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Local Collagen-Gentamicin for Prevention of Sternal Wound Infections
Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In cardiac surgery, sternal wound infection (SWI) continues to be one of the most serious postoperative complications. Coagulase-negative staphylococci (CoNS) have become the most common causative agents of SWI. Prophylaxis with intravenous beta-lactam antibiotics (cephalosporins or in Sweden most commonly isoxazolyl penicillins) is routinely practised. However, many CoNS species are resistant to beta-lactam antibiotics. Vancomycin is often the only effective antibiotic available for treatment of these infections, but its use for routine prophylaxis is strongly discouraged because of the risk of increasing the selection of resistant bacteria.

The aim of this work was to develop and evaluate a new technique for antibiotic prophylaxis in cardiac surgery consisting of application of drug eluting collagen-gentamicin sponges in the sternal wound in addition to conventional intravenous antibiotics.

The antibiotic concentrations in the wound and serum achieved by routine intravenous dicloxacillin prophylaxis and those after application of local collagen-gentamicin in the sternal wound were investigated. These studies showed dicloxacillin levels adequate for prevention of infections by methicillin-susceptible staphylococci, and extremely high gentamicin levels in the wound fluid, during the first 8-12 hours postoperatively with the local application.

Two thousand cardiac surgery patients were then randomised to routine prophylaxis with intravenous isoxazolyl penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. The primary end-point was any sternal wound infection within two months postoperatively.

Evaluation was possible in 983 and 967 patients in the treatment and control groups, respectively. The incidence of any sternal wound infection was 4.3% in the treatment group and 9.0 % in the control group (relative risk = 0.47, (95% confidence interval 0.33 to 0.68); P<0.001). The most common microbiological agents were CoNS, followed by Staphylococcus aureus. Local gentamicin reduced the incidence of SWIs caused by all major, clinically important microbiological agents except Propionibacterium acnes.

Assignment to the control group, high body mass index, diabetes mellitus, younger age, single or double internal mammary artery, left ventricular ejection fraction less than 35% and longer operation time were independent risk factors for SWI in a multivariable risk factor analysis.

In patients with additional sternal fixation wires (> six wires) the collagen-gentamicin prophylaxis was associated with an approximately 70 % reduction in the incidence of SWI at all depths and the application of collagen sponges between sternal halves may require particular attention regarding the stability of fixation.

A cost effectiveness analysis showed that the application of local collagen-gentamicin as prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.

Routine use of the described prophylaxis in all adult cardiac surgery patients could be recommended.

Place, publisher, year, edition, pages
Institutionen för medicin och vård , 2006.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 937
Keyword [en]
Cardiac surgery, Sternal wound infection, Mediastinitis, Antibiotics, Gentamicin, Prophylaxis, Cost-effectiveness, Staphylococcus, Randomised controlled trial
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-7125ISBN: 91-85497-75-4 (print)OAI: oai:DiVA.org:liu-7125DiVA: diva2:22203
Public defence
2006-03-31, Aulan, B-huset, Universitetssjukhuset, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2006-07-20 Created: 2006-07-20 Last updated: 2009-08-22
List of papers
1. Antibiotic concentrations in serum and wound fluid after local gentamicin or intravenous dicloxacillin prophylaxis in cardiac surgery
Open this publication in new window or tab >>Antibiotic concentrations in serum and wound fluid after local gentamicin or intravenous dicloxacillin prophylaxis in cardiac surgery
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2003 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 4, 251-254 p.Article in journal (Refereed) Published
Abstract [en]

One important aim of antibiotic prophylaxis in cardiac surgery is preventing mediastinitis and thus it would appear to be relevant to study the antibiotic concentrations in pericardial/mediastinal fluid. Local administration of gentamicin in the wound before sternal closure is a novel way of antibiotic prophylaxis and could be effective against bacteria resistant to intravenous antibiotics. This study measured dicloxacillin concentrations in 101 patients in serum and wound fluid following intravenous administration of dicloxacillin. Similarly, concentrations of gentamicin in serum and wound fluid were determined in 30 patients after administration of 260 mg gentamicin in the wound at sternal closure. Median dicloxacillin concentrations in serum and wound fluid at sternal closure were 59.4 and 55.35 mg/l, respectively. Gentamicin levels in the wound were very high (median 304 mg/l), whereas serum concentrations were low (peak median 2.05 mg/l). Dicloxacillin, 1 g given intravenously, according to the clinical protocol, resulted in levels in serum and wound fluid at sternal closure likely to prevent Staphylococcus aureus infections. Locally administered gentamicin resulted in high local concentrations, potentially effective against agents normally considered resistant.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13924 (URN)10.1080/003655400310000184 (DOI)
Available from: 2006-07-20 Created: 2006-07-20 Last updated: 2017-12-13
2. Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial
Open this publication in new window or tab >>Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial
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2005 (English)In: The Annals of Thoracic Surgery, ISSN 0003-4975, Vol. 79, no 1, 153-161 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Sternal wound infections remain a major cause of morbidity after cardiac surgery. Vancomycin is often the only effective antibiotic available for their treatment but its use for routine prophylaxis is inadvisable for ecological reasons. Local application of gentamicin produces high antibiotic concentrations in the wound. We aimed to determine whether this treatment could have an additive effect on the incidence of sternal wound infections when combined with routine prophylaxis.

