COVID-19 Vaccine Effectiveness and Digital Pandemic Surveillance in Germany (eCOV Study): Web Application-Based Prospective Observational Cohort Study.

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.

Corticosteroids as risk factor for COVID-19-associated pulmonary aspergillosis in intensive care patients.

PURPOSE: Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. METHODS: We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. RESULTS: Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112-8.697) and SAPS (OR 1.063, CI95 1.028-1.098) to be independent risk factors for CAPA. CONCLUSION: In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA. TRIAL REGISTRATION: Registration number DRKS00024578, Date of registration March 3rd, 2021.

Participatory disease surveillance for a mass gathering - a prospective cohort study on COVID-19, Germany 2021.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Pet husbandry as a risk factor for colonization or infection with MDR organisms: a systematic meta-analysis.

BACKGROUND: MDR organisms (MDROs) pose a relevant risk for patients in modern healthcare. Although ownership of pet animals is common and owners and pets commonly live in close contact, it is still unclear whether pet ownership may be considered as a risk factor for MDRO acquisition prior to hospitalization. METHODS: We performed three separate meta-analyses in accordance with the PRISMA guidelines, assessing contact to pets as a risk factor for acquisition of MRSA, VRE and MDR Gram-negatives [namely third-generation cephalosporin-resistant Enterobacterales (3GCRE) and carbapenem-resistant Enterobacterales (CRE)]. RESULTS: We calculated an increased risk of MRSA carriage for dog owners [risk ratio (RR) 2.28, 95% CI 1.47-3.56]. Meta-analysis did not show a significantly higher risk for 3GCRE colonization among owners of different pet species compared with non-pet owners (RR 1.18, 95% CI 0.83-1.68 for pet owners in general, RR 0.88, 95% CI 0.56-1.40 for dog owners, RR 1.16, 95% CI 0.58-2.34 for cat owners, RR 1.34, 95% CI 0.43-4.18 for rodent owners, RR 0.91, 95% CI 0.38-2.18 for bird owners, and RR 2.34, 95% CI 0.33-16.63 for lizard/frog owners). For VRE, there were insufficient data to perform a meta-analysis. CONCLUSIONS: Our analyses suggest contact to pet animals is a risk factor for MRSA, but not for 3GCRE/CRE acquisition. Evaluation of the underlying literature suggested a possible role of pet animals as: (i) vectors for the transmission of MDROs between livestock and humans; as well as (ii) a reservoir for MDROs. Pets, therefore, may promote transmission and reinfection of humans.

Periorbital infections and conjunctivitis due to Panton-Valentine Leukocidin (PVL) positive Staphylococcus aureus in children.

BACKGROUND: Colonisation with Panton-Valentine Leukocidin expressing strains of Staphylococcus aureus (PVL + SA) is characterised by recurrent skin and soft tissue infections. While periorbital and orbital infections are common in children and frequently caused by S. aureus the role of PVL + SA in recurrent eye infections has not been studied. This study aimed to detect and report frequency and recurrence of periorbital or orbital infections as additional symptoms of PVL + SA colonisation in children. METHODS: We conducted a retrospective cohort study of pediatric patients who were treated for PVL + SA skin and soft tissue infection in our in- and outpatient clinics in Berlin, Germany from January 2012 to January 2017. We identified cases with periorbital or orbital infections in the year prior to the first PVL + SA evidence. In these cases, we conducted follow-up interviews by phone to determine recurrence of symptoms after the completion of decolonisation procedures. RESULTS: Fifty pediatric patients (age range: one week to 17 years) were evaluated and treated for PVL + SA infections in the reported time period. 19 patients (38%) reported periorbital infection or conjunctivitis, with recurrent hordeola as the most frequent finding (n = 9; 18%). Reappearance of hordeola (n = 5) was associated with recurrence of skin and soft tissue infections and/or de novo detection of PVL + SA. No further hordeola or other eye infections occurred after successful decolonisation. CONCLUSION: Our findings suggest a frequent involvement of periorbital skin in children with PVL + SA infections. Pediatric patients with recurrent periorbital infections might benefit from PVL + SA screening and consecutive decolonisation procedures.

