Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven ...early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned 1:1 using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 0·6% of 866 neonates in the procalcitonin group vs 4 0·5% of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 0·7% of 745 neonates in the procalcitonin group vs 4 0·6% of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
The rise in antimicrobial resistance has become a serious global health problem. Restrictive use of antibiotics seems the only option to temper this accession since research in new antibiotics has ...halted. Antimicrobial stewardship programmes rely on quick access to susceptibility data. This study evaluated the concept of bacterial cell count monitoring as a fast method to determine susceptibility. Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains were tested for amoxicillin/piperacillin and gentamicin by three conventional methods (VITEK2 registered , Etest registered and broth-macrodilution). Bacterial cell count monitoring reliably predicted susceptibility after 90min for Escherichia coli and after 120min for Pseudomonas aeruginosa and Staphylococcus aureus without any minor, major or very major discrepancies. Time-to-result was reduced by 74%, 83% and 76%, respectively. Bacterial cell count monitoring shows great potential for rapid susceptibility testing.Original Abstract: Clin Microbiol Infect 2013; 19: 286-291
Aim
This study assessed the feasibility and obtrusiveness of measuring salivary oxytocin in preterm infants receiving Kangaroo care, because this is a period of maximal bonding or co‐regulation. We ...also analysed possible influential determinants, including maternal oxytocin.
Methods
The saliva of preterm infants and their mothers was collected prior to, and during, Kangaroo care using cotton swabs and pooled into vials until sufficient volumes were obtained to measure oxytocin levels using a radioimmunoassay. The obtrusiveness of the infants’ collections was measured with a Likert scale.
Results
Saliva was collected unobtrusively prior to, and during, 30 Kangaroo care sessions in 21 preterm infants. This resulted in three vials with sufficient volumes of before‐Kangaroo care saliva and three with during‐Kangaroo care saliva. Oxytocin was detectable in all six vials. The Kangaroo care duration and the intensity of the mother–infant interaction before and during Kangaroo care seemed to be the most important determinants, and these should preferably be standardised in any future trials.
Conclusion
Oxytocin was measured unobtrusively in the pooled saliva of preterm infants both before and during Kangaroo care and could therefore be investigated as a biomarker in future studies.
A new way to analyze supramolecular dendritic architectures is reported by making use of 13C NMR and 31P NMR. Two ethylene glycol guest molecules have been synthesized containing a 13C labeled ...carboxylic acid headgroup (2) and a phosphonic acid headgroup (3). The binding of these guests to urea-adamantyl modified poly(propylene imine) dendrimers has been investigated with 13C NMR and 31P NMR next to 1D and 2D 1H NMR techniques. Different amounts of guest 2 have been added to fifth generation dendrimer 1e, and the observed chemical shift values in 13C NMR were fitted to a model that assumes 1:1 binding between guest and binding site. An association constant of 400 ± 95 M-1 is obtained for guest 2 with 41 binding sites per dendrimer. When different amounts of phosphonic acid guest 3 are added to dendrimer 1e, two different signals are observed in 31P NMR. Deconvolution gives the fractions of free and bound guest, resulting in an association constant of (4 ± 3) × 104 M-1 and 61 ± 1 binding sites. A statistical analysis shows that guest 2 forms a “polydisperse supramolecular aggregate”, while guest 3 is able to form a “monodisperse supramolecular aggregate” when the amount of guest is high enough. The NMR results are compared with dynamic light scattering experiments, and a remarkable agreement is found. Phosphonic acid guest 3 is able to exchange with guest 2, which is in agreement with the obtained association constants, and shows that these techniques can be used to analyze multicomponent dendritic aggregates.
Selective guest ejection: Up to eight guest molecules are assembled at the periphery of a third‐generation dendrimer. Collision‐induced dissociation mass spectrometry has demonstrated that the guests ...are removed very selectively in a one‐by‐one manner (see spectrum).
The supramolecular chemistry of the third generation poly(propyleneimine) dendrimers (1) having adamantylurea end groups was investigated using multidimensional NMR on a 750 MHz spectrometer. A ...stable complex (3) is formed when 1 is combined with cyanobiphenyl guest molecules (2) having glycinylurea type end groups. Proton connectivities were obtained from 2D 1H−H TOCSY experiment. The 13C and 1H resonances were correlated from the 2D 1H−13C gHSQC experiment. Spatial proximity of the host−guest molecules was determined from a 2D 1H−1H NOESY experiment. Evidence of the specific binding interactions responsible for the stable complex of 1 with 2 was obtained from 1H−1H interactions determined from the NOESY spectrum.
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