Implantable Antibiotic Sponge Fails to Reduce Surgical Wound Infection Rate

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.