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European Journal of Surgical Oncology 2000; 26: 363366

doi:10.1053/ejso.1999.0899, available online at on

Antibiotic prophylaxis for post-operative wound infection in clean

elective breast surgery

R. Gupta, D. Sinnett, R. Carpenter, P. E. Preece and G. T. Royle

Department of Surgery, Royal South Hants Hospital, Southampton, Department of Surgery,

Charing Cross Hospital, London, Department of Surgery, St Bartholomews Hospital, London and
Department of Surgery, Ninewells Hospital & Medical School, Dundee, UK

Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients
undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin
1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing
clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic
prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no
significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required
in clean, elective breast surgery. 2000 Harcourt Publishers Ltd
Key words: antibiotic prophylaxis; post-operative infections.

Introduction ecacy in other elective operations in order to reduce

infective complications. Our study was conducted to assess
Carcinoma of the breast aects one in 12 women in the whether prophylactic antibiotics would reduce the rate of
UK. Surgery, in the form of mastectomy or local excision post-operative infection.
with or without axillary clearance, remains the primary
treatment of choice, as the majority are locally invasive at
the time of presentation. Patients will often require adjuvant Methods
therapy in the form of chemotherapy or radiotherapy.
Overall these treatment regimes result in a local recurrence We have performed a prospective, randomized, observer
rate of less than 10%.1 Non-invasive breast carcinoma is blind, placebo-controlled study in four dierent centres in
usually treated with wide local excision, without the need order to assess the ecacy of a single dose of antibiotic
for axillary clearance.2,3 (1.2 g Augmentin200 mg clavulanic acid and 1000 mg
Wound infection occurs in approximately 10% of women amoxycillin), in women undergoing definitive surgery for
undergoing curative surgery for breast carcinoma, and seems malignant breast disease. This study was granted ethical
to be particularly common following axillary clearance. approval by the local hospital ethics committees of all
Wound infection is also common where definitive surgery four participating centres (Royal South Hants Hospital,
follows a recent open biopsy. Despite the risk of morbidity Southampton; Charing Cross Hospital, London; St
the need for staging means that axillary clearance remains Bartholomews Hospital, London and Ninewells Hospital,
part of the management protocol for breast cancer. Dundee, UK). All patients gave written, informed consent
Wound infection usually occurs between 5 and 21 days prior to inclusion in this study. Patients were randomized
following surgery in approximately 10% of patients. The to receive the antibiotic or placebo (20 ml 0.9% sterile saline)
causative organism is often Staphylococcus aureus although by reference to a computer generated list. Where the study
Staphylococcus albus and coliforms or bacteroides may be agent was administered the anaesthetist was instructed to
the cause. The presence of mammary duct ectasia is reconstitute the antibiotic from vials of sterile powder. It
associated with an increased risk of wound infection. It is was then administered to the patients as a single intravenous
often not possible to make this diagnosis, however, until bolus injection through a peripherally placed 22 gauge
after surgery has been performed. The occurrence of wound intravenous cannula, shortly after the induction of
infection can have an adverse impact on the psychological anaesthesia but before the first incision was made. The
welfare of the patient and her subsequent management. placebo was administered in the same way as a single bolus
Prophylactic antibiotics have been used with considerable injection of sterile saline. At no time until the breaking of
the code was the investigator made aware of whether the
active agent or the placebo was administered, so making
Correspondence to: Mr G. T. Royle. this study observer blind.

