Intervention Review

You have free access to this content

Prophylactic antibiotics to prevent surgical site infection after breast cancer surgery

  1. Daniel J Jones1,*,
  2. Frances Bunn2,
  3. Sophie V Bell-Syer3

Editorial Group: Cochrane Wounds Group

Published Online: 9 MAR 2014

Assessed as up-to-date: 5 DEC 2013

DOI: 10.1002/14651858.CD005360.pub4


How to Cite

Jones DJ, Bunn F, Bell-Syer SV. Prophylactic antibiotics to prevent surgical site infection after breast cancer surgery. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD005360. DOI: 10.1002/14651858.CD005360.pub4.

Author Information

  1. 1

    University of York, Department of Health Sciences, York, UK

  2. 2

    University of Hertfordshire, Centre for Research in Primary and Community Care, Hatfield, Hertfordshire, UK

  3. 3

    Royal United Hospital, Bath, UK

*Daniel J Jones, Department of Health Sciences, University of York, Seebohm Rowntree Building, York, YO10 5DD, UK. ugm4djj@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 9 MAR 2014

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Breast cancer accounts for one in 10 of all new cancer cases diagnosed around the world each year (Bray 2004) and is the leading cause of cancer death in women (Pisani 1999). Surgery for removal of breast cancer has been common practice for centuries (Donegan 1995) and this is normally used as part of a multi-faceted approach to care with the aim of curing the patient of their cancer in early stage tumours or prolonging life for others (NICE 2002). Surgical intervention ranges from removing the breast and associated axillary lymph nodes, to lumpectomy with or without sentinel node biopsy (Harris 2004). Whilst the risk of breast cancer for men is only 1%, treatment for men is very similar to that of women (Harris 2004). As with all surgical procedures, breast cancer surgery runs the risk of complications. One such risk is postoperative surgical site infection (SSI), even though breast cancer surgery is considered a 'clean surgical procedure'. Clean surgical procedures, as defined by Haley 1985, are those which have a low risk of bacterial contamination during the surgery.Some women have immediate breast reconstruction; however this group of patients has a higher risk of SSI (Spauwen 2000).

Despite internationally recognised infection control guidelines (Mangram 1999), the incidence of SSI in those being treated for breast cancer is thought to range between 3% (Lefebvre 2000) and 15% (Witt 2003). This is a higher incidence of infection than the 3.4% SSI rate associated with clean surgical techniques (Vazquez-Aragon 2003). A recent review (Pittet 2005) found that women who had been treated for breast cancer and who had immediate reconstruction had a SSI rate of between 0% and 53%, whilst non-cancer patients undergoing the same reconstructive surgery had an average rate of 2.5%. There are several factors that are documented as increasing the risk of infection for surgical patients generally. These include: patient risk factors, e.g. diabetes, obesity or smoking (Haley 1985; Mangram 1999); surgical technique, e.g. aseptic technique (Ritter 1988); and type of surgery, e.g. whether the wound is contaminated (Gruendemann 2001). In addition, surgery for breast cancer has several risk factors that make this patient group more susceptible to infection, including use of chemotherapy prior to surgery (neo-adjuvant chemotherapy); technique of diagnostic biopsy; re-operation for recurrence or to achieve better tumour margins; reconstructive surgery with implants and seroma accumulation and drainage (Morris 1988; Tran 2003). Infection may lead to significant morbidity for the patient, delay in adjuvant treatment, such as radiotherapy, and increased cost of care if the patient requires supplementary treatment due to infection (Coello 1993).

Pre- and perioperative antibiotics have been shown to reduce the risk of postoperative infection in several patient groups (the term "perioperative" refers to administration between induction of anaesthetic and the patient leaving the recovery room) (Gruendemann 2001; Majoribanks 2004; SIGN 2008a). In colorectal surgery antibiotic prophylaxis has been found to reduce long and short-term morbidity, decrease length of hospital stay and lower the overall cost of care (SIGN 2008a). However, the use of prophylactic antibiotics in preventing infection is still a controversial issue and their routine use is not common in breast cancer surgery. Some feel that a clean surgical procedure should not require prophylactic antibiotics (Sheridan 1994) and that the use of pre- or perioperative antibiotics merely masks the symptoms of infection until after the patient is discharged (Wagman 1990). In addition increased antibiotic use may lead to antibiotic resistance (PHLS 2000) and adverse effects such as clostridium difficile infection that causes gastro-intestinal problems (SIGN 2008a). In order to clarify the situation, this systematic review evaluated the effectiveness of pre- or perioperative antibiotics in reducing the incidence of postoperative infections in patients undergoing breast cancer surgery.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To determine the effects of prophylactic antibiotics on SSI after breast cancer surgery.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomised controlled trials (RCTs) and controlled clinical trials (where patients were allocated by quasi-random methods such as alternation, case records numbers or days of the week).

 

Types of participants

People with breast cancer undergoing breast surgery with or without immediate re-construction as part of their treatment.

We included studies that involved mixed patient groups (i.e. cancer and non-cancer, other surgeries or breast implants not as part of cancer treatment) as long as it was possible to extract separate data for those undergoing surgery primarily to treat breast cancer.

 

Types of interventions

Any pre- or perioperative antibiotics used as prophylaxis where there was no known infection and where the use of antibiotics was the only systematic treatment difference between comparison groups.

We only included trials of one antibiotic compared with another if there was a control or placebo arm, as benefit from prophylactic antibiotics has not yet been established in this patient group.

Definitions of key terms:

  • 'Antibiotic regimen' describes the characteristics of the antibiotic treatment, i.e. type of antibiotic, route, dose, number of doses and timing of administration.
  • 'Preoperative antibiotic prophylaxis' is antibiotic therapy given within 24 hours prior to surgery, solely for prophylaxis (i.e. not for an infection that is already suspected).
  • 'Perioperative antibiotic prophylaxis' is antibiotic therapy administered between commencement of induction of surgery and the patient leaving the recovery room.

Comparisons of interest were as follows.

  • Preoperative antibiotic compared with no antibiotic or placebo.
  • Perioperative antibiotics compared with no antibiotic or placebo.
  • Head to head comparisons of antibiotics.

 

Types of outcome measures

 

Primary outcomes

  1. Incidence of postsurgical breast surgical site (wound) infection (SSI)*. Where possible, this should be reported as the number of participants in each group with a clinically significant infection. Research demonstrates that 98% of acute SSIs related to non-implant breast surgery occur within 28 days (Mitchell 1999). However, where there is surgical re-construction, guidelines recommend that this time is increased to one year post surgery (Mangram 1999). Therefore we included all studies that present data on acute SSI within one year of surgery.
  2. Adverse reactions (e.g. anaphylaxis, gastro-intestinal or skin rash).

*Surgical site infection: ideally this will be defined using outcomes from a validated assessment tool such as ASEPSIS (Wilson 1986) which are based on CDC definitions (Mangram 1999).

 

Secondary outcomes

  1. Death.
  2. Delay in adjuvant cancer treatment because of breast wound infection.
  3. Time to wound healing.
  4. Time to infection.
  5. Readmission to hospital.
  6. Cost of care (should be a comparison between the treatment and control group).

 

Search methods for identification of studies

 

Electronic searches

See Appendix 1 for the search strategy used for the second update of this review.

For the third update of this review we revised the search strategies and searched the following electronic databases over all years:

  • the Cochrane Wounds Group Specialised Register (searched 5 December 2013);
  • the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 11);
  • The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2013, Issue 11)
  • Ovid MEDLINE (1946 to November Week 3 2013);
  • Ovid EMBASE (1974 to 2013 Week 48);
  • Ovid MEDLINE (In-Process & Other Non-Indexed Citations 03 December, 2013);
  • EBSCO CINAHL (1982 to 20 December 2013).

