You are on page 1of 15

Techniques in Coloproctology

https://doi.org/10.1007/s10151-018-1814-1

REVIEW

Topical antimicrobial prophylaxis in colorectal surgery


for the prevention of surgical wound infection: a systematic review
and meta-analysis
R. L. Nelson1 · A. Kravets2 · R. Khateeb2 · M. Raza2 · M. Siddiqui2 · I. Taha2 · A. Tummala2 · R. Epple2 · S. Huang2 ·
M. Wen2

Received: 2 April 2018 / Accepted: 26 June 2018


© Springer International Publishing AG, part of Springer Nature 2018

Abstract
Background Among the techniques investigated to reduce the risk of surgical wound infection or surgical space infection
(SSI) in patients having colorectal surgery are topical application of antimicrobials (antibiotics and antiseptics) to the open
wound or immediately after closure. The aim of the present study was to perform a systematic review of the literature on
those treatments, with the exception of antibiotic ointments applied to closed skin, which are adequately assessed elsewhere,
and a meta-analysis.
Methods Only randomized trials of patients having only colorectal surgery were included in this review. Studies were sought
in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, Clinical Trials.gov, and the World Health Organiza-
tion Internet clinical trials register portal. In addition, reference lists of included studies and other published reviews were
screened. Meta-analysis was performed for all included studies and subgroup analyses done for each individual interven-
tion. Risk of bias was assessed for each included study, paying particular attention to the preoperative antibiotic prophylaxis
used in each study. Sensitivity analyses were done to investigate heterogeneity of the analyses, excluding those studies with
a significant risk of bias issues. Absolute risk reduction (RR) was calculated. The overall quality of the evidence for each
individual intervention was assessed using the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) approach, and was classified as high, moderate, low or very low.
Results A total of 30 studies are included in this review with 5511 patients, 665 of whom had SSI. The interventions included:
10 studies of gentamicin impregnated sponge or beads wound inlays, 4 studies of chlorhexidine impregnated suture, 11
studies of direct wound lavage or powder application or injection of antibiotics before closure, 4 studies of ionized silver
dressing applied to the closed skin, and 1 study of vitamin E oil applied to the open wound. All but one study used preopera-
tive antibiotic prophylaxis in addition to topical procedures, although, in some studies, the systemic antibiotic prophylaxis
was not the same between groups or varied significantly from the recommended guidelines. Use of gentamycin sponge did
not decrease SSI (RR 0.93, 95% CI 0.75–1.16; low-quality evidence) even after including only the studies of abdominal
wounds (RR 1.02, 95% CI 0.80–1.30; low-quality evidence). However, sensitivity analysis excluding studies at high risk
of bias decreased the heterogeneity and increased the effect of the prophylaxis for all wounds (RR 0.5, 95% CI 0.33–0.78;
low-quality evidence) and for abdominal wounds only (RR 0.38, 95% CI 0.20–0.72; moderate-quality evidence). Chlorhex-
idine impregnated suture showed no effect on SSI (RR 0.79, 95% CI 0.56–1.10; low-quality evidence) and an increased
efficacy after sensitivity analysis (RR 0.42, 95% CI 0.22–0.79; low-quality evidence). Antibiotic lavage showed a significant
decrease in SSI (RR 0.45, 95% CI 0.26–0.79; low-quality evidence) which increased after sensitivity analysis (RR 0.33, 95%
CI 0.15–0.72; moderate-quality evidence). Application of silver dressing to the closed wound resulted in a decrease of SSI
(RR 0.55, 95% CI 0.35–0.85; moderate-quality evidence). The one study of topical vitamin E oil applied to the open wound
showed a significant risk reduction (RR 0.22, 95% CI 0.05–0.98; low-quality evidence).
Conclusions Each of these interventions appears to be effective in decreasing SSI, but the number of studies for each is small
and the quality of evidence is very low to moderate. Within the various outcomes of GRADE assessment, even a moderate
classification suggests that further studies may well have very different results.. No randomized trials exist of combinations

Extended author information available on the last page of the article

13
Vol.:(0123456789)
Techniques in Coloproctology

of two or more of the above interventions to see if there is a combined effect. Future studies should make sure that the anti-
biotic used preoperatively is uniform within a study and is consistent with the current guidelines. Deviation from this leads
to a significant heterogeneity and risk of bias.

Keywords Colorectal surgery · Surgical site infection · Topical antimicrobial prophylaxis

Introduction surgery for suspected infections of the colon or rectum


including appendicitis, diverticulitis, and other suspected
It has been established that prophylactic antibiotics admin- perforations of the small or large bowel were excluded. Also
istered by mouth or intravenous injection before surgery excluded were topical treatments for anorectal disease.
in patients having colorectal surgery can lower the risk of The comparator was no topical treatment, a sponge with-
surgical wound infection from the neighborhood of 40% to out gentamicin, unimpregnated suture material, or lavage
about 10% [1, 2]. Methods to diminish that risk even further with saline alone. The outcome assessed was surgical wound
are being investigated, including combined preoperative oral infection of the abdominal or perineal wound, also known as
and intravenous antibiotic administration with and without superficial and deep surgical space infection (SSI) [9], and
mechanical bowel cleansing [3–5], application of antibiotic excluding organ space infection (OSI).
ointments to the closed surgical wound [6], and hyperoxia Only randomized-controlled trials were included without
[7]. In addition, several antimicrobials have been applied to restriction as to date or language.
the open wound during closure [8] or just after closure. This MEDLINE and EMBASE were searched as well as the
systematic review will focus on the latter method of surgi- Cochrane clinical trials register and the clinical trials reg-
cal space infection (SSI) prophylaxis without overlapping istries Clinicaltrials.gov (https​://clini​caltr​ials.gov/) and the
with the previously published systematic review of antibiotic World Health Organization Internet clinical trials registry
ointments applied to a closed surgical wound in colorectal portal (http://www.who.int/ictrp​/searc​h/en/) (see below) to
surgery [6]. The interventions applied topically to surgical 8/24/2017. The Cochrane, Medline, and EMBASE search
wounds include application of antimicrobial agents of all strategies are reported in Appendix 1.
types, applied in the following manner:
Gentamicin impregnated collagen sponge inlay in the Study selection and review
open wound: the sponge is collagen and absorbable. 130 g
of gentamicin are present in each sponge and released after Screening of each title, abstract and full text, data abstrac-
skin closure. Gentamicin beads are also used often in per- tion, data entry, and risk of bias assessments were all con-
ineal wounds to fill dead space. The control group either had ducted by at least three reviewers. All differences were
no sponge or sponge with no gentamicin. resolved by group discussion. The risk of bias of each study
Chlorhexidine impregnated suture The suture is absorb- was assessed against key criteria: random sequence genera-
able and usually polyglactin, polydioxanone, or similar, and tion, allocation concealment, blinding of participants, per-
is applied to the peritoneum and fascia, with skin closed as sonnel and outcome assessors, incomplete outcome data,
normal. and selective outcome reporting [10]. An additional risk
Antibiotic powder, lavage, or injection The antibiotic may of bias was discovered upon review of the included studies
be applied as a powder to an open subcutaneous wound, as and assessed. It was related to the preoperative antibiotic
a liquid wash before or after fascial closure or by injection prophylaxis in each study. When studies were found where
into subcutaneous fat. preoperative prophylaxis deviated significantly from estab-
Silver Ionized silver dressings are applied to the closed lished guidelines or varied significantly within a single study
abdominal wound. population, it was felt that the effect of the topical antibiotic
Vitamin E oil is applied to the subcutaneous tissues would be clouded by that deviation or variation, introducing
before skin closure. significant bias. Those studies were excluded in sensitivity
analyses (see below).
Authors were contacted for missing data. When data after
randomization on SSI were unavailable, if it was outcome
Materials and methods data and could be assigned to a treatment group, they were
considered as treatment failures [11].
Studies included in this review were conducted on patients Clinical heterogeneity was assessed in the performance of
of both sexes and all ages having operations only upon the the surgery, or administration of the treatment, the veracity
colon and rectum. Studies of patients having colorectal of the diagnosis, and the accuracy and timing of the outcome

