Healthcare-Associated Infections and the Use of Antibiotics in German Hospitals­Results of the Point Prevalence Survey of 2022 and Comparison With Earlier Findings.

BACKGROUND: A national point prevalence survey (PPS) of healthcare-associated infections (HAI) and antibiotic use (AU) was carried out in Germany in 2022 in the framework of the European PPS conducted by the European Centre for Disease Prevention and Control (ECDC). The objective was to determine the prevalence of HAI and AU in German hospitals and to compare the obtained values with those of the most recent previous PPS, which was carried out in 2016. METHODS: The German National Reference Center for the Surveillance of Nosocomial Infections was entrusted with the organization of the PPS of 2022. As recommended by the ECDC, each hospital in a representative sample of 50 hospitals was invited to participate, and all other interested hospitals in Germany were also able to participate if desired. The data were collected by specially trained hospital staff in May, June, and July 2022. The definitions and methods put forth by the ECDC were used. RESULTS: Data from 66 586 patients in 252 hospitals were included. The prevalence of HAI in all participating hospitals was 4.9%, and that of AU was 26.9%. The HAI and AU prevalences were essentially unchanged in comparison to 2016. The most common types of HAI were surgical site infection (23.5%), lower respiratory tract infection (21.6%), and urinary tract infection (19.0%). CONCLUSION: HAI were just as frequent in 2022 as in 2016, affecting approximately one in twenty hospitalized patients on any given day.

Surveillance of infections of surgical sites and lower respiratory tracts should be combined: experiences from the German surveillance module for operated patients (OP-KISS), 2018 to 2022.

BackgroundSurveillance of lower respiratory tract infections (LRTI) of operated patients conventionally focuses on intubated patients in intensive care units (ICU). Post-operative immobilisation increases the risk of LRTI not associated with ventilators. Operated patients, however, have thus far not been a primary target for LRTI surveillance.AimWe aimed to describe the applied LRTI surveillance method in the German surveillance module for operated patients (OP-KISS) and to report data between 2018 and 2022.MethodsSurveillance of LRTI can be performed voluntarily in addition to surgical site infection (SSI) surveillance in OP-KISS. We calculated LRTI rates per 100 operations for all procedures combined, as well as for individual surgical groups and procedures. Additionally, a combined post-operative infection rate (SSI and LRTI) was calculated.ResultsSurveillance of LRTI was performed in 4% of all participating OP-KISS departments and for 2% (23,239 of 1,332,438) of all procedures in the OP-KISS database. The pooled LRTI rate was 0.9 per 100 operations, with marked differences between different types of surgery (3.6 for lobectomies, 0.1 for traumatology and orthopaedics). The share of LRTI among all post-operative infections was highly variable. For lobectomies, the LRTI rate was higher than the SSI rate (3.6 vs 1.5 per 100 operations).ConclusionSurveillance of post-operative LRTI is not yet widely adopted by German hospitals. Based on the data in this study, lobectomies represent a prime target for post-operative LRTI surveillance.

Risk factors for transmission of carbapenem-resistant Acinetobacter baumannii in outbreak situations: results of a case-control study.

