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Antibiotics in penetrating abdominal trauma: Comparison of ticarcillin plus clavulanic acid with gentamicin plus clindamycin
Antibiotics in Penetrating Abdominal Trauma Comparison of Ticarcillin plus Clavulanic Acid with Gentamicin plus Clindamycin
A comparative trial of ticarcillin plus clavulanlc acid with gentamicin plus clindamycin was conducted in 85 patients who sustained pena bating abdominal wounds. The antibiotic regimens were given for 24 hours. The overall wound and/or intra-abdominal infection rate was 5.9 percent. Patients who sustained gunshot wounds to hollow viscera were at highest risk. lnfectlon developed In one of 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid and In four of 32 (12 percent) patients who received gentamlcln plus clindamycin. These differences were not statistically significant. These data support the use of short-course (24-hour) antibiotic therapy In this clinical setting and demonstrate that ticarcillin plus clavulanlc acid is efficacious as a preventive antibiotic combination.
TIMOTHY C. FABIAN, M.D. SANDRA J. BOLDREGHINI, R.N. Memphis,
Tennessee
From the Department of Surgery, University of Tennessee Center for the Health Sciences, Memphis, Tennessee. This work was supported, in part, by a grant from Bsecham Laboratories. Requests for reprints should be addressed to Dr. Timothy C. Fabian, Department of Surgery, University of Tennessee Center for the Health Sciences, 988 Court Avenue, Room E228, Memphis, Tennessee 38183.
November
Prophylactic antibiotics are most commonly used today in surgical procedures that can be classified as clean-contaminated or in those that require implantation of prosthetic material. Clean-contaminated cases have a relatively high incidence of infection without preoperative prophylaxis. Though infections are uncommon in clean cases utilizing prosthetic implant devices, when they develop, the infections yield serious morbidity and high mortality. Patients sustaining penetrating wounds to the abdomen have a high incidence of gastrointestinal tract injuries with peritoneal contamination. Such cases are at least clean-contaminated and, with massive fecal or gastric contamination, are more appropriately classified as contaminated or dirty. In recent studies, infection rates of the wound or peritoneal cavity in these patients have been reported ranging from 6.5 to 20 percent [l-4]. Antibiotics are given to these patients after contamination and before infection develops. Hence, the term preventive, rather than prophylactic or therapeutic, is a more apt descriptive adjective. The antibiotics usually chosen for patients with penetrating abdominal wounds are those with coverage against the colonic flora, since these injuries yield the most serious infectious complications [2,5]. These regimens cover gram-negative aerobic and anaerobic rods and, to a lesser degree, gram-positive cocci. A combination of gentamicin and clindamytin is a very commonly utilized regimen. Ticarcillin also exhibits reasonable activity against these pathogens, but it is susceptible to beta-lactamases produced by gram-negative enterics and Staphylococcus aureus. Combining ticarcillin with the beta-lactamase inhibitor, clavulanic acid, would seem to significantly enhance its activity against infecting organisms in penetrating abdominal wounds. This article reports the results of a clinical trial comparing a gentamicin plus clindamycin combination with ticarcillin plus clavulanic acid for prevention of wound and/or intra-abdominal infection in patients with penetrating abdominal trauma.
29, 1985
The
American
Journal
of Medicine
Volume
79
(ruppl
5B)
157
TABLE
I
Demographic Characteristics with Penetrating Abdominal
Characteristics
Ticarciliin plus Ciavuianlc Acid
Gentamicin plus Ciindamycin
40
29
5
3
16-43 27
17-60 29
47 6
27 5
Sex Male Female Age (years) Range Average Race Black
White
TABLE
II
Assodiated Penetrating
Diseases in Patients AWdminal Trauma
Disease
Ill
Gentamicin plus Ciindamycin
1 6
0 3
0
1
2
1
1
0
1
1
Tyg of Injury in Patients with Penetrating Abdominal Trauma
lope of Wound
Ticrrciiiin plus Clavuianlt Acid
Gunshot Stab Total
TABLE
with
Ticaniilln plus Ciavulanic Acid
Asthma Hypertension Mitral valve prolapse Pancreatitis PeptiC ulcer Seizures
TABLE
of Patients Trauma
Gentamicin plus Clindamycin
29
18
24
14
53
32
Incidence of Postoperative Related to Type of Injury
IV
Infection
RESULTS Infection
Type of Wound
Number
Numbar
Percent
Stab
47 38
4 1
8.5 2.6
Total
85
5
5.9
Gunshot
PATIENTS
AND METHODS
The study was a prospective, randomized trial conducted over a six-month period at the City of Memphis Hospital. Patients selected were those undergoing exploratory laparotomy for management of penetrating abdominal injury. All patients entering the emergency department with a penetrating
199
November
29,1985
The American
wound to the torso, from the nipple line to the gluteal crease, were considered for entry into the study. Essentially all such patients with wounds secondary to gunshots underwent exploratory laparotomy, whereas those with stab wounds underwent abdominal exploration if the anterior fascia was found to be violated during local wound exploration or if obvious signs of peritoneal irritation were present. One hundred patients or their legal guardians gave consent for study entry. Patients were excluded if they had known sensitivities to any of the study drugs, associated medical conditions making evaluation difficult, or renal failure as evidenced by a serum creatinine level of more than 2.5 mg/dl. Patients were randomly assigned by their hospital numbers to one of the two treatment groups. Patients with a hospital number in which the final digit was even received gentamicin plus clindamycin, whereas those with a hospital number in which the final digit was odd received ticarcillin plus clavulanic acid. Sixty-one patients received ticarcillin plus clavuianic acid and 39 received gentamicin plus clindamycin. All medications were given intravenously over a 20- to 30-minute period. Dosages were as follows: gentamicin 1.5 mg/kg per dose, clindamycin 600 mg per dose, ticarcillin 3 g per dose, clavulanic acid 100 mg per dose. The first doses were given immediately after consent was obtained after admission to the emergency department. Gentamicin and clindamycin were given eight hours later, and a third and final dose was given eight hours after the second. Ticarcillin and clavulanic acid were given at four-hour intervals and discontinued 24 hours after admission. Complete blood cell count, platelet count, liver enzymes, bilirubin, blood urea nitrogen, creatinine, albumin, electrolytes, and urinalysis were performed at admission and one day after the last antibiotic dose to evaluate for possible toxicity. At iaparotomy, aerobic and anaerobic culture specimens were obtained from all injured hollow viscera and from the peritoneal cavity at the time of closure. All aerobic isolates were tested for antibiotic sensitivity by the disk diffusion method, and anaerobic isolates by a broth-disk elution technique [6,7]. Efficacy of the antibiotics was determined by the prevention of postoperative infections of either the wound or peritoneal cavity. Infection was defined as finding purulent discharge or material in either location.
Journal
of Mediclna
One hundred patients entered the study and 15 had to be excluded from evaluation, leaving 85 evaluable cases. Eight of the nonevaluable patients were randomly assigned to receive ticarcillin plus clavulanic acid and seven to receive gentamicin plus clindamycin. Three exclusions were due to death during or shortly after surgery, with death resulting from uncontrollable hemorrhage; two of the patients who died were assigned to receive gentamitin plus clindamycin. The other 12 exclusions resulted from dosage errors in that these patients received fewer doses than required by protocol. Wound or peritoneal sep sis did not subsequently develop in any of these 12. The demographic characteristics of both study groups are shown in Table I. Most of the patients (90 percent)
Volume 79 (suppl 5B)
SYMPOSIUM
TABLE
were men in their mid-20s, and most (87 percent) were black. There were no significant demographic differences between the treatment groups. Associated illnesses are displayed in Table II. Because of their young age, the patients were fairly healthy. Ten percent of the patients were hypertensive, which is explained by the preponderance of black patients. Both groups were again similar with respect to associated diseases. All evaluable patients sustained either stab or gunshot wounds as the mechanism of injury. Patients with gunshot wounds are more prone to infection than patients with stab wounds because of the greater extent of tissue damage and generally greater number of organ injuries. Table Ill displays the type of injury in relation to the antibiotic regimen. Gunshot wounds occurred in 55 percent of the patients treated with gentamicin plus clindamycin, and in 58 percent of patients treated with ticarcillin plus clavulanic acid. In five of the 85 (5.9 percent) patients, infections developed. Table IV shows infectious morbidity relative to the type of injury. Infection developed in four of 47 (8.5 percent) patients with gunshot wounds and in only one of 38 (2.6 percent) patients with stab wounds. Those patients with injuries to the large intestine are generally at highest risk of postoperative infection because of bacterial colonization. Table V illustrates the randomization procedure with respect to gastrointestinal tract (hollow viscus) injury and subsequent infection. Of the 53 patients who received ticarcillin plus clavulanic acid, 55 percent had gastrointestinal injury, 21 percent had intraabdominal organ injuries but no gastrointestinal injury, and 24 percent had negative findings on laparotomy. The corresponding percentages for the patients who received gentamicin plus clindamycin are 59, 28, and 23 percent, respectively. Four of the five infections occurred in those with gastrointestinal tract injuries. The organ injuries in the two groups are listed in Table VI. The treatment failures in each group are listed in Table VII. Wound infection occurred in one of the 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid. Infection developed in four of the 32 (12 percent) patients
TABLE Age of Patient
VIII
Summary
of Data Pertaining
Mechanism
Regimen
39
Gunshot
wound
33
Gunshot
wound
17
Stab wound
30
Gunshot
wound
22
Gunshot
wound
Gentamicin plus clindamycin Gentamicin plus clindamycin Gentamicin plus clindamycin Ticarcillin plus clavulanic acid Gentamicin plus clindamycin
to Patients
ON BETA-IACTAMASE
V
INHIBITION-FABIAN
Incidence of Postoperatlve Infection Related to Presence or Absence of Hollow Viscus Gastrointestinal Injury
Ticanillln
Gastrointestinal injury No gastrointestinal injury Negative findings laparotomy
29 (3.4)’
19 (16)
40 (8.3)
9 (11)
20 (5)
13 (0)
4 (0)
17 (0)
53 (1.9)
32 (12)
85 (5.9)
11 (0)
in parentheses
VI
are percent
with infection.
Incidence of Postoperative Infection Associated with Organ Injury infection Number of
injuries
Organ Liver Spleen Stomach Small bowel Colon Major vascular Other
Number
17 7 19 28 17 7 18
Total
VII
Treatment
Type of Infection
Failures Ticarciilin plus Ciavulanlc Acid
Gentamicin plus Clindamycin
Wound intra-abdominal Both
1 0 0
2 0 2
Total
1 (1.9)
4 (12)
with Infection
inferior
Infecting Organisms
mesenteric
vein,
bowel,
E. co&
H. influenzae
Enterococci,
wound
Small bowel, gallbladder
November 29, 1985
5.9 14 5.3 IO 12 14 28
113
TABLE
Small bowel, spleen Colon
Small
Percent
1 1 1 3 2 1 5
Organs injured
Kidney
GOth Regimens
on
Total
TABLE
Gentamicin plus Clindamycin
plus Clavuianic Acid
injuly
*Numbers
and BOLDREGHINI
S. aureus, rectum, stomach,
bladder,
pancreas
liver, pancreas,
The American Journal of Medlcfne
Klebsiella Proteus
mirabilis
E. coli, Klebsiella, Pseudomonas aeruginosa, enterococci Enterocccci
Volume 79 (auppi 56)
159
who received gentamicin plus clindamycin; two had wound infections, and two had both wound and intraperitoneat infections. Application of chi-square analysis to the data demonstrated no statistically significant difference between the two treatment groups. A summary of the data concerning patients with infection is presented in Table VIII. No adverse effects could be attributed to any of the antibiotics. There were no deaths among the 85 evaluable patients. COMMENTS
Afthough several investigators have demonstrated the efficacy of prophylactic antibiotics in elective clean-contaminated surgery [8-121, the same cannot be said for penetrating trauma. There have been no prospective, placebo-controlled studies reported up to this time. Given the medicolegal climate of today, it is questionable whether such will be undertaken. Regardless, there is some precedent for objectively justifying the early use of antibiotics to prevent infection in this situation. In 1972, Fullen et al [13] reported a retrospective analysis of antibiotic usage in 295 patients who sustained penetrating abdominal wounds. They noted that when antibiotics were given to victims of penetrating abdominal trauma shortly after admission versus administration beginning postop eratively, the infection rates were 7 and 30 percent, respectively. These data correlate very well with the animal work reported by Burke [14], which has been the founda-
1.
2.
3.
4.
5.
8.
7.
8.
150
Mbawa NC, Rose RA, Schumer W: Evaluation of efficacy of cefoxitin in the prevention of abdominal trauma infections. Am Swg 1983; 49: 582-585. Fabian TC, Hoefling SJ, Strom PR, Stone HH: Use of antibiotic prophylaxis in penetrating abdominal trauma. Clin Ther 1982; 5: 38-47. Hofstetter SR, Pachter HL, Bailey AA, Coppa GF: A prospective comparison of two regimens of prophylactic antibiotics in abdominal trauma: cefoxitin versus triple drug. J Trauma 1984; 24: 397-310. Moore FA, Moore EE, Mill MR: Preoperative antibiotics for abdominal gunshot wounds: a prospective, randomized study. Am J Surg 1983; 148: 782-785. Gentry LO, Feliciano DV, Lea AS, Short HD, Mattox KL, Jordan GL: Perioperative antibiotic therapy for penetrating injuries of the abdomen. Ann Surg 1984; 200: 581-588. Barry AL, Thornsberry C: Susceptibility testing: diffusion tests. In: Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ, eds. Manual of clinical microbiology. Washington, DC: American Society of Microbiology, 1985; 978-987. Sutter VL: Susceptibility testing of anaerobes. In: Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ, eds. Manual of clinical microbiology. Washington, DC: American Society of Microbiology, 1985; 988-990. Chetlin SH, Elliott DW: Preoperative antibiotics in biliary sur-
November
29,lgeg
The
American Journal
of MuMine
tion for rational application of antibiotic prophylaxis. Delaying the administration of antibiotics beyond three to four hours after contamination appears to be of liffle or no benefit. The optimal duration of treatment with antibiotics in penetrating abdominal trauma appears to parallel that for elective prophylaxis. Stone et al [15] first demonstrated that 24-hour coverage was equal in efficacy to fiveday antibiotic administration in patients with penetrating abdominal injury. Subsequent reports have substantiated the efficacy of this short, perioperative dosage approach [2,13,18]. The 5.9 percent overall infection rate in the current report would seem to further support that principle. Considering the variety of organisms isolated from the infections in this study (Table VIII), which is to be expected with gastrointestinal tract injury, the addition of clavulanic acid to ticarcillin would appear to be a good regimen for patients with penetrating abdominal trauma. The majority of these organisms are potential beta-lactamase producers. The fact that infection developed in only one of 53 patients randomly assigned to receive ticarcillin plus clavulanic acid substantiates the efficacy of this combination. Assuming that no beta error in statistical interpretation is present, ticarcillin plus clavulanic acid is at least as effective in preventing postoperative sepsis in penetrating abdominal trauma as is the combination of gentamicin plus clindamycin.
9.
10.
11.
12.
13.
14.
15.
16.
Volume
gery. Arch Surg 1973; 107: 319-323. Evans C, Pollock AV: The reductiin of surgical wound infections by prophylactic parenteral cephaloridine: a controlled clinical tnat. Br J Surg 1973; 80: 434-437. Keiahlev MRB. Drvsdale RB. Quoraishi AH. et al: Antibiotics in biiary disease: the relativelmportance of antibiitic concentration in bile and serum. Gut 1978; 17: 495-500. Polk HC Jr, Lopez-Mayor JF: Postoperative wound infection: a prospective study of determinant factors and prevention. Surgery 1989; 88: 97-102. Stone HH, Hooper CA, Kolb LD, et al: Antibiotic prophylaxis in gastric, biliary, and colonic surgery. Ann Surg 1978; 184: 443450. Fullen WD, Hunt J, Altemeier WA: Prophylactic antibiotics in penetrating wounds of the abdomen. J Trauma 1972; 12: 282288. Burke JF: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1981; 59: 181-188. Stone HH, Haney BB, Kolb LD, et al: Prophylactic and preventive antibiotic therapy: timing, duration, and economics. Ann Surg 1979; 189: 891-898. Oreskovich AM, Dellinger EP, Lennard ES, et al: Duration of preventive antibiotic administration for penetrating abdominal trauma. Arch Surg 1982; 117: 200-205.
79 (8uppl58)
A comparative trial of ticarcillin plus clavulanlc acid with gentamicin plus clindamycin was conducted in 85 patients who sustained pena bating abdominal wounds. The antibiotic regimens were given for 24 hours. The overall wound and/or intra-abdominal infection rate was 5.9 percent. Patients who sustained gunshot wounds to hollow viscera were at highest risk. lnfectlon developed In one of 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid and In four of 32 (12 percent) patients who received gentamlcln plus clindamycin. These differences were not statistically significant. These data support the use of short-course (24-hour) antibiotic therapy In this clinical setting and demonstrate that ticarcillin plus clavulanlc acid is efficacious as a preventive antibiotic combination.
TIMOTHY C. FABIAN, M.D. SANDRA J. BOLDREGHINI, R.N. Memphis,
Tennessee
From the Department of Surgery, University of Tennessee Center for the Health Sciences, Memphis, Tennessee. This work was supported, in part, by a grant from Bsecham Laboratories. Requests for reprints should be addressed to Dr. Timothy C. Fabian, Department of Surgery, University of Tennessee Center for the Health Sciences, 988 Court Avenue, Room E228, Memphis, Tennessee 38183.
November
Prophylactic antibiotics are most commonly used today in surgical procedures that can be classified as clean-contaminated or in those that require implantation of prosthetic material. Clean-contaminated cases have a relatively high incidence of infection without preoperative prophylaxis. Though infections are uncommon in clean cases utilizing prosthetic implant devices, when they develop, the infections yield serious morbidity and high mortality. Patients sustaining penetrating wounds to the abdomen have a high incidence of gastrointestinal tract injuries with peritoneal contamination. Such cases are at least clean-contaminated and, with massive fecal or gastric contamination, are more appropriately classified as contaminated or dirty. In recent studies, infection rates of the wound or peritoneal cavity in these patients have been reported ranging from 6.5 to 20 percent [l-4]. Antibiotics are given to these patients after contamination and before infection develops. Hence, the term preventive, rather than prophylactic or therapeutic, is a more apt descriptive adjective. The antibiotics usually chosen for patients with penetrating abdominal wounds are those with coverage against the colonic flora, since these injuries yield the most serious infectious complications [2,5]. These regimens cover gram-negative aerobic and anaerobic rods and, to a lesser degree, gram-positive cocci. A combination of gentamicin and clindamytin is a very commonly utilized regimen. Ticarcillin also exhibits reasonable activity against these pathogens, but it is susceptible to beta-lactamases produced by gram-negative enterics and Staphylococcus aureus. Combining ticarcillin with the beta-lactamase inhibitor, clavulanic acid, would seem to significantly enhance its activity against infecting organisms in penetrating abdominal wounds. This article reports the results of a clinical trial comparing a gentamicin plus clindamycin combination with ticarcillin plus clavulanic acid for prevention of wound and/or intra-abdominal infection in patients with penetrating abdominal trauma.
29, 1985
The
American
Journal
of Medicine
Volume
79
(ruppl
5B)
157
TABLE
I
Demographic Characteristics with Penetrating Abdominal
Characteristics
Ticarciliin plus Ciavuianlc Acid
Gentamicin plus Ciindamycin
40
29
5
3
16-43 27
17-60 29
47 6
27 5
Sex Male Female Age (years) Range Average Race Black
White
TABLE
II
Assodiated Penetrating
Diseases in Patients AWdminal Trauma
Disease
Ill
Gentamicin plus Ciindamycin
1 6
0 3
0
1
2
1
1
0
1
1
Tyg of Injury in Patients with Penetrating Abdominal Trauma
lope of Wound
Ticrrciiiin plus Clavuianlt Acid
Gunshot Stab Total
TABLE
with
Ticaniilln plus Ciavulanic Acid
Asthma Hypertension Mitral valve prolapse Pancreatitis PeptiC ulcer Seizures
TABLE
of Patients Trauma
Gentamicin plus Clindamycin
29
18
24
14
53
32
Incidence of Postoperative Related to Type of Injury
IV
Infection
RESULTS Infection
Type of Wound
Number
Numbar
Percent
Stab
47 38
4 1
8.5 2.6
Total
85
5
5.9
Gunshot
PATIENTS
AND METHODS
The study was a prospective, randomized trial conducted over a six-month period at the City of Memphis Hospital. Patients selected were those undergoing exploratory laparotomy for management of penetrating abdominal injury. All patients entering the emergency department with a penetrating
199
November
29,1985
The American
wound to the torso, from the nipple line to the gluteal crease, were considered for entry into the study. Essentially all such patients with wounds secondary to gunshots underwent exploratory laparotomy, whereas those with stab wounds underwent abdominal exploration if the anterior fascia was found to be violated during local wound exploration or if obvious signs of peritoneal irritation were present. One hundred patients or their legal guardians gave consent for study entry. Patients were excluded if they had known sensitivities to any of the study drugs, associated medical conditions making evaluation difficult, or renal failure as evidenced by a serum creatinine level of more than 2.5 mg/dl. Patients were randomly assigned by their hospital numbers to one of the two treatment groups. Patients with a hospital number in which the final digit was even received gentamicin plus clindamycin, whereas those with a hospital number in which the final digit was odd received ticarcillin plus clavulanic acid. Sixty-one patients received ticarcillin plus clavuianic acid and 39 received gentamicin plus clindamycin. All medications were given intravenously over a 20- to 30-minute period. Dosages were as follows: gentamicin 1.5 mg/kg per dose, clindamycin 600 mg per dose, ticarcillin 3 g per dose, clavulanic acid 100 mg per dose. The first doses were given immediately after consent was obtained after admission to the emergency department. Gentamicin and clindamycin were given eight hours later, and a third and final dose was given eight hours after the second. Ticarcillin and clavulanic acid were given at four-hour intervals and discontinued 24 hours after admission. Complete blood cell count, platelet count, liver enzymes, bilirubin, blood urea nitrogen, creatinine, albumin, electrolytes, and urinalysis were performed at admission and one day after the last antibiotic dose to evaluate for possible toxicity. At iaparotomy, aerobic and anaerobic culture specimens were obtained from all injured hollow viscera and from the peritoneal cavity at the time of closure. All aerobic isolates were tested for antibiotic sensitivity by the disk diffusion method, and anaerobic isolates by a broth-disk elution technique [6,7]. Efficacy of the antibiotics was determined by the prevention of postoperative infections of either the wound or peritoneal cavity. Infection was defined as finding purulent discharge or material in either location.
Journal
of Mediclna
One hundred patients entered the study and 15 had to be excluded from evaluation, leaving 85 evaluable cases. Eight of the nonevaluable patients were randomly assigned to receive ticarcillin plus clavulanic acid and seven to receive gentamicin plus clindamycin. Three exclusions were due to death during or shortly after surgery, with death resulting from uncontrollable hemorrhage; two of the patients who died were assigned to receive gentamitin plus clindamycin. The other 12 exclusions resulted from dosage errors in that these patients received fewer doses than required by protocol. Wound or peritoneal sep sis did not subsequently develop in any of these 12. The demographic characteristics of both study groups are shown in Table I. Most of the patients (90 percent)
Volume 79 (suppl 5B)
SYMPOSIUM
TABLE
were men in their mid-20s, and most (87 percent) were black. There were no significant demographic differences between the treatment groups. Associated illnesses are displayed in Table II. Because of their young age, the patients were fairly healthy. Ten percent of the patients were hypertensive, which is explained by the preponderance of black patients. Both groups were again similar with respect to associated diseases. All evaluable patients sustained either stab or gunshot wounds as the mechanism of injury. Patients with gunshot wounds are more prone to infection than patients with stab wounds because of the greater extent of tissue damage and generally greater number of organ injuries. Table Ill displays the type of injury in relation to the antibiotic regimen. Gunshot wounds occurred in 55 percent of the patients treated with gentamicin plus clindamycin, and in 58 percent of patients treated with ticarcillin plus clavulanic acid. In five of the 85 (5.9 percent) patients, infections developed. Table IV shows infectious morbidity relative to the type of injury. Infection developed in four of 47 (8.5 percent) patients with gunshot wounds and in only one of 38 (2.6 percent) patients with stab wounds. Those patients with injuries to the large intestine are generally at highest risk of postoperative infection because of bacterial colonization. Table V illustrates the randomization procedure with respect to gastrointestinal tract (hollow viscus) injury and subsequent infection. Of the 53 patients who received ticarcillin plus clavulanic acid, 55 percent had gastrointestinal injury, 21 percent had intraabdominal organ injuries but no gastrointestinal injury, and 24 percent had negative findings on laparotomy. The corresponding percentages for the patients who received gentamicin plus clindamycin are 59, 28, and 23 percent, respectively. Four of the five infections occurred in those with gastrointestinal tract injuries. The organ injuries in the two groups are listed in Table VI. The treatment failures in each group are listed in Table VII. Wound infection occurred in one of the 53 (1.9 percent) patients who received ticarcillin plus clavulanic acid. Infection developed in four of the 32 (12 percent) patients
TABLE Age of Patient
VIII
Summary
of Data Pertaining
Mechanism
Regimen
39
Gunshot
wound
33
Gunshot
wound
17
Stab wound
30
Gunshot
wound
22
Gunshot
wound
Gentamicin plus clindamycin Gentamicin plus clindamycin Gentamicin plus clindamycin Ticarcillin plus clavulanic acid Gentamicin plus clindamycin
to Patients
ON BETA-IACTAMASE
V
INHIBITION-FABIAN
Incidence of Postoperatlve Infection Related to Presence or Absence of Hollow Viscus Gastrointestinal Injury
Ticanillln
Gastrointestinal injury No gastrointestinal injury Negative findings laparotomy
29 (3.4)’
19 (16)
40 (8.3)
9 (11)
20 (5)
13 (0)
4 (0)
17 (0)
53 (1.9)
32 (12)
85 (5.9)
11 (0)
in parentheses
VI
are percent
with infection.
Incidence of Postoperative Infection Associated with Organ Injury infection Number of
injuries
Organ Liver Spleen Stomach Small bowel Colon Major vascular Other
Number
17 7 19 28 17 7 18
Total
VII
Treatment
Type of Infection
Failures Ticarciilin plus Ciavulanlc Acid
Gentamicin plus Clindamycin
Wound intra-abdominal Both
1 0 0
2 0 2
Total
1 (1.9)
4 (12)
with Infection
inferior
Infecting Organisms
mesenteric
vein,
bowel,
E. co&
H. influenzae
Enterococci,
wound
Small bowel, gallbladder
November 29, 1985
5.9 14 5.3 IO 12 14 28
113
TABLE
Small bowel, spleen Colon
Small
Percent
1 1 1 3 2 1 5
Organs injured
Kidney
GOth Regimens
on
Total
TABLE
Gentamicin plus Clindamycin
plus Clavuianic Acid
injuly
*Numbers
and BOLDREGHINI
S. aureus, rectum, stomach,
bladder,
pancreas
liver, pancreas,
The American Journal of Medlcfne
Klebsiella Proteus
mirabilis
E. coli, Klebsiella, Pseudomonas aeruginosa, enterococci Enterocccci
Volume 79 (auppi 56)
159
who received gentamicin plus clindamycin; two had wound infections, and two had both wound and intraperitoneat infections. Application of chi-square analysis to the data demonstrated no statistically significant difference between the two treatment groups. A summary of the data concerning patients with infection is presented in Table VIII. No adverse effects could be attributed to any of the antibiotics. There were no deaths among the 85 evaluable patients. COMMENTS
Afthough several investigators have demonstrated the efficacy of prophylactic antibiotics in elective clean-contaminated surgery [8-121, the same cannot be said for penetrating trauma. There have been no prospective, placebo-controlled studies reported up to this time. Given the medicolegal climate of today, it is questionable whether such will be undertaken. Regardless, there is some precedent for objectively justifying the early use of antibiotics to prevent infection in this situation. In 1972, Fullen et al [13] reported a retrospective analysis of antibiotic usage in 295 patients who sustained penetrating abdominal wounds. They noted that when antibiotics were given to victims of penetrating abdominal trauma shortly after admission versus administration beginning postop eratively, the infection rates were 7 and 30 percent, respectively. These data correlate very well with the animal work reported by Burke [14], which has been the founda-
1.
2.
3.
4.
5.
8.
7.
8.
150
Mbawa NC, Rose RA, Schumer W: Evaluation of efficacy of cefoxitin in the prevention of abdominal trauma infections. Am Swg 1983; 49: 582-585. Fabian TC, Hoefling SJ, Strom PR, Stone HH: Use of antibiotic prophylaxis in penetrating abdominal trauma. Clin Ther 1982; 5: 38-47. Hofstetter SR, Pachter HL, Bailey AA, Coppa GF: A prospective comparison of two regimens of prophylactic antibiotics in abdominal trauma: cefoxitin versus triple drug. J Trauma 1984; 24: 397-310. Moore FA, Moore EE, Mill MR: Preoperative antibiotics for abdominal gunshot wounds: a prospective, randomized study. Am J Surg 1983; 148: 782-785. Gentry LO, Feliciano DV, Lea AS, Short HD, Mattox KL, Jordan GL: Perioperative antibiotic therapy for penetrating injuries of the abdomen. Ann Surg 1984; 200: 581-588. Barry AL, Thornsberry C: Susceptibility testing: diffusion tests. In: Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ, eds. Manual of clinical microbiology. Washington, DC: American Society of Microbiology, 1985; 978-987. Sutter VL: Susceptibility testing of anaerobes. In: Lennette EH, Balows A, Hausler WJ Jr, Shadomy HJ, eds. Manual of clinical microbiology. Washington, DC: American Society of Microbiology, 1985; 988-990. Chetlin SH, Elliott DW: Preoperative antibiotics in biliary sur-
November
29,lgeg
The
American Journal
of MuMine
tion for rational application of antibiotic prophylaxis. Delaying the administration of antibiotics beyond three to four hours after contamination appears to be of liffle or no benefit. The optimal duration of treatment with antibiotics in penetrating abdominal trauma appears to parallel that for elective prophylaxis. Stone et al [15] first demonstrated that 24-hour coverage was equal in efficacy to fiveday antibiotic administration in patients with penetrating abdominal injury. Subsequent reports have substantiated the efficacy of this short, perioperative dosage approach [2,13,18]. The 5.9 percent overall infection rate in the current report would seem to further support that principle. Considering the variety of organisms isolated from the infections in this study (Table VIII), which is to be expected with gastrointestinal tract injury, the addition of clavulanic acid to ticarcillin would appear to be a good regimen for patients with penetrating abdominal trauma. The majority of these organisms are potential beta-lactamase producers. The fact that infection developed in only one of 53 patients randomly assigned to receive ticarcillin plus clavulanic acid substantiates the efficacy of this combination. Assuming that no beta error in statistical interpretation is present, ticarcillin plus clavulanic acid is at least as effective in preventing postoperative sepsis in penetrating abdominal trauma as is the combination of gentamicin plus clindamycin.
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gery. Arch Surg 1973; 107: 319-323. Evans C, Pollock AV: The reductiin of surgical wound infections by prophylactic parenteral cephaloridine: a controlled clinical tnat. Br J Surg 1973; 80: 434-437. Keiahlev MRB. Drvsdale RB. Quoraishi AH. et al: Antibiotics in biiary disease: the relativelmportance of antibiitic concentration in bile and serum. Gut 1978; 17: 495-500. Polk HC Jr, Lopez-Mayor JF: Postoperative wound infection: a prospective study of determinant factors and prevention. Surgery 1989; 88: 97-102. Stone HH, Hooper CA, Kolb LD, et al: Antibiotic prophylaxis in gastric, biliary, and colonic surgery. Ann Surg 1978; 184: 443450. Fullen WD, Hunt J, Altemeier WA: Prophylactic antibiotics in penetrating wounds of the abdomen. J Trauma 1972; 12: 282288. Burke JF: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1981; 59: 181-188. Stone HH, Haney BB, Kolb LD, et al: Prophylactic and preventive antibiotic therapy: timing, duration, and economics. Ann Surg 1979; 189: 891-898. Oreskovich AM, Dellinger EP, Lennard ES, et al: Duration of preventive antibiotic administration for penetrating abdominal trauma. Arch Surg 1982; 117: 200-205.
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