13
Techniques in Coloproctology

assessment. In addition, as mentioned above, heterogeneity Absolute risk reduction was calculated by the number of
related to preoperative antibiotic prophylaxis was assessed. controls with SSI per 1000 patients (rate × 1000) multiplied
Methodological heterogeneity was sought in the differential by the risk ratio and confidence intervals for each interven-
risks of bias assessments between studies. Statistical hetero- tion, both in the full comparisons and the sensitivity analyses
geneity was calculated in Revman [12]. It was defined as a (Table 2).
Chi-square (p < 0.10) and I-square (I2) (> 60%).
Subgroup analyses were done to investigate the individ-
ual interventions, or anatomic specificity of an intervention, Results
and to investigate sources of heterogeneity in meta-analyses.
Sensitivity analyses were done eliminating the studies found Search
to be of poor quality to assess the robustness of the results
of the meta-analysis as well as their effect on heterogeneity. The preferred reporting items for systematic reviews and
Data were analyzed using Revman 5.3. Results were meta-analyses: (PRISMA) flowchart for our search are
expressed as risk ratios and 95% confidence intervals for shown in Fig. 1. Ultimately, 30 eligible studies in 29 publi-
the dichotomous outcomes, using the random-effects model cations were found [17–45] (Table 1).
when a significant heterogeneity was seen. Trials were excluded from this review if they were found
The Grades of Recommendation, Assessment, Develop- to involve only oral or intravenous antibiotics or were stud-
ment and Evaluation (GRADE) [13, 14] approach was used ies in which colorectal surgery which patients were a sub-
to classify the quality of evidence for all included studies group in a broader cohort with no evidence that they were
and each intervention into one of four grades: segregated at randomization. Isolating colorectal surgery in
such analyses is prone to confounding and type 1 error [46].
1. High Further research is very unlikely to change our Third, antibiotic ointments applied to the closed abdomi-
confidence in the estimate of effect nal wound in colorectal surgery were not included in this
2. Moderate Further research is likely to have an impact on review, since they have been very thoroughly reviewed and
our confidence in the estimate of effect and may change recently reported elsewhere [7]. There is one exception here;
the estimate; a three arm study of control, silver dressing, and mupirocin
3. Low Further research is very likely to have an important applied to a closed abdominal wound [41]. This study was
impact on our confidence on the estimate of effect and is not included in the Heal reports [7]. Besides a comparison of
likely to change the estimate; silver to its control in this study, the mupirocin arm was also
4. Very low Any estimate of effect is very uncertain. compared separately to the same control group and included
for completeness in the antibiotic group.
Each intervention began with a HIGH quality of evidence In some studies, the lavage of the abdominal wound was
and was downgraded either 0, 1, or 2 points for each of the performed after fascial closure. In others, the peritoneal cav-
five factors listed below to MODERATE, LOW, or VERY ity was lavaged before fascial closure, a wash which inevi-
LOW depending on how seriously (one or two steps down) tably would include the subcutaneous tissues. They were,
the factor impacted the data. therefore, included. None of the ampicillin studies fall into
the latter group.
1. Risk of bias as described above
2. Inconsistency (unexplained heterogeneity and thus
inconsistency of results); − 1 for Heterogeneity > 0.001; Results of interventions
− 2 for Heterogeneity < 0.001. [15];
3. Indirectness (indirect or atypical populations, interven- The interventions described in the included studies and their
tions, controls, and outcomes; for instance, a surrogate sensitivity analyses are listed in Table 2.
outcome for SSI such as fever.) In addition to Table 2, the results of the meta-analyses
4. Imprecision, as made evident by wide confidence inter- are shown in forest plots for all included studies (Figs. 2,
vals, small study size, two or fewer studies, and/or fewer 3) and the subgroups of each specific intervention (Figs. 4,
than 100 SSI events (− 1) or fewer than 50 events (− 2) 5, 6, 7 and 8). Forest plots of the sensitivity analyses are
in that comparison (except when events (SSI) became not shown, except for the one paired with Fig. 2, displaying
rare in a sufficient population). Random error in that those studies excluded in the sensitivity analyses (Fig. 3).
case is too great [16]. The results for other sensitivity analyses are only shown in
5. Publication bias: Evidence either graphically in funnel Tables 2 and 3.
plots or from review of trials registries that many poten- Subgroup analyses were done within two specific interven-
tially included studies have not been published. tions. In the gentamicin impregnated collagen sponge studies,

13
Techniques in Coloproctology

the abdominal wound was also assessed separately, excluding


the studies that examined the perineal wound. Assessment of
SSI is more difficult in the perineum due to dead spaces in the
pelvis (Fig. 4). In the second, for topical antibiotics, ampicil-
lin, the most commonly tested topical antibiotic, was assessed
excluding other antibiotics (Fig. 6). Besides ampicillin, the fol-
lowing antibiotics were examined: cefotetan [32], gentamicin/
metronidazole [34], cefazolin [37], penicillin [38], clindamy-
cin/gentamicin [40], and mupirocin [41].
The sensitivity analyses were done excluding those seven
studies with issues described in the methods concerning pre-
operative antibiotic prophylaxis. These are marked as a high
risk of bias in column E of the risk-of-bias figures of the forest
plots in Figs. 2, 3, 4, 5, 6, 7 and 8 [17, 22, 28, 35, 37–39]. In
addition, three other studies were excluded from sensitivity
analyses, the first two due to excessive attrition after randomi-
zation and the inability to obtain group assignments of those
lost to follow-up [27, 34] (Column D in the Forest Plots’ Risk
of Bias) and the third, because it used hospital numbers as
an allocation assignment technique [21] (Column A), all of
these introduced serious risk of bias. Interestingly, in the last
study [21], the gentamicin sponge was wrapped around the
anastomosis. This was the only study in which that was done.
No sensitivity analysis was done for silver dressings as
none of these risks of bias applied and for vitamin E, since
there was only one study. The magnitude of the protective
effect was increased in each sensitivity analysis.
No deductions in GRADE were made due to Indirectness
or Publication bias. Publication bias was investigated in a
funnel plot (Fig. 9) [47]. The asymmetry was not conclusive
in that regard.
Table 3 displays the interventions and sensitivity analy-
ses, the heterogeneity for each comparison including the
sensitivity analyses, the GRADE score, the GRADE score
rationale, and the absolute risk reduction from each interven-
tion when compared to the control risk of SSI in each com-
parison group with confidence intervals for that reduction.
In addition to the magnitude of the protective effect being
increased for each analysis in the paired sensitivity analyses
(Table 2), the heterogeneity for each comparison for which
sensitivity analyses were done was diminished in all com-
parisons except for the antibiotic lavage/powder/injection
group, in some cases markedly. The quality of the evidence
in GRADE was not altered because of the decline in preci-
sion in each sensitivity analysis (Table 2), except for All
Topical, Antibiotic, and Ampicillin comparisons (Table 3).

Fig. 1  Preferred Reporting Items for Systematic Reviews and Meta-


Analyses (PRISMA) flowchart
Discussion

This is a grouping of very heterogeneous methods to dimin-


ish the risk of SSI of the abdominal wound after colorectal
surgery. It could have been the topic of six separate reports.

13
Techniques in Coloproctology

Table 1  Included studies Antimicrobial intervention Number of included References


studies

Gentamicin impregnated collagen sponge(s) or beads 10 studies [17–26]


Chlorhexidine impregnated fascial suture (Triclosan) 4 studies [27–30]
Antibiotics delivered by injection, lavage or powder or in one 11 studies [31–41]
case, wound dressing
Ionized silver dressing applied to the closed wound 4 studies [41–44]
Vitamin E oil applied to the open wound 1 study [45]

Table 2  Topical antimicrobial prophylaxis for colorectal surgery


Intervention test Reference #s Comparator # Studies # Partici- #Surgical wound Risk ratio and 95%
pants test/ infections test/ confidence interval
control control

1. All topical No treatment or placebo 30 2757/2754 268/397 0.57; 0.43–0.75


[17–45]
2. All topical; SA No treatment or placebo 20 1520/1517 102/236 0.46; 0.34–0.61
[17, 18, 21–27, 30, 33, 38–45]
3. Gentamycin sponge (total) [17–26] No treatment or placebo 10 919/928 129/140 0.93: [0.75, 1.16]
4. Gentamycin sponge (total); SA [18–20, 23–26] No treatment or placebo 7 408/414 29/58 0.51: [0.33, 0.78]
5. Gentamycin sponge abdominal wound only [17, No treatment or placebo 5 595/604 106/105 1.02: [0.80, 1.30]
20, 22, 23, 26]
6. Gentamycin sponge abdominal wound only; SA No treatment or placebo 3 197/206 12/33 0.38: [0.20, 0.72]
[20, 23, 26]
7. Triclosan [27–30] Plain suture 4 635/644 54/70 0.79: [0.56, 1.10]
8. Triclosan; SA [29, 30] Plain suture 2 297/297 13/31 0.42: [0.22, 0.79]
9. Antibiotic lavage/ powder/injection [31–41] No treatment or placebo 11 900/882 57/131 0.45: [0.26, 0.79]
10. Antibiotic lavage/ powder/injection; SA No treatment or placebo 6 512/506 32/91 0.33: [0.15, 0.72]
[31–33, 36, 40, 41]
11. Ampicillin powder [31, 33, 35, 36, 39] No treatment 5 476/470 17/69 0.28: [0.10, 0.78]
12. Ampicillin powder; SA [31, 33, 36] No treatment 3 345/338 11/49 0.26: [0.07, 0.91]
13. Silver [41–44] Placebo 4 249/246 26/47 0.55: [0.35, 0.85]
14. Vitamin E [45] No treatment 1 54/54 2/9 0.22: [0.05, 0.98]

SA sensitivity analyses, excluding studies from analyses due to serious risk of bias
Bold risk ratios are statistically significant

There are only a few published reports about each interven- the wound to the Center for Disease Control and Preven-
tion. However, the interventions are applied to patients in tion (CDC) criteria. No surrogate outcomes were used in
more or less the same way, and it is assumed that each inter- the analyses of this review. As mentioned above, the preop-
vention is effective by the same mechanism, the suppression erative antibiotic prophylaxis was variable and not always
of bacterial growth in the subcutaneous space. Each inter- appropriate, though, in the sensitivity analyses, preoperative
vention in its sensitivity analysis showed a significant ability prophylaxis was much more uniform.
to diminish SSI risk. There are no reports of combinations
of any two or more of the interventions reported above, i.e., Interventions
whether there might be an additive effect of combined topi-
cal therapies. Within the studies of gentamicin sponges or beads, there is
The SSI rates were somewhat higher in all these compari- 1 study that stood out as larger and of greater weight (42.2
sons than would be expected in the controls. Only one was and 56.4% in the abdominal wound only subgroup) in the
near the anticipated 10% or 100 per 1000 patients [27–30] analyses than any of the others [17]. In its findings, it was
(Fig. 5). The rest were 40–90% higher. The detection of also an outlier, showing a significant benefit for the con-
SSI was pretty uniform among studies, from frank pus in trol group (RR = 1.47; CI 1.10–1.96) (Fig. 2). Preoperative

