Abstract:This study aimed to construct drug-loading and drug-releasing quantitative equations for gentamicin sponges in addition to realizing a gentamicin sponge for wound infection prevention and treatment. Methods: Sterile sponges were cut into pieces of 1×1 × 0.5 cm and immersed in 40, 16, 8, 4, 1.6, 0.8, or 0 mg/mL of gentamicin solution for 12, 24, 48, 96, or 120 h to evaluate their gentamicin loading. The sponges were subsequently immersed in the gentamicin solution of different concentrations for 48 h, air-dried… Show more
“…A striking example of this phenomenon was the first large-scale RCT to address the effectiveness of gentamicin in SWI prophylaxis where the authors, in order to facilitate handling, did not follow the manufacturer’s instructions to implant the sponge; in this study, the sponge was soaked in saline prior to placing it between the sternal halves 21 , which washed away the gentamicin and resulted in no reduction in SSIs. This was later confirmed in an in-vitro study 33 . Servito et al soaked the gauze in vancomycin solution placed it on the sternal edges at the time of surgery and then removed the gauze before rewiring the sternum at conclusion of the surgery 5 .…”
Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35–0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18–0.64]; p < 0.001) and gentamicin (0.58 [0.39–0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32–0.65]; p < 0.001 and 0.60 [0.44–0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43–0.83]; p = 0.003) and superficial SWIs (0.54 [0.32–0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations’ activity: vancomycin against gram-negative strains: 0.20 (0.01–4.18) and gentamicin against gram-positive strains: 0.42 (0.28–0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.
“…A striking example of this phenomenon was the first large-scale RCT to address the effectiveness of gentamicin in SWI prophylaxis where the authors, in order to facilitate handling, did not follow the manufacturer’s instructions to implant the sponge; in this study, the sponge was soaked in saline prior to placing it between the sternal halves 21 , which washed away the gentamicin and resulted in no reduction in SSIs. This was later confirmed in an in-vitro study 33 . Servito et al soaked the gauze in vancomycin solution placed it on the sternal edges at the time of surgery and then removed the gauze before rewiring the sternum at conclusion of the surgery 5 .…”
Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35–0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18–0.64]; p < 0.001) and gentamicin (0.58 [0.39–0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32–0.65]; p < 0.001 and 0.60 [0.44–0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43–0.83]; p = 0.003) and superficial SWIs (0.54 [0.32–0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations’ activity: vancomycin against gram-negative strains: 0.20 (0.01–4.18) and gentamicin against gram-positive strains: 0.42 (0.28–0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.
“…The original P. aeruginosa concentration was adjusted to 10 10 CFU/mL, 10 9 CFU/mL, 10 8 CFU/mL and 10 7 CFU/mL, based on the number of colonies. 13 , 14 Figure 1 Establishment of stable S-AKI mice model. ( A ) The LB medium with amplified P. aeruginosa .…”
Section: Methodsmentioning
confidence: 99%
“…S-AKI was induced by incision infection with P. aeruginosa . 13–15 A 5 mm median incision was made on the back of the mice to expose the right paravertebral muscle. A 50 μL suspension of bacteria was smeared on the right paravertebral muscle.…”
Section: Methodsmentioning
confidence: 99%
“…The original P. aeruginosa concentration was adjusted to 10 10 CFU/mL, 10 9 CFU/mL, 10 8 CFU/mL and 10 7 CFU/mL, based on the number of colonies. 13,14 did not receive any intervention. Mice in the sham group received only back incisions after being anesthetized.…”
Section: Bacterial Strain and Suspension Preparationmentioning
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