Clinical Studies

Orthopaedic Studies

Johnson B, Starks I, et al. The effect of care bundle development on surgical site infection after hemi-arthroplasty: An 8 year review. J Trauma 2012; Vol 72, No. 5 1375-1379

Analyzed 1,830 Hemiarthroplasites. Statistical analysis of data collected by the SSISS during the period commencing October 2001 and ending June 2009. The care bundle underwent three phases of development during this period. The first care bundle comprised antibiotic prophylaxis in the form of three doses of cefuroxime (1.5 g) administered intravenously along with aqueous iodine as surgical preparation solution and clips for skin closure. The second care bundle consisted of a single dose of cefuroxime (1.5 g) and gentamicin (240 mg) administered intravenously at induction with double skin prep using alcoholic chlorhexidine and again clips for skin closure (Table 1). The final stage of care bundle development involved changing the single dose of cefuroxime to co-amoxiclav (1.2 g) and implantation of a 6 cm  4 cm gentamicin-impregnated equine collagen containing 192 mg gentamicin sulfate under the fascial layer at wound closure. Skin closure was done using subcuticular sutures.

Main Findings

  • Use of gentamicin impregnated collagen sponges as an adjunct to IV prophylaxis is recommended to prevent SSI in patients undergoing hemiarthroplasty.
  • The care bundle including gentamicin collagen sponges also showed a reduction in SSI caused by MRSA. The high profile national targets to decrease hospital acquired infections and MRSA bacteremias may be addressed by adopting this care bundle.
  • The author recommends adoption of the care bundle approach as a significant adjunct to reducing SSI in hemiarthroplasty patients. It seems particularly effective and well-targeted to MRSA prophylaxis. The care bundle is a simple and cost effective improvement in this patient cohort.

 

Rohde V, Meyer B, Schaller C et al. Spondylodiscitis after lumbar discectomy: Incidence and a proposal for prophylaxis. Spine 1998;23:615-620.

Analyzed 1652 consecutive patients undergoing microneurosurgical procedures for lumbar disc herniation. 1 x Collatamp in the cleared disc space (1134 pts) vs routine procedure (508 pts).

Main Findings

  • Post-op spondylodiscitis: 0% (Collatamp) vs 3.7% (control), p<0.00001.

 

Von Hasselbach C, Klinic  und Pharmakokinetik von Kollagen-Gentamicin als Adjuvante Lokaltherapie Knöcherner Infektionen. Unfallchirurg 1989;92:459-470

Analyzed 58 cases of osteomyelitis . Collatamp placed adjacent to infected bone.

Main Findings

  • 55/58 patients remained free of osteomyelitis reinfection for 3 months at study closure, of the 55 patients free of reinfection, 29 had been free of reinfection for over 1 year.

 

Lütten C, Lorenz H, Thomas W. Exchange of operation with hip and knee joint endoprosthesis. Chir Praxis 1989;40:287-291

Analyzed 13 hip and 9 knee revision arthroplasties. Mixture of spongy bone and Collatamp to fill defects + routine systemic antibiotics.

Main Findings

  • Infection prophylaxis successful in all cases with follow-up of between 4.5 and 18 months.  Confirmed clincially and by X-ray investigation, as well as tomography/scintigraphy in selected patients.  

 

Ascherl R, Stemberger A, Lechner F et al. Treatment of local infections with collagen-gentamicin.

Analysed 54 patients with post-traumatic or post-operative osteomyelitis.  14 post-traumatic OM, 11 post-operative OM, 2 hematogenic OM, 27 septic prosthesis loosening. Collatamp placed into infected bone after debridement.  Unknown amount of CG used but possibly 1 sheet.

Main Findings

  • 33 patients with non-toxic serum concen-trations.  Only one patient with a maximum level 3.5 µg/ml at 12 hours. 
  • Occasional wound secrection as CG resorbs, 2 cases with wound reddening for 7 days.
  • 27% relapse with post-operative OM
  • 0% relapse with hematogenic OM
  • 14.8% relapse septic prosthesis loosening
  • 26% relapse overall

 

Jerosch J, Hoffstetter I. et al. Septic Arthritis:  Arthroscopic Management with Local Antibiotic Treatment, Acta Orthopaedica Belgica 1995; 61 (2):  126 – 132

Analyzed 12 patients with septic arthritis: 9 knee, 2 elbow, 1 shoulder; 3 cases hematogenous infection, 4 cases post-op infection, 5 cases infection followed intra-articular injection. Via arthroscope, knee was cleaned and depending upon severity of infection, various treatment modalities were instituted. A single college and gentamicin sheet was inserted arthroscopically into joint at end of procedure. Patients also received IV antibiotics. Oral antibiotics as necessary for 6 weeks to 4 months until ESR and CRP were normal.

