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
BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.a2812 (Published 15 January 2009) Cite this as: BMJ 2009;338:a2812All rapid responses
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Heal et al1 add good evidence to the common plastic surgery practice
(in the
UK) of chloramphenicol ointment on cutaneous wounds, in order to prevent
surgical site infection. There is an impressively honest wound infection
rate
and a soundly prospectively designed study to avoid a type II error2. The
treatment and control groups both benefit from the potential “moist wound
environment” from the use of ointment, which was demonstrated nearly half
a century ago3. Although the main concern, which is alluded to, with the
use
of chloramphenicol relates to the risk of aplastic anaemia1. This risk is
indeed
low, maybe I in 30 to 50,0004, therefore only a few clinicians will ever
see
such a problem in their lifetimes. The risk of aplastic anaemia is not
only dose
related but also idiosyncratic. Death has been reported following topical
usage, and absorption has been reported following skin application4.
Although these are only case reports, with such a grave potential
consequence chloramphenicol ointment should be avoided5. Especially when
there are numerous alternatives, such as Polyfax (which contains polymyxin
and bacitracin), that do not have such fatal risks. Staphylococcus aureus
and
Pseudomonas were the only isolates in the study, which would be covered by
Polyfax.
In the methodology Heal et al state saline was used at one centre and
chlorhexidine was used at the other two sites for the preoperative wash.
Therefore an analysis of the infection rates from the different practises
would
be useful to clarify any potential difference from this. Although a
difference is
unlikely, as a study of 1810 patients demonstrated no difference between
soap and chlorhexidine7, and the Cochrane metanalysis finds no definitive
evidence of a significantly better preoperative wash regimen6.
The types of lesions are described in the study (benign and
malignant) but
not their infective potential as to whether the lesions were ulcerated or
open
wounds. The type of surgery correlates well with infection; with clean
surgery
having a 5.9%, clean contaminated 10.7% and contaminated 24.3% rates8. An
ulcerated Basal cell carcinoma moves the type of procedure from clean to a
higher category dependent on the lesion, and a consequent higher
likelihood
of infection. Simple manoeuvres can lead to a dramatic decrease in
surgical
site infections from 33.3% to 3.7% by ensuring the decrusting of lesions,
use
of monofilament sutures, and meticulous asepsis for minor surgical
procedures9. Therefore greater infection control may be achieved through
meticulous surgical attention and technique, rather than the use of a
potentially fatal (albeit remote) topical antibiotic that has
alternatives.
1. Heal CF, Buettner PG, Cruickshank R, Graham D, Browning S,
Pendergast J,
et al. 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. BMJ 2009;338:a2812.
2. Chung KC, Kalliainen LK, Spilson SV, Walters MR, Kim HM. The prevalence
of negative studies with inadequate statistical power: an analysis of the
plastic surgery literature. Plast Reconstr Surg 2002;109(1):1-6;
discussion 7-
8.
3. Winter GD. Formation of the scab and the rate of epithelization of
superficial wounds in the skin of the young domestic pig. Nature
1962;193:293-4.
4. Erel E, Platt AJ, Ramakrishnan V. Chloramphenicol use in plastic
surgery. Br
J Plast Surg 1999;52(4):326-7.
5. Doona M, Walsh JB. Topical chloramphenicol is an outmoded treatment.
BMJ 1998;316(7148):1903.
6. Edwards PS, Lipp A, Holmes A. Preoperative skin antiseptics for
preventing
surgical wound infections after clean surgery. Cochrane Database Syst Rev
2004(3):CD003949.
7. Kalantar-Hormozi AJ, Davami B. No need for preoperative antiseptics in
elective outpatient plastic surgical operations: a prospective study.
Plast
Reconstr Surg 2005;116(2):529-31.
8. Twum-Danso K, Grant C, al-Suleiman SA, Abdel-Khader S, al-Awami MS,
al-Breiki H, et al. Microbiology of postoperative wound infection: a
prospective study of 1770 wounds. J Hosp Infect 1992;21(1):29-37.
9. Tahir A TO. Reducing infections in cutaneous oncology defects
reconstructed using skin grafts. Eur J Plast Surg 2005;28:27-31.
Competing interests:
None declared
Competing interests: No competing interests
Heal et al report a reduction in wound infection risk with the use of
topical antibiotics after skin surgery. They do however report a very high
control group infection risk rate and have ignored the influence of pre-
existing skin pathogen carriage as indicated by the appearance of the
lesion surface before surgery. Our prospective study shows that this
significantly increases the risk of wound infection.
We have shown that patients whose lesion preoperatively had a crusted
or ulcerated skin surface were significantly more likely to develop
clinical wound infections compared to those with a normal or scaly skin.
We included all patients attending for 1-stage excision biopsy in our
dermatology department, over a 12 month period, who were able to attend
for post-operative follow-up.
We categorised patients into groups according to the pre-operative
surface of their skin lesion; i.e. intact or broken (scaly, crusted or
ulcerated), and recorded the patient’s age, sex, diameter of the lesion,
use of topical antibiotics, time to follow-up and experience of the
dermatologist excising the lesion. Overall 174 out of 179 patients
completed our study, with 81 patients (47%) having intact skin overlying
their lesion. In the 93 patients with broken skin, 45% had scaly surfaces,
35% crusted, and 19% an ulcerated surface. We found a significantly
increased risk of infection (p<0.05) in patients who had either a
crusted/ ulcerated skin surfaces versus intact, or an ulcerated surface
versus scaly surface. Infection risk was not affected by the use of
perioperative topical antibiotics, site of the lesion, closure technique
or surgeon experience. Staphylococcus aureus was the causative organism in
90% of infections. Patient age was a significant risk factor, and older
patients were more likely to have lesions with a broken skin surface. Our
overall infection risk was 3.5% in lesions with an intact surface, 12% for
scaly lesions, 18% for crusted lesions and 33% for ulcerated lesions.
