Erfahrung mit der Durchführung von Surveillance und Feedback verfügt, konnten durch spezifische Angebote Verbesserungen erzielt werden. Dies unterstreicht die Bedeutung eines strukturierten und effektiven Feedbacks für den Erfolg von Surveillancemaßnahmen. Dennoch bleiben relevante Fragen offen und bedürfen weiterer Untersuchung: Was sind strukturelle Risikofaktoren die zur Erklärung von Qualitätsunterschieden in der Anwendung führen? Welche Anwendungsstrategien verlangsamen die Entwicklung antibiotischer Resistenzen im Besonderen? Welche praxistauglichen Maßnahmenbündel führen am effektivsten zu einer rationalen Anwendung antiinfektiver Substanzen? Wie lassen sich diese Strategien am effizientesten in Krankenhäusern umsetzen

Staphylococcus Aureus Bacteriuria as a Predictor of In-Hospital Mortality in Patients with Staphylococcus Aureus Bacteremia. Results of a Retrospective Cohort Study

Staphylococcus aureus bloodstream infection (SA-BSI) is an infection with increasing morbidity and mortality. Concomitant Staphylococcus aureus bacteriuria (SABU) frequently occurs in patients with SA-BSI. It is considered as either a sign of exacerbation of SA-BSI or a primary source in terms of urosepsis. The clinical implications are still under investigation. In this study, we investigated the role of SABU in patients with SA-BSI and its effect on the patients' mortality. We performed a retrospective cohort study that included all patients in our university hospital (Charité Universitätsmedizin Berlin) between 1 January 2014 and 31 March 2017. We included all patients with positive blood cultures for Staphylococcus aureus who had a urine culture 48 h before or after the first positive blood culture. We identified cases while using the microbiology database and collected additional demographic and clinical parameters, retrospectively, from patient files and charts. We conducted univariate analyses and multivariable Cox regression analysis to evaluate the risk factors for in-hospital mortality. 202 patients met the eligibility criteria. Overall, 55 patients (27.5%) died during their hospital stay. Cox regression showed SABU (OR 2.3), Pitt Bacteremia Score (OR 1.2), as well as moderate to severe liver disease (OR 2.1) to be independent risk factors for in-hospital mortality. Our data indicates that SABU in patients with concurrent SA-BSI is a prognostic marker for in-hospital death. Further studies are needed for evaluating implications for therapeutic optimization

Redundant Anaerobic Antimicrobial Prescriptions in German Acute Care Hospitals: Data from a National Point Prevalence Survey

Despite limited indications, redundant anaerobic antimicrobial prescriptions (RAAPs) are frequent. The objective of this study was to assess the prevalence and characteristics of RAAPs in German acute care hospitals. In a retrospective data analysis, antimicrobial prescriptions from a point prevalence survey on antimicrobial use in German acute care hospitals in 2016 were analyzed and RAAPs were identified. RAAPs were defined as a patient simultaneously receiving any of the following combinations: Penicillin/beta-lactamase inhibitor (PenBLI) plus clindamycin; PenBLI plus metronidazole; PenBLI plus moxifloxacin; PenBLI plus carbapenem; carbapenem plus clindamycin; carbapenem plus metronidazole; carbapenem plus moxifloxacin; clindamycin plus metronidazole; clindamycin plus moxifloxacin; and metronidazole plus moxifloxacin. Data from 64,412 patients in 218 hospitals were included. Overall, 4486 patients (7%) received two or more antimicrobials. In total, 441 RAAP combinations were identified. PenBLI plus metronidazole was the most common anaerobic combination (N = 166, 38%). The majority of RAAPs were for the treatment of community-acquired (N = 258, 59%) infections. Lower respiratory tract infections (N = 77; 20%) and skin/soft tissue infections (N = 76; 20%) were the most frequently recorded types of infections. RAAPs are common in German hospitals. Reducing redundant antimicrobial coverage should be a key component of future antimicrobial stewardship activities

Increase in consumption of alcohol-based hand rub in German acute care hospitals over a 12 year period

Background: Hand hygiene plays a crucial role in the transmission of pathogens and the prevention of healthcare-associated infections. In 2007, a voluntary national electronic surveillance tool for the documentation of consumption of alcohol-based hand rub (AHC) was introduced as a surrogate for hand hygiene compliance (HAND-KISS) and for the provision of benchmark data as feedback.The aim of the study was to determine the trend in alcohol-based hand rub consumption between 2007 and 2018. Materials and methods: In this cohort study, AHC and patient days (PD) were documented on every ward in participating hospitals by trained local staff. Data was collected and validated in HAND-KISS. Intensive care units (ICU), intermediate care units (IMC), and regular wards (RW) that provided data during the study period between 2007 until 2018 were included into the study. Results: In 2018, 75.2% of acute care hospitals in Germany (n=1.460) participated. On ICUs (n=1998) mean AHC increased 1.74 fold (95%CI 1.71, 1.76; p<.0001) from 79.2ml/PD to 137.4ml/PD. On IMCs (n=475) AHC increased 1.69 fold (95%CI 1.60, 1.79; p<.0001) from 41.4ml/PD to 70.6ml /PD..On RWs (n=14,857) AHC was 19.0ml/PD in 2007 and increased 1.71 fold (95%CI 1.70, 1.73; p<.0001) to 32.6ml/PD in 2018. Conclusions: AHC in German hospitals increased on all types of wards during the past 12years. Surveillance of AHC is widely established in German hospitals. Large differences among medical specialties exist and warrant further investigation

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis

[Background] Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered.[Methods] In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005–2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded.[Results] We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a “missed” PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%).[Conclusions] During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.Peer reviewe

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study

BACKGROUND: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. METHODS: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-upexcluded. RESULTS: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; CONCLUSIONS: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty

Building ProteomeTools based on a complete synthetic human proteome.

We describe ProteomeTools, a project building molecular and digital tools from the human proteome to facilitate biomedical research. Here we report the generation and multimodal liquid chromatography-tandem mass spectrometry analysis of \u3e330,000 synthetic tryptic peptides representing essentially all canonical human gene products, and we exemplify the utility of these data in several applications. The resource (available at http://www.proteometools.org) will be extended to \u3e1 million peptides, and all data will be shared with the community via ProteomicsDB and ProteomeXchange