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We present the case of a 72-year-old female patient with acute contained rupture of a biological composite graft, 21 months after replacement of the aortic valve and the ascending aorta due to an aortic dissection. Auramine-rhodamine staining of intraoperative biopsies showed acid-fast bacilli, but classical culture and molecular methods failed to identify any organism. Metagenomic analysis indicated infection with Mycobacterium chelonae, which was confirmed by target-specific qPCR. The complexity of the sample required a customized bioinformatics pipeline, including cleaning steps to remove sequences of human, bovine ad pig origin. Our study underlines the importance of multiple testing to increase the likelihood of pathogen identification in highly complex samples.

Summary Background Conflicting results have been published on the impact of contact precautions (CPs) on reduction of transmission of multi-drug-resistant micro-organisms (MDROs) in the endemic setting. Ambiguous definitions coupled with low adherence partly explain these differences. Aim We prospectively monitored the level of adherence to CPs and aimed to relate it to in-hospital transmission of MDROs. Methods Between January 2016 and March 2018, all patients under CPs underwent continuous monitoring of adherence to CPs by routine on-site visits on days 0, 3 and 7 after initiating CPs using a standardized checklist. The protocol included 10 interventions that were routinely checked such as CP sign at the door as well as wearing of gowns and gloves upon entry to the patient room. Patients requiring CPs were defined as colonized or infected with MDROs (meticillin-resistant Staphylococcus aureus (MRSA), non-Escherichia coli extended-spectrum beta lactamase (ESBL) Enterobacterales, vancomycin-resistant enterococci (VRE) and carbapenem-resistant Gram-negative micro-organisms (CRGN)) as well as patients infected with respiratory viruses, norovirus, scabies and hypervirulent strains of Clostridioides difficile. Findings Overall, data from 13,756 CP records from 1378 visits of 812 patients were analysed. Adherence varied between 93% and 100% for each intervention, except for “separate space for contaminated material” with an adherence of 5.3–6.1%. The incidence of in-hospital transmission during the study period was extremely low for MRSA, VRE, non-E.coli ESBL Enterobacterales and CRGN with 0.00–0.064 cases/1000 patient days. Conclusion High adherence coupled with continuous monitoring of CPs correlated with a very low in-hospital transmission rate. These results indicate that CPs are highly effective if routine monitoring of adherence is implemented.

Background The optimal extent of screening of contact patients (CoPat) after exposure to patients infected or colonized with vancomycin-resistant enterococci (VRE) remains controversial. Methods We retrospectively developed a new risk stratification for screening patients exposed to VRE, based on data from three outbreaks—two with Enterococcus faecium vanB and one with Enterococcus faecium vanA involving 1096 CoPat—in a low endemic setting. We classified them into four risk groups: three on environmental exposure, one by healthcare exposure: high (sharing the same room/bathroom with a VRE-colonized patient), medium (hospitalization in the same room after a VRE-colonized patient’s discharge until terminal disinfection including ultraviolet C (UVc)-disinfection), low (hospitalized in the same room within three weeks before the VRE-colonized patient), and “staff” (screening of patients having the same medical care team). Results VRE-transmission occurred in 7.9% in the high-risk group compared to 0.6% and 0% in the medium and low risk groups. There was a significant trend to higher rates of transmission by risk level of exposure (p Conclusion Based on this stratification, we recommend to focus screening of exposed CoPat on the high-risk and “staff” group, saving resources and costs, but larger studies will allow to further improve the yield of VRE screening in the outbreak setting.

