20
Injury(199L) 22, (I), 20-24
Printed in Great Britain
Short-course antibiotic prophylaxis in penetrating abdominal injuries: ceftriaxone versus cefoxitin D. Demetriades, M. Lakhoo, A. Pezikis, D. Charalambides, D. Pantanowitz and C. So&mos Department
of Surgery, Baragwanath
Hospital and the University
This was a prospective, randomized sfudy of 123 patienfs with penetrating abdominal injuries. The patients received ceftriaxone or cefoxitin for24 h [in fhe presence of colonic injuy, 48 h). The overall incidence of abdominal sepsis was 7.3 per cenf (ceffriaxone 5 per cenf, cefoxifin 9.5 per cenf, P> 0.05). Colonic injury was the most important risk factor for the development of septic complications. Other factors, such as the weapon wed, a prehospital time longer than 4 h, shock on admission, multiple organ injuries, and small bowel pe$mafion, did not influence fhe incidence of sepsis.
Introduction Sepsis is the most common cause of postoperative morbidity and mortality in patients with penetrating abdominal injuries. Good surgical judgement and technique remain the cornerstone for the prevention of postoperative sepsis. However, there is no doubt that antibiotics contributed significantly in reducing septic complications, especially in cases with hollow viscus perforation. Various antibiotic combinations have been used successfully, but recent studies have focused on newer cephalosporins as single-agent prophylaxis. The duration of antibiotic prophylaxis and the importance of various risk factors for abdominal sepsis remain a controversial issue. In the present study we compared the efficacy of short-course prophylaxis of two cephalosporins and we investigated the significance of various possible risk factors in the development of traumarelated complications.
Patients and methods This was a prospective study and included all patients who had a laparotomy for penetrating abdominal trauma. The patients were randomized to receive ceftriaxone 1 g every 24 h or cefoxitin 1 g every 6 h. The antibiotics were started as soon as possible in the casualty area and were continued for 24 h postoperatively. If there was color& injury the prophylaxis was continued for another 24 h. The abdomen was entered by means of a midline laparotomy and repair of the injured organs were performed as necessary. Primary repair was carried out in the majority of colonic injuries. It is our policy to reserve colostomy for patients with extensive colonic damage or severe peritoneal contamination (Deme0 1991 Butterworth-Heinemann 0020_1383/91/01002C45
Ltd
of the Witwatersrand,
South Africa
triades et al., 1985). The abdomen was copiously irrigated with normal saline if there was gross contamination. Closed drains were inserted as judged necessary by the operating surgeon. Wound cultures for aerobes and anaerobes were obtained before skin closure. The wound was washed with normal saline and the skin was always closed. Postoperatively, the patients were assessed for any evidence of abdominal sepsis, pneumonia, or urinary tract infection. An abdominal wound was considered to be infected if there was pus, exudate containing pathogenic organisms, or erythema requiring opening of the wound or administration of antibiotics. Pneumonia was diagnosed if there was fever, purulent sputum, and infiltrate on the chest film. Intra-abdominal abscess formation was suspected on clinical and ultrasonographic findings, and confirmed by percutaneous aspiration or operation. Patients were excluded from the studv if: 1. The time from injury to admission was greater than 12 hours; 2. There was a history of allergy to cephalosporins; 3. There was no peritoneal penetration; 4. There was an associated open fracture; 5. The patient died within 48 h of the operation; 6. The patient was chosen initially for conservative management and subsequently required an operation.
Results Patients The criteria for inclusion in the study were fulfilled by 123 patients. Of these, 60 patients received ceftriaxone and 63 received cefoxitin. The two groups were well matched with regard to age, sex, weapon of injury, time from injury to admission, time from admission to operation, shock on admission, associated extra-abdominal injuries, type and number of organs injured, and duration of operation (Tublesl, U). The time from injury to admission varied from 10 min to 12 h. Many of the patients were transferred from peripheral clinics. There were 25 patients with colonic injuries. The transverse colon was injured in 13 patients, the left colon in 10, and the right colon in 2 cases. Primary repair was performed on 22 (88 per cent) of the cases (92 per cent in the ceftriaxone group, 85 per cent cefoxitin group). The culture results of the incision wound are shown in TableIII.
Demetriades et al.: Short-course antibiotics in penetrating abdominal injuries Table I. Penetrating abdominal injuries (N= 123)
Age (years* SE) Sex Weapon knife bullet Shock on admission Time from injury to admission (min+SE) Time from admission to operation
(minf SE) Duration of operation (min f SE) Drains No. of organs injured per patient Patients with 33 organs injured
Table IV. Septic complications*
Ceftfiaxone (N=60)
Cefoxitin (N=63)
28fl.l 54M. 6F
30f1.3 61 M, 2F
46 14 10
42 21 6
133+15
143&16
101 fll 103f6 29 1.63 8
112+16 121 It7 35 1.66 13
Ceftriaxone (N = 60)
Cefoxitin (N=63)
Total (%)
17 27 10 12 7 8 5 4 2 2
18 22 19 13 12 8 5 4 4 4 4 1 3
35 (28) 49 (40) 29 (24) 25 (20) 19 (15) 16 (13) 10 (8) 8 (7) 6 (5) 6 (5) 5 (4) 1 (0.8) 5 (4)
:, 2
Table III. Bacteriology of the incision wound
Staph. epidermidis Staph. aureus Strept. 6 Enterococcus E. Co/i Bacillus species Diphtheroid
Ceftriaxone (N= 7)
Cefoxitin (N=9)
3 1 1 5
3 2 1 3
Wound sepsis Intra-abdominal abscess Faecal fistula Pneumonia
‘Two patients developed more than one complication.