BACKGROUND: An increase in patients with multidrug-resistant organisms and associated outbreaks during the COVID-19 pandemic have been reported in various settings, including low-endemic settings. Here, we report three distinct carbapenem-resistant Acinetobacter baumannii (CRAB) outbreaks in five intensive care units of a university hospital in Berlin, Germany during the COVID-19 pandemic. METHODS: A case-control study was conducted with the objective of identifying risk factors for CRAB acquisition in outbreak situations. Data utilized for the case-control study came from the investigation of three separate CRAB outbreaks during the COVID-19 pandemic (August 2020- March 2021). Cases were defined as outbreak patients with hospital-acquired CRAB. Controls did not have any CRAB positive microbiological findings and were hospitalized at the same ward and for a similar duration as the respective case. Control patients were matched retrospectively in a 2:1 ratio. Parameters routinely collected in the context of outbreak management and data obtained retrospectively specifically for the case-control study were included in the analysis. To analyze risk factors for CRAB acquisition, univariable and multivariable analyses to calculate odds ratios (OR) and 95% confidence intervals (CI) were performed using a conditional logistic regression model. RESULTS: The outbreaks contained 26 cases with hospital-acquired CRAB in five different intensive care units. Two exposures were identified to be independent risk factors for nosocomial CRAB acquisition by the multivariable regression analysis: Sharing a patient room with a CRAB patient before availability of the microbiological result was associated with a more than tenfold increase in the risk of nosocomial CRAB acquisition (OR: 10.7, CI: 2.3-50.9), while undergoing bronchoscopy increased the risk more than six times (OR: 6.9, CI: 1.3-38.1). CONCLUSIONS: The risk factors identified, sharing a patient room with a CRAB patient and undergoing bronchoscopy, could point to an underperformance of basic infection control measure, particularly hand hygiene compliance and handling of medical devices. Both findings reinforce the need for continued promotion of infection control measures. Given that the outbreaks occurred in the first year of the COVID-19 pandemic, our study serves as a reminder that a heightened focus on airborne precautions should not lead to a neglect of other transmission-based precautions.

[The structural and spatial design of German intensive care units from the point of view of infection control measures : Survey among ICU-KISS participants]. / Die bauliche Struktur der deutschen Intensivstationen aus dem Blickwinkel der Infektionsprävention : Eine Umfrage unter den ITS-KISS-Teilnehmern.

INTRODUCTION: Intensive care unit (ICU) structural and spatial design may play a role in infection prevention and control. METHODS: Between 09/2021 and 11/2021 we performed an online survey among ICUs in Germany, Austria and Switzerland. RESULTS: A total of 597 (40%) of the invited ICUs answered the survey; 20% of the ICUs were built before 1990. The median number of single rooms with interquartile range is 4 (IQR 2-6). The median total room number is 8 (IQR 6-12). The median room size is 19 (IQR 16-22) m2 for single rooms and 31 (26-37.5) m2 for multiple bed rooms. Furthermore, 80% of ICUs have sinks and 86.4% have heating, ventilation, air conditioning (HVAC) systems in patient rooms. 54.6% of ICUs must store materials outside of storage rooms due to lack of space and only 33.5% have a room dedicated to disinfection and cleaning of used medical devices. Comparing ICUs built before 1990 and after 2011 we could show a slightly increase of single rooms (3 [IQR 2-5] before 1990 vs. 5 [IQR 2-8] after 2011; p < 0.001). DISCUSSION: A large proportion of German ICUs do not meet the requirements of German professional societies regarding the number of single rooms and size of the patient rooms. Many ICUs lack storage space and other functional rooms. CONCLUSION: There is an urgent need to support the construction and renovation of intensive care units in Germany with adequate funding.

Etiology of nosocomial infections in intensive care patients in German hospitals: An analysis of trends between 2008 and 2022.

PURPOSE: Data from the intensive care component of the German hospital infection surveillance system (KISS) was used to investigate the epidemiology of pathogens responsible for the most frequent device-associated infections and their development over time. METHOD: The 10 most common pathogens were identified for ventilator-associated lower respiratory tract infections (VALRTI), catheter associated urinary tract infections (CAUTI), and central venous catheter associated bloodstream infections (CVC-BSI). The development over time was analyzed based on three five-year time periods: 2008-2012, 2013-2017, 2018-2022. RESULTS: Data from 1425 ICUs were included together with 121,762 device-associated infections with 138,299 isolated pathogens. A remarkable and significant increase in the frequency of Klebsiella spp. was found for VALRTI, that was almost twice as high during 2018-2022 compared to 2008-2012. For CAUTI, there was a significant increase of all Enterobacterales with the most prominent increase in Klebsiella spp. With regard to CVC-BSI, the situation for coagulase-negative staphylococci and E. coli was relatively stable; while there was a significant increase in Enterococcus spp. and Klebsiella spp. and a decrease in S. aureus. CONCLUSION: Knowledge about the current frequency of pathogens responsible for nosocomial infections in intensive care units is important for guiding empirical antimicrobial therapy. Data from national nosocomial infection surveillance systems can provide relevant information about the development of pathogens.

