Protocol for a prospective cohort study: Prevention of Transmissions by Effective Colonisation Tracking in Neonates (PROTECT-Neo).

INTRODUCTION: Transmissions of opportunistic bacterial pathogens between neonates increase the risk of infections with negative repercussions, including higher mortality, morbidity and permanent disabilities. The probability of transmissions between patients is contingent on a set of intrinsic (patient-related) and extrinsic (ward-related) risk factors that are not clearly quantified. It is the dual objective of the Prevention of Transmissions by Effective Colonisation Tracking-Neo study to determine the density of transmission events in a level III neonatal intensive care unit (NICU) and to identify risk factors that may be causally associated with transmission events. METHODS AND ANALYSIS: A full cohort of patients treated in a 17-bed level III NICU will be prospectively followed and transmission events between two or more patients will be documented. A transmission event occurs when isogenic isolates from two different patients can be identified. Isolates will be obtained by routine weekly screening. Isogenicity will be determined by whole-genome sequencing. During the study, relevant intrinsic and extrinsic risk factors will be recorded. Specimen and data will be collected for 1 year. We postulate that transmission density increases during episodes when demand for intensive care cannot be met by existing staff, and that threshold dynamics have a bearing on cohorting and hand hygiene performance. Poisson logistic regression, proportional hazard and multilevel competing risk models will be used to estimate the effect of explanatory variables. ETHICS AND DISSEMINATION: This study has been approved by the local ethics committee (study ID 287/18). The results will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders. TRIAL REGISTRATION NUMBER: The German Clinical Trials Registry (DRKS00017733); Pre-results.

Measuring the in-hospital costs of Pseudomonas aeruginosa pneumonia: methodology and results from a German teaching hospital.

BACKGROUND: Pseudomonas aeruginosa-related pneumonia is an ongoing healthcare challenge. Estimating its financial burden is complicated by the time-dependent nature of the disease. METHODS: Two hundred thirty-six cases of Pseudomonas aeruginosa-related pneumonia were recorded at a 2000 bed German teaching hospital between 2011 and 2014. Thirty-five cases (15%) were multidrug-resistant (MDR) Pseudomonas aeruginosa. Hospital- and community-acquired cases were distinguished by main diagnoses and exposure time. The impact of Pseudomonas aeruginosa-related pneumonia on the three endpoints cost, reimbursement, and length of stay was analyzed, taking into account (1) the time-dependent nature of exposure, (2) clustering of costs within diagnostic groups, and (3) additional confounders. RESULTS: Pseudomonas aeruginosa pneumonia is associated with substantial additional costs that are not fully reimbursed. Costs are highest for hospital-acquired cases (€19,000 increase over uninfected controls). However, community-acquired cases are also associated with a substantial burden (€8400 when Pseudomonas aeruginosa pneumonia is the main reason for hospitalization, and €6700 when not). Sensitivity analyses for hospital-acquired cases showed that ignoring or incorrectly adjusting for time-dependency substantially biases results. Furthermore, multidrug-resistance was rare and only showed a measurable impact on the cost of community-acquired cases. CONCLUSIONS: Pseudomonas aeruginosa pneumonia creates a substantial financial burden for hospitals. This is particularly the case for nosocomial infections. Infection control interventions could yield significant cost reductions. However, to evaluate the potential effectiveness of different interventions, the time-dependent aspects of incremental costs must be considered to avoid introduction of bias.

Contribution of specific pathogens to bloodstream infection mortality in neutropenic patients with hematologic malignancies: Results from a multicentric surveillance cohort study.

Bloodstream infection (BSI) remains a serious complication in patients with hematologic malignancies and neutropenia. The risk factors for mortality after BSI and the contributions of BSI pathogens to mortality remain incompletely understood. We evaluated first BSI among adult neutropenic patients undergoing high-dose chemotherapy for hematologic malignancies in the setting of (a) an early disease stage of autologous (auto-HSCT) or allogeneic (allo-HSCT) hematopoietic stem cell transplantation or (b) for acute leukemia. Risk factors for intensive care admission and all-cause mortality were analyzed by multivariable logistic regression 7 and 30 days after onset of the first BSI in the first neutropenic episode. Between 2002 and 2015, 9080 patients met the study inclusion criteria, and 1424 (16%) developed BSIs, most of them during the first week of neutropenia. Mortality during neutropenia within 7 days and 30 days after BSI onset was 2.5% and 5.1%, respectively, and differed considerably between BSI pathogens. Both 7-day and 30-day mortalities were highest for Pseudomonas aeruginosa BSI (16.7% and 26.7%, respectively) and lowest for BSI due to coagulase-negative Staphylococcus spp. (CoNS) and Streptococcus spp. BSI pathogens were independently associated with 7-day mortality included P aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., and enterococci. Only gram-negative BSI and candidemia were associated with admission to intensive care within 7 days after BSI onset. BSI caused by P aeruginosa continues to carry a particularly poor prognosis in neutropenic patients. The unexpected association between enterococcal BSI and increased mortality needs further study.

Impact of fluoroquinolone prophylaxis during neutropenia on bloodstream infection: Data from a surveillance program in 8755 patients receiving high-dose chemotherapy for haematologic malignancies between 2009 and 2014.

OBJECTIVES: Antibacterial chemoprophylaxis with fluoroquinolones (FQPx) has been commonly used in cancer patients with neutropenia, but its efficacy has been challenged by the emergence of fluoroquinolone resistance. METHODS: The impact of FQPx on bloodstream infections (BSI) during neutropenia after high-dose chemotherapy for haematologic malignancies was evaluated through a multicenter hospital infection surveillance system for the period 2009-2014. RESULTS: Among 8755 patients (4223 allogeneic [allo-] HSCT, 3602 autologous [auto-] HSCT, 930 high-dose chemotherapy for acute leukemia [HDC]), 5302 (61%) had received FQPx. Administration of FQPx was associated with fewer Gram-negative BSI in the overall study cohort patients (4.6% vs. 7.7%, adjusted subdistribution hazard ratio [aSHR] 0.59, 95%CI 0.50-0.70), in patients with HDC (3.7% vs. 9.2%, adjusted subdistribution hazard ratio [aSHR] 0.40, 95%CI 0.22-0.70) and auto-HSCT patients (4% vs. 9%, aSHR 0.43, 95%CI 0.33-0.56). In HDC patients, FQPx was associated with a marked reduction in all-cause mortality during neutropenia (2.3% vs. 7.8%, aSHR 0.30, 95%CI 0.15-0.58). Patients receiving FQPx had significantly more BSIs due to ESBL-positive Enterobacteriacea (0.8 vs. 0.3%, RR 2.2, 95%CI 1.17-4.26). BSIs by MRSA (n = 5) and VRE (n = 11) were rare in our cohort. CONCLUSIONS: As used in the participating centers, FQPx was associated with reduced Gram-negative BSI and improved survival among HDC patients. Among HSCT patients, the benefits were less clear. If adapted to local resistance patterns and patient characteristics, FQPx still may be useful in the management of patients with haematologic malignancies.

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.