We used the following search strategy in the Cochrane Central Register of Controlled Trials (CENTRAL):

#1 MeSH descriptor: [Surgical Wound Infection] explode all trees 2643
#2 MeSH descriptor: [Surgical Wound Dehiscence] explode all trees 346
#3 (surg* near/5 infect*):ti,ab,kw 4032
#4 (surg* near/5 wound*):ti,ab,kw 4427
#5 (surg* near/5 site*):ti,ab,kw 1016
#6 (surg* near/5 incision*):ti,ab,kw 1043
#7 (surg* near/5 dehisc*):ti,ab,kw 385
#8 (wound* near/5 dehisc*):ti,ab,kw 551
#9 (wound* near/5 infect*):ti,ab,kw 4440
#10 (wound near/5 disruption*):ti,ab,kw 42
#11 (wound next complication*):ti,ab,kw 420
#12 {or #1-#11} 8341
#13 MeSH descriptor: [Breast Neoplasms] explode all trees and with qualifiers: [Surgery - SU] 1627
#14 ((breast next cancer*) near/5 surg*):ti,ab,kw 756
#15 ((breast next neoplasm*) near/5 surg*):ti,ab,kw 919
#16 ((breast next carcinoma*) near/5 surg*):ti,ab,kw 47
#17 MeSH descriptor: [Mastectomy] explode all trees 1212
#18 MeSH descriptor: [Mammaplasty] explode all trees 218
#19 (mastectomy or mammaplasty):ti,ab,kw 2029
#20 MeSH descriptor: [Breast] explode all trees and with qualifiers: [Surgery - SU] 97
#21 {or #13 #20} 3148
#22 MeSH descriptor: [Anti-Bacterial Agents] explode all trees 8601
#23 (antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin or sulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin) 21709
#24 #22 or #23 25029
#25 #12 and #21 and #24 33

The search strategies for Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL can be found in Appendix 2, Appendix 3 and Appendix 4 respectively. We combined the MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision); Ovid format (Lefebvre 2011). We combined the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (SIGN 2008b). We applied no language or date restrictions.

 

Searching other resources

In addition, we screened references in all articles found by the above search strategy for further studies. We contacted experts in the field and interest groups to try and obtain access to unpublished or ongoing work. We followed up conference proceedings and grey literature that was considered to be potentially eligible for inclusion by both authors by contacting the study authors for further information.

 

Data collection and analysis

 

Selection of studies

Two review authors independently examined the title and abstract of citations identified by the search. We obtained all reports of potentially eligible trials as full-text articles and two review authors independently applied the inclusion criteria, resolving disagreements by discussion.

 

Data extraction and management

Two review authors independently extracted trial data using a specifically designed data extraction tool. We extracted data on study risk of bias (as defined below), antibiotic intervention (i.e. drug name, dose route, duration of treatment), setting, source of funding, length of follow-up and outcomes.

 

Assessment of risk of bias in included studies

For this update two review authors independently assessed each included study using the Cochrane Collaboration tool for assessing risk of bias (Higgins 2011). This tool addresses six specific domains, namely sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other issues (e.g. extreme baseline imbalance) (see Appendix 5 for details of criteria on which the judgement was based). We assessed blinding and completeness of outcome data for each outcome separately. We completed a 'Risk of bias' table for each eligible study. We discussed any disagreement amongst all review authors to achieve a consensus. We presented assessment of risk of bias using a 'Risk of bias' summary figure, which presents all of the judgements in a cross-tabulation of study by entry. This display of internal validity indicates the weight the reader may give the results of each study.

 

Assessment of heterogeneity

We assessed heterogeneity between study results using the I2 statistic (Higgins 2003). This examined the percentage of total variation across studies due to heterogeneity rather than chance. We considered values of I2 over 75% to indicate a high level of heterogeneity and would have resulted in a random-effects model being applied or not pooling results.

 

Data synthesis

Where possible for each trial we calculated the risk ratio (RR) of infection and 95% confidence interval (95% CI), such that a risk ratio of greater than one indicates a higher risk of infection in the first group named. We reported continuous data (i.e. number of days to infection), where possible, as mean difference (MD) with 95% CI.

Methods of synthesising the studies were dependent on trial quality, design and heterogeneity. We explored both clinical and statistical heterogeneity. In the absence of clinical and statistical heterogeneity we applied a fixed-effect model to pool data. Where synthesis was inappropriate we have presented a narrative overview.

 

Subgroup analysis and investigation of heterogeneity

As patients undergoing reoperation, reconstruction with or without implants and patients receiving neo-adjuvant chemotherapy are documented as having a higher risk of infection (Tran 2003) we conducted a prespecified subgroup analysis of each of these factors where there were sufficient data available. The proposed subgroups were:

  • patients undergoing immediate reconstruction without implants (i.e. TRAM flap);
  • patients undergoing immediate reconstruction with implants (i.e. silicone or saline); and
  • patients who have received chemotherapy (excluding hormone treatment) prior to surgery.

 

Sensitivity analysis

Since there is evidence that the quality of allocation concealment particularly affects the result of studies (Schulz 1995), we examined the effect of excluding studies judged to have inadequate allocation concealment in a prespecified sensitivity analysis.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

 

Results of the search

We identified two further studies which met the inclusion criteria for this third update (Cabaluna 2012; Gulluoglu 2013) and excluded one study (Nicholas 2007). A further four abstracts which were considered to be multiple publications of the same study were awaiting assessment pending clarification from the study authors, these are now excluded as the study authors have not responded to our requests for further clarification (Kumar 2005). In total eleven studies met the inclusion criteria for this version of the review (Amland 1995; Bold 1998; Cabaluna 2012; Chow 2000; Gulluoglu 2013; Gupta 2000; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990; Yetim 2010).

 

Included studies

 

Participants

Of the eleven studies, eight (Bold 1998; Cabaluna 2012; Chow 2000; Gulluoglu 2013; Gupta 2000; Paajanen 2009; Wagman 1990; Yetim 2010) included women only, one almost entirely women (Hall 2006) and two (Amland 1995; Platt 1990) may have contained male and female breast surgery participants, although this could not be established from the data presented in the report or by contacting the authors. All of these studies included breast cancer patients as one of multiple patient groups being analysed. The studies were conducted between 1990 and 2013. Study sizes ranged between 44 (Yetim 2010) and 618 (Hall 2006). In total 2867 participants were included for meta-analysis, 1439 in treatment arms and 1428 in control arms. These studies were conducted in the hospital setting, were single-centre trials and were conducted in eight different countries. Country of origin for studies were: Australia (Hall 2006), Norway (Amland 1995), United States of America (Bold 1998; Platt 1990; Wagman 1990), Japan (Chow 2000), Finland (Paajanen 2009), The Philipines (Cabaluna 2012), Turkey (Gulluoglu 2013; Yetim 2010) and United Kingdom (Gupta 2000). All included studies had been published.

 

Types of surgery

Types of participants included patients undergoing plastic surgery (Amland 1995), herniorrhaphy or breast surgery (Platt 1990), axillary lymph node dissection for breast cancer (Bold 1998) and primary, non-reconstructive surgery for breast cancer (Cabaluna 2012; Gulluoglu 2013; Gupta 2000; Hall 2006; Wagman 1990). One study (Chow 2000) was designed to look at inflammatory rather than infective episodes, however discrete data on infection rates were presented and therefore the study was eligible for inclusion. Two studies looked at axillary lymph node dissection as part of breast cancer treatment (Bold 1998; Gulluoglu 2013). One study (Paajanen 2009) looked at core needle biopsy and primary, non-reconstructive surgery for breast cancer. The four remaining studies (Cabaluna 2012; Gupta 2000; Wagman 1990; Yetim 2010) looked solely at breast cancer patients receiving primary, non-reconstructive surgery for breast cancer.

