In vitro investigations of Staphylococcus aureus biofilms in physiological fluids suggest that current antibiotic delivery systems may be limited.

Orthopaedic surgical site infections, especially when a hardware is involved, are associated with biofilm formation. Clinical strategies for biofilm eradication still fall short. The present study used a novel animal model of long-bone fixation with vancomycin- or gentamicin-controlled release and measured the levels of antibiotic achieved at the site of release and in the surrounding tissue. Then, using fluids that contain serum proteins (synovial fluid or diluted serum), the levels of vancomycin or gentamicin required to substantially reduce colonising bacteria were measured in a model representative of either prophylaxis or established biofilms. In the in vivo model, while the levels immediately adjacent to the antibiotic release system were up to 50× the minimal inhibitory concentration in the first 24 h, they rapidly dropped. At peripheral sites, values never reached these levels. In the in vitro experiments, Staphylococcus aureus biofilms formed in serum or in synovial fluid showed a 5-10 fold increase in antibiotic tolerance. Importantly, concentrations required were much higher than those achieved in the local delivery systems. Finally, the study determined that the staged addition of vancomycin and gentamicin was not more efficacious than simultaneous vancomycin and gentamicin administration when using planktonic bacteria. On the other hand, for biofilms, the staged addition seemed more efficacious than adding the antibiotics simultaneously. Overall, data showed that the antibiotics' concentrations near the implant in the animal model fall short of the concentrations required to eradicate biofilms formed in either synovial fluid or serum.

The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study.

BACKGROUND: Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. METHODS: Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time. RESULTS: We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371, p < 0.05). Bland-Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. CONCLUSIONS: Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number ACTRN12615000945527 (Registered 9/9/2015).

Responsiveness of Noninvasive Continuous Cardiac Output Monitoring During the Valsalva Maneuver.

To describe the baseline hemodynamic variables and response time of hemodynamic changes associated with the Valsalva maneuver using noninvasive continuous cardiac output monitoring (Nexfin). Hemodynamic monitoring provides an integral component of advanced clinical care and the ability to monitor response to treatment interventions. The emergence of noninvasive hemodynamic monitoring provides clinicians with an opportunity to monitor and assess patients rapidly with ease of implementation. However, the responsiveness of this method in tracking dynamic changes that occur has not been fully elucidated. A prospective observational study was conducted involving 44 healthy volunteers (age = 38 ±12 years). Participants performed a Valsalva maneuvers to illicit dynamic changes in blood pressure, cardiac output, cardiac index, systemic vascular resistance index (SVRI), and stroke volume. Changes in these hemodynamic parameters were monitored while performing repeated standardized Valsalva maneuvers. Baseline hemodynamic values were obtained in all 44 participants, and showed an interaction with age, accompanying a significant decline in cardiac index (r = -.66, p < .05) and stroke volume (r = -.68,p < .05), and an increase in SVRI (r = .67, p < .05) with increasing age. The Valsalva maneuver, performed in 20 participants, resulted in a change of 10% from baseline blood pressure and cardiac index, which was detected within 4.53 s (SD = 4.36) and 3.31 s (SD = 2.21), respectively. Noninvasive continuous cardiac monitoring demonstrated the ability to rapidly detect logical and predictable hemodynamic changes. These observations suggest that such Nexfin technology may have useful clinical applications.

Immunohistochemical evaluation of canine carcinomas with monoclonal antibody B72.3.

Monoclonal antibody (MAb) B72.3 reacts with a tumor-associated glycoprotein, designated TAG-72. TAG-72 has been identified in many human carcinomas but generally is not found in normal human tissues. Because of its proven utility in the diagnosis of human carcinomas, MAb B72.3 was applied to several different types of canine carcinomas. Five types of formalin-fixed, paraffin-embedded canine carcinomas were evaluated for immunoreactivity with MAb B72.3 by use of an avidin biotin immunoperoxidase complex method. Samples were considered positive when > or = 5% of all malignant cells contained a distinct intracellular stain. Immunoreactivity for MAb B72.3 was observed in 6/9 (67%) pulmonary adenocarcinomas, 7/13 (54%) transitional cell carcinomas, 7/11 (64%) mammary adenocarcinomas, 7/11 (64%) nasal adenocarcinomas, and 1/2 (50%) prostatic adenocarcinomas. The average cellular staining for positive carcinomas was 25%. Normal canine tissues from similar anatomic sites had little or no individual cell immunoreactivity. These preliminary results indicate that some canine carcinomas may express a tumor-associated antigen that is similar to TAG-72 and that MAb B72.3 immunoreactivity may be of diagnostic significance in classifying animal tumors.