Although topical antibiotics may be beneficial to patients undergoing
minor skin surgery, our experience highlights the importance of
controlling for the integrity of skin surface in such a study. Thus,
because we cannot be sure that Heal’s two groups shared similar wound
infection risk rates, as judged by their pre-treatment skin surface
changes, this study needs to be repeated controlling for the integrity of
preoperative skin surface.
Competing interests:
None declared
Competing interests: No competing interests
Heal and colleagues’ report on the effect of application of
chloramphenicol to wounds after elective skin biopsies had been taken in a
primary care setting.
The premise for the study is based on what plastic surgeons have known for
many years - that topical chloramphenicol minimises skin infections after
surgery. The title suggest that the anatomical location or surgical
circumstances makes the surgical wound "high risk" though the reality is
that the described surgery is classified as low risk as it is performed as
a elective procedure of a non-infected and normal skin area. However, the
most important finding of the study is that the current practices, under
which such skin biopsies are performed, generate an eye watering infection
rate of 11%. The authors fail to appreciate that this 5-fold increase of
what would be an acceptable 2% infection rate is of much greater clinical
importance than the reduction that the topical chloramphenicol achieves.
The reason for this high infection rate and the possible explanation as to
why the topical chloramphenicol did not achieve the desired lowering of
infection rate could be found in the skin preparation prior to surgery and
not in the geographical location as alluded to by the authors. It would
appear that many of the patients did not have the skin decontaminated
prior to surgery as normal saline was often used instead of conventional
antiseptic (chlorhexidine, bethadine or alcohol). It would therefore be of
interest to know whether the preoperative skin preparation were evenly
divided between the research and infection groups and if so what further
steps the authors suggest to take to investigate the health risk that the
current practice represent.
Competing interests:
None declared
Competing interests: No competing interests
Heal and colleagues (and the authors of the accompanying editorial)
have
overlooked the single most important determinant of post operative wound
infection in cutaneous surgery i.e. - contaminated surgery on lesions with
high
levels of pathogenic bacteria: - ulcerated basal cell carcinomas account
for the
majority of these cases and although 71% of the lesions removed in this
study
were non-melanoma skin cancers, no mention is made of pre-existing
ulceration.
The 11% control rate of infection in this study was high - and may
reflect a
failure to recognize this risk. Poor surgical technique - overtight or
excessive
suturing, the creation of tissue 'dead' spaces and haematoma formation -
also
increase the risk of infection in otherwise clean cutaneous surgery.
The ulcerated basal cell carcinoma is at risk of post-operative wound
infection
and with the increasing incidence of skin cancer and cutaneous surgery
this
should be recognized. Antibiotic prophylaxis is accepted for contaminated
surgery in other sites - such as the bowel - and is no less important in
these
cases.
Competing interests:
Twenty years experience in
dermatological surgery
Competing interests: No competing interests
re topical chloramphenicol
We would like to thank our colleagues for their interesting and
helpful comments, and would like to address some issues raised in our
response below.
We were already aware from previous studies (1) that our infection
rate following minor surgery is very high compared with similar cohorts.
(2) The reason for this is unclear, but may be related to our hot and
humid environment. (3) The high infection rate was the main reason for
investigating the effectiveness of chloramphenicol. With a lower infection
rate a much higher sample size would have been required to show a relevant
difference between groups with statistical confidence, making such a study
almost unfeasible.(4)
Interestingly, the overall incidence of infection in the practice
which used normal saline as skin preparation was 6.5% (36/550), while it
was 11.6% (31/266) and 11.5% (18/156) in the two practices which used
chlorhexidine. However, as numbers are quite small, and there are several
other factors involved, we do not think this is of clinical significance.
A Cochrane meta-analysis did not find definitive evidence of a
significantly better preoperative skin preparation. (5)
There are many different potential confounding factors which may
affect infection rate, and it is difficult for any study to measure all
these factors adequately. We did not specifically record the integrity of
the skin surface or the presence of ulceration in our study. However the
numbers of basal cell carcinoma (BCC) and Squamous cell carcinoma (SCC)
were balanced in both intervention and control groups at baseline.
Considering the large sample size and meticulous randomisation, we would
hope that the presence of ulceration would be balanced in both groups and
therefore should not affect our findings. In previous secondary data
analysis we found that BCC, SCC, diabetes, and excisions from the lower
limbs to be risk factors for infection. (6)
(1) Heal C, Buettner P, Raasch B, Browning S, Graham D, Bidgood R, et
al. Can sutures get wet? Prospective randomised controlled trial of wound
management in general practice. Brit Med J 2006; 332(7549):1053-6.
(2) Dixon AJ, Dixon MP, Askew DA, Wilkinson D. Prospective study of
wound infections in dermatologic surgery in the absence of prophylactic
antibiotics. Dermatol Surg 2006; 32(6):819-26; discussion 26-7.
(3) Mills SJC, Holland DJ, Hardy AE. Operative field contamination by
the sweating surgeon. Aust NZ J Surg 2000; 32:826-7.
(4) Platt R. Antibiotic prophylaxis in clean surgery: does it work?
Should it be used if it does? New Horiz 1998; 6(2 Suppl): S53-7.
(5) Edwards PS, Lipp A, Holmes A. Preoperative skin antiseptics for
preventing surgical wound infections after clean surgery. Cochrane
Database Syst Rev 2004(3):CD003949.
(6) Heal C, Buettner P, Browning S. Risk factors for wound infection
after minor surgery in general practice. Med J Aust 2006; 185(5): 255-8.
Competing interests:
None declared
Competing interests: No competing interests