460
Acta OrthoD Scand 1990: 61 (5):460-462
Short-term cefotaxime prophylaxis reduces the failure rate in lower limb amputations
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Rolf Norlin', Aril Fryden*, Lennart Nilsson3and Steffan hsehn3
The effect of prophylaxis with a broad-spectrum antibiotic agent in lower limb amputations was studied in a prospective, randomized investigation of 38 patients. Nineteen received cefotaxime (Claforana) and 19 served as controls. Three patients died in the immediate postoperative period. In the treatment group, 15/18 healed compared with 10117 controls (P c 0.001). We concluded that short-term cefotaxime prophylaxis increases the chances to achieve good stump healing.
Antibiotic prophylaxis in lower limb amputations is still disputed. Some reports on series where methicillin, cefoxitin, or amoxycillin/clavulanic acid was used showed encouraging results (4, 6, 7), whereas metronidazole + penicillin showed no effect on postoperative infections (3). One study suggested that penicillin G is equally effective as cefuroxime (1). The microbiologic flora in stump infections includes mostly Staphylococcus aureus and various gramnegative enterobacteria. These are usually sensitive to cefotaxime (2), which also penetrates bone tissue (8) and produces an active metabolite (desacetylcefotaxime) with possible synergistic effect (5). Therefore, we chose to study this drug as a short-term prophylactic.
Patients and methods All 38 patients, both diabetics and patients with arteriosclerosis, who had a lower limb amputation due to ischemia during 1986-1988 were included. Patients with antibiotic treatment within 3 days before surgery were excluded. Three levels of amputations were used: above-the-knee, through-the-knee, and
Departments of Orthopedics', Infectious Diseases2, and Clinical Bacteriology3, University Hospital, Linkoping, S-581 85 Sweden
below-the-knee (Table 1). Patients were randomized to standard treatment without antibiotics (controls) or to cefotaxime prophylaxis (treatment group). Cefotaxime (Claforan@)was given as an infusion, 2 g in 100 mL sterile water or saline for 20 min. The infusion was started 1 h before surgery and then 8 and 16 h later. No other prophylactic was given. All the patients received the same dose. Thirty-eight patients were included, 19 in the control group (mean age 76 [46-891 years) and 19 in the treatment group (mean age 79 [47-941 years). Clinical assessment of healing was done during a 3-week period after surgery. Wound infections and additional surgery-revision or reamputation-were recorded. Swab cultures were taken from all the wound before surgery. During surgery a tissue sample was taken for culture from the proximal part of the amputated leg. Samples were taken from the drainage fluid 8 h and 24 h postoperatively. Both aerobic and anaerobic cultures were performed on the drainage fluid.
Table 1. Etiology and amputation level in 38 patients with and without cefotaxime prophylaxis (controlltreatment)
Diabetes Arterlosclerosis Total
A
T
B
Total
211
W1
317
3i2
3/2 363
8/6
5/9 14/10
11/13
38
5t3
A above-, T through-, B below the-knee amputation.
461
Acta orthop Scand 1990: 61 15): 460-462
Table 2. Healing rate at 3 weeks postoperatively. For abbreviations, see Table 1. Healedlnonhealed Group
A
T
8
Total
211 410
2/0
1112 516
1513 1017
Table 4. Cefotaxime concentration in serum, tissue, and drainage fluid. The values do not include the metabolite desacetylcefotaxime,which also has antibacterial activity (5) Mean
Treatment Control
111
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Preop culture
Intraoplpostop culture
No isolate Staphyiawmus aureus
011 411
Oram-negative enterobacteria S. aureus in combination with gram-negative bacteria Combinations of varlous gram-negative bacteria
2/1
18/14 012 111
313
010
112
010
Range
1 hour after infusion
Serum (mgn) Tissue (kg/g) Table 3. Outcome of bacterial cultures. Treatmenticontrol
SD
8 hours after infusion Serum (mgR) Drainage fluid (pg/L)
54.6
0.8
6.7 2.1
32.8 8.5
9.9-131 2.3-38
7.8
0.3-23 0.6-5.5
1.3
MICw: StaphylrxxxMls aureus 2 mgk. gram-negative bacteria 2 0.5 rng/L.
