Intraincisional antibiotics in laparotomy wounds

Intraincisional Antibiotics in Laparotomy Wounds FLEMMING MOESGAARD, M.D., MOGENS LYKKEGAARD-NIELSEN,M.D., PH.D., TAGE JUSTESEN, M.D.

From the Department of Surgical Gastroenterology, Rigshospitalet, Universit3~of Copenhagen, Copenhagen, Denmark

Moesgaard F, Lykkegaard-Nielsen M, Justesen T. Intraincisional antibiotics in laparotomy wounds. Dis Colon Rectum 1984;27:172-175. Concentrations of ampicillin after intraincisional instillation in laparotomy wounds were measured in ten patients undergoing appendectomy. Ampicillin, 1 gin, was instilled under the fascia and I gm in the subcutaneous space during wound closure. Wound secretion was collected every two hours during the first 24 postoperative hours by cannulation of a fine perforated drain placed in the subcutaneous space. Ampicillin was determined by a disk diffusion method. During the first eight hours the median concentration of ampicillin in wound secretion exceeded 1000 microgram/ml; 14 hours and 20 hours after wound closure the median concentrations were 73 and 14 microgram/ ml, respectively. The effect of ampicillin in high concentrations on "resistant" strains of Bacteroides [ragilis was demonstrated in an in vitro experiment. It is concluded that in colorectal surgery the effect on wound sepsis of intraincisional antibiotics as an addition to systemic antibiotic prophylaxis should be evaluated in a clinical trial. [Key words: Intraincisional antibiotics; Ampicillin; Wound sepsis]

disappearance rates of ampicillin applied to the subcutaneous space of laparotomy wounds before closure of the skin. Patients and Methods

T h e investigation comprised ten patients undergoing appendectomy, eight w o m e n and two men. T h e median age was 44 years, with a range of 17 to 78 years. All patients had normal renal function, evaluated from two determinations of serum creatinine. Informed consent was obtained. T h e median length of the appendectomy wounds was 7 cm. After appendectomy the peritoneal layer was closed with a continuous suture and the fascia and skin with interrupted sutures. During closure of the wound, 1 gm of ampicillin powder (Pentrexyl| was applied to the subfascial space and 1 gm to the subcutaneous space. Before closure of the skin a small drain (charriere 10) with as m a n y side holes as possible was placed in the subcutaneous space covering the whole length of the wound, and the drain was brought out through a separate stab incision (Fig. 1). Postoperatively, w o u n d secretion was collected from the entire length of the w o u n d by suction through a smaller catheter (charri~re 17) inserted into the drain. Insertion and collection of w o u n d secretion was performed 15 minutes after w o u n d closure, and then every two hours for 20 hours. Concentrations of ampicillin in w o u n d secretion were determined by a disk diffusion method, z

ANTIBIOTIC PROPHYLAXIS is necessary and justified in colorectal surgery to lower the rate of infectious complications. 1 Perioperative systemic administration of antibiotics, beginning with prophylaxis just before surgery, does not prevent intraoperative contamination of the w o u n d with bacteria from the gut, but limits its consequences by the presence of antimicrobial agents in fluids and tissue. Despite the use of systemic antibiotic prophylaxis, w o u n d sepsis rates of about 10 per cent are c o m m o n after colorectal surgery, indicating an insufficient concentration/ penetration of antibiotics in these patients. In order to evaluate the possible benefit of topical use of antibiotics as an addition to perioperative systemic antibiotic prophylaxis, we investigated concentrations and Received for publication August 12, 1983. Address reprint requests to Dr. Lykkegaard-Nielsen: 31 Sofievej, DK-2900 Hellerup, Denmark.

172

Volume 27 Number 3

I.APAROTOMY

~, ~ _=_

......

,,~,v _-,

173

WOUNDS

Fascia Peritoneum

FIG. I. Drain (charri6re 10) with multiple side holes brought out from the appendectomy wound through a separate stab incision. Wound secretion was collected by repeated cannulations of the drain with a smaller disposable tube. Inhibition of Bacteroides Jragilis by high concentrations of ampicillin was studied in an in vitro experiment comprising five strains recently isolated from h u m a n blood cultures. All five strains had been found resistant to ampicillin by the disk diffusion susceptibility test (10 #g/disk, PDM Biodisk| indicating an MIC-value above 64 #g/ml. The strains were grown overnight in PeptoneYeast extract broth (PY) in an anaerobic glove box, and diluted ten-fold in T2-buffer 3 to a concentration of 107 C F U / m l . From this dilution a further ten-fold dilution was made into (a) PY with 1000 #g ampicillin/ml, (b) PY without ampicillin, and (c) T2-buffer. All tubes were incubated anaerobically at 35~ and the bacteria were counted after 4, 8, and 24 hours by ten-fold serial dilution in T2-buffer and plated on Brain Heart Infusion agar plates supplemented with 5 per cent horse blc~)d. Concentrations of ampicillin in cultures (a) were determined after 4, 8, and 24 hours by the disk diffusion method. 2 Results

