Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment.

BACKGROUND/AIMS: Lanthanum carbonate (LC, FOSRENOL) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy. METHODS: Patients from four previous trials entered this study. RESULTS: Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium x phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system. CONCLUSIONS: LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.

Clinafloxacin versus piperacillin/tazobactam in the treatment of severe skin and soft-tissue infections in adults at a Veterans Affairs medical center.

BACKGROUND: Severe skin and soft-tissue infections (SSTIs), particularly diabetic foot infections, are a source of considerable morbidity and mortality. Inappropriate antimicrobial therapy may contribute to the increasing emergence of bacterial resistance, as well as to increased health care costs. Thus, there is a continuing search for reasonably safe, well-tolerated, and effective antimicrobial agents that are less susceptible to the development of resistance than older agents. OBJECTIVE: The Department of Veterans Affairs (VA) Medical Center in Nashville, Tennessee, was I site in a multicenter, Phase III, randomized, investigator-blinded clinical trial comparing the safety and efficacy of clinafloxacin with those of piperacillin/tazobactam in the treatment of adult patients with SSTI. METHODS: Over an 18-month period, patients aged > or = 18 years with physical findings of acute bacterial SSTI requiring hospitalization and intravenous antimicrobial therapy were randomized in a 1:1 ratio to receive either clinafloxacin 200 mg IV every 12 hours or piperacillin/tazobactam 3.375 g IV every 6 hours. After a minimum of 3 days of intravenous therapy, a switch to oral therapy with clinafloxacin 200 mg PO every 12 hours or amoxicillin/clavulanate 500 mg PO every 8 hours could be made in the respective treatment groups. RESULTS: The center enrolled 84 patients (42 in each group), all but I of whom were male, reflecting the typical VA medical center population. The mean age was 60 years (range, 36-80 years) in the clinafloxacin group and 65 years (range, 35-87) in the piperacillin/tazobactam group; the latter group was significantly older (P = 0.0482), which could have affected recovery rates. Sixty-six patients were white and 18 were black. The mean ( +/- SD) duration of treatment was 10.69 +/- 5.34 days in the clinafloxacin group and 12.07 +/- 5.06 days in the piperacillin/tazobactam group; the mean length of stay was 10.83 +/- 10.28 days and 14.95 +/- 19.20 days, respectively. Fifty-three (63%) patients were switched to oral therapy (21 in the clinafloxacin group, 32 in the piperacillin/tazobactam group). The most commonly isolated pathogens were Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Enterobacter cloacae. Clinical cure rates and microbiologic eradication rates were similar between the 2 treatments. The piperacillin/ tazobactam arm experienced more all-cause adverse events than the clinafloxacin arm, although the difference was not statistically significant. The clinafloxacin arm experienced significantly more adverse events (eg, photosensitivity) that were judged by the investigator to be drug related (P = 0.034). CONCLUSIONS: In this study population of hospitalized adults, clinafloxacin was as effective as piperacillin/tazobactam in the treatment of complicated SSTIs. Appropriate precautions must be taken against exposure to sunlight and ultraviolet light in patients receiving clinafloxacin, and adequate monitoring is necessary. Further investigation is necessary into how the phototoxic effects of the flu oroquinolones can be limited.

A last resort modality using cryofiltration apheresis for the treatment of cold hemagglutinin disease in a Veterans Administration hospital.

Cold hemagglutinin disease is a cold autoimmune hemolytic anemia (cAIHA) caused by an autoantibody, such as IgM, directed against the I-antigen present on the surface of erythrocytes. Cold exposure can activate this system causing hemolysis, hemagglutination, microvascular thrombosis, or acrocyanosis. Thus, surgical procedures requiring hypothermia, such as coronary artery bypass surgery, present a significant problem in patients with cAIHA. The purpose of this study was to evaluate the safety and effectiveness of cryofiltration apheresis (CFA), used as a last resort, for the treatment of cAIHA. Effectiveness was evaluated by clinical assessment and laboratory evaluations of cold agglutinin titer, immunoglobulins, and other plasma proteins. Safety was evaluated by vital signs, monitoring, and laboratory measurements of complements, hematology and blood chemistry. Five patients with cAIHA were treated by CFA using the cryoglobulin (CG) filter (Pall Medical, Ann Arbor, MI, USA). Four patients received only one CFA procedure, while one patient received four CFA treatments. The cold agglutinin titers were fairly low, ranging from 1 : 1 to 1 : 2048. However, a wide thermal amplitude(4-37 degrees C) was observed in most patients. Two out of five patients responded favorably with reduction in titer. The two responders had acute forms of cAIHA with serum positive for cryoglobulins. The three non-responders had chronic forms of cAIHA with negative cryoglobulins. CFA effectively removed cryoprotein precipitates while conserving other plasma components. The CG filter was biocompatible with no complement activation or observed complications due to CFA or CG filter. While the mechanism of action in treating this type of patient population with CFA is unknown, the plausible theories are discussed.