Strengthening the role of hospital leadership in infection control (LEAD-IC) - a multimodal educational intervention in German acute care hospitals.

BACKGROUND: The effect of leadership support for adherence to infection control and prevention (IPC) measures has been demonstrated. To expand this support, a target group-specific educational study for chief medical officers (CMO) was implemented and its influence on IPC indicators was investigated. METHODS: A controlled cohort study was conducted between 2018 and 2019. The intervention based on an initial workshop, an e-learning course, and a final meeting. Participants' activities involving IPC management were surveyed. Consumption of alcohol hand rub (AHR) and incidence density of hospital-associated (HA) Clostridioides difficile-associated infections (CDI) were analyzed. RESULTS: Eight percent of 360 CMOs invited participated in the initial workshop; 70% of those participants registered for the online course. Overall, 43% completed the post-intervention questionnaire, in which 85% of respondents reported increased collaboration with relevant stakeholders. The pre-intervention median AHR consumption was higher in the intervention group than in the control group. Both groups showed an increase (38.6 (interquartile range (IQR) 33.6; 45.0) to 41.9 ml/patient day (PD) (IQR 35.0; 56.6) and 33.4 (IQR 28.3; 40.8) to 35.8 ml/ PD (IQR 31.6; 43.2), respectively). Pre-intervention median HA CDI cases were lower in the intervention group than in the control group. Both groups reported a decrease (0.22 (IQR 0.17; 0.33) to 0.19 cases/1000 PD (IQR 0.15; 0.26) and 0.32 (IQR 0.2; 0.48) to 0.22 cases/1000 PD (IQR 0.11; 0.33), respectively). CONCLUSION: Multimodal IPC training of CMOs is worthwhile and can lead to changes in IPC-relevant cooperation in hospitals. IPC training of hospital management should be further intensified.

Towards interoperability in infection control: a standard data model for microbiology.

The COVID-19 pandemic has made it clear: sharing and exchanging data among research institutions is crucial in order to efficiently respond to global health threats. This can be facilitated by defining health data models based on interoperability standards. In Germany, a national effort is in progress to create common data models using international healthcare IT standards. In this context, collaborative work on a data set module for microbiology is of particular importance as the WHO has declared antimicrobial resistance one of the top global public health threats that humanity is facing. In this article, we describe how we developed a common model for microbiology data in an interdisciplinary collaborative effort and how we make use of the standard HL7 FHIR and terminologies such as SNOMED CT or LOINC to ensure syntactic and semantic interoperability. The use of international healthcare standards qualifies our data model to be adopted beyond the environment where it was first developed and used at an international level.

Association of ward-level antibiotic consumption with healthcare-associated Clostridioides difficile infections: an ecological study in five German university hospitals, 2017-2019.

