Postgrad Med J: first published as 10.1136/pgmj.52.611.567 on 1 September 1976. Downloaded from Postgraduate Medical Journal (September 1976) 52, 567-570.

Chemoprophylaxis in surgery K. E. F. HOBBS Ch.M., F.R.C.S. Royal Free Hospital School of Medicine, London

Summary penicillin. Now there are in excess of 2000 antibiotic The literature on the prophylactic use in surgery of compounds available, together with a variety of disinfectants, antibiotics and the chemotherapeutic other chemotherapeutic and disinfectant agents. agents is reviewed. It is concluded that there is little When the dramatic effects of penicillin and its early place for the routine use of antibiotics or chemo- successors were observed in the treatment of infec- therapeutic agents except in a very few conditions. tion it seemed logical to believe that if these com- Disinfectants do have a part to play in skin steriliza- pounds were used early enough they would also tion and in the reduction of postoperative wound prevent infection. Physicians thought Ehrlich's infection. However, none of the compounds yet 'magic bullet' had been found. Although this was replaces careful technique and standard surgical pro- theoretically logical, in practice the infecting organ- cedure. isms rapidly developed a resistance to the antibiotics used (Barber and Rozwadowska-Dowzenko, 1948).

Introduction In addition, it seemed that the destruction of some Protected by copyright. Prophylaxis is described as 'the preventive treat- relatively innocuous bacteria allowed the growth of ment of disease' in the Shorter Oxford English other resistant and far more virulent organisms. Price Dictionary and so the place of antiseptics, antibiotics and Sleigh (1970) report an increased mortality in a and other chemotherapeutic agents in the prevention neurosurgical unit when prophylactic ampicillin was of complications of surgery will be discussed in this used and the death rate did not fall until the drug was paper. stopped. Another serious problem now commonly A review of the value of chemoprophylaxis in observed is that antibiotics induce sensitivity surgery is necessary because postoperative wound reactions in some patients, the effects ofwhich can be infections are reported to be costing the National disastrous. So it is necessary to review very critically Health Service about £22-3 million a year in addi- any attempts to reduce the excessive incidence of tional bed occupancy (Gilmore and Sanderson, infection following surgery. 1975a). This fact alone would justify attempts at reducing infection, but in addition and perhaps of Skin preparation greater importance is the fact that these complica- Since the skin is colonized by a variety of orga- http://pmj.bmj.com/ tions add to the discomfort and inconvenience of nisms, some of which if introduced into the tissue patients undergoing surgery. However, wound may become pathogenic, it is obvious that attempts infections are not the only complications of surgery to reduce the numbers of organisms, both on the attributable to bacteria, and prophylaxis for chest patient's skin before cutting the surface and on the infections, endocarditis and bacteraemia will be surgeon's hands before gloving, are necessary. mentioned in this review. Techniques for this have varied from scrubbing with soap and water to annointing the skin with various History compounds. Although total sterilization is im- on September 25, 2021 by guest. Probably the first description of the use of pro- possible, preparations such as 3YO hexachlorophane phylactic techniques against infection following in detergent (Phisohex), povidone-iodine detergent surgery was by Hippocrates, who irrigated wounds (Disadine) and 4YO chlorhexidine detergent (Hibi- with wine. Since then, mercuric chloride was used by scrub) seem effective (Smylie, Logie and Smith, 1973). Arabian physicians in the Middle Ages, followed by Scrubbing with soap and water alone has been known various other compounds until carbolic was intro- for many years to be counter-productive, probably duced by Lister in 1867. The real advent of the use of because quiescent organisms in the deeper parts of chemoprophylaxis as we know it today was in the the hair follicles are brought to the surface, thus early 1940s with the commercial development of increasing the number of organisms on the surface Correspondence: Academic Department of Surgery, and facilitating their invasion into traumatized Royal Free Hospital, Pond Street, London NW3 2QG. tissues. Postgrad Med J: first published as 10.1136/pgmj.52.611.567 on 1 September 1976. Downloaded from 568 K. E. F. Hobbs

