BACKGROUND: The prophylactic administration of antimicrobial agents to surgical patients has become standard practice to minimize the risk for postsurgical infection. During surgery, factors such as renal clearance, fluid administration, and blood loss contribute to drug concentrations achieved in the blood and tissues. The aminoglycoside gentamicin was chosen to investigate these factors because it is used for standard antimicrobial prophylaxis in colorectal surgery. OBJECTIVE: The aim of this study was to investigate the effects of surgical blood loss and fluid volume replacement on gentamicin concentrations in serum and in 3 tissue types (subcutaneous fat, epiploic fat, and colonic wall) in patients undergoing colorectal surgery. METHODS: This uncontrolled, open-label study was conducted at the Aretaieion Hospital (Athens, Greece) between November 2002 and March 2003. Patients selected for this study were scheduled to undergo elective colorectal surgery of ? 2-hour duration with general and epidural anesthesia and to receive gentamicin as major antimicrobial prophylaxis. Blood and tissue samples were obtained concurrently at specific times throughout each procedure. The effect of intraoperative blood loss on gentamicin concentrations and its pharmacokinetic properties was determined. RESULTS: Sixteen patients completed the study (11 men, 5 women; white race, 16 patients [100%]; mean [SD] age, 61 [3] years [range, 39-80 years]). Mean (SEM) serum gentamicin concentration was found to be insufficient; the maximum plasma drug concentration/minimum inhibitory concentration (MIC) ratio was <8:1 for pathogens commonly isolated in the surgical unit of the hospital (MIC: 1-4 microg/mL). The mean (SEM) concentration at first surgical incision was 7.83 (0.82) microg/mL and decreased to 2.60 (0.28) microg/mL at skin closure, resulting in borderline effectiveness even for susceptible gram-positive microorganisms (MIC approximately 1.0). Initially, mean (SEM) tissue gentamicin concentrations in subcutaneous fat, epiploic fat, and colonic wall were low (2.02 [0.34] microg/mL, 2.41 [0.42] microg/mL, and 1.93 [0.38] microg/mL, respectively) and decreased approximately 1.0 microg/mL ( approximately 50%) by skin closure. Statistically significant positive correlations were found between gentamicin concentrations in serum and tissues (P </= 0.03). A strong negative correlation was found between the intravenously administered fluids and gentamicin concentrations in serum and tissues (P </= 0.04). CONCLUSIONS: In this study, the administration of a 2-mg/kg dose of gentamicin as antimicrobial prophylaxis during colorectal surgery associated with significant intraoperative blood loss and therefore requiring significant fluid replacement did not achieve concentrations of the drug above MICs for gram-negative microorganisms throughout the procedures in either serum or tissue samples.
BACKGROUND: The prophylactic administration of antimicrobial agents to surgical patients has become standard practice to minimize the risk for postsurgical infection. During surgery, factors such as renal clearance, fluid administration, and blood loss contribute to drug concentrations achieved in the blood and tissues. The aminoglycosidegentamicin was chosen to investigate these factors because it is used for standard antimicrobial prophylaxis in colorectal surgery. OBJECTIVE: The aim of this study was to investigate the effects of surgical blood loss and fluid volume replacement on gentamicin concentrations in serum and in 3 tissue types (subcutaneous fat, epiploic fat, and colonic wall) in patients undergoing colorectal surgery. METHODS: This uncontrolled, open-label study was conducted at the Aretaieion Hospital (Athens, Greece) between November 2002 and March 2003. Patients selected for this study were scheduled to undergo elective colorectal surgery of ? 2-hour duration with general and epidural anesthesia and to receive gentamicin as major antimicrobial prophylaxis. Blood and tissue samples were obtained concurrently at specific times throughout each procedure. The effect of intraoperative blood loss on gentamicin concentrations and its pharmacokinetic properties was determined. RESULTS: Sixteen patients completed the study (11 men, 5 women; white race, 16 patients [100%]; mean [SD] age, 61 [3] years [range, 39-80 years]). Mean (SEM) serum gentamicin concentration was found to be insufficient; the maximum plasma drug concentration/minimum inhibitory concentration (MIC) ratio was <8:1 for pathogens commonly isolated in the surgical unit of the hospital (MIC: 1-4 microg/mL). The mean (SEM) concentration at first surgical incision was 7.83 (0.82) microg/mL and decreased to 2.60 (0.28) microg/mL at skin closure, resulting in borderline effectiveness even for susceptible gram-positive microorganisms (MIC approximately 1.0). Initially, mean (SEM) tissue gentamicin concentrations in subcutaneous fat, epiploic fat, and colonic wall were low (2.02 [0.34] microg/mL, 2.41 [0.42] microg/mL, and 1.93 [0.38] microg/mL, respectively) and decreased approximately 1.0 microg/mL ( approximately 50%) by skin closure. Statistically significant positive correlations were found between gentamicin concentrations in serum and tissues (P </= 0.03). A strong negative correlation was found between the intravenously administered fluids and gentamicin concentrations in serum and tissues (P </= 0.04). CONCLUSIONS: In this study, the administration of a 2-mg/kg dose of gentamicin as antimicrobial prophylaxis during colorectal surgery associated with significant intraoperative blood loss and therefore requiring significant fluid replacement did not achieve concentrations of the drug above MICs for gram-negative microorganisms throughout the procedures in either serum or tissue samples.
Authors: Bradley D Menz; Esmita Charani; David L Gordon; Andrew J M Leather; S Ramani Moonesinghe; Cameron J Phillips Journal: Infect Drug Resist Date: 2021-12-07 Impact factor: 4.003