OBJECTIVES: To analyse the influence of antibiotic consumption on healthcare-associated healthcare onset (HAHO) Clostridioides difficile infection (CDI) in a German university hospital setting. METHODS: Monthly ward-level antibiotic consumption measured in DDD/100 patient days (pd) and CDI surveillance data from five university hospitals in the period 2017 through 2019 were analysed. Uni- and multivariable analyses were performed with generalized estimating equation models. RESULTS: A total of 225 wards with 7347 surveillance months and 4 036 602 pd participated. With 1184 HAHO-CDI cases, there was a median incidence density of 0.17/1000 pd (IQR 0.03-0.43) across all specialties, with substantial differences among specialties. Haematology-oncology wards showed the highest median incidence density (0.67/1000 pd, IQR 0.44-1.01), followed by medical ICUs (0.45/1000 pd, IQR 0.27-0.73) and medical general wards (0.32/1000 pd, IQR 0.18-0.53). Multivariable analysis revealed carbapenem (mostly meropenem) consumption to be the only antibiotic class associated with increased HAHO-CDI incidence density. Each carbapenem DDD/100 pd administered increased the HAHO-CDI incidence density by 1.3% [incidence rate ratio (IRR) 1.013; 95% CI 1.006-1.019]. Specialty-specific analyses showed this influence only to be valid for haematological-oncological wards. Overall, factors like ward specialty (e.g. haematology-oncology ward IRR 2.961, 95% CI 2.203-3.980) or other CDI cases on ward had a stronger influence on HAHO-CDI incidence density (e.g. community-associated CDI or unknown association case in same month IRR 1.476, 95% CI 1.242-1.755) than antibiotic consumption. CONCLUSIONS: In the German university hospital setting, monthly ward-level carbapenem consumption seems to increase the HAHO-CDI incidence density predominantly on haematological-oncological wards. Furthermore, other patient-specific factors seem to be equally important to control HAHO-CDI.

Increasing numbers and complexity of Staphylococcus aureus bloodstream infection-14 years of prospective evaluation at a German tertiary care centre with multi-centre validation of findings.

OBJECTIVES: Staphylococcus aureus bloodstream infection (SAB) is a common and severe infection. This study aims to describe temporal trends in numbers, epidemiological characteristics, clinical manifestations, and outcomes of SAB. METHODS: We performed a post-hoc analysis of three prospective SAB cohorts at the University Medical Centre Freiburg between 2006 and 2019. We validated our findings in a large German multi-centre cohort of five tertiary care centres (R-Net consortium, 2017-2019). Time-dependent trends were estimated using Poisson or beta regression models. RESULTS: We included 1797 patients in the mono-centric and 2336 patients in the multi-centric analysis. Overall, we observed an increasing number of SAB cases over 14 years (6.4%/year and 1000 patient days, 95% CI: 5.1% to 7.7%), paralleled by an increase in the proportion of community-acquired SAB (4.9%/year [95% CI: 2.1% to 7.8%]) and a decrease in the rate of methicillin-resistant-SAB (-8.5%/year [95% CI: -11.2% to -5.6%]). All of these findings were confirmed in the multi-centre validation cohort (6.2% cases per 1000 patient cases/year [95% CI: -0.6% to 12.6%], community-acquired-SAB 8.7% [95% CI: -1.2% to 19.6%], methicillin-resistant S. aureus-SAB -18.6% [95% CI: -30.6 to -5.8%]). Moreover, we found an increasing proportion of patients with multiple risk factors for complicated/difficult-to-treat SAB (8.5%/year, 95% CI: 3.6% to 13.5%, p < 0.001), alongside an overall higher level of comorbidities (Charlson comorbidity score 0.23 points/year, 95% CI: 0.09 to 0.37, p 0.005). At the same time, the rate of deep-seated foci such as osteomyelitis or deep-seated abscesses significantly increased (6.7%, 95% CI: 3.9% to 9.6%, p < 0.001). A reduction of in-hospital mortality by 0.6% per year (95% CI: 0.08% to 1%) was observed in the subgroup of patients with infectious diseases consultations. DISCUSSION: We found an increasing number of SAB combined with a significant increase in comorbidities and complicating factors in tertiary care centres. The resulting challenges in securing adequate SAB management in the face of high patient turnover will become an important task for physicians.

Central-line associated bloodstream infections in intensive care units before and after implementation of daily antiseptic bathing with chlorhexidine or octenidine: a post-hoc analysis of a cluster-randomised controlled trial.

