Objectives: Carbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system. Methods: Meropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS). Results: In total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n ¼ 388, 43%), Escherichia coli (n ¼ 264, 30%) and Enterobacter cloacae complex (n ¼ 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with bla OXA-48 being predominant (38%, 336/892), followed by bla NDM-1 (16%, 145/892). For the first time in the Netherlands, bla OXA-181 , bla OXA-232 and bla VIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse. Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are bla OXA-48 and bla NDM-1. There was a clear association between species, carbapenemase allele and susceptibility to meropenem.

Abstract Objective Much has been invested in big data analytics to improve health and reduce costs. However, it is unknown whether these investments have achieved the desired goals. We performed a scoping review to determine the health and economic impact of big data analytics for clinical decision-making. Materials and Methods We searched Medline, Embase, Web of Science and the National Health Services Economic Evaluations Database for relevant articles. We included peer-reviewed papers that report the health economic impact of analytics that assist clinical decision-making. We extracted the economic methods and estimated impact and also assessed the quality of the methods used. In addition, we estimated how many studies assessed “big data analytics” based on a broad definition of this term. Results The search yielded 12 133 papers but only 71 studies fulfilled all eligibility criteria. Only a few papers were full economic evaluations; many were performed during development. Papers frequently reported savings for healthcare payers but only 20% also included costs of analytics. Twenty studies examined “big data analytics” and only 7 reported both cost-savings and better outcomes. Discussion The promised potential of big data is not yet reflected in the literature, partly since only a few full and properly performed economic evaluations have been published. This and the lack of a clear definition of “big data” limit policy makers and healthcare professionals from determining which big data initiatives are worth implementing.

Staphylococcus aureus bacteraemia (SAB) is associated with high-mortality and complication rates. A multidisciplinary approach is needed to predict, detect and treat complications. In this pre- and post-intervention study, we investigated the effects of a hospital-wide protocol for diagnosis, classification and treatment of SAB. It was hypothesized that complications and endocarditis would be better identified and treated. Medical records of SAB patients admitted in 2011 and 2012 (pre) were analysed. In 2013, a protocol, describing risk factors, diagnostic classification and recommended treatment, was implemented. In 2014 and 2015 (post), SAB patients were followed prospectively. Transthoracic (TTE) or transoesophageal cardiac ultrasound (TEE) was chosen following a decision tree. A resident internal medicine acted as contact person. Pre-intervention, 98 patients were eligible for analysis compared to 85 patients post-intervention. Age and number of risk factors were slightly higher post-intervention; other baseline characteristics were similar. Most SAB-patients were classified as complicated (89 and 82% pre- and post-intervention, respectively). Follow-up blood cultures drawn within 2 days after initiating treatment increased from 51 to 85%. Cardiac ultrasounds increased from 44 to 83% for TTE and 13 to 24% for TEE. Endocarditis was more frequently diagnosed (4 vs. 12%). Additionally, duration of antibiotic therapy increased. The 3-month mortality did not change significantly (33% pre-intervention vs. 35% post-intervention; p > 0.05). Introduction of a hospital-wide protocol for SAB management increased standard of care, created awareness among clinicians to properly classify SAB, search for endocarditis and adapt duration of antibiotic treatment. Mortality did not decrease.

Low dose methotrexate is used increasingly often in the treatment of rheumatoid arthritis. Severe complications due to toxicity of the lung or bone marrow occur infrequently. This report describes a 71 year old woman with longstanding rheumatoid arthritis who developed pleuritis, a pulmonary infiltrate, and pancytopenia during treatment with low dose methotrexate. Fatal respiratory insufficiency followed, and cultures from the lung after death showed Nocardia asteroides. Laboratory findings were as follows: erythrocyte sedimentation rate 120 mm/h; haemoglobin 118 g/l; packed cell volume 0-37; white blood cell count 1-2 x 109/l with 66% neutrophils, 8% bands, 19% lymphocytes, and 7% monocytes; platelet count 40x 109/1; urea 9-1 mmol/1; creatinine 108 gmol/l; bilirubin 11 FImol/l; alkaline phosphatase 130 U/1; serum aspartate aminotransferase 31 U/1; serum alanine aminotransferase 29 U/1; lactic dehydrogenase 434 U/l (normal <320 U/1); albumin 22-1 g/l, arterial blood gas analysis: pH 7T50, Pao2 63 mmHg, Paco2 34 mmHg, bicarbonate 27 mmol/l.An electrocardiogram showed sinus tachycardia at a rate o-f 140/min and high voltages, indicating left ventricular hypertrophy. Admission chest radiograph showed an enlarged cardiac silhouette and some pleural fluid at the left base. Lung scintigraphy showed small perfusion defects matched with ventilation. Echocardiography disclosed a large left ventricle with mitral valve insufficiency without vegetations. Methotrexate was discontinued, oxygen was given (2 litres/min), prednisone was increased to 25 mg/day, and she received cefpirome (fourth generation cephalosporin) intravenously. Her clinical condition improved and arterial Pao2 rose to 80 mmHg. After six days white blood cell and platelet count became normal. Ten days after admission she developed fever (39°C) and a productive cough. Klebsiella was cultured from her sputum. Repeated chest radiographs showed no changes. She was treated with ceftriaxone. She remained feverish and her general condition worsened. A chest radiograph showed progression 'of pleural fluid and an infiltrate at the left base (fig 1). She was treated with oxygen, diuretics, and antibiotics, without showing improvement. It was her repeated request not to be resuscitated and that no

Antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, but the estimated number of additional recurrent episodes in the Netherlands (40 per year) was rather limited.