 

Length of follow-up

Length of follow-up from surgery ranged from five days (Chow 2000) to six months (Yetim 2010). One study (Gupta 2000) followed up patients between 10 and 14 days post discharge, but did not document the length of hospital stay for these patients.

 

Source of funding

Three studies (Amland 1995; Bold 1998; Platt 1990) stated that they were sponsored by a pharmaceutical company (Pfizer AS, Smith Kline & Beecham and Smith Kline & French laboratories, respectively). One study (Wagman 1990) was funded by the American Cancer Society and another (Paajanen 2009) by the Finnish cultural foundation. The source of funding was not reported in the other studies.

 

Antibiotics used

The antibiotics evaluated included:

  • azithromycin, single dose decided according to body weight, taken 8 pm the night before surgery (Amland 1995).
  • oral clarithromycin (500mg) for 10 doses (Chow 2000).
  • intravenous augmentin (1.2g) (Gupta 2000).
  • a single dose of intravenous flucloxacillin (2g) (Hall 2006).
  • cefazolin (six doses) (Wagman 1990).
  • a single dose of intravenous dicloxacillin (1g) (Paajanen 2009).
  • a single dose of cefonicid (1g) (Bold 1998; Platt 1990).
  • a single dose of intravenous cefazolin (1g) (Cabaluna 2012)
  • a single dose of intravenous ampicillin-sulbactam (1g) (Gulluoglu 2013)
  • collagen plus gentamycin sulphate (200mg) inserted under the surgical wound prior to surgical closure (Yetim 2010).

Five studies (Bold 1998; Cabaluna 2012; Gulluoglu 2013; Platt 1990; Wagman 1990) are very similar in terms of length of follow-up, choice of antibiotic and type of surgery undertaken. All studies had similar inclusion and exclusion criteria.

 

Immediate reconstruction with or without implants

No eligible studies evaluating prophylactic antibiotics for reconstructive surgery (with or without implants) were identified. Whilst three studies (Amland 1995; Baker 2000; Franchelli 1994) included patients undergoing reconstructive surgery, we excluded the studies following scrutiny. It was not clear that the patients had undergone surgery as part of breast cancer treatment (Amland 1995; Franchelli 1994) whilst one study was excluded because the research was addressing the needs of dental patients who have existing implants (Baker 2000).

 

Neo-adjuvant chemotherapy

Two studies included patients who had received neo-adjuvant chemotherapy (Bold 1998; Platt 1990).

 

Excluded studies

We excluded a total of 27 studies for the following reasons: two were reviews, 11 were not RCTs or quasi RCTs, one was a multiple drug comparison excluded as there was no placebo or control arm. One compared different regimens and doses, but had no control or placebo arm. We excluded one study as it could not be obtained from the British Library. Four abstracts were excluded as they may have been multiple publications of the same study and clarification could not be obtained from the authors. Five studies did not provide discrete data for breast cancer patients and two were found to be studies focused on other types of surgery (see Characteristics of excluded studies table).

 

Risk of bias in included studies

See 'Risk of bias' summary figure: Figure 1. Studies were judged to be at overall unclear or high risk of bias if they were described as unclear or at high risk of bias in the majority of the domains.

 FigureFigure 1. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

 

Allocation

 

Sequence generation

Eleven studies were described as RCTs, but only eight adequately generated the randomisation sequence by reporting the use of computer-generated numbers or sequences of blocks of 10 and were at low risk of bias for this domain (Amland 1995; Bold 1998; Cabaluna 2012; Chow 2000; Gulluoglu 2013; Gupta 2000; Hall 2006; Wagman 1990). Three studies were classified as unclear as the authors failed to report the method by which randomisation sequence was generated (Paajanen 2009; Platt 1990; Yetim 2010).

 

Allocation concealment

Adequate allocation concealment was described for eight studies (Bold 1998; Cabaluna 2012; Gulluoglu 2013; Gupta 2000; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990) and they were therefore at low risk of bias. Three of these studies used the hospital pharmacy to generate the allocation for participants (Bold 1998; Platt 1990; Wagman 1990). One study stated that consecutive patients were allocated to group by a computer program (Chow 2000) however the method of allocation was not described and two studies used sealed opaque sequentially numbered envelopes (Gupta 2000; Hall 2006). One study reported the use of both hospital pharmacy as well as sealed, opaque, sequentially numbered envelopes (Paajanen 2009). In the remaining three studies the method of allocation concealment was not described (Amland 1995; Chow 2000; Yetim 2010) and therefore they are classified as at unclear risk of bias.

 

Blinding

 

Blinding (participants and treatment providers - all outcomes)

Adequate blinding of participants and treatment providers was clearly reported in seven trials and therefore these were at low risk of bias (Amland 1995; Bold 1998; Cabaluna 2012; Gupta 2000; Paajanen 2009; Platt 1990; Wagman 1990). Three trials were classified as having inadequate blinding of both participants and treatment providers mainly because the control groups were not blinded as they were not given any treatment. (Chow 2000; Gulluoglu 2013; Yetim 2010). Whilst blinding was not specifically reported by Hall 2006 the antibiotic was administered after the induction of anaesthesia therefore it is possible that blinding was adequate but as there was no statement by the study authors we judged this to be unclear.

 

Blinding (outcome assessors - all outcomes)

Nine studies described adequate blinding of outcome assessors and these were at low risk of measurement bias. All antibiotic compared with placebo studies stated that the key physician was unaware of patient allocation until data collection was complete (Amland 1995; Cabaluna 2012; Chow 2000; Gulluoglu 2013; Gupta 2000; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990). In one study it remained unclear if the outcome assessors were adequately blinded (Bold 1998) and in another (Yetim 2010) it was judged that the nature of the collagen implants under the wound site would unblind the outcome assessors.

 

Incomplete outcome data

In ten studies we judged the loss to follow-up to be low, with similar numbers of participants lost in both control and treatment groups and valid reasons given (Amland 1995; Bold 1998; Cabaluna 2012; Chow 2000; Gulluoglu 2013; Gupta 2000; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990). In one study (Yetim 2010) the study was judged to be unclear for this domain because the authors stated that patients would be followed up for six months post surgery but only reported data at seven days.

We judged six studies to have undertaken an ITT analysis either because they explicitly reported this or because there were no drop outs from the study and the numbers of participants in the groups analysed at the final follow up of the study were the same as those randomised at the outset (Amland 1995; Cabaluna 2012; Gulluoglu 2013; Gupta 2000; Hall 2006; Paajanen 2009). Intention-to-treat analysis was not reported in the other five studies (Bold 1998; Chow 2000; Platt 1990; Wagman 1990; Yetim 2010).

 

Selective reporting

The study protocols were not available but all the important outcome measures stated in the methods section are reported in the results and therefore we judged this domain to be at low risk of bias for all studies.

 

Other potential sources of bias

We judged seven trials to be at low risk of bias for this domain because there was no imbalance in the baseline characteristics and the studies appeared free from other forms of bias (Cabaluna 2012; Chow 2000; Gupta 2000; Hall 2006; Paajanen 2009; Wagman 1990; Yetim 2010). In three remaining studies (Amland 1995; Bold 1998; Platt 1990) there was some funding reported from pharmaceutical companies but it was unclear the extent of the industry involvement and we have adopted a cautious approach by judging there to be a high risk of bias. One study (Gulluoglu 2013) highlighted a difference in the baseline characteristics, stating that patients in the control group had significantly more frequent open surgical biopsies than those in the prophylaxis group, as a result this study was judged at a high risk of bias for this domain.

