Br. J. Surg. Vol. 61 (1974) 133-135

The reduction of surgical wound infections by topical cephaloridine: a controlled clinical trial C H R I S T I N E EVANS, A. V. P O L L O C K A N D I . L. R O S E N B E R G *

SUMMARY Four hundred and one consecutive patients having surgical operations were studied. Of these, 188 cases selected at random had 1 g of cephaloridine in 2 rnl of water instilled into the wound before closure, the remainder being controls. In the group receiving cepha- ioridine 9 per cent of the wounds became infected and in the control group 22.1 per cent. The difierence could have arisen by chance less than once in a thousand times.

THE vast amount of literature on infection in surgical wounds indicates that this important complication has not yet been brought under control. Refinements in the design and sterilization of operating theatres are of doubtful efficacy (Report, 1964; Shaw et al., 1973). Surgical wards, on the other hand, are now being built which materially reduce the risk of exogenous infec- tion (Davidson et at., 1971; Smylie et at., 1971).

Nevertheless, the majority of wounds that become infected do so because they have been contaminated during the operation from an endogenous source (usually the opening of a hollow viscus), and in attempting to prevent these infections many surgeons habitually use antibiotics.

Seal, 1970; Longland et al., 1971; Stoker and Ellis, 1972). Gilmore et al. (1973) have shown a significant reduction of wound infection after appendicectomy by local application of a povidone iodine or poly- antibiotic powder by aerosol.

However, a bacitracin-polymyxin-neomycin powder (Caro and Reynolds, 1967; Jackson et al., 1971) and noxytiolin (Bird et a]., 1971; Stoker and Ellis, 1971) had no significant effect on wound infection rates.

A controlled clinical trial (Evans and Pollock, 1973) has shown that cephaloridine in three parenteral doses reduces the rate of wound infection. It was therefore decided to investigate the effect of topical cephaloridine for the same purpose.

Materials and methods Having tried various methods of application of cephaloridine to wounds, we concluded that it was best applied as a strong solution (1 g in 2 ml of water). Inaccuracy of dosage and the introduction of a diluting powder (such as lactose) were influential arguments against the use of dry cephaloridine. The volume of solution was limited to 2 ml as the purpose was to leave the whole dose in the wound rather than

Table I: INFECTION RATE IN CLEAN AND CONTAMINATED WOUNDS Cephalorid ine No cephaloridine

Wounds No. No. infected Per cent No. No. infected Per cent ZZ P

Clean Total 79 3 3.8 107 6 5.6 0.3 NS Arterial 12 2 16.7 4 1 25.0 0.1 NS Non-arterial 67 1 1.5 103 5 4.9 I .3 NS

Total 109 14 12.8 106 41 38.7 18.84 <0.001 Colorectal 23 7 30.4 19 14 73.7 7.78 10.01 Other 86 7 8.1 87 27 3 1 .o 14.35 < 0.001

Total 188 17 9.0 213 47 22.1 12.62 < 0.00 I

Contaminated

NS, Not significant.

Trials of parenteral antibiotics, with the exception of cephaloridine (Polk and Lopez-Mayor, 1969 ; Evans and Pollock, 1973), have given disappointing results (Fekety et al., 1969; Conte et al., 1972) and their routine use may encourage the emergence of resistant organisms (Garrod, 1972).

Topical antibiotic prophylaxis, on the other hand, has given more promising results in numerous trials. Wound infection rates have been reduced by the local application of penicillin, ampicillin, kanamycin, tetra- cycline and cephalothin (Ryan, 1967; Hopson et al., 1968; Moylan and Brockenbrough, 1968; Waterman eta]., 1968; Rickett and Jackson, 1969; Mountain and

to irrigate with a large volume and waste most of the antibiotic.

In a general surgical practice all the operation cases involving a sutured incision more than 3 cm long (except the perineal wound of an abdomino- perineal excision of the rectum) were allotted to one of two groups by the toss of a coin. In one group cephaloridine solution was instilled into the wound before closure, and the second comprised the untreated controls. At the end of the operation details of the case were recorded on punch cards and filed

* Scarborough Hospital, Yorkshire.

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Christine Evans et al.

separately from the patient's notes in order to avoid observer bias.

All the patients were seen by one of the authors for at least 4 weeks after surgery. When the wound discharged pus in hospital a swab was taken for culture, and the cephaloridine sensitivity of the isolated micro-organisms was tested by the Multidisc method. As in previous trials, no restrictions were placed on antibiotic therapy when clinically indicated, but prophylactic antibiotics (other than oral agents for bowel preparation) were not used.

Wound infection has been defined as the discharge of pus from the wound (Ljungqvist, 1964; Pollock and Tindal, 1972). This was usually a small amount (e.g. a stitch abscess) but sometimes a wound abscess developed which required evacuation, and some infections followed the discharge of wound haem- atomas. The slight seropurulent discharge commonly found after removal of a rubber drain was not regarded as a wound infection.

