Antibiogram in Cutibacterium Acnes: A Comprehensive Study of Oral and Topical Treatments for Acne in the Indian Population

Antibiogram in Cutibacterium Acnes: A Comprehensive Study of Oral and Topical Treatments for Acne in the Indian Population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Antibiogram in Cutibacterium Acnes: A Comprehensive Study of Oral and Topical Treatments for Acne in the Indian Population Rochelle Monteiro, beena Anthony, Ramesh Bhat This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5892820/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Injudicious antibiotic therapy in acne has resulted in significant dissemination of cross-resistant strains of Cutibacterium acnes (C. acnes). Resistance patterns vary in different studies, corresponding to the geographic location, and study methods. Prior studies have shown a high resistance to azithromycin, erythromycin and clindamycin and high sensitivity to macrolide antibiotics. There is a paucity of studies evaluating the efficacy of topical anti-acne agents.Our objective was to isolate C.acnes from acne lesions ,and to evaluate the antibiotic susceptibility of oral and topical antibiotics in acne. As antibiotic sensitivity patterns vary with time and prescribing practices, our study aimed to evaluate these patterns, as there is limited data available on Antimicrobial resistance(AMR) in India. Swabs from acne pustules from 124 patients, aged 12 years and above, were obtained and inoculated into selective media for C. acnes and blood agar for isolation of aerobic organisms, gram staining and species identification of Cutibacterium. The isolated bacteria were cultured and evaluated for antibiotic sensitivity using standard disc diffusion techniques. Statistical analysis was performed on SPSS23 software. In our study, the average age of the patients was 21.34 ± 4.2 years, a majority (63.7%) were females. Cutibacterium was isolated in 74.19% of patients. Among oral antibiotics minocycline was the most sensitive to C. acnes (97%); the highest resistance to C. acnes was seen with erythromycin (84%). Topically, benzoyl peroxide had higher sensitivity (48%), and adapalene (95%) and azelaic acid (83%) showed the least antimicrobial activity against C. acnes.The results prove that sensitivity patterns to oral antibiotics remain similar to previous studies. Topical Clindamycin resistance is lower than previously reported resistance rates. Topical benzoyl peroxide showed lower antimicrobial activity in comparison to prior studies. AMR in acne continues to be a concern. Hence the need to maintain stringent guidelines for antibiotic usage in acne. Figures Figure 1 Figure 2 Background Acne vulgaris is one of the most common skin disorders worldwide, affecting around 67–95% of adolescents. Although acne is not an infective disorder, oral and topical antibiotics have remained the mainstay of therapy.[ 1 ] The pathogenesis of acne is multifactorial and involves abnormal follicular keratinization, excessive sebum production, inflammation, and the modification in the distribution of clusters of Cutibacterium acnes (C.acnes). Other important contributing factors are dysseborrhoea, and external triggers such as diet, cosmetics, and stress. Recent focus has been on the skin microbiome wherein changes in the distribution of strains or species, and/or pathogenic alteration of these species despite stable distribution, contribute towards the development of acne. In other words, disruption of the skin barrier with alteration of the skin microbiome results in the proliferation of C. acnes.[ 2 ] C. acnes is a gram-positive rod, non-spore forming, preferential anaerobe, which is an exclusive bacterial inhabitant of facial sebaceous follicles and an important part of the microbiota of healthy human skin. It acts on multiple stages in acne by modulating keratinocyte differentiation, increasing local inflammation, inducing microcomedo formation, lipogenesis and sebum production.[ 3 ] C.acnes has additional interactions with markers of innate immunity such as toll-like receptors, matrix metalloproteinase, protease activated receptors, antimicrobial peptides, and pro-inflammatory cytokines[ 4 – 7 ] Thus C acnes has multiple pathogenic mechanisms in acne. Despite the non-infective nature of acne, topical and systemic antibiotics form the mainstay of antibiotic therapy in most countries. Antibiotics in acne are used mainly for their anti-inflammatory action. However, indiscriminate usage led to widespread antimicrobial resistance (AMR). Resistance rates increased gradually in the 1970’s and 80’s up to 25%, increasing to 50–60% in the 1990’s and peaking at 75% in the 2000’s. Recent years have shown a gradual decrease in AMR rates probably owing to stringent antibiotic stewardship policies. [ 8 ] Resistance rates vary in different geographical areas, due to differences in prescribing patterns and inconsistent laboratory methods of ascertaining bacterial resistance. However worldwide resistance rates to erythromycin and clindamycin remain elevated. High resistance rates to azithromycin, clarithromycin have been observed in India, Japan and China. Most of the topically used antibiotics in acne have developed resistance over the years due to frequent usage and cross-resistance acquired from oral antibiotic usage.