07487983/00/040363+04 $35.00/0 2000 Harcourt Publishers Ltd

364 R. Gupta et al.

Table 1. Number of patients recruited and suitable for final analysis recording the incidence of adverse events. An adverse event
was defined as one where patients answered positively to
Treatment group
the question Do you feel dierently in any way since the
Augmentin Placebo Total last visit? If the patient responded yes details of the
treatment emergent adverse event and its severity, including
Randomized 177 180 357 its relationship to the study agent, were documented in the
Screened 177 180 357
Completed study 156 157 313 relevant case report forms. The relationship to the study
Valid for ecacy analysis 174 177 351 agent was judged by the investigator to be unassessable,
unrelated, probably unrelated or probably related. All
Table 2. Demographic details of study patients (meanSD) adverse experiences were coded from the verbatim term
according to the World Health Organization adverse
Augmentin Placebo reaction terminology dictionary by body system and
(n=174) (n=177)
preferred term. This method of detecting adverse events was
Age (years) 5611.7 5811.1 in accordance with the Good Clinical Practice Guidelines of
Height (cm) 1626.4 1626.0 the time.
Weight (kg) 63.6 (43.6108.1) 64.5 (44.7104.7) The incidence of wound infection was compared between
treatment groups using the chi-squared test. A two-tailed
Median (range).
test with significance level of 5% was performed. The main
The randomization list was generated by computer. The analysis was performed on the control population, which
randomization codes were kept in sealed envelopes. Codes excluded patients who did not receive the injection of the
were sequentially allocated to randomized patients. Neither study agent and those who had no follow-up assessments.
the patient nor any of the sta involved with this study We aimed to recruit 500 patients over a 2 year period,
were aware of the allocation of treatment until after the allocating 250 to each of the study arms. Allowing for
study had been completed. withdrawals it was estimated that 200 patients in each
The patients who were included in this study were 18 treatment group would be required to detect a dierence of
years of age or over. There was no upper age limit. All 7% in the wound infection rate. This calculation was based
patients had a diagnosis of breast cancer, based on previous on the assumption that the infection rate would be 3% in
histological evidence or from a combination of cytology the Augmentin group and 10% in the placebo group, with
and mammography. All patients had either a mastectomy a significance level of 0.05 and 80% power.
or a wide local excision, with or without axillary clearance,
as definitive treatment for their disease. No patient was
entered into the study more than once. Patients known to Results
have a hypersensitivity to penicillin were excluded from
this study, as were patients who were taking concurrent In total 357 patients were recruited from all of the four
antimicrobial therapy at the time, or within 72 hours of centres. The period of the study was from 13 January 1992
planned surgery for any reason. Pregnant patients, or those until 4 January 1994. Table 1 shows details of these patients.
known to be suering from renal impairment (serum Although 357 patients were recruited, a total of 351
creatinine >200 mol/l) or liver failure (liver function tests produced data suitable for ecacy analysis. Of the patients
greater than twice the upper limit of normal), were also in the Augmentin group five (3.1%) were withdrawn due to
excluded. a violation of the protocol. One patient (0.6%) in this group
The primary end point was the incidence of wound was withdrawn for an unspecified reason. In the placebo
infection. This was defined as discharge from the wound or group eight patients (4.8%) were withdrawn due to protocol
erythema indicative of cellulitis (>5 mm from the wound) violation and one (0.6 %) due to the existence of concurrent
at any time during the study period, either before or after disease. Protocol violations resulted in six patients being
discharge from hospital. The wound characteristics were excluded from the intention-to-treat group. In two,
assessed in terms of the presence of healing, marked prophylaxis was given, in three no operation was performed
echymosis, lymphocoele, erythema, serous exudate, purulent and in one no post-treatment assessment were recorded.
exudate, abscess and wound breakdown. Secondary These rules were not specified in the protocol. Patients who
endpoints included febrile morbidity. These included could be evaluated regarding the ecacy of treatment were
duration of post-operative hospital stay, delay in progressing defined as those who received at least one dose of the study
to chemotherapy radiotherapy or surgical cosmesis due to agent or placebo.
wound infection and the incidence of chest or urinary Table 2 gives demographic details of the patients in the
infection, septicaemia or other infections. Febrile morbidity study. It can be seen that the patients were similar in this
was defined as an increase in the patients temperature to respect. It can be seen that patients in both groups were
above 38.0C on two separate occasions (excluding the similar in terms of age, height and weight. Table 3 gives
24 hours in the immediate post-operative period). Post- pre-operative and operative details of these patients and
operative hospital stay was defined as (date of Table 4 gives their staging details: again it can be seen that
dischargedate of operation) +1. The wound was assessed patients in both groups had similar numbers of operative
and further progress monitored at a routine outpatient clinic procedures.
attendance 1014 days following discharge. Table 5 gives details of wound swabs. Seventeen swabs
The tolerability of the study agent was also assessed by were taken from the wounds of 14 patients in the Augmentin
Antibiotic prophylaxis for post-operative wound infection 365

Table 3. Pre-operative and operative details of study patients

Augmentin Placebo

Open biopsy in previous 4 weeks 53 (30.6%) 43 (24.4%)

Days prior to definitive surgery 25 (1160) 25 (447)
WLE following previous open biopsy 1 (0.6%) 5 (2.8%)
WLE with axillary clearance 65 (37.4%) 56 (31.6%)
Mastectomy alone 11 (6.3%) 14 (7.9%)
Axillary clearance alone 19 (9.2%) 18 (10.2%)
Mastectomy with axillary clearance 71 (40.8%) 76 (42.9%)
Duration of operation (minutes) 50 (15180) 50 (15180)
Drain insertion 171 (98.3%) 172 (97.7%)

Median (range). WLE: wide local incision.

