Does single application of topical chloramphenicol to high risk sutured wounds reduce incidence of wound infection after minor surgery? Prospective randomised placebo controlled double blind trial

Limitations

The study had several limitations. Various characteristics influence the occurrence of infections; although we recorded information on as many variables as possible, ensuring that the baseline data were comparable proved difficult. For example, inadequate data were recorded on suture size and occupation, so we could not compare these factors. In addition, the prevalence of diabetes and of other medically important conditions was probably under-recorded, and power to analyse these subgroups was limited. Surgical training and technique of the general practitioners involved is a potential confounder that would be difficult to quantify and was not recorded. However, we adjusted the statistical analysis for the cluster sampling, taking the doctor as the primary sampling unit. The type of skin preparation used by the three participating practices differed, but we found no previously published evidence that this makes any difference to infection rates.21 A total of 42 participants were lost to follow-up. If all 21 participants who were lost to follow-up in the intervention group had developed an infection, the rates of infection in both groups would have been similar (10.4% and 11.0%); however, we believe that this scenario is extremely unlikely.

Diagnosis of infection—even when guidelines are used—is still subjective, and inter-observer and intra-observer variation may occur.20 The definition we used is the most widely implemented standard definition of wound infection,19 and by developing our own wound assessment scale we hoped to reduce the subjectivity of diagnosis of infection. We have no evidence to support the intra-practice and inter-practice reproducibility of measurement and recording procedures.

The study did not have an arm in which no ointment was applied, so we do not know if the ointment itself had any pro-infective or anti-infective properties. The ointment base of Chloromycetin consists of a mixture of soft white paraffin, liquid paraffin, and plastibase 30W, which is a plasticised hydrocarbon gel consisting of 95% mineral oil and 5% polyethylene glycol. We could not get information about the exact proportions of these constituents from the manufacturer. Our placebo ointment consisted of 50% soft white paraffin and 50% liquid paraffin and was not completely identical to the ointment base of Chloromycetin as it did not contain plastibase 30W. We cannot determine if this substance has an effect on infection, although we think that this is unlikely. Our trial used only a single dose of chloramphenicol ointment. We have no reason to surmise that repeated doses might lead to a greater reduction in infection rate.

Generalisability

Some limits to generalising these findings exist. The population of Mackay is slightly older than the general Australian population and has a lower median household income.22 Mackay is a provincial town in tropical North Queensland. The climate is hot and humid, with a mean daily maximum temperature ranging between 24.2°C and 30°C during the summer months and a relative humidity of 75-79%.23 These tropical conditions could increase sweat production and produce damp dressings, which might reduce the effectiveness of wound dressings as a potential barrier against exogenous bacteria.24 25 26 This would make wounds more prone to infection in a tropical environment, so the results may not necessarily be generalisable to a temperate climate, although no published evidence shows that heat and humidity increase infection rates. This might also explain why our infection rates were higher than suggested by previous data from temperate climates.11 12 13

Antibiotic use

Some concern exists about the overuse of topical antibiotics resulting in antibiotic resistance. British and Australian guidelines suggest that use of topical antibiotics should be restricted because of the capacity of most topical drugs to select resistant micro-organisms and to cause sensitisation. The guidelines also suggest that antimicrobials recommended for topical use should be selected from classes not in use for systemic treatment.3 27 A contrary argument says that the potential for antimicrobial resistance with topical antibiotics is actually lower than with systemic antibiotics because of the higher local concentration achieved by topical delivery.28 Patterns of antimicrobial activity and resistance have been examined for other antibiotic ointments.29 30 However, no evidence exists, over three decades of extensive use worldwide, to show that, with the exception of mupirocin, topical antibiotics administered on an outpatient basis contribute to any emerging resistance pattern.28 Chloramphenicol eye drops have been shown to be effective in the treatment of methacillin resistant Staphylococcus aureus ocular surface infections.31

Some concern also exists about the incidence of allergic contact dermatitis with use of topical antibiotics. For topical neomycin, this has been shown to be as high as 11% in a population referred for diagnostic patch testing.32 However, some evidence shows that the incidence of this reaction is as low as 1% when the ointment is used in the general population.28 The reaction is much more common among patients previously exposed to neomycin ointment.32 Contact allergy has been reported with the use of chloramphenicol ointment, but the incidence is thought to be low.33 34 Although any connection between the use of topical chloramphenicol and aplastic anaemia is unlikely,7 8 our study was not large enough to fully assess the risk in this setting.

Antibiotic prophylaxis is probably prescribed excessively or inappropriately for dermatological surgery and is thought to be best reserved for patients at high risk.19 35 36 No data are available on the current prescribing habits of Australian general practitioners regarding oral or topical antibiotic prophylaxis for minor excisions. Although no evidence is available on what reduction in the rate of infection we might reasonably expect from the use of oral prophylactic antibiotics for minor excisions, some evidence shows a 50% reduction in risk of infection when perioperative oral antibiotic prophylaxis is used after clean surgery.17 A similar reduction in infection rate from a single dose of topical antibiotic, as in this study, may encourage a reduction in the use of oral antibiotics.

The decision to prescribe antibiotic prophylaxis is complicated; in addition to efficacy, the antibiotic costs, adverse effects, and resistance should be taken into account. However, in some circumstances, topical delivery of antibiotic may be preferable to systemic administration.3 27 The results of this study could encourage the judicial use of topical antibiotics after minor skin surgery. However, topical chloramphenicol would be unlikely to produce a worthwhile absolute reduction in infection rates in low risk settings in developed countries. Future research could explore the possibility that important reductions may be seen in higher risk wounds or in more resource poor settings.

Conclusion

This study suggests that application of a single dose of topical chloramphenicol to high risk sutured wounds after minor surgery produces a moderate absolute reduction in infection rate.