Epidemiology of Surgical Site Infections With Staphylococcus aureus in Europe: Protocol for a Retrospective, Multicenter Study

Background: Surgical site infections (SSIs) are among the most common hospital acquired infections. While the incidence of SSI in certain indicator procedures is the subject of ongoing surveillance efforts in hospitals and health care systems around the world, SSI rates vary markedly within surgical categories and are poorly represented by routinely monitored indicator procedures (eg, mastectomy or hernia surgery). Therefore, relying on indicator procedures to estimate the burden of SSI is imprecise and introduces bias as hospitals may take special precautions to achieve lower SSI rates. The most common cause of SSI is Staphylococcus aureus (S. aureus), as recently confirmed by a Europe-wide point-prevalence study conducted by the European Centre for Disease Prevention and Control (ECDC). Objective: The primary objective of this study is to determine the overall and procedure-specific incidence of S. aureus SSI in Europe. Secondary objectives are the overall and procedure-specific outcomes as well as the economic burden of S. aureus SSI in Europe. Explorative objectives are to characterize the composition of the surgical patient population and to estimate the number of patients at risk for S. aureus SSI. Methods: A retrospective, multinational, multicenter cohort study (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe [SALT] study) with a nested case-control part will be conducted. The study will include all surgical procedures at a participating center in order to prevent selection bias and strengthen the understanding of SSI risk by determining the incidence for all common surgical procedures. Data will be assessed in the cohort population, including 150,000 adult patients who underwent any surgical procedure in 2016, and the case-control population. We will match patients establishing S. aureus SSI 1:1 with controls from the same center. Data on demographics, surgery, and microbiology will be exported from electronic files. More detailed data will be captured from the case-control population. The SALT study will include 13 major or academic surgical centers in Europe, comprising 3 in France, 4 in Germany, 2 in Italy, 3 in Spain, and 1 in the United Kingdom. Sites were selected using a feasibility questionnaire. Results: The SALT study is currently recruiting patients. The aim is to complete recruitment in February 2018 and to close the database in September 2018. The final results are expected by the end of 2018. Conclusions: Results of the SALT study will help to better understand the precise risk of certain procedures. They will also provide insight into the overall and procedure-specific incidence and outcome as well as the economic burden of S. aureus SSI in Europe. Findings of the study may help guide the design of clinical trials for S. aureus vaccines

Staphylococcus aureus surgical site infection rates in 5 European countries

Objective: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe. Methods: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching. Results: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure. Conclusions: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017)

Colonization and infection with extended spectrum beta-lactamase producing Enterobacteriaceae in high-risk patients - Review of the literature from a clinical perspective

Background: The prevalence of extended-spectrum -lactamase producing Enterobacteriaceae (ESBL-E) is increasing worldwide. ESBL-E are known to colonize different body sites and cause bloodstream infections (BSI), pneumonia, intra-abdominal infections and urinary tract infections. Even though ESBL-E-related morbidity and mortality in high-risk patients - patients receiving immunosuppressants or chemotherapy, as well as those treated in an ICU - is considerable, the management of ESBL-E in these populations has not been systematically reviewed. Methods: For the purpose of this review, ICU patients, patients in hematology and oncology wards and transplant recipients were considered high-risk. An English-language Medline search was conducted to identify literature on epidemiology, risk factors, clinical impact and measures of infection control regarding ESBL-E in high-risk patients published between June 2002 and May 2013. Results: Using the above described methodology, 43 relevant articles regarding high-risk patients and - for areas where literature on exclusively high-risk patients is scarce - 17 articles in standard risk settings were identified. The evidence on epidemiology, associated risk factors, treatment and hygiene measures were summarized. Discussion: This review gives a complete overview on the management of ESBL-E in the high-risk setting

Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Analysis of Fluconazole, Isavuconazole, Itraconazole, Hydroxy-Itraconazole, Posaconazole, and Voriconazole in Human Plasma and Serum

Background: A fast and easy-to-use liquid chromatographytandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed and validated for therapeutic drug monitoring. Methods: Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. Isotope-labeled analogues for each analyte were used as internal standards. Chromatographic separation was achieved using a 50 u 2.1 mm, 1.9 mm polar Hypersil Gold C18 column and mobile phase consisting of 0.1% formic acid/acetonitrile (45%/55%, vol/vol) at a flow rate of 340 mu L/min. The triazoles were simultaneously detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring mode with positive heated electrospray ionization within a single runtime of t = 3.00 minutes. Results: Linearity of all azole concentration ranges was verified by the Mandel test and demonstrated for all azoles. All calibration curves were linear and fitted using least squares regression with a weighting factor of the reciprocal concentration. Limits of detection (mu g/L/L) were FLZ, 9.3; ISZ, 0.3; ITZ, 0.6; OH-ITZ, 8.6; PSZ, 3.4; and VRZ, 2.1. The lower limits of quantitation (mu g/L/liter) were FLZ, 28.3; ISZ, 1.0; ITZ, 1.7; OH-ITZ, 26.2; PSZ, 10.3; and VRZ, 6.3. Intraday and interday precisions ranged from 0.6% to 6.6% for all azoles. Intraday and interday accuracies (% bias) of all analytes were within 10.5%. In addition, we report on a 29-year-old white woman (94 kg body weight) with a history of acute myeloid leukemia who underwent stem cell transplantation. Because of diagnosis of aspergillus pneumonia, antifungal pharmacotherapy was initiated with different application modes and dosages of ISZ, and plasma concentrations were monitored over a time period of 6 months. Conclusions: A precise and highly sensitive liquid chromatographytandem mass spectrometry method was developed that enables quantification of triazoles in plasma and serum matrix across therapeutically relevant concentration ranges. It was successfully implemented in our therapeutic drug monitoring routine service and is suitable for routine monitoring of antifungal therapy and in severely ill patients

