Journal of Antimicrobial Chemotherapy (1999) 44, 287-290
© 1999 The British Society for Antimicrobial Chemotherapy
Brief report |
Ceftriaxone versus vancomycin prophylaxis in cardiovascular surgery
a The Deaconess Hospital in Helsinki b The Deaconess Hospital in Helsinki Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland c The Deaconess Hospital in Helsinki Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
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Abstract |
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The efficacy of antibiotic prophylaxis in cardiac surgery was compared between 97 patients receiving a single 2 g dosage of ceftriaxone and 103 receiving 500 mg of vancomycin iv every 6 h for 48 h. The overall infection rate was 13.4% in the ceftriaxone and 10.7% in the vancomycin group. Four (4%) wound infections, including one mediastinitis, occurred in the ceftriaxone group and five (5%) in the vancomycin group, with no statistically significant difference. The findings of this study support the adequacy of a simple single dose of ceftriaxone prophylaxis in cardiac surgery, at least in hospitals with low incidence of vancomycin-resistant staphylococcal infections.
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Introduction |
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Despite antibiotic prophylaxis, wound infection after coronary artery bypass grafting (CABG) develops in 5% of patients. 1 Cephalosporins widely used for prophylaxis show broad antibacterial action and low toxicity. Single-dose ceftriaxone, a third-generation cephalosporin, is effective. 2,3 The practice of antibiotic prophylaxis in our centre has involved use of a 48 h course of vancomycin. This study compared the efficacy of this narrow-spectrum glycopeptide 4 with a single dose of ceftriaxone.
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Materials and methods |
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This prospective, randomized study comprised 200 consecutive patients undergoing elective heart surgery in our centre after 1 May, 1994. Patients with serum creatinine levels higher than 17 mg/L were excluded. The basic data, operative details and postoperative events are in Tables I and II. The majority (189) underwent CABG, with additional mitral valve repair in one and carotid endarterectomy in two patients. Surgical procedures on 11 patients were composite graft replacement (two), aortic valve replacement (seven), mitral valve repair (one) and reconstruction of the ascending aorta (one).
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Those born in an odd year (97 patients) received a single 2 g dosage of ceftriaxone iv. Vancomycin iv 500 mg every 6 h for 48 h was given to those born in an even year (103 patients). The first dose was given 45 to 60 min before the surgical incision through a peripheral cannula and before inserting intravascular lines. The urinary catheter was inserted immediately after the infusion.
A chest X-ray was taken preoperatively and on the third postoperative day. Preoperative laboratory tests included C-reactive protein (CRP), serum creatinine and haemoglobin levels, white blood cell count, alkaline phosphatase analysis, liver transaminase analysis and urinalysis with bacterial culture. These were repeated on the third and seventh postoperative day. A questionnaire concerning infections after discharge was sent to each patient after 2 months with a 100% reply rate.
The criterion for wound infection was purulent secretion. Mediastinitis was diagnosed by a combination of clinical signs and the results of wound and blood cultures and computed tomography. For significant bacteriuria the criterion was bacterial growth >10 5 cfu/mL. Diagnosis of respiratory infection was based upon fever and pulmonary infiltration on chest X-rays.
Independent sample t-tests and Pearson's 
2, where appropriate, were used to test for significant differences between the
groups. Values of P < 0.05 were considered statistically significant.
The study was approved by the Ethics Committee of the Deaconess Hospital in Helsinki.
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Results |
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Hospital mortality was 4% (eight patients). No significant side-effects due to prophylactic antibiotics were observed in either group.
No significant difference between study groups was found for the factors in Table I or in operative and postoperative events (Table II). Preoperative asymptomatic bacteriuria appeared in eight patients (8%) in the ceftriaxone and in two (2%) in the vancomycin group (P < 0.05). The haemoglobin value on the third postoperative day was lower (107 ± 10 g/L) in the ceftriaxone group (P < 0.05).
The overall rate of infection was 13.4% in the ceftriaxone group and 10.7% in the vancomycin group, with no statistically significant difference. When the seven urinary tract infections in the ceftriaxone and the four in the vancomycin group were excluded, the infection rates were 6.2% and 6.8%.
One case of mediastinitis due toStaphylococcus epidermidis occurred in the ceftriaxone group; after mediastinal revision, irrigation with vancomycin (500 mg/1000 mL saline) for 7 days and concomitant iv antibiotics, a second revision with omentoplasty was required before recovery. Purulent infections of the sternal wound in two patients in the ceftriaxone and in four in the vancomycin group were due to S. epidermidis in three cases and other coagulase-negative staphylococciin one case. One sternal wound infection in the ceftriaxone group was anaerobic, and one in the vancomycin group was due to Escherichia coli. Purulent infection of the lower limb donor site was found in one patient in each group. No methicillin-resistant Staphylococcus aureus(MRSA) infection occurred.
Pneumonic infiltration on the chest X-ray was diagnosed in two patients in each group on the seventh postoperative day. One developed a peptic ulcer with perforation and peritonitis, but recovered after surgical treatment.