BACKGROUNDS: Antiseptic bathing did not reduce central-line (CL) associated bloodstream infection (CLABSI) rates in intensive care units (ICU) according to a recent cluster randomised controlled trial (cRCT). However, this analysis did not consider baseline infection rates. Our post-hoc analysis of this cRCT aimed to use a before-after comparison to examine the effect of daily bathing with chlorhexidine, octenidine or water and soap (control) on ICU-attributable CLABSI rates. METHODS: A post-hoc analysis of a multi-center cRCT was done. ICUs that did not yet perform routine antiseptic bathing were randomly assigned to one of three study groups applying daily bathing with 2% chlorhexidine-impregnated cloths, 0.08% octenidine wash mitts or water and soap (control) for 12 months. Baseline data was assessed 12 months before the intervention started when all ICUs routinely used water and soap. Poisson regression and generalised estimating equation models were applied to identify changes of CLABSI rates per 1000 CL days between intervention and baseline periods in each study group. RESULTS: The cRCT was conducted in 72 ICUs (24 per study group) including 76,139 patients in the baseline and 76,815 patients in the intervention period. In the chlorhexidine group, incidence density of CLABSI was reduced from 1.48 to 0.90 CLABSI per 1000 CL days comparing baseline versus intervention period (P = 0.0085). No reduction was observed in the octenidine group (1.26 versus 1.47 CLABSI per 1000 CL days, P = 0.8735) and the control group (1.20 versus 1.17, P = 0.3298). Adjusted incidence rate ratios (intervention versus baseline) were 0.63 (95%CI 0.46-0.87, P = 0.0172) in the chlorhexidine, 1.17 (95% CI 0.79-1.72, P = 0.5111) in the octenidine and 0.98 (95% CI 0.60-1.58, P = 0.9190) in the control group. Chlorhexidine bathing reduced CLABSI with gram-positive bacteria, mainly coagulase-negative staphylococci (CoNS). CONCLUSIONS: In this post-hoc analysis of a cRCT, the application of 2% chlorhexidine-impregnated cloths reduced ICU-attributable CLABSI. This preventive effect of chlorhexidine was restricted to CLABSI caused by gram-positive pathogens (CoNS). In contrast, 0.08% octenidine wash mitts did not reduce CLABSI rates in ICUs. Trial registration Registration number DRKS00010475, registration date August 18, 2016.

Screening for Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become less common in Germany in recent years. In this paper, we report data from the MRSA module of the Hospital Infection Surveillance System (Krankenhaus-Infektionen- Surveillance-System, KISS) for the years 2006-2021. We also describe the association of MRSA rates with the frequency of patient screening for MRSA and discuss the findings. METHODS: Participation in the MRSA KISS module is voluntary. Once a year, the participating hospitals submit structural data, information on cases in which MRSA was detected (both colonizations and infections; both detected on admission and nosocomially acquired), and the number of nasal swabs taken for the detection of MRSA to the German National Reference Center for the Surveillance of Nosocomial Infections. Statistical analyses were performed with R software. RESULTS: The number of hospitals participating in the MRSA module rose from 110 in 2006 to 525 in 2021. From 2006 onward, the overall MRSA prevalence in German hospitals increased, reaching a maximum of 1.04 cases per 100 patients in 2012. The prevalence on admission fell by 44% from 0.96 in 2016 to 0.54 in 2021. The incidence density of nosocomial MRSA fell by an average of 12% per year, from 0.27 per 1000 patient-days in 2006 to 0.06 in 2021, while MRSA screening frequency increased sevenfold by 2021. The nosocomial incidence density was stable, independently of the screening frequency. CONCLUSION: MRSA rates in German hospitals fell markedly from 2006 to 2021, reflecting a general trend. The incidence density was no higher in hospitals with a low or moderate screening frequency than in those with a high one. Thus, a targeted, riskadapted MRSA screening strategy on hospital admission can be recommended.