Concentrations of ampicillin in wound secretions from the subcutaneous space are shown in Figure 2. Eight hours after wound closure the median concentration of ampicillin was still above 1000 # g per ml w o u n d secretion; even 14 hours after closure of the wound a substantial a m o u n t of ampicillin was still present in the subcutaneous space (median 73 #g/ml, interquartile range 28-150 #g/ml). Ampicillin was still present in w o u n d secretion in all patients 20 hours after w o u n d closure. T h e effect of initially high concentrations of ampicillin (1000 # g / m l PY-medium) on the growth of resistant strains of B. ]ragilis is shown in Figure 3. Within 8 hours bacterial concentrations decreased from 106 to 103-104 CFU/ml, and by 24 hours a further reduction to about 10~ C F U / m l was observed. A normal growth of B. fragilis was seen in growth medium (PY) without ampicillin, whereas no growth took place in the non-nutrient diluent (T2-buffer). The initial concentration of 1000 i~g ampicillin/ml gradually decreased during the 24 hour in vitro experiment, and after 4, 8, and 24 hours, concentra-

lq(;. 2. Concentrations of ampicillin in wound secretion from the subcutaneous spacein ten patients after intra-incisional application of 1 gm ampicillin, o--o = median. Shaded area represents interquartile range. tions of ampicillin were reduced to 130 # g / m l , 90 #g/ml, and 30 #g/ml, respectively. Discussion

T h e advantage of topical application of antibiotics is, of course, the possibility of obtaining high concentrations of antimicrobial agents in the wound, In a previously published investigation of antibiotic concentrations after topical application in the wound, only a small number of patients were studied, and the measurements were limited to the first postoperative hours. 4 The

174

MOESGAARD, ET AL.

investigation showed considerable differences between patients, probably because w o u n d secretion was obtained by direct suction on the subcutaneous drain itself. We gave u p this method after a pilot study because of unreliable results, originating from uncontrolled release of

FIG.3. Growth of five strains of B. fragilis resistant to ampicillin. Median and range in growth medium (o--o--o), in non-nuuiem diluent (x--x--x), and in growth medium containing 1000tsg ampicillin/ml (o--o--o).

Dis. Col. gr Rect.

March1984

antibiotic adherent along the outlet of the drain. In the present investigation, the subcutaneous drain with multiple side holes was cannulated with a disposable smaller drain every time w o u n d secretion was obtained, and differences between patients were rather small (Fig. 2). With the present method, the extent to which a subcutaneous drain influences both the disappearance rate of antibiotics and the a m o u n t of wound secretion produced is, of course, still uncertain. T h e median concentration of ampicillin in w o u n d secretion 15 minutes after wound closure was 3.9 X 104 # g / m l , and the concentration remained above 1000 ktg/ml for eight hours (Fig. 2). By 14 hours the lower interquartile range of 28 ttg ampicillin per ml wound secretion still exceeds the m a x i m u m concentration to be expected in w o u n d secretion after intravenous administration of 1 gm ampicillin. 5 It appears from Figure 3 that high concentrations of ampicillin had a pronounced effect on "resistant" strains of B. fragilis. T h e concentrations of ampicillin used in the in vitro experiment (Fig. 3) were, however, considerably lower than those obtained in the patients investigated. In the present investigation the appendectomy w o u n d was chosen as a representative of laparotomy wounds, firstly because it is possible to keep within a preplanned size of the wound, thereby investigating wounds of similar size. Secondly, it was necessary to limit antibiotic prophylaxis to topical application of ampicillin, and this proved ethical, since none of the patients developed w o u n d abscess or other infectious complications. Ampicillin was chosen since this antibiotic has been used topically in several controlled clinical trials. In colorectal surgery, use of antibiotics topically in the w o u n d as an addition to oral antibiotic bowel preparation has proved valuable in controlled clinical trials. 6-8 In terms of antibiotic prophylaxis in colorectal surgery, however, perioperative systemic administration of antibiotics is preferred by m a n y to oral antibiotic bowel preparation2 While oral antibiotic bowel preparation aims at a decontamination of the gut in order to minimize or prevent intraoperative contamination from taking place, the intention behind perioperative systemic antibiotic prophylaxis is to combat intraoperative contamination of the w o u n d by the presence of therapeutic concentrations of antibiotics in blood and tissues. Obviously, therefore, it cannot be taken for granted that the clinical experience from the use of topical antibiotics as an addition to oral antibiotic bowel preparation is also valid with perioperative systemic antibiotic prophylaxis. In recently published controlled trials of systemic antibiotic prophylaxis in colorectal surgery, w o u n d sepsis rates are reduced to 7 to 15 per cent in treated groups. ~~ It is difficult, however, to accept a w o u n d sepsis rate of about 10 per cent, but whether this can be further reduced by application of