Table II. Organ injuries in 123 patients
Extra-abdominal injuries Small bowel Stomach Colon Diaphragm Liver Spleen Vessels Pancreas Kidneys Gallbladder Common bile duct Negative operation
21
Ceftriaxone (N= 1.2)
Cefoxitin (N=9)
8 1 0 2 2 1 1
3 1 1 2 3 1 0
Table V. Risk factors for septic complications
Small bowel injuries Colonic injuries Knife wounds Bullet wounds BP 9OmmHg BP 90mmHg Three injured organs Two injured organs Prehospital time > 4 h Prehospital time c 4 h
Number of Patients
Incidence of abdominal sepsis
49 25 87 36 16 107 21 102 23 100
4.1% 24% 5.7% 8.3% 5.7% 7.5% 9.5% 8.8% 8.7% 7%
P< 0.01 P> 0.05 P> 0.05 P> 0.05 P> 0.05
compared with 2 per cent for patients with no colonic trauma (PC 0.01). The complication rate was similar in both antibiotic groups. Analysis of the various risk factors for the development of septic complications showed that colonic injuries were associated with a significantly higher incidence of sepsis than small bowel or solid organ injuries. There was no difference in the incidence of sepsis between knife and bullet injuries. Shock on admission, the presence of multiple intra-abdominal injuries, and prehospital time longer than 4 h, did not increase the rate of septic complications. Details are shown in Table V. Eighteen patients in the ceftriaxone group and 19 patients in the cefoxitin group had a temperature higher than 38°C for a total of 28 days and 32 days, respectively (P> 0.05). The hospitalization in the ceftriaxone group was 6.45 f 0.33 (ff SE) days and in the cefoxitin group was 8.50 f 0.90 days. This difference was statistically significant (PcO.05). The three cases of intraabdominal sepsis in the cefoxitin group had a prolonged hospitalization (> 8 weeks). If these cases are excluded, the hospitalization was very similar in both groups (6.26 f 0.24 us 6.42 f 0.28; P> 0.05).
Complications
There was no sepsis-related mortality. The overall incidence of septic complications was 13 per cent (11.7 per cent in the ceftriaxone group and 14.3 per cent in the cefoxitin group, P> 0.05). The overall incidence of abdominal sepsis was 7.3 per cent (9 patients), (ceftriaxone group 5 per cent, cefoxitin group 9.5 per cent, P> 0.05). Details of the complications are shown in TableIV. The complications included two intra-abdominal abscesses which were drained percutaneously, one abscess which resulted in eight laparotomies (cefoxitin group), and two faecal fistulae which were managed non-operatively. The most common organism cultured from the site of abdominal sepsis was enterococcus (four cases), followed by E. coli (three cases), Klebsielh (one case), and Enterobacter (one case). In one patient no organism was isolated. The overall incidence of abdominal sepsis in the 25 patients with colonic injuries was 24 per cent
Discussion Although there is no substiMe for good surgery, there is no doubt that antibiotic prophylaxis has significantly contributed to decreasing the incidence and severity of abdominal sepsis following penetrating trauma. Better understanding of the bacterial flora of the gastrointestinal tract has led to a better choice of antibiotics. Normally the concentration of bacteria in the stomach is very low due to the inhibitory effect of acid. The small bowel contains 106-* colonies/ml, the ileum being more heavily populated. Aerobic bacteria, mainly Streptc~occtls, dominate the proximal small bowel, while the microflora in the distal ileum is quite similar to that in the colon. The concentration of bacteria increases dramatically beyond the ileocaecal valve (Rush and Nichols, 1986). Bacteroidesfragilis is the most common anaerobe.
22
Injury: the British Journal of Accident Surgery (1991) Vol. 22/No. I
Table VI. Trauma-related sepsis in various prospecitve
studies Duration of treament (h)
Overall trauma related sepsis (%)
Intra-abdominal abscess (%)
Mortality due to sepsis (%)
Ref.
Antibiotic
No. of patients
Nichols et al. (1984)
Cefoxitin Clind/gent
70 75
120 120
20 23
Lou et al. (1985)
Cefamandole Carbenicillin
47 58
120 120
8.5 20.7
4.3 12.1
2.1 1.7
Rowlands and Ericcson (1984)
Cefamandole Cefoxitin Clind/tobra Moxalactam Clind/tobra
51 54 46 47 45
72 72 72 120 120
20 20 11 2 9
10 7 9
? ? ? ? ?
Gentry et al. (1984)
Cefamandole Cefoxitin Tricarcillin/tobra
51 50 51
48 48 48
19.7 6 9.9
11.8 6 5.8
3.9 2 0
Jones et al. (1985)
Cafamondole Cefoxitin Clind/tobra
78 94 85
48 48 48
29 13 20
5.1 5.3 3.5
0 6.2 4.1
Hofstetter et al. (1984)
Cefoxitin Ampicaminog/clind
69 50
24 24
12.9 12
4.3 2.0
0 0
Present study
Ceftriaxone Cefoxitin
60 63
11.7 14.3
1.7 3.2
0 0
24-48 24-48
9 9
4.4
0 0
Clind = clindamycin. Gent = gentamycin. Tobra= tobramycin.
Many other bacteria are part of the colonic flora: Klebsiella, enterobacter, PsarAonom~~~, Bacferoides species and peptostreptococcus. Thus, in intestinal perforations the peritoneal contamination is usually mixed. Clinical and experimental studies have shown that antibiotic prophylaxis in intestinal perforation is most effective when it covers both aerobes and anaerobes (Thadepalli et al., 1973; Weinstein et al., 1975). Combinations of antibiotics, such as penicillin/aminoglycoside/metranidazole or clindamycin/aminoglycoside have been popular in prophylaxis for penetrating abdominal trauma. However, the newer, broad spectrum cephalospor-ins offer the advantages of less toxicity and greater ease of administration. In the present study we chose to evaluate cefoxitin and ceftriaxone. Cefoxitin is a second-generation cephalosporin with good cover against most aerobes and anaerobes in the bowel. It has been shown that in abdominal trauma it is at least as effective as the various popular antibiotic combinations (Gentry et al., 1984; Hofstetter et al., 1984; Nichols et al., 1984; Jones et al., 1985; Dellinger et al., 1986). Ceftriaxone is a third-generation cephalosporin with an exceptionally long plasma elimination half-time (8 h). A single daily dose provides effective tissue concentrations against most pathogens for a period of 24 h (Scully et al., 1984). Its efficacy in abdominal trauma has not yet been tested. It is less effective against bacteroides species than cefoxitin. Neither of these two antibiotics is effective against enterococcus or Pseudomonas. Results with both antibiotics in this study compare favourably with those reported in other studies (Table VI). Bacferoides did not result in any therapeutic failures, despite inadequate in uifro cover by ceftriaxone. Its MIC90 (minimal inhibitory concentration for 90 per cent of the strains) for Bucferoides is 32 pg/ml. After an intravenous injection of 1 g ceftriaxone the plasma concentration is higher than 32 pg/ml for the first 12 h, thereafter dropping to lower levels to reach 13.2 pg/ml at 24 h (Scully et al., 1984). It is possible that antibiotic prophylaxis may not be necessary for longer than 12 h. Dellinger et al. (1986), in a prospective,
randomized study, found that for patients with penetrating abdominal injuries a 12 h course of antibiotics was as effective as a 5-day course. Psettdomonas was also not found to be the cause of any therapeutic failure, although neither of the two cephalosporins used offers significant cover against this pathogen. This finding supports the view that Psardomonas infection is not common initially in patients with penetrating abdominal injuries. However, this organism may play an important role in later hospital intra-abdominal sepsis (Nichols et al., 1984; Lou et al., 1985; Lou et al., 1988). Administration of an aminoglycoside for prophylaxis does not seem to be justified (Nichols et al., 1984; Lou et al., 1985; Lou et al., 1988). Enterococcus was isolated in four patients with abdominal sepsis, and in two of them it was the sole pathogen cultured from the area of sepsis. It is generally accepted that enterococcus may cause endocarditis and biliary and urinary tract infections. However, its significance in abdominal sepsis is controversial (Burke, 1961; Dougherty, 1984; Feliciano et al., 1986). Lou et al. (1985, 1988) suggested that routine antibiotic cover against enterococcus is not justified. The duration of antibiotic ‘prophylaxis’ is an important and unresolved issue. In elective surgery there is no need for prophylaxis longer than 12 h. However, in trauma antibiotics are not prophylactic in the same sense as in elective surgery. The trauma patient has already established peritoneal contamination at the time of admission and antibiotics are therapeutic rather than prophylactic. (O’Donnel et al., 1978; Scoy and Wilkowske, 1983; Rush and Nichols, 1986). For this reason most authors empirically give antibiotics for 3 to 7 days (O’Donnell et al., 1978; Nichols et al., 1984; Nelson et al., 1986; Lou et al., 1988). However, prolonged administration of antibiotics alters the patient’s endogenous flora, promotes the emergence of resistant organisms, may mask a significant intra-abdominal infection, increases the risk of side-effects, and is expensive. Most importantly, there is no clinical evidence that long-course prophylaxis is more effective than a short course. In the present study the standard duration of antibiotic administra-
Demetriades et al.: Short-course antibiotics in penetrating abdominal injuries
Bon was 24 h postoperatively (for colonic injuries 48 h) and the results compare favourably with those in studies with longer-course prophylaxis. Similar results were reported by other studies (Table VI). Dellinger et al. (1986) in a prospective, randomized study found that a 12-h antibiotic course was as effective as a S-day course. Hofstetter et al. (1984) recommended a 24-h course. Another important issue regarding antibiotic prophylaxis is the time of commencement of the antibiotic. In elective surgery, prophylaxis is effective only if the antibiotic is given preoperatively. However, there is no doubt that antibiotics can influence the development of infections in penetrating abdominal injuries, even though they are administered after injury and contamination has occurred. Burke (1961) demonstrated in an experimental model that antibiotics did not alter the inflammatory response if they were delayed for more than 3 h following contamination. For this reason many authors excluded patients with times longer than 3 or 4 h from injury to antibiotic administration from antibiotic trials (Rowlands and Ericcson, 1984; Jones et al., 1985; Dellinger et al., 1986). Our study did not confirm this view. We included all patients with prehospital times up to 12 h. There were 23 patients with prehospital times longer than 4 h, and the incidence of infection was the same as in patients with shorter times. In a prospective study of 65 1 patients with penetrating abdominal wounds, we found that a delay of a few hours in commencing treatment did not increase the incidence of abdominal sepsis (Demetriades and Rabinowitz, 1987). However, the length of this ‘safe’ delay has not been defined. Various risk factors have been identified as increasing sepsis in penetrating abdominal injuries. All studies agree that the primary determinant for the development of abdominal sepsis is the presence of colonic perforation (Gentry et al., 1984; Jones et al., 1985; Dellinger et al., 1986; Nelson et al., 1986; Lou et al., 1988). This was confirmed in the present series, where 24 per cent of patients with colonic injuries developed a septic complication. The presence of a colostomy is an important factor for the development of abdominal sepsis (Nichols et al., 1984; Demetriades and Rabinowitz, 1987); it is an open source of faecal contamination near the laparotomy incision and has potential communication with the peritoneal cavity through its abdominal wall exit. In a series of 134 patients with colonic injuries, colostomy was associated with a much higher incidence of sepsis than primary repair (27 per cent us 11 per cent) (Demetriades and Rabinowitz, 1987). Small bowel perforation was not found to be a significant risk factor, although the small bowel is not sterile. The incidence of sepsis in isolated solid organ injuries was zero compared with 4.1 per cent for small bowel injuries and 24 per cent for colonic injuries. Gunshot injuries have been identified as a risk factor in many studies (O’Donnell et al., 1978; Feliciano et al., 1986). In the present series, knife and gunshot injuries were associated with the same incidence of septic complications (8.3 per cent us 5.7 per cent). This also applied to the colonic injuries (23.5 per cent us 25 per cent). However, it must be emphasized that we deal mainly with low-velocity injuries, and there is no doubt that in high-velocity bullet wounds the infectious complications will be much higher. Shock on admission and the presence of multiple organ injuries ( >, 3 organs) have been described as risk factors for the development of abdominal sepsis (Nichols et al., 1984; Jones et al., 1985; Rush and Nichols, 1986). None of these situations was found in the present series to be associated
23
with increased sepsis. The presence of any of these factors is generally considered as an absolute contraindication for primary repair in left colonic injuries. This is not our experience and we perform repair despite the presence of either or both of these factors (Demetriades et al., 1985).
Conclusions Ceftriaxone is as effective as cefoxitin for antibiotic prophylaxis in penetrating abdominal injuries. It is the first time that ceftriaxone has been tested in the trauma situation and it seems to be an attractive option due to its once-a-day administration. This is particularly important in busy hospitals. Of all possible risk factors for the development of postoperative sepsis analysed, only injury to the colon was found to be significant.
References Burke J. F. (1961)The effective period of preventive
antibiotic action in experimental incisions and dermal lesions. Surgery 50, 161. Dellinger E. P., Wertz H. J. Lennard E. S. et al. (1986) Efficacy of short-course antibiotic prophylaxis after penetrating intestinal injury. Arch. Surg. 121, 23. Demetriades D. and Rabinowitz B. (1987) Indications for operation in abdominal stab wounds: A prospective study of 651 patients. Ann. Surg. 205, 129. Demetriades D., Rabinowitz B., Sofianos C. et al. (1985) The management of colon injuries by primary repair or colostomy. Br. 1. Surg. 72, 881. Dougherty S. H. (1984)Role of enterococcus in intra-abdominal sepsis. Am. J Surg. 148, 308. Feliciano D. V., Gentry L. O., Bitondo C. G. et al. (1986) Single agent cephalosporin prophylaxis for penetrating abdominal trauma. Am. J Surg. 152, 684. Gentry L. O., Feliciano D. V., Lea S. et al. (1984) Perioperative antibiotic therapy for penetrating injuries of the abdomen. Ann. Surg. 200, 561. Hofstetter R. S., Pachter H. L., Bailey A. A. et al. (1984) A prospective comparison of two regimens of prophylactic antibiotics in abdominal trauma: Cefoxitin versus triple drug. J. Trauma 24, 307. Jones R. C., Thal E. R., Johnson N. A. et al. (1985) Evaluation on antibiotic therapy following penetrating abdominal trauma. Ann. Surg. 201, 576. Lou M. A., Thadepalli H. and Mandal A. F. (1988)Safety and efficacy of mezlocillin: A single-drug therapy for penetrating abdominal trauma. J. Trauma 28, 1541. Lou M. A., Thadepalli H., Sims E. H. et al. (1985)Comparison of cefamandole and carbenicillin in preventing sepsis following penetrating abdominal trauma. Am. Surg. 5 1,580. Nelson R. M., Benitez P. R., Newell M. A. et al. (1986) Single-antibiotic use for penetrating abdominal trauma. Arch. Surg. 121, 153. Nichols R. L., Smith J. W., Klein D. B. et al. (1984)Risk of infection after penetrating abdominal trauma. N. Engi. 1. Med. 311, 1065. O’Donnell V. A., Lou M. A., Alexander J. L. et al. (1978) Role of antibiotics in penetrating abdominal trauma. Am. Surg. 44,574. O’Donnell V., Mandal A. K., Lou M. A. et al. (1978)Evaluation of carbenicillin and a comparison of clindamycin and gentamycin combined therapy in penetrating abdominal trauma. Surg. Gynecol. Obstet. 147, 525.
24
Injury: the British Journal of Accident Surgery (1991) Vol. 22/No.
Rowlands B. J. and Ericcson C. D. (1984) Comparative studies of antibiotic therapy after penetrating abdominal trauma. Am. 1. Surg. 148, 791. Rush D. S. and Nichols R. L. (1986) Risk of infection following penetrating abdominal trauma: A selective review. Yule J Biol. Med. 59,395. Scoy R. E. and Wilkowske C. J. (1983)Prophylactic use of antimicrobial agents. Mayo Clin. Proc. 58,241. hlly B. E., Fu K. P. and Neu H. C. (1984) Pharmacokinetics of ceftriaxone after intravenous infusion and intramuscular injection. Am. 1, Med. 7, 112. Thadepalli H., Gorbach S., Broide P. et al. (1973) Abdominal trauma, anaerobes, and antibiotics. Strrg. Gynecol. Obsfef. 137,
270.
I
Weinstein W. M., Onderdonk A. B., Barlett J. G. et al. (1975) Antimicrobial therapy of experimental intra-abdominal sepsis. J. Infect.Dis. 132, 282.
Paper accepted
17 April
1990.
Requestsfor reprintsshouldbe addressedto: D. Demetriades, Department of Surgery, University of the Witwatersrand, Medical School, York Road, Parktown 2193,Johannesburg, Republic of South Africa.
Injury(199L) 22, (I), 20-24
Printed in Great Britain
Short-course antibiotic prophylaxis in penetrating abdominal injuries: ceftriaxone versus cefoxitin D. Demetriades, M. Lakhoo, A. Pezikis, D. Charalambides, D. Pantanowitz and C. So&mos Department
of Surgery, Baragwanath
Hospital and the University
This was a prospective, randomized sfudy of 123 patienfs with penetrating abdominal injuries. The patients received ceftriaxone or cefoxitin for24 h [in fhe presence of colonic injuy, 48 h). The overall incidence of abdominal sepsis was 7.3 per cenf (ceffriaxone 5 per cenf, cefoxifin 9.5 per cenf, P> 0.05). Colonic injury was the most important risk factor for the development of septic complications. Other factors, such as the weapon wed, a prehospital time longer than 4 h, shock on admission, multiple organ injuries, and small bowel pe$mafion, did not influence fhe incidence of sepsis.
Introduction Sepsis is the most common cause of postoperative morbidity and mortality in patients with penetrating abdominal injuries. Good surgical judgement and technique remain the cornerstone for the prevention of postoperative sepsis. However, there is no doubt that antibiotics contributed significantly in reducing septic complications, especially in cases with hollow viscus perforation. Various antibiotic combinations have been used successfully, but recent studies have focused on newer cephalosporins as single-agent prophylaxis. The duration of antibiotic prophylaxis and the importance of various risk factors for abdominal sepsis remain a controversial issue. In the present study we compared the efficacy of short-course prophylaxis of two cephalosporins and we investigated the significance of various possible risk factors in the development of traumarelated complications.
Patients and methods This was a prospective study and included all patients who had a laparotomy for penetrating abdominal trauma. The patients were randomized to receive ceftriaxone 1 g every 24 h or cefoxitin 1 g every 6 h. The antibiotics were started as soon as possible in the casualty area and were continued for 24 h postoperatively. If there was color& injury the prophylaxis was continued for another 24 h. The abdomen was entered by means of a midline laparotomy and repair of the injured organs were performed as necessary. Primary repair was carried out in the majority of colonic injuries. It is our policy to reserve colostomy for patients with extensive colonic damage or severe peritoneal contamination (Deme0 1991 Butterworth-Heinemann 0020_1383/91/01002C45
Ltd
of the Witwatersrand,
South Africa
triades et al., 1985). The abdomen was copiously irrigated with normal saline if there was gross contamination. Closed drains were inserted as judged necessary by the operating surgeon. Wound cultures for aerobes and anaerobes were obtained before skin closure. The wound was washed with normal saline and the skin was always closed. Postoperatively, the patients were assessed for any evidence of abdominal sepsis, pneumonia, or urinary tract infection. An abdominal wound was considered to be infected if there was pus, exudate containing pathogenic organisms, or erythema requiring opening of the wound or administration of antibiotics. Pneumonia was diagnosed if there was fever, purulent sputum, and infiltrate on the chest film. Intra-abdominal abscess formation was suspected on clinical and ultrasonographic findings, and confirmed by percutaneous aspiration or operation. Patients were excluded from the studv if: 1. The time from injury to admission was greater than 12 hours; 2. There was a history of allergy to cephalosporins; 3. There was no peritoneal penetration; 4. There was an associated open fracture; 5. The patient died within 48 h of the operation; 6. The patient was chosen initially for conservative management and subsequently required an operation.
Results Patients The criteria for inclusion in the study were fulfilled by 123 patients. Of these, 60 patients received ceftriaxone and 63 received cefoxitin. The two groups were well matched with regard to age, sex, weapon of injury, time from injury to admission, time from admission to operation, shock on admission, associated extra-abdominal injuries, type and number of organs injured, and duration of operation (Tublesl, U). The time from injury to admission varied from 10 min to 12 h. Many of the patients were transferred from peripheral clinics. There were 25 patients with colonic injuries. The transverse colon was injured in 13 patients, the left colon in 10, and the right colon in 2 cases. Primary repair was performed on 22 (88 per cent) of the cases (92 per cent in the ceftriaxone group, 85 per cent cefoxitin group). The culture results of the incision wound are shown in TableIII.
Demetriades et al.: Short-course antibiotics in penetrating abdominal injuries Table I. Penetrating abdominal injuries (N= 123)
Age (years* SE) Sex Weapon knife bullet Shock on admission Time from injury to admission (min+SE) Time from admission to operation
(minf SE) Duration of operation (min f SE) Drains No. of organs injured per patient Patients with 33 organs injured
Table IV. Septic complications*
Ceftfiaxone (N=60)
Cefoxitin (N=63)
28fl.l 54M. 6F
30f1.3 61 M, 2F
46 14 10
42 21 6
133+15
143&16
101 fll 103f6 29 1.63 8
112+16 121 It7 35 1.66 13
Ceftriaxone (N = 60)
Cefoxitin (N=63)
Total (%)
17 27 10 12 7 8 5 4 2 2
18 22 19 13 12 8 5 4 4 4 4 1 3
35 (28) 49 (40) 29 (24) 25 (20) 19 (15) 16 (13) 10 (8) 8 (7) 6 (5) 6 (5) 5 (4) 1 (0.8) 5 (4)
:, 2
Table III. Bacteriology of the incision wound
Staph. epidermidis Staph. aureus Strept. 6 Enterococcus E. Co/i Bacillus species Diphtheroid
Ceftriaxone (N= 7)
Cefoxitin (N=9)
3 1 1 5
3 2 1 3
Wound sepsis Intra-abdominal abscess Faecal fistula Pneumonia
‘Two patients developed more than one complication.
Table II. Organ injuries in 123 patients
Extra-abdominal injuries Small bowel Stomach Colon Diaphragm Liver Spleen Vessels Pancreas Kidneys Gallbladder Common bile duct Negative operation
21
Ceftriaxone (N= 1.2)
Cefoxitin (N=9)
8 1 0 2 2 1 1
3 1 1 2 3 1 0
Table V. Risk factors for septic complications
Small bowel injuries Colonic injuries Knife wounds Bullet wounds BP 9OmmHg BP 90mmHg Three injured organs Two injured organs Prehospital time > 4 h Prehospital time c 4 h
Number of Patients
Incidence of abdominal sepsis
49 25 87 36 16 107 21 102 23 100
4.1% 24% 5.7% 8.3% 5.7% 7.5% 9.5% 8.8% 8.7% 7%
P< 0.01 P> 0.05 P> 0.05 P> 0.05 P> 0.05
compared with 2 per cent for patients with no colonic trauma (PC 0.01). The complication rate was similar in both antibiotic groups. Analysis of the various risk factors for the development of septic complications showed that colonic injuries were associated with a significantly higher incidence of sepsis than small bowel or solid organ injuries. There was no difference in the incidence of sepsis between knife and bullet injuries. Shock on admission, the presence of multiple intra-abdominal injuries, and prehospital time longer than 4 h, did not increase the rate of septic complications. Details are shown in Table V. Eighteen patients in the ceftriaxone group and 19 patients in the cefoxitin group had a temperature higher than 38°C for a total of 28 days and 32 days, respectively (P> 0.05). The hospitalization in the ceftriaxone group was 6.45 f 0.33 (ff SE) days and in the cefoxitin group was 8.50 f 0.90 days. This difference was statistically significant (PcO.05). The three cases of intraabdominal sepsis in the cefoxitin group had a prolonged hospitalization (> 8 weeks). If these cases are excluded, the hospitalization was very similar in both groups (6.26 f 0.24 us 6.42 f 0.28; P> 0.05).
Complications
There was no sepsis-related mortality. The overall incidence of septic complications was 13 per cent (11.7 per cent in the ceftriaxone group and 14.3 per cent in the cefoxitin group, P> 0.05). The overall incidence of abdominal sepsis was 7.3 per cent (9 patients), (ceftriaxone group 5 per cent, cefoxitin group 9.5 per cent, P> 0.05). Details of the complications are shown in TableIV. The complications included two intra-abdominal abscesses which were drained percutaneously, one abscess which resulted in eight laparotomies (cefoxitin group), and two faecal fistulae which were managed non-operatively. The most common organism cultured from the site of abdominal sepsis was enterococcus (four cases), followed by E. coli (three cases), Klebsielh (one case), and Enterobacter (one case). In one patient no organism was isolated. The overall incidence of abdominal sepsis in the 25 patients with colonic injuries was 24 per cent
Discussion Although there is no substiMe for good surgery, there is no doubt that antibiotic prophylaxis has significantly contributed to decreasing the incidence and severity of abdominal sepsis following penetrating trauma. Better understanding of the bacterial flora of the gastrointestinal tract has led to a better choice of antibiotics. Normally the concentration of bacteria in the stomach is very low due to the inhibitory effect of acid. The small bowel contains 106-* colonies/ml, the ileum being more heavily populated. Aerobic bacteria, mainly Streptc~occtls, dominate the proximal small bowel, while the microflora in the distal ileum is quite similar to that in the colon. The concentration of bacteria increases dramatically beyond the ileocaecal valve (Rush and Nichols, 1986). Bacteroidesfragilis is the most common anaerobe.
22
Injury: the British Journal of Accident Surgery (1991) Vol. 22/No. I
Table VI. Trauma-related sepsis in various prospecitve
studies Duration of treament (h)
Overall trauma related sepsis (%)
Intra-abdominal abscess (%)
Mortality due to sepsis (%)
Ref.
Antibiotic
No. of patients
Nichols et al. (1984)
Cefoxitin Clind/gent
70 75
120 120
20 23
Lou et al. (1985)
Cefamandole Carbenicillin
47 58
120 120
8.5 20.7
4.3 12.1
2.1 1.7
Rowlands and Ericcson (1984)
Cefamandole Cefoxitin Clind/tobra Moxalactam Clind/tobra
51 54 46 47 45
72 72 72 120 120
20 20 11 2 9
10 7 9
? ? ? ? ?
Gentry et al. (1984)
Cefamandole Cefoxitin Tricarcillin/tobra
51 50 51
48 48 48
19.7 6 9.9
11.8 6 5.8
3.9 2 0
Jones et al. (1985)
Cafamondole Cefoxitin Clind/tobra
78 94 85
48 48 48
29 13 20
5.1 5.3 3.5
0 6.2 4.1
Hofstetter et al. (1984)
Cefoxitin Ampicaminog/clind
69 50
24 24
12.9 12
4.3 2.0
0 0
Present study
Ceftriaxone Cefoxitin
60 63
11.7 14.3
1.7 3.2
0 0
24-48 24-48
9 9
4.4
0 0
Clind = clindamycin. Gent = gentamycin. Tobra= tobramycin.
Many other bacteria are part of the colonic flora: Klebsiella, enterobacter, PsarAonom~~~, Bacferoides species and peptostreptococcus. Thus, in intestinal perforations the peritoneal contamination is usually mixed. Clinical and experimental studies have shown that antibiotic prophylaxis in intestinal perforation is most effective when it covers both aerobes and anaerobes (Thadepalli et al., 1973; Weinstein et al., 1975). Combinations of antibiotics, such as penicillin/aminoglycoside/metranidazole or clindamycin/aminoglycoside have been popular in prophylaxis for penetrating abdominal trauma. However, the newer, broad spectrum cephalospor-ins offer the advantages of less toxicity and greater ease of administration. In the present study we chose to evaluate cefoxitin and ceftriaxone. Cefoxitin is a second-generation cephalosporin with good cover against most aerobes and anaerobes in the bowel. It has been shown that in abdominal trauma it is at least as effective as the various popular antibiotic combinations (Gentry et al., 1984; Hofstetter et al., 1984; Nichols et al., 1984; Jones et al., 1985; Dellinger et al., 1986). Ceftriaxone is a third-generation cephalosporin with an exceptionally long plasma elimination half-time (8 h). A single daily dose provides effective tissue concentrations against most pathogens for a period of 24 h (Scully et al., 1984). Its efficacy in abdominal trauma has not yet been tested. It is less effective against bacteroides species than cefoxitin. Neither of these two antibiotics is effective against enterococcus or Pseudomonas. Results with both antibiotics in this study compare favourably with those reported in other studies (Table VI). Bacferoides did not result in any therapeutic failures, despite inadequate in uifro cover by ceftriaxone. Its MIC90 (minimal inhibitory concentration for 90 per cent of the strains) for Bucferoides is 32 pg/ml. After an intravenous injection of 1 g ceftriaxone the plasma concentration is higher than 32 pg/ml for the first 12 h, thereafter dropping to lower levels to reach 13.2 pg/ml at 24 h (Scully et al., 1984). It is possible that antibiotic prophylaxis may not be necessary for longer than 12 h. Dellinger et al. (1986), in a prospective,
randomized study, found that for patients with penetrating abdominal injuries a 12 h course of antibiotics was as effective as a 5-day course. Psettdomonas was also not found to be the cause of any therapeutic failure, although neither of the two cephalosporins used offers significant cover against this pathogen. This finding supports the view that Psardomonas infection is not common initially in patients with penetrating abdominal injuries. However, this organism may play an important role in later hospital intra-abdominal sepsis (Nichols et al., 1984; Lou et al., 1985; Lou et al., 1988). Administration of an aminoglycoside for prophylaxis does not seem to be justified (Nichols et al., 1984; Lou et al., 1985; Lou et al., 1988). Enterococcus was isolated in four patients with abdominal sepsis, and in two of them it was the sole pathogen cultured from the area of sepsis. It is generally accepted that enterococcus may cause endocarditis and biliary and urinary tract infections. However, its significance in abdominal sepsis is controversial (Burke, 1961; Dougherty, 1984; Feliciano et al., 1986). Lou et al. (1985, 1988) suggested that routine antibiotic cover against enterococcus is not justified. The duration of antibiotic ‘prophylaxis’ is an important and unresolved issue. In elective surgery there is no need for prophylaxis longer than 12 h. However, in trauma antibiotics are not prophylactic in the same sense as in elective surgery. The trauma patient has already established peritoneal contamination at the time of admission and antibiotics are therapeutic rather than prophylactic. (O’Donnel et al., 1978; Scoy and Wilkowske, 1983; Rush and Nichols, 1986). For this reason most authors empirically give antibiotics for 3 to 7 days (O’Donnell et al., 1978; Nichols et al., 1984; Nelson et al., 1986; Lou et al., 1988). However, prolonged administration of antibiotics alters the patient’s endogenous flora, promotes the emergence of resistant organisms, may mask a significant intra-abdominal infection, increases the risk of side-effects, and is expensive. Most importantly, there is no clinical evidence that long-course prophylaxis is more effective than a short course. In the present study the standard duration of antibiotic administra-
Demetriades et al.: Short-course antibiotics in penetrating abdominal injuries
Bon was 24 h postoperatively (for colonic injuries 48 h) and the results compare favourably with those in studies with longer-course prophylaxis. Similar results were reported by other studies (Table VI). Dellinger et al. (1986) in a prospective, randomized study found that a 12-h antibiotic course was as effective as a S-day course. Hofstetter et al. (1984) recommended a 24-h course. Another important issue regarding antibiotic prophylaxis is the time of commencement of the antibiotic. In elective surgery, prophylaxis is effective only if the antibiotic is given preoperatively. However, there is no doubt that antibiotics can influence the development of infections in penetrating abdominal injuries, even though they are administered after injury and contamination has occurred. Burke (1961) demonstrated in an experimental model that antibiotics did not alter the inflammatory response if they were delayed for more than 3 h following contamination. For this reason many authors excluded patients with times longer than 3 or 4 h from injury to antibiotic administration from antibiotic trials (Rowlands and Ericcson, 1984; Jones et al., 1985; Dellinger et al., 1986). Our study did not confirm this view. We included all patients with prehospital times up to 12 h. There were 23 patients with prehospital times longer than 4 h, and the incidence of infection was the same as in patients with shorter times. In a prospective study of 65 1 patients with penetrating abdominal wounds, we found that a delay of a few hours in commencing treatment did not increase the incidence of abdominal sepsis (Demetriades and Rabinowitz, 1987). However, the length of this ‘safe’ delay has not been defined. Various risk factors have been identified as increasing sepsis in penetrating abdominal injuries. All studies agree that the primary determinant for the development of abdominal sepsis is the presence of colonic perforation (Gentry et al., 1984; Jones et al., 1985; Dellinger et al., 1986; Nelson et al., 1986; Lou et al., 1988). This was confirmed in the present series, where 24 per cent of patients with colonic injuries developed a septic complication. The presence of a colostomy is an important factor for the development of abdominal sepsis (Nichols et al., 1984; Demetriades and Rabinowitz, 1987); it is an open source of faecal contamination near the laparotomy incision and has potential communication with the peritoneal cavity through its abdominal wall exit. In a series of 134 patients with colonic injuries, colostomy was associated with a much higher incidence of sepsis than primary repair (27 per cent us 11 per cent) (Demetriades and Rabinowitz, 1987). Small bowel perforation was not found to be a significant risk factor, although the small bowel is not sterile. The incidence of sepsis in isolated solid organ injuries was zero compared with 4.1 per cent for small bowel injuries and 24 per cent for colonic injuries. Gunshot injuries have been identified as a risk factor in many studies (O’Donnell et al., 1978; Feliciano et al., 1986). In the present series, knife and gunshot injuries were associated with the same incidence of septic complications (8.3 per cent us 5.7 per cent). This also applied to the colonic injuries (23.5 per cent us 25 per cent). However, it must be emphasized that we deal mainly with low-velocity injuries, and there is no doubt that in high-velocity bullet wounds the infectious complications will be much higher. Shock on admission and the presence of multiple organ injuries ( >, 3 organs) have been described as risk factors for the development of abdominal sepsis (Nichols et al., 1984; Jones et al., 1985; Rush and Nichols, 1986). None of these situations was found in the present series to be associated
23
with increased sepsis. The presence of any of these factors is generally considered as an absolute contraindication for primary repair in left colonic injuries. This is not our experience and we perform repair despite the presence of either or both of these factors (Demetriades et al., 1985).
Conclusions Ceftriaxone is as effective as cefoxitin for antibiotic prophylaxis in penetrating abdominal injuries. It is the first time that ceftriaxone has been tested in the trauma situation and it seems to be an attractive option due to its once-a-day administration. This is particularly important in busy hospitals. Of all possible risk factors for the development of postoperative sepsis analysed, only injury to the colon was found to be significant.
References Burke J. F. (1961)The effective period of preventive
antibiotic action in experimental incisions and dermal lesions. Surgery 50, 161. Dellinger E. P., Wertz H. J. Lennard E. S. et al. (1986) Efficacy of short-course antibiotic prophylaxis after penetrating intestinal injury. Arch. Surg. 121, 23. Demetriades D. and Rabinowitz B. (1987) Indications for operation in abdominal stab wounds: A prospective study of 651 patients. Ann. Surg. 205, 129. Demetriades D., Rabinowitz B., Sofianos C. et al. (1985) The management of colon injuries by primary repair or colostomy. Br. 1. Surg. 72, 881. Dougherty S. H. (1984)Role of enterococcus in intra-abdominal sepsis. Am. J Surg. 148, 308. Feliciano D. V., Gentry L. O., Bitondo C. G. et al. (1986) Single agent cephalosporin prophylaxis for penetrating abdominal trauma. Am. J Surg. 152, 684. Gentry L. O., Feliciano D. V., Lea S. et al. (1984) Perioperative antibiotic therapy for penetrating injuries of the abdomen. Ann. Surg. 200, 561. Hofstetter R. S., Pachter H. L., Bailey A. A. et al. (1984) A prospective comparison of two regimens of prophylactic antibiotics in abdominal trauma: Cefoxitin versus triple drug. J. Trauma 24, 307. Jones R. C., Thal E. R., Johnson N. A. et al. (1985) Evaluation on antibiotic therapy following penetrating abdominal trauma. Ann. Surg. 201, 576. Lou M. A., Thadepalli H. and Mandal A. F. (1988)Safety and efficacy of mezlocillin: A single-drug therapy for penetrating abdominal trauma. J. Trauma 28, 1541. Lou M. A., Thadepalli H., Sims E. H. et al. (1985)Comparison of cefamandole and carbenicillin in preventing sepsis following penetrating abdominal trauma. Am. Surg. 5 1,580. Nelson R. M., Benitez P. R., Newell M. A. et al. (1986) Single-antibiotic use for penetrating abdominal trauma. Arch. Surg. 121, 153. Nichols R. L., Smith J. W., Klein D. B. et al. (1984)Risk of infection after penetrating abdominal trauma. N. Engi. 1. Med. 311, 1065. O’Donnell V. A., Lou M. A., Alexander J. L. et al. (1978) Role of antibiotics in penetrating abdominal trauma. Am. Surg. 44,574. O’Donnell V., Mandal A. K., Lou M. A. et al. (1978)Evaluation of carbenicillin and a comparison of clindamycin and gentamycin combined therapy in penetrating abdominal trauma. Surg. Gynecol. Obstet. 147, 525.
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Injury: the British Journal of Accident Surgery (1991) Vol. 22/No.
Rowlands B. J. and Ericcson C. D. (1984) Comparative studies of antibiotic therapy after penetrating abdominal trauma. Am. 1. Surg. 148, 791. Rush D. S. and Nichols R. L. (1986) Risk of infection following penetrating abdominal trauma: A selective review. Yule J Biol. Med. 59,395. Scoy R. E. and Wilkowske C. J. (1983)Prophylactic use of antimicrobial agents. Mayo Clin. Proc. 58,241. hlly B. E., Fu K. P. and Neu H. C. (1984) Pharmacokinetics of ceftriaxone after intravenous infusion and intramuscular injection. Am. 1, Med. 7, 112. Thadepalli H., Gorbach S., Broide P. et al. (1973) Abdominal trauma, anaerobes, and antibiotics. Strrg. Gynecol. Obsfef. 137,
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Weinstein W. M., Onderdonk A. B., Barlett J. G. et al. (1975) Antimicrobial therapy of experimental intra-abdominal sepsis. J. Infect.Dis. 132, 282.
Paper accepted
17 April
1990.
Requestsfor reprintsshouldbe addressedto: D. Demetriades, Department of Surgery, University of the Witwatersrand, Medical School, York Road, Parktown 2193,Johannesburg, Republic of South Africa.