The mother as most important risk factor for colonization of very low birth weight (VLBW) infants with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E).

OBJECTIVES: This study aimed to determine the prevalence of and risk factors for colonization with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) and methicillin-resistant Staphylococcus aureus (MRSA) in very low birth weight (VLBW; <1500 g) infants and their mothers. METHODS: This investigation was conducted in the perinatal centre at the Charité Berlin between May 2012 and June 2013. VLBW infants and their mothers were screened for colonization with ESBL-E and MRSA. Demographic and clinical data were obtained from the German nationwide surveillance system for nosocomial infections in VLBW infants (NEO-KISS) and used to perform univariate and multivariate analyses. RESULTS: Of 209 VLBW infants, 12 (5.7%) were colonized with ESBL-E. Eighteen of 209 (8.6%) ESBL-E-tested neonates were related to an ESBL-E-positive mother. Univariate analysis, strain typing and multivariate analysis (OR 7.4, 95% CI 2.1-26.7, P = 0.002) identified an ESBL-E-positive mother and maternal-neonatal transmission as a main source of colonization. The prevalence of MRSA was 2.3% (5 of 221) among VLBW infants. One of the 221 (0.5%) MRSA-tested neonates was related to an MRSA-positive mother. No risk factors for transmission of MRSA could be detected in this study. CONCLUSIONS: Our study demonstrated that maternal-neonatal transmission of ESBL-E from mother to child is an important risk factor for colonization of VLBW infants. As a consequence, routine ESBL-E screening of neonates and mothers should be considered as a means of reducing neonatal morbidity and mortality.

Molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae from bloodstream infections and risk factors for mortality.

The prevalence of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae is growing worldwide. Infections with these bacteria are suspected to be related to increased mortality. We aimed to estimate the distribution of ESBL genotypes and to assess the impact on mortality associated with ESBL positivity in cases of bloodstream infection (BSI) due to K. pneumoniae. We performed a cohort study on patients with K. pneumoniae BSI between 2008 and 2011. Presence of ESBL genes was analyzed by PCR and sequencing. Risk factors for mortality were analyzed by Cox-proportional hazard regression. We identified 286 ESBL-negative (81%) and 66 (19%) ESBL-positive cases. 97% (n = 64) of the ESBL-positive isolates were susceptible for meropenem. The most common ESBL genotypes were CTX-M-15 (60%), SHV-5 (27%) and CTX-M-3 (5%). Significant risk factors for mortality were chronic pulmonary disease (HR 1.747) and moderate/severe renal disease (HR 2.572). ESBL positivity was not associated with increased mortality.

Forecasting antimicrobial resistance evolution.

Antimicrobial resistance (AMR) is a major global health issue. Current measures for tackling it comprise mainly the prudent use of drugs, the development of new drugs, and rapid diagnostics. Relatively little attention has been given to forecasting the evolution of resistance. Here, we argue that forecasting has the potential to be a great asset in our arsenal of measures to tackle AMR. We argue that, if successfully implemented, forecasting resistance will help to resolve the antibiotic crisis in three ways: it will (i) guide a more sustainable use (and therefore lifespan) of antibiotics and incentivize investment in drug development, (ii) reduce the spread of AMR genes and pathogenic microbes in the environment and between patients, and (iii) allow more efficient treatment of persistent infections, reducing the continued evolution of resistance. We identify two important challenges that need to be addressed for the successful establishment of forecasting: (i) the development of bespoke technology that allows stakeholders to empirically assess the risks of resistance evolving during the process of drug development and therapeutic/preventive use, and (ii) the transformative shift in mindset from the current praxis of mostly addressing the problem of antibiotic resistance a posteriori to a concept of a priori estimating, and acting on, the risks of resistance.

Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL + -Staphylococcus aureus infections.

Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic. We thus aimed to (1) investigate how PVL exerts its pathogenicity on neutrophils and (2) identify factors that could help to explain the predisposition of patients with recurring infections. We provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH oxidase and reactive oxygen species production. Moreover, through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, and as such they were unable to kill S. aureus. Furthermore, we found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to be killed at a low PVL concentration than control neutrophils. Neutrophils from patients that experience recurring PVL-positive infections may thus be more sensitive to PVL-induced NET formation, which might impair their ability to combat the infection.

