Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.

Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.

Large variations were found in the type of β-lactams tested, the patients selected for TDM and drug assay methods. Significant variation observed in the PK/PD targets and dose adjustment strategies used supports the need for further studies that robustly define PK/PD targets for ICU patients to ensure a greater consistency of practice for dose adjustment strategies for optimizing β-lactam dosing with TDM.

BackgroundCorrect antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.MethodsThis was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.ResultsWe obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% fT>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% fT>MIC.ConclusionsIn this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.