From wild-type to Omicron: changes in SARS-CoV-2 hospital cluster dynamics. Observations from a German tertiary care hospital.

Aim: SARS-CoV-2 hospital clusters are a challenge for healthcare systems. There is an increased risk of infection for both healthcare workers (HCWs) and patients; cluster countermeasures are also a drain on resources for the wards affected. We analysed to which extent characteristics and dynamics of SARS-CoV-2 clusters varied throughout the pandemic at a German university hospital. Methods: Patient and/or HCW clusters from 10/2020 to 04/2022 were included in the study and grouped by virus variant into i.) clusters comprised of the presumably predominant wild-type, Alpha or Delta (WAD) SARS-COV-2 variants, and ii.) clusters comprised predominantly of Omicron subtype cases. The two groups were compared for specific characteristics and dynamics. Results: Forty-two SARS-CoV-2 clusters and 528 cases were analysed. Twenty-one clusters and 297 cases were attributed to the WAD and 21 clusters and 231 cases to the Omicron group. There were no significant differences in median size (8 vs. 8 cases, p=0.94) or median duration (14 vs. 12 days; p=0.48), nor in the percentage of HCWs involved (46.8% vs. 50.2%; p=0.48). Patients in the WAD group were older (median 75 vs. 68 years of age; p≤0.05). The median time from cluster onset to case onset was significantly shorter for the Omicron group (median 6 vs. 11 days; p≤0.05). Conclusions: Omicron clusters exhibited a more rapid dynamic, forcing all parties involved to adapt to the increased workload. Compared to excessive community case counts, constant Omicron cluster-affiliated case counts and stable cluster characteristics suggest an improved compliance with IPC countermeasures.

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.

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.

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).

A streamlined method for the fast and cost-effective detection of bacterial pathogens from positive blood cultures for the BacT/ALERT blood culture system using the Vitek MS mass spectrometer.

BACKGROUND AND OBJECTIVE: Prompt pathogen identification of blood stream infections is essential to provide appropriate antibiotic treatment. Therefore, the objective of this prospective single centre study was to establish an inexpensive, fast and accurate protocol for bacterial species identification with SDS protein-extraction directly from BacT/Alert® blood culture (BC) bottles by VitekMS®. RESULTS: Correct species identification was obtained for 198/266 (74.4%, 95%-CI = [68.8%, 79.6%]) of pathogens. The protocol was more successful in identifying 87/96 (91.4%, 95%-CI = [83.8%, 93.2%]) gram-negative bacteria than 110/167 (65.9%, 95%-CI = [58.1%, 73.0%]) gram-positive bacteria. The hands-on time for sample preparation and measurement was about 15 min for up to five samples. This is shorter than for most other protocols using a similar lysis-centrifugation approach for the combination of BacT/Alert® BC bottles and the Vitek® MS mass spectrometer. The estimated costs per sample were approx. 1.80€ which is much cheaper than for commercial kits. CONCLUSION: This optimized protocol allows for accurate identification of bacteria directly from blood culture bottles for laboratories equipped with BacT/Alert® blood culture bottles and VitekMS® mass spectrometer.

Development and validation of BLOOMY prediction scores for 14-day and 6-month mortality in hospitalised adults with bloodstream infections: a multicentre, prospective, cohort study.

BACKGROUND: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. METHODS: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. FINDINGS: Between Feb 1, 2017, and Jan 31, 2019, 2568 (61·5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23·75% (95% CI 22·15-25·44; 610 of 2568 patients) and the 6-month mortality rate was 41·55% (39·54-43·59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0·873, 95% CI 0·849-0·896) and 6-month mortality (0·807, 0·784-0·831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61·32% (95% CI 51·81-70·04), a specificity of 86·36% (83·80-88·58), a positive predictive value (PPV) of 37·57% (30·70-44·99), and a negative predictive value (NPV) of 94·35% (92·42-95·80). The BLOOMY 6-month score showed a sensitivity of 69·93% (61·97-76·84), a specificity of 66·44% (61·86-70·73), a PPV of 40·82% (34·85-47·07), and a NPV of 86·97% (82·91-90·18). INTERPRETATION: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections. FUNDING: DZIF German Center for Infection Research. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.

Risk factors for nosocomial SARS-CoV-2 infections in patients: results from a retrospective matched case-control study in a tertiary care university center.

