The prophylaxis of surgical wound infection: is cefuroxime any better than cephaloridine?

The prophylaxis of surgical wound infection: is cefuroxime any better than cephaloridine?

%urnal of ISmpitaZ Infection (1982) 3, 143-148 The prophylaxis of surgical wound infection is cefuroxime any better than cephaloridine? A. D. Maye...

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%urnal

of ISmpitaZ Infection

(1982)

3, 143-148

The prophylaxis of surgical wound infection is cefuroxime any better than cephaloridine? A. D. Mayer,

S. S. Brennan, I. R. Pickford, and A. V. Pollock

Mary

:

Evans

Scarborough Hospital, Scarborough, North Yorkshire Y012 6QL Summary:

A double-blind, prospective, random-controlled clinical trial of a single prophylactic dose of cephaloridine or cefuroxime at induction of anaesthesia for 456 abdominal operations failed to show any significant differences between them. Wound infection rates ranged from 5.0 per cent in clean operations to 45.5 per cent in those in which two or more species of enterobacteria were cultured from the subcutaneous tissues at the end of operation. Cephaloridine remains, therefore, our control against which to judge the prophylactic eficacy of the newer antibiotics.

Introduction For many years we have used a single dose of cephaloridine as prophylaxis against wound infection in abdominal operations. We compared intra-incisional cephaloridine with gentamicin (Pollock and Rosenberg, 1974), framycetin (Pollock and Evans, 1975), ampicillin (Pollock, Leaper and Evans, 1977), povidone iodine and saline irrigation (Pollock, Froome and Evans, 1978) and clindamycin (Greenall et al., 1979) in a series of controlled clinical trials, but failed to find a better regimen. We then showed (Greenall et al., 1981) that a single dose intravenously at induction of anaesthesia was as effective as the same dose into the wound at the end of the operation. At no time have we encountered any evidence of the nephrotoxicity which may complicate longer courses of cephaloridine, particularly if frusemide is given at the same time. We recognize, however, that cephaloridine has theoretical disadvantages; it has little or no effect on strains of Bacteroides, Pseudomonas or Enterobacter spp., and is destroyed by certain /3-lactamases. Cefuroxime is more resistant to j3-lactamases and laboratory work and open trials held promise that it might be a more effective agent for the prevention of wound infections. We therefore put this hypothesis to the test of a controlled trial. Patients and methods Five hundred consecutive patients having abdominal operations under the care of one surgeon were randomly allocated to receive an intravenous injection of either cephaloridine 1 g or cefuroxime 1.5 g at induction of anaesthesia. The two antibiotics were in identical ampoules and were distinguished only by a number. o195-6701/82/02014:

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The code relating number to antibiotic was not broken until after the trial was completed. We excluded children under the age of 12, incisions in the groin for simple hernias, patients with a history of penicillin allergy and those given antibiotics pre-operatively (except orally for preparation of the colon). During operations, swabs were taken of incised viscera and of the subcutaneous tissues before skin closure. These were immediately placed in cooked meat broth and incubated in the operating theatre suite, subsequently being transferred to the department of microbiology for aerobic and anaerobic subculture and species identification by standard methods. The progress of all patients was followed for at least a month (since one-quarter to one-third of all wound infections reveal themselves after the patient has gone home) and infection was defined as the discharge of pus from the wound. Infected wounds were classified as major (when the infection was accompanied by constitutional disturbances including pyrexia and the patient’s stay in hospital was prolonged) or minor (which was more of a nuisance than a menace). Sterile, serosanguinous discharges were counted separately. All wet wounds in hospital were cultured, but most of those which manifested themselves at home were not. All other infective complications were recorded. The trial was approved by the Hospital Ethical Committee and, since both arms of the trial offered direct benefit to patients, informed consent was not sought. Statistical analysis was by calculation of x2 with correction for continuity, and the probability of a fl error was calculated.

Results

Clinical : wound infections Forty-four patients were excluded from analysis: 11 whose cephalosporin was omitted, four whose uninfected incisions were re-opened within 14 days, 13 who died within 14 days without evidence of wound infection, one who absconded and could not be traced, and 15 who presented with septic peritonitis due to perforations of the appendix or colon. Detailed analysis is, therefore, confined to 456 patients, 223 of whom received cephaloridine and 233 cefuroxime. The most important determinant of wound infection is the presence of bacteria in the subcutaneous tissues at the end of the operation and we have, therefore, classified operations (Pollock, 1979) into clean (no detectable visceral or parietal bacterial contamination apart from skin saprophytes), potentially contaminated (positive visceral, negative parietal, culture), lightly contaminated (a single species of a potential pathogen in the parietal culture) and heavily contaminated (two or more species in the parietal culture). There are, however, other factors which increase the rate of wound infection, notably obesity (a thickness of subcutaneous fat of 2.5 cm or more), vertical mattress skin sutures (Mayer et al., 1981), and ileo-colorectal operations in patients who have not been prepared both mechanically and with a combination of antiaerobic and anti-anaerobic drugs (Pollock et al., 1975). The first two risk factors