Prophylaxis of wound infections tion, bisacodyl suppositories and repeated enemas There has been a wealth of literature in recent for 5 days before surgery (Rosenberg et al., 1971). A years reporting surveys which have been carried out very recent publication (Goldring et al., 1975) has to investigate the effects of antibiotics and other shown a significant reduction of both aerobic and chemotherapeutic agents in preventing operative anaerobic colonic microflora and subsequently wound infection. Observations have included postoperative wound infection when patients were studies on patients who have been treated with these treated with oral metronidazole in combination with compounds systematically, while others have de- kanamycin before gut surgery. One hopes this scribed their use locally in the wounds. However, all regime will be of value, but in view of previous these papers are difficult to analyse because controls optimistic reports subsequently being disproved, one are unsatisfactory and there is confusion between should remain sceptical until other workers have clean, clean-contaminated and contaminated cases. verified these observations. A clean case is defined as one in which surgery is Patients having surgery for peritonitis have a very carried out under aseptic conditions without opening high incidence of wound infection which needs any infected structure, a clean-contaminated case as reducing. Various combinations of treatments have one in which there is no overt infection but during been used including peritoneal lavage with saline the operation an infected structure, for example the solutions and noxytiolin or wound irrigation with large bowel, is opened; and a contaminated case as noxytiolin (Frazer-Moodie, 1974), or antibiotics. one in which surgery is carried out for or in the Despite Altemeier, Culbertson and Hummell's (1968) presence of overt infection such as peritonitis or claim that prophylactic antibiotics increased wound trauma. In the latter group, and probably the clean- infection, most reports suggest a slight reduction in contaminated group too, any antibiotic treatment infection rate. However, resistant strains and anti- must really be regarded as being therapeutic rather biotic sensitivity develop, each producing its own than prophylactic. When these reports are reviewed problems. Protected by copyright. there is some evidence to suggest that initially a new When disinfectant compounds such as noxytiolin antibiotic used either systemically or locally will were used in rats, treated animals had a higher reduce the incidence of wound infection in the clean mortality rate than untreated controls. In the cases (Gilmore and Sanderson, 1975b; Stoker and clinical situation, no difference in wound infection Ellis, 1972; Evans, Pollock and Rosenberg, 1974). rate was observed between treated patients and However, resistant strains develop very rapidly and untreated cases (King et al., 1975). This suggests so it has been suggested that the continued use of there is a specific contra-indication to the use of such such treatment as a general procedure is contra- compounds. indicated (Lowbury and Ayliffe, 1974). Following wound irrigation or spray with anti- It seems pertinent to discuss in more detail pro- biotics, resistant organisms in other patients in the phylaxis in surgery on the large bowel. This is one ward have been observed (Hughes, 1970). However, field in which various chemotherapeutic agents are the local use of povidone-iodine does seem to have a being used pre-operatively for prophylaxis. The valuable effect, in reducing the infection rate literature is most confused and is well reviewed by (Gilmore and Sanderson, 1975a). Probably the best http://pmj.bmj.com/ Forgan-Smith (1975). The idea of sterilizing the technique for reducing wound sepsis in these patients large bowel has been found to be impossible; only is still adequate drainage or delayed primary skin the composition of the flora changes and antibiotic- closure techniques. resistant strains rapidly appear (Altemeier, Hummel and Hill, 1966). The danger is that the patient treated with neomycin or phthalylsulphathiazole Chest infections before surgery is regarded by the surgeon as having Chest surgery in the mid-1960s was always 'been prepared' and 'had his gut sterilized'. The 'covered' by routine antibiotics. However, this was on September 25, 2021 by guest. psychological effect of this is to lull the surgeon into good for the surgeon's peace of mind but did not a false sense ofsecurity. This may lead to a disastrous stand up to critical examination when tested with situation, since the gut organisms at this stage are controlled trials. There is only a little evidence in the more likely to be antibiotic-resistant strains which literature that there is any value in this