Povidone Iodine vs Chlorhexidine Gluconate in Alcohol for Preoperative Skin Antisepsis: A Randomized Clinical Trial.

Importance: Preoperative skin antisepsis is an established procedure to prevent surgical site infections (SSIs). The choice of antiseptic agent, povidone iodine or chlorhexidine gluconate, remains debated. Objective: To determine whether povidone iodine in alcohol is noninferior to chlorhexidine gluconate in alcohol to prevent SSIs after cardiac or abdominal surgery. Design, Setting, and Participants: Multicenter, cluster-randomized, investigator-masked, crossover, noninferiority trial; 4403 patients undergoing cardiac or abdominal surgery in 3 tertiary care hospitals in Switzerland between September 2018 and March 2020 were assessed and 3360 patients were enrolled (cardiac, n = 2187 [65%]; abdominal, n = 1173 [35%]). The last follow-up was on July 1, 2020. Interventions: Over 18 consecutive months, study sites were randomly assigned each month to either use povidone iodine or chlorhexidine gluconate, each formulated in alcohol. Disinfectants and skin application processes were standardized and followed published protocols. Main Outcomes and Measures: Primary outcome was SSI within 30 days after abdominal surgery and within 1 year after cardiac surgery, using definitions from the US Centers for Disease Control and Prevention's National Healthcare Safety Network. A noninferiority margin of 2.5% was used. Secondary outcomes included SSIs stratified by depth of infection and type of surgery. Results: A total of 1598 patients (26 cluster periods) were randomly assigned to receive povidone iodine vs 1762 patients (26 cluster periods) to chlorhexidine gluconate. Mean (SD) age of patients was 65.0 years (39.0-79.0) in the povidone iodine group and 65.0 years (41.0-78.0) in the chlorhexidine gluconate group. Patients were 32.7% and 33.9% female in the povidone iodine and chlorhexidine gluconate groups, respectively. SSIs were identified in 80 patients (5.1%) in the povidone iodine group vs 97 (5.5%) in the chlorhexidine gluconate group, a difference of 0.4% (95% CI, -1.1% to 2.0%) with the lower limit of the CI not exceeding the predefined noninferiority margin of -2.5%; results were similar when corrected for clustering. The unadjusted relative risk for povidone iodine vs chlorhexidine gluconate was 0.92 (95% CI, 0.69-1.23). Nonsignificant differences were observed following stratification by type of surgical procedure. In cardiac surgery, SSIs were present in 4.2% of patients with povidone iodine vs 3.3% with chlorhexidine gluconate (relative risk, 1.26 [95% CI, 0.82-1.94]); in abdominal surgery, SSIs were present in 6.8% with povidone iodine vs 9.9% with chlorhexidine gluconate (relative risk, 0.69 [95% CI, 0.46-1.02]). Conclusions and Relevance: Povidone iodine in alcohol as preoperative skin antisepsis was noninferior to chlorhexidine gluconate in alcohol in preventing SSIs after cardiac or abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03685604.

Post-Acute Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Viral Variant and Vaccination Status: A Multicenter Cross-Sectional Study.

BACKGROUND: Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS: We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status. RESULTS: Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1-2 vaccinations (P = .028) and 0.49 with ≥3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08-3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS: Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Results of a Prospective Multicenter Cohort.

BACKGROUND: The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed. METHODS: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence. RESULTS: Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores. CONCLUSIONS: Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Risk and symptoms of COVID-19 in health professionals according to baseline immune status and booster vaccination during the Delta and Omicron waves in Switzerland-A multicentre cohort study.

