E U ROSU R V E I L L A N C E Vol . 14 · I ssu e 2 · 15 J an ua ry 20 09 · w w w. e urosurve illance. o rg 1 S u r v e i ll a n c e a n d o u t b r e a k r e p o r t s Lo n g -t e r m Cry p t o s p o r i d i u m t y p i n g r e v e a L s t h e a e t i o L o g y a n d s p e c i e s -s p e c i f i c e p i d e m i o L o g y o f h u m a n c r y p to s p o r i d i o s i s i n en g L a n d a n

We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

Identifying children likely to develop critical illness can be difficult. The assessment tool developed from the advanced paediatric life support guidelines on identifying sick children appears to be sensitive but not specific. If the C&VPEWS was used as a trigger to activate a rapid response team to assess the child, the majority of calls would be unnecessary.

ObjectiveTo assess (1) how well validated existing paediatric track and trigger tools (PTTT) are for predicting adverse outcomes in hospitalised children, and (2) how effective broader paediatric early warning systems are at reducing adverse outcomes in hospitalised children.DesignSystematic review.Data sourcesBritish Nursing Index, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Management Information Centre, Medline, Medline in Process, Scopus and Web of Knowledge searched through May 2018.Eligibility criteriaWe included (1) papers reporting on the development or validation of a PTTT or (2) the implementation of a broader early warning system in paediatric units (age 0–18 years), where adverse outcome metrics were reported. Several study designs were considered.Data extraction and synthesisData extraction was conducted by two independent reviewers using template forms. Studies were quality assessed using a modified Downs and Black rating scale.Results36 validation studies and 30 effectiveness studies were included, with 27 unique PTTT identified. Validation studies were largely retrospective case-control studies or chart reviews, while effectiveness studies were predominantly uncontrolled before-after studies. Metrics of adverse outcomes varied considerably. Some PTTT demonstrated good diagnostic accuracy in retrospective case-control studies (primarily for predicting paediatric intensive care unit transfers), but positive predictive value was consistently low, suggesting potential for alarm fatigue. A small number of effectiveness studies reported significant decreases in mortality, arrests or code calls, but were limited by methodological concerns. Overall, there was limited evidence of paediatric early warning system interventions leading to reductions in deterioration.ConclusionThere are several fundamental methodological limitations in the PTTT literature, and the predominance of single-site studies carried out in specialist centres greatly limits generalisability. With limited evidence of effectiveness, calls to make PTTT mandatory across all paediatric units are not supported by the evidence base.PROSPERO registration numberCRD42015015326

Antibiotic penetration to the infection site is critical for obtaining a good clinical outcome in patients with ventilator-associated pneumonia (VAP). Surprisingly few studies have quantified the penetration of ␤-lactam agents into the lung, as measured by the ratio of area under the concentration-time curve (AUC) in epithelial lining fluid (ELF) to AUC in plasma (AUC ELF /AUC plasma ratio). These have typically involved noninfected patients. This study examines the penetration and pharmacodynamics of meropenem in the ELF among patients with VAP. Meropenem plasma and ELF concentration-time data were obtained from patients in a multicenter clinical trial. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer (big nonparametric adaptive grid [BigNPAG]). A Monte Carlo simulation was performed to estimate the range of ELF/ plasma penetration ratios one would expect to observe in patients with VAP, as measured by the AUC ELF / AUC plasma ratio. The range of AUC ELF /AUC plasma penetration ratios predicted by the Monte Carlo simulation was large. The 10th percentile of lung penetration was 3.7%, while the 90th percentile of penetration was 178%. The variability of ELF penetration is such that if relatively high ELF exposure targets are required to attain multilog kill or resistance suppression for bacteria like Pseudomonas aeruginosa, then even receiving the largest licensed dose of meropenem with an optimal prolonged infusion may not result in target attainment for a substantial fraction of the population.Ventilator-associated pneumonia (VAP) remains a frequent cause of morbidity and mortality among intensive care unit patients despite advances in antimicrobial therapy, better supportive care modalities, and the use of a wide range of preventive measures (1, 26). Prompt delivery of empirical therapy for patients likely to have VAP is of paramount importance, since delays in appropriate antibiotic therapy have been associated with deleterious outcomes (1,18,19,24,25). An important consideration when selecting empirical therapy for VAP is the agent's ability to adequately penetrate the infected site and achieve sufficient concentrations for the desired endpoint. For extracellular respiratory tract pathogens, the determination of drug concentration in epithelial lining fluid (ELF) currently provides the best estimate for ascertaining the degree of antibiotic exposure for these organisms in patients with 12,[15][16][17]21,25,27,28).While it is well established that the efficacy of an antibiotic regimen largely depends on its penetration in the infection site, relatively few studies have focused on the penetration of antibiotics into the ELF (3-8, 12, 15-17, 21, 23, 25, 27, 28). Of those available, most have been among patients treated with fluoroquinolones and macrolides (12,15,16,23,27,28). A surprisingly small body of data is available for the penetration of ␤-lactam agents into the ELF. In the older li...