[ 8 ] We conducted this study to determine the antibiotic sensitivity rates to commonly used oral antibiotics and topical antibiotics and anti-inflammatory agents in our geographic area. Antibiotics are used indiscriminately for acne and other infective conditions. Topical antibiotics are available over the counter in India, and this too has added to the burden of AMR. Thus, we aimed to determine the efficacy of the current prescribing regimens for acne and to ascertain if antibiotic stewardship policies introduced in recent years have been effective in curtailing the burden of AMR. Methods A total of 124 patients diagnosed to have moderate to severe acne vulgaris, attending the Dermatology outpatient department for a period of 2 years, at a tertiary care hospital were included in this prospective study, after obtaining institutional ethics clearance. All ethical procedures were followed with respect to data collection and processing. The study was registered under the Clinical Trial Registry of India (REF/2016/03/010997). A sample size of 124 was included at 10% allowable error (e), 95% confidence interval based on the study by Biswal et al 9 where p = 66% and the formula n = z α 2 (1-p)/e 2 .The study aimed at isolating C. acnes and evaluating the sensitivity and resistance patterns to commonly used oral antibiotics and topical anti-acne agents. The inclusion criteria were age above 12 years and patients with moderate to severe acne. The following patients were excluded, patients who had used oral or topical antibiotics in the past one month ,intake of oral isotretinoin in the past 2 months, any other facial lesions. The drug washout period was calculated based on the half-life of the oral and topical agents. Basic clinical data (age, gender) were noted at the time of enrolment. An informed consent or assent was obtained as applicable. Specimen collection The area of collection was cleaned with 70% ethyl alcohol and the specimen was obtained after unroofing the closed papule/pustule with a sterile blood lancet or expressed using a comedone extraction in case of open comedones. The material obtained was transported without delay, under anaerobic conditions to the microbiology laboratory. A tiny quantity of the specimen obtained was transferred onto a sterile slide for gram staining. Processing of the sample The remaining specimen was transferred to a sterile tube containing 0.5ml of phosphate buffer (pH7.4) and vortex mixed for 30 seconds to disperse the bacteria. For the isolation of Cutibacterium, the vortexed sample was inoculated onto sheep blood agar and Cutibacterium selective agar in 4 quadrants to obtain a semi-quantitation and then placed in a Beckton and Dickinson (BD) Gas Pak EZ sachet (anaerobe gas generating pouch system with indicator) and incubated at 37 0 C for 48 hours. After incubation, the characteristic large, white to yellow dry colonies were presumptively identified as Cutibacterium species using biochemical tests and confirmed with MALDI-TOF (Matrix-Assisted Laser Desorption Ionization- Time of flight) in doubtful cases. Disc diffusion technique The Cutibacterium colonies identified were subjected to antimicrobial susceptibility testing on Brucella blood agar in an anaerobic environment using BD Gas Pak EZ sachets by Kirby-Bauer disc diffusion techniques, according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The antimicrobial agents used for testing were as follows: Doxycycline (30µg/disc), Minocycline (30µg/disc), Tetracycline(30µg/disc), Erythromycin (15 µg/disc), Azithromycin (15µg/disc), Roxithromycin (30µg/disc), Ampicillin(10µg/disc) procured from HI-media Pvt Ltd Mumbai. For the topical agents, sterile Whatman No.1 filter paper discs saturated with the respective agents namely: Clindamycin (0.1%), Tretinoin (0.05%), Adapalene (0.1%), Benzoyl peroxide (2.5%), Azelaic acid (10%) were used to test the antimicrobial susceptibility. The zone of inhibition was measured and expressed in millimeters. The results were interpreted as resistant or sensitive according to the zone diameter interpretive chart. Statistical analysis The collected data was summarized by frequency and percentage. The Chí-square test was performed for goodness of fit to compare the frequency within the group. Comparison among different groups of antibiotics was not performed. The analysis was performed in SPSS 23 software. The level of significance was 5%. Results