Background Rapid pathogen identification from positive blood cultures may help optimize empiric antibiotic therapy quickly by reducing unnecessary broad spectrum antibiotic use and may improve patient outcomes. The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) identifies 24 pathogens directly from positive blood cultures without subculture. 3 resistance genes are included. We aimed to compare the time to optimal antibiotic therapy between BF-FA-BCIP and conventional identification. Methods We performed a single-center retrospective case-control before-after study of 386 cases (November 2018 to October 2019) with BF-FA-BCIP compared to 414 controls (August 2017 to July 2018) with conventional identification. The primary study endpoint was the time from blood sampling to implementation of optimal antimicrobial therapy. Secondary endpoints were time to effective therapy, length of hospital stay, and in-hospital and 30-day mortality. Outcomes were assessed using cause-specific Cox Proportional Hazard models and logistic regressions. Results We included 800 patients with comparable baseline characteristics. Main sources of blood stream infection (BSI) were urinary tract infection and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7% for case and control groups, respectively). Overall, 212 positive blood cultures were considered as contaminations. Identification results were available after a median of 21.9 hours by the BF-FA-BCIP and 44.3 hours by the conventional method. Patients with BF-FA-BCIP received the optimal therapy after a median of 25.5 hours (95%CI 21.0 - 31.2) as compared to 45.7 hours (95%CI 37.7 - 51.2) in the control group (Figure 1). We found no effect of the identification method on secondary outcomes. Kaplan-Meier curve representing the probability of implementing the optimal therapy at any given time according to the identification method (Standard vs. BF-FA-BCIP). Shaded ribbons represent the 95 % confidence interval (CI). The vertical dashes represent censored data. The vertical dotted lines represent the median time, i.e. the time at which 50 % of the patients obtained the optimal therapy, for the two methods. Median (95 % CI) time to optimal therapy is 45.7 (37.7 - 51.4) hours with the Standard method and 25.5 (21.0- 31.2) hours with Biofire. The tables below the curves present the numbers expecting optimal therapy according to the bacteria identification method, as well as the number of censored data in parenthesis. Panel A shows data from 0 to 900 hours. Panel B shows the data from 0 to 90 hours to better visualize how the probability to implement optimal therapy varies in the first 72 hours. Conclusion In conclusion, rapid pathogen identification by BF-FA-BCIP was associated with an almost 24h earlier initiation of the optimal antibiotic therapy in BSI. However, the overall benefit for individual patients seems to be limited. Future studies should assess the cost-effectiveness and impact on the prevention of antibiotic resistance using this diagnostic approach. Disclosures All Authors: No reported disclosures

We report the first documented in-hospital patient-to-patient-transmission of a blaVIM-2 integron between isolates of Pseudomonas alcaligenes and P. aeruginosa. Molecular typing looking only for difference within species may fail to detect nosocomial transmission of resistance genes.

Summary Background Healthcare-associated infections (HAIs) lead to high morbidity and mortality. Data for HAIs in psychiatric hospitals are scarce, and are not derived from long-term surveillance. Aim To assess the impact of an infection control service on the prevalence of HAIs in a psychiatric hospital over an 18-year period. Methods In 1999, a professional infection control service was initiated at the University Psychiatric Hospital in Basel, Switzerland, with a part-time infection control nurse, a hospital epidemiologist, and administrative support. In addition to monitoring rates of multi-drug-resistant pathogens, eight prevalence studies using definitions outlined by the Centers for Disease Control and Prevention (CDC) were conducted between 2001 and 2018. For the primary outcome, a Poisson regression model was fitted to confirm cases of HAIs, standardized for patients at risk as a model offset. Findings Overall, the predicted prevalence of nosocomial infections decreased from 3.7% (95% confidence interval (CI) 2.2–5.3%) in 2001 to 1.0% (95% CI 0.2–1.8%) in 2018 after introduction of an infection control service (incidence ratio rate (IRR) for yearly decrease of 0.93, 95% CI 0.87–0.98, P=0.007). Conclusions Implementation of an infection control service may lead to a significant long-term decrease in HAIs, even in an institution caring for patients with low risk for HAIs, such as in psychiatric hospitals. In addition, epidemics and clusters were rapidly contained. Infection control services from acute-care hospitals should be expanded to psychiatric institutions, in order to decrease the incidence of HAIs and meet new challenges in times of emergence of multi-drug-resistant pathogens.

Background Emergence of colistin resistance has been related to increased use in clinical settings, following global spread of carbapenem-resistant Gram-negative bacteria. Use of colistin in animal production may constitute a further source of spread of resistant strains to humans. We sought to determine risk factors for human colonisation or infection with colistin-resistant Escherichia coli and Klebsiella pneumoniae in a setting where colistin is mainly used for animal production. Methods: This retrospective matched case–control study was performed during a 5-year period at two university-affiliated hospitals in Basel, Switzerland. Conditional univariable logistic regression was used to calculate odds ratios (OR) for colistin resistance. All variables found to be significant in univariable analyses were included in the conditional multivariable regression model using stepwise forward and backward selection. Results: Forty-two cases (33 with colistin-resistant E. coli, 9 with colistin-resistant K. pneumoniae) and 126 matched controls were identified. Baseline characteristics, comorbidities, prior exposure to antibiotics and healthcare settings did not differ between cases and controls, except for prior exposure to carbapenems, hospitalisation and stay abroad during the prior 3 months. In multivariable analyses, only prior exposure to carbapenems remained associated with colistin resistance (OR: 5.00; 95% confidence interval (95% CI): 1.19–20.92; p = 0.028). Conclusion: In a low-endemicity setting for carbapenem resistance, prior exposure to carbapenems was the only risk factor for colonisation or infection with colistin-resistant E. coli or K. pneumoniae. Prior exposure to colistin was not significantly associated with detection of colistin resistance, which mainly occurred in the absence of concurrent carbapenem resistance.