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infection

were evenly distributed between the two groups (Table I), whereas it happened by chance that there were more unprepared colons in the cefuroxime group, with seven more wound infections. We have not found old ageper seto be an important risk factor, its apparent influence being due to the higher proportion of contaminated operations required by the elderly (Table II). Table I. Distribution

of

risk

~UC~OYS

Cefuroxime

Cephaloridine

-___ Obesity Vertical mattress skin sutures Unprepared colon

Wound infections o/ :o

Total 75 169 11

10 (13.3) 21 (12.4) 4 (36.4)

Total 81 167 22

--Wound infections % 10 (12.3) 22 (13.2) 11 (50.0)

Table II. The influence of age on zcound infection Age under 65 Wound infections Total Clean Potentially contaminated Lightly contaminated Heavily contaminated Total

121 86 53 26 286

Major 94

Minor 01 :0

0 0 1 (1.9) 0 1 (0.3)

5 (4.1) 5 (5.8) 5 (9.4) 11 (42.3) 26 (9.1)

Age 65 and over ~__Wound infections Major Minor Total 9; % 78 30 ;; 170

0 0 2 (6.1) 3 (10.3) 5 (2.9)

7 (21.2) 10 (34.5) 23 (13.5)

In the whole series there were six major wound infections and 49 minor, a total incidence of 10.7 per cent. There were no significant differences between the cephaloridine and cefuroxime groups in any category of bacterial contamination (Table

III).

Thirty-nine

other patients

Table III.

(8.6 per cent) in the clean and potentially

Wound infections and prophylaxis Cephaloridine

Total Clean Potentially contaminated Lightly contaminated Heavily contaminated Total

100 :: 22239

Cefuroxime

Wound infections I_Major Minor ”/cl ”0 0 0 1 (2.3) 1 (3.4) 2 (0.9)

3 3 5 13 24

(3.0) (5.9) (11.6) (44.8) (10.8)

Total 99 65 43 232:

Wound infections -..Major Minor ‘:a y:, 0 0 2 (4.7) 2 (7.7) 4 (1.7)

6 4 7 8 25

(6.1) (6.2) (16.3) (30.8) (10.7)

A. D. Mayer et al.

146

contaminated groups discharged sterile serum, and 25 of these acquired organisms from the ward environment and subsequently became infected (secondary infection). In no case did these organisms match those discovered on visceral culture during the operation. We also considered the rates of wound infection according to the hollow viscus opened (Table IV) and found that, again, cephaloridine and cefuroxime were equally effective. Table

IV.

Wound infections according to viscus opened Cephaloridine Wound

Viscus

incised

None Stomach, duodenum jejunum Gall bladder and ducts Appendix Ileum, colon and rectum (prepared) Ileum, colon and rectum (unprepared) Urinary tract Total

Cefuroxime infections

Major “/

Minor 0, /O

31

0

1 (3.2)

15 ;I

0 :

31

1 (3.2)

Total

Wound

infections

Major %

Minor %

23

0

2 (8.7)

1 (6.7) 35 (11.1) (4.2)

24 ;;

: 0

3 (12.5) 43 (8.5) (6.9)

9 (29.0)

27

0

4 (14.8)

22

; (18.2)

; (31.8)

4 (1.7)

25 (10.7)

Total

Calculation of the p (Type II) error showed that the chance of having missed a 50 per cent difference in effectiveness between these two antibiotics was 13 per cent, and for a 20 per cent difference the chance was 55 per cent.

Clinical : other infections Ninety-two infective complications (apart from wound infections) were recorded. Some patients had more than one such complication and they were equally divided between the cephaloridine and cefuroxime groups. There were 19 and 21 urinary tract infections, 20 and 19 chest infections, three and five intraperitoneal abscesses and three and two other infections, respectively.