Major Findings

  • 10 out of 12 patients were cured by single operation there were no cases of secondary bone involvement.
  • In one case, seven revisions , both arthroscopic and open, were necessary for cure
  • All patients at time of follow-up were able to realize painless joint with full ROM
  • The author alludes to some difficulty in handling moistened strips of call attempt for arthroscopic insertion into a joint

 

Ipsen T, Jorgensen I, et al. Gentamicin-collagen sponge for local applications, Acta Orthop Scand 1991 62 (6) 592 – 594

Analyzed 10 patients with osteomyelitis.  Clinical and radiographic signs with cutaneous fistuali-zation. Duration of infection 1/12 - 21 years. Systemic antibiotics 5 days then orally 7 weeks.  Debridement of bone and sequestra, excised fistula. 1 - 5 sponges (mean = 2.7 sponges). Wound drains used to measure local gentamicin levels.

Main Findings

  • 1 year post-op, no patients with signs of osteomyelitis.
  • No signs of local or systemic reactions, nephro or oto-toxicity noted.
  • This is important as some patients received 5 sponges.

 

Wernet E, Ekkernkamp A, et al.  Collagenous Sponge Containing Antibiotics in Osteitis Therapy, Unfallchirurg 1992; 95   259 – 264

Analyzed 47 patients with acute or chronic osteitis. 1 or 2 sponges placed into bone after de-bridement and tissue flaps. Wound drains used to measure local levels.

 

Sweiringa A, Goosen J, Jansman F, et al. In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection, Serum value in 19 patients, Acta Orthopaedica, 79: 5, 637 — 642

19 patients with a hip or knee arthroplasty and an acute surgical site infection from 1998 through 2004. Between 2 and 5 collagen sponges with an average of 3.6 sponges per patient.  All patients received open surgical debridement, pulse irrigation and  retained prosthesis prior to sponge insertion. Acute infection defined as superficial or deep within one year after implantation of the Prosthesis.

Main Findings

  • Excellent discussion of gentamicin pharmacokinetics and the bioavailability of gentamicin at operative sites for local therapyat beginning of paper.  End of paper discusses PMMA pharmacokinetics very well.
  • Serum gentamicin concentrations measured postop at six, 12, 18, and 24 hours and then again after each consecutive 24 hour period until gentamycin no longer detectable
  • The average peak serum gentamicin concentration was 4.2 µg/mL
  • Initial serum concentration was 3.2 -27.2 µg/mL in 4.5 - 6 hours.
  • After 24 hours The serum concentration was below 2 µg / ml
  • All but two patients had reduced creatinine clearances
  • There was no association between the number of sponges applied and the peak gentamycin serum concentrations
  • Gentamicin serum levels decreased to non-toxic levels 1 day after sponges inserted.
  • Gentamicin-loaded sponges may be useful as adjuvant treatment.
  • Unfortunately, the study doesn't indicate the outcome of the prosthesis infections.

 

Logroscino G, Spinelli M S, Santagada P A, et al Prevention and treatment of knee periprosthetic infection with antibiotic composites sponges Acta Bio Medica 2011 (82) Supplement 23 – 26

Case study of single patient. Collatamp used when prosthesis removed and antibiotic spacer inserted and in second stage when new prosthesis inserted 6 weeks after first stage.

 

Ciriello V, Maccauro G, Ziranu A, et al Collatamp® EG sponges in the management of open fractures. Acta Bio Medica 2011 (82) Supplement 27 – 32

Case study of single patient. Pre-op administration of cephazolin and gentamicin.  Then 2 sheets of Collatamp used in femur and 'additional sheets in tibial fracture'.

 

Maccauro G, Muratori F, Spinelli M S, et al Haemostatic antibiotic collagen devices in orthopaedic oncologic surgery. Acta Bio Medica 2011 (82) Supplement 33 -  37

Case study of single patient. Very brief description of Collatamp use in cases outlined in findings.

 

Cardiothoracic Studies

Raja S. Local application of gentamicin-containing collagen implant in the prophylaxis and treatment of surgical site infection following cardiac surgery. International Journal of Surgery, 2012 (10) Supplement 10 – 14

Analyzed nine publications regarding gentamicin-containing collagen implants, surgical site infections, wound infections, and cardiac surgery.

