Presumptive Antibiotics in Tube Thoracostomy for Traumatic Hemopneumothorax: A Prospective, Multicenter American Association for the Surgery of Trauma

Study

Forrest O. Moore, MD, FACS Trauma, Critical Care & Acute Care Surgery Banner Healthcare System Phoenix, AZ

Address correspondence to: Forrest O. Moore, MD, FACS Trauma, Critical Care & Acute Care Surgery Banner Healthcare System Phoenix, AZ Moore677@aol.com Phone: (480) 284-1703

INTRODUCTION Post-traumatic empyema and pneumonia are potential complications of tube thoracostomy (TT), and presumptive antibiotics have been advocated by some to decrease the incidence of these infections. Because the practice of administering presumptive antibiotics to decrease the incidence of infectious complications in tube thoracostomy is controversial, the Eastern Association for the Surgery of Trauma (EAST) Practice Management Guidelines Work Group published guidelines in 1998 and updated those guidelines in 2012 (publication pending). The 2012 work group made the following recommendations:

There is insufficient published evidence to support any recommendation either for or against the use of presumptive antibiotics to reduce the incidence of empyema and pneumonia in tube thoracostomy for traumatic hemopneumothorax.

This statement was based on English studies published between 1977 and 2011 and vary in quality and in outcome. The two most recent, randomized, controlled studies showed no reduction in either empyema or pneumonia. Gonzalez et al. published the results of their randomized, prospective study of the role of prophylactic antibiotics for TT in patients with isolated chest trauma. They concluded that patients who received antibiotics had significant reductions in infectious complications and suggested that patients who undergo TT for chest trauma would benefit from prophylactic antibiotics. The complications of empyema and pneumonia were not evaluated separately in their

article. A randomized, prospective study published by Maxwell et al. in 2004 concluded that presumptive antibiotics did not reduce the incidence of either empyema or pneumonia. The study was divided into three groups. Group A (77 patients) received cefazolin until TT was removed; group B (76 patients) received cefazolin for 24 hours, then placebo until TT was removed; and group C (71 patients) received placebo for the entire duration of TT. Group A did not develop any empyemas, however an incidence of 6.5% (5/77) was noted for pneumonia. Group B had an incidence of empyema in 2.6% (2/76) and pneumonia in 7.9% (6/76). Group C had an incidence of empyema in 5.6% (4/71) and pneumonia 4.2% (3/71). However, this 3-year study was terminated because of poor patient accrual that resulted in less than 20% of the predicted number of patients needed (approximately 1200 needed). The practice of antibiotic prophylaxis in TT after chest trauma remains controversial for numerous reasons. The timing of administration of antibiotics may explain why antibiotics given post-injury, and prior to TT in traumatic hemopneumothorax, may not be as effective as those given truly prophylactically. In surgical cases, adequate antibiotic tissue levels are reached when administered prior to incision, thereby reducing the incidence of surgical site infection. The term prophylactic may not be accurate after trauma, as contamination of the pleural space has already occurred at the time of injury, prior to antibiotic administration. Drug concentrations in the tissues are not achieved before contamination, and therefore, should be considered presumptive therapy when antibiotics are given post-injury. In addition, several studies did not control for mechanism of injury (penetrating versus blunt) or did not specify the mechanism of injury. Two of these studies also reported presumptive antibiotics in TT for