 

Effects of interventions

 

Preoperative antibiotics compared with placebo or no antibiotic (ten trials, 2823 participants)

Seven studies (Amland 1995; Bold 1998; Cabaluna 2012; Gupta 2000; Paajanen 2009; Platt 1990; Wagman 1990) compared preoperative antibiotics with placebo. Three studies (Chow 2000; Hall 2006; Gulluoglu 2013) compared preoperative antibiotics with no treatment.

 

Incidence of postoperative wound infection

All ten trials recorded incidence of wound infection as an outcome. Results are presented as risk ratio (RR) where the risk ratio is the risk of infection in the intervention group divided by the risk of infection in the control group. A risk ratio of less than one indicates fewer infections in the intervention group. Two studies compared cefonicid with placebo (Bold 1998; Platt 1990), one compared azithromycin with placebo (Amland 1995), one compared augmentin with placebo (Gupta 2000), two compared cefazolin with placebo (Cabaluna 2012; Wagman 1990), one compared flucloxacillin with no treatment (Hall 2006), one compared ampicillin-sublactam with no treatment (Gulluoglu 2013), one compared dicloxacillin with placebo (Paajanen 2009) and one compared clarithromycin with no treatment (Chow 2000). One study (Chow 2000) reported no infections in either group but in the remaining nine trials there were fewer infections in the groups treated with antibiotics, this was statistically significant in one study (Gulluoglu 2013) which considered overweight and obese breast cancer patients. In the other eight trials the results were not statistically significant ( Analysis 1.1).

In addition pooling the two studies which compared cefonicid with placebo (Bold 1998; Platt 1990) showed a statistically significant reduction in infection associated with preoperative antibiotics (RR 0.56, 95% confidence interval (CI) 0.33 to 0.95) ( Analysis 1.2). Pooling the two studies which compared cefazolin with placebo (Cabaluna 2012; Wagman 1990) showed no significant reduction in infection (RR 0.82, 95% CI 0.47 to 1.42)

We pooled all the trials using a fixed-effect model as there was no evidence of heterogeneity (I2 = 0%). The pooled risk ratio shows that giving preoperative antibiotics significantly reduces the risk of wound infection after breast cancer surgery (RR 0.67, 95% CI 0.53 to 0.85) ( Analysis 1.1). We carried out a sensitivity analysis to exclude one study (Chow 2000), as this study had short follow-up, only compared antibiotics with no antibiotic and reported inflammation rather than infection as its primary outcome. Sensitivity analysis demonstrated no effect from removing Chow from the pooled analysis.

One study (Bold 1998) documented infection rates in those who received neo-adjuvant chemotherapy; there was no statistically significant difference between the groups treated with cefonicid compared with the placebo group (RR 0.21, 95% CI, 0.01 to 4.12) ( Analysis 1.4). Another study provided details of the number of patients who had previously received chemotherapy (Platt 1990) but did not report separate data on infection rates for these patients.

Since there is evidence that the quality of allocation concealment influences study results (Schulz 1995) we examined the effect of excluding studies judged to have inadequate allocation concealment in a prespecified sensitivity analysis. We judged two studies (Amland 1995; Chow 2000) to have unclear allocation concealment. Removing these studies from the meta-analysis resulted in a pooled RR of 0.67 (95% CI 0.52 to 0.85) which was still significantly in favour of prophylactic antibiotics.

 

Cost of care

Two studies (Bold 1998; Gulluoglu 2013) reported the cost of care ( Analysis 1.5). In one study (Bold 1998) the cost did not include the cost of operation or associated stay in hospital, but calculated the cost of any additional care or medications (i.e. antibiotic prophylaxis, postoperative antibiotics or wound care). They found that the average cost per patient was USD 49.80 in the antibiotic prophylaxis group and USD 364.87 in the control group. The majority of this cost difference was accounted for in patients readmitted to hospital for wound complications. In the other study (Gulluoglu 2013) little detail is given regarding what the cost included. The report states it calculated "SSI-related treatment cost". The study reported that the control group had a significantly higher cost (USD 20.26) when compared with the treatment group (USD 8.48).

 

Adverse reactions to treatment

Six studies (Bold 1998; Gupta 2000; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990) reported adverse events (please refer to other data tables for adverse effects from antibiotics under antibiotic versus none or placebo) ( Analysis 1.6). Seven studies reported there were no adverse events (Bold 1998; Cabaluna 2012; Gulluoglu 2013; Hall 2006; Paajanen 2009; Platt 1990; Wagman 1990) and one study (Gupta 2000) reported 41 adverse events (23%) in the treatment group and 33 (18%) in the control group, but no details were reported on type of adverse events. Although we contacted authors for clarification about the nature of these events, they did not reply. The remaining three studies made no mention of adverse events in the study report.

 

Death

No studies presented information on deaths.

 

Time to wound healing

No studies presented information on time to wound healing.

 

Delay in adjuvant cancer treatment caused by SSI

No studies presented information on delays in adjuvant cancer treatments due to SSI.

 

Time to onset of infection

Four studies reported time to onset of infection ( Analysis 1.7), however they all provided the mean time to onset of infection and not a range and therefore we have not combined this in a meta-analysis. Two studies (Gupta 2000; Platt 1990) documented similar mean times to onset of infection: 12 and 11 days in the intervention group and 11 and 10 days in the control group respectively. Wagman 1990 documented mean time of onset of infection of 17.7 days in the intervention group and 9.6 days in the control group. Gulluoglu 2013 states that the time to onset of infection was similar in both the control and intervention group. The study provides a table of data with a range of onset of infection times. The majority of infections (62%) were detected between 3 and 7 days postoperatively.

 

Readmission to hospital

Three studies (Bold 1998; Gulluoglu 2013; Platt 1990) reported readmission rates following treatment. In one study (Gulluoglu 2013) no patients required readmission to hospital. In the other two studies, due to heterogeneity (I2 = 70.8%) we did not pool results. One study (Bold 1998) reported statistically significantly lower readmission rates in those treated with prophylactic antibiotics (RR 0.11, 95% CI 0.01 to 0.88) ( Analysis 1.8) and a shorter duration of readmission (placebo group 5.9 days, prophylaxis group 3.0 days); the other study found no reduction in readmission rates (RR 1.0, 95% CI 0.29 to 3.42) ( Analysis 1.8). As such no conclusions can be drawn on this outcome.

 

Perioperative antibiotics compared with placebo or no antibiotic (one trial, 44 participants)

One study (Yetim 2010) compared perioperative antibiotics with no antibiotic.

 

Incidence of postoperative wound infection

This small study at overall high risk of bias presented wound infection as an outcome. The study compared gentamycin-infused collagen (Gentacoll) inserted perioperatively with no antibiotic. There were no infections in the antibiotic-treated group compared with four infections in the control group. Whilst the study author stated this to be significantly better in favour of the antibiotic group this was not replicated in our analysis (RR 0.11, 95% CI 0.01 to 1.95) ( Analysis 2.1).

 

Cost of care

The study did not report the cost of care.

 

Adverse reactions to treatment

The study did not report any adverse reactions to treatment.

 

Deaths

The study did not report any information on deaths.

 

Delay in adjuvant cancer treatment caused by SSI

The study did not report any information on delays in adjuvant cancer treatment caused by SSI.

 

Time to onset of infection

The study did not report any information on the time to onset of infection.

 

Readmission to hospital

The study reports that two patients in the control group had to be readmitted for parenteral antibiotics as a result of wound infection. No patients in the antibiotic group were readmitted.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

This review found that preoperative antibiotics significantly reduce the risk of SSI in people undergoing surgery for breast cancer when compared with placebo or no treatment. Of the nine studies that reported data on adverse events only one found an increase of events in the intervention group, however detailed information about the nature of the adverse events was not given and adverse events were generally poorly reported across the included studies. In addition data for some of the outcomes, including deaths, delays in adjuvant cancer treatments, cost and readmissions were reported by few of the included studies. We found one study that evaluated perioperative antibiotics compared with no antibiotic; this small study found that perioperative antibiotics did not significantly reduce the incidence of SSI. We found no studies evaluating antibiotics for breast reconstruction at the time of the initial surgery.

