Pharmacokinetics of Prophylactic Ampicillin–Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass

Abstract

Antibiotic concentrations must be maintained at an adequate level throughout cardiovascular surgery to prevent surgical site infection. This study aimed to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used antibiotic prophylaxis regimen, to maintain adequate concentrations throughout the course of cardiovascular surgery with cardiopulmonary bypass (CPB). The total plasma concentrations of ampicillin were monitored in 8 patients after ampicillin (1 g)-sulbactam (0.5 g) administration via initial intravenous infusion and subsequent CPB priming. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin. The mean values for the volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 15.8 4.1 L, 0.505 0.186 h 1 , 1.52 0.47 h, and 7.72 2.72 L/h, respectively. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered every 3, 4, 6, and 12 h after the start of CPB, the predicted free trough plasma concentrations of ampicillin were 15.20, 8.25, 2.74, and 0.13 µg/mL, respectively. Therefore, an every-6-h regimen was needed to maintain the free ampicillin concentration at more than 2 µg/mL during cardiovascular surgery with CPB. We suggest that the dose and dosing interval for ampicillin-sulbactam should be adjusted to optimize the efficacy and safety of treatment, according to the minimum inhibitory concentrations for methicillin-sensitive Staphylococcus aureus isolates at each institution. Registration number: UMIN000007356.Key words ampicillin; sulbactam; cardiovascular surgery; prophylaxis; cardiopulmonary bypass The United States Centers for Disease Control National Nosocomial Infections Surveillance system demonstrated that surgical site infection (SSI) is the most frequently reported nosocomial infection, accounting for 14-16% of such infections among hospitalized patients and 38% in surgical patients.1) According to the Japan Nosocomial Infections Surveillance Open Report 2013, the incidence of SSI in cardiovascular surgery was 1.5-4.8%. 2)Postoperative SSIs are a major cause of postoperative morbidity and mortality in patients undergoing cardiac surgery. SSIs of the sternal wound and underlying mediastinum occur in 0.4-4% of cardiac surgical operations.3) The administration of antibiotic prophylaxis in patients treated with cardiothoracic operations can reduce the rate of SSI, and placebo-controlled trials of cardiothoracic antibiotic prophylaxis have found a benefit in preventing postoperative wound infections. 4)Cardiopulmonary bypass (CPB) is a technique that is nearly exclusively used by cardiac surgeons and has profound effects on the volume of distribution (V d , L) and elimination kinetics for a variety of drugs, including commonly used antibiotic prophylaxis agents.3) Antibiotic prophylaxis should be selected according to the type of surgery, with administration starting within 60 min of the skin incision. When the duration of...

Negative pressure wound therapy for patients with mediastinitis: A meta‐analysis

“…Complications include adult respiratory distress syndrome, acute renal failure, and pneumonia. 21,22 The treatment of mediastinal inflammation is generally open drainage, but there are certain problems with this type of treatment, such as inadequate drainage of pus and long treatment time. 23 The advantage of continuous negative pressure drainage is that it generates a sub-atmospheric negative pressure in the soft tissue by continuous uninterrupted vacuum suction so that the continuously generated harmful substances such as exudate and pus as a bacterial propagation medium are continuously removed.…”

“…Delayed diagnosis and inappropriate mediastinal drainage are the main causes of high mortality. Complications include adult respiratory distress syndrome, acute renal failure, and pneumonia 21,22 …”

Dose optimization of β-lactams antibiotics in pediatrics and adults: A systematic review

“…A total of 32 studies were reported in adults, of which 11 articles were on penicillins ( Lodise et al, 2007a ; Lorente et al, 2009 ; Roberts et al, 2010 ; Dow et al, 2011b ; Yost and Cappelletty, 2011 ; De Waele J. et al, 2014 ; De Waele J. J. et al, 2014 ; Sime F. B. et al, 2015 ; Laterre et al, 2015 ; Yokoyama et al, 2015 ; Yokoyama et al, 2016 ), 11 on cephalosporin ( Hanes et al, 2000 ; Joynt et al, 2001 ; Nicolau et al, 2001 ; Buijk et al, 2002 ; Lodise et al, 2007b ; Lorente et al, 2007 ; Roberts et al, 2007 ; Chapuis et al, 2010 ; Carlier et al, 2014 ; Cousson et al, 2015 ; Kang et al, 2020 ), 10 on carbapenems ( Lorente et al, 2006 ; Sakka et al, 2007 ; Cheatham et al, 2008 ; Dow et al, 2011a ; Crandon et al, 2011 ; Hsaiky et al, 2013 ; De Waele J. J. et al, 2014 ; Lu et al, 2016 ; Yokoyama et al, 2018 ; Kothekar et al, 2020 ) and 1 on other β-lactams (aztreonam) ( Cies et al, 2017a ) ( Table 2 ). One randomized controlled trial was conducted on temocillin in patients with intra-abdominal and lower respiratory tract infections ( Laterre et al, 2015 ).…”

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