Background Conflicting results have been published on the impact of contact precautions, as outlined by CDC, HIPAC and ESCMID guidelines, on reduction of transmission of multidrug-resistant organisms (MDRO). Ambiguous definitions coupled with low adherence to these partly explain the differences on impact of contact precautions on transmission of MDROs. We therefore monitored compliance with contact precautions and correlated the level of adherence with in-hospital transmission of MDROs. Methods Between January 2016 and March 2018, all patients under contact precautions underwent routine monitoring of adherence to contact precautions by routine on site visits on day 0 (+1), 3 (+/−1) and 7(+/−3) after initiating of contact precautions using a predefined standardized checklist. The protocol includes 10 interventions that are routinely checked such as contact precaution sign at the door and wearing gowns and gloves before entering the room. Patients requiring contact precautions were defined as colonized or infected with MDROs (MRSA, non-E. coli ESBL-Enterobacteriaceae (NEC-ESBL), VRE and carbapenemase-producing organisms) as well as patients infected with RSV, norovirus and hypervirulent strains of C. difficile. Results Overall, data of 1,414 visits of 812 patients under contact precautions were assessed. During the observation period, overall adherence was between 93–99% for each intervention, except for separate space for contaminated material with a very low adherence between 5.4 and 6.1%. The incidence of in-hospital transmission was extremely low for MRSA, VRE and NEC-ESBL with 0.02–0.1/100,000 patient days. Conclusion Continuous monitoring of the quality of contact precautions showed excellent overall adherence correlating with a very low in-hospital transmission of MDROs, encouraging monitoring as an integrated part of contact precautions. Disclosures All authors: No reported disclosures.

Background Clostridium difficile infection (CDI) remains a major health problem worldwide. Antibiotic use, in general, and clindamycin and ciprofloxacin, in particular, have been implicated in the pathogenesis of CDI. Here, we hypothesized that antibiotics that are highly active in vitro against C. difficile are less frequently associated with CDI than others. The primary goals of our study were to determine if antibiotic susceptibility and CDI are associated and whether the antimicrobial susceptibility of C. difficile changed over the years. Methods and results We examined a large panel of C. difficile strains collected in 2006-2008 at the University Hospital of Zurich. We found that the antimicrobial susceptibilities to amoxicillin/clavulanate, piperacillin/tazobactam, meropenem, clindamycin, ciprofloxacin, ceftriaxone, metronidazole and vancomycin were similar to those reported in the literature and that they are similar to those reported in other populations over the last two decades. Antibiotic activity did not prevent CDI. For example, thre use of meropenem, which is highly active against all strains tested, was a clear risk factor for CDI. Most of the antibiotics tested also showed a higher minimum inhibitory concentration distribution than that of EUCAST. All strains were susceptible to metronidazole. One strain was resistant to vancomycin. Conclusions Antibiotic susceptibilities of the collection of C. difficile from the University Hospital of Zurich are similar to those reported by others since the 1980. Patients treated with carbapenems and cephalosporins had the highest risk of developing CDI irrespective of the antimicrobial activity of carbapenems., BMC Infectious Diseases, 14, ISSN:1471-2334

BACKGROUND: Broad-range 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) is used for detection and identification of bacterial pathogens in clinical specimens from patients with a high suspicion for infection. However, prospective studies addressing the impact and clinical value of broad-range bacterial 16S rRNA gene amplification for diagnosis of acute infectious diseases in nonselected patient populations are lacking. METHODS: We first assessed the diagnostic performance of 16S rRNA gene PCR compared with routine bacterial culture. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of acute infections using samples that tested negative by routine bacterial culture; the corresponding patients' data were evaluated by detailed medical record reviews. RESULTS: Results from 394 specimens showed a high concordance of >90% for 16S rRNA gene PCR and routine bacterial culture, indicating that the diagnostic performance of PCR for acute bacterial infections is comparable to that of bacterial culture, which is currently considered the gold standard. In thisprospective study, 231 specimens with a negative result on routine bacterial culture were analyzed with PCR, and patients' clinical data were reviewed. We found that broad-range 16S rRNA gene PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 42.9%, 100%, 100%, and 80.2% for culture-negative bacterial infections. CONCLUSIONS: This study defines the role of 16S rRNA gene PCR for diagnosis of culture-negative bacterial infections. Our data show that 16S rRNA gene PCR is particularly useful for identification of bacterial pathogens in patients pretreated with antibiotics.

Clinical isolates that are difficult to identify by conventional means form a valuable source of novel human pathogens. We report on a 5-year study based on systematic 16S rRNA gene sequence analysis. We found 60 previously unknown 16S rRNA sequences corresponding to potentially novel bacterial taxa. For 30 of 60 isolates, clinical relevance was evaluated; 18 of the 30 isolates analyzed were considered to be associated with human disease.