antibiotics, cephalosporins, empirical antimicrobial therapy, surgical prophylaxis, surgical site infection
M Morgan. Surgery And Cephalosporins: A Marriage Made In Heaven Or Time For Divorce?. The Internet Journal of Surgery. 2005 Volume 8 Number 1.
For many years now, surgeons have used cefuroxime and metronidazole for both prophylaxis and treatment of infections. Times and microbes have changed since the introduction of the cefuroxime in 1978. Cephalosporins are ineffective against the common pathogens causing surgical site infection (SSI) and are associated with superinfection. The argument is made for surgeons and microbiologists to take their local infecting organisms / sensitivity patterns into account when formulating prophylaxis as well as empirical therapy guidelines for individual surgical sites.
For many years now, surgeons have used cefuroxime and metronidazole (often endearingly referred to as “ceph and met”) for both prophylaxis and treatment of infections. No doubt many would argue that “ceph and met” have served well and that the incidence of surgical post-operative infection is within expected limits for the degree of infection risk. Times and microbes have changed, though, since the introduction of the cefuroxime by Glaxo in 1978. The majority of organisms causing surgical site infection (SSI) post-operatively are staphylococci including
Cephalosporins, perhaps more so than any other class of drugs, have been associated with superinfection with MRSA (2,3,4), vancomycin resistant enterococci (VRE) (5,6,7),
The consequences of deep post-operative infections can be dire. This is especially true of surgical graft infections. Vascular graft infections occur in around 7.8% of patients and prosthetic hip and knee infections in 3.1 and 1.9% respectively (1). Untreated, an infected femoral graft leads to amputation while an infected aortic graft means almost certain mortality. Even with adequate treatment the mortality and amputation rates are high (14). Infected orthopaedic grafts lead to loss of use of the limb, often permanently. MRSA is often the commonest single organism causing vascular graft infection and this infection has been shown to develop despite cepahlosporin prophylaxis (14).
It is thus essential to administer effective antimicrobial prophylaxis according to the accepted scientific principles. In the UK these were laid out by the Scottish Intercollegiate Guidance Network (SIGN) (15). The basic principles are:
The antibiotics selected for prophylaxis must cover the most common pathogens. The chosen antibiotic must reflect local, disease specific information about the common pathogens and their antimicrobial susceptibility.
The aim is to achieve maximum concentrations of an effective antimicrobial at the target tissues at time of operation. This is because most organisms causing early surgical infection –especially those of prosthetic grafts- are skin organisms (e.g. staphylococci) that land on the open wound at the time of operation.
With few exceptions (noted in the document), all drugs are given IV as a single dose at induction (roughly 1/2 hour before operation, 1 hour if IM) unless otherwise stated. There is no evidence to support multiple doses beyond the peri-operative period.
The SIGN guidelines (Annex 4) (15) correctly state that
It is with above evidence and data in mind, that microbiologists and pharmacists in Cumbria have developed a new “standard surgical regime” for prophylaxis. This regime is applicable where broad-spectrum cover including anti-anaerobic, MRSA and pseudomonas spp. is required. The regime and example indications for surgical prophylaxis are given in table I. It can equally be used for empirical therapy pending culture and sensitivity results, when narrower spectrum agents may be employed. We concur with SIGN that glycopeptides are not suitable for routine surgical prophylaxis as they are expensive and require up to 48 hours for serum levels to achieve a steady state. Further, vancomycin requires IV infusion over at least 100 minutes. Thus the glycopeptides are best kept as “reserve” drugs. However, glycopeptides have been successfully used in surgical prophylaxis involving prosthetic implants in Europe and the USA (16,17). Gentamicin on the other hand, has broad-spectrum Gram-positive and negative activity (including
We are not recommending this regime for every institution and other European and UK regions are also advised to take their local infecting organisms and their sensitivity patterns into account when formulating prophylaxis as well as empirical therapy guidelines. It has to be remembered, however, that prophylaxis does not prevent the late haematogenous infection of prosthetic joints and antibiotics should be administered prior to bacteraemia inducing procedures such as dental extraction and urinary catheterisation. Audit of early and late postoperative infections pre- and post- introduction of any new regime such as this one is desirable. However, as prosthetic joint infections are low incidence diseases (see above), large numbers of patients would have to be recruited and monitored and this is perhaps more suited to a multi-centre study.
In conclusion, there is compelling evidence that cephalosporins are ineffective against the common pathogens causing SSIs and that they are associated with superinfection; strong grounds for divorce indeed. Thus it is time for the surgeons to break their long-lasting relationship with the cephalosporins and court “new” antibiotics effective against today's pathogens, both for prophylaxis and empirical therapy.