BACKGROUND: Factors contributing to the spread of SARS-CoV-2 outside the acute care hospital setting have been described in detail. However, data concerning risk factors for nosocomial SARS-CoV-2 infections in hospitalized patients remain scarce. To close this research gap and inform targeted measures for the prevention of nosocomial SARS-CoV-2 infections, we analyzed nosocomial SARS-CoV-2 cases in our hospital during a defined time period. METHODS: Data on nosocomial SARS-CoV-2 infections in hospitalized patients that occurred between May 2020 and January 2021 at Charité university hospital in Berlin, Germany, were retrospectively gathered. A SARS-CoV-2 infection was considered nosocomial if the patient was admitted with a negative SARS-CoV-2 reverse transcription polymerase chain reaction test and subsequently tested positive on day five or later. As the incubation period of SARS-CoV-2 can be longer than five days, we defined a subgroup of "definite" nosocomial SARS-CoV-2 cases, with a negative test on admission and a positive test after day 10, for which we conducted a matched case-control study with a one to one ratio of cases and controls. We employed a multivariable logistic regression model to identify factors significantly increasing the likelihood of nosocomial SARS-CoV-2 infections. RESULTS: A total of 170 patients with a nosocomial SARS-CoV-2 infection were identified. The majority of nosocomial SARS-CoV-2 patients (n = 157, 92%) had been treated at wards that reported an outbreak of nosocomial SARS-CoV-2 cases during their stay or up to 14 days later. For 76 patients with definite nosocomial SARS-CoV-2 infections, controls for the case-control study were matched. For this subgroup, the multivariable logistic regression analysis revealed documented contact to SARS-CoV-2 cases (odds ratio: 23.4 (95% confidence interval: 4.6-117.7)) and presence at a ward that experienced a SARS-CoV-2 outbreak (odds ratio: 15.9 (95% confidence interval: 2.5-100.8)) to be the principal risk factors for nosocomial SARS-CoV-2 infection. CONCLUSIONS: With known contact to SARS-CoV-2 cases and outbreak association revealed as the primary risk factors, our findings confirm known causes of SARS-CoV-2 infections and demonstrate that these also apply to the acute care hospital setting. This underscores the importance of rapidly identifying exposed patients and taking adequate preventive measures.

Implementation of an automated cluster alert system into the routine work of infection control and hospital epidemiology: experiences from a tertiary care university hospital.

BACKGROUND: Early detection of clusters of pathogens is crucial for infection prevention and control (IPC) in hospitals. Conventional manual cluster detection is usually restricted to certain areas of the hospital and multidrug resistant organisms. Automation can increase the comprehensiveness of cluster surveillance without depleting human resources. We aimed to describe the application of an automated cluster alert system (CLAR) in the routine IPC work in a hospital. Additionally, we aimed to provide information on the clusters detected and their properties. METHODS: CLAR was continuously utilized during the year 2019 at Charité university hospital. CLAR analyzed microbiological and patient-related data to calculate a pathogen-baseline for every ward. Daily, this baseline was compared to data of the previous 14 days. If the baseline was exceeded, a cluster alert was generated and sent to the IPC team. From July 2019 onwards, alerts were systematically categorized as relevant or non-relevant at the discretion of the IPC physician in charge. RESULTS: In one year, CLAR detected 1,714 clusters. The median number of isolates per cluster was two. The most common cluster pathogens were Enterococcus faecium (n = 326, 19 %), Escherichia coli (n = 274, 16 %) and Enterococcus faecalis (n = 250, 15 %). The majority of clusters (n = 1,360, 79 %) comprised of susceptible organisms. For 906 alerts relevance assessment was performed, with 317 (35 %) alerts being classified as relevant. CONCLUSIONS: CLAR demonstrated the capability of detecting small clusters and clusters of susceptible organisms. Future improvements must aim to reduce the number of non-relevant alerts without impeding detection of relevant clusters. Digital solutions to IPC represent a considerable potential for improved patient care. Systems such as CLAR could be adapted to other hospitals and healthcare settings, and thereby serve as a means to fulfill these potentials.

Postoperative Tropheryma whipplei endophthalmitis - a case report highlighting the additive value of molecular testing.

Introduction.Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1-2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple's disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.

Improved performance of the artus Mycobacterium tuberculosis RG PCR kit in a low incidence setting: a retrospective monocentric study.

Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious threat to global health. However, rapid and reliable MTBC detection along with RIF/INH susceptibility testing are challenging in low prevalence countries due to the higher rate of false positives. Here, we provide the first performance data for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323 respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well as by mycobacterial culture and microscopy. We propose retesting of specimens in duplicate and consideration of a determined cycle-threshold value cut-off greater than 34, as this significantly increases accuracy, specificity, and negative predictive value without affecting sensitivity. Furthermore, we tested fourteen MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using an identical DNA extraction protocol for both assays does not impair downstream genotypic testing for RIF and INH susceptibility. In conclusion, our procedure optimizes the use of the artus MTB assay with workload efficient methods in a low incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus assays allows rapid and accurate detection of MTBC and RIF/INH resistance.