BACKGROUND: Knowledge about protection conferred by previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or vaccination against emerging viral variants allows clinicians, epidemiologists, and health authorities to predict and reduce the future Coronavirus Disease 2019 (COVID-19) burden. We investigated the risk and symptoms of SARS-CoV-2 (re)infection and vaccine breakthrough infection during the Delta and Omicron waves, depending on baseline immune status and subsequent vaccinations. METHODS AND FINDINGS: In this prospective, multicentre cohort performed between August 2020 and March 2022, we recruited hospital employees from ten acute/nonacute healthcare networks in Eastern/Northern Switzerland. We determined immune status in September 2021 based on serology and previous SARS-CoV-2 infections/vaccinations: Group N (no immunity); Group V (twice vaccinated, uninfected); Group I (infected, unvaccinated); Group H (hybrid: infected and ≥1 vaccination). Date and symptoms of (re)infections and subsequent (booster) vaccinations were recorded until March 2022. We compared the time to positive SARS-CoV-2 swab and number of symptoms according to immune status, viral variant (i.e., Delta-dominant before December 27, 2021; Omicron-dominant on/after this date), and subsequent vaccinations, adjusting for exposure/behavior variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, thereof 591 during the Omicron period. Compared to group N, the hazard ratio (HR) for (re)infection was 0.33 (95% confidence interval [CI] 0.22 to 0.50, p < 0.001) for V, 0.25 (95% CI 0.11 to 0.57, p = 0.001) for I, and 0.04 (95% CI 0.02 to 0.10, p < 0.001) for H in the Delta period. HRs substantially increased during the Omicron period for all groups; in multivariable analyses, only belonging to group H was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with reduction of breakthrough infection risk in groups V (aHR 0.68, 95% CI 0.54 to 0.85, p = 0.001) and H (aHR 0.67, 95% CI 0.45 to 1.00, p = 0.048), largely observed in the early Omicron period. Group H (versus N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and participants with booster vaccination (versus nonboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.001) reported less symptoms during infection. Important limitations are that SARS-CoV-2 swab results were self-reported and that results on viral variants were inferred from the predominating strain circulating in the community at that time, rather than sequencing. CONCLUSIONS: Our data suggest that hybrid immunity and booster vaccination are associated with a reduced risk and reduced symptom number of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously noninfected individuals, booster vaccination might reduce the risk of symptomatic Omicron infection, although this benefit seems to wane over time.

Identifying the drivers of multidrug-resistant Klebsiella pneumoniae at a European level.

Beta-lactam- and in particular carbapenem-resistant Enterobacteriaceae represent a major public health threat. Despite strong variation of resistance across geographical settings, there is limited understanding of the underlying drivers. To assess these drivers, we developed a transmission model of cephalosporin- and carbapenem-resistant Klebsiella pneumoniae. The model is parameterized using antibiotic consumption and demographic data from eleven European countries and fitted to the resistance rates for Klebsiella pneumoniae for these settings. The impact of potential drivers of resistance is then assessed in counterfactual analyses. Based on reported consumption data, the model could simultaneously fit the prevalence of extended-spectrum beta-lactamase-producing and carbapenem-resistant Klebsiella pneumoniae (ESBL and CRK) across eleven European countries over eleven years. The fit could explain the large between-country variability of resistance in terms of consumption patterns and fitted differences in hospital transmission rates. Based on this fit, a counterfactual analysis found that reducing nosocomial transmission and antibiotic consumption in the hospital had the strongest impact on ESBL and CRK prevalence. Antibiotic consumption in the community also affected ESBL prevalence but its relative impact was weaker than inpatient consumption. Finally, we used the model to estimate a moderate fitness cost of CRK and ESBL at the population level. This work highlights the disproportionate role of antibiotic consumption in the hospital and of nosocomial transmission for resistance in gram-negative bacteria at a European level. This indicates that infection control and antibiotic stewardship measures should play a major role in limiting resistance even at the national or regional level.

Impact of baseline SARS-CoV-2 antibody status on syndromic surveillance and the risk of subsequent COVID-19-a prospective multicenter cohort study.

BACKGROUND: In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. METHODS: Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. RESULTS: A total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. CONCLUSIONS: Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months.

Impact of an electronic alert on prescription patterns of meropenem, voriconazole and caspofungin.

BACKGROUND: Antimicrobial stewardship programs promote the appropriate use of antimicrobial substances through the implementation of evidence-based, active and passive interventions. We analyzed the effect of a computer-assisted intervention on antimicrobial use in a tertiary care hospital. METHODS: Between 2011 and 2016 we introduced an electronic alert for patients being prescribed meropenem, voriconazole and caspofungin. At prescription and at day 3 of treatment, physicians were informed about the risk related to these antimicrobial substances by an electronic alert in the medical records. Physicians were invited to revoke or confirm the prescription and to contact the infectious disease (ID) team. Using interrupted time series regression, the days of therapy (DOTs) and the number of prescriptions before and after the intervention were compared. RESULTS: We counted 64,281 DOTs for 5549 prescriptions during 4100 hospital stays. Overall, the DOTs decreased continuously over time. An additional benefit of the alert could not be observed. Similarly, the number of prescriptions decreased over time, without significant effect of the intervention. When considering the three drugs separately, the alert impacted the duration (change in slope of DOTs/1000 bed days; P = 0.0017) as well as the number of prescriptions (change in slope of prescriptions/1000 bed days; P < 0.001) of voriconazole only. CONCLUSIONS: The introduction of the alert lowered prescriptions of voriconazole only. Thus, self-stewardship alone seems to have a limited impact on electronic prescriptions of anti-infective substances. Additional measures such as face-to-face prompting with ID physicians or audit and feedback are indispensable to optimize antimicrobial use.