Table 11: WOUND INFECTION RATE IN OBESE AND NON-OBESE PATIENTS

No. of No. of Patients wounds infections Per cent y 2 P

s:,") 2.48 NS 0 bese 61 15 Non-obese 334 49

Table 111: WOUND INFECTION RATE IN YOUNG AND OLD PATIENTS

No. of No. of Patients wounds infections Percent -/2 P

Young (under 243 33 13.67

} 2.60 60 years) Old (60 years 158 31 19.6

and over) I NS

Results Four hundred and six patients were originally studied but 5 were excluded from analysis because they died (without wound infections) within 4 weeks of opera- tion. The remaining 401 patients comprised 188 who received topical cephaloridine and 213 who did not. There was no evidence in any patient of cephaloridine allergy or toxicity.

Table Z shows the classification of these cases into clean (those with no potential for endogenous infec- tion) and contaminated (cases involving the opening of hollow viscera or excision of infected lesions). These groups have each been further divided, wounds for arterial surgery in the lower limb being separated from other clean wounds because they are more likely to become infected (Evans and Pollock, 1973; Shaw et al., 1973), and wounds for colorectal surgery and perforated appendicitis from other contaminated wounds for the same reason.

Three clean wounds out of 79 (3.8 per cent) became infected in the cephaloridine-treated patients compared with 6 out of 107 (5.6 per cent) in the control group. The difference is not statistically significant (xz = 0.3, P > 0.5).

In the group of patients with contaminated wounds, cephaloridine prophylaxis reduced the infection rate from 41 out of 106 (38.7 per cent) in the controls to 14 out of 109 (12.8 per cent) in the treated subjects. The difference is highly significant (xz = 18.84, P<O.oOl).

Apart from the nature and site of operation, the rate of wound infection is influenced by other factors including age and obesity (defined as a thickness of subcutaneous fat of 2.5 cm or more) (Welch, 1891 ; Davidson et al., 1971 ; Evans and Pollock, 1973). Their influence has once again been shown (Tables I I and I I I ) ,

Table IV: ORGANISMS ISOLATED FROM lNFECTED WOUNDS

Cephaloridine N o cephaloridine Clean Contaminated Clean Contaminated

~ _ _ _ - Organisms + + - Total + t- - - -

Staphylococcus pyogenes 0 0 2 0 2 0 9 0 13 (coagulase positive)

(coagulase negative)

Escherichia coli 0 1 - 1 0 0 I I 2 17 Proteus spp. 0 0 I 1 2 0 5 2 I I Pseudomonas aeruginosa 0 0 0 1 0 0 0 2 3 Enterobacter aerogenes 0 1 0 0 0 0 0 0 1 Streptococcus faecolis 1 0 1 0 0 0 2 0 4 Bacteroides fragilis 0 0 0 1 0 0 0 2 3 Clustridium welchii 0 0 0 0 0 0 4 0 4 Klebsiella aerogenes 0 0 0 0 0 0 I 0 1

Staphylococcus epiderwiidis 2 0 1 0 I 0 7 0 I I

Intestinal organisms 1 2 4 4 2 0 23 8 44 7

-!-, Sensitive to cephaloridine. -, Not sensitive to cephaloridine.

Table V: CEPHALORIDINE SENSITIVITY OF ORGANISMS ISOLATED FROM INFECTED WOUNDS

With cephaloridine Without cephaloridine No. resistant No. resistant

Total organisms to cephaloridine Per cent Total organisms to cephaloridine Per cent 16 6 37.5 52 8 15.4

The difference is not significant (z2 = 3.66, P20.05).

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Topical cephaloridine and wound infections

but the numbers are too small to show statistical significance.

Sixty-four wounds became infected and all but 7 late infections were studied bacteriologically. Seven wound swabs were sterile, leaving 50 cultures which yielded 68 organisms, 24 of which were staphylococci and 44 intestinal bacteria. In 12 wounds two organisms were isolated and in 3 wounds, three. The distribution is shown in Table ZV. The percentage of organisms resistant to cephaloridine was more than twice as great in the treated wounds as in the controls (Table V ) but the difference lacks significance on x2 testing,

Discussion The number of wound infections was reduced by the use of topical cephaloridine from 4.9 per cent to 1.5 per cent in clean non-arterial cases and from 38.7 per cent to 12.8 per cent in contaminated cases. Trials of other topical antibiotics are in progress, but as the control group must (on ethical grounds) receive cephaloridine, a much larger series will be needed to show any further improvement.

More resistant organisms (37.5 per cent) were encountered in cephaloridine-treated wounds than in control wounds (15.4 per cent). In a recent publication on the role of parenteral cephaloridine in the reduction of wound infections (Evans and Pollock, 1973) the incidence of cephaloridine resistance of organisms isolated from wounds in treated patients was 25.7 per cent compared with 18.5 per cent in control patients.

There appears to be a danger of encouraging the growth of resistant organisms by using cephaloridine as a prophylactic against wound infection, but at present the benefits far outweigh the disadvantages.

Acknowledgement We gratefully acknowledge the assistance of Dr R. D. Foord of Glaxo Laboratories Ltd, who also provided the cephaloridine (Ceporin).

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