Table 4. Staging details of study patients in the placebo group had signs of a chest infection during
the course of this study. Three patients in the Augmentin
Augmentin Placebo
group and one in the placebo group had a urinary tract
Tumour score 1 63 (41.7%) 73 (48.3%) infection. Two patients in the Augmentin group and one in
Tumour score 2 77 (51.0%) 69 (45.7%) the placebo group had other infections during the course
Nodal involvement 61 (38.1%) 62 (39.5%) of the study. There were no cases of septicaemia in this
Distant metastases 0 2 (1.2%)
The median duration of hospital stay in both groups was
5 days; the overall duration of hospital stay was 172 days.
Table 5. Details of wound swabs of study patients A delay in the clinical management of the patients with
regard to chemotherapy, radiotherapy or surgical cosmesis
Augmentin Placebo as a result of wound infection was reported in 17 (10.2%)
n=164 n=170 cases in the Augmentin group compared with nine (5.4%)
Number of patients (swabs) 14 (17) 20 (30) in the placebo group.
Number of bacteriologically A total of 74 adverse events were reported by 59 (17.2%)
positive swabs 11 21 patients during the course of this study. Thirty-one (18.2%)
patients were in the Augmentin group who reported a total
of 41 such events, compared with 28 (16.2%) patients in the
placebo group who reported 33. The dierence between the
Table 6. Incidence of wound infection in study patients
two groups in the number of patients reporting at least one
Augmentin Placebo adverse event was not statistically significant (P=0.62).
n=164 n=170

Wound infection (%) 29 (17.7) 32 (18.8)

Dierence between groups 1.1% Discussion
95% confidence interval 9.4%, 7.1%
P-value 0.79
Day on which infection first observed 12 11 Amoxycillinclavulanic acid has been a popular and eective
Range 324 625 antibiotic in comparative trials of antibiotics. In a series of
non-contaminated operations dierent doses of this agent
were found to be equally eective in preventing infective
complications.4 In another trail of non-contaminated intra-
group, of which 11 were bacteriologically positive. In the abdominal operations it was compard with the combination
placebo group 30 swabs were taken from 20 patients: of of cefuroxime and metroniodazole. Again, similar rates
these 21 were bacteriologically positive. Table 6 gives the of infective complications were found.5 Comparison with
incidence of wound infection in patients. The wound cephradine/metronidazole,6 mezlocillin7 and gentamicin8
infection rate was similar in both groups, but was not produced similar results.
statistically significantly dierent. Furthermore, four Patients with appendicitis undergoing operative treatment
patients in each group were reported to have wound have been studied. Comparison of amoxycillinclavulanic
infections during their hospital stay whilst 28 (17.1%) in the acid with metronidazole9 demonstrated similar post-
Augmentin group and 29 (17.1%) in the placebo group had operative infective complication rates even in those patients
wound infections following their discharge from hospital. who had gangrenous appendicitis. Elderly patients
An episode of febrile morbidity was experienced at least undergoing elective colorectal operations are at high risk
once by five (2.9%) patients in the Augmentin group and of post-operative infective complications. In a study of such
six (3.5%) in the placebo group. Two patients experienced operations amoxycillinclavulanic acid was compared with a
two episodes each. The incidence of febrile morbidity was combination of gentamicin and metronidazole.10 The overall
not statistically significantly dierent. rates of abdominal or perineal wound infection, intra-
One patient in the Augmentin group and three patients abdominal abscess and systemic sepsis were similar in the
366 R. Gupta et al.

two groups. Another study of these patients comparing in at-risk abdominal surgery. Postgrad Med J 1992; 68: 8116.
amoxycillinclavulanic acid with gentamicin and 5. Palmer B, Mannur K, Ross W. An observer blind trial of
co-amoxyclav versus cefuroxime plus metronidazole in the
clindamycin demonstrated a lower rate if intra-abdominal prevention of postoperative wound infection after general
septic complications required reoperation.11 surgery. J Hosp Infec 1994; 26: 28792.
Similar rates of post-operative infective complications 6. Tehan S, Lamb Y. Ciprofloxacin versus amoxycillin/clavulanic
were reported in a study comparing amoxycillinclavulanic acid in the treatment of urinary tract infections in general
practice. J Antimicrob Chemother 1989; 24: 2359.
acid with cefotaxime or cefamandole1214 in patients 7. Menzies D, Gilbert J, Shepherd M, Rogers T. A comparison
undergoing biliary operations. Amoxycillinclavulanic acid between amoxycillin/clavulanate and mezlocillin in abdominal
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M, van Vroonhoven T, Verhoef J. Amoxycillin-clavulanate
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Augmentin in the prevention of sepsis after appendicectomy.
influence the incidence of this or any other infective Br J Surg 1985; 72: 5713.
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