Inadequate Perioperative Prophylaxis and Postsurgical Complications After Graft Implantation Are Important Risk Factors for Subsequent Vascular Graft Infections: Prospective Results From the Vascular Graft Infection Cohort Study.

BACKGROUND: Reconstructive vascular surgery has become increasingly common. Vascular graft infections (VGIs) are serious complications, leading to increased morbidity and mortality. Previously described risk factors for VGIs include groin incisions, wound infections, and comorbidities. We aimed to identify modifiable predictors for VGIs as targets for infection prevention strategies. METHODS: Participants of the prospective Vascular Graft Infection Cohort (VASGRA) with surgery between 2013 and 2017 were included. The observation time was calculated from surgery until a confirmed VGI or the last follow-up. Variables were assessed by infection status, using non-parametric tests. Univariable and multivariable Cox proportional hazard regression models, adjusted for demographic factors, were applied to assess risk factors for a VGI. RESULTS: A total of 438 predominantly male (83.1%) patients with a median age of 71 years (interquartile range [IQR] 63 - 76) contributed to 554 person years of follow-up. Thereof, 39 (8.9%) developed a VGI, amounting to an incidence rate of 7.0/100 person years. We found incisional surgical site infections (adjusted hazard ratio [aHR] 10.09, 95% CI 2.88 - 35.34); hemorrhage (aHR 4.92, 1.28-18.94); renal insufficiency (aHR 4.85, 1.20 - 19.61); inadequate perioperative prophylaxis in patients with an established antibiotic treatment, compared to the additional application of perioperative prophylaxis (aHR 2.87, 95% CI 1.17 - 7.05); and procedure time increases of 1-hour intervals (aHR 1.22, 95% CI 1.08 - 1.39) to be risk factors for VGIs. CONCLUSIONS: We identified procedure time; inadequate perioperative prophylaxis, especially among patients with an established antibiotic treatment; and several postsurgical infectious and non-infectious complications as modifiable, predictive factors for VGIs and, therefore, as keys to improved surveillance programs and prevention strategies. CLINICAL TRIALS REGISTRATION: NCT01821664.

The TransFLUas influenza transmission study in acute healthcare - recruitment rates and protocol adherence in healthcare workers and inpatients.

BACKGROUND: Detailed knowledge about viral respiratory disease transmission dynamics within healthcare institutions is essential for effective infection control policy and practice. In the quest to study viral transmission pathways, we aimed to investigate recruitment rates and adherence of healthcare workers (HCWs) and hospital inpatients with a study protocol that involves prospective surveillance based on daily mid-turbinate nasal swabs and illness diaries. METHODS: Single center prospective surveillance of patients and HCWs in three different hospital departments of a tertiary care center during an entire influenza season in Switzerland. Inpatients and acute care HCWs were asked to provide mid-turbinate nasal swabs and illness diaries on a daily basis. Study protocol adherence and recruitment rates were the primary outcomes of interest. RESULTS: A total 251 participants (59 (23.5%) health care workers and 192 (76.5%) inpatients) were recruited from three different hospital wards. Recruitment rates differed between HCWs (62.1% of eligible HCWs) and inpatients (32.5%; P < 0.001), but not within HCWs (P = 0.185) or inpatients (P = 0.301) of the three departments. The total number of study-days was 7874; 2321 (29.5%) for inpatients and 5553 (70.5%) for HCWs. HCWs were followed for a median of 96 days (range, 71-96 days) and inpatients for 8 days (range, 3-77 days). HCWs provided swabs on 73% (range, 0-100%) of study days, and diaries on 77% (range 0-100%). Inpatients provided swabs and diaries for 83% (range, 0-100%) of days in hospital. In HCWs, increasing age, working in internal medicine and longer duration of total study participation were positively associated with the proportion of swabs and diaries collected. Adherence to the study protocol was significantly lower in physicians as compared to nurses for both swabs (P = 0.042) and diaries (P = 0.033). In inpatients, no association between demographic factors and adherence was detected. Conclusions Prospective surveillance of respiratory viral disease was feasible in a cohort of inpatients and HCWs over an entire influenza season, both in terms of recruitment rates and adherence to a study protocol that included daily specimen collection and illness diaries. TRIAL REGISTRATION: clinicaltrials.gov NCT02478905 . Date of registration June 23, 2015.

Association of Cutibacterium avidum Colonization in the Groin With Obesity: A Potential Risk Factor for Hip Periprosthetic Joint Infection.

