Rasmus Leistner

Introduction: The World Health Organization has declared carbapenem-resistant organisms a research and development priority. Although ceftazidime–avibactam was approved around a decade ago, there is still a lack of prospective data on the treatment of resistant pathogens with this agent. Methods: We conducted a prospective, observational, single-center, investigator-initiated study of patients treated with ceftazidime–avibactam for infections caused by carbapenem-resistant organisms. The primary outcome was clinical cure 14 days after the initiation of ceftazidime-avibactam treatment. Secondary outcomes, which were assessed on day 30, included microbiological failure, development of resistance, all-cause mortality, and length of stay in the intensive care unit. Results: A total of 50 patients were included in the study. At baseline, the median Charlson Comorbidity Index and Sequential Organ Failure Assessment Score were 5.5 and 7. Approximately three-quarters of the patients were treated in an intensive care unit and had undergone mechanical ventilation within the previous 7 days prior to the commencement of ceftazidime–avibactam treatment. Half of the patients were diagnosed with nosocomial pneumonia. Most infections were caused by Pseudomonas aeruginosa (48%) and Klebsiella pneumonia (28%). Clinical cure at day 14 was achieved in 59% of patients. Four deaths (9%) and two cases of microbiological failure (4%) were observed. The median length of stay in the intensive care unit was 14 days. There was no emergence of resistance to ceftazidime–avibactam. Discussion: Our study contributes to the growing body of evidence supporting the effectiveness of ceftazidime–avibactam in treating infections caused by carbapenem-resistant organisms. In this cohort of critically ill patients, our results in terms of both clinical success and survival are in the upper range compared to those from mainly retrospective and some prospective studies. Although the benefits of ceftazidime–avibactam have been demonstrated in this and other studies, it must be prescribed cautiously to ensure it remains effective.

Background: Carriage of multidrug-resistant organisms (MDROs) in humans constitutes an important public health concern. Cross-transmission of bacteria between animals and humans has been demonstrated before. Aim: Our aim was to quantify the risk factor ‘pet ownership’ for MDRO colonisation in hospital patients. Methods: We performed a matched case–control study from 2019 to 2022 in Berlin, Germany and compared MDRO-positive and MDRO-negative patients in terms of contact with pets and other risk factors for MDRO acquisition. Patients completed a questionnaire-based interview and provided nasal and rectal swabs. Pet owners provided swab samples from the throat and stool of their pets (dogs and cats). Phenotypically matching samples of owners and pets were analysed via whole genome sequencing. Results: The analyses included 2,891 patients. Reported pet ownership was 17.7% in MDRO-positives (154/871) and 23.4% in MDRO-negatives (472/2,020). Among 397 owner–pet pairs, we identified one pair sharing genotypically indistinguishable pathogens (0.3%). A risk factor analysis of pet ownership was performed for carriers of meticillin-resistant Staphylococcus aureus (MRSA) (OR = 0.662; 95% CI: 0.343–1.277), vancomycin-resistant enterococci (VRE) (OR = 0.764; 95% CI: 0.522–1.118) and multidrug-resistant Gram-negative bacteria (MDR-GNB) (OR = 0.819; 95% CI: 0.620–1.082). Colonisation with MDRO was rare in pets, and dogs were more often colonised than cats (MRSA: 0% vs 0%, VRE: 1.5% vs 1.0%, MDR-GNB: 17.2% vs 3.6%). Conclusion: Transmission of MDROs between humans and pets is possible though rare. In an urban living space, neither cat nor dog ownership appears as a relevant risk factor for MDRO carriage in hospital patients.

