Arch Orthop Trauma Surg (1990) 109 : 72-74

Archives°'Orthopaedic .dTrauma Surgery © Springer-Verlag 1990

Antibiotic prophylaxis in lower-extremity amputations due to ischemia A prospective, randomized trial of Cephalothin versus Methicillin S. Thomsen 2, B .W. Jakobsen I, J. O. Wethelund 1, J. Dalsgaard 2, H . N . Gregersen 2, and U. Lucht 1 1Department of Orthopedic Surgery E, Aarhus Municipal Hospital, Aarhus, Denmark 2Department of Orthopedic Surgery O, Aalborg Hospital, Aalborg, Denmark

Summary. T h e efficiency of prophylactic antibiotic therapy in a m p u t a t i o n surgery was studied in a prospective, r a n d o m i z e d trial of a first-generation cephalosporin (cephalothin) c o m p a r e d with a n a r r o w - s p e c t r u m betalactam stable penicillin (methicillin). Eighty-eight patients received cephalothin 2 g × 4 on the day of operation, while 86 patients received methicillin I g x 4. T h e patients were followed up for 21 days. Infected w o u n d s o c c u r r e d in 14.8% of the patients in the cephalothin group, c o m p a r e d with 14% in the methicillin group. T h e frequency of deep infections was 10.2% versus 4.7% (P = 0.1611). T h e r e a m p u t a t i o n frequency was 18.2% in the cephalothin g r o u p c o m p a r e d with 12.8% in the methicillin group; the frequency of b e l o w - k n e e r e a m p u tation was 18.4% versus 7.7% ( P = 0.1469). N o clostridial infections were found. T h e study did not d e m o n strate any significant difference b e t w e e n cephalothin and methicillin in the prophylaxis for lower-extremity amputations, although the latter drug t e n d e d to be the best choice.

In recent years, prophylactic use of antibiotics in amputation of the lower extremities for ischemia has b e e n suggested [13]. Thus, in a controlled study of cefoxitin, the secondary infection rates decreased f r o m 39% in the placebo g r o u p to 17% in the antibiotic group. T h e rea m p u t a t i o n frequency was lowered f r o m 28% to 10%, and in the antibiotic group no clostridial infections were observed [17]. It was concluded that a b r o a d - s p e c t r u m cephalosporin should be used as a prophylactic antibiotic. Several retrospective studies have d e m o n s t r a t e d the n e e d for prophylactic antibiotics especially targeted at clostridia [1, 5, 15]. M a n y microbiologists, however, disagree on the prophylactic use of b r o a d - s p e c t r u m antibiotics. T h e aim of the present prospective, r a n d o m i z e d investigation was to reveal the prophylactic effect of two of the m o s t beta-lactam-resistant antibiotics in patients undergoing a m p u t a t i o n of the lower extremities for ischemia. Offprint requests to: S.T. Thomsen, Svalegaardsvej 35, DK-9000

Aalborg, Denmark

Patients and methods All patients admitted to the participating departments for amputation due to arteriosclerosis during the period from January 1985 through December 1986 were entered into the study. After informed consent the patients were allocated, by random numbers, to prophylactic treatment with cephalothin or methicillin. Excluded were patients who: (a) received antibiotic treatment within 48h of the amputation; (b) had a history of allergic reaction to penicillins; (c) were pregnant; (d) had previously participated in the study with the same extremity; (e) had a renal insufficiency; (f) refused consent to participate in the study. Five doses of either 2g cephalothin or l g methicillin were given in the first 24 h, starting 0.5-1h before the skin incision was made and continuing at intervals of 6 h. The following preoperative procedures were carried out by the authors: aerobic and anaerobic cultures were prepared from all wounds with an exudate. Using Stuart's medium, dry necroses were evaluated; in case of sepsis, blood was drawn for culture, and a urine specimen was taken for culture. Postoperatively, aerobic and anaerobic cultures were taken from the drain at removal, as well as from infected stumps and dry necroses. A urine specimen was sent on the 7th postoperative day. The choice of amputation level was based on clinical findings, distal blood pressure, and the skin-perfusion pressure [7-10, 18, 19]. Usually, a below-knee amputation was performed when the skin-perfusion pressure (SPP) was -> 40 mm Hg, a through-knee amputation with the SPP between 40 and 20mmHg, and an above-knee amputation when the SPP was -< 20 mmHg. For below-knee amputations the Persson operative technique was used, for above-knee amputations a myoplastic technique [16]. A suction drain was used and was removed after 1-3 days. The stumps were bandaged with soft bandages, which were changed weekly for patients without complications. Sutures were removed after 3 weeks. Points for evaluation in the study were primary healing, dry necrosis, superficial and deep infection, revision, and reamputation at the same or higher level. After randomized assignment, a total of 174 patients were included. Thirteen patients, six in the cephalothin group and seven in the methicillin group, were excluded because of death within 3 weeks. None of these had stump problems. For comparison of pairs of numbers, Fisher's exact probability test or the chi-square test was used.