technique may produce wound infections or peritonitis (Laszlo et al., 1973). The chest infections that difficult to treat. The postoperative incidence of developed in patients who received antibiotics were, wound and other infectious complications has been if anything, worse than in the control groups. Pre- shown to be similar in the 'prepared' and 'unpre- and postoperative physiotherapy and, where neces- pared' groups. One report has shown that the use of sary, tracheal toilet and bronchoscopy are far more phthalylsulphathiazole was of value in large bowel effective. Even neonates requiring postoperative preparation only when it was accompanied by purga- ventilation in whom pneumonia is a common Postgrad Med J: first published as 10.1136/pgmj.52.611.567 on 1 September 1976. Downloaded from Chemoprophylaxis in surgery 569 complication should not receive antibiotics without antibiotics need to be considered is that in which are a very good reason (Davies, 1975). those who are therapeutically immunosuppressed or who have depressed defences for other reasons Foreign materials (Davidson, Smith and Smylie, 1971). In these cases The insertion of foreign materials into the body the theoretical advantages of prophylaxis need to be such as prosthetic heart valves, prosthetic joints or weighed against the disadvantages, and treatment internal fixation of bones presents special problems. should only be started with care and after considera- Initially these operations were all 'covered' by tion of the potentially infecting organisms. various broad-spectrum antibiotics. The place of Surgery in the obstructed biliary and urinary tracts antibiotic cover in these cases has not yet been readily predisposes to bacteraemia, especially if the adequately defined. The nature of the materials and insult is invasive without immediate relief of obstruc- the surgical techniques employed probably contri- tion. An example of this is percutaneous trans- bute more to the reduction in infection rate than any hepatic cholangiography in the investigation of large drugs. Antibiotics may be instilled locally (Scales, duct obstructive cholestatic jaundice. Ideally, once Towers and Roantree, 1972), although the compli- obstruction has been proved, then immediate cations of this have not been investigated and may drainage is essential. Occasionally, this is impossible still outweigh the advantages. Such treatment at and systemic antibiotics appropriate to the poten- present is no substitute for meticulous attention to tially infective organism have been used. The asepsis during the operation. literature on this is very poor at present and this is a field in which careful study is indicated to allow a Valuable chemoprophylaxis rational approach. It is unlikely that chemotherapy Gas gangrene infections complicate leg amputa- will replace adequate drainage. tions and extensive necrotic tissue damage following major trauma, especially in the presence of arterial Conclusions Protected by copyright. insufficiency. Since the causative organisms are It would seem that the initial prospects that chemo- sensitive to penicillin, all patients having a limb therapeutic agents would act prophylactically to amputation should be treated prophylactically with reduce the incidence of infection in surgery have not penicillin or an alternative antibiotic if the patient is been sustained. Apart from a few isolated occasions, sensitive to this. Consideration should be given to chemoprophylaxis with antibiotics is not only similar therapy in surgery for major trauma and valueless but may increase the morbidity and burns. However, in the case of bums, owing to the mortality of the treated patient. If may be said that rapid development of resistant strains of bacteria there is greater scope for antibiotic abuse in pro- (Lowbury, 1972), care should be exercised in their phylaxis than treatment (Gilmore and Sanderson, use and perhaps local disinfectants such as silver 1975b). Chemoprophylaxis does not replace careful nitrate or silver sulphadiazine are preferable to surgery and meticulous postoperative care. antibiotics, reserving these for the treatment of In 1920 Lord Moynihan said 'every operation in systemic bacteraemia. surgery is an experiment in bacteriology'. Have we