Background: An increase in the incidence of hip periprosthetic joint infections caused by Cutibacterium avidum has recently been detected after hip arthroplasty with an anterior surgical approach. We raised the question of whether skin colonization with C. avidum differs between the anterior and the lateral thigh as areas of surgical incision fields. Methods: Between February and June 2017, we analyzed skin scrapings from the groin and the anterior and lateral thigh in patients undergoing a primary hip arthroplasty. We anaerobically cultured plated swab samples for Cutibacterium spp. for ≥7 days. Univariate logistic regression analysis was used to explore associations between body mass index (BMI) and colonization rate at different sites. Results: Twenty-one of 65 patients (32.3%) were colonized with C. avidum at any site, mainly at the groin (n = 16; 24.6%), which was significantly higher at the anterior (n = 5; 7.7%; P = .009) or lateral (n = 6; 9.2%; P = .02) thigh. Patients colonized with C. avidum did not differ from noncolonized patients in age or sex, but their BMIs were significantly higher (30.1 vs 25.6 kg/m2, respectively; P = .02). Furthermore, increased BMI was associated with colonization at the groin (odds ratio per unit BMI increase, 1.15; 95% confidence interval; 1.03-1.29; P = .01). Conclusions: The groin, rather than the anterior thigh, showed colonization for C. avidum in obese patients. Further studies are needed to evaluate current skin disinfection and draping protocols for hip arthroplasty, particularly in obese patients.

Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART.

BACKGROUND: The major obstacle to cure of HIV type-1 infection is the presence of the HIV reservoir, hidden from the immune system and insensitive to combined antiretroviral therapy (cART). Eradication approaches have been hindered by the difficulty for accurately monitoring its size in vivo, especially in the lymphoid organs. Humanized mouse models are a valuable tool for systematically assess the efficacy of therapeutic interventions in reducing the HIV reservoir. Nonetheless, persistence of the HIV reservoir over time, in the presence of cART, has yet to be analyzed in this in vivo model. FINDINGS: We found that the proviral DNA as well as the total DNA were very stable in the spleen and mesenteric lymph node irrespective of the length of cART. Notably, the amount of proviral DNA was very similar in the spleen and lymph node. Furthermore, we observed a correlation between the percentage of splenic human CD4+ T-cells with total HIV DNA, between the number of human CD38 + CD8+ T-cells in the spleen with the amount of integrated HIV DNA, and eventually between the hCD4/hCD8 ratio in the spleen with integrated as well as total HIV DNA implying that the CD8+ T cells influence the size of the HIV reservoir. CONCLUSIONS: Here, we demonstrated the stability of this reservoir in humanized mice irrespective of the length of cART, confirming the relevancy of this model for HIV latency eradication investigations. Notably, we also found correlates between the frequency of CD4+ T-cells, their activation status and viral parameters, which were analogous to the ones in HIV-infected patients. Thus, hu-mice represent a very valuable HIV latency model.

Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells.

BACKGROUND: Humanized mice (hu mice) are based on the transplantation of hematopoietic stem and progenitor cells into immunodeficient mice and have become important pre-clinical models for biomedical research. However, data about their hematopoiesis over time are scarce. We therefore characterized leukocyte reconstitution in NSG mice, which were sublethally irradiated and transplanted with human cord blood-derived CD34+ cells at newborn age, longitudinally in peripheral blood and, for more detailed analyses, cross-sectionally in peripheral blood, spleen and bone marrow at different time points. RESULTS: Human cell chimerism and absolute human cell count decreased between week 16 and 24 in the peripheral blood of hu mice, but were stable thereafter as assessed up to 32 weeks. Human cell chimerism in spleen and bone marrow was maintained over time. Notably, human cell chimerism in peripheral blood and spleen as well as bone marrow positively correlated with each other. Percentage of B cells decreased between week 16 and 24, whereas percentage of T cells increased; subsequently, they levelled off with T cells clearly predominating at week 32. Natural killer cells, monocytes and plasmacytoid dendritic cells (DCs) as well as CD1c + and CD141+ myeloid DCs were all present in hu mice. Proliferative responses of splenic T cells to stimulation were preserved over time. Importantly, the percentage of more primitive hematopoietic stem cells (HSCs) in bone marrow was maintained over time. CONCLUSIONS: Overall, leukocyte reconstitution was maintained up to 32 weeks post-transplantation in our hu NSG model, possibly explained by the maintenance of HSCs in the bone marrow. Notably, we observed great variation in multi-lineage hematopoietic reconstitution in hu mice that needs to be taken into account for the experimental design with hu mice.

Transmission of Mycobacterium chimaera from Heater-Cooler Units during Cardiac Surgery despite an Ultraclean Air Ventilation System.

