Combination Effects of Clindamycin and Benzoyl Peroxide Against Cutibacterium acnes.

Topical clindamycin has been accepted as being effective, safe and well tolerated in the treatment of acne for decades. Topical clindamycin comes in various vehicles, including gel, lotion, solution and foam. Choosing the proper vehicle is dependent on patient preference, tolerability and application site. Widespread usage of topical antibiotics has led to a greater proportion of resistant strains of Propionibacterium acnes. As a result of the increasing resistance, clindamycin monotherapy is no longer considered a first-line acne treatment. Currently, combination treatment with benzoyl peroxide has helped to prevent antibiotic resistance. In addition, novel combinations, such as clindamycin phosphate 1.2% or tretinoin 0.025% gel, have been proven to be superior to clindamycin monotherapy in reducing acne lesion counts.

Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris. When used in combination, they promise greater efficacy than either individual agent used alone and the combined use of benzoyl peroxide with topical antibacterial has been shown to decrease the emergence of antibacterial resistant species. The objective was to determine the efficacy and safety of a combination benzoyl peroxide plus clindamycin in a gel formulation compared with each of its 2 active constituents in gel vehicle, and gel vehicle given alone in the treatment of acne vulgaris. In this 10-week, multicenter, double-blind trial, 480 patients with moderate to moderately severe acne were randomized to receive twice-daily treatment with 5% benzoyl peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clindamycin, or vehicle. Significantly greater reductions in the number of inflammatory and total lesions were demonstrated in patients using combination therapy compared with those using any of its 3 individual components. Likewise, both physicians' and patients' global evaluations showed significantly greater improvements with the combination therapy than with its individual components. The most frequent adverse effect, dry skin, occurred to a similar extent in the combination and benzoyl peroxide treatment groups. The improved efficacy obtained with the combination therapy was accompanied by a tolerability profile similar to that of benzoyl peroxide alone, making this new combination product an alternative antimicrobial therapy for acne vulgaris.

Cutibacterium acnes persists despite topical clindamycin and benzoyl peroxide

The objective of this study was to evaluate the rates of clindamycin and erythromycin resistance among group B Streptococcus (GBS)-positive isolates cultured from pregnant women in an upstate New York community hospital. All GBS-positive perinatal rectovaginal cultures obtained from January 2010 through October 2011 were tested for resistance to erythromycin and clindamycin. Among the 688 GBS-positive cultures, clindamycin resistance was found in 38.4% and erythromycin resistance was found in 50.7%. Rates of GBS resistance to clindamycin and erythromycin are much higher than reported in earlier U.S. studies, suggesting both increasing resistance and regional variation in resistance. These findings lend strong support to the CDC and American College of Obstetricians and Gynecologists (ACOG) recommendations that clindamycin use for intrapartum antibiotic prophylaxis be restricted to penicillin-allergic women at high risk of anaphylaxis and that GBS isolates be tested for antibiotic resistance prior to the use of clindamycin in these women.

<p class="abstract"><strong>Background:</strong> Acne vulgaris is majorly affecting adolescent population with profound negative impact on the quality of life (QOL). The objectives of the present study was to evaluate adapalene 0.1% alone vs combination therapy of adapalene 0.1% with benzoyl peroxide (BPO) 2.5% and adapalene 0.1% with clindamycin 1% in the treatment of acne vulgaris and to analyse health related QOL using the cardiff acne disability index (CADI).</p><p class="abstract"><strong>Methods:</strong> This prospective, observational study of 12 months duration involved patients who were being treated with adapalene alone and adapalene combined with either clindamycin or benzoyl peroxide in the normal course of treatment. Efficacy of treatment and QOL was assessed by the comprehensive acne severity system (CASS) and CADI respectively.<strong></strong></p><p class="abstract"><strong>Results:</strong> A total of 180 patients were enrolled (n=60 in each group). Male: female ratio was 1: 2.52. 76.7% patients were of adolescent age with the Mean age of 21.17±3.28 years. Average age of onset was 18.03±2.80 years. Most patients had moderate grade of acne (51%) followed by mild grade (46%) and almost clear (3%). Face was the common site, followed by back and chest. There was a statistically significant improvement in both number of lesions and also QOL in all the three treatment groups (p<0.0001).</p><p class="abstract"><strong>Conclusions:</strong> Topical adapalene 0.1% is efficacious in the treatment of acne vulgaris both alone as well as in combination with topical benzoyl peroxide 2.5% and topical clindamycin 1%. Adapalene also has positive influence on the QOL alone as well as in combination but no superiority of one group over the other was observed with regard to efficacy as well as QOL.</p><p> </p>