Main Findings

  • Six out of eight studies demonstrated that prophylactic use of gentamicin-containing collagen implants (GCCI) significantly reduce the wound infection rate following cardiac surgery (via sternotomy) compared to standard treatment alone.
  • The adjunctive use of GCCI is particularly beneficial in high-risk subjects e.g. diabetes and obese patients.
  • GCCI significantly improve the morbidity associated with SSI following cardiac surgery by shortening the recovery phase and length of hospital stay; reducing the need for surgical revision and use of antibiotics.
  • GCCI have been shown to be cost saving across a wide spectrum of patients.
  • A further study has shown that GCCI may also have a therapeutic role to play in patients with deep sternal wounds.

 

Friberg Ö, Svedjeholm R, Söderquist B, Granfeldt H, Vikerfors T, Källman J. Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial. Ann Thorac Surg 2005;79:153e62.

Analyzed 1,950 patients undergoing cardiac surgery through median sternotomy e including operations in the ascending aorta. Treated with gentamicin-penicillin implant plus IV isoxazolyl-penicillin.

Main Findings

  • Wound infection (<2 months post-operatively): 4.3% (Collatamp G) vs 9.0% (control), p < 0.001.
  • Early reoperation for bleeding: 2.3% (Collatamp G) vs 4.0% (control), p=0.021.
  • Antibiotic treatment: 11.6% (Collatamp G) vs 18.0% (control), p < 0.001.

 

Eklund AM, Valtonen M, Werkkala KA. Prophylaxis of terna wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery. J Hosp Infect 2005;59:108e12.

Analyzed 542 patients undergoing elective CABG surgery via a median sternotomy, with cardiopulmonary bypass. Treated with gentamicin-collagen implant plus IV antibiotics.

Main Findings

  • Wound infection (<3 months post-operatively): 4.0% (Collatamp G) vs 5.9% (control)

 

Schersten H. Modified prophylaxis for preventing deep sternal wound infection after cardiac surgery. APMIS 2007;115:1025e8.

Analyzed 2,026 prospective patients undergoing cardiac surgery. Treated with gentamicin-collagen implant plus IV isoxazolyl-penicillin.

Main Findings

  • Wound infection (mediastinitis): 0.75% (Collatamp G) vs 1.9% (control), p < 0.05.

 

Friberg Ö, Dahlin L-G, Källman J, Kihlström E, Söderquist B, Svedjeholm R. Collagen-gentamicin implant for prevention of sternal wound infection; long term follow-up of effectiveness. Interact Cardio Vasc Thorac Surg 2009;9:454e8.

Analyzed 2326 patients undergoing cardiac surgery, including surgery of the thoracic aorta operated via full median sternotomy. Treated with gentamicin-collagen implant plus IV isoxazolyl-penicillin.

Main Findings

  • Wound infection (<60 days post-operatively): 3.7% (Collatamp G) vs 9.0% (control), p < 0.001.
  • Surgical revision: 1.8% (Collatamp G) vs 3.9% (control), p < 0.001.

 

Bennett-Guerrero E, Ferguson Jr TB, Lin M, Garg J, Mark DB, Scavo Jr VA, et al. Effect of an implantable gentamicin-collagen sponge on sternal wound infections following cardiac surgery: a randomized trial. JAMA 2010;304:755e62.

Analyzed 1,502 patients undergoing cardiac surgery and at high-risk for sterna wound infections. 1,006 with diabetes and 1,137 with a BMI greater than 30. Treated with gentamicin collagen implant plus IV antibiotics.

Main Findings

  • Wound infection (<90 days post-operatively): Incidence of all types of wound infection: 8.4%
  • Incidence deep wound infection: 1.9% (Collatamp G) vs 2.5% (control).
  • Incidence superficial wound infection: 6.5% (Collatamp G) vs 6.1% (control).
  • Re-hospitalisation for sternal wound infection (<90 days post-operatively): 3.1% (Collatamp G) vs 3.2% (control).

 

Cohen G, Fremes S, Sever J, Moussa GT, Christakis GT, Goldman BS. Mitigation of sternal wound infection by application of a gentamicin impregnated collagen sponge at the time of sternal closure. In: presented at the Canadian cardiovascular congress; 2010. [Abstract 495].

Analyzed 216 patients undergoing cardiac surgery via sternotomy. Treated with gentamicin-collagen implant plus standard treatment.

Main Findings

  • Wound infection: 0.0% (Collatamp G) vs 9.0% (control), p ¼ 0.0220.

 

Raja SG, Salhiyyah K, Ra!q MU, Felderhof J, Amrani M. Impact of gentamicincollagen sponge on incidence of sternal wound infection in high-risk cardiac surgery patients: a propensity score analysis. In: presented at the World society of cardio-thoracic surgeons congress. Berlin: June 2011. [Abstract SOP55].