Out of the 124 cases, most of the patients belonged to the age group 10–20 years (53.2%), followed by 20–30 years (45.2%) (Table 1 ). Females outnumbered males comprising 63.7% of the study group. Most of the patients had grade 3 acne (45.2%), followed by grade 2(28.2%). Bacterial growth was present in 80.6% of the total cases. Cutibacterium acnes was isolated from a majority of the cases (74.2%)(Fig. 1 a,c), staphylococcus epidermidis from 5.6%, and staphylococcus aureus from 0.8% of the cases. In 19.4% of patients there was no bacterial growth. Table 1 Clinical & microbiological profile of patients AGE 10–20 53% 21–30 45% Above 30 2% GENDER Female 64% Male 36% GRADE 1 14% 2 28% 3 45% 4 13% BACTERIAL GROWTH Absent 19% Present 81% ISOLATE No growth 19% C acnes 74% staphylococcus epidermidis 6% staphylococcus aureus 1% Among the oral antibiotics studied, the highest antibacterial activity against C. acnes was seen with minocycline (97%) and doxycycline (90.8%)(Fig. 1 b). This was followed by ampicillin (72.4%), tetracycline (48%), clindamycin (32.7%),and azithromycin (31.6%). The lowest antimicrobial action against C. acnes was observed with Roxithromycin (17.3%) and Erythromycin (11.2%). As these values were measured as a zone of inhibition, statistical comparisons were not applicable. The highest antimicrobial resistance to C. acnes were noted to the macrolide antibiotics such as erythromycin (88.8%), roxithromycin (82.7%), azithromycin (68.4%) and clindamycin (67.3%).(Fig. 2 ) Among the topical agents, the highest antimicrobial action against C. acnes was seen with benzoyl peroxide (48%).Benzoyl peroxide (BP) is an anti-inflammatory agent, with known antimicrobial action against C.acnes. The antibacterial activity noted with BP in our study was higher than a commonly used antibiotic i.e., clindamycin. Topical adapalene (95%), azelaic acid (87%), tretinoin (63.3%), and clindamycin (60.8%) had least efficacy in inhibiting C. acnes in vitro (Fig. 1 d). Topical clindamycin, the only antibacterial agent studied, showed low propensity in inhibiting C.acnes, thus both oral and topical clindamycin are less efficacious in acne. Discussion In our study, most patients were female, with the mean age being 21.5 ± 4.2 years. Cutibacterium acnes was the most common bacterial isolate. Among oral antibiotics, minocycline showed the highest antimicrobial activity against C.acnes and erythromycin showed the highest resistance to C.acnes. Topical BP showed higher antimicrobial action against C. acnes in comparison to other topically tested agents and azelaic acid had the lowest antimicrobial activity against C.acnes. Most of these findings are in concordance with previous literature[ 3 ], except the sensitivity pattern of azelaic acid, which has been described as possessing significant antimicrobial action to C. acnes in earlier studies.[ 9 ] Previous studies included patients with a similar age distribution 2,10–15 , most patients being < 25 years of age. 1,10,14 Grade 2 acne was the commonest in previous studies, which contrasts with our study where grade 3 acne lesions were predominant (45%). The isolation rates of Cutibacterium from acne lesions were comparable in prior studies, varying from 66% compared to 74.2% in our study.[ 2 , 10 , 12 , 13 ] Cutibacterium acnes (74.2%) was the most common isolate in our study, with a minority of acne lesions harboring staphylococcus epidermidis (5.6%) and staphylococcus aureus (S.aureus) (0.80%).S.aureus had higher isolation rates in previous studies. [ 10 , 14 ] Female patients outnumbered males in a majority of previous studies, as observed in our study where 63.7% of recruited patients were female.[ 1 , 11 – 15 ] Studies by Biswal (37%), Schaffer (42%) showed a lower number of females. [ 10 , 13 ] Overall AMR rates between 2010–2020 were highest in Hong-Kong (58.4%), Greece (42%), Colombia (37.5%), and lowest in Australia (9%). Resistance to the macrolide-lincosamide-streptogramin (MLS) antibiotics such as erythromycin, clindamycin, azithromycin, clarithromycin has showed worsening rates from 2010 onwards, especially in countries like China, India, Greece, and Egypt. Antibiotics with special local interest, used more frequently in a particular geographical area, have also shown to develop high resistance, e.g., azithromycin, clarithromycin in India, Mexico and China.[ 8 ] Our study was in concordance with most of these studies, showing high resistance rates to the macrolide antibiotics. Roxithromycin, although not frequently used for acne and not previously studied, showed high resistance rates to C. acnes. This may be explained by the phenomenon of cross-resistance described to the MLS antibiotics. A previous study in North India[ 16 ] showed comparable resistance rates, except to azithromycin (100% vs 68.4% in our study). Even though the study was in the same country, resistance rates have shown variation within the same countries in previous studies.