In the treatment group, serum samples for determination of cefotaxime were taken. At surgery a blood sample and a tissue sample from the leg were taken simultaneously. Before the second infusion and 24 h after surgery, drainage-fluid samples and blood samples were taken for cefotaxime determination. All the samples were immediately frozen at -20 "C to prevent metabolism of cefotaxime. Fischer's exact test was used for evaluation of the results.
positive cultures, of which 5 also showed growth of gram-negative bacteria. The intraoperative tissue cultures and the postoperative drainage-fluid cultures yielded growth in l patient in the treatment group and in 3 patients in the control group (Table 3). Cefotaxime concentrations in both serum and tissue were well above MIC90 for both Staphylococcus aureus ( 2 mg/L) and gram-negative bacteria (20.5 mg/L; Table 4).
Results
Discussion
Out of the 38 patients initially included, 3 patients died because of cardiovascular complications in the immediate postoperative period-2 in the control group and 1 in the treatment group. One was an AK amputee and 2 were TK amputees. Thus, 17 patients in the control group and 18 in the treatment group remained for evaluation. In the treatment group, 15 of the 18 patients healed compared with only 10 out of 17 in the control group (P < 0.001; Table 2). In BK amputees, 11/13 healed in the treatment group and 5/11 in the control group (P < 0.01). All nonhealing patients needed either revision (1 case) or reamputation (9 cases) at a higher level. The others showed uneventful healing. There was no obvious difference between diabetics and nondiabetics as far as healing frequency was concerned. The predominant bacterial isolates were Staphylococcus aureus, which was identified in 11 of the
Lower-limb amputation has a high frequency of failure. From a functional point of view, it is of major importance to perform a successful amputation at the lowest possible level. A nonhealing BK amputation often leads to a secondary AK amputation. Very little has been written about antibiotic prophylaxis in lower-limb amputation. Some previous studies have indicated (1, 3, 4, 6, 7) that antibiotics may be used prophylactically, but data are conflicting, and there is still no general agreement on the use of antibiotic prophylaxis in amputations. A mixed microbiologic flora is commonly present, and includes both S. aureus and various gram-negative enterobacteria. It is questionable whether penicillin G is equally effective as cefuroxime (1). Previous studies have failed to report either on bacterial cultures and concentrations of administered antibiotics (1,3,4,6, 7).
462
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Our conclusion that cefotaxime has a beneficial prophylactic effect is also supported by the finding that cefotaxime was present in serum, tissue, and drainage fluid in adequate concentrations.
References 1. Friis H. Penicillin G versus cefuroxime for prophylaxis in lower limb amputation. Acta Orthop Scand 1987; 58: 666-8. 2. Ode B, Forsgren A, Walder M. Sensitivity of 523 blood culture isolates to 33 antibiotics. Scand J Infect Dis 1984; 16: 61-71. 3. Hares M M, Downing R, Marsh J. Failure of metronidazole/penicillin oral prophylaxis to prevent amputation stump infection. Lancet 1980; May 10: 1028-9.
Acta Orthop Scand 1990; 61 (5):460-462
4. Huizinga W K, Robbs J V, Kritzinger N A. Prevention
of wound sepsis in amputations by pen-operative antibiotic cover with an amoxycillin-clavulanicacid combination. S A Med J 1983; 63: 71-3. 5. Jones R N, Barry A L, Thomsbeny C. Antimicrobial activity of desacetylcefotaxime alone and in combination with cefotaxime: evidence of synergy. Rev Jnf Dis 1982; 4 suppl, 366-13. 6 . Mpller B N, Krebs B. Antibiotic prophylaxis in lower limb amputation. Acta Orthop Scand 1985; 56: 327-9. 7. Sonne-Holm S, Boeckstyns M, Menck H, Sinding A, Leicht P, Dichmann 0, Rag J B, Baekgaard N, Ostri P, G@trikJ K. Prophylactic antibiotics in amputations of the lower extremity for ischemia. J Bone Joint Surg (Am) 1985,67(5): 800-3. 8. Makiyama T, Asai T. Study on transfer of cefotaxime into bone tissue. Drugs 1988; 35(suppl2): 88-92.
Acta OrthoD Scand 1990: 61 (5):460-462
Short-term cefotaxime prophylaxis reduces the failure rate in lower limb amputations
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Rolf Norlin', Aril Fryden*, Lennart Nilsson3and Steffan hsehn3
The effect of prophylaxis with a broad-spectrum antibiotic agent in lower limb amputations was studied in a prospective, randomized investigation of 38 patients. Nineteen received cefotaxime (Claforana) and 19 served as controls. Three patients died in the immediate postoperative period. In the treatment group, 15/18 healed compared with 10117 controls (P c 0.001). We concluded that short-term cefotaxime prophylaxis increases the chances to achieve good stump healing.
Antibiotic prophylaxis in lower limb amputations is still disputed. Some reports on series where methicillin, cefoxitin, or amoxycillin/clavulanic acid was used showed encouraging results (4, 6, 7), whereas metronidazole + penicillin showed no effect on postoperative infections (3). One study suggested that penicillin G is equally effective as cefuroxime (1). The microbiologic flora in stump infections includes mostly Staphylococcus aureus and various gramnegative enterobacteria. These are usually sensitive to cefotaxime (2), which also penetrates bone tissue (8) and produces an active metabolite (desacetylcefotaxime) with possible synergistic effect (5). Therefore, we chose to study this drug as a short-term prophylactic.
Patients and methods All 38 patients, both diabetics and patients with arteriosclerosis, who had a lower limb amputation due to ischemia during 1986-1988 were included. Patients with antibiotic treatment within 3 days before surgery were excluded. Three levels of amputations were used: above-the-knee, through-the-knee, and
Departments of Orthopedics', Infectious Diseases2, and Clinical Bacteriology3, University Hospital, Linkoping, S-581 85 Sweden
below-the-knee (Table 1). Patients were randomized to standard treatment without antibiotics (controls) or to cefotaxime prophylaxis (treatment group). Cefotaxime (Claforan@)was given as an infusion, 2 g in 100 mL sterile water or saline for 20 min. The infusion was started 1 h before surgery and then 8 and 16 h later. No other prophylactic was given. All the patients received the same dose. Thirty-eight patients were included, 19 in the control group (mean age 76 [46-891 years) and 19 in the treatment group (mean age 79 [47-941 years). Clinical assessment of healing was done during a 3-week period after surgery. Wound infections and additional surgery-revision or reamputation-were recorded. Swab cultures were taken from all the wound before surgery. During surgery a tissue sample was taken for culture from the proximal part of the amputated leg. Samples were taken from the drainage fluid 8 h and 24 h postoperatively. Both aerobic and anaerobic cultures were performed on the drainage fluid.
Table 1. Etiology and amputation level in 38 patients with and without cefotaxime prophylaxis (controlltreatment)
Diabetes Arterlosclerosis Total
A
T
B
Total
211
W1
317
3i2
3/2 363
8/6
5/9 14/10
11/13
38
5t3
A above-, T through-, B below the-knee amputation.
461
Acta orthop Scand 1990: 61 15): 460-462
Table 2. Healing rate at 3 weeks postoperatively. For abbreviations, see Table 1. Healedlnonhealed Group
A
T
8
Total
211 410
2/0
1112 516
1513 1017
Table 4. Cefotaxime concentration in serum, tissue, and drainage fluid. The values do not include the metabolite desacetylcefotaxime,which also has antibacterial activity (5) Mean
Treatment Control
111
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Preop culture
Intraoplpostop culture
No isolate Staphyiawmus aureus
011 411
Oram-negative enterobacteria S. aureus in combination with gram-negative bacteria Combinations of varlous gram-negative bacteria
2/1
18/14 012 111
313
010
112
010
Range
1 hour after infusion
Serum (mgn) Tissue (kg/g) Table 3. Outcome of bacterial cultures. Treatmenticontrol
SD
8 hours after infusion Serum (mgR) Drainage fluid (pg/L)
54.6
0.8
6.7 2.1
32.8 8.5
9.9-131 2.3-38
7.8
0.3-23 0.6-5.5
1.3
MICw: StaphylrxxxMls aureus 2 mgk. gram-negative bacteria 2 0.5 rng/L.