Surgical site infection surveillance in German hospitals: a national survey to determine the status quo of digitalization.

BACKGROUND: Surveillance of surgical site infections (SSI) relies on access to data from various sources. Insights into the practices of German hospitals conducting SSI surveillance and their information technology (IT) infrastructures are scarce. The aim of this study was to evaluate current SSI surveillance practices in German hospitals with a focus on employed IT infrastructures. METHODS: German surgical departments actively participating in the national SSI surveillance module "OP-KISS" were invited in August 2020 to participate in a questionnaire-based online survey. Depending on whether departments entered all data manually or used an existing feature to import denominator data into the national surveillance database, departments were separated into different groups. Selected survey questions differed between groups. RESULTS: Of 1,346 invited departments, 821 participated in the survey (response rate: 61%). Local IT deficits (n = 236), incompatibility of import specifications and hospital information system (n = 153) and lack of technical expertise (n = 145) were cited as the most frequent reasons for not using the denominator data import feature. Conversely, reduction of workload (n = 160) was named as the main motivation to import data. Questions on data availability and accessibility in the electronic hospital information system (HIS) and options to export data from the HIS for the purpose of surveillance, yielded diverse results. Departments utilizing the import feature tended to be from larger hospitals with a higher level of care. CONCLUSIONS: The degree to which digital solutions were employed for SSI surveillance differed considerably between surgical departments in Germany. Improving availability and accessibility of information in HIS and meeting interoperability standards will be prerequisites for increasing the amount of data exported directly from HIS to national databases and laying the foundation for automated SSI surveillance on a broad scale.

Quantification of time delay between screening and subsequent initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales: A post hoc subgroup analysis of the R-GNOSIS WP5 Trial.

OBJECTIVES: The aim of this study was to quantify the time delay between screening and initiation of contact isolation for carriers of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E). METHODS: This study was a secondary analysis of contact isolation periods in a cluster-randomized controlled trial that compared 2 strategies to control ESBL-E (trial no. ISRCTN57648070). Patients admitted to 20 non-ICU wards in Germany, the Netherlands, Spain, and Switzerland were screened for ESBL-E carriage on admission, weekly thereafter, and on discharge. Data collection included the day of sampling, the day the wards were notified of the result, and subsequent ESBL-E isolation days. RESULTS: Between January 2014 and August 2016, 19,122 patients, with a length of stay ≥2 days were included. At least 1 culture was collected for 16,091 patients (84%), with a median duration between the admission day and the day of first sample collection of 2 days (interquartile range [IQR], 1-3). Moreover, 854 (41%) of all 2,078 ESBL-E carriers remained without isolation during their hospital stay. In total, 6,040 ESBL-E days (32% of all ESBL-E days) accrued for patients who were not isolated. Of 2,078 ESBL-E-carriers, 1,478 ESBL-E carriers (71%) had no previous history of ESBL-E carriage. Also, 697 (34%) were placed in contact isolation with a delay of 4 days (IQR, 2-5), accounting for 2,723 nonisolation days (15% of ESBL-E days). CONCLUSIONS: Even with extensive surveillance screening, almost one-third of all ESBL-E days were nonisolation days. Limitations in routine culture-based ESBL-E detection impeded timely and exhaustive implementation of targeted contact isolation.

Age as a risk factor for surgical site infections: German surveillance data on total hip replacement and total knee replacement procedures 2009 to 2018.