Analyzed 194 patients undergoing cardiac surgery via sternotomy. Treated with gentamacin-collagen implant plus standard treatment.

Main Findings

  • Wound infection: Incidence of superficial wound infection: 2.1% (Collatamp G) vs 6.2% (control), p = 0.01.
  • Incidence of deep wound infection: 2.1% (Collatamp G) vs 3.1% (control).
  • Post-operative complications – Need for intraaortic balloon pump: 2.1% (Collatamp G) vs 5.2% (control), p=0.04.
  • Post-operative complications – Need for haemofiltration: 3.1% (Collatamp G) vs 7.2% (control), p ¼ 0.02.

 

Schimmer C, Özkur M, Sinha B, Hain J, Gorski A, Hager B, et al. Gentamicincollagen sponge reduces sternal wound complications after heart surgery: a controlled, prospectively randomized, double-blind study. J Thorac Cardiovasc Surg 2012;143:194e200.

Analyzed 720 patients undergoing median sternotomy. Treated with gentamicin-collagen implant plus IV antibiotics

Main Findings

  • Wound infection (<30 days) – Incidence of deep wound infection: 0.56% (Collatamp G) vs 3.52% (control), p=0.014).
  • Wound infection (<30 days) – Incidence of superficial wound infection: 1.98% (Collatamp G) vs 2.98% (control).

 

Leyh RG, Bartels C, Sievers HH. Adjuvant treatment of deep sternal wound infection with collagenous gentamicin. Ann Thorac Surg 1999;68:1648e51.

Analyzed 42 patients with deep sterna wound infection following cardiac surgery. Treated with gentamicin-collagen implant.

Main Findings

  • Drainage samples were clear of infection for all 42 patients prior to removal and no re-infection occurred within 6 months of surgical debridement.

 

Other Surgical Studies

Kwasny O, Bockhorn G, Vecsei V.  The Use of Gentamicin Collagen Floss in the Treatment of Infections in Trauma Surgery   Unknown Source Publication

Analyzed 90 patients over 3 years with postoperative or post-traumatic infections. Undisclosed amount of CG used. Soft tissue pts treated with debridement, CG and primary closure.

Main Findings

  • Excellent brief overview of gentamicin mechanics, resistance and local antibiotic effect.
  • Measured serum and drain fluid gentamicin levels for 3 days in 6 patients who received 2 sponges for osteomyelitis.  No toxicity noted.     
  • 41 patients with soft tissue infections.  39 had primary wound healing.  2 patients required repeat debridement  and closure.  No cases of relapse.
  • 49 patients with osteitis. 45 (95%) resolved successfully. 
  • No nephro or ototoxicity. No allergic response.

 

Main Findings

  • 44 patients had complete healing. 39 patients (83%) primary healing, 5 (10.6%) patients required 1 -3 repeat surgeries.  Thus 93.7%
  • 3 (6.3%) had persistent fistualization.
  • No general toxic reactions, nephro-toxic or ototoxic reactions or allergies seen.
  • Control group 16.7% persistent fistualization.

 

Neut D, van de Belt H, van Horn, J, et al,  Residual gentamicin  release from antibiotic-loaded PMMA beads after 5 years of implantation, Biomaterials 2003; (24), 1829 – 1831

Case study of single patient. Beads removed and anti-biotic elution measured.

Main Findings

  • Good paper to help understand mechanics of PMMA beads
  • Septopal chain of 30 beads, with each bead containing 4.5 mg of gentamicin
  • Despite being implanted for five years, beads were able to release measurable amounts of gentamicin ( 0. 4µg per bead), without breaking the cement matrix
  • There is  great concern for sub-inhibitory antibiotic concentrations leading to resistance.
  • Infectious bacteria recovered from surface of beads. Gentamycin-resistant coagulase-negative staphylococci were identified. MIC was 10 µg per ML, well above limit for gentamicin resistance ( 4 µg / ML]
  • Authors are careful to indicate that any biomaterial left in the human body must be considered as a potential focus for infection.
  • Author also comments on the need for a biodegradable antibiotic-loaded bead for antibiotic delivery system

 

Diefenbeck M, Muckley T, Hofmann O. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury, Int J. Care Injured 2006 (37), S95 - S104

Comparison of PMMA beads, collagen-gentamicin fleece (Collatamp G) and antibiotic spacers. 

 

Logroscino G, Malbera G, Pagano E, et al The use of Collatamp® EG in Total Hip Arthroplasty. Acta Bio Medica 2011 (82) Supplement 17 – 22

Case study of single patient. 2 sponges, divided into 2 equal parts.  2 implanted into femoral canal and 2 into acetabular cavity.