Surgery, in patients with proved rheumatic heart advanced beyond that today? In one way I believe http://pmj.bmj.com/ disease or septal defects, even if it is of a minor we have. Today the science of microbiology has nature such as dental treatment, may be complicated developed greatly; surgeons now have professional by endocarditis. However, if the patient is pre- microbiological colleagues with whom they can treated with antibiotics appropriate to the potentially collaborate to discuss problems of infection. By this infecting organisms, the risk can be reduced. means I believe we are approaching the time when Another group of patients at risk from infection our operations will cease to be experiments in are those with sickle-cell disease. Since any systemic bacteriology and will become safe, controlled, infection may precipitate a crisis, the use of pro- therapeutic procedures which are free from infec- on September 25, 2021 by guest. phylactic antibiotics has been suggested for these tion. patients. However, the literature on the subject is sparse and we must await the results of controlled References trials before formulating definitive policies in this ALTEMEIER, W.A., CULBERTSON, W.R. & HUMMELL, R.P. field. (1968) Surgical consideration of endogenous infections- sources, types and methods of control. Surgical Clinics of Quiescent pulmonary tuberculosis can be acti- North America, 48, 277. vated by major abdominal surgery. The National ALTEMEIER, W.A., HUMMELL, R.P. & HILL, E.O. (1966) Tuberculosis Advisory Council of Australia (1972) Prevention of infection in colon surgery. Archives of recommended the use of prophylactic treatment in Surgery, 93, 226. such cases. BARBER, M. & ROZWADOWSKA-DOWZENKO, M. (1948) In- fection by penicillin-resistant staphylococci. The Lancet, Another group of patients in whom prophylactic ii, 641. Postgrad Med J: first published as 10.1136/pgmj.52.611.567 on 1 September 1976. Downloaded from 570 K. E. F. Hobbs

DAVIDSON, A.l., SMITH, G. & SMYLIE, H.G. (1971) A bac- pulmonary complications of surgical operation. British teriological study of the immediate environment of a Journal of Surgery, 60, 129. surgical wound. British Journal of Surgery, 58, 326. LISTER, J. (1867) On the antiseptic principle in the practice of DAVIES, P.A. (1975) Antimicrobial therapy in the neonatal surgery. Lancet, ;;, 353. period. British Journal of Hospital Medicine, 14, 517. LOWBURY, E.J.L. (1972) Prevention and treatment of sepsis EVANS, C., POLLOCK, A.V. & ROSENBERG, I.L. (1974) The in burns. Proceedings of the Royal Society of Medicine, 65, reduction of surgical wound infections by topical cephalo- 25. ridine: a controlled clinical trial. British Journal ofSurgery, LOWBURY, E.J.L. & AYLIFFE, G.A.J. (1974) Drug Resistance 61, 133. in Antimicrobial Therapy, p. 7. Thomas, Springfield, Illinois. FORGAN-SMITH, W.R. (1975) Antibiotics and surgery. MOYNIHAN, SIR BERKELEY G.A. (1920) The ritual of a surgical British Journal of Hospital Medicine, 14, 529. operation. British Journal of Surgery, 8, 27. FRAZER-MOODIE, A. (1974) Prevention of wound infection NATIONAL TUBERCULOSIS ADVISORY COUNCIL (1972) Treat- after appendicectomy. Journal of the Royal College of ment of tuberculosis with particular reference to chemo- Surgeons of Edinburgh, 19, 121. therapy, 3rd Ed. Australian Government Publishing GILMORE, OJ.A. & SANDERSON, P.J. (1975a) Prophylactic Service. interparietal povidone-iodine in abdominal surgery. PRICE, D.J.E. & SLEIGH, J.D. (1970) Control of infection due British Journal of Surgery, 62, 792. to Klebsiella aerogenes in a neurosurgical unit by with- GILMORE, OJ.A. & SANDERSON, P.J. (1975b) An antibiotic drawal of all antibiotics. Lancet, ii, 1213. policy for surgical patients. Annals of the Royal College of ROSENBERG, I.L., GRAHAM, N.G., DE DOMBAL, F.T. & Surgeons of England, 57, 204. GOLIGHER, J.C. (1971) Preparation of the intestine in patients undergoing major large bowel surgery, mainly for GOLDRING, J., SCOTr, A., MCNAUGHT, W. & GILLESPIE, G. neoplasms of the colon and rectum. British Journal of (1975) Prophylactic oral antimicrobial agents in elective Surgery, 58, 266. colonic surgery. Lancet, ii, 997. SCALES, J.T., TOWERS, A.G. & ROANTREE, B.M. (1972) The HUGHES, W.H. (1970) The irreducible minimum in cross- influence of antibiotic therapy on wound inflammation and infection control and isolation nursing. Journal ofHygiene, sepsis associated with orthopaedic implants. A long-term 68, 379. clinical survey. Acta orthopaedica scandinavica, 43, 85. KING, D.W., GURRY, J.F., ELLIS-PEGLER, R.B. & BROOKE, SMYLIE, H.G., LOGIE, J.R.C. & SMITH, G. (1973) From B.N. (1975) The effect of noxytiolin (Noxyflex) in perito- Phisohex to Hibiscrub. British Medical Journal, 4, 586. nitis due to perforated appendicitis. Brirish Journal of STOKER, T.A.M. & ELLIS, H. (1972) Wound antibiotics in Protected by copyright. Surgery, 62, 659. gastro-intestinal surgery. Comparison of ampicillin with LASZLO, G., ARCHER, G.C., DARRELL, J.H., DAWSON, J.M. & penicillin and sulphadiazine. British Journal of Surgery, 61, FLETCHER, C.M. (1973) The diagnosis and prophylaxis of 133. http://pmj.bmj.com/ on September 25, 2021 by guest.