Background: The COVID-19 pandemic posed significant challenges to global health systems. Efficient public health responses required a rapid and secure collection of health data to improve the understanding of SARS-CoV-2 and examine the vaccine effectiveness (VE) and drug safety of the novel COVID-19 vaccines. Objective: This study (COVID-19 study on vaccinated and unvaccinated subjects over 16 years; eCOV study) aims to (1) evaluate the real-world effectiveness of COVID-19 vaccines through a digital participatory surveillance tool and (2) assess the potential of self-reported data for monitoring key parameters of the COVID-19 pandemic in Germany. Methods: Using a digital study web application, we collected self-reported data between May 1, 2021, and August 1, 2022, to assess VE, test positivity rates, COVID-19 incidence rates, and adverse events after COVID-19 vaccination. Our primary outcome measure was the VE of SARS-CoV-2 vaccines against laboratory-confirmed SARS-CoV-2 infection. The secondary outcome measures included VE against hospitalization and across different SARS-CoV-2 variants, adverse events after vaccination, and symptoms during infection. Logistic regression models adjusted for confounders were used to estimate VE 4 to 48 weeks after the primary vaccination series and after third-dose vaccination. Unvaccinated participants were compared with age- and gender-matched participants who had received 2 doses of BNT162b2 (Pfizer-BioNTech) and those who had received 3 doses of BNT162b2 and were not infected before the last vaccination. To assess the potential of self-reported digital data, the data were compared with official data from public health authorities. Results: We enrolled 10,077 participants (aged ≥16 y) who contributed 44,786 tests and 5530 symptoms. In this young, primarily female, and digital-literate cohort, VE against infections of any severity waned from 91.2% (95% CI 70.4%-97.4%) at week 4 to 37.2% (95% CI 23.5%-48.5%) at week 48 after the second dose of BNT162b2. A third dose of BNT162b2 increased VE to 67.6% (95% CI 50.3%-78.8%) after 4 weeks. The low number of reported hospitalizations limited our ability to calculate VE against hospitalization. Adverse events after vaccination were consistent with previously published research. Seven-day incidences and test positivity rates reflected the course of the pandemic in Germany when compared with official numbers from the national infectious disease surveillance system. Conclusions: Our data indicate that COVID-19 vaccinations are safe and effective, and third-dose vaccinations partially restore protection against SARS-CoV-2 infection. The study showcased the successful use of a digital study web application for COVID-19 surveillance and continuous monitoring of VE in Germany, highlighting its potential to accelerate public health decision-making. Addressing biases in digital data collection is vital to ensure the accuracy and reliability of digital solutions as public health tools.