Antibiotic usage in German hospitals: results of the second national prevalence study.

OBJECTIVES: Data on antibiotic usage (AU) are helpful for improvement of antibiotic stewardship. This study describes findings and targets for quality improvement in German hospitals identified in a national point prevalence survey of healthcare-associated infections and AU. METHODS: The survey was organized by the German National Reference Centre for Surveillance of Nosocomial Infections (NRZ) as part of a pan-European survey organized by the European Centre for Disease Prevention and Control (ECDC). Infection control personnel of participating hospitals were trained in methodology and performed the survey in September and October 2011. Data on the antimicrobials prescribed (e.g. compounds and indications) were analysed by the NRZ. In order to submit national data to the ECDC, a representative sample of 46 hospitals was generated, although other hospitals were invited to participate in the survey if interested. RESULTS: In total, 41,539 patients were surveyed in 132 hospitals. AU prevalence in these hospitals and in the representative sample did not differ significantly [25.5% (95% CI 24.5%-26.6%) and 23.3% (95% CI 21.3%-25.5%), respectively]. AU rates were higher compared with a previous survey in 1994. Antimicrobials were administered for treatment in 70% and prophylaxis in 30% of cases. Surgical prophylaxis (SP) was prolonged (>1 day) in 70% of cases. Indication was documented in patients' charts in 73% of administrations. The most frequently used agents were cefuroxime (14.3%), ciprofloxacin (9.8%) and ceftriaxone (7.5%). CONCLUSIONS: The study identified several points for improvement, e.g. the large amount of prolonged SP, the extensive use of broad-spectrum antibiotics and the high percentage of antibiotic administration without documented indication.

Environmental cleaning to prevent hospital-acquired infections on non-intensive care units: a pragmatic, single-centre, cluster randomized controlled, crossover trial comparing soap-based, disinfection and probiotic cleaning.

Background: The impact of environmental hygiene on the occurrence of hospital-acquired infections (HAIs) remains a subject of debate. We determined the effect of three different surface-cleaning strategies on the incidence of HAIs. Methods: Between June 2017 and August 2018 we conducted a pragmatic, cluster-randomized controlled crossover trial at 18 non-ICU wards in the university hospital of Berlin, Germany. Surfaces in patient rooms on the study wards were routinely cleaned using one of three agents: Soap-based (reference), disinfectant and probiotic. Each strategy was used on each ward for four consecutive months (4m-4m-4m). There was a one-month wash-in period at the beginning of the study and after each change in strategy. The order of strategies used was randomized for each ward. Primary outcome was the incidence of HAIs. The trial was registered with the German Clinical Trials Register, DRKS00012675. Findings: 13,896 admitted patients met the inclusion criteria, including 4708 in the soap-based (reference) arm, 4535 in the disinfectant arm and 4653 in the probiotic arm. In the reference group, the incidence density of HAIs was 2.31 per 1000 exposure days. The incidence density was similar in the disinfectant arm 2.21 cases per 1000 exposure days (IRR 0.95; 95% CI 0.69-1.31; p = 0.953) and the probiotic arm 2.21 cases per 1000 exposure days (IRR 0.96; 95% CI 0.69-1.32; p = 0.955). Interpretation: In non-ICU wards, routine surface disinfection proved not superior to soap-based or probiotic cleaning in terms of HAI prevention. Thus, probiotic cleaning could be an interesting alternative, especially in terms of environmental protection. Funding: Federal Ministry of Education and Research of Germany (03Z0818C). Bill and Melinda Gates Foundation (INV-004308).

Clinical Evidence for the Use of Octenidine Dihydrochloride to Prevent Healthcare-Associated Infections and Decrease Staphylococcus aureus Carriage or Transmission-A Review.

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.

Infection control strategies for healthcare workers during COVID-19 pandemic in German hospitals: A cross-sectional study in march-april 2021.