Cutibacterium acnes, a resident bacterium of the skin, is a target for antimicrobial treatment of acne vulgaris, because it exacerbates inflammation. Recently, antimicrobial-resistant C. acnes strains have been isolated worldwide, and their prevalence has led to failure of antimicrobial treatment. This study aimed to analyze the antimicrobial resistance of C. acnes strains isolated from Japanese patients with acne vulgaris who visited the hospital and dermatological clinics between 2019 and 2020. Resistance rates to roxithromycin and clindamycin increased during 2019 to 2020 compared with those during 2013 to 2018. Additionally, the proportion of doxycycline-resistant and low-susceptibility strains (minimum inhibitory concentration [MIC] ≥8μg/mL) increased. No difference in clindamycin resistance rates between patients with and without a history of antimicrobial use was observed during 2019 to 2020, which were significantly higher for patients with a history than for patients without a history during 2016 to 2018. The proportion of high-level clindamycin-resistant strains (MIC ≥256 μg/mL) gradually increased; particularly, the resistance rate was 2.5 times higher in 2020 than that in 2013. The proportion of strains showing high-level clindamycin resistance that also have the exogenous resistance genes erm(X) or erm(50), which confer high resistance, showed a strong positive correlation (r=0.82). Strains with the multidrug resistance plasmid pTZC1 encoding erm(50) and tet(W) genes were frequent in clinic patients. Notably, most strains with erm(X) or erm(50) were classified as single-locus sequence types A and F (traditional types IA1 and IA2). Our data show that the prevalence of antimicrobial-resistant C. acnes is increasing in patients with acne vulgaris attributable to acquisition of exogenous genes in specific strains. To control the increasing prevalence of antimicrobial-resistant strains, it is important to select the appropriate antimicrobials while taking into consideration the latest information on resistant strains.

Introduction & Objective: Psoriasis in special areas is difficult to treat and causes significant disease burden. Approved systemic therapies for moderate to severe plaque psoriasis in pediatric patients are limited and require subcutaneous injection. Apremilast, a unique oral immunomodulator that inhibits phosphodiesterase-4, is approved in multiple countries for use in adults with psoriasis, regardless of severity. In this study, the efficacy of apremilast for psoriasis in special areas in pediatric patients was assessed over 16 weeks. Materials & Methods: SPROUT (NCT03701763) is a phase 3, randomized, double-blind, placebo-controlled study in patients 6-17 years with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age and randomized 2:1 to receive apremilast (weight-based 20 mg or 30 mg twice-a-day) or placebo for 16 weeks, then apremilast through week 52. Scalp Physician Global Assessment (ScPGA) response, modified sPGA of genitalia (sPGA-G) response, Whole Body Itch-Numeric Rating Scale (WBI-NRS) response, and change from baseline in Children’s Dermatology Life Quality Index (CDLQI) were assessed through week 16. Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 101 (41.2%) were 6-11 years and 144 (58.8%) were 12-17 years; 120 (49.0%) patients weighed ≥20 to <50 kg and 125 (51.0%) weighed ≥50 kg. At baseline, 81.0% of the patients treated with apremilast and 84.1% of patients treated with placebo had moderate to severe scalp psoriasis (ScPGA ≥3). Significantly more patients achieved ScPGA response at week 16 with apremilast vs placebo (36.4% vs 18.8%; P=0.0091). At baseline, 110 patients (44.9%; 45.4% apremilast and 43.9% placebo) had moderate to severe genital psoriasis (sPGA-G ≥3). Achievement of sPGA-G response at week 16 was numerically greater with apremilast vs placebo (39.2% vs 25.0%), although not significant, possibly due to small sample size (apremilast: n=74; placebo: n=36). Significantly more patients achieved WBI-NRS response at week 16 with apremilast vs placebo (52.0% vs 32.1%; P=0.0110). Greater improvements in CDLQI were seen at week 16 with apremilast vs placebo (least-squares mean change from baseline −5.1 vs −3.2; P=0.0009). Adverse events were consistent with the known apremilast safety profile. In 21 patients vaccinated during the study (including for COVID-19, influenza, diphtheria, pertussis, tetanus, meningococcus, and hepatitis B), no new safety issues occurred. Conclusions: Apremilast significantly improved scalp psoriasis, itch, and quality of life in pediatric patients with moderate to severe psoriasis. At week 16, patients with moderate to severe genital psoriasis showed a trend toward improvement, although not significant due partially to the sample size.