Die Umgebungsreinigung im Krankenhaus ist neben der Händehygiene eine wichtige Säule für die Prävention nosokomialer Infektionen und multiresistenter Erreger. Die weit verbreitete Verwendung von Antiseptika und Desinfektionsmitteln wird mit einer gesteigerten Toleranz klinischer Isolate gegenüber diesen Substanzen, der Entwicklung von Kreuzresistenzen mit Antibiotika und anderen potenziell schädlichen Auswirkungen auf Gesundheit und Umwelt in Verbindung gebracht. Insbesondere können die derzeit häufig verwendeten chemischen Desinfektionsmittel wie Glucoprotamin, Aldehyde und quaternäre Ammoniumverbindungen toxische Phenol- und Aldehyddämpfe bilden, die für die Gesundheit und die Umwelt problematisch sind. Daher sind alternative Technologien gefragt, um die Palette der derzeit verfügbaren Desinfektionsmittel zu ergänzen. Idealerweise sollten sie natürlich mindestens ebenso wirksam, aber weniger schädlich für die Umwelt und das Wohlbefinden der Beschäftigten im Gesundheitswesen sein. Probiotische Reinigungsprodukte sind eine neue Art der Reinigungsmittel für Oberflächen im Gesundheitswesen. Sie enthalten gesundheitsfördernde, sogenannte probiotische Mikroorganismen, wie z.B. Bazillus-, Lactobazillus- oder Bifidobakterien-Arten. Damit stellen sie eine potentiell nachhaltigere und biologisch abbaubare Alternative zu herkömmlichen chemischen Desinfektionsmitteln dar. Im Jahr 2022 veröffentlichte das Robert-Koch-Institut (RKI) neue Empfehlungen zur Reinigung und Desinfektion von Oberflächen im Krankenhaus [1]. Die Verwendung von probiotischen Reinigungsmitteln in Krankenhäusern wurde damals noch nicht empfohlen, da die vorhandene Evidenz zu diesem Zeitpunkt nicht ausreichte, allerdings wurden probiotische Reinigungsmittel als zukunftsweisende Technologie erwähnt. Herkömmliche Desinfektionsmittel wirken nicht selektiv, indem sie alle Mikroorganismen auf Krankenhausoberflächen reduzieren. Bei der Neubesiedlung nach der Desinfektion können unerwünschte Mikroorganismen wie Krankheitserreger von einem geringeren Konkurrenzdruck um Ressourcen im Lebensraum profitieren und sich schnell wieder ansiedeln. Im Gegensatz dazu beruht die Wirkungsweise der Probiotika auf dem Prinzip des kompetetiven Ausschlusses (competitive exclusion). Probiotische Mikroorganismen, welche die Krankenhausumgebung besiedeln, konkurrieren mit potenziellen Krankheitserregern um Nährstoffe und Lebensraum. Einige probiotische Bakterien können sogar sekundäre Metaboliten absondern, die ihnen einen Überlebensvorteil verschaffen. Darüber hinaus sind einige probiotische Arten in der Lage, Pathogene an der Bildung von Biofilmen zu hindern, indem sie die Adhäsion und Koaggregation von Pathogenen verringern, den Zellstoffwechsel stören und/oder die Kommunikation der Pathogene untereinander, das sog. Quorum Sensing, beeinträchtigen. Somit bietet die probiotische Reinigung eine umweltfreundliche und wirksame Methode zur Aufrechterhaltung von Sauberkeit und Hygiene in verschiedenen Bereichen des Gesundheitswesens, indem sie sich den natürlichen Wettbewerb zwischen nützlichen Bakterien und schädlichen Krankheitserregern zunutze macht. An der Charité wurden zwei Versuche mit probiotischen Reinigungsmitteln durchgeführt. In der ersten Studie wurde eine neurologische Station abwechselnd mit einem probiotischen Reinigungsmittel, einem herkömmlichen Oberflächenreiniger auf Seifenbasis und einem Desinfektionsmittel gereinigt [2]. Die Analyse des Krankenhausmikrobioms zeigte eine signifikant höhere biologische Vielfalt in Zusammenhang mit der probiotischen Reinigung. Außerdem verringerte das probiotische Reinigungsprodukt im Vergleich zur chemischen Desinfektion das Auftreten von Pseudomonas spp. in Umweltproben. Darüber hinaus zeigte die Studie auch eine Verringerung antimikrobieller Resistenzgene in Umweltproben nach der Reinigung mit Probiotika im Vergleich zu chemischen Desinfektionsmitteln. Die zweite Studie konzentrierte sich auf die Frage, ob die verschiedenen Strategien bei der Reinigung der Krankenhausumgebung auch Auswirkungen auf die Raten nosokomialer Infektionen haben können [3]. Diese Frage wurde in einer randomisierten, Cluster-kontrollierten Studie mit Crossover-Design untersucht. Die Studie wurde auf insgesamt 18 Normalstationen durchgeführt. Desinfektionsmittel, seifenbasierte Reinigungsmittel und Probiotika waren in Bezug auf die Prävention von nosokomialen Infektionen und dem Aufkommen multiresistenter Bakterien vergleichbar wirksam. Die routinemäßige und weit verbreitete Anwendung von probiotischen Reinigungsmitteln in Krankenhäusern erfordert allerdings Vorschriften, Sicherheitsstandards und Qualitätskontrollen, die von Behörden festgelegt, befolgt und überwacht werden müssen, um die Patientensicherheit zu gewährleisten. Die Europäische Union hat sich bereits mit Produkten befasst, die Mikroorganismen – wie beispielsweise Probiotika – enthalten. Darin legen die Autoren fest, dass jegliche Mikroorganismen, die Detergenzien absichtlich zugesetzt werden, genau definiert sein müssen. Das bedeutet, diese Mikroorganismen müssen eine ATCC-Nummer (American Type Culture Collection) haben, in einer offiziell anerkannten internationalen Bakteriensammlung hinterlegt sein (International Depository Authority [IDA]) oder durch Sequenzierung der 16S ribosomalen DNA bzw. vergleichbare geeignete Methoden genau identifiziert und öffentlich zugänglich sein. Solche Vorschriften und ihre Einhaltung sind auch auf nationaler Ebene erforderlich, um die Patientensicherheit zu gewährleisten. Die probiotische Reinigung ist eine vielversprechende und innovative Technologie für die Umgebungsreinigung im...

Introduction: The COVID-19 pandemic challenged health systems worldwide to collect data broadly, rapidly, and safely to better understand the virus and respond dynamically to new developments. As new variants require new vaccines, adaptive and scalable study solutions were needed to test...

Background: The antiseptic agent octenidine dihydrochloride (OCT) is used for skin preparation, for Staphylococcus aureus decolonization, and within bundles for the prevention of catheter-related or surgical site infections (SSIs). Here, we review the evidence for the effects of OCT from clinical studies. Methods: Review of studies published in the Medline, Scopus, and Cochrane databases until August 2022, performed in clinical settings and reporting on effects of OCT on S. aureus carriage/transmission, SSI prevention, and prevention of intensive care unit (ICU)-related or catheter-related bloodstream and insertion site infections. Results: We included 31 articles. The success of S. aureus decolonization with OCT-containing therapies ranged between 6 and 87%. Single studies demonstrated that OCT application led to a reduction in S. aureus infections, acquisition, and carriage. No study compared OCT for skin preparation before surgical interventions to other antiseptics. Weak evidence for the use of OCT for pre-operative washing was found in orthopedic and cardiac surgery, if combined with other topical measures. Mostly, studies did not demonstrate that daily OCT bathing reduced ICU-/catheter-related bloodstream infections with one exception. Conclusions: There is a need to perform studies assessing the clinical use of OCT compared with other antiseptics with respect to its effectiveness to prevent nosocomial infections.