Background: Healthcare workers (HCW) are at risk of getting infected with COVID-19 at work. To prevent such incidents and provide a safe environment in hospitals, comprehensive infection control strategies are necessary. We aimed to collect information on COVID-19 infection control strategies regarding personal protective equipment (PPE), regulations during breaks for HCW and dissemination of pandemic-related information. Methods: We invited infection control practitioners from 987 randomly selected German hospitals in March-April 2021 to participate in our cross-sectional online survey. We categorized the hospital based on bed capacity (≤499 beds = small; ≥500 beds = large). Fisher's exact test was performed and p < 0.05 defined as statistically significant. Findings: 100 participants completed the questionnaire. Small hospitals were more directive about requiring FFP2 respirators (63%), whereas larger hospitals more often gave their HCW a choice between these and medical masks (67%). For the care of COVID-19 and suspected COVID-19 cases, >90% of the participants recommended the use of gloves. Notably, gloves were recommended beyond COVID-19 in 30% of the hospitals. During meal breaks various strategies were followed. Conclusion: Recommendations for PPE varied across hospital sizes, which could be due to different assessments of necessity and safety. Regulations during breaks varied strongly which illustrates the need for clear official guidelines.

Lack of evidence for Epstein-Barr virus infection in myasthenia gravis thymus.

A role for Epstein-Barr virus (EBV) in myasthenia gravis pathogenesis has been suggested recently. Using in situ hybridization for the detection of the EBV-encoded RNAs and EBNA1-specific immunohistochemistry, we found no latently infected cells in a series of thymus specimens from patients with myasthenia gravis showing lymphofollicular thymitis. In addition, using immunohistochemistry and an antibody specific for the viral immediate early protein BZLF1, no evidence of lytic EBV infection was seen in these cases. Our results therefore do not support a direct role of thymic EBV infection in the pathogenesis of myasthenia gravis.

Skin Infections Due to Panton-Valentine Leukocidin-Producing S. Aureus.

BACKGROUND: Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (PVL-SA) strains are frequently associated with large, recurring abscesses in otherwise healthy young individuals. The typical clinical presentation and the recommended diagnostic evaluation and treatment are not widely known. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to international recommendations. RESULTS: PVL-SA can cause leukocytolysis and dermatonecrosis through specific cell-wall pore formation. Unlike other types of pyoderma, such conditions caused by PVL-SA have no particular site of predilection. In Germany, the PVL gene can be detected in 61.3% (252/411) of skin and soft tissue infections with S. aureus. Skin and soft tissue infections with PVL-SA recur three times as frequently as those due to PVL-negative S. aureus. They are diagnosed by S. aureus culture from wound swabs and combined nasal/pharyngeal swabs, along with PCR for gene detection. The acute treatment of the skin abscesses consists of drainage, followed by antimicrobial therapy if needed. Important secondary preventive measures include topical cleansing with mupirocin nasal ointment and whole-body washing with chlorhexidine or octenidine. The limited evidence (level IIb) concerning PVL-SA is mainly derived from nonrandomized cohort studies and experimental analyses. CONCLUSION: PVL-SA skin infections are easily distinguished from other skin diseases with targeted history-taking and diagnostic evaluation.

Is There an Association between Intra-Operative Detection of Pathogens in Subcutaneous Tissue and Surgical Site Infections? Results from a Prospective Study.