Background: Clindamycin, a lincosamide antibiotic, was the 125th most prescribed medicine in the US in 2020. Topical formulations that combine clindamycin with benzoyl peroxide or a retinoid are commonly used for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding the development of gastrointestinal (GI) adverse events (AEs), the real-world incidence of these AEs with topical clindamycin is unknown. The objective is to provide an overview of safety data for topical clindamycin when used for AV treatment.
 Methods: Safety data from published literature on PubMed® (case reports, clinical trials data, retrospective data), previously unpublished worldwide pharmacovigilance data (from January 1, 1900-December 31, 2022), and two unpublished retrospective cohort studies of US electronic medical records (EMR; January 1, 2011 to January 31, 2019) were reviewed, with a focus on inflammatory bowel disease (IBD) and GI AEs following topical clindamycin monotherapy or combination treatment
 Results: There have been only 4 published case reports of topical clindamycin-associated GI AEs, which were all published between the years 1981-1997. In 8 published pivotal phase 3 clinical trials of topical clindamycin monotherapy or combination treatment for AV, GI-related AEs were reported in 1.4% of clindamycin-treated participants (38/2,672; safety populations). According to the pharmacovigilance data, the rate of GI-related adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). In 1 published retrospective report, there were 0 reports of colitis from the 1,124 patients estimated to have received topical clindamycin prescriptions in the years 1977-1980. In the first retrospective EMR study, results indicate that physicians prescribe topical clindamycin for AV treatment equally to patients with a history of IBD (19.0%; 98/515) or without (20.7%; 14,495/70,151). The second retrospective EMR study showed that among patients with AV and an initial prescription for topical clindamycin (monotherapy or combination; n=18,012), there were 3 (0.02%) incident cases of pseudomembranous colitis within 30 days; none of these cases had a history of IBD.
 Conclusions: A review of published case reports, clinical trials safety data, worldwide pharmacovigilance data, and retrospective US prescription data demonstrate that GI events—including colitis or pseudomembranous colitis—in patients exposed to topical clindamycin is extremely low, regardless of IBD history.
 Support: Ortho Dermatologics

To the Editor—We read the recent article by Rahimian et al. with great interest, and we applaud the authors for their efforts in addressing the role of treatment with mupirocin for recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and skin structure infections. We hypothesize that one potential reason for the high rate of recurrence of skin and skin structure infections observed by Rahimian et al. in patients with MRSA nasal colonization treated with mupirocin (6 [32%] of 19) may be plasmid-mediated resistance to mupirocin. In a prior publication, Shastry et al. demonstrated that there was a very high level of clindamycin resistance in their population of men who have sex with men (63 [63%] of 100). We have demonstrated that clindamycin resistance and mupirocin resistance are both encoded on a single plasmid, pUSA03, that is frequently identified in multidrug-resistant strains of community-associated MRSA genotype USA300. We have noted that the pUSA03-positive USA300 subclone is particularly prevalent as a cause of skin and skin structure infections in the population of men who have sex with men in San Francisco and Boston. Most notably, this subclone was the pathogen in skin and skin structure infections in men who have sex with men who had no history of prior clindamycin or mupirocin use, suggesting person-to-person transmission of the multidrug-resistant USA300 clone. With respect to the study by Rahimian et al., it would be of great interest to know (1) how many of the 19 patients treated with mupirocin had initial infecting and nasal colonizing strains resistant to both clindamycin and mupirocin (thus suggesting the presence of pUSA03) and (2) how many of these patients were men who have sex with men. Although the findings of Rahimian et al. indicate that an attempt at decolonization with mupirocin may not be beneficial in preventing recurrent disease due to community-associated MRSA in their patient population, the effect of decolonization with mupirocin in a population with lower rates of clindamycin and mupirocin resistance in colonizing and/or infecting MRSA strains remains undetermined.

The effect of pretreatment of the pilosebaceous unit on Cutibacterium acnes burden during shoulder arthroplasty: a randomized controlled trial.

Background: Antibiotic resistance is a global concern, with several countries reporting resistance in >50% of Cutibacterium acnes (C. acnes) strains. Combination formulations containing an antibiotic and the antimicrobial benzoyl peroxide (BPO) may reduce this resistance risk, especially with prolonged use. This four-part study tested susceptibility of 31 C. acnes clinical strains to antibiotics alone or in combination with BPO.
 Methods: Part 1: C. acnes susceptibility to single-drug antibiotics was assessed via minimum inhibitory concentration (MIC) values obtained from epsilometer tests, with lower MIC indicating higher susceptibility. Part 2: Susceptibility to fixed-dose antibiotic/BPO combination products (branded/in-development) was determined by measuring zone of inhibition using agar diffusion method, with larger diameter indicating increased bacterial inhibition. Part 3: The effect (synergistic, additive, antagonistic, or neutral) of combining clindamycin with BPO on C. acnes inhibition was evaluated using a checkerboard assay, wherein two test compounds are combined in varying concentrations. Part 4: Development of resistance was assessed using serial passage of bacterial cultures in increasing concentrations of clindamycin alone or in combination with BPO.
 Results: Part 1: All antibiotics tested—clindamycin, doxycycline, erythromycin, and minocycline—had similar activity. Susceptibility was highly strain dependent, as some C. acnes strains had elevated MIC—an indication of resistance—against different antibiotics. Part 2: For the 6 C. acnes strains that had no inhibitory zone (0 cm) with clindamycin alone, formulations with BPO enhanced activity against the same isolates (range: 0.8-2.2 cm with clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1%, clindamycin phosphate 1.2%/BPO 5%, or clindamycin phosphate 1.2%/BPO 3.75%). Part 3: The combination of clindamycin and BPO resulted in an additive effect for 4 of the 7 acne-associated strains tested and was neutral for 3 strains. Part 4: Bacterial cultures repeatedly exposed to a combination of clindamycin and BPO did not develop resistance to C. acnes, which occurred with exposure to antibiotic alone.
 Conclusions: Overall, antibiotic susceptibility was highly strain dependent and antibiotic formulations with BPO exhibited enhanced activity against less susceptible C. acnes strains. Fixed combinations of BPO with an antibiotic may improve antimicrobial activity and protect against resistance development.
 
 Funding: Ortho Dermatologics.

Acne vulgaris or acne is a condition of chronic inflammation of the pilosebaceous unit. Topical clindamycin and topical benzoyl peroxide (BP) are therapy with antibacterial and anti-inflammatory effects. The pharmacist's role during self-medication services and the knowledge possessed by the patient are needed to produce the correct drug use. This study aimed to determine the relationship between knowledge and accuracy of using topical benzoyl peroxide and clindamycin self-medication either alone or in combination with students of Brawijaya University with Acne vulgaris. This research was conducted online which is observational analytic with a cross-sectional design. The sampling technique used was a purposive sampling technique based on inclusion and exclusion criteria and 105 respondents were obtained. Student knowledge was measured using a Guttman scale questionnaire with right and wrong answer choices. The accuracy of student use was measured using semi-open questions with multiple-choice answers and essays. The results showed that the respondents had good knowledge (79.05%), sufficient (20.95%), and less (0.00%). Meanwhile, the results of the accuracy of the use of therapy showed that students were correct (60.00%) and not correct (40.00%). The results of the Spearman correlation test showed a significant positive relationship between knowledge and the accuracy of using self-medicated topical benzoyl peroxide and clindamycin therapy (p = 0.012; r = 0.245). Based on the study results, it is concluded that there is a significant positive relationship between knowledge and the accuracy of using self-medicated topical benzoyl peroxide and clindamycin therapy in Brawijaya University students with Acne vulgaris.

Optimal management of staphylococcal scalded skin syndrome (SSSS) has not been established. Clindamycin may benefit patients via inhibition of ribosomal toxin production, but resistance patterns suggest penicillinase-resistant penicillins or cephalosporins should be the first line. Our goal was to describe demographic and clinical characteristics of SSSS patients at our institution, delineate bacterial resistance patterns, and examine outcomes of varying therapeutic strategies in SSSS. We performed a retrospective review of patients under the age of 18 with confirmed clinical SSSS diagnosis by the dermatology consult team at the University of North Carolina (UNC) Hospitals from January 2008 to April 2017. Median hospital and ICU length of stay (LOS) were compared using a Wilcoxon Rank Sum Test. We found 59 SSSS patients. Coverage with clindamycin and vancomycin versus absence of that combination was associated with shorter ICU LOS. Although trending toward reduced hospital LOS, this was not significantly altered with the use of vancomycin and clindamycin after adjustment for multiple comparisons. Individual use of either clindamycin or vancomycin did not significantly alter overall hospital or ICU LOS. Among 24 patients with a pathogen identified on culture, 18 (75.0%) revealed resistance to clindamycin, and 2 (8.3%) revealed MRSA. Clindamycin resistance is more prevalent in hospitalized SSSS patients compared to our pediatric outpatient population. The combination of vancomycin and clindamycin results in shorter ICU LOS. Individual use of clindamycin or vancomycin does not significantly reduce hospital or ICU LOS after adjustment for multiple comparisons.

Introduction: Acne guidelines recommend the addition of benzoyl peroxide (BPO) to antibiotics to reduce resistance in Cutibacterium acnes (C. acnes). Pairing the antibiotic/BPO combination with a retinoid, such as adapalene, may further increase treatment efficacy, although research on adapalene’s antibacterial activity is limited. To determine if adapalene improves antimicrobial activity, this in vitro study evaluated minimum inhibitory concentration (MIC) of clindamycin, adapalene, and BPO alone or in combination against both susceptible and resistant C. acnes isolates. Methods: Part 1a: C. acnes sensitivity to clindamycin, adapalene, or BPO was assessed via MIC values obtained by the broth microdilution method, with lower MIC indicating higher susceptibility. Part 1b: The effect (synergistic, additive, antagonistic, or indifferent [no interaction]) of combining adapalene with clindamycin or BPO on C. acnes inhibition was evaluated using a checkerboard assay, wherein two test compounds are combined in varying concentrations. Part 2: Susceptibility to single formulations of clindamycin, adapalene, and BPO, and fixed-dose combination formulations of an antibiotic (clindamycin or erythromycin) with BPO was determined by measuring antibacterial zone of inhibition using agar diffusion method, with larger diameter indicating increased bacterial inhibition. Results: Part 1a: Clindamycin demonstrated strain-dependent activity (MIC range: <0.125-64 μg/ml), while BPO and adapalene had no/low activity as indicated by high MIC (>512 and >64, respectively) against the 6 acne-associated strains tested. Part 1b: The combination of adapalene with clindamycin resulted in an additive effect for 3 and no interaction for 1 strain, whereas adapalene with BPO did not result in any interaction against the 4 acne-associated strains tested. Part 2: Activity of single formulations varied, with adapalene 0.1% having no activity (zone of inhibition: 0 cm) against any of the 8 acne-associated C. acnes strains tested. The fixed-dose combination formulations had generally similar activity against all strains tested (range: 0.9-5 cm). Conclusions: In these in vitro analyses, adapalene and BPO had no/low activity against C. acnes, whereas clindamycin alone or in combination formulations demonstrated strain-dependent activity. The relatively high MIC of BPO is not unexpected and aligns with previous studies in which the in vitro activity of BPO was low compared to its high in vivo antimicrobial activity. Further, addition of the retinoid adapalene had an additive effect on the antimicrobial activity of clindamycin against 3 out of 4 C. acnes strains tested, but no effect on the activity of BPO in vitro. Taken together, these data suggest that when combined with clindamycin/BPO, adapalene may enhance antimicrobial activity, while also bringing its own, unique retinoid mechanism of action to the triple combination, adding to clindamycin's bacteriostatic and anti-inflammatory properties. Funding: Ortho Dermatologics

Objective: Combination therapy is currently the preferred acne treatment. We conducted this study to compare the efficacy and tolerability of 0.1% adapalene with 1% clindamycin versus 0.1% adapalene with 2.5% benzoyl peroxide (BPO) in the treatment of acne vulgaris. Methods: This study was conducted over a period of 1 year from September 2014 to September 2015. One-hundred patients aged 14 to 30 years with mild to moderate acne vulgaris were included. The patients were randomly allocated to 2 equal groups (n = 50 in each group), and received a topical combination of 0.1% adapalene with 1% clindamycin andtopical combination of 0.1% adapalene with 2.5% BPO, respectively). The efficacy and tolerability of two treatments were compared. The unpaired student t test was used to compare the difference in continuous variables between 2 groups, while the chi-square test or Fisher exact test was used for categorical variables. Results: One-hundred patients with mild to moderate acne vulgaris were randomly allocated to 2 equal groups (n = 50 in each group). After 12 weeks of treatment, there were no significant differences between the adapalene-clindamycin and adapalene-BPO in the mean reductions in the numbers of non-inflammatory lesions (11.16 ± 8.01 and 11.12 ± 8.62, respectively), inflammatory papules (49.78 ± 37.57 and 50.48 ± 36.57, respectively), and total lesions (67.50 ± 44.59 and 70.12 ± 46.83, respectively). The incidence of a burning sensation was significantly greater in the adapalene-BPO group than the adapalene-clindamycin group (32% vs. 6%; P = 0.002). Conclusion: Topical adapalene plus clindamycin and adapalene plus BPO had similar efficacies in the treatment of acne. Adapalene with clindamycin was better tolerated than adapalene with BPO.