Volume 27 Number 3

LAPAROTOMY

a n t i b i o t i c s in t h e w o u n d at c l o s u r e as a n a d d i t i o n to t h e p e r i o p e r a t i v e s y s t e m i c a d m i n i s t r a t i o n of a n t i b i o t i c s is u n k n o w n , since c o n t r o l l e d trials h a v e n o t b e e n p u b lished. 16 W e c o n s i d e r t h a t a c l i n i c a l trial is j u s t i f i e d by the f i n d i n g s in the p r e s e n t i n v e s t i g a t i o n of very h i g h a n d l o n g - l a s t i n g c o n c e n t r a t i o n s of a n t i b i o t i c in the w o u n d after t o p i c a l a p p l i c a t i o n .

References 1. Baum ML, Anish DS, Chalmers TC, et al. A survey of clinical trials of antibiotic prophylaxis in colon surgery: evidence against further use of no-treatment controls. N Engl J Med 1981; 305:795-9. 2. Rosdahl VT, Vejlsgaard V. Rosdahl N, Vejlsgaard R. A micromethod for determination of antibiotics in serum. Dan Med Bull 1969; 16:133-9. 3. Meynell GG, Meynell E. Theory and practice in experimental bacteriology. Cambridge: University Press, 1970. 4. Greenall MJ, Atkinson JE, Evans M, Pollock AV. Single dose antibiotic: prophylaxis of surgical wound sepsis: which route of administration is best. A controlled clinical trial of intraincisional against intravenous cephaloridine. J Antimicroh Chemother 1981;7:223-7. 5. Bagley DH, Mac I..owry J, Beazley RM, Gorschboth C, Ketcham AS. Antibiotic concentration in human wound fluid after intravenous administration. Ann Surg 1978;188:202-8.

WOUNDS

175

6. Nash AG, Hugh TB. Topical ampicillin and wound infection in colon surgery. Br Med J 1967;1:471-2. 7. Andersen B, Korner B. ~stergaard AH. Topical ampicillin against wound infection after colorectal surgery. Ann Surg 1972; 176:129-32. 8. Evans C, Pollock AV, Rosenberg II.. The reduction of surgical wound infections by topical cephaloridine: a controlled clinical trial. Br J Stag 1974;61:133-5. 9. Editorial. Bowel preparation for surgery. Lancet 1978;2:1132-3. 10. Hunt PS, Francis JK, Peck G, Fan'ell K, Sail A. Tinidazole in the prevention of wound infection after elective colorectal surgery. Med J Aust 1979;1:107-9. 11. Stone HH, Haney BB, Kolb LD, Geheber CE, Hooper CA. Prophylactic and preventive antibiotic therapy. Ann Surg 1979;189: 691-8. 12. Higgins AF, Lewis A, Ncxme P, Hole ML. Single and multiple dose of co-trimoxazole and metronidazole in colorectal surgery. Br J Surg 1980;67:90-2. 13. Hughes ESR, McDermott I-F, White A, Masterton JP. C,ephaloridine prophylaxis in resection of the large intestine. Aust NZ J Surg 1981;49:434-7. 14. I.indhagen J, Hadziomerovic A, Nordlund S, Zbornik J. Comparison of systemic prophylaxis with metronidazole-fosfomycin and metronidazole-cephalothin in elective colorectal surgery. Acta Chir Scand 1981;147:277-83. 15. T&nqvist A, Ekelund G, Fosgren I., et al. Single dose doxycycline prophylaxis and peroperative bacteriological culture in elective colorectal surgery. Br J Surg 1981:68:565-8. 16. Polk HC. The proper use of local antimicrobial agents in wounds. Invited commentary. World J Surg 1980;4:433-7.

Announcement THE DEPARTMENT OF SURGERY AND THE PAGE AND WILI.IAM BLACK P O S T - G R A D U A T E S C H O O L O F M E D I C I N E O F T H E M O U N T SINAI S C H O O L O F M E D I C I N E A postgraduate course entitled, "Recent Advances in Anorectal Surgery," will be offered on Saturday, April 14, 1984 at the M o u n t Sinai Medical Center, New York, New York. T h e course will be under the direction of Changyul Oh, M.D. with T h o m a s M. Heimann, M.D., David Moss, M.D., and J e r o m e D. Waye, M.D. and will run from 9:00 A.M. to 5:00 P.M. ] ' h e Page and William Black Post-Graduate School of Medicine of the Mount Sinai School of Medicine (CUNY) designates this c o n t i n u i n g medical education activity for six hours and 30 minutes in Category I of the Physician's Recognition Award of the American Medical Association. For further information, contact Director, T h e Page and William Black Post-Graduate School of Medicine, Mount Sinai School of Medicine, One Gustave L. I~evy Place, New York, New York 10029. T e l e p h o n e (212) 650-6737.