BackgroundOlder age is frequently cited as a risk factor for healthcare-associated infections in general, and surgical site infections (SSIs) specifically.AimWe aimed to investigate the correlation between age and SSI occurrence.MethodsData on total hip replacement (THR) and total knee replacement (TKR) surgeries and resulting SSIs documented in the German national surveillance network from a 10-year period from 2009 to 2018 were selected for analysis. SSI rates and adjusted odds ratios (AOR) were calculated and a multivariable analysis to determine risk factors for SSI occurrence was conducted.ResultsA total of 418,312 THR procedures resulting in 3,231 SSIs, and 286,074 TKR procedures with 1,288 SSIs were included in the analyses. For THR, SSI rates were higher in older age groups when compared with the reference age group of 61-65 years. A significantly higher risk was observed in the 76-80 years age group (AOR: 1.21, 95% CI: 1.05-1.4). An age of ≤ 50 years was associated with a significantly lower SSI risk (AOR: 0.64, 95% CI: 0.52-0.8). For TKR, a similar correlation was observed, with the exception of the youngest age group (≤ 52 years), which was shown to have an SSI risk equal to that of the knee prosthesis reference age group (78-82 years).ConclusionA strong correlation between increasing age and SSI occurrence was observed for both procedure types. The results of our analyses provide a basis to consider future targeted SSI prevention measures for different age groups.

Split k-mer analysis compared to cgMLST and SNP-based core genome analysis for detecting transmission of vancomycin-resistant enterococci: results from routine outbreak analyses across different hospitals and hospitals networks in Berlin, Germany.

The increase of Vancomycin-resistant Enterococcus faecium (VREfm) in recent years has been partially attributed to the rise of specific clonal lineages, which have been identified throughout Germany. To date, there is no gold standard for the interpretation of genomic data for outbreak analyses. New genomic approaches such as split k-mer analysis (SKA) could support cluster attribution for routine outbreak investigation. The aim of this project was to investigate frequent clonal lineages of VREfm identified during suspected outbreaks across different hospitals, and to compare genomic approaches including SKA in routine outbreak investigation. We used routine outbreak laboratory data from seven hospitals and three different hospital networks in Berlin, Germany. Short-read libraries were sequenced on the Illumina MiSeq system. We determined clusters using the published Enterococcus faecium-cgMLST scheme (threshold ≤20 alleles), and assigned sequence and complex types (ST, CT), using the Ridom SeqSphere+ software. For each cluster as determined by cgMLST, we used pairwise core-genome SNP-analysis and SKA at thresholds of ten and seven SNPs, respectively, to further distinguish cgMLST clusters. In order to investigate clinical relevance, we analysed to what extent epidemiological linkage backed the clusters determined with different genomic approaches. Between 2014 and 2021, we sequenced 693 VREfm strains, and 644 (93 %) were associated within cgMLST clusters. More than 74 % (n=475) of the strains belonged to the six largest cgMLST clusters, comprising ST117, ST78 and ST80. All six clusters were detected across several years and hospitals without apparent epidemiological links. Core SNP analysis identified 44 clusters with a median cluster size of three isolates (IQR 2-7, min-max 2-63), as well as 197 singletons (41.4 % of 475 isolates). SKA identified 67 clusters with a median cluster size of two isolates (IQR 2-4, min-max 2-19), and 261 singletons (54.9 % of 475 isolates). Of the isolate pairs attributed to clusters, 7 % (n=3064/45 596) of pairs in clusters determined by standard cgMLST, 15 % (n=1222/8500) of pairs in core SNP-clusters and 51 % (n=942/1880) of pairs in SKA-clusters showed epidemiological linkage. The proportion of epidemiological linkage differed between sequence types. For VREfm, the discriminative ability of the widely used cgMLST based approach at ≤20 alleles difference was insufficient to rule out hospital outbreaks without further analytical methods. Cluster assignment guided by core genome SNP analysis and the reference free SKA was more discriminative and correlated better with obvious epidemiological linkage, at least recently published thresholds (ten and seven SNPs, respectively) and for frequent STs. Besides higher overall discriminative power, the whole-genome approach implemented in SKA is also easier and faster to conduct and requires less computational resources.

Resolving colistin resistance and heteroresistance in Enterobacter species.

Species within the Enterobacter cloacae complex (ECC) include globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)-9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate.

SAPS2, APACHE2, SOFA, and Core-10-TISS upon admission as risk indicators for ICU-acquired infections: a retrospective cohort study.