Results Descriptive data for the 187 patients participating in the study are shown in Tables 1 and 2. T h e characteristics showed no significant differences ( P values > 0 . 0 8 6 ) .

73

S. Thomsen et al.: Antibiotic prophylaxis in lower-extremity amputations Table 1. Descriptive data for 187 patients

Number of patients Sex ratio (F/M) Age (years) Diabetes mellitus Preoperative infections Dry gangrene Wet gangrene Trauma, others

Cephalothin

Methicillin

Statistics

94 0.92 (45/49) 72 (45-94) 28 45 13 44 7

93 1.82 (60/33) 72 (40-93) 26 45 8 45 11

NS NS NS NS NS NS NS NS

fection. Fifty-six per cent of these (10 of 18) showed growth of the same species that had been found preoperatively; consequently, 44% of the patients with postoperative Staphylococcus aureus infection had been infected during the operation or in the postoperative period. Twelve per cent (3 of 25) showed gram-negative cultures, all of which were also found in the preoperative cultures. Regarding general complications, no allergic reactions or renal impairment were seen.

Discussion Table 2. Amputation levels

Amputation

Cephalothin

Methicillin

Statistics

Above-knee Through-knee Below-knee Foot

25 13 50 6

33 11 42 7

NS NS NS NS

The results of 174 patients undergoing amputation of the lower extremity for ischemia are shown in Table 3. Primary healing of the stump occurred in 70.5% (62 of 88) of the cephalothin group and in 72.1% (62 of 86) of the methicillin group. Dry necrosis occurred in 14.8% (13 of 88) of the cephalothin group and in 14% (12 of 86) of the methicillin group. The frequency of postoperative wound infection was 14.8% (13 of 88) in the cephalothin group and 14% (12 of 86) in the methicillin group. Deep infection occurred in 10.2% (9 of 88) of the cephalothin group and in 4.7% (4 of 86) of the methicillin group; the difference was not significant (P = 0.1611). The reamputation frequency (Table 4) of the cephalothin group was 18.2% (16 of 88) compared with 12.8% (11 of 86) of the methicillin group (P = 0.3094). In belowknee amputation the reamputation frequencies were 18.4% (9 of 49) for the cephalothin group and 7.7% (3 of 39) for the methicillin group; this also was not significant (P -- 0.1469). In one patient Clostridiurn perfringens was cultured preoperatively, but the patient had no clinical or microbiological infection postoperatively. No other clostridial infections were observed. Postoperative bacterial cultures showed 72% (18 of 25) Staphylococcus aureus in-

For amputation surgery, prophylactic penicillin has been advocated mainly because of the risk of clostridial infection [6, 14, 15]. After 2-7 days' treatment with penicillin, however, the reported postoperative infection rate has been over 50% ; this is not superior to the rate without prophylaxis. The types of antibiotics and the duration of treatment are often debated. Our choice of antibiotics was determined by the wish to use drugs that were effective against clostridia and, recognizing that the main bacteriological problem was Staphylococcus aureus, they should belong to the group of very stable betalactam antibiotics. In order to disturb the normal flora of the body as little as possible, a further criterion was that they should be narrow-spectrum antibiotics. Studies have shown that the administration of antibiotics immediately before the operation is effective in preventing inoculi from causing infection [2, 3]. However, prophylaxis for longer than 3 days seems unnecessary [4, 14]. Sonne-Holm et al. [17] and B . M . M ¢ l l e r [12] showed good results with 1 day of treatment. The present study of 1-day treatment with cephalothin or methicillin showed results that are comparable to those of 1 day cefoxitin treatment, for which SonneHolm et al. [17] reported 17% postoperative wound infections, and to 2-day treatment with amoxycillinclavulanic acid, for which Huzinga et al. [11] reported 13% postoperative wound infections. Sonne-Holm et al. [17] concluded that a broad-spectrum antibiotic was imperative in prophylaxis. Although we found lower infection rates and lower reamputation frequencies in the methicillin group, our study showed no significant difference between cephalo-

Table 3. Results of 174 patients

Amputation

Number

Dead

C

C

M

Healing M

Sepsis

Primary healing

Necrosis Necrosis

Superficial infection

Deep infection

C

M

C

M

C

M

C

M

C

M

Abobe-knee Through-knee Below-knee Foot

22 11 49 6

32 9 39 6

3 2 1 0

1 2 3 1

21 6 32 3

28 5 26 3

0 3 10 0

2 1 8 1

1 0 3 0

1 1 5 1

0 2 4 3

1 2 0 1

0 1 1 0

2 1 1 0

Total

88

86

6

7

62

62

13

12

4

8

9

4

2

4

C, Cephalothin; M, methicillin

74

S. Thomsen et al.: Antibiotic prophylaxis in lower-extremity amputations

Table 4. Reamputation rates Reamputation Same level

Higher level

Revision

C

M

C

M

C

M

Above-knee Through-knee Below-knee Foot

0 0 0 1

0 0 1 0

0 4 9 2

1 4 3 2

0 0 0 1

0 0 0 3

Total

1

1

15

10

1

3

C, Cephalothin; M, methicillin

thin a n d methicillin. A c c o r d i n g l y , w e c a n n o t a g r e e t h a t t h e r e is a n y a d v a n t a g e to using e i t h e r a b r o a d - s p e c t r u m or a n a r r o w - s p e c t r u m c e p h a l o s p o r i n i n s t e a d o f a b e t a l a c t a m - s t a b l e penicillin in t h e p r o p h y l a x i s of l o w e r extremity amputations. We recommend a beta-lactamstable penicillin which p r e s e r v e s m o r e o f t h e n o r m a l bacterial flora of the body. D e s p i t e a t t e m p t s to i n c r e a s e the f r e q u e n c y o f p r i m a ry s t u m p h e a l i n g b y using v a r i o u s m e t h o d s to assist in d e t e r m i n i n g t h e a m p u t a t i o n level [ 7 - 1 0 , 18, 19] a n d a n t i b i o t i c p r o p h y l a x i s , o u r s t u d y shows t h a t t h e infection r a t e a n d t h e r e a m p u t a t i o n f r e q u e n c y a r e still r a t h e r high. This is e s p e c i a l l y t r u e r e g a r d i n g t h r o u g h - k n e e amp u t a t i o n s a n d a m p u t a t i o n s of t h e foot. B e t t e r results m i g h t b e o b t a i n e d b y p a y i n g m o r e a t t e n t i o n to surgical t e c h n i q u e a n d b y u p g r a d i n g a m p u t a t i o n surgery.

References 1. Ayliffe GAJ, Lowbury EJL (1969) Sources of gas gangrene in hospital. Br Med J 2 : 333-337 2. Bowers WH, Wilson FC, Greene WB (1973) Antibiotic prophylaxis in experimental bone infections. J Bone Joint Surg [Am] 55 : 795-807 3. Burke JF (1961) The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50:161-168

4. Chodak GW, Plaut ME (1977) Use of systemic antibiotics for prophylaxis in surgery. Arch Surg 112 : 326-334 5. Editorial (1969) Postoperative gas gangrene. Br Med J 3 : 665666 6. Hares MM, Downing R, Marsh J (1980) Failure of metronidazole/penicillin oral prophylaxis to prevent amputation stump infection. Lancet I: 1028-1029 7. Holstein P, Lassen NA (1973) Radioisotope clearance technique for measurement of distal blood pressure in skin and muscles. Scand J Clin Lab Invest [Suppl] 128 : 143-147 8. Holstein P, Sager P, Lassen NA (1979) Wound healing in below-knee amputations in relation to skin perfusion pressure. Acta Orthop Scand 50: 49-58 9. Holstein P, Dovey H, Lassen NA (1979) Wound healing in above-knee amputations in relation to skin perfusion pressure. Acta Orthop Scand 50 : 59-60 10. Holstein P (1982) Level selection in leg amputation for arterial occlusive disease. Acta Orthop Scand 53 : 821-831 11. Huizinga WKJ, Robbs JV, Kritzinger NA (1983) Prevention of wound sepsis in amputation by peri-operative antibiotic cover with an amoxycillin-clavulanic acid combination. S Afr Med J 63 : 71-73 12. M011er BN, Krebs B (1985) Antibiotic prophylaxis in lower limb amputation. Acta Orthop Scand 56 : 327-329 13. Nichols RL (1981) Use of prophylactic antibiotics in surgical practice. Am J Med 70 : 686-692 14. Nelson CL, Green TG, et al (1983) One day versus seven days of preventive antibiotic therapy in orthopedic surgery. Clin Orthop 176: 258-263 15. Parker MT (1969) Postoperative clostridial infections in Britain. Br Med J 3 : 671-676 16. Persson BM (1974) Sagittal incision for below-knee amputation in ischemic gangrene. J Bone Joint Surg [Br] 56:110-114 17. Sonne-Holm S, Menck H, Boeckstyns M, et al (1985) Prophylactic antibiotics in amputation of the lower extremity for ischemia. A placebo-controlled, randomized trial of cefoxitin. J Bone Joint Surg [Am] 67 : 800-803 18. St¢ckel M, Br0chner-Mortensen J (1981) A simple and reliable method for determination of skin perfusion pressure in patients with severe occlusive arterial disease. Clin Physiol 1 : 471-477 19. St¢ckel M, Ovesen J, Br¢chner-Mortensen J, Emneus H (1982) Standardized photoelectric technique as routine method for selection of amputation level. Acta Orthop Scand 53: 875-878

Received 11 June, 1988

Antibiotic prophylaxis in lower-extremity amputations due to ischemia. A prospective, randomized trial of cephalothin versus methicillin.

The efficiency of prophylactic antibiotic therapy in amputation surgery was studied in a prospective, randomized trial of a first-generation cephalosp...
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