A cohort study on breakthrough invasive fungal infections in high-risk patients receiving antifungal prophylaxis

Antifungal prophylaxis is recommended for haematological patients at high risk of invasive fungal infections (IFIs). Incidence, optimal therapeutic management and outcome of breakthrough IFIs (bIFIs) are largely unknown. To assess bIFI incidence, treatment and outcomes, data on patients undergoing AML remission-induction and consolidation chemotherapy and from allogeneic HSCT recipients on antifungal prophylaxis with itraconazole, micafungin or posaconazole were extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut). bIFIs were classified according to revised EORTC/MSG criteria. From January 2004 to April 2013, 250 AML patients with 329 hospitalizations and 409 HSCT patients with 496 hospitalizations were identified. In AML patients, there were 16 (6.4%) proven or probable bIFIs and 44 (17.6%) possible bIFIs. In HSCT patients, there were 14 (3.4%) proven or probable bIFIs and 37 (9.0%) possible bIFIs. Proven cases included five candidaemias, two mucormycoses, three aspergilloses and one fusariosis. The most frequent choice for bIFI treatment was liposomal amphotericin B in AML patients (21/60; 35.0%) and continuation of posaconazole prophylaxis in HSCT patients (16/51; 31.4%). In HSCT recipients, survival on day 365 was significantly lower in bIFI patients (AML, 63.3% versus 70.0%; P=0.297; HSCT, 49.0% versus 66.8%; P=0.012). Comparison of continuation of prophylaxis versus switch of antifungal class as first-line treatment showed no significant difference regarding response to treatment and survival. Rates of bIFIs observed in our population were comparable to previous data. There was no clear shift towards rare species, as previously reported. A high variety of treatment approaches was observed

Digital monitoring and management of patients with advanced or metastatic non-small cell lung cancer treated with cancer immunotherapy and its impact on quality of clinical care:interview and survey study among health care professionals and patients

Abstract Background: Cancer immunotherapy (CIT), as a monotherapy or in combination with chemotherapy, has been shown to extend overall survival in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). However, patients experience treatment-related symptoms that they are required to recall between hospital visits. Digital patient monitoring and management (DPMM) tools may improve clinical practice by allowing real-time symptom reporting. Objective: This proof-of-concept pilot study assessed patient and health care professional (HCP) adoption of our DPMM tool, which was designed specifically for patients with advanced or metastatic NSCLC treated with CIT, and the tool’s impact on clinical care. Methods: Four advisory boards were assembled in order to co-develop a drug- and indication-specific CIT (CIT+) module, based on a generic CIT DPMM tool from Kaiku Health, Helsinki, Finland. A total of 45 patients treated with second-line single-agent CIT (ie, atezolizumab or otherwise) for advanced or metastatic NSCLC, as well as HCPs, whose exact number was decided by the clinics, were recruited from 10 clinics in Germany, Finland, and Switzerland between February and May 2019. All clinics were provided with the Kaiku Health generic CIT DPMM tool, including our CIT+ module. Data on user experience, overall satisfaction, and impact of the tool on clinical practice were collected using anonymized surveys—answers ranged from 1 (low agreement) to 5 (high agreement)—and HCP interviews; surveys and interviews consisted of closed-ended Likert scales and open-ended questions, respectively. The first survey was conducted after 2 months of DPMM use, and a second survey and HCP interviews were conducted at study end (ie, after ≥3 months of DPMM use); only a subgroup of HCPs from each clinic responded to the surveys and interviews. Survey data were analyzed quantitatively; interviews were recorded, transcribed verbatim, and translated into English, where applicable, for coding and qualitative thematic analysis. Results: Among interim survey respondents (N=51: 13 [25%] nurses, 11 [22%] physicians, and 27 [53%] patients), mean rankings of the tool’s seven usability attributes ranged from 3.2 to 4.4 (nurses), 3.7 to 4.5 (physicians), and 3.7 to 4.2 (patients). At the end-of-study survey (N=48: 19 [40%] nurses, 8 [17%] physicians, and 21 [44%] patients), most respondents agreed that the tool facilitated more efficient and focused discussions between patients and HCPs (nurses and patients: mean rating 4.2, SD 0.8; physicians: mean rating 4.4, SD 0.8) and allowed HCPs to tailor discussions with patients (mean rating 4.35, SD 0.65). The standalone tool was well integrated into HCP daily clinical workflow (mean rating 3.80, SD 0.75), enabled workflow optimization between physicians and nurses (mean rating 3.75, SD 0.80), and saved time by decreasing phone consultations (mean rating 3.75, SD 1.00) and patient visits (mean rating 3.45, SD 1.20). Workload was the most common challenge of tool use among respondents (12/19, 63%). Conclusions: Our results demonstrate high user satisfaction and acceptance of DPMM tools by HCPs and patients, and highlight the improvements to clinical care in patients with advanced or metastatic NSCLC treated with CIT monotherapy. However, further integration of the tool into the clinical information technology data flow is required. Future studies or registries using our DPMM tool may provide insights into significant effects on patient quality of life or health-economic benefits