Heater-cooler units (HCUs) were recently identified as a source of Mycobacterium chimaera causing surgical site infections. We investigated transmission of this bacterium from HCUs to the surgical field by using a thermic anemometer and particle counter, videotape of an operating room equipped with an ultraclean laminar airflow ventilation system, and bacterial culture sedimentation plates in a nonventilated room. Smoke from the HCU reached the surgical field in 23 s by merging with ultraclean air. The HCU produced on average 5.2, 139, and 14.8 particles/min in the surgical field at positions Off, On/oriented toward, and On/oriented away, respectively. Culture plates were positive for M. chimaera <5 m from the HCU in the test room. These experiments confirm airborne transmission of M. chimaera aerosols from a contaminated HCU to an open surgical field despite ultraclean air ventilation. Efforts to mitigate infectious risks during surgery should consider contamination from water sources and airflow-generating devices.

Reemergence of Mycobacterium chimaera in Heater-Cooler Units despite Intensified Cleaning and Disinfection Protocol.

Invasive Mycobacterium chimaera infections after open-heart surgery have been reported internationally. These devastating infections result from aerosols generated by contaminated heater-cooler units used with extracorporeal circulation during surgery. Despite intensified cleaning and disinfection, surveillance samples from factory-new units acquired during 2014 grew nontuberculous mycobacteria after a median of 174 days.

The Roles of the Charlson Comorbidity Index and Time to First Antibiotic Dose as Predictors of Outcome in Pneumococcal Community-Acquired Pneumonia.

PURPOSE: In this retrospective study, we aimed to investigate the role of comorbidities using the Charlson comorbidity index (CCI) and time to first antibiotic dose (TFAD) in patients with pneumococcal community-acquired pneumonia (PCAP). METHODS: All consecutive ER admissions with PCAP who were hospitalized in the University Hospital, Zurich between 2006 and 2012 were included. The primary outcome was to determine possible determinants of all-cause in-hospital mortality (ACIHM). The second endpoint was to detect risk factors for adverse events (AEs) and determinants of length of stay (LOS). RESULTS: 108 subjects (mean age 57.6 years) were included. The median (IQR) CCI was 4 (1, 8). The median (IQR) TFAD was 210 (150, 280) min. ACIHM was 6.5 % (7/108), and median (IQR) LOS was 9 (6, 14) days. PCAP-related AEs were observed in 57 cases (52.8 %). In the multivariable analysis, neither CCI nor TFAD was associated with the outcome measures. Pneumonia severity index (PSI) was the only statistically significant predictor of ACIHM (HR 1.31/10 point increase, 95 % CI 1.12-1.53, p = 0.001) and AE rate (OR 1.31, 95 % CI 1.15-1.50, p < 0.001). CONCLUSIONS: In this study including comparatively young patients with rather mild disease severity, we found no strong evidence supporting that CCI or TFAD influenced short-term outcome measures of PCAP. Yet, pneumonia severity appears to be the most important factor for the outcome.

Herd effect from influenza vaccination in non-healthcare settings: a systematic review of randomised controlled trials and observational studies.

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34-1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26-0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43-0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved.

Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators: the NORDIC ICD randomized clinical trial.

AIMS: This trial was designed to test the hypothesis that shock efficacy during follow-up is not impaired in patients implanted without defibrillation (DF) testing during first implantable cardioverter-defibrillator (ICD) implantation. METHODS AND RESULTS: Between February 2011 and July 2013, 1077 patients were randomly assigned (1 : 1) to first time ICD implantation with (n = 540) or without (n = 537) DF testing. The intra-operative DF testing was standardized across all participating centres, and all ICD shocks were programmed to 40 J irrespective of DF test results. The primary end point was the average first shock efficacy (FSE) for all true ventricular tachycardia and fibrillation (VT/VF) episodes during follow-up. The secondary end points included procedural data, serious adverse events, and mortality. During a median follow-up of 22.8 months, the model-based FSE was found to be non-inferior in patients with an ICD implanted without a DF test, with a difference in FSE of 3.0% in favour of the no DF test [confidence interval (CI) -3.0 to 9.0%, Pnon-inferiority <0.001 for the pre-defined non-inferiority margin of -10%). A total of 112 procedure-related serious adverse events occurred within 30 days in 94 patients (17.6%) tested compared with 89 events in 74 patients (13.9%) not tested (P = 0.095). CONCLUSION: Defibrillation efficacy during follow-up is not inferior in patients with a 40 J ICD implanted without DF testing. Defibrillation testing during first time ICD implantation should no longer be recommended for routine left-sided ICD implantation.

Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery.

AIMS: We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. METHODS AND RESULTS: Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. CONCLUSION: Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens.