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Pre- and postoperative prophylactic use of cephaloridine
Pre- and Postoperative Prophylactic Use of Cephaloridine A Study of 201 Cases MARCUS
L. DILLON,
RAYMOND
The major factors demonstrated to influence the development of wound infection are the number and type of infecting organisms, disease affecting the host immunologic capability to respond, local factirs (such as foreign bodies) which may enhance the development of an infection by two- to a hundred thousand-fold, and the method of reporting [I-3]. As more controlled prospective studies are being reported, the efficacy of prophylactic antibiotics is becoming established for operations in which the possibility of infection is high and host resistance is low. The importance of prophylactic antibiotics in clean wounds in which the number of bacteria is small and host resistance is good is difficult to evaluate because of the marked effects which local wound factors can have on enhancement [4-e]. This is a report on 201 patients who received cephaloridine prophylactically for five to seven days to prevent wound infection. There were eleven infections or 5.5 per cent. Material
and Methods
Cephaloridine was given to one hundred thirteen patients preoperatively and to eighty-eight patients postoperatively. There were seven infections (6,2 per cent) in the preoperative prophylactic group and four infections (4.6 per cent) in the postoperative group. Table I shows the dosage schedules used. Twenty patients received cephaloridine intravenously for one to four days and then intramuscularly. At the start of the study, recommended dosage schedules had not been established. The large number of patients who were given 1 gm intramuscularly every eight hours probably reflects the fact that the drug was packaged in 1 gm vials, blood levels had been maintained for eight hours [7], and the patients appreciated having only three injections a day. All of the pa-
W. POSTLETHWAIT,
Volume
122, July 1971
MD, Durham,
North Carolina
tients in whom infection developed had been on this dosage schedule. The distribution of patients was similar when the operations were classified as clean or potentially dirty. In the preoperative antibiotic group eighty-seven (‘77 per cent) were clean and twenty-six (23 per cent) potentially dirty. In the postoperative antibiotic group sixty (67.5 per cent) were clean and twenty-eight (32.5 per cent) potenti,ally dirty. The distribution of infections in relation to this classification is shown in Table II. The distribution of patients as to similarity of operation was good except in two groups. Twenty-seven of thirty patients with open heart surgery received preoperative antibiotics, and only nine of twenty-nine patients h’aving intestinal surgery received preoperative antibiotics. A summary of the operation, location of the wound infected, the organisms involved, and the sensitivity of the organism to cephaloridine are given for the preoperative and for postoperative antibiotic group in Tables III and IV, respectively. Comments
On cursory examination, the infection rate seems inordinately high, but three of the infections in clean wounds occurred in femoral wounds in association with lymphoceles. Two other draining lymphoceles occurred in the preoperative proTABLE I
Dosage Schedule for Cephaloridine
Patients
Per cent
Dosage
120
59.5
1 gm intramuscularly every eight hours
29 14 11 7 20
14.5 7.0 5.5 3.5 10.0
1 gm intramuscularly every six hours 0.5 gm intramuscularly every six hours 0.5 gm intramuscularlyeveryeight hours 1 gm intramuscularly every four hours 3 to 9 gm intravenously per day
TABLE II
Infection Rates with Prophylactic Antibiotics Preoperative Antibiotics
Cases From the Department of Surgery, Veterans Administration Hospital and Duke Medical Center, Durham, North Carolina. This work was sup ported by a grant from Eli Lilly and Co.