We found one systematic review and meta analysis on the effects of antibiotic prophylaxis for breast cancer surgery which also concluded that prophylactic antibiotics reduce SSIs (Tejirian 2006). Another systematic review (Sajid 2012) also considered non breast cancer patients and concluded that prophylactic antibiotics reduce the incidence of SSIs.Two non-systematic reviews (D'Amico 2001; Hall 2000) did not draw any firm conclusions. Similar systematic reviews in other types of clean surgery are scarce and have produced varied results (Gillespie 2010; Sanchez-Manuel 2007).

We found only eleven studies with a total of 2867 participants; not many considering the number of people affected globally by breast cancer. Whilst it is encouraging that a statistically significant result was found it is possible that the numbers are not adequate to evaluate fully the risks and benefits of antibiotic prophylaxis for breast cancer surgery. In addition, although we found some trials that included people having immediate breast reconstruction we excluded them as we were unable to obtain discrete data specifically for breast cancer patients.

Whilst all efforts were made to obtain unpublished data, all the included studies had been published, therefore there is potential for publication bias. Testing for publication bias was not done due to the small number of studies obtained.

Although there was no statistical heterogeneity only four studies compared the same antibiotic using the same regimen (Bold 1998; Cabaluna 2012; Platt 1990; Wagman 1990), therefore we were unable to make conclusions about the most effective antibiotic and regimen. Other recent research has, however, recommended that antibiotic prophylaxis should generally be administered as a single dose preoperatively in order to maximise benefit and minimise adverse effects from treatment (SIGN 2008a).

In general the included trials were at low risk of bias for the main domains of sequence generation and allocation concealment. Three studies had unclear allocation concealment (Amland 1995; Chow 2000; Yetim 2010) and excluding these studies from the analysis made little difference to the result. One study (Chow 2000) had a follow-up of only five days. As the average time to onset of infection in the other included studies ranged between 11 to 17.7 days it may have been appropriate to specify in the protocol a minimum length for follow-up. However, excluding data from this study made no difference to the overall outcomes. However, we judged one study (Yetim 2010) which compared perioperative antibiotics with no antibiotic to be at high risk of bias overall due to a failure of blinding and insufficient information given regarding selection bias.

Overall, there are sufficient data from this review to suggest that antibiotic prophylaxis reduces surgical site infections in those undergoing non-reconstructive breast cancer surgery. However further research would be required to establish the best protocols for practice.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

Preoperative prophylactic antibiotics reduce the risk of a SSI in people undergoing breast cancer surgery. However, this review does not establish the most effective antibiotic regimen to use.

 
Implications for research

Further large, high-quality randomised controlled trials are needed to establish the most effective prophylactic antibiotic protocols. Analysis of secondary outcomes, such as adverse events, delays in adjuvant cancer treatments and costs of care, would aid the development of well considered and useful protocols and standards for practice. In addition trials need to evaluate the use of antibiotics in women undergoing immediate breast reconstruction.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

The authors would like to thank referees from the Cochrane Wounds Group (Nicky Cullum, Mieke Flour, Andrew Jull, Rachel Richardson and Allyson Lipp) and from the Cochrane Breast Cancer group (Sharon Parker and Liz Lostumbo) for their comments to improve the review. Melanie Cunningham and Karen Hanscombe both contributed as authors of the original review but have not participated in any of the subsequent updates and are no longer involved.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. Preoperative antibiotics versus none or placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Wound infections102823Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.53, 0.85]

    1.1 Preoperative antibiotic versus placebo
71784Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.56, 0.97]

    1.2 Preoperative antibiotic versus none
31039Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.28, 0.81]

 2 Wound infection cefonicid2747Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.33, 0.95]

 3 Wound infection cefazolin2336Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.47, 1.42]

 4 Infection rates in those who received neo-adjuvant chemo147Risk Ratio (M-H, Fixed, 95% CI)0.21 [0.01, 4.12]

 5 Cost of careOther dataNo numeric data

 6 Adverse effects from antibioticsOther dataNo numeric data

    6.1 Preoperative antibiotics versus placebo
Other dataNo numeric data

    6.2 Preoperative antibiotics versus none
Other dataNo numeric data

 7 Time to onset of infectionOther dataNo numeric data

    7.1 Preoperative antibiotic versus placebo
Other dataNo numeric data

 8 Readmission to hospital2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    8.1 Preoperative antibiotics versus placebo
2784Risk Ratio (M-H, Random, 95% CI)0.39 [0.04, 3.49]

 
Comparison 2. Perioperative antibiotics compared with no antibiotic

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Wound infection1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Search strategy for the second update of this review - 2011

 

Electronic searches

For the second update of this review we searched the following electronic databases:

  • the Cochrane Wounds Group Specialised Register (searched 31 August 2011);
  • the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3);
  • Ovid MEDLINE (2008 to August Week 3 2011);
  • Ovid EMBASE (1980 to 2011 Week 34);
  • Ovid MEDLINE (In-Process & Other Non-Indexed Citations August 30, 2011);
  • EBSCO CINAHL (2008 to 25 August 2011).

We used the following search strategy in the Cochrane Central Register of Controlled Trials (CENTRAL):

#1 MeSH descriptor Surgical Wound Infection explode all trees
#2 surg* NEAR/5 infection*
#3 surgical NEAR/5 wound*
#4 (postoperative or post-operative) NEAR/5 infection*
#5 MeSH descriptor Preoperative Care explode all trees
#6 (preoperative or pre-operative) NEXT care
#7 MeSH descriptor Perioperative Care explode all trees
#8 (perioperative or peri-operative) NEXT care
#9 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8)
#10 MeSH descriptor Breast Neoplasms explode all trees with qualifier: SU
#11 (breast NEXT cancer) NEAR/5 surg*
#12 (breast NEXT neoplasm*) NEAR/5 surg*
#13 (breast NEXT carcinoma*) NEAR/5 surg*
#14 MeSH descriptor Mastectomy explode all trees
#15 MeSH descriptor Mammaplasty explode all trees
#16 mastectomy or mammaplasty
#17 MeSH descriptor Breast explode all trees with qualifier: SU
#18 (#10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17)
#19 MeSH descriptor Anti-Bacterial Agents explode all trees
#20 (antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin or sulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin)
#21 (#19 OR #20)
#22 (#9 AND #18 AND #21)

The search strategies for Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL can be found in Appendix 2, Appendix 3 andAppendix 4 respectively. We combined the MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision); Ovid format. We combined the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN). We applied no language or date restrictions.

 

Searching other resources

In addition, we screened references in all articles found by the above search strategy for further studies. We contacted experts in the field and interest groups to try and obtain access to unpublished or ongoing work. We followed up conference proceedings and grey literature that was considered to be potentially eligible for inclusion by both authors by contacting the study authors for further information.

