Efficacy of Post-operative Antibiotic Prophylaxis for Thoracic Surgery Requiring Tube Thoracostomy

Extended Antibiotic Prophylaxis for the Prevention of Infectious Complications Associated With Tube Thoracostomy in Patients Undergoing Elective General Thoracic Surgery: A Double-Blind, Placebo-Controlled, Randomized Trial

The purpose of this study is to evaluate if post-operative antibiotic prophylaxis decreases infectious complications when compared to pre-operative antibiotics alone, in patients undergoing elective thoracic surgery requiring tube thoracostomy (chest tube).

Study Overview

• Status: Completed
• Conditions: Antibiotic Prophylaxis
• Intervention / Treatment: Drug: cefazolin or vancomycin; Drug: Placebo

Detailed Description

There is currently no evidence-based standard for the extended use of prophylactic antibiotics in patients receiving thoracic surgery that results in the placement of a tube thoracostomy (chest tube). The rationale for this prophylaxis is that antibiotics directed at typical skin flora may reduce the rate of infectious complications, such as surgical site infection and empyema.

Currently, clinicians' approach to post-operative antibiotic prophylaxis in patients undergoing tube thoracostomy associated with thoracic and cardio-thoracic surgery varies widely. While reducing the infectious complications of thoracic surgery is an important goal, it is also important to reduce the use of unnecessary antibiotics. As there is equipoise on the benefit of extended antibiotic prophylaxis for tube thoracostomy, our study will examine two prevailing clinical practices and attempt to determine if one leads to better patient outcomes.

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18 years or older undergoing elective thoracic surgery at Brigham & Women's Hospital. The majority of these patients will be undergoing lung resection for either the evaluation of a lung mass, or for the removal of a known malignancy. Some participants may be undergoing biopsy or removal of a mediastinal mass.
• Undergoing thoracic surgery procedure expected to require tube thoracostomy.
• Ability to give informed consent

Exclusion Criteria:

• Patients undergoing the following complex thoracic surgical procedures:

  • Pneumonectomy
  • Decortication
  • Chemical pleurodesis
  • Pleurectomy
  • Lung volume reduction
  • Esophagectomy

• Patients with the following conditions:

  • Prior diagnosis of empyema or lung abscess.
  • Cystic fibrosis
  • Known or suspected pneumonia pre-operatively.
  • Known hypersensitivity to beta-lactam antibiotics and vancomycin
  • Current or recent antibiotic use within one week of surgery.
  • Anticipated requirement for postoperative antibiotic in addition to 48 hours of cefazolin or vancomycin.
  • Renal insufficiency with estimated creatinine clearance <60 ml/minute.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antibiotic; Participants received intravenous (IV) cefazolin or vancomycin (for participants allergic to cephalosporin) immediately following surgery for 48 hours or until all chest tubes were removed, whichever occurred first.	Drug: cefazolin or vancomycin; Cefazolin IV every eight hours post-operatively for 48 hours or until all chest tubes were removed, whichever occurred first. Participants under 80 kg received 1 gram of cefazolin and participants who were 80 kg or more received 2 grams of cefazolin. Participants who were penicillin-allergic received 1 gram of vancomycin every 12 hours for 48 hours or until all chest tubes were removed, whichever occurred first.; Other Names: Cefazolin (Ancef); Vancomycin (Vancocin)
Placebo Comparator: Placebo; Participants received IV placebo-matching antibiotics immediately following surgery for 48 hours or until all chest tubes were removed, whichever occurred first.	Drug: Placebo; Participants received IV placebo for 48 hours post-operatively or until all chest tubes were removed, whichever occurred first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced At Least One Postoperative Infectious Complication	Infectious complications include: surgical site infection, empyema, pneumonia, and the occurrence of Clostridium difficile colitis within 28 days of surgery. Participants are only counted once regardless of how many different infectious complications they had.	Up to 28 days after surgery
Number of Participants Who Experienced Surgical Site Infection	Surgical Site Infection: Superficial surgical site infection - involves only skin or subcutaneous tissue around incision and has at least one of the following criteria:purulent drainageorganisms isolated from aseptically obtained culturepain or tenderness, localized swelling, redness or heat and the incision deliberately opened by a surgeondiagnosis of a superficial wound infection by a surgeon; Deep surgical site infection - involves deep soft tissues e.g. fascia or muscle and has at least one of the following:purulent drainage from the incision but not from the organ/space of the surgical sitedeep incision spontaneously dehisces or deliberately opened by surgeon when patient has at least one of following signs or symptoms - fever (>38°C), localized pain or tenderness.an abscess or evidence of infection involving incision is found on direct examination, histopathologic or radiographic examinationdiagnosis of a deep wound infection	Up to 28 days after surgery
Number of Participants Who Experienced Pneumonia	Pneumonia: A new infiltrate on chest x-ray associated with at least three of the following: fever (>38°C); purulent sputum; leukopenia (white blood cell [WBC] count of <4000/µL) or leukocytosis (WBC count of >11000/µL); sputum culture with pathogenic bacteria; increased oxygen requirements	Up to 28 days after surgery
Number of Participants Who Experienced Empyema	Empyema: Positive pleural culture result or purulence within the thoracic space and leukocytosis or fever (>38°C).	Up to 28 days after surgery
Number of Participants Who Experienced Clostridium (C) Difficile Colitis	C. Difficile Colitis: Positive for C difficile toxin assay results and any 1 of the following: new diarrhea; ileus or toxic megacolon; leukopenia (WBC count of <4000/µL) or leukocytosis (WBC count of >11000/µL); findings from sigmoidoscopy, colonoscopy, or histopathologic examination consistent with C difficile infection	Up to 28 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Received Additional Antibiotics for Any Reason Within 28 Days After Surgery	The number of participants who needed any additional non-study antibiotics for any reason after randomization.	Up to 28 days after surgery
Number of Participants Who Needed Reoperation	The number of participants who needed reoperations for any reason from the time after the first surgery to the end of the 28-day follow-up period.	Up to 28 days after surgery
Length of Hospital Stay	The length of hospital stay is the number of days the participant remained in the hospital.	From day of surgery to discharge (up to 35 days)
Time to Removal of Chest Tubes	Time to removal of chest tubes is the number of days from the time of chest tube placement to time they were removed.	From day of surgery to removal of chest tubes (up to 33 days)
Number of Participants With Allergic Reactions	The number of participants with an allergic reaction to a drug.	Up to 28 days after surgery
All-Cause Mortality	All-cause mortality is the number of deaths that occurred during the study period, regardless of the cause.	Up to 28 days after surgery

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Lindsey Baden, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Oxman DA, Issa NC, Marty FM, Patel A, Panizales CZ, Johnson NN, Licona JH, McKenna SS, Frendl G, Mentzer SJ, Jaklitsch MT, Bueno R, Colson Y, Swanson SJ, Sugarbaker DJ, Baden LR. Postoperative antibacterial prophylaxis for the prevention of infectious complications associated with tube thoracostomy in patients undergoing elective general thoracic surgery: a double-blind, placebo-controlled, randomized trial. JAMA Surg. 2013 May;148(5):440-6. doi: 10.1001/jamasurg.2013.1372.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: January 7, 2009
• First Submitted That Met QC Criteria: January 7, 2009
• First Posted (Estimate): January 8, 2009

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Thoracic Surgery; Chest Tube; Antibiotic Prophylaxis
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefazolin
• Other Study ID Numbers: 2007p002164