Background: Surgical site infections (SSIs) are a common complication in visceral surgery. Pathogens causing SSIs vary depending on the type of surgery. Patients and Methods: Within the scope of the Reduction of Postoperative Wound Infections by Antiseptica (RECIPE) trial we analyzed the pathogens cultured in intra-operative, subcutaneous swabs and in swabs from SSI in a single-center, prospective, randomized controlled study. Definition of SSI complied with the criteria of the U.S. Centers for Disease Control and Prevention (CDC). Results: The overall rate of SSI was 28.2% in 393 patients. Colorectal surgery was performed in 68.2% of elective laparotomies. Pathogens were more often detected in intra-operative subcutaneous swabs in patients who developed SSIs than in patients who did not develop SSIs (64.4% vs. 38.0%; p < 0.001). Enterococci were found in 29.1% of intra-operative swabs in patients with SSIs, followed by Escherichia coli in 15.5%. A higher rate of Enterococcus faecium was found in patients with anemia versus those without anemia (9.2% vs. 2.3%; p = 0.006) and in patients who smoked versus those who did not (11.8% vs. 3.6%; p = 0.008). A positive subcutaneous swab (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.47-4.29; p = 0.001), pre-operative anemia (OR, 1.84; 95% CI, 1.08-3.13; p = 0.016), and renal insufficiency (OR, 2.15; 95% CI, 1.01-4.59; p = 0.048) were risk factors for SSIs. Conclusions: There is an association between the intra-operative detection of pathogens in subcutaneous tissue and the development of SSIs in visceral surgery. The most prevalent pathogens causing SSIs were enterococci and Escherichia coli. More efforts are justified to reduce subcutaneous colonization with pathogens, for example by using intra-operative wound irrigation with polyhexanide solution. This trial is registered at www.ClinicalTrials.gov (ID: NCT04055233).

Comparative analysis of surface sanitization protocols on the bacterial community structures in the hospital environment.

OBJECTIVES: In hospital hygiene, it remains unclear to what extent surface contamination might represent a potential reservoir for nosocomial pathogens. This study investigates the effects of different sanitization strategies on the microbial structures and the ecological balance of the environmental microbiome in the clinical setting. METHODS: Three cleaning regimes (disinfectants, detergents, and probiotics) were applied subsequently in nine independent patient rooms at a neurological ward (Charité, Berlin). Weekly sampling procedures included three different environmental sites: floor, door handle, and sink. Characterization of the environmental microbiota and detection of antibiotic resistance genes (ARGs) were performed by 16S rRNA sequencing and multiplex Taq-Man qPCR assays, respectively. RESULTS: Our results showed a displacement of the intrinsic environmental microbiota after probiotic sanitization, which reached statistical significance in the sink samples (median 16S-rRNA copies = 138.3; IQR: 24.38-379.5) when compared to traditional disinfection measures (median 16S rRNA copies = 1343; IQR: 330.9-9479; p < 0.05). This effect was concomitant with a significant increase in the alpha-diversity metrics in both the floor (p < 0.001) and the sink samples (p < 0.01) during the probiotic strategy. We did not observe a sanitization-dependent change in relative pathogen abundance at any tested site, but there was a significant reduction in the total ARG counts in the sink samples during probiotic cleaning (mean ARGs/sample: 0.095 ± 0.067) when compared to the disinfection strategy (mean ARGs/sample: 0.386 ± 0.116; p < 0.01). DISCUSSION: The data presented in this study suggest that probiotic sanitization is an interesting strategy in hospital hygiene management to be further analyzed and validated in randomized clinical studies.

Bacterial colonization dynamics and antibiotic resistance gene dissemination in the hospital environment after first patient occupancy: a longitudinal metagenetic study.

BACKGROUND: Humans spend the bulk of their time in indoor environments. This space is shared with an indoor ecosystem of microorganisms, which are in continuous exchange with the human inhabitants. In the particular case of hospitals, the environmental microorganisms may influence patient recovery and outcome. An understanding of the bacterial community structure in the hospital environment is pivotal for the prevention of hospital-acquired infections and the dissemination of antibiotic resistance genes. In this study, we performed a longitudinal metagenetic approach in a newly opened ward at the Charité Hospital (Berlin) to characterize the dynamics of the bacterial colonization process in the hospital environment after first patient occupancy. RESULTS: The sequencing data showed a site-specific taxonomic succession, which led to stable community structures after only a few weeks. This data was further supported by network analysis and beta-diversity metrics. Furthermore, the fast colonization process was characterized by a significant increase of the bacterial biomass and its alpha-diversity. The compositional dynamics could be linked to the exchange with the patient microbiota. Over a time course of 30 weeks, we did not detect a rise of pathogenic bacteria in the hospital environment, but a significant increase of antibiotic resistance determinants on the hospital floor. CONCLUSIONS: The results presented in this study provide new insights into different aspects of the environmental microbiome in the clinical setting, and will help to adopt infection control strategies in hospitals and health care-related buildings. Video Abstract.