MD, Durham, North Carolina
Clean Dirty
Number 87 26
Number of Infections 3 (3.5%) 4 (15.4%)
Postoperative Antibiotics Number 60 28
Number of Infections 10.7%) 3 (10.3%)
61
Dillon and Postlethwait
rABLE
III
Preoperative
Prophylactic
Antibiotics
Wound Operation
Organism and Sensitivity
Infected Clean Cases
1. Open mitral replace-
Thorax
Proteus
ment 2. Aortoiliac
femoral
Femoral
Aerobacter-Klebsiella
(S)
endarterectomy 3. Aortoiliac femoral
Femoral
Aerobacter-Klebsiella
(S)
endarterectomy
mirabilis
(R)
Escherichia coli (S) Staphylococcus albus (S) Dirty Cases
1. Amputation 2. Revision
of toe
Stump
Staphylococcus Gram-negative
of amputation
Stump
Staphylococcus aureus (S) 10 ml of pus obtained by needle aspiration from the wound was not cultured Proteus mirabilis (S)
3. Cervical sympathectomy
4. Femoral
Neck
popliteal
vein
Femoral
aureus (S) rod (R)
bypass Key: S = sensitive dine.
TABLE
to cephaloridine;
Postoperative
IV
R = resistant
Prophylactic
Antibiotics Organism and Sensitivity
Wound Infected
Operation
to cephalori-
Clean Cases
1. Open mitral
Streptococcus fecalis Aerobacter-Klebsiella Staphylococcus albus (S) Mima polymorpha (R) Escherichia coli (S)
Bilateral Femoral
valvulotomy
Dirty Cases
1. Cholecystectomy 2. Gastric
Abdominal staysuture Abdominal
resection
wound Abdominal wound
3. Cholecystojejunostomy
Key: S = sensitive dine.
TABLE V
Comparative
aureus
(S)
Proteus vulgaris (R) Streptococcus fecalis (S) Escherichia coli (S) Intermediate coli #l (R) Intermediate coli #2 (S)
to cephaloridine;
Prophylactic Use of Cephaloridine
62
Staphylococcus
R = resistant
Infection
Rates
Selective Use of Other Antibiotics
Per cent
Number of Patients
to cephalori-
Cases
Number of Patients
Clean
147
2.7
75
a
Dirty
54
13.0
54
35
Per cent
No Antibiotics Given Number of Patients
Per cent
149 64
2.1 8.0
phylactic group, without local inflammation or positive culture, and are not listed as infections. The development of a lymphocele after iliofemoral vascular procedures is probably a much more frequent complication than has been recognized. Mori [I] found an incidence as high as 65 per cent after radical #pelvic lymphadenectomy and noted that the more lymphatics interrupted, the higher the incidence ,of lymphocele. The seriousness of this complication in vascular surgery depends on the association of plastic graft materials with wound breakdown. The fourth infected clean case occurred with a resi,stant organism after thoracic wound disruption from closed cardiac massage. All of the potentially dirty cases in which preoperative prophylactic antibiotics had been given and which became infected had a major contributing factor of surgical judgment. The toe amputation was inadequate with ischemic necrosis of the wound edges preceding the infection. The revised amputation was for osteomyelitis and the wound was closed at the time of revision. The cervical sympathectomy was performed in the presence of an early piostoperative Staphylococcus aureus hernia infection. The femoropopliteal vein bypass was performed before adequate debridement was carried out in a patient with osteomyelitis of the heel due to Proteus mirabilis sensitive to cephaloridine. One patient in the postoperative prophylactic group became infected after pancreatitis which required drainage of the pancreas on the fourth and sixth postoperative days. The data do not reflect appreciable differences from the start of prophylactic antibiotic therapy but emphasize the influences of host resistance, coexisting disease, inherent complications of certain operative procedures, and the influence which surgical judgment has on the ,subsequent development of postoperative infectton. To have an antibiotic capable of compensating fior all these contingencies would, indeed, be fortunate. A comparison of infection rates, using cephaloridine prophylactically, to infection rates when antibiotics are used at the discretion of the surgeon is given in Table V [8]. This is of some practical importance since in the general practice of surgery the use of antibi&.ics is by discretion. The infection rate is lowest in that group (of patients in whom the surgeon thought that antibiotics were not neoeasary and highest in those patients the surgeon thought needed antibiotics. A judgment as to need was not made for patients receiving cephaloridine and it appears to be a very effective antibiotic to use prcnphylactically. Almost 80 per cent of the anti-
The American
Journal
of Surgery
Prophylactic
biotics used selectively were combinations of penicillin and streptomycin or others with gram-positive and gram-negative spectra except cephaloridine which was not available. Summary
Cephaloridine was used as a prophylactic antibiotic preoperatively in one hundred thirteen patients and postoperatively in eighty-eight. The inordinately high infection rates (preoperative prophylactic group, 6.2 per cent; postoperative prophylactic group, 4.6 per cent) are analyzed and found to be associated with factors that enhance the possibility of wound infection beyond the capabilities of all antibiotics. Antibiotics cannot yet be used as substitutes for maintenance of sterile technic, application of basic surgical principles, judgment in selection, and timing of surgical procedures.