In the treatment group, serum samples for determination of cefotaxime were taken. At surgery a blood sample and a tissue sample from the leg were taken simultaneously. Before the second infusion and 24 h after surgery, drainage-fluid samples and blood samples were taken for cefotaxime determination. All the samples were immediately frozen at -20 "C to prevent metabolism of cefotaxime. Fischer's exact test was used for evaluation of the results.
positive cultures, of which 5 also showed growth of gram-negative bacteria. The intraoperative tissue cultures and the postoperative drainage-fluid cultures yielded growth in l patient in the treatment group and in 3 patients in the control group (Table 3). Cefotaxime concentrations in both serum and tissue were well above MIC90 for both Staphylococcus aureus ( 2 mg/L) and gram-negative bacteria (20.5 mg/L; Table 4).
Results
Discussion
Out of the 38 patients initially included, 3 patients died because of cardiovascular complications in the immediate postoperative period-2 in the control group and 1 in the treatment group. One was an AK amputee and 2 were TK amputees. Thus, 17 patients in the control group and 18 in the treatment group remained for evaluation. In the treatment group, 15 of the 18 patients healed compared with only 10 out of 17 in the control group (P < 0.001; Table 2). In BK amputees, 11/13 healed in the treatment group and 5/11 in the control group (P < 0.01). All nonhealing patients needed either revision (1 case) or reamputation (9 cases) at a higher level. The others showed uneventful healing. There was no obvious difference between diabetics and nondiabetics as far as healing frequency was concerned. The predominant bacterial isolates were Staphylococcus aureus, which was identified in 11 of the
Lower-limb amputation has a high frequency of failure. From a functional point of view, it is of major importance to perform a successful amputation at the lowest possible level. A nonhealing BK amputation often leads to a secondary AK amputation. Very little has been written about antibiotic prophylaxis in lower-limb amputation. Some previous studies have indicated (1, 3, 4, 6, 7) that antibiotics may be used prophylactically, but data are conflicting, and there is still no general agreement on the use of antibiotic prophylaxis in amputations. A mixed microbiologic flora is commonly present, and includes both S. aureus and various gram-negative enterobacteria. It is questionable whether penicillin G is equally effective as cefuroxime (1). Previous studies have failed to report either on bacterial cultures and concentrations of administered antibiotics (1,3,4,6, 7).
462
Acta Orthop Downloaded from informahealthcare.com by Southern Taiwan University of Science and Technology on 10/27/14 For personal use only.
Our conclusion that cefotaxime has a beneficial prophylactic effect is also supported by the finding that cefotaxime was present in serum, tissue, and drainage fluid in adequate concentrations.
References 1. Friis H. Penicillin G versus cefuroxime for prophylaxis in lower limb amputation. Acta Orthop Scand 1987; 58: 666-8. 2. Ode B, Forsgren A, Walder M. Sensitivity of 523 blood culture isolates to 33 antibiotics. Scand J Infect Dis 1984; 16: 61-71. 3. Hares M M, Downing R, Marsh J. Failure of metronidazole/penicillin oral prophylaxis to prevent amputation stump infection. Lancet 1980; May 10: 1028-9.
Acta Orthop Scand 1990; 61 (5):460-462
4. Huizinga W K, Robbs J V, Kritzinger N A. Prevention
of wound sepsis in amputations by pen-operative antibiotic cover with an amoxycillin-clavulanicacid combination. S A Med J 1983; 63: 71-3. 5. Jones R N, Barry A L, Thomsbeny C. Antimicrobial activity of desacetylcefotaxime alone and in combination with cefotaxime: evidence of synergy. Rev Jnf Dis 1982; 4 suppl, 366-13. 6 . Mpller B N, Krebs B. Antibiotic prophylaxis in lower limb amputation. Acta Orthop Scand 1985; 56: 327-9. 7. Sonne-Holm S, Boeckstyns M, Menck H, Sinding A, Leicht P, Dichmann 0, Rag J B, Baekgaard N, Ostri P, G@trikJ K. Prophylactic antibiotics in amputations of the lower extremity for ischemia. J Bone Joint Surg (Am) 1985,67(5): 800-3. 8. Makiyama T, Asai T. Study on transfer of cefotaxime into bone tissue. Drugs 1988; 35(suppl2): 88-92.