METHODS: Two thousand cardiac surgery patients were randomized to routine prophylaxis with intravenous isoxazolyl-penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. Endpoint was any sternal wound infection within 2 months postoperatively. Evaluations were double-blind and made on an intention-to-treat basis.

RESULTS: Evaluation was possible in 967 and 983 patients in the control and treatment groups, respectively. The incidence of sternal wound infection was 4.3% in the treatment group and 9.0% in the control group (relative risk 0.47; 95% confidence interval 0.33–0.68; p < 0.001). Early reoperation for bleeding was more common in the treatment group (4.0% vs 2.3%, p = 0.03). No difference in postoperative renal function was noted.

CONCLUSIONS: Local collagen-gentamicin reduced the risk for postoperative sternal wound infections. Further studies are warranted to confirm these results, particularly with regard to deep infections.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13925 (URN)10.1016/j.athoracsur.2004.06.043 (DOI)
Available from: 2006-07-20 Created: 2006-07-20 Last updated: 2009-05-14
3. Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups
Open this publication in new window or tab >>Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups
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2006 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, Vol. 40, no 2, 117-125 p.Article in journal (Refereed) Published
Abstract [en]

Objectives. In a randomized trial addition of local collagen-gentamicin in the sternal wound reduced the rate of sternal wound infection (SWI) to about 50% compared to intravenous prophylaxis alone. The aim of the present study was to evaluate the economic rationale for its use in every-day clinical practice. This includes the question whether high-risk groups that may have particular benefit should be identified.

Design. For each patient with SWI in the trial the costs attributable to the SWI were calculated. Risk factors for SWI were identified and any heterogeneity of the effect of the prophylaxis examined.

Results. The mean cost of a SWI was about 14500 Euros. A cost effectiveness analysis showed that the prophylaxis was cost saving. The positive net balance was even higher in risk groups. Assignment to the control group, overweight, diabetes, younger age, mammarian artery use, left ventricular ejection fraction < 35% and longer operation time were independent risk factors for infection.

Conclusion. The addition of local collagen-gentamicin to intravenous antibiotic prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.

Keyword
Cardiac Surgery; Cardiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13926 (URN)10.1080/14017430500363024 (DOI)
Available from: 2006-07-20 Created: 2006-07-20
4. Incidence, microbiological findings and clinical presentation of sternal wound infections after cardiac surgery with and without local gentamicin prophylaxis
Open this publication in new window or tab >>Incidence, microbiological findings and clinical presentation of sternal wound infections after cardiac surgery with and without local gentamicin prophylaxis
2007 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 26, no 2, 91-97 p.Article in journal (Refereed) Published
Abstract [en]

Sternal wound infection (SWI) is a serious complication after cardiac surgery. In a previous randomized controlled trial, the addition of local collagen-gentamicin in the sternal wound before wound closure was found to significantly reduce the incidence of postoperative wound infections compared with the routine intravenous prophylaxis of isoxazolyl-penicillin only. The aims of the present study were to analyse the microbiological findings of the SWIs from the previous trial as well as to correlate these findings with the clinical presentation of SWI. Differences in clinical presentation of SWIs, depending on the causative agent, could be identified. Most infections had a late, insidious onset, and the majority of these were caused by staphylococci, predominantly coagulase-negative staphylococci. The clinically most fulminant infections were caused by gram-negative bacteria and presented early after surgery. Local administration of gentamicin reduced the incidence of SWIs caused by all major, clinically important bacterial species. Propionibacterium acnes was identified as a possible cause of SWI and may be linked to instability in the sternal fixation. There was no indication of an increase in the occurrence of gentamicin-resistant bacterial isolates in the treatment group. Furthermore, the addition of local collagen-gentamicin reduced the incidence of SWIs caused by methicillin-resistant coagulase-negative staphylococci. This technique warrants further evaluation as an alternative to prophylactic vancomycin in settings with a high prevalence of methicillin-resistant Staphylococcus aureus.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13927 (URN)10.1007/s10096-006-0252-6 (DOI)
Available from: 2006-07-20 Created: 2006-07-20 Last updated: 2017-12-13
5. Reduced deep sternal wound infection rate in patients with more than six sternal fixation wires and local collagen-gentamicin as prophylaxis
Open this publication in new window or tab >>Reduced deep sternal wound infection rate in patients with more than six sternal fixation wires and local collagen-gentamicin as prophylaxis
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2006 (English)Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13928 (URN)
Available from: 2006-07-20 Created: 2006-07-20

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