What is the standard dose of benzoyl peroxide for preoperative reduction in Cutibacterium acnes to reduce postoperative C. acnes infection and reoperation?

Is there evidence for using benzoyl peroxide gel preoperatively to reduce postoperative Cutibacterium acnes (C. acnes) infection?

Comment by InpharmD Researcher

Published literature have reported the successful use of benzoyl peroxide gel preoperatively to reduce postoperative Cutibacterium acnes bacterial load, and subsequently risk of postoperative C. acnes infection, when compared to a control or a non-benzoyl peroxide treatment arm. These results were observed primarily with the 5% gel strength, although durations of use, dosage schedules, and formulations widely varied.

All

Background

A 2023 meta-analysis evaluated the safety and efficacy of benzoyl peroxide (BPO) for reducing Cutibacterium acnes (C. acnes) in the shoulder. A total of 10 surgical studies were included for analysis, all of which utilized 5% BPO alone or in combination with other agents (i.e., clindamycin, chlorhexidine/alcohol). The rate of C. acnes positivity was significantly lower in patients who received 5% BPO compared to patients who did not (odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09 to 0.27; p<0.00001). In patients who received 5% BPO + clindamycin, the rate of positivity for C. acnes was also significantly lower compared to non-BMO (OR 0.20; 95% CI 0.11 to 0.40; p<0.00001). Overall, use of 5% BPO resulted in a significantly lower risk of C. acnes positivity (OR 0.21; 95% CI 0.15 to 0.30; p<0.00001). No difference in C. acnes positivity was found when comparing BPO and BPO + clindamycin (OR 1.00; 95% CI 0.32 to 3.13; p= 1.00). It should be noted that the rate of adverse events was significantly higher with 5% BPO compared to non-BPO (OR 6.04; 95% CI 1.34 to 27.22; p= 0.02). While some publication bias was present in the analysis, there were low levels of heterogeneity. The authors determined that BPO can decrease C. acnes in the shoulder to prevent infection; however, the combination of BPO and clindamycin does not enhance such effects. [1]

A 2022 systematic review and meta-analysis compared the efficacy of chlorhexidine gluconate (CHG) and BPO in reducing C. acnes burden in the shoulder before surgery. A total of ten studies (N= 589 patients) were included, comprised of 6 randomized controlled trials (RCTs), two prospective cohort studies, and two case series. Of eight studies assessing BPO efficacy, 7 used 5% BPO solution, while 1 used a 10% solution; treatment schedules prior to skin culturing varied, as well as drug formulations (i.e., gel versus ointment). Overall, BPO use resulted in a significant reduction in positive cultures versus CHG (risk ratio [RR] 0.46; 95% CI 0.27 to 0.77; p<0.009). C. acnes burden was also significantly reduced in sebaceous glands, dermal layer, and anterior and posterior portal sites after application of 5% BPO. Due to limited data on follow-up, however, conclusions of BPO efficacy in prevention of indolent infections is uncertain. [2]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there evidence for using benzoyl peroxide gel preoperatively to reduce postoperative Cutibacterium acnes (C. acnes) infection?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Table 1 for your response.

Table 1

Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure
Design	Randomized control trial N= 100
Objective	To investigate the effectiveness of preoperative skin preparation with benzoyl peroxide (BPO) gel in reducing Cutibacterium acnes (C. acnes) infection in patients undergoing shoulder surgery
Study Groups	Treatment group (BPO; n= 45) Control group (soap; n= 55)
Inclusion Criteria	Patients scheduled for elective shoulder surgery who could comply with the study protocol
Exclusion Criteria	Patients younger than 20 years old, language barriers or cognitive impairment, and/or had previous surgical scars in the shoulder area
Methods	Eligible patients were randomized into two groups: a control group following standard local guidelines with regular soap and a BPO group using the BPO gel. The intervention involved applying a 5% BPO gel to the shoulder area for two days before surgery. All surgeries took place in an operating room with laminar airflow, and preoperative skin preparation was done using 0.5% chlorhexidine solution in 70% ethanol. Skin swabs were taken before and after skin preparation, after skin closure, and punch biopsies were collected for analysis. Bacterial cultures were performed to assess C. acnes colonization, with the first author conducting the analyses in a blinded manner.
Duration	October 2017 to December 2019
Outcome Measures	Primary: reduction in C. acnes bacterial load on the skin before and after surgical skin preparation in patients undergoing shoulder surgery Secondary: presence of C. acnes in biopsies, compliance with preoperative skin preparation protocols, and comparison of bacterial load between control and BPO groups
Baseline Characteristics		Control group (soap) (n= 55)	Treatment group (BPO) (n= 45)
	Age, years	65 ± 13	63 ± 13
	Male	40	23
	Approach, DP/Sup	36/17*	35/10
	Smokers	3	2
	OR time, min	87 ± 31	102 ± 40
	Side effects	0	0
	Abbreviations= DP: deltopectoral; Sup: superior; OR: operating room *Two patients with superficial swabs only.
Results	Endpoint	Control group (n= 55)	BPO group (n= 45)	p-value
	Swab_c No. of patients with detectable C. acnes Total viable count, cfu/mL	55 2900	42 1300	0.088 0.027*
	Swab₁ No. of patients with detectable C. acnes Total viable count, cfu/mL	50 2250	26 20	<0.001* <0.001*
	Swab₂ No. of patients with detectable C. acnes Total viable count, cfu/mL	12 0	2 0	0.004* 0.021*
	Swab₃ No. of patients with detectable C. acnes Total viable count, cfu/mL	34 1300	21 50	0.326 0.040*
	Swab_c: Preoperative area, Contralateral shoulder Swab₁: Preoperative area, Surgical side Swab₂: Immediately before skin incision, Surgical side Swab₃: After skin closure, sterile field, Surgical side All samples swabbed 15 times back and forth. *p < 0.05
Adverse Events	No adverse reactions (e.g., erythema, scaling, shedding, itching) were reported.
Study Author Conclusions	Preoperative BPO treatment of the shoulder may be an effective method to decrease bacterial skin load of C acnes from skin incision until wound closure.
InpharmD Researcher Critique	While the benzoyl peroxide 5% topical gel application regimen appeared to result in statistically significant reductions in acnes vs the regular soap regimen, the clinical utility of this surrogate outcome is unclear, as benzoyl peroxide 5% topical gel also resulted in a larger proportion of patients with subsequent deep surgical site infections (6.6%) vs the regular soap group (3.6%). Because the primary and secondary outcomes were not explicitly stated, the study may not have been designed to reliably detect significant differences in subsequent deep surgical infections, increasing the risk of this statistically significant difference observed being due to a type 1 error, rather than being a difference that truly exists. A larger study population with randomization more balanced with respect to bacterial load at baseline may help to confirm these results to better inform clinical inferences.

References:

Scheer VM, Jungeström MB, Serrander L, Kalén A, Scheer JH. Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure. J Shoulder Elbow Surg. 2021;30(6):1316-1323. doi:10.1016/j.jse.2020.12.019

Background

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there evidence for using benzoyl peroxide gel preoperatively to reduce postoperative Cutibacterium acnes (C. acnes) infection?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Table 1 for your response.

Table 1

Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure
Design	Randomized control trial N= 100
Objective	To investigate the effectiveness of preoperative skin preparation with benzoyl peroxide (BPO) gel in reducing Cutibacterium acnes (C. acnes) infection in patients undergoing shoulder surgery
Study Groups	Treatment group (BPO; n= 45) Control group (soap; n= 55)
Inclusion Criteria	Patients scheduled for elective shoulder surgery who could comply with the study protocol
Exclusion Criteria	Patients younger than 20 years old, language barriers or cognitive impairment, and/or had previous surgical scars in the shoulder area
Methods	Eligible patients were randomized into two groups: a control group following standard local guidelines with regular soap and a BPO group using the BPO gel. The intervention involved applying a 5% BPO gel to the shoulder area for two days before surgery. All surgeries took place in an operating room with laminar airflow, and preoperative skin preparation was done using 0.5% chlorhexidine solution in 70% ethanol. Skin swabs were taken before and after skin preparation, after skin closure, and punch biopsies were collected for analysis. Bacterial cultures were performed to assess C. acnes colonization, with the first author conducting the analyses in a blinded manner.
Duration	October 2017 to December 2019
Outcome Measures	Primary: reduction in C. acnes bacterial load on the skin before and after surgical skin preparation in patients undergoing shoulder surgery Secondary: presence of C. acnes in biopsies, compliance with preoperative skin preparation protocols, and comparison of bacterial load between control and BPO groups
Baseline Characteristics		Control group (soap) (n= 55)	Treatment group (BPO) (n= 45)
	Age, years	65 ± 13	63 ± 13
	Male	40	23
	Approach, DP/Sup	36/17*	35/10
	Smokers	3	2
	OR time, min	87 ± 31	102 ± 40
	Side effects	0	0
	Abbreviations= DP: deltopectoral; Sup: superior; OR: operating room *Two patients with superficial swabs only.
Results	Endpoint	Control group (n= 55)	BPO group (n= 45)	p-value
	Swab_c No. of patients with detectable C. acnes Total viable count, cfu/mL	55 2900	42 1300	0.088 0.027*
	Swab₁ No. of patients with detectable C. acnes Total viable count, cfu/mL	50 2250	26 20	<0.001* <0.001*
	Swab₂ No. of patients with detectable C. acnes Total viable count, cfu/mL	12 0	2 0	0.004* 0.021*
	Swab₃ No. of patients with detectable C. acnes Total viable count, cfu/mL	34 1300	21 50	0.326 0.040*
	Swab_c: Preoperative area, Contralateral shoulder Swab₁: Preoperative area, Surgical side Swab₂: Immediately before skin incision, Surgical side Swab₃: After skin closure, sterile field, Surgical side All samples swabbed 15 times back and forth. *p < 0.05
Adverse Events	No adverse reactions (e.g., erythema, scaling, shedding, itching) were reported.
Study Author Conclusions	Preoperative BPO treatment of the shoulder may be an effective method to decrease bacterial skin load of C acnes from skin incision until wound closure.
InpharmD Researcher Critique	While the benzoyl peroxide 5% topical gel application regimen appeared to result in statistically significant reductions in acnes vs the regular soap regimen, the clinical utility of this surrogate outcome is unclear, as benzoyl peroxide 5% topical gel also resulted in a larger proportion of patients with subsequent deep surgical site infections (6.6%) vs the regular soap group (3.6%). Because the primary and secondary outcomes were not explicitly stated, the study may not have been designed to reliably detect significant differences in subsequent deep surgical infections, increasing the risk of this statistically significant difference observed being due to a type 1 error, rather than being a difference that truly exists. A larger study population with randomization more balanced with respect to bacterial load at baseline may help to confirm these results to better inform clinical inferences.

References: