Infection
Sophie Amalie Blirup-Plum, Thomas Bjarnsholt, Henrik Elvang Jensen, Kasper Nørskov Kragh, Bent Aalbæk, Hans Gottlieb, Mats Bue, Louise Kruse Jensen
Department of Veterinary and Animal Sciences, University of Copenhagen; Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen; Department of Veterinary and Animal Sciences, University of Copenhagen; Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen; Department of Veterinary and Animal Sciences, University of Copenhagen; Department of Orthopedic Surgery, Herlev Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Veterinary and Animal Sciences, University of Copenhagen
Background: CERAMENTTM|G is an absorbable gentamicin loaded bio-composite, trusted by several clinical studies as an on-site vehicle of antibiotics for the treatment of chronic osteomyelitis.
Purpose / Aim of Study: We aimed to assess the sole effect of CERAMENTTM|G, i.e. without additional systemic antibiotic therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.
Materials and Methods: Osteomyelitis was induced in nine pigs by inoculation of 104 CFU of Staphylococcus aureus into a drill hole in the left tibia. After one week, the pigs were allocated into three groups. Group A (n=3) received no treatment during the study period (19 days). Group B (n=3) and C (n=3) received limited or extensive debridement 7 days post inoculation, respectively, followed by injection of CERAMENTTM|G into the bone voids. The pigs were euthanized 10 (Group C) and 12 (Group B) days after the intervention.
Findings / Results: All animals demonstrated confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENTTM|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the peak post-mortem gentamicin concentrations in CERAMENTTM|G and surrounding bone tissue samples were 16.6 µg/mL and 6.2 µg/mL, respectively.
Conclusions: CERAMENTTM|G may not be used as a standalone alternative to extensive debridement or be used without the addition of systemic antibiotics.
Department of Veterinary and Animal Sciences, University of Copenhagen; Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen; Department of Veterinary and Animal Sciences, University of Copenhagen; Costerton Biofilm Center, Department of Immunology and Microbiology, University of Copenhagen; Department of Veterinary and Animal Sciences, University of Copenhagen; Department of Orthopedic Surgery, Herlev Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Veterinary and Animal Sciences, University of Copenhagen
Background: CERAMENTTM|G is an absorbable gentamicin loaded bio-composite, trusted by several clinical studies as an on-site vehicle of antibiotics for the treatment of chronic osteomyelitis.
Purpose / Aim of Study: We aimed to assess the sole effect of CERAMENTTM|G, i.e. without additional systemic antibiotic therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.
Materials and Methods: Osteomyelitis was induced in nine pigs by inoculation of 104 CFU of Staphylococcus aureus into a drill hole in the left tibia. After one week, the pigs were allocated into three groups. Group A (n=3) received no treatment during the study period (19 days). Group B (n=3) and C (n=3) received limited or extensive debridement 7 days post inoculation, respectively, followed by injection of CERAMENTTM|G into the bone voids. The pigs were euthanized 10 (Group C) and 12 (Group B) days after the intervention.
Findings / Results: All animals demonstrated confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENTTM|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the peak post-mortem gentamicin concentrations in CERAMENTTM|G and surrounding bone tissue samples were 16.6 µg/mL and 6.2 µg/mL, respectively.
Conclusions: CERAMENTTM|G may not be used as a standalone alternative to extensive debridement or be used without the addition of systemic antibiotics.
Pelle Hanberg, Mats Bue, Kristina Öbrink-Hansen, Maja Thomassen, Kjeld Søballe, Maiken Stilling
Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Infectious Diseases, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important.
Purpose / Aim of Study: We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.
Materials and Methods: Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.
Findings / Results: Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 µg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 µg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared with Group C (p=0.08).
Conclusions: Administration of cefuroxime (1.5 g) in the 15-45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release.
Department of Orthopaedic Surgery, Horsens Regional Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Infectious Diseases, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital; Department of Orthopaedic Surgery, Aarhus University Hospital
Background: Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important.
Purpose / Aim of Study: We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.
Materials and Methods: Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.
Findings / Results: Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 µg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 µg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared with Group C (p=0.08).
Conclusions: Administration of cefuroxime (1.5 g) in the 15-45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release.
Josephine Olsen Kipp, Pelle Hanberg, Josefine Slater, Line Møller Nielsen, Stig Storgaard Jakobsen, Maiken Stilling, Mats Høy Bue
Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital ; Orthopaedic Research Unit, Aarhus University Hospital ; Department of Clinical Biochemistry, Aarhus University Hospital ; Department of Orthopaedic Surgery, Aarhus University Hospital ; Department of Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital
Background: Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations.
Purpose / Aim of Study: To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.
Materials and Methods: Eight female pigs were assigned to receive 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in tibial cancellous bone adjacent to the intraosseous cannula, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained. Samples were collected for 12 hours.
Findings / Results: High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28- 5,295) µg/mL, which remained high throughout the sampling period with a mean end concentration of 278 (range 2.7- 1,362.7) µg/mL after 690 min. The mean (standard derivation (SD)) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. For the intramedullary canal, in the synovial fluid of the knee joint, and subcutaneous tissue, comparable mean peak drug concentration and mean time to peak drug concentration were found in the range of 7.5-8.2 µg/mL and 45-70 min, respectively.
Conclusions: Tibial intraosseous administration of vancomycin provided high mean concentrations in tibial cancellous bone throughout a 12-hour period, but with an immediate and high systemic absorption. The concentrations in cancellous bone had an unpredictable and wide range of peak concentration. Low mean concentrations were found in all the remaining compartments. Our findings suggest that intraosseous vancomycin administration in proximal tibial cancellous bone only is relevant as treatment in cases requiring high local concentrations nearby the intraosseous cannula.
Orthopaedic Research Unit, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital ; Orthopaedic Research Unit, Aarhus University Hospital ; Department of Clinical Biochemistry, Aarhus University Hospital ; Department of Orthopaedic Surgery, Aarhus University Hospital ; Department of Orthopaedic Surgery, Aarhus University Hospital; Orthopaedic Research Unit, Aarhus University Hospital
Background: Systemically administered vancomycin may provide insufficient target-site concentrations. Intraosseous vancomycin administration has the potential to overcome this concern by providing high target-site concentrations.
Purpose / Aim of Study: To evaluate the local bone and tissue concentrations following tibial intraosseous vancomycin administration in a porcine model.
Materials and Methods: Eight female pigs were assigned to receive 500 mg diluted vancomycin (50 mg/mL) through an intraosseous cannula into the proximal tibial cancellous bone. Microdialysis was applied for sampling of vancomycin concentrations in tibial cancellous bone adjacent to the intraosseous cannula, in cortical bone, in the intramedullary canal of the diaphysis, in the synovial fluid of the knee joint, and in the subcutaneous tissue. Plasma samples were obtained. Samples were collected for 12 hours.
Findings / Results: High vancomycin concentrations were found in the tibial cancellous bone with a mean peak drug concentration of 1,236 (range 28- 5,295) µg/mL, which remained high throughout the sampling period with a mean end concentration of 278 (range 2.7- 1,362.7) µg/mL after 690 min. The mean (standard derivation (SD)) peak drug concentration in plasma was 19 (2) µg/mL, which was obtained immediately after administration. For the intramedullary canal, in the synovial fluid of the knee joint, and subcutaneous tissue, comparable mean peak drug concentration and mean time to peak drug concentration were found in the range of 7.5-8.2 µg/mL and 45-70 min, respectively.
Conclusions: Tibial intraosseous administration of vancomycin provided high mean concentrations in tibial cancellous bone throughout a 12-hour period, but with an immediate and high systemic absorption. The concentrations in cancellous bone had an unpredictable and wide range of peak concentration. Low mean concentrations were found in all the remaining compartments. Our findings suggest that intraosseous vancomycin administration in proximal tibial cancellous bone only is relevant as treatment in cases requiring high local concentrations nearby the intraosseous cannula.
Sahar Moeini, Hans Gottlieb, Tue Smith Jørgensen, Malene Ringholm Bæk Larsen, Stig Brorson
Department of Orthopaedic Surgery, Zealand University Hospital Koege; Department of Orthopaedic Surgery, Herlev University Hospital; Department of Orthopaedic Surgery, Hvidovre University Hospital; Department of Orthopaedic Surgery, Zealand University Hospital Koege; Department of Orthopaedic Surgery, Zealand University Hospital Koege
Background: Chronic foot ulcers have extensive consequences for diabetic patients’ quality of life and increases risks of amputation and death.