13
Techniques in Coloproctology

Fig. 2  All included studies

antibiotic prophylaxis varied within the study, apparently studies remaining in the sensitivity analysis (Fig. 4), there is
depending on the site in a multi-site trial. This introduced serious random error, and more and larger studies are needed
an additional variable into the study. In this and six other before guidelines are developed in this context (see below).
studies, the preoperative antibiotic prophylaxis was variable Chlorhexidine also raises the issue of what constitutes an
enough or deviated enough from accepted guidelines [2] to antiseptic and what is an antibiotic. Almost any definition
exclude these studies in the sensitivity analyses. Studies with that was found leads to exceptions, e.g., antibiotics are taken
a significant attrition and data loss [10] and inappropriate systemically and antiseptics applied topically, yet most of
allocation sequence generation [10] were also excluded. the interventions in this review are topical antibiotics. There-
The effect of these sensitivity analyses was to lower sta- fore, in this review, all interventions were described together
tistical heterogeneity, sometimes markedly, and increase as antimicrobial.
the magnitude of the therapeutic effect of the interventions The studies of topical antibiotics encompass many differ-
(Tables 2, 3). With the improved therapeutic effect, there ent antibiotics, but only ampicillin is seen in enough studies
is also loss of power in these analyses. Statistical signifi- to be segregated into a subgroup. In a systematic review
cance must then be viewed with caution, as in the analyses of [48] of ampicillin, ampicillin in lieu of preoperative antibi-
chlorhexidine impregnated suture (Triclosan). With only two otics was effective, but, when combined with preoperative

13
Techniques in Coloproctology

Fig. 3  Sensitivity analysis: all studies, minus those with risk of bias issues. Excluded studies have no means and confidence intervals shown in
this forest plot. Note the change in heterogeneity and summary statistic compared with Fig. 2

antibiotic prophylaxis, it had no added beneficial effect of all incisions. Several representative systematic reviews are
(Table 3). Perhaps, more studies of an antibiotic better tai- summarized in Table 4 [48, 50–60]. One of those that was
lored to colonic flora would be more effective. limited to colorectal surgery only assessed perineal wounds
Silver has been used to heal open wounds for over in patients having abdominoperineal excision [60].
50 years [49]. However, its use in prophylaxis for SSI is
very recent (Fig. 6). Therefore, the number of randomized
trials is still small [50]. A proposed advantage of silver over Conclusions
antibiotic topical prophylaxis is the avoidance of develop-
ment of antibiotic resistance, though the magnitude of the Guidelines published concerning the recommended proph-
risk of antibiotic resistance in the context of topical prophy- ylaxis for SSI prevention across many surgical specialties
laxis is not known. do not yet mention topical therapy for colorectal surgery
Vitamin E is new to this field, described as an immu- [61, 62]. At a meeting of the Cochrane Collaboration 10 or
nomodulatory antioxidant in dermatologic disorders [45]. 15 years ago, it was stated that 85% of the published guide-
lines in the United States were not evidence based. Since
Other systematic reviews and current clinical that time, it has become apparent that statistical significance
guidelines and the support of experts in the field were not sufficient to
advance an idea into clinical practice. As is shown above,
Numerous systematic reviews have been published related the quality of the accumulated evidence must be assessed as
to these interventions. For most, colorectal surgery, if men- well. Within the various outcomes of GRADE assessment,
tioned at all, was a small portion of a larger group of studies even a moderate classification suggests that further studies

13
Techniques in Coloproctology

Fig. 4  Gentamicin collagen sponge and beads: all studies and abdominal wound only

Fig. 5  Chlorhexidine impregnated fascial suture (triclosan)

may well have very different results. Preoperative antimicro- presented to an individual patient that is the issue. They all
bial prophylaxis for colorectal surgery has achieved a High may help and there were no significant harms described in
GRADE classification [2], stating that placebo controlled any of these published trials. Further high-quality studies are
trials are no longer needed. All the interventions described needed for each intervention before patients can be assured
in this review are available for use, but it is how they are that their outcomes will be improved by their use and that
this will be evident in the published guidelines.

13
Techniques in Coloproctology

Fig. 6  Antibiotic powder, lavage, or injection for the abdominal wound

Fig. 7  Ionized silver dressing on the closed abdominal wound

Fig. 8  Vitamin E oil to NO NOT “to”, in the abdominal wound

13
Techniques in Coloproctology

Table 3  Topical antimicrobial prophylaxis for colorectal surgery grade, heterogeneity, and absolute risk reduction due to the intervention
Intervention Inconsistency Total GRADE Rationale Absolute risk reduction: Risk reduction and 95%
heterogeneity strength of evidence control rate/1000 patients confidence interval
score

1 All topical 0.00001; 62% − 4; Very low Risk of bias (− 2) 146 with SSI in controls 62 fewer SSI in All topical
Inconsistency (− 2) [36–82]
2. All topical; SA 0.06; 35% − 2; Low Risk of bias 156 84 fewer; [61– 103]
Inconsistency
3. Gentamycin sponge 0.007; 60% − 2; Low Risk of bias 151 11; [− 24–38]
(total) Inconsistency
4. Gentamycin sponge 0.53; 0% − 2; Low Risk of bias 140 69; [31–94]
(total); SA Imprecision
5. Sponge (abdominal 0.001; 78% − 2; Low Risk of bias 174 − 3; [− 52–35]
wound only) Inconsistency
6. Sponge (abdominal 0.24; 30% − 1; Moderate Imprecision (-1) 160 99; [45–128]
wound only); SA
7. Triclosan 0.09; 53% − 2; Low Risk of bias (-2) 109 23; [− 11–48]
8. Triclosan; SA 0.64; 0% − 2; Low Imprecision (-2) 104 60; [22–81]
9. Antibiotic lavage/pow- 0.002; 63% − 2; Low Risk of bias 149 82; [31–110]
der/injection Inconsistency
10. Antibiotic lavage/ 0.005;70% − 1; Moderate Inconsistency 180 121; [50–153]
powder/injection; SA
11. Ampicillin powder 0.01; 69% − 4; Very low Risk of bias (− 2) 147 106; [32–132]
Imprecision
Inconsistency
12. Ampicillin powder; SA 0.03; 70% − 2; Low Imprecision 145 107; [13–135]
Inconsistency
13. Silver 0.18; 39% − 1; Moderate Imprecision 191 86; [29–124]
14. Vitamin E Only 1 study − 2; Low Imprecision (− 2) 169 130; [3–159]

SA sensitivity analyses, excluding studies from analysis with serious risk of bias
Bold risk reductions are statistically significant

Fig. 9  Funnel plot of all studies

13
Techniques in Coloproctology

Table 4  Related systematic reviews


Author refer- CRS only: # Included Meta-anal- HeteroGe- Risk of bias GRADE Special Publication Quantified
ence test Year Studies ysis neity features included efficacy
also in this
review

Politano No NS No No No No Global 1 No
Silver [51] 2013
Charalam- No 15 Yes Yes Yes No 4 Yes
bous 2003 OR = 0.927 CI
Ampicillin 0.27–1.72
[48]
Li Silver No 9 Yes Yes Yes Yes 4 RR = 0.92 CI
[52] 2017 0.66–1.29
RR = 0.62; CI
0.28–1.41
for Colo-
rectal
Daoud No 15 Yes No Yes No Complex 3 Yes
Triclosan 2013 stats p = 0.00053
[53]
de Bruin No 9 No No No No 4 Yes
Gentamicin 2010 p < 0.01
sponge
[54]
Elsohl No 5 Yes Yes Yes Yes Funnel plot 3 Yes
Triclosan 2017 p = 0.15
[55]
Heal No 14 Yes Yes Yes Yes Cochrane None Yes
Antibiotic 2016, 2017 Review RR 0.61
on a closed CI 0.42–0.87
wound [56]
de Jonge No 21 Yes Yes Yes Yes TSC 4 Yes
Triclosan 2017 p = 0.001
[57]
Lv Yes 8 Yes Yes Yes: too No Geography 8 Yes
Gentamy- 2016 positive RR = 0.73
cinsponge CI 0.47–1.12
[58]
Mueller Subgroup 6 with anti- Yes Yes No No Most inclu- 5 Yes
Lavage [59] mixed microbials sions were p < 0.0001 but
analysis saline vs. not quite the
2015 nothing comparison
needed
Musters Yes APR 8: Mixed No No Yes No 3 Not exactly.
Gentamycin 2015 RCT & Perineal
sponge NRT wounds only
[60]
Sandini 61 Yes 6 Yes No Yes No Funnel plot 4 Yes
Triclosan 2016 OR = 0.81
CI 0.58–1.13

CRS colorectal surgery only, GRADE grading of recommendations assessment, development and evaluation, APR abdominoperineal resection;
NS not specified, RCT​randomized-controlled trial, NRT0 non-randomized trial

13
Techniques in Coloproctology

Compliance with ethical standards MEDLINE search strategy

Conflict of interest The authors declare that they have no conflict of Ovid MEDLINE (1950 to 08/24/2017)
interest.

Ethical approval This article does not contain any studies with human 1. exp Surgical Wound Infection/
participants performed by any of the authors. 2. exp Postoperative Complications/
3. exp Bacterial Infections/
Informed consent For this type of study formal consent is not required.
4. exp Infection/
5. exp Sepsis/
6. (postoperative complication* or infection* or sepsis).
Appendix 1: search strategy mp.
7. 1 or 2 or 3 or 4 or 5 or 6
Cochrane central (latest issue) 8. exp Antiinfective Agents/
9. exp Antibacterial Agents/
1. MeSH descriptor: [Surgical Wound Infection] explode 10. exp Antibiotic Prophylaxis/
all trees 11. exp Triclosan/
2. MeSH descriptor: [Postoperative Complications] 12. (antiinfective or antibiotic* or antimicrobial* or anti-
explode all trees bacterial* or triclosan* or prophylaxis or premedica-
3. MeSH descriptor: [Bacterial Infections] explode all tion or disinfect* or antiseptic*).mp.
trees 13. 8 or 9 or 10 or 11 or 12
4. MeSH descriptor: [Infection] explode all trees 14. exp Colorectal Surgery/
5. MeSH descriptor: [Sepsis] explode all trees 15. exp Colon/su [Surgery]
6. (postoperative complication* or infection* or 16. exp Rectum/su [Surgery]
sepsis):ti,ab,kw 17. exp Colectomy/
7. (#1 or #2 or #3 or #4 or #5 or #6) 18. ((colon* or rect* or colorect*) and (surgery or opera-
8. MeSH descriptor: [Antiinfective Agents] explode all tion or resection)).mp.
trees 19. (colectom* or colostom*).mp.
9. MeSH descriptor: [Antibacterial Agents] explode all 20. 14 or 15 or 16 or 17 or 18 or 19
trees 21. 7 and 13 and 20
10. MeSH descriptor: [Antibiotic Prophylaxis] explode all 22. randomized-controlled trial.pt.
trees 23. controlled clinical trial.pt.
11. MeSH descriptor: [Triclosan] explode all trees 24. randomized.ab.
12. (antiinfective or antibiotic* or antimicrobial* or anti- 25. placebo.ab.
bacterial* or triclosan* or prophylaxis or premedica- 26. clinical trial.sh.
tion or disinfect* or antiseptic*):ti,ab,kw 27. randomly.ab.
13. (#8 or #9 or #10 or #11 or #12) 28. trial.ti.
14. MeSH descriptor: [Colorectal Surgery] explode all 29. 22 or 23 or 24 or 25 or 26 or 27 or 28
trees 30. humans.sh.
15. MeSH descriptor: [Colon] explode all trees and with 31. 29 and 30
qualifier(s): [Surgery - SU] 32. 21 and 31
16. MeSH descriptor: [Rectum] explode all trees and with
qualifier(s): [Surgery - SU] EMBASE search strategy
17. MeSH descriptor: [Colectomy] explode all trees
18. ((colon* or rect* or colorect*) and (surgery or opera- Ovid EMBASE (1974–08/24/2017)
tion or resection)):ti,ab,kw
19. (colectom* or colostom*):ti,ab,kw 1. exp surgical infection/
20. (#14 or #15 or #16 or #17 or #18 or #19) 2. exp postoperative complication/pc [Prevention]
21. (#7 and #13 and #20) 3. exp bacterial infection/
4. exp sepsis/
5. (postoperative complication* or infection* or sepsis).
mp.
6. 1 or 2 or 3 or 4 or 5
7. exp antiinfective agent/

13
Techniques in Coloproctology

8. exp antibiotic prophylaxis/ 5. Intravenous versus Combined Oral and Intravenous Antimicrobial
9. exp disinfectant agent/ Prophylaxis for the Prevention of Surgical Site Infection in Elec-
tive Colorectal Surgery (COMBINE). https​://Clini​caltr​ials.gov.
10. (antiinfective or antibiotic* or antimicrobial* or anti- NCT02618720. Accessed 3 July 2018
bacterial* or triclosan* or prophylaxis or premedica- 6. Greif R, Akça IO, Horn EP, Kurz A, Sessler DI (2000) Supple-
tion or disinfect* or antiseptic*).mp. mental perioperative oxygen to reduce the incidence of surgical-
11. 7 or 8 or 9 or 10 wound infection. N Engl J Med 342:161–167
7. Heal CF, Banks JL, Lepper P, Kontopantelis E, van Driel ML
12. exp colorectal surgery/ (2017) Meta-analysis of randomized and quasi-randomized clini-
13. exp colon surgery/ cal trials of topical antibiotics after primary closure for the preven-
14. exp rectum surgery/ tion of surgical-site infection. Br J Surg 104(9):1123–1130. https​
15. exp colon/su [Surgery] ://doi.org/10.1002/bjs.10588​. Epub 28 Jun 2017
8. McHugh SM, Collins CJ, Corrigan MA, Hill ADK, Humphreys H
16. exp rectum/su [Surgery] (2011) The role of topical antibiotics used as prophylaxis in surgi-
17. ((colon* or rect* or colorect*) and (surgery or opera- cal site infection prevention. J Antimicrob Chemother 66:693–701
tion or resection)).mp. 9. Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveil-
18. (colectom* or colostom*).mp. lance definition of health care-associated infection and criteria for
specific types of infections in the acute care setting. Am J Infect
19. 12 or 13 or 14 or 15 or 16 or 17 or 18 Control 36(5):309–332
20. 6 and 11 and 19 10. Higgins JPT, Green S (eds) (2011) Cochrane Handbook for sys-
21. CROSSOVER PROCEDURE.sh. tematic reviews of interventions Version 5.1.0 [updated March
22. DOUBLE-BLIND PROCEDURE.sh. 2011]. The Cochrane Collaboration. http://handb​ook.cochr​ane.
org. Accessed 3 July 2018
23. SINGLE-BLIND PROCEDURE.sh. 11. Armijo-Olivo S, Warren (2009) Magee. Intention to Treat, com-
24. (crossover* or cross over*).ti,ab. pliance, drop outs and how to deal with missing data in clinical
25. placebo*.ti,ab. research: a review. Phys Ther Rev 14(1):36–49
26. (doubl* adj blind*).ti,ab. 12. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a
meta-analysis. Stat Med 21(11):1539–1558
27. allocat*.ti,ab. 13. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Nor-
28. trial.ti. ris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, Rind D,
29. RANDOMIZED-CONTROLLED TRIAL.sh. Meerpohl J, Dahm P, Schünemann HJ (2011) GRADE guidelines:
30. random*.ti,ab. 1. Introduction-GRADE evidence profiles and summary of find-
ings tables. J Clin Epidemiol 64(4):383–394
31. 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 14. GRADE Handbook. http://gdt.guide​lined​evelo​pment​.org/centr​
32. (exp animal/ or exp invertebrate/ or animal.hw. or non- al_prod/_design​ /client​ /handbo​ ok/handbo​ ok.html. Accessed 3 July
human/) not (exp human/ or human cell/ or (human or 2018
humans or man or men or wom?n).ti.) 15. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand
M, Alonso-Coello P, Glasziou P, Jaeschke R, Akl EA, Norris S,
33. 31 not 32 Vist G, Dahm P, Shukla VK, Higgins J, Falck-Ytter Y, Schüne-
34. 20 and 33 mann HJ, GRADE Working Group. (2011) GRADE guidelines:
7. Rating the quality of evidence–inconsistency. J Clin Epidemiol
64(12):1294–1302. https:​ //doi.org/10.1016/j.jcline​ pi.2011.03.017
16. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind
D, Devereaux PJ, Montori VM, Freyschuss B, Vist G, Jaeschke R,
Williams JW Jr, Murad MH, Sinclair D, Falck-Ytter Y, Meerpohl
References J, Whittington C, Thorlund K, Andrews J, Schünemann HJ (2011)
GRADE guidelines 6. Rating the quality of evidence–imprecision.
1. Baum ML, Anish DS, Chalmers TC, Sacks HS, Smith H Jr, J Clin Epidemiol 64(12):1283–1293
Fagerstrom RM (1981) A survey of clinical trials of antibiotic
prophylaxis in colon surgery: evidence against further use of no-
treatment controls. N Engl J Med 305:795–799
Included studies
2. Nelson RL, Gladman E, Barbateskovic M (2014) Antimicrobial
prophylaxis for colorectal surgery. Cochrane Database Syst Rev 17. Bennett-Guerrero E, Pappas TN, Koltun WA, Fleshman JW, Lin
9(5):1 M, Garg J et al (2010) Gentamicin-collagen sponge for infection
3. Bellows CF, Mills KT, Kelly TN, Gagliardi G (2011) Combination prophylaxis in colorectal surgery. N Engl J Med 363:103–149
of oral non-absorbable and intravenous antibiotics versus intrave- 18. Collin A, Gustafsson UM, Smedh K, Pahlman L, Graf W, Folkes-
nous antibiotics alone in the prevention of surgical site infections son J (2013) Effect of local gentamicin-collagen on perineal
after colorectal surgery: a meta-analysis of randomized controlled wound complications and cancer recurrence after abdominoper-
trials. Tech Coloproctol 15(4):385–395 ineal resection: a multi-centre randomized controlled trial. Colo-
4. Anjum N, Ren J, Wang G, Li G, Wu X, Dong H, Wu Q, Li J rectal Dis Off J Assoc of Coloproctol G B Irel 15(3):341–346
(2017) A randomized control trial of preoperative oral antibiotics 19. Gruessner U, Clemens M, Pahlplatz PV, Sperling P, Witte J,
as adjunct therapy to systemic antibiotics for preventing surgical Rosen HR (2001) Improvement of perineal wound healing by
site infection in clean contaminated, contaminated, and dirty type local administration of gentamicin-impregnated collagen fleeces
of colorectal surgeries. Dis Colon Rectum 60(12):1291–1298 after abdominoperineal excision of rectal cancer. Am J Surg
182(5):502–509

13
Techniques in Coloproctology

20. Haase O, Raue W, Bohm B, Neuss H, Scharfenberg M, 36. Ostergaard AH, Wamberg P (1981) Topical or oral antibiotics
Schwenk W (2005) Subcutaneous gentamicin implant to reduce against wound infection in colorectal surgery. Aktuelle Probleme
wound infections after loop-ileostomy closure: a randomized, in Chirurgie Orthopadie 19:105–107
double-blind, placebo-controlled trial. Dis Colon Rectum 37. Quendt J, Blank I, Seidel W (1996) Perioperative antibiotic
48(11):2025–2031 prophylaxis by transperitoneal and subcutaneous application
21. Nowacki MP, Rutkowski A, Oledzki J, Chwalinski M (2005) during elective colorectal surgery. A prospective randomized
Prospective, randomized trial examining the role of gentamycin- comparative study [Peritoneale und subkutane Applikation von
containing collagen sponge in the reduction of postoperative Cefazolin als perioperative Antibiotikaprophylaxe bei kolorek-
morbidity in rectal cancer patients: early results and surprising talen Operationen. Prospektive randomisierte Vergleichsstudie bei
outcome at 3-year follow-up. Int J Colorectal Dis 20(2):114–120 200 Patienten]. Langenbecks Arch Chir 381(6):318–322
22. Pochhammer J, Zacheja S, Schaffer M (2015) Subcutaneous appli- 38. Raahave D (1981) High-dose penicillin to prevent postoperative
cation of gentamicin collagen implants as prophylaxis of surgical wound sepsis after ileocolorectal operations. Scand J Gastroen-
site infections in laparoscopic colorectal surgery: a randomized, terol 16(6):789–793
double-blinded, three-arm trial. Langenbeck’s Archives of Sur- 39. Raahave D, Hesselfeldt P, Pedersen T, Zachariassen A, Kann D,
gery 400(1):1–8 Hansen OH (1989) No effect of topical ampicillin prophylaxis in
23. Reith HB, Mittelkotter U, Niedmann M, Debus S, Kozuschek W elective operations of the colon or rectum. Surg Gynecol Obstet
(1996) Modification of laparotomy wound healing in colon sur- 168(2):112–114
gery by local antibiotic administration [Beeinflussung der Lapa- 40. Ruiz-Tovar J, Santos J, Arroyo A, Llavero C, Armaanzas L,
rotomiewundheilung in der Kolonchirurgie durch lokale Antibio- Lopez-Delgado A et al (2012) Effect of peritoneal lavage with
tikaapplikation]. Zentralblatt fur Chirurgie 121 Suppl:84–85 clindamycin-gentamicin solution on infections after elective colo-
24. Rosen HR, Marczell AP, Czerwenka E, Stierer MO, Spoula H, rectal cancer surgery. J Am Coll Surg 214(2):202–207
Wasl H (1991) Local gentamicin application for perineal wound 41. Ruiz-Tovar J, Llavero C, Morales V, Gamallo C (2015) Total
healing following abdominoperineal rectum excision. Am J Surg occlusive ionic silver-containing dressing vs mupirocin ointment
162(5):438–441 application vs conventional dressing in elective colorectal sur-
25. Rutkowski A, Zajac L, Pietrzak L, Bednarczyk M, Byszek A, gery: effect on incisional surgical site infection. J Am Coll Surg
Oledzki J et al (2014) Surgical site infections following short- 221(2):424–429
term radiotherapy and total mesorectal excision: results of a ran- 42. Biffi R, Fattori L, Bertani E, Radice D, Rotmensz N, Misitano P
domized study examining the role of gentamicin collagen implant et al (2012) Surgical site infections following colorectal cancer
in rectal cancer surgery. Tech Coloproctol 18(10):921–928 surgery: a randomized prospective trial comparing common and
26. Rutten HJ, Nijhuis PH (1997) Prevention of wound infection in advanced antimicrobial dressing containing ionic silver. World J
elective colorectal surgery by local application of a gentamicin- Surg Oncol 10:94
containing collagen sponge. Eur J Surg 578:31–5 43. Krieger BR, Davis DM, Sanchez JE, Mateka JJ, Nfonsam VN,
27. Baracs J, Huszar O, Sajjadi SG, Peter Horvath O (2011) Surgi- Frattini JC et al (2011) The use of silver nylon in preventing surgi-
cal site infections after abdominal closure in colorectal surgery cal site infections following colon and rectal surgery. Dis Colon
using Triclosan-coated absorbable suture (PDS Plus) vs. uncoated Rect 54(8):1014–1019
sutures (PDS II): a randomized multicenter study. Surg Infect 44. Siah CJ, Yatim J (2011 Dec) Efficacy of a total occlusive ionic
12(6):483–489 silver-containing dressing combination in decreasing risk of surgi-
28. Mattavelli I, Rebora P, Doglietto G, Dionigi P, Dominioni L, cal site infection: an RCT. J Wound Care 20(12):561–568
Luperto M et al (2015) Multi-center randomized controlled trial 45. Alias D, Ruiz-Tovar J, Moreno A, Manso B, Diaz G, Duran M
on the effect of triclosan-coated sutures on surgical site infection et al (2017) Effect of subcutaneous sterile vitamin E ointment on
after colorectal surgery. Surg Infect 16(3):226–235 incisional surgical site infection after elective laparoscopic colo-
29. Nakamura T, Kashimura N, Noji T, Suzuki O, Ambo Y, Nakamura rectal cancer surgery. Surg Infect 18(3):287–292
F et al (2013) Triclosan-coated sutures reduce the incidence of
wound infections and the costs after colorectal surgery: a rand-
omized controlled trial. Surgery 153(4):576–583 Discussion references
30. Rasic Z, Schwarz D, Adam VN, Sever M, Lojo N, Rasic D et al
(2011) Efficacy of antimicrobial Triclosan-coated polyglactin 910 46. Sedgwick P (2014) Randomized controlled trials and subgroup
(Vicryl* Plus) suture for closure of the abdominal wall after colo- analysis. Br Med J 349:g7513. https​://doi.org/10.1136/bmj.g7513​
rectal surgery. Coll Antropol 35(2):439–443 47. Sterne AC, Egger M, Smith DG (2001) Investigating and dealing
31. Andersen B, Ostergaard AH (1972) Topical Ampicillin against with publication bias and other biases in meta-analysis. Br Med J
wound infection in colorectal surgery. Ann Surg 172(2):129–132 323:101–105
32. Greig J, Morran C, Gunn R, Mason B, Sleigh D, McArdle C 48. Charalambous CP, Tryfonidis M, Swindell R, Lipsett AP (2003)
(1987) Wound sepsis after colorectal surgery: the effect of cefo- When should old therapies be abandoned? A modern look at old
tetan lavage. Chemioterapia 6(2):595–596 studies on topical ampicillin. J Infect 47(3):203–209 (Erratum in:
33. Juul P, Merrild U, Kronborg O (1985) Topical ampicillin in addi- J Infect. 2008 Apr;56(4):297. Charalambous, Charalambos [cor-
tion to a systematic antibiotic prophylaxis in elective colorectal rected to Charalambous, Charalambos P] )
surgery: a prospective randomised study. Dis Colon Rectum 49. Atiyeh BS, Costagliola M, Hayek SN, Dibo SA (2007) Effect of
28(11):804–806 silver on burn wound infection control and healing: review of the
34. Moesgaard F, Nielsen ML, Hjortrup A, Kjersgaard P, Sorensen literature. Burns 33(2):139–148. (Epub 29 Nov 2006)
C, Larsen PN et al (1989) Intraincisional antibiotic in addition to 50. Li HZ, Zhang L, Chen JX, Zheng Y, Zhu XN (2017) Silver-
systemic antibiotic treatment fails to reduce wound infection rates containing dressing for surgical site infection in clean and clean-
in contaminated abdominal surgery. A controlled clinical trial. Dis contaminated operations: a systematic review and meta-analysis
Colon Rectum 32(1):36–38 of randomized controlled trials. J Surg Res 215:98–107. https​://
35. Nash AG, Hugh TB (1967) Topical ampicillin and wound infec- doi.org/10.1016/j.jss.2017.03.040. (Epub 2 Apr 2017)
tion in colon surgery. BMJ 1(5538):471–472 51. Politano AD, Campbell KT, Rosenberger LH, Sawyer RG (2013)
Use of silver in the prevention and treatment of infections: silver

13
Techniques in Coloproctology

review. Surg Infect (Larchmt) 14(1):8–20. https:​ //doi.org/10.1089/ wound irrigation to reduce surgical site infections after abdomi-
sur.2011.097. (Epub 28 Feb 2013) nal surgery: a systematic review and meta-analysis. Langenbecks
52. de Bruin AF, Gosselink MP, van der Harst E, Rutten HJ (2010) Arch Surg 400(2):167–181. https​://doi.org/10.1007/s0042​3-015-
Local application of gentamicin collagen implants in the prophy- 1279-x. (Epub 14 Feb 2015)
laxis of surgical site infections following gastrointestinal surgery: 59. Musters GD, Burger JW, Buskens CJ, Bemelman WA, Tanis PJ
a review of clinical experience. Tech Coloproctol 14(4):301–310. (2015) Local application of gentamicin in the prophylaxis of
https​://doi.org/10.1007/s1015​1-010-0593-0. (Epub 29 Jun 2010) perineal wound infection after abdominoperineal resection: a
53. Daoud FC, Edmiston CE Jr, Leaper D (2014) Meta-analysis systematic review. World J Surg 39(11):2786–2794. https​://doi.
of prevention of surgical site infections following incision clo- org/10.1007/s0026​8-015-3159-5.
sure with Triclosan-coated sutures: robustness to new evidence. 60. Sandini M, Mattavelli I, Nespoli L, Uggeri F, Gianotti L (2016)
Surg Infect (Larchmt) 15(3):165–181. https​://doi.org/10.1089/ Systematic review and meta-analysis of sutures coated with Tri-
sur.2013.177. (Epub 16 Apr 2014) closan for the prevention of surgical site infection after elective
54. Elsolh B, Zhang L, Patel SV (2017 May) The Effect of Antibi- colorectal surgery according to the PRISMA statement. Medicine
otic-coated sutures on the incidence of surgical site infections (Baltimore). 95(35):e4057. https​://doi.org/10.1097/MD.00000​
in abdominal closures: a meta-analysis. J Gastrointest Surg 00000​00405​7
21(5):896–903. https​: //doi.org/10.1007/s1160​5 -017-3357-6. 61. Allegranzi B, Bischoff P, de Jonge S, Kubilay NZ, Zayed B,
(Epub 18 Jan 2017) Gomes SM, Abbas M, Atema JJ, Gans S, van Rijen M, Boer-
55. Heal CF, Banks JL, Lepper PD, Kontopantelis E, van Driel ML meester MA, Egger M, Kluytmans J, Pittet D, Solomkin JS, WHO
(2016) Topical antibiotics for preventing surgical site infection in Guidelines Development Group (2016) New WHO recommen-
wounds healing by primary intention. Cochrane Database Syst dations on reoperative measures for surgical site infection pre-
Rev 7;11:CD011426 vention: an evidence-based global perspective. Lancet Infect Dis
56. de Jonge SW, Atema JJ, Solomkin JS, Boermeester MA (2017) 16(12):e276–e287. https:​ //doi.org/10.1016/S1473-​ 3099(16)30398​
Meta-analysis and trial sequential analysis of triclosan-coated -X. (Epub 2 Nov 2016)
sutures for the prevention of surgical-site infection. Br J Surg 62. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC,
104(2):e118–e133. https​://doi.org/10.1002/bjs.10445​. (Epub 17 Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, Del-
Jan 2017) linger EP, Itani KMF, Berbari EF, Segreti J, Parvizi J, Blanchard
57. Lv YF, Wang J, Dong F, Yang DH (2016) Meta-analysis of local J, Allen G, Kluytmans JAJW, Donlan R, Schecter WP (2017)
gentamicin for prophylaxis of surgical site infections in colo- Healthcare infection control practices advisory committee. Cent-
rectal surgery. Int J Colorectal Dis 31(2):393–402. https​://doi. ers for disease control and prevention guideline for the prevention
org/10.1007/s0038​4-015-2454-9. (Epub 27 Nov 2015) of surgical site infection, 2017. JAMA Surg 152(8):784–791. https​
58. Mueller TC, Loos M, Haller B, Mihaljevic AL, Nitsche U, Wil- ://doi.org/10.1001/jamas​urg.2017.0904
helm D, Friess H, Kleeff J, Bader FG (2015) Intra-operative

Affiliations

R. L. Nelson1 · A. Kravets2 · R. Khateeb2 · M. Raza2 · M. Siddiqui2 · I. Taha2 · A. Tummala2 · R. Epple2 · S. Huang2 ·


M. Wen2

2
* R. L. Nelson Honors College, University of Illinois at Chicago, Chicago,
altohorn@uic.edu IL, USA
1
Epidemiology/Biometry Division, University of Illinois
School of Public Health, 1603 West Taylor, Chicago, IL,
USA

13

You might also like