Volume
122, July 1971
Use of Cephaloridine
References 1. Burke JF: Wound infection and early inflammation. Monogr Sorg Sci 1: 301, 1964. 2. Cohen LS. Peketv FR. Cluff LE: Studies of the epidemio,logy’of staihylkoccal infection. V. The repoking of hospital-acquired infection. JAMA 180: 805, 1962. 3. Elek WD, Conen PE: The virulence of Staphylococcus pyrogens for man. A study of the problems of wound infection. Brit J Exp Path 38: 573, 1957. 4. Alexander JW, Altemier WA: Penicillin prophylaxis of experimental staphylococcal wound infection. Surg Gynec Obstet 120: 243, 1965. 5. Bernard HR, Cole WR: The prophylaxis of surgical infection. The effect of prophylactic antimicrobial drugs on the incidence of infection following potentially contaminated operations. Surgery 56: 151, 1964. 6. Polk HC Jr., Lopez-Major JF: Postoperative wound infection. A prospective study of determimnant factors and prevention. Surgery 66: 97, 1969. 7. Kislak JW, Steinhauer BW, Finland M: Cephaloridine; activity in vitro and absorption and urinary excretion in normal young men. Amer J Med Sci 251: 433, 1966. 8. Dillon ML, Postlethwait RW, Bowling KA: Operative wound cultures and wound infections. Ann Surg 170: 1029, 1969.
63
L. DILLON,
RAYMOND
The major factors demonstrated to influence the development of wound infection are the number and type of infecting organisms, disease affecting the host immunologic capability to respond, local factirs (such as foreign bodies) which may enhance the development of an infection by two- to a hundred thousand-fold, and the method of reporting [I-3]. As more controlled prospective studies are being reported, the efficacy of prophylactic antibiotics is becoming established for operations in which the possibility of infection is high and host resistance is low. The importance of prophylactic antibiotics in clean wounds in which the number of bacteria is small and host resistance is good is difficult to evaluate because of the marked effects which local wound factors can have on enhancement [4-e]. This is a report on 201 patients who received cephaloridine prophylactically for five to seven days to prevent wound infection. There were eleven infections or 5.5 per cent. Material
and Methods
Cephaloridine was given to one hundred thirteen patients preoperatively and to eighty-eight patients postoperatively. There were seven infections (6,2 per cent) in the preoperative prophylactic group and four infections (4.6 per cent) in the postoperative group. Table I shows the dosage schedules used. Twenty patients received cephaloridine intravenously for one to four days and then intramuscularly. At the start of the study, recommended dosage schedules had not been established. The large number of patients who were given 1 gm intramuscularly every eight hours probably reflects the fact that the drug was packaged in 1 gm vials, blood levels had been maintained for eight hours [7], and the patients appreciated having only three injections a day. All of the pa-
W. POSTLETHWAIT,
Volume
122, July 1971
MD, Durham,
North Carolina
