Use of linezolid in neonatal and pediatric inpatient facilities--results of a retrospective multicenter survey.

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

Patient-related outcomes of patellofemoral arthroplasty: experience of a single center.

PURPOSE: The purpose of this prospective study was to present the experience of a single center on patellofemoral arthroplasty, in terms of patient-related outcomes. METHOD: From January 2005 to January 2016, 42 patients with isolated patellofemoral osteoarthritis were treated. The patients were assessed using the Oxford Knee Score preoperatively, and one, five, and eight year(s) after surgery. The data of the patients were analyzed using linear mixed effects models. A P value of 0.05 was considered statistically significant. RESULTS: Among 42 patients who underwent patellofemoral arthroplasty, only 25 patients (31 limbs involved) had records up to 5 years. There was a significant clinical improvement of Oxford Knee Score postoperatively (P < 0.05), lowering the score on average by 10.4 ± 1.5 one year after surgery and 8.9 ± 1.9 five years after surgery. This improvement was independent of the types of implants (P > 0.05), gender (P > 0.05), age (P < 0.05), and body mass index (BMI) (P < 0.05). CONCLUSION: Patellofemoral arthroplasty can significantly improve the knee function, and this improvement is independent of the type of implant, gender, age, and BMI. However, further studies will need to assess the long-term outcomes of PFA.

Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release.

In this study, the release of gentamicin as a function of time was measured for six different gentamicin-loaded bone cements and related with the surface roughness, porosity and wettability of the cements. Initial release rates varied little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000, Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h. The total amounts of gentamicin released after 1 week varied between 4.0 and 5.3% of the total amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos. Palamed released after 1 week significantly more of the gentamicin incorporated (17.0%). The wettability of all cements was similar (water contact angles between 70 and 80 degrees), but the surface roughness and the porosity of the cements varied markedly. Initial release rates increased with surface roughness, although the correlation coefficient was low (0.64), while total amounts released increased linearly (correlation coefficient 0.97) with the bulk porosity of the cements. Consequently, it can be concluded that the release kinetics of gentamicin from bone cements is controlled by a combination of surface roughness and porosity.

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements.

In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos, and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials 21 (2000) 1981) measured kinetics of antibiotic release by these cement brands. The influence of gentamicin release on biofilm formation was quantified by expressing the number of colony-forming units on gentamicin-loaded cement relative to the number of viable organisms on unloaded cement of the same brand. Biofilms formed on all gentamicin-loaded cements, despite the release of antibiotics, followed a consistent pattern in time with a maximum number of colony-forming units per unit cement area found between 24 and 30 h after inoculation. None of the gentamicin-loaded cements showed a reduction in biofilm formation relative to unloaded cements within 6 h after inoculation, whereas only gentamicin-loaded CMW1 and Palacos reduced biofilm formation 24 h after inoculation. Alternatively, CMW Endurance, CMW2000, and Palamed did not exhibit any initial reductions in biofilm formation, but effects started after 72, 48, and 72 h, respectively. Biofilm reduction by gentamicin-loaded CMW3 lasted the longest from 24 to 72 h. Interestingly, each cement seemed to have a different "window-of-effectiveness" with regard to reduction in biofilm formation that did not relate with the gentamicin-release kinetics. Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements.

Experimental pancreatitis: Effect of plasma and dextran on pancreatic blood flow.

In spite of extensive investigations, many aspects of the hemodynamic changes occurring in acute pancreatitis are understood poorly. A dog model was established in which continuous measurements of pancreatic arterial blood flow, cardiac output, and mean arterial blood pressure were made using electromagnetic flow probes and a pressure transducer, respectively. Pancreatitis was induced and the animals were monitored for 3 hours. In addition, control animals (group I) without pancreatitis also were done. All animals 50 ml of saline in the first hours. Three methods of therapy then were instituted in the dogs with pancreatitis and their effects were recorded. group I 6 dogs control animals no pancreatitis saline 50 ml/hr group II 10 dogs saline 50 ml/hr group III 6 dogs plasma 15 ml/kg over 45 min then saline 50 ml/hr group IV 10 dogs saline 50 ml and 1.5 ml/kg of dextran 40/hr These results confirm the observations made previously using a transillumination technique--that the pancreatic circulation rapidly reduces in acute pancreatitis. Administration of plasma produced a significant (P less than 0.05) but transient increase in the cardiac output and pancreatic blood flow; however, the blood pressure remained low. Dextran 40 minimally increased cardiac output, but it significantly improved the blood pressure and maintained the pancreatic blood flow. Low-dose, low-molecular weight dextran 40 appears to help to maintain pancreatic blood flow in acute pancreatitis. The possible mechanisms concerning the made of action of dextran 40 will be discussed.

Carnitine levels in severe infection and starvation: a possible key to the prolonged catabolic state.

Tissue carnitine levels have been measured in man and the dog. Skeletal muscle carnitine levels rise in the dog with starvation to roughly twice the normal level. An equal degree of starvation plus peritonitis is associated with unchanged skeletal muscle carnitine levels. In the presence of peritonitis, sequential skeletal muscle biopsies show a progressive fall in the tissue carnitine levels with a subsequent rise in those animals which survive and clear their peritonitis. Normal human skeletal muscle levels are essentially the same as in the dog. A combination of sepsis and starvation in man is associated with essentially unchanged skeletal muscle carnitine levels, whereas pure sepsis without starvation is associated with decreased skeletal muscle carnitine levels. It is suggested that these changes are in the direction expected for a limitation of fat catabolism and, in the presence of a limited exogenous source of glucose, that this would result secondarily in a protein catabolic state to supply glucose for the body's energy needs.