 

Appendix 2. Ovid MEDLINE search strategy

1 exp Surgical Wound Infection/ (28294)
2 exp Surgical Wound Dehiscence/ (6260)
3 (surg* adj5 infect*).tw. (18792)
4 (surg* adj5 wound*).tw. (10115)
5 (surg* adj5 site*).tw. (11417)
6 (surg* adj5 incision*).tw. (6420)
7 (surg* adj5 dehisc*).tw. (585)
8 (wound* adj5 dehisc*).tw. (2813)
9 (wound* adj5 infect*).tw. (22384)
10 (wound adj5 disrupt*).tw. (350)
11 wound complication*.tw. (2992)
12 or/1-11 (80916)
13 exp Breast Neoplasms/su [Surgery] (30204)
14 (breast cancer* adj5 surg*).tw. (6097)
15 (breast neoplasm* adj5 surg*).tw. (36)
16 (breast carcinoma* adj5 surg*).tw. (609)
17 exp Mastectomy/ (23306)
18 exp Mammaplasty/ (8405)
19 (mastectomy or mammaplasty).tw. (15479)
20 exp Breast/su [Surgery] (5305)
21 or/13-20 (50942)
22 exp Anti-Bacterial Agents/ (537825)
23 (antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin or sulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin).tw. (266425)
24 22 or 23 (634056)
25 12 and 21 and 24 (175)
26 Randomized controlled trials/ (103066)
27 Single-Blind Method/ (19669)
28 Double-Blind Method/ (132149)
29 Crossover Procedure/ (0)
30 (random$ or factorial$ or crossover$ or cross over$ or cross-over$ or placebo$ or assign$ or allocat$ or volunteer$).ti,ab. (1039219)
31 (doubl$ adj blind$).ti,ab. (116870)
32 (singl$ adj blind$).ti,ab. (11180)
33 or/26-32 (1116089)
34 exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/ (17778990)
35 human/ or human cell/ (13712248)
36 and/34-35 (13712248)
37 34 not 36 (4066742)
38 33 not 37 (992785)
39 25 and 38 (46)

 

Appendix 3. Ovid EMBASE search strategy

1 exp surgical infection/ (17291)
2 exp wound dehiscence/ (7784)
3 (surg* adj5 infect*).tw. (18838)
4 (surg* adj5 wound*).tw. (9077)
5 (surg* adj5 site*).tw. (14367)
6 (surg* adj5 incision*).tw. (7513)
7 (surg* adj5 dehisc*).tw. (637)
8 (wound* adj5 dehisc*).tw. (3036)
9 (wound* adj5 infect*).tw. (21393)
10 (wound adj5 disrupt*).tw. (311)
11 wound complication*.tw. (3233)
12 or/1-11 (74860)
13 exp Breast Tumor/su [Surgery] (34682)
14 (breast cancer* adj5 surg*).tw. (7357)
15 (breast neoplasm* adj5 surg*).tw. (16)
16 (breast carcinoma* adj5 surg*).tw. (492)
17 exp mastectomy/ (27258)
18 exp breast reconstruction/ (11159)
19 (mastectomy or mammaplasty).tw. (14647)
20 exp Breast Surgery/ (38660)
21 or/13-20 (55407)
22 exp antibiotic agent/ (589638)
23 (antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin or sulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin).tw. (219686)
24 or/22-23 (658872)
25 12 and 21 and 24 (304)
26 Randomized controlled trials/ (42188)
27 Single-Blind Method/ (17133)
28 Double-Blind Method/ (91694)
29 Crossover Procedure/ (34738)
30 (random$ or factorial$ or crossover$ or cross over$ or cross-over$ or placebo$ or assign$ or allocat$ or volunteer$).ti,ab. (1049911)
31 (doubl$ adj blind$).ti,ab. (98333)
32 (singl$ adj blind$).ti,ab. (10782)
33 or/26-32 (1093705)
34 exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/ (12313060)
35 human/ or human cell/ (9544901)
36 and/34-35 (9544609)
37 34 not 36 (2768451)
38 33 not 37 (946515)
39 25 and 38 (57)

 

Appendix 4. EBSCO CINAHL search strategy

S36 S23 AND S35
S35 S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33 or S34
S34 MH "Quantitative Studies"
S33 TI placebo* or AB placebo*
S32 MH "Placebos"
S31 TI random* allocat* or AB random* allocat*
S30 MH "Random Assignment"
S29 TI randomi?ed control* trial* or AB randomi?ed control* trial*
S28 AB ( singl* or doubl* or trebl* or tripl* ) and AB ( blind* or mask* )
S27 TI ( singl* or doubl* or trebl* or tripl* ) and TI ( blind* or mask* )
S26 TI clinic* N1 trial* or AB clinic* N1 trial*
S25 PT Clinical trial
S24 MH "Clinical Trials+"
S23 S10 AND S18 AND S22
S22 S19 OR S20 OR S21
S21 AB ( antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin orsulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin )
S20 TI ( antibiotic* or clindamycin or cefuroxime or cefuroxim or ceftazidime or ofloxacin or levofloxacin or azithromycin orsulbactam or ampicillin or mezlocillin or oxacillin or vancomycin or tobramycin or ciprofloxacin )
S19 (MH "Antibiotics+")
S18 S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17
S17 (MH "Breast/SU")
S16 TI ( mastectomy or mammaplasty ) or AB ( mastectomy or mammaplasty )
S15 (MH "Mastectomy+")
S14 TI breast carcinoma* N5 surg* or AB breast carcinoma* N5 surg*
S13 TI breast neoplasm* N5 surg* or AB breast neoplasm* N5 surg*
S12 TI breast cancer* N5 surg* or AB breast cancer* N5 surg*
S11 (MH "Breast Neoplasms/SU")
S10 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9
S9 TI wound complication* or AB wound complication*
S8 TI wound* N5 dehisc* or AB wound* N5 dehisc*
S7 TI surg* N5 dehisc* or AB surg* N5 dehisc*
S6 TI surg* N5 incision* or AB surg* N5 incision*
S5 TI surg* N5 site* or AB surg* N5 site*
S4 TI surg* N5 wound* or AB surg* N5 wound*
S3 TI surg* N5 infection* or AB surg* N5 infection*
S2 (MH "Surgical Wound Infection")
S1 (MH "Surgical Wound Dehiscence")

 

Appendix 5. Risk of bias criteria

 

1.  Was the allocation sequence randomly generated?

 
Low risk of bias

The investigators describe a random component in the sequence generation process such as: referring to a random number table; using a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.

 
High risk of bias

The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.

 
Unclear

Insufficient information about the sequence generation process to permit judgement of low or high risk of bias.

 

2.  Was the treatment allocation adequately concealed?

 
Low risk of bias

Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation); sequentially-numbered drug containers of identical appearance; sequentially-numbered, opaque, sealed envelopes.

 
High risk of bias

Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

 
Unclear

Insufficient information to permit judgement of low or high risk of bias. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.

 

3.  Blinding - was knowledge of the allocated interventions adequately prevented during the study?

 
Low risk of bias

Any one of the following.

  • No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by lack of blinding.
  • Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
  • Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of others unlikely to introduce bias.

 
High risk of bias

Any one of the following.

  • No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.
  • Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.
  • Either participants or some key study personnel were not blinded, and the non-blinding of others likely to introduce bias.

 
Unclear

Any one of the following.

  • Insufficient information to permit judgement of low or high risk of bias.
  • The study did not address this outcome.

 

4. Were incomplete outcome data adequately addressed?

 
Low risk of bias

Any one of the following.

  • No missing outcome data.
  • Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias).
  • Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.
  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size.
  • Missing data have been imputed using appropriate methods.

 
High risk of bias

Any one of the following.

  • Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups.
  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate.
  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size.
  • ‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.
  • Potentially inappropriate application of simple imputation.

 
Unclear

Any one of the following.

  • Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomised not stated, no reasons for missing data provided).
  • The study did not address this outcome.

 

5. Are reports of the study free of suggestion of selective outcome reporting?

 
Low risk of bias

Any of the following.

  • The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way.
  • The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon)

 
High risk of bias

Any one of the following.

  • Not all of the study’s pre-specified primary outcomes have been reported.
  • One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified.
  • One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect).
  • One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.
  • The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

 
Unclear

Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.

 

6. Other sources of potential bias

 
Low risk of bias

The study appears to be free of other sources of bias.