tients in whom infection developed had been on this dosage schedule. The distribution of patients was similar when the operations were classified as clean or potentially dirty. In the preoperative antibiotic group eighty-seven (‘77 per cent) were clean and twenty-six (23 per cent) potentially dirty. In the postoperative antibiotic group sixty (67.5 per cent) were clean and twenty-eight (32.5 per cent) potenti,ally dirty. The distribution of infections in relation to this classification is shown in Table II. The distribution of patients as to similarity of operation was good except in two groups. Twenty-seven of thirty patients with open heart surgery received preoperative antibiotics, and only nine of twenty-nine patients h’aving intestinal surgery received preoperative antibiotics. A summary of the operation, location of the wound infected, the organisms involved, and the sensitivity of the organism to cephaloridine are given for the preoperative and for postoperative antibiotic group in Tables III and IV, respectively. Comments
On cursory examination, the infection rate seems inordinately high, but three of the infections in clean wounds occurred in femoral wounds in association with lymphoceles. Two other draining lymphoceles occurred in the preoperative proTABLE I
Dosage Schedule for Cephaloridine
Patients
Per cent
Dosage
120
59.5
1 gm intramuscularly every eight hours
29 14 11 7 20
14.5 7.0 5.5 3.5 10.0
1 gm intramuscularly every six hours 0.5 gm intramuscularly every six hours 0.5 gm intramuscularlyeveryeight hours 1 gm intramuscularly every four hours 3 to 9 gm intravenously per day
TABLE II
Infection Rates with Prophylactic Antibiotics Preoperative Antibiotics
Cases From the Department of Surgery, Veterans Administration Hospital and Duke Medical Center, Durham, North Carolina. This work was sup ported by a grant from Eli Lilly and Co.
MD, Durham, North Carolina
Clean Dirty
Number 87 26
Number of Infections 3 (3.5%) 4 (15.4%)
Postoperative Antibiotics Number 60 28
Number of Infections 10.7%) 3 (10.3%)
61
Dillon and Postlethwait
rABLE
III
Preoperative
Prophylactic
Antibiotics
Wound Operation
Organism and Sensitivity
Infected Clean Cases
1. Open mitral replace-
Thorax
Proteus
ment 2. Aortoiliac
femoral
Femoral
Aerobacter-Klebsiella
(S)
endarterectomy 3. Aortoiliac femoral
Femoral
Aerobacter-Klebsiella
(S)
endarterectomy
mirabilis
(R)
Escherichia coli (S) Staphylococcus albus (S) Dirty Cases
1. Amputation 2. Revision
of toe
Stump
Staphylococcus Gram-negative
of amputation
Stump
Staphylococcus aureus (S) 10 ml of pus obtained by needle aspiration from the wound was not cultured Proteus mirabilis (S)
3. Cervical sympathectomy
4. Femoral
Neck
popliteal
vein
Femoral
aureus (S) rod (R)
bypass Key: S = sensitive dine.
TABLE
to cephaloridine;
Postoperative
IV
R = resistant
Prophylactic
Antibiotics Organism and Sensitivity
Wound Infected
Operation
to cephalori-
Clean Cases
1. Open mitral
Streptococcus fecalis Aerobacter-Klebsiella Staphylococcus albus (S) Mima polymorpha (R) Escherichia coli (S)
Bilateral Femoral
valvulotomy
Dirty Cases
1. Cholecystectomy 2. Gastric
Abdominal staysuture Abdominal
resection
wound Abdominal wound
3. Cholecystojejunostomy
Key: S = sensitive dine.
TABLE V
Comparative
aureus
(S)
Proteus vulgaris (R) Streptococcus fecalis (S) Escherichia coli (S) Intermediate coli #l (R) Intermediate coli #2 (S)
to cephaloridine;
Prophylactic Use of Cephaloridine
62
Staphylococcus
R = resistant
Infection
Rates
Selective Use of Other Antibiotics
Per cent
Number of Patients
to cephalori-
Cases
Number of Patients
Clean
147
2.7
75
a
Dirty
54
13.0
54
35
Per cent
No Antibiotics Given Number of Patients
Per cent
149 64
2.1 8.0
phylactic group, without local inflammation or positive culture, and are not listed as infections. The development of a lymphocele after iliofemoral vascular procedures is probably a much more frequent complication than has been recognized. Mori [I] found an incidence as high as 65 per cent after radical #pelvic lymphadenectomy and noted that the more lymphatics interrupted, the higher the incidence ,of lymphocele. The seriousness of this complication in vascular surgery depends on the association of plastic graft materials with wound breakdown. The fourth infected clean case occurred with a resi,stant organism after thoracic wound disruption from closed cardiac massage. All of the potentially dirty cases in which preoperative prophylactic antibiotics had been given and which became infected had a major contributing factor of surgical judgment. The toe amputation was inadequate with ischemic necrosis of the wound edges preceding the infection. The revised amputation was for osteomyelitis and the wound was closed at the time of revision. The cervical sympathectomy was performed in the presence of an early piostoperative Staphylococcus aureus hernia infection. The femoropopliteal vein bypass was performed before adequate debridement was carried out in a patient with osteomyelitis of the heel due to Proteus mirabilis sensitive to cephaloridine. One patient in the postoperative prophylactic group became infected after pancreatitis which required drainage of the pancreas on the fourth and sixth postoperative days. The data do not reflect appreciable differences from the start of prophylactic antibiotic therapy but emphasize the influences of host resistance, coexisting disease, inherent complications of certain operative procedures, and the influence which surgical judgment has on the ,subsequent development of postoperative infectton. To have an antibiotic capable of compensating fior all these contingencies would, indeed, be fortunate. A comparison of infection rates, using cephaloridine prophylactically, to infection rates when antibiotics are used at the discretion of the surgeon is given in Table V [8]. This is of some practical importance since in the general practice of surgery the use of antibi&.ics is by discretion. The infection rate is lowest in that group (of patients in whom the surgeon thought that antibiotics were not neoeasary and highest in those patients the surgeon thought needed antibiotics. A judgment as to need was not made for patients receiving cephaloridine and it appears to be a very effective antibiotic to use prcnphylactically. Almost 80 per cent of the anti-
The American
Journal
of Surgery
Prophylactic
biotics used selectively were combinations of penicillin and streptomycin or others with gram-positive and gram-negative spectra except cephaloridine which was not available. Summary
Cephaloridine was used as a prophylactic antibiotic preoperatively in one hundred thirteen patients and postoperatively in eighty-eight. The inordinately high infection rates (preoperative prophylactic group, 6.2 per cent; postoperative prophylactic group, 4.6 per cent) are analyzed and found to be associated with factors that enhance the possibility of wound infection beyond the capabilities of all antibiotics. Antibiotics cannot yet be used as substitutes for maintenance of sterile technic, application of basic surgical principles, judgment in selection, and timing of surgical procedures.
Volume
122, July 1971
Use of Cephaloridine
References 1. Burke JF: Wound infection and early inflammation. Monogr Sorg Sci 1: 301, 1964. 2. Cohen LS. Peketv FR. Cluff LE: Studies of the epidemio,logy’of staihylkoccal infection. V. The repoking of hospital-acquired infection. JAMA 180: 805, 1962. 3. Elek WD, Conen PE: The virulence of Staphylococcus pyrogens for man. A study of the problems of wound infection. Brit J Exp Path 38: 573, 1957. 4. Alexander JW, Altemier WA: Penicillin prophylaxis of experimental staphylococcal wound infection. Surg Gynec Obstet 120: 243, 1965. 5. Bernard HR, Cole WR: The prophylaxis of surgical infection. The effect of prophylactic antimicrobial drugs on the incidence of infection following potentially contaminated operations. Surgery 56: 151, 1964. 6. Polk HC Jr., Lopez-Major JF: Postoperative wound infection. A prospective study of determimnant factors and prevention. Surgery 66: 97, 1969. 7. Kislak JW, Steinhauer BW, Finland M: Cephaloridine; activity in vitro and absorption and urinary excretion in normal young men. Amer J Med Sci 251: 433, 1966. 8. Dillon ML, Postlethwait RW, Bowling KA: Operative wound cultures and wound infections. Ann Surg 170: 1029, 1969.
63