[ 8 ] This can explain the differing AMR rates between our study and the aforementioned study. The antibiotic prescribing practices vary greatly among different regions, also a highlighted awareness about the resistance to azithromycin in the last few years has led to reduction in the usage of this drug for acne in our region. This may explain the difference in resistance rates, along with other factors, such as sampling techniques, laboratory methods, and interpretation of growth. The most sensitive oral antibiotics were minocycline (97%), and doxycycline (90.8%) as reported by previous studies.[ 8 ] Thus, fortunately AMR has not yet been acquired by the newer tetracyclines, hence stringent guidelines should be continued to be enforced to sustain this. Although ampicillin showed a high sensitivity rate (72%) in vitro, this does not translate into clinical efficacy. Ampicillin is a hydrophilic drug, hence its limited penetration into the sebum rich acne follicle reduces its clinical efficacy in acne. In contrast, the macrolide and tetracycline antibiotics are lipophilic, which explain their increased efficacy due to their ability to penetrate the lipid-rich acne lesion.[ 17 ] Among the topical anti-acne agents, a majority were sensitive to benzoyl peroxide (48%). BP is known to have bactericidal activity against C. acnes[ 18 ], however in our study the antimicrobial activity was found to be lower in comparison. BP has no reported resistance to date; hence the reduced sensitivity may be a matter of concern.[ 19 ]The antimicrobial activity of azelaic acid has been attributed to maintenance of an optimum pH and higher concentrations in vitro to exert its maximum bactericidal activity.[ 18 ] Since we did not mimic these conditions, it may explain the reduced efficacy against C. acnes in vitro. In our study azelaic acid showed high resistance to C.acnes (87%). Whether this resistance translates to in vivo usage, or azelaic acid has indeed developed resistance to C. acnes, need to be further elucidated in future studies. Retinoids although used extensively in acne for their keratolytic and comedolytic effects,[ 18 ] have no activity against inhibition of C. acnes as evidenced by their resistance rates, adapalene (95%) and tretinoin (63.3%). The only topical antibiotic studied was clindamycin, and akin to its oral counterpart, showed high resistance rates (60.8%). Topical monotherapy of clindamycin[ 19 ], along with over-the-counter prescribing practices in our region and widespread usage in acne are the possible causes. Antibiotic resistance to C. acnes has been reported worldwide, however resistance rates vary according to the geographical area, the prevalent antibiotic prescribing patterns, methods of isolation of C. acnes and cross-resistance. The heterogeneity in the available data from various studies, makes interpretation and comparison of resistance patterns challenging.[ 8 ] Even within the same country and during the same chronological period of the study, differences in resistance patterns have shown great variation, especially in large countries like China and India. [ 10 , 11 ] The present study was not without limitations. Current practices involve usage of genotypic analysis by Polymerase chain reaction, study of the phylotype 1 of C.acnes which is associated with acne which we could not incorporate due to financial constraints. Our study was performed in a tertiary care teaching hospital where the laboratory facilities are limited. Other AMR evaluation methods such as E-strip, EUCLAST (European Committee on Antimicrobial Susceptibility Testing) to determine the minimum inhibitory concentration (MIC) are not standardized, many drugs used against acne are not included, the cut-off values very in different countries making comparison to other studies difficult to interpret. The p values vary because differences in prescribing patterns in different countries lead to different resistance patterns and MIC values. Country or region-specific MIC values to C.acnes would make comparison more standardized. Thus, standardized determination of AMR is difficult to achieve. Conclusion AMR in acne continues to be a threat. Resistance to MLS antibiotics is high, similar to previous studies. Minocycline and doxycycline continue to be the most sensitive antibiotics against C. acnes. Topical BP, although effective, does not show very high efficacy against C. acnes. Unlike previous reports, our study shows limited antimicrobial action of azelaic acid in acne. Resistance to topical clindamycin persists. Although few drugs show efficacy against C.acnes, their irrational usage may induce resistance in the near future. Topical monotherapy should be avoided and combination therapies, preferably a retinoid with BP or clindamycin may be used. The need of