Dexmedetomidine is an α-2-receptor agonist which might be used as an additive to local anaesthetics for various regional anaesthetic techniques. We therefore designed this prospective, double-blinded, controlled volunteer study to investigate the effects of dexmedetomidine as an adjuvant to ropivacaine on peripheral nerve block. Ultrasound-guided ulnar nerve block (UNB) was performed in 36 volunteers with either 3 ml ropivacaine 0.75% (R), 3 ml ropivacaine 0.75% plus 20 µg dexmedetomidine (RpD), or 3 ml ropivacaine 0.75% plus systemic 20 µg dexmedetomidine (RsD). UNB-related sensory and motor scores were evaluated. Sensory onset time of UNB was not different between the study groups, whereas motor onset time was significantly faster in Group RpD when compared with the other study groups [mean (sd)] [21 (15) vs 43 (25) min in Group RsD and 47 (36) min in Group R, P<0.05 Group RpD vs other groups]. The duration of sensory block was 350 (54) min in Group R, 555 (118) min in Group RpD, and 395 (40) min in Group RsD (P<0.01 Group RpD vs other groups, P<0.05 Group RsD vs Group R). Motor block duration was similar to the duration of sensory block. A profound prolongation of UNB of ∼60% was detected with perineural dexmedetomidine when added to 0.75% ropivacaine. The systemic administration of 20 µg dexmedetomidine resulted in a prolongation of ∼10% during UNB with 0.75% ropivacaine. Eudra-CT No.: 2012-000030-19.

Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agentsin vitro. This might explain the somewhat contradictory results obtained from different studies. Simplein vitromodels which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Withinin vitrotest systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibioticsin vitrobecome even more urgent. In addition, the quantitative relationship between the effects of protein bindingin vitroandin vivoneeds to be established, since the physiological conditions differ. General recommendations for testing the impact of protein bindingin vitroare suggested.

Although azithromycin is extensively used in the treatment of respiratory tract infections as well as skin and skin-related infections, pharmacokinetics of azithromycin in extracellular space fluid of soft tissues, i.e., one of its therapeutic target sites, are not yet fully elucidated. In this study, azithromycin concentration-time profiles in extracellular space of muscle and subcutaneous adipose tissue, but also in plasma and white blood cells, were determined at days 1 and 3 of treatment as well as 2 and 7 days after the end of treatment. Of all compartments, azithromycin concentrations were highest in white blood cells, attesting for intracellular accumulation. However, azithromycin concentrations in both soft tissues were markedly lower than in plasma both during and after treatment. Calculation of the area under the concentration-time curve from 0 to 24 h (AUC _0–24 )/MIC ₉₀ ratios for selected pathogens suggests that azithromycin concentrations measured in the present study are subinhibitory at all time points in both soft tissues and at the large majority of observed time points in plasma. Hence, it might be speculated that azithromycin's clinical efficacy relies not only on elevated intracellular concentrations but possibly also on its known pleotropic effects, including immunomodulation and influence on bacterial virulence factors. However, prolonged subinhibitory azithromycin concentrations at the target site, as observed in the present study, might favor the emergence of bacterial resistance and should therefore be considered with concern. In conclusion, this study has added important information to the pharmacokinetic profile of the widely used antibiotic drug azithromycin and evidentiates the need for further research on its potential for induction of bacterial resistance.

Dislocation rates of continuous peripheral nerve block are poorly described even though this technique is frequently used in clinical practice. The present study was designed to evaluate dislocation rates over time of interscalene and femoral nerve catheters under defined experimental circumstances. Ultrasound (US) monitoring was used to detect the position of the perineural catheters. Twenty volunteers received US-guided interscalene and femoral nerve catheters. The volunteers performed standardized physical exercises in regular intervals and the position of both catheters was examined by US confirmation of the spread of fluid. The maximal time of investigation in each volunteer was 6 h. The main outcome parameters were the overall dislocation rates and the cumulative dislocation rates at a given time point. We observed an overall dislocation rate of 15% (5% for interscalene catheters, 25% for femoral nerve catheters) and a significant correlation between time and rate of dislocations (r=0.99, P=0.001). US visualization of the spread of fluid was possible in all cases. This is the first dedicated evaluation of dislocation rates of peripheral nerve catheters (PNCs) via US investigation. Both movement and time are considerable factors for perineural catheter displacement. US is useful for the performance of PNCs and for the continuous detection of the spread of fluid relative to the nerve and adjacent anatomical structures. Translational research is required to confirm the study results in the clinical practice. DRKS00003494.

Objective: The present study was performed to test the ability of fosfomycin to penetrate into the CSF of neurointensive care patients with ventriculostomy-associated ventriculitis. Patients and methods: Six patients requiring neurointensive care monitoring, including extraventricular drainage due to secondary obstructive hydrocephalus, were enrolled into the study. All patients received 8 g of fosfomycin intravenously three times a day over a period of at least 5 days. Concentrations of fosfomycin in the CSF and plasma were measured after single-dose administration and at steady state. Results: Mean values of the fosfomycin area under the time–concentration curves for the dosing interval of 8 h (AUC₈) were 929 ± 280 and 225 ± 131 mg·h/L for plasma and CSF after single-dose administration, respectively (P < 0.03). The ratios of the AUC₈ for CSF to the AUC₈ for plasma were 0.23 ± 0.07 after a single dose and 0.27 ± 0.08 following multiple doses (P > 0.05, not significant). Additional in vitro experiments have shown that fosfomycin exerts non-concentration-dependent microbial growth inhibition. At steady state, the time above MIC (t > MIC) values were 98%, 92% and 61% for pathogens with MIC values of 8, 16 and 32 mg/L, respectively. Conclusion: The present pharmacokinetic study indicates that 8 g of fosfomycin three times per day should provide sufficient antimicrobial concentrations in the CSF for the overall treatment period. Thus, the co-administration of fosfomycin could be useful for the treatment of ventriculitis caused by susceptible pathogens.

Background: This study was designed to examine the spread of local anesthetic (LA) via magnetic resonance imaging after a standardized ultrasound-guided thoracic paravertebral blockade. Methods: Ten volunteers were enrolled in the study. We performed ultrasound-guided single-shot paravertebral blocks with 20 ml mepivacaine 1% at the thoracic six level at both sides on two consecutive days. After each paravertebral blockade, a magnetic resonance imaging investigation was performed to investigate the three-dimensional spread of the LA. In addition, sensory spread of blockade was evaluated via pinprick testing. Results: The median (interquartile range) cranial and caudal distribution of the LA relative to the thoracic six puncture level was 1.0 (2.5) and 3.0 (0.75) [=4.0 vertebral levels] for the left and 0.5 (1.0) and 3.0 (0.75) [=3.5 vertebral levels] for the right side. Accordingly, the LA distributed more caudally than cranially. The median (interquartile range) number of sensory dermatomes which were affected by the thoracic paravertebral blockade was 9.8 (6.5) for the left and 10.7 (8.8) for the right side. The sensory distribution of thoracic paravertebral blockade was significantly larger compared with the spread of LA. Conclusions: Although the spread of LA was reproducible, the anesthetic effect was unpredictable, even with a standardized ultrasound-guided technique in volunteers. While it can be assumed that approximately 4 vertebral levels are covered by 20 ml LA, the somatic distribution of the thoracic paravertebral blockade remains unpredictable. In a significant percentage, the LA distributes into the epidural space, prevertebral, or to the contralateral side.