 
High risk of bias

There is at least one important risk of bias. For example, the study:

  • had a potential source of bias related to the specific study design used; or
  • had extreme baseline imbalance; or
  • has been claimed to have been fraudulent; or
  • had some other problem.

 
Unclear

There may be a risk of bias, but there is either:

  • insufficient information to assess whether an important risk of bias exists; or
  • insufficient rationale or evidence that an identified problem will introduce bias.

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 5 December 2013.


DateEventDescription

4 March 2014New citation required but conclusions have not changedThird update, conclusions remain unchanged.

4 March 2013New search has been performedNew search, two further studies included (Cabaluna 2012; Gulluoglu 2013) and five studies excluded.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 2, 2005
Review first published: Issue 2, 2006


DateEventDescription

23 September 2011New citation required but conclusions have not changedNew authors added to the review

31 August 2011New search has been performedSecond update, new searches, two studies added (Paajanen 2009; Yetim 2010), two studies excluded (Esposito 2006; Sanguinetti 2009).

11 August 2009AmendedContact details updated.

24 October 2008New search has been performedOne new trial added. Conclusions unchanged.

28 July 2008AmendedConverted to new review format.

18 December 2005New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Daniel Jones: contributed to the second and took the lead for the third update of this review, screened records for eligibility, extracted data, undertook the risk of bias assessment and updated the review text.
Frances Bunn: provided methodological support, screened records, extracted data, helped to write the review and undertook the updating of the review.
Sophie Bell-Syer: contributed to the second and third update of this review, screened records for eligibility, extracted data, undertook the risk of bias assessment and commented on the review update.

Contributions of editorial base:
Nicky Cullum: edited the review, advised on methodology, interpretation and review content. Approved the final review and review update prior to submission.
Sally Bell-Syer: co-ordinated the editorial process. Advised on methodology, interpretation and content. Edited and copy edited the review. Screened studies for the updated review and edited the updated review.
Ruth Foxlee: designed the search strategy and edited the search methods section for the update.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • University of Hertfordshire, UK.
  • Department of Health Sciences, University of York, York, UK.

 

External sources

  • NIHR/Department of Health (England), (Cochrane Wounds Group), UK.

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Amland 1995 {published data only}
  • Amland PF, Andenaes K, Samdal F, Linaas E, Sandsmark M, Abeyholm F, et al. A prospective double-blind, placebo-controlled trial of a single dose of azithromycin on postoperative wound infections in plastic surgery. Plastic and Reconstructive Surgery 1995;96(6):1378-83.
Bold 1998 {published data only}
  • Bold RJ, Mansfield PF, Berger DH, Pollock RE, Sinletary SE, Ames FC, et al. Prospective randomised, double-blind study of prophylactic antibiotics in axillary lymph node dissection. American Journal of Surgery 1998;176(3):239-43.
Cabaluna 2012 {published data only}
  • Cabaluna ND, Galicia RM, Yray MDS. A randomized, double-blinded placebo-controlled clinical trial of the routine use of preoperative antibiotic prophylaxis in modified radical mastectomy. World Journal of Surgery 2012;37:59-66.
Chow 2000 {published data only}
  • Chow LW, Yuen KY, Woo PC, Wei W. Clarithromycin attenuates mastectomy-induced acute inflammatory response. Clinical and Diagnostic Laboratory Immunology 2000;7(6):925-31.
Gulluoglu 2013 {published data only}
  • Gulluoglu B, Guler S, Ugurlu U. Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients. Annals of Surgery 2013;257(1):37-43.
Gupta 2000 {published data only}
  • Gupta R, Sinnett D, Carpenter R, Preece PE, Royle GT. Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery. European Journal of Surgical Oncology 2000;26(4):363-6.
Hall 2006 {published data only}
Paajanen 2009 {published data only}
  • Paajanen H, Hermunen H. Does preoperative core needle biopsy increase surgical site infections in breast cancer surgery? Randomized study of antibiotic prophylaxis. Surgical Infections 2009;10(4):317-21.
Platt 1990 {published data only}
  • Platt R, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, Bryan CS, et al. Perioperative antibiotic prophylaxis for hernioplasty and breast surgery. New England Journal of Medicine 1990;322(3):153-60.
Wagman 1990 {published data only}
  • Wagman LD, Tegtmeier B, Beatty JD, Kloth DD, Kokal WA, Riihimaki DU, et al. A prospective, randomised double-blind study of the use of antibiotics at the time of mastectomy. Surgery, Gynecology and Obstetrics 1990;170(1):12-6.
Yetim 2010 {published data only}
  • Yetim I, Ozkan OV, Dervisoglu A, Erzurumlu K, Canbolant E. Effect of local gentamycin application on healing and wound infection in patients with modified radical mastectomy: a prospective randomised study. Journal of International Medical Research 2010;38(4):1442-7.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Baker 2000 {published data only}
  • Baker KA. Antibiotic prophylaxis for selected implants and devices. CDA Journal 2000;28(35):620-6.
Baker 2005 {published and unpublished data}
  • Baker E, Kumar S, Whetter D, Melling A, Leaper D. Does warming effect wound healing profiles following breast surgery?. European wound management association conference; 2005, 15-17 September; Stuttgart, Germany 2005;2:68.
Bertin 1998 {published data only}
Boyd 1981 {published data only}
D'Amico 2001 {published data only}
  • D'Amico DF, Parimbelli P, Ruffolo C. Antibiotic prophylaxis in clean surgery: breast surgery and hernia repair. Journal of Chemotherapy 2001;13(1):108-11.
Erfle 2002 {published data only}
  • Erfle V, Schoen A, Marquart KH, Pawlita M. [HGF-Strategiefond 'Infektabwehr und Krebspaevention'. Impfstoff gegen krebs-Infektionsabwehr und Krebspraevention. Abschlussbericht. GSF- Forschungszentrum fuer Umwelt und Gesundhiet Neuherberg GmbH Oberschleissheim (DE)]. SIGLE. 2002.
Esposito 2006 {published data only}
  • Esposito S, Leone S, Noviello S, Ianniello F, Marvaso A, Cuniato V, et al. Antibiotic prophylaxis in hernia repair and breast surgery: a prospective randomised study comparing piperacillin/tazobactam versus placebo. Journal of Chemotherapy 2006;18(3):278-84.
Exener 1992 {published data only}
  • Exner K, Lang E, Borsche A, Lemperle G. Efficacy, tolerability and pharmokinetics of teicoplanin in patients undergoing breast surgery. European Journal of Surgery 1992;Suppl 567:9-12.
Franchelli 1994 {published data only}
  • Franchelli S, Leone MS, Vigna E, Rapsosio E, Cafierio F, Constantini M, et al. Perioperative teicoplanin prophylaxis in patients undergoing breast reconstruction with the abdominal wall. A case control study. Minerva Chirurgica 1994;49(1):59-60.
Hall 2000 {published data only}
Kumar 2005 {published and unpublished data}
  • Kumar S, Melling A, Wong PF, Whetter D, Leaper DJ. Wound infection prophylaxis in breast surgery: a randomised controlled trial comparing the efficacy of antibiotics and perioperative wound warming. British Journal of Surgery 2005;92(1):67.
LeRoy 1991 {published data only}
Lewis 1995 {published data only}
Melling 2005 {published and unpublished data}
  • Melling A, Kumar S, Whetter D, Baker L, Leaper D. A comparison of warming with antibiotics or both on the rate of surgical site infection after breast surgery. European wound management association conference; 2005, 15-17 September; Stuttgart, Germany 2005;Thursday 14:00-15:30; V25-3:67.
Melling 2006 {published and unpublished data}
  • Melling A, Kumar S, Whetter D, Baker E, Leaper D. Local warming may enhance the effect of prophylactic antibiotics in breast surgery. 16th conference of the european wound management association; 2006, 18-20 May; Prague, Czech Republic. 2006:88, Abstract no.109.
Morimoto 1998 {published data only}
Nicholas 2007 {published data only}
  • Nicholas P, Yazdan Y, Marie Pierre C, Sylvia G, Jean Charles N, Daniele L, et al. Prevention of surgical site infection after breast cancer surgery by targeted prophylaxis antibiotic in patients at high risk of surgical site infection. Journal of Surgical Oncology 2007;96(2):124-9.
Pennel 2004 {published data only}
  • Pennel N, Fournier C, Giard S, Lefebvres D. A prospective evaluation of antibiotic prophylaxis for breast surgery following previous chemotherapy. Bulletin du Cancer 2004;91(5):445-8.
Platt 1992 {published data only}
  • Platt R, Zucker JR, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, et al. Prophylaxis against wound infection following hernioplasty or breast surgery. Journal of Infectious Diseases 1992;166(3):556-60.
Platt 1993 {published data only}
  • Platt R, Zucker JR, Zaleznik DF, Hopkins CC, Dellinger EP, Karchmer AW, et al. Perioperative antibiotic prophylaxis and wound infection following breast surgery. Journal of Antimicrobial Chemotherapy 1993;31(Suppl B):43-8.
Sanguinetti 2009 {published data only}
  • Sanguinetti A, Rosato L, Cirocchi R, Barberini F, Pezzolla A, Cavallaro G, et al. Antibiotic prophylaxis in breast surgery. Preliminary results of a multicenter randomised study on 1400 cases [Antibiotico profilassi in Chirurgia Senologica Risultati preliminari di uno studio multicentrico randomizzato su 1400 casi trattati]. Annali Italiani di Chirurgia 2009;80(4):275-9.
Sasaki 1988 {published data only}
  • Sasaki F, Takada N, Hata Y, Kyunoh K, Uchino J. A study on the transfer of cefbuperazone into postoperative exudate in patients subjected to cancer mastectomy or thyroidectomy. Japanese Journal of Antibiotics 1988;466:114-20.
Serletti 1994 {published data only}
Shamilov 1991 {published data only}
  • Shamilov AK, Smolianskaia AZ. The antibiotic prophylaxis of postoperative complications in breast cancer patients. Antibiotiki i Khimioterapiia 1991;36(6):43-4.
Spicher 2003 {published data only}
  • Spicher I, Beer GM, Minder J, Ruef Ch, Szucs T, Meyer VE. Perioperative antibiotic prophylaxis at the clinic of reconstructive surgery of the university hospital Zurich [Zur umsetzung einer perioperativen antibiotikapropylaxe an der klinik fur wiederstellungschirugie des universitatsspitals Zurich]. Swiss Surgery 2003;9(1):9-14.
Sultan 1989 {published data only}
  • Sultan S, Ahmed R, Mufti T, Mohammad G, Nawaz M. Use of prophylactic antibiotics in clean surgical cases - a prospective trial of various regimens. Journal of Pakistan Medical Association 1989;39(1):9-12.
Thomas 1999 {published data only}
  • Thomas R, Alivino P, Cortino GR, Accardo R, Rinaldo M, Pizzorusso M, et al. Long acting versus short acting cephalosporins for preoperative prophylaxis in breast surgery: a randomised double-blind trial involving 1,766 patients. Chemotherapy 1999;45(3):217-23.