Improvement in blood flow through a critical arterial stenosis by defibrination with ancrod.

Using electromagnetic flow probes, cardiac output and hind limb blood flow were measured in dogs in which one hind limb had been rendered ischemic. Four dogs served as controls; seven were defibrinated by intravenous infusion of ancrod, 1 unit/kg, over a 30-minute period. In both groups, hematocrit readings remained constant, but cardiac output fell (this was attributed to barbiturate anesthesia), as did flow in the normal hind limb. In the controls after three hours, flow in the ischemic hind limb had decreased by 34%, but in the treated animals it had increased by 20%. The difference was statistically significant (P less than .001). The selective increase in blood flow in the ischemic limb may be explained by the greater reduction in blood viscosity at low shear rates achieved by defibrination.

Hepatic blood flow measurement.

Although many experimental studies have been made to determine the total hepatic blood flow in steady circulatory states, very few have been done in unsteady states of either circulatory overload or underload. In this experiment, a comparison is made between total hepatic blood flow measured by the single injection of indocyanine green and the electromagnetic flow methods in the dog, in which circulatory overload was induced by dextran 40 infusion. While there was close correlation between the values obtained by the two methods in normal dogs, following dextran infusion the indirect indocyanine green method overestimated hepatic blood flow by 40% to 60%, using the electromagnetic method as a comparison standard. The reason for this discrepancy is not elucidated by these studies.

Does edematous pancreatitis exist in biliary-related pancreatitis? A hemodynamic and histologic study of the progression of bile-induced pancreatitis.

The progression of pancreatitis induced in dogs by either single or hourly injections of two different bile solutions was monitored to determine whether acute necrotizing pancreatitis developed through an earlier mild interstitial form. In this model of biliary-related pancreatitis, acute interstitial pancreatitis could not be produced. The earliest lesion produced, although having the macroscopic appearance of edematous pancreatitis, was histologically a mild necrotizing form of the disease. If the bile solution was of sufficient concentration, then further injections resulted in progression of the pancreatitis from this mild form of scattered areas of focal acinar necrosis through coalescence of these areas to areas of parenchymal hemorrhage. Pancreatic blood flow, measured through its arterial inflow, increased during the earliest phase of the disease, but then decreased as the disease progressed.

Effectiveness of normal saline solution, dextran 40 or dextran 75, and aprotinin (Trasylol) on renal blood flow preservation during acute canine pancreatitis.

A decrease in renal blood flow is believed to be important in the genesis of the acute renal failure of acute pancreatitis. In some instances, this decrease is undoubtedly due to hypovolemia, whereas in other instances, a circulating vasotoxic agent, possibly trypsin, has been incriminated. Using a canine model of pancreatitis induced by retrograde injection of bile along the pancreatic duct, the effects on renal blood flow of correcting the hypovolemia or administering aprotinin (a trypsin inhibitor) were studied using externally applied flow probes. Correcting the hypovolemia with N saline solution had no effect; the renal blood flow continued to decrease (p less than 0.05). When dextran 40 or dextran 75 was employed, the decrease in renal blood flow was prevented. After the administration of aprotinin, the renal blood flow actually increased (p less than 0.025) compared with preadministration values. It appears that aprotinin may have played a role in preventing this serious complication of pancreatitis.

Pathophysiology of acute pancreatitis: evaluation of the effect and mode of action of steroids in experimental pancreatitis in dogs.

Three experiments were performed to evaluate the effects and hemodynamic changes brought about by steroids in experimental pancreatitis in dogs. The results show (1) a significant improval in survival in steroid-treated groups, (2) no difference in cardiac output or mean blood pressure between groups, (3) a decrease in relative pancreatic arterial blood flow in the untreated animals, and (4) an increase in arterial flow to the pancreas after steroid therapy. The experiments suggest that the reversal of reduced pancreatic flow may be important in improving the prognosis.

Experimental acute pancreatitis in dogs and effects of steroids. A light and electron microscopic study with reference to pathogenesis.

Acute pancreatitis was induced in 39 dogs by injecting 10 ml of autologous bile into the pancreatic duct system. Of these dogs, 19 received hydrocortisone. As control, used were two normal dogs and six that were injected with 10 ml of normal saline solution into the pancreatic duct. Of all, 14 dogs were examined by electron microscope. All dogs that were injected with bile developed acute pancreatitis and histologically the lesion produced was acute necrotizing pancreatitis. Dogs treated with steroids showed an improved survival and a reduction in the severity of the acinar lesion. Ultrastructurally, pancreatic changes in these animals were mainly in the acinar cells and capillaries. Although ultrastructural lesions were similar in animals treated with steroids, steroid therapy appeared to be associated with an improved structural preservation of the acinar cells. These results suggest that the bile infusion method is reliable in producing acute necrotizing pancreatitis and that steroid administration is associated with an improved survival and reduction of the severity of the pancreatic lesion. The pathogenetic mechanism in this model and the mode of action of steroids were suggested by the ultrastructural study.

Acute pancreatitis - ischaemia or hyperaemia?

There is no accepted specific treatment for acute pancreatitis in man in spite of extensive investigations. Evidence is presented based on histology, vascular and blood flow studies to support the hypothesis that acute pancreatitis is unlike most inflammatory conditions since a rapid and severe ischaemia develops in the pancreas. In dogs for example there is an instant and maintained reduction in pancreatic blood flow reducing by 72% at 3 hours. Various treatments have been advocated in acute pancreatitis. Based upon the effect of dextran 40 in improving pancreatic blood flow and percentage cardiac output, it would appear to be a treatment of choice in acute pancreatitis.