Purpose / Aim of Study: The aim of this trial was to assess the feasibility of conducting a larger clinical trial to evaluate the clinical effect of inforatio technique on healing of diabetic foot ulcers.
Materials and Methods: Inforatio technique is a newly developed procedure where small punch biopsies are taken from the wound bed to promote healing. This study was a feasibility trial conducted at an outpatient wound care clinic at Zealand University Hospital. 12 diabetic patients with foot ulcers were included. During a 90-day follow-up, participants visited the clinic five times and received inforatio technique once to twice. Photographs of the ulcers were taken at each trial visit and wound area was measured by digital wound planimetry. If participants attended the outpatient clinic after follow-up, ulcers were observed for complete healing until 140 days from baseline. Feasibility was assessed with regard to recruitment; acceptability; burden; benefits; protocol adherence; and harmful effects.
Findings / Results: During follow-up; four ulcers had complete healing (33%, 95%CI: [10-65]); five ulcers had a reduction in wound area; and three ulcers had an increase in area. Ten of the participants attended the outpatient clinic after follow-up and six of them had complete healing of their ulcer within 140 days from baseline. The recruitment rate was one patient per 8th day, and the retention rate was 100%. All participants reported a positive experience of participation. There were no patient-reported or observed harmful effects.
Conclusions: No harmful effects were reported, and patient acceptability and participant adherence was promising. Thus, a larger clinical trial for evaluating the clinical effect of inforatio technique is considered feasible to conduct. Results for complete healing witnin 140 days was promising compared to proportions of healing reported in the literature for diabetic foot ulcers treated with standard wound care. If inforatio technique has the expected prositive effect on healing of diabetic foot ulcers, it may benefit patients worldwide.
Department of Orthopaedic Surgery, Zealand University Hospital Koege; Department of Orthopaedic Surgery, Herlev University Hospital; Department of Orthopaedic Surgery, Hvidovre University Hospital; Department of Orthopaedic Surgery, Zealand University Hospital Koege; Department of Orthopaedic Surgery, Zealand University Hospital Koege
Background: Chronic foot ulcers have extensive consequences for diabetic patients’ quality of life and increases risks of amputation and death.
Purpose / Aim of Study: The aim of this trial was to assess the feasibility of conducting a larger clinical trial to evaluate the clinical effect of inforatio technique on healing of diabetic foot ulcers.
Materials and Methods: Inforatio technique is a newly developed procedure where small punch biopsies are taken from the wound bed to promote healing. This study was a feasibility trial conducted at an outpatient wound care clinic at Zealand University Hospital. 12 diabetic patients with foot ulcers were included. During a 90-day follow-up, participants visited the clinic five times and received inforatio technique once to twice. Photographs of the ulcers were taken at each trial visit and wound area was measured by digital wound planimetry. If participants attended the outpatient clinic after follow-up, ulcers were observed for complete healing until 140 days from baseline. Feasibility was assessed with regard to recruitment; acceptability; burden; benefits; protocol adherence; and harmful effects.
Findings / Results: During follow-up; four ulcers had complete healing (33%, 95%CI: [10-65]); five ulcers had a reduction in wound area; and three ulcers had an increase in area. Ten of the participants attended the outpatient clinic after follow-up and six of them had complete healing of their ulcer within 140 days from baseline. The recruitment rate was one patient per 8th day, and the retention rate was 100%. All participants reported a positive experience of participation. There were no patient-reported or observed harmful effects.
Conclusions: No harmful effects were reported, and patient acceptability and participant adherence was promising. Thus, a larger clinical trial for evaluating the clinical effect of inforatio technique is considered feasible to conduct. Results for complete healing witnin 140 days was promising compared to proportions of healing reported in the literature for diabetic foot ulcers treated with standard wound care. If inforatio technique has the expected prositive effect on healing of diabetic foot ulcers, it may benefit patients worldwide.