According to the questionnaires, no severe infections occurred after discharge. Altogether 35 patients received antibiotics postoperatively with no significant difference between study groups.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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This study indicates that prophylaxis with either single-dose ceftriaxone or 48 h vancomycin was effective in preventing infections following cardiac surgery. Coagulase-negative staphylococci were the most frequent pathogens, causing sternal infections in five patients (71%). S. epidermidis and S. aureus are the most common pathogens following cardiac surgery, accounting for almost two-thirds of infections. 5 With its effective antistaphylococcal activity, 4 vancomycin prophylaxis is directed especially against staphylococci—the main reason for its use in cardiac surgery.
When assayed 24 h after injection, the ceftriaxone concentration in plasma exceeded the MICs for pathogens commonly associated with cardiac surgery. 6 High concentrations were measured also in the mediastinal fluid. 7 This long-lasting activity is considered one of the factors making single-dose ceftriaxone as effective as 48 h prophylaxis. 2,3
The frequency of infectious sternal and wound complications in the two study groups was comparable, 4% in the ceftriaxone and 5% in the vancomycin group, which is in accordance with earlier reports. 1,2 No appreciable difference existed in frequency of mediastinitis, wound infection or pneumonia. Significant bacteriuria, often due to urinary catheters, was more frequent in patients receiving ceftriaxone (seven) than vancomycin (four) prophylaxis, an unexpected finding perhaps explained by the higher frequency of bacteriuria preoperatively (P < 0.05) in the ceftriaxone group.
Use of vancomycin instead of cephalosporins is often indicated in hospitals with a high incidence of MRSA infections. On the other hand, an important factor supporting the choice of cephalosporin rather than vancomycin prophylaxis is the emerging problem of vancomycin-resistant S. aureus(VRSA), at least in hospitals with low levels of MRSA infection. 8 Heterogeneously resistant VRSA developing into VRSA upon exposure to vancomycin has recently been thought to explain frequent therapeutic failure in MRSA infection. 9 The major concern associated with the prophylactic use of vancomycin in the past has been the emergence of vancomycin-resistant enterococci (VRE), especially in institutions with MRSA or methicillin-resistant S. epidermidis (MRSE) 8. The necessity for vancomycin prophylaxis should be carefully evaluated, and a less problematic regimen chosen instead.
Administration of a single 2 g dose of systemic ceftriaxone appears to provide good prophylaxis against development of wound infection in patients undergoing cardiac operations. In addition, it has the benefit of simple administration and reduced cost. 2,3 To reach statistical power, a national study with several hundred patients is needed. 10 However, this study was prospective and is the first report comparing 48 h vancomycin with single-dose ceftriaxone prophylaxis. By showing an equal infection rate between study groups, these preliminary results support the use of single 2 g dose ceftriaxone prophylaxis in cardiac surgery.
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Notes |
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* Correspondence address: Helsinki University Central Hopsital, Department of Surgery, pl 260, Haartmaninkatu 4, FIN-00290 Helsinki, Finland. Tel: +358-9-4711; Fax: +358-9-471 5858; E-mail: ulla.s.salminen{at}netsonic.fi
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References |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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1 . Slaughter, M. S., Olson, M. M., Lee, J. T. & Ward, H. B. (1993). A fifteen-year wound surveillance study after coronary artery bypass. Annals of Thoracic Surgery 56,1063 –8.[Abstract]
2 . Sisto, T., Laurikka, J. & Tarkka, M. (1994). Ceftriaxone versus cefuroxime for infection prophylaxis in coronary bypass surgery. Scandinavian Journal of Thoracic and Cardiovascular Surgery28 , 143–8.[Web of Science][Medline]
3 . Hall, J. C., Christiansen, K., Carter, M. J., Edwards, M. G., Hodge, A. J., Newman, M. A. et al. (1993). Antibiotic prophylaxis in cardiac operations. Annals of Thoracic Surgery 56, 916–22.[Abstract]
4 . Farber, B. F., Karchmer, A. W., Buckley, M. J. & Moellering, R. C. (1983). Vancomycin prophylaxis in cardiac operations: determination of an optimal dosage regimen. Journal of Thoracic and Cardiovascular Surgery 85, 933–5.[Abstract]
5 . Ariano, R. E. & Zhanel, G. G. (1991). Antimicrobial prophylaxis in coronary bypass surgery: a critical appraisal. Drug Intelligence and Clinical Pharmacy 25,478 –84.
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Bryan, C. S., Morgan, S. L., Jordan, A. B., Smith, C. W.,
Sutton, J. P. & Gangemi, J. D. (1984). Ceftriaxone levels in blood and tissue
during cardiopulmonary bypass surgery. Antimicrobial Agents and Chemotherapy 25, 37–9.
7 . Almassi, G. H., Edmiston, C. E. & Olinger, G. N. (1989). Tissue and mediastinal fluid levels of a long-acting cephalosporin in cardiac surgical patients. Current Therapeutic Research 45, 447–52.
8 . Barie, P. S. (1998) Antibiotic-resistant Gram-postive cocci: implications for surgical practice. World Journal of Surgery 22, 118–26.[Web of Science][Medline]
9 . Hiramatsu, K., Aritaka, N., Hanaki, H., Kawasati, S., Hosada, Y., Hori, S. et al. (1998). Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 350, 1670–3.
10
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Leaper, D. J. (1998). Use of antibiotic
prophylaxis in clean non-implant wounds. Journal of Antimicrobial Chemotherapy 41, 501–4.
Received 26 October 1998; returned 29 January 1999; revised 12 March 1999; accepted 23 April 1999
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