BACKGROUND The COVID-19 pandemic posed significant challenges to global health systems. Efficient public health responses required a rapid and secure collection of health data to improve the understanding of SARS-CoV-2 and examine the vaccine effectiveness (VE) and drug safety of the novel COVID-19 vaccines. OBJECTIVE This study (COVID-19 study on vaccinated and unvaccinated subjects over 16 years; eCOV study) aims to (1) evaluate the real-world effectiveness of COVID-19 vaccines through a digital participatory surveillance tool and (2) assess the potential of self-reported data for monitoring key parameters of the COVID-19 pandemic in Germany. METHODS Using a digital study web application, we collected self-reported data between May 1, 2021, and August 1, 2022, to assess VE, test positivity rates, COVID-19 incidence rates, and adverse events after COVID-19 vaccination. Our primary outcome measure was the VE of SARS-CoV-2 vaccines against laboratory-confirmed SARS-CoV-2 infection. The secondary outcome measures included VE against hospitalization and across different SARS-CoV-2 variants, adverse events after vaccination, and symptoms during infection. Logistic regression models adjusted for confounders were used to estimate VE 4 to 48 weeks after the primary vaccination series and after third-dose vaccination. Unvaccinated participants were compared with age- and gender-matched participants who had received 2 doses of BNT162b2 (Pfizer-BioNTech) and those who had received 3 doses of BNT162b2 and were not infected before the last vaccination. To assess the potential of self-reported digital data, the data were compared with official data from public health authorities. RESULTS We enrolled 10,077 participants (aged ≥16 y) who contributed 44,786 tests and 5530 symptoms. In this young, primarily female, and digital-literate cohort, VE against infections of any severity waned from 91.2% (95% CI 70.4%-97.4%) at week 4 to 37.2% (95% CI 23.5%-48.5%) at week 48 after the second dose of BNT162b2. A third dose of BNT162b2 increased VE to 67.6% (95% CI 50.3%-78.8%) after 4 weeks. The low number of reported hospitalizations limited our ability to calculate VE against hospitalization. Adverse events after vaccination were consistent with previously published research. Seven-day incidences and test positivity rates reflected the course of the pandemic in Germany when compared with official numbers from the national infectious disease surveillance system. CONCLUSIONS Our data indicate that COVID-19 vaccinations are safe and effective, and third-dose vaccinations partially restore protection against SARS-CoV-2 infection. The study showcased the successful use of a digital study web application for COVID-19 surveillance and continuous monitoring of VE in Germany, highlighting its potential to accelerate public health decision-making. Addressing biases in digital data collection is vital to ensure the accuracy and reliability of digital solutions as public health tools.

Mass gatherings (MGs) such as music festivals and sports events have been associated with a high risk of SARS-CoV-2 transmission. On-site research can foster knowledge of risk factors for infections and improve risk assessments and precautionary measures at future MGs. We tested a web-based participatory disease surveillance tool to detect COVID-19 infections at and after an outdoor MG by collecting self-reported COVID-19 symptoms and tests. We conducted a digital prospective observational cohort study among fully immunized attendees of a sports festival that took place from September 2 to 5, 2021 in Saxony-Anhalt, Germany. Participants used our study app to report demographic data, COVID-19 tests, symptoms, and their contact behavior. This self-reported data was used to define probable and confirmed COVID-19 cases for the full “study period” (08/12/2021 – 10/31/2021) and within the 14-day “surveillance period” during and after the MG, with the highest likelihood of an MG-related COVID-19 outbreak (09/04/2021 – 09/17/2021). A total of 2,808 of 9,242 (30.4%) event attendees participated in the study. Within the study period, 776 individual symptoms and 5,255 COVID-19 tests were reported. During the 14-day surveillance period around and after the MG, seven probable and seven PCR-confirmed COVID-19 cases were detected. The confirmed cases translated to an estimated seven-day incidence of 125 per 100,000 participants (95% CI [67.7/100,000, 223/100,000]), which was comparable to the average age-matched incidence in Germany during this time. Overall, weekly numbers of COVID-19 cases were fluctuating over the study period, with another increase at the end of the study period. COVID-19 cases attributable to the mass gathering were comparable to the Germany-wide age-matched incidence, implicating that our active participatory disease surveillance tool was able to detect MG-related infections. Further studies are needed to evaluate and apply our participatory disease surveillance tool in other mass gathering settings.