spontaneous pneumothoraces, a non-traumatic patient population. This heterogeneity confounds which patient population may actually benefit from presumptive antibiotics. Furthermore, while the Centers for Disease Control and Prevention have definitions for the diagnosis of empyema and pneumonia, few studies adhered to these definitions. Several studies used non-standard or no standard definition for both empyema and pneumonia. In the era of emerging resistant organisms, antibiotic prophylaxis is typically limited to 24 hours duration and is usually a first-generation cephalosporin for the penicillin-allergic patient. First-generation cephalosporins provide adequate coverage for Staphylococcus aureus, the most common infectious organism in post-traumatic empyema. Only three studies from the 1998 guidelines used a first-generation cephalosporin. The remaining studies used suboptimal Staphylococcus aureus coverage or used suboptimal dosing. Only one study limited antibiotic prophylaxis to 24 hours. Gonzalez et al. published the results of their randomized, prospective trial using cefazolin as the presumptive antibiotic in the group of 71 patients who received antibiotics, compared to the group of 68 patients who received placebo (albumin). However, antibiotics were given during the entire length of TT placement, averaging 4.9 days. As previously noted, they concluded that infectious complications were significantly reduced, however, when empyema and pneumonia were analyzed separately, the reduction was not significantly different. Maxwells randomized, controlled study compared two antibiotic regimens and one placebo regimen. Of concern was the increased incidence of resistant organisms in patients receiving antibiotics, including MRSA and Pseudomonas aeruginosa. The study concluded that presumptive antibiotics

were of minimal benefit considering the need to treat large numbers of patients to prevent a single empyema. This conclusion combined with the emergence of resistant organisms found the use of presumptive antibiotics for TT in chest trauma to be unwise.

SUMMARY No single published study, nor the combination of several studies, has been powered to adequately address the practice of administering presumptive antibiotics in TT for traumatic hemopneumothorax to decrease the incidence of empyema or pneumonia. Until a large and likely multicenter trial can be performed, the routine practice of presumptive antibiotics in TT for chest trauma will remain controversial.

STUDY OBJECTIVES To perform an adequately powered multicenter study to determine if presumptive antibiotics in TT for traumatic hemopneumothorax reduce the incidence of empyema or pneumonia.

HYPOTHESIS Presumptive antibiotics in TT for traumatic hemopneumothorax do not reduce the incidence of empyema or pneumonia.

TYPE AND DURATION OF STUDY Two year, prospective, observational, multicenter study.

INCLUSION/EXCLUSION CRITERIA All patients, including pediatric and pregnant patients, with blunt or penetrating trauma, who undergo TT for traumatic hemopneumothorax. Initially will exclude patients if they receive antibiotics for other reasons (i.e. open fractures and procedures/surgeries such as exploratory laparotomy or rib plating), however, dependent upon patient accrual, these patients may ultimately be included. Patients are excluded if they are receiving antibiotics at the time of presentation (pre-injury prescription). Patients who develop empyema or pneumonia (and require antibiotics) are clearly included.

DATA COLLECTION/OUTCOMES Groups will be divided into three: 1) no antibiotics 2) one dose of antibiotics pre-/periprocedural (within one hour of placement) 3) antibiotics for 24 hours, and demographics and outcomes compared including: age, ISS, AIS, GCS, mechanism of injury, days on mechanical ventilation, ICU length of stay, hospital length of stay, incidence of Clostridium difficile colitis, and type and duration of antibiotic use. Infectious complications (empyema and pneumonia) associated with TT will be evaluated separately and compared among each group, including the method of diagnosis. Empyema is defined as having a positive pleural culture or pus within the pleural space. Pneumonia is defined as a new or evolving infiltrate on chest radiograph with any of the following: 1) purulent sputum 2) positive blood culture or 3) positive sputum culture or protected brush specimen >103 or bronchoalveolar lavage >104 or 105 (institutionspecific) CFUs.

ANALYSIS Univariate analysis of patient demographics, injury characteristics, and trauma center characteristics with respect to the antibiotic regimen employed will be performed to identify potential confounders. These variables will be used to create a propensity score of receiving a single dose of antibiotics compared to no antibiotics. A 1:1 matching method will be employed based upon patients propensity score and those treated with antibiotics will be compared to those without to determine if the relative risk of the outcomes (empyema and pneumonia) are affected by the antibiotic treatment. Secondary

binary outcomes will be assessed in a similar manner while continuous outcomes will be assessed by t-test.

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