PURPOSE: Early identification of high-risk patients is an important component in improving infection prevention. The SAPS2, APACHE2, Core-10-TISS, and SOFA scores are already widely used to estimate mortality, morbidity and nursing workload, but this study evaluated their usefulness in assessing a patient's risk of ICU-acquired infection. METHODS: We conducted a retrospective cohort study by analyzing all patient admissions to seven ICUs at Charité Berlin, Germany in 2017 and 2018. The four scores were documented by physicians on the day of admission. The infection control staff monitored daily whether the patients experienced lower respiratory tract infections (LRTIs), urinary tract infections (UTIs), or primary blood stream infections (PBSIs). For each combination of scoring system and infection type, an adjusted Fine and Gray model was fitted. RESULTS: We analyzed 5053 ICU admissions and observed at least one ICU-acquired infection in N = 253 patients (incidence density: 4.73 per 1000 days). 59.0% (N = 2983) of the patients were male, median age was 66 years (IQR 55-77) and median length of stay was 6 days (IQR 4-12). All models showed that patients with a higher score value were at higher risk for ICU-acquired first PBSI, LRTI, or UTI, except for the model of APACHE2 and PBSI. Patients with a SAPS2 score of > 50 points showed an increased risk of infection of sHR = 2.34 for PBSIs (CI 1.06-5.17, p < 0.05), sHR = 2.33 for LRTIs (1.53-2.55, p < 0.001) and sHR = 2.25 for UTIs (1.23-4.13, p < 0.01) when compared to the reference group with 0-30 points. CONCLUSIONS: The result of this study showed that admission scores of SAPS2, Core-10-TISS, APACHE2, and SOFA might be adequate indicators for assessing a patient's risk of ICU-acquired infection.

Vancomycin-resistant Enterococcus faecium: admission prevalence, sequence types and risk factors-a cross-sectional study in seven German university hospitals from 2014 to 2018.

OBJECTIVES: Assessment of vancomycin-resistant Enterococcus faecium (VREfm) prevalence upon hospital admission and analysis of risk factors for colonization. METHODS: From 2014 to 2018, patients were recruited within 72 hours of admission to seven participating German university hospitals, screened for VREfm and questioned for potential risk factors (prior multidrug-resistant organism detection, current/prior antibiotic consumption, prior hospital, rehabilitation or long-term care facility stay, international travel, animal contact and proton pump inhibitor [PPI]/antacid therapy). Genotype analysis was done using cgMLST typing. Multivariable analysis was performed. RESULTS: In 5 years, 265 of 17,349 included patients were colonized with VREfm (a prevalence of 1.5%). Risk factors for VREfm colonization were age (adjusted OR [aOR], 1.02; 95% CI, 1.01-1.03), previous (aOR, 2.71; 95% CI, 1.87-3.92) or current (aOR, 2.91; 95% CI, 2.60-3.24) antibiotic treatment, prior multidrug-resistant organism detection (aOR, 2.83; 95% CI, 2.21-3.63), prior stay in a long-term care facility (aOR, 2.19; 95% CI, 1.62-2.97), prior stay in a hospital (aOR, 2.91; 95% CI, 2.05-4.13) and prior consumption of PPI/antacids (aOR, 1.29; 95% CI, 1.18-1.41). Overall, the VREfm admission prevalence increased by 33% each year and 2% each year of life. 250 of 265 isolates were genotyped and 141 (53.2%) of the VREfm were the emerging ST117. Multivariable analysis showed that ST117 and non-ST117 VREfm colonized patients differed with respect to admission year and prior multidrug-resistant organism detection. DISCUSSION: Age, healthcare contacts and antibiotic and PPI/antacid consumption increase the individual risk of VREfm colonization. The VREfm admission prevalence increase in Germany is mainly driven by the emergence of ST117.

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany.

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals.