Prospective, open-label investigation of the pharmacokinetics of daptomycin during cardiopulmonary bypass surgery.

As methicillin-resistant Staphylococcus aureus (MRSA) becomes more prevalent, vancomycin is becoming increasingly used as a prophylaxis against surgical-site infections for cardiothoracic surgeries. However, vancomycin administration can be challenging, and the pharmacokinetics of alternative antibiotics in this setting are poorly understood. The primary objective of this investigation was to describe the pharmacokinetics of daptomycin in patients undergoing coronary artery bypass graft surgery. We enrolled 15 patients undergoing coronary artery bypass surgery requiring cardiopulmonary bypass. Each subject was administered a single open-label dose of daptomycin (8 mg/kg of body weight) for surgical prophylaxis. Fourteen daptomycin plasma samples were collected. Safety outcomes between subjects who received daptomycin and 15 control subjects who received the standard-of-care antibiotic were compared. The mean maximal concentration of daptomycin (C(max)) was 84.4 ± 27.1 µg/ml; the mean daptomycin concentration during the cardiopulmonary bypass procedure was 33.2 ± 11.4 µg/ml and was 30.9 ± 12.7 µg/ml at sternum closure. Mean daptomycin concentrations at 12, 18, 24, and 48 h were 22.7 ± 9.7, 16.2 ± 8.2, 12.0 ± 4.7, and 3.5 ± 2.3 µg/ml, respectively. Mean daptomycin concentrations were consistently above the MIC at which 90% of the tested isolates are inhibited (MIC90) for S. aureus and S. epidermidis during the cardiopulmonary bypass procedure. Daptomycin was not associated with surgical-site infections or differences in adverse events compared to findings for control subjects. We found that a single dose of daptomycin at 8 mg/kg was well tolerated and achieved adequate plasma concentrations against common pathogens associated with surgical-site infections after cardiothoracic surgery. Daptomycin may be considered an alternative surgical prophylaxis antibiotic for patients undergoing cardiothoracic bypass surgery who are unable to receive vancomycin.

Hiatal hernia, lower esophageal sphincter incompetence, and effectiveness of Nissen fundoplication in the spectrum of gastroesophageal reflux disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a spectrum of disease that includes nonerosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Treatment outcomes for patients with different stages have differed in many studies. In particular, acid suppressant medication therapy is reported to be less effective for treating patients with NERD and Barrett's esophagus. The aims of this study were to investigate (1) the role of mechanical factors including hiatal hernia and lower esophageal sphincter (LES) competence in the spectrum of GERD and (2) outcomes of Nissen fundoplication. METHODS: From the records of patients who had undergone laparoscopic Nissen fundoplication after an abnormal pH study, we identified 50 symptomatic consecutive patients with each of the GERD stages: (1) NERD, (2) mild ERD, defined as esophagitis that was healed with acid suppression therapy, (3) severe ERD, defined as esophagitis that persisted despite medical therapy, and (4) BE. Exclusion criteria were normal distal esophageal acid exposure, esophageal pH monitoring performed elsewhere, antireflux surgery less than 1 year previously or previous fundoplication, and a named esophageal motility disorder or distal esophageal low amplitude hypomotility. Patients who could not be contacted for the study were also excluded. All patients completed a detailed preoperative questionnaire; underwent preoperative upper gastrointestinal endoscopy, stationary manometry, and distal esophageal pH monitoring; and were interviewed at least 1 year after operation. RESULTS: One hundred sixty patients meeting the entry criteria were studied. The mean follow-up period was 36.7 months. The only significant preoperative symptom difference was that patients with BE had more moderately severe or severe dysphagia compared to patients with NERD. Patients with severe ERD or BE had a significantly higher prevalence of hiatal hernia, lower LES pressures, and more esophageal acid exposure. Hiatal hernia and hypotensive LES were present in most patients with severe ERD or BE but in only a minority of patients with NERD or mild ERD. Surgical therapy resulted in similarly excellent symptom outcomes for patients in all GERD categories. CONCLUSIONS: Compared to mild ERD and NERD, severe ERD and BE are associated with significantly greater loss of the mechanical antireflux barrier as reflected in the presence of hiatal hernia and LES measurements. Restoration of the antireflux barrier and hernia reduction by laparoscopic Nissen fundoplication provides similarly excellent symptom control in all patients.