Bacteriblogy The organisms cultured from pus are shown in Table V. Thirteen of the 55 patients (23.6 per cent) with wound infections discharged pus at home and no swabs were taken. In the remaining 42, pus swabs grew enterobacteria in 35 (83-3 per cent), Staphylococcusaureus in three (one in the cephaloridine and two in the cefuroxime group, mixed Staph. aureus and enterobacteria in two (both in

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infection

the cefuroxime group) and Staph. epidermidis in two. In the 37 pus cultures which yielded enterobacteria, the organisms matched at least one of those cultured during operation in 30 (81.1 per cent). Table

V. Organisms

cultured

from primary Cephaloridine

wound infections Cefuroxime

One organism Staphylococcus aureus Klebsiella spp. Escherichia coli Streptococcus faecalis Clostridium perfringens Proteus spp. Pseudomonas spp. Staph. epidermidis %Llore than one organism E. coli . Klebsiella SDV. Bacteroidesyragilis Str. faecalis Cl. perfringens Proteus spp. Pseudomonas spp. Str. pyogenes Staph. epidermidis Staph. aureus

15 4 5 6 2 i

1 4

0

9 : 6 0 3 0 0 4 2

Discussion

We have used cephaloridine for the prophylaxis of surgical wound infection in a series of controlled clinical trials for 10 years and it is encouraging that we cannot detect any lessening of its efficacy, when compared with a relatively new cephalosporin. Perhaps this is because cephaloridine is available only in parenteral form and there has been no widespread prescribing by community doctors. In addition, it is the policy of our unit not to prescribe it for treatment. We introduced the bacterial classification of abdominal surgical wounds, based on broth culture of visceral and parietal swabs, because it reflected clear-cut differences in wound infection rates and was readily applicable without special techniques of quantitative microbiology. We recognize that the presence of two or more species of enterobacteria in the subcutaneous tissue at the end of an operation does not necessarily mean heavy contamination in terms of numbers of bacteria, but the classification works and is therefore worthwhile continuing. The relatively high probability of a Type II error is disturbing, but this is an aspect of all trials in which no difference is apparent between two treatments. In order to reduce the 6 error to an acceptable (20 per cent) chance of missing a 20 per cent difference between the two arms of the present trial, twice as many

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et al.

patients would have to be admitted. All we can say is that we have failed to show that either antibiotic is better, or worse, than the other. Neither antibiotic has much activity against Bacteroides spp., and the superior stability of cefuroxime against some fi-lactamases does not appear to be important in the context of the organisms contaminating the wound during an abdominal operation. The cost of a single dose of 1 g of cephaloridine is E1.06, and of a single dose of 1.5 g of cefuroxime E5.88. Cephaloridine will remain our standard prophylactic in future trials until we find a better. We are indebted to Glaxo Research Ltd. for the cephaloridine Yorkshire Regional Health Authority for financial support.

and cefuroxime,

and to the

References Greenall, M. J., Atkinson, J. E., Evans, M. & Pollock, A. V. (1981). Single-dose antiis best? biotic prophylaxis of surgical wound sepsis: which route of administration Journal of Antimicrobial Chemotherapy 7, 223-227. Greenall,.M. J., Froome, K., Evans, M. & Pollock, A. V. (1979). The influence of intraincisional clindamycin on the incidence of wound sepsis after abdominal operations. Journal of Antimicrobial Chemotherapy 5, 51 I-516. Mayer, A. D., Godfrey, P. J., Evans, M. & Pollock, A. V. (1981). Skin sutures: a potent cause of wound infection in abdominal surgery. BritishJournal of Surgery 68, 367-368. Pollock, A. V. (1979). Surgical wound sepsis. Lancet i, 1283-1286. Pollock, A. V., Arnot, R. S., Leaper, D. J. & Evans, M. (1978). The effect of antimicrobial bowel preparation on the incidence of primary wound sepsis after colorectal surgery. Surgery, Gynecology and Obstetrics 147, 909-912. Pollock, A. V. & Evans, M. (1975). The prophylaxis of surgical wound sepsis with cephaloridine: experiences in 2491 general surgical operations and reporting a controlled clinical trial with framycetin. Journal of Antimicrobial Chemotherapy 1, (Supplement), 71-83. Pollock, A. V., Froome, K. & Evans, M. (1978). The bacteriology of primary wound sepsis in potentially contaminated abdominal operations: the effect of irrigation, povidone iodine and cephaloridine on the sepsis rate assessed in a clinical trial. British Journal of Surgery 65, 76-80. Pollock, A, V., Leaper, D. J. & Evans? M. (1977). Single-dose intra-incisional antibiotic prophylaxis of surgical wound sepsrs : a controlled trial of cephaloridine and ampicillin. British Journal of Surgery 64, 322-325. Pollock, A. V. & Rosenberg, I. L. (1974). Cephaloridine and gentamicin in the prophylaxis of surgical wound infection. British Medical Journal 2, 558-559.