Additional references

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
Bray 2004
Coello 1993
Donegan 1995
  • Donegan WL, Spratt JS. Cancer of the Breast. Missouri: Elsevier Science, 1995.
Gillespie 2010
Gruendemann 2001
Haley 1985
  • Haley RW, Culver DH, Mead Morgan W, White JW, Emori GT, Hooton TM. Identifying patients at high risk of surgical wound infection. American Journal of Epidemiology 1985;121(2):206-15.
Harris 2004
  • Harris JR (Ed). Diseases of the Breast. Philadelphia: Lippincott Williams & Wilkins, 2004.
Higgins 2003
Higgins 2011
  • Higgins JPT, Altman DG, on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group (Editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Lefebvre 2000
  • Lefebvre D, Penel N, Deberles MF, Fournier C. Incidence and surgical wound infection risk factors in breast cancer surgery. Presse Medicale 2000;29(35):1927-32.
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J, on behalf of the Cochrane Information Retrieval Methods Group. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Majoribanks 2004
  • Majoribanks J, Callis K, Jordan V. Antibiotic prophylaxis for elective hysterectomy. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD004637]
Mangram 1999
  • Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for the prevention of surgical site infection. Infection Control and Hospital Epidemiology 1999;20(4):247-78.
Mitchell 1999
Morris 1988
  • Morris DM, Robinson K. The effect of method of biopsy and timing of mastectomy on the development of post mastectomy non sociocomial wound infection. Journal of the Louisiana State Medical Society 1988;140(37):363-6.
NICE 2002
  • National Institute for Clinical Excellence. Improving outcomes in breast cancer: Manual update. NICE 2002:http://www.mccn.nhs.uk/userfiles/documents/Improving_outcomes_breastcancer_manual.pdf.
PHLS 2000
  • Public Health Laboratory Service (PHLS). Antimicrobial resistance in 2000. England and Wales. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1194947317696 2000.
Pisani 1999
Pittet 2005
  • Pittet B, Montandon D, Pittet D. Infection in breast implants. Lancet Infectious Diseases 2005;5(2):94-106.
Ritter 1988
  • Ritter MA, Marmion P. The exogenous sources and controls of microorganisms in the operating room. Orthopaedic Nursing 1988;7(4):23-8.
Sajid 2012
Sanchez-Manuel 2007
Schulz 1995
  • Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408-12.
Sheridan 1994
  • Sheridan RL, Tompkins RG, Burke JF. Prophylactic antibiotics and their role in the prevention of surgical wound infection. Advances in Surgery. Year Book Medical, 1994:43-65.
SIGN 2008a
  • Scottish Intercollegiate Guidelines Network (SIGN). Benefits and risks of antibiotic prophylaxis. Antibiotic prophylaxis in surgery: a national clinical guideline. Available at http://www.sign.ac.uk/pdf/sign104.pdf. Scottish Intercollegiate Guidelines Network, 2008:9-12.
SIGN 2008b
  • Scottish Intercollegiate Guidelines Network (SIGN). Search filters. http://www.sign.ac.uk/methodology/filters.html#random (accessed 14 August 2008).
Spauwen 2000
  • Spauwen PHM, Wobbes T, Van Der Sluis RF. Immediate breast reconstruction: results and satisfaction. European Journal of Plastic Surgery 2000;23:211-3.
Tejirian 2006
  • Tejirian T, DiFronzo A, Haigh PI. Antibiotic prophylaxis for preventing wound infection after breast surgery: a systematic review and meta analysis. Journal of the American College of Surgeons 2006;203(5):729-34.
Tran 2003
  • Tran CL, Langer S, Brodwick-Villa G, DiFronzo LA. Does re-operation predispose to post-operative wound infection in women undergoing operation for breast cancer?. American Surgery 2003;69(10):852-6.
Vazquez-Aragon 2003
  • Vazquez-Aragon P, Lizan-Garcia M, Cascales-Sanchez P, Villar-Canovas MT, Garcia-Olmo D. Nosocomial infection and related risk factors in a general surgery setting: a prospective study. Journal of Infection 2003;46(1):17-22.
Wilson 1986
  • Wilson APR, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet 1986;1(8476):311-3.
Witt 2003
  • Witt A, Yavuz D, Walchetseder C, Strohmer H, Kubista E. Preoperative core needle biopsy as an independent risk factor for wound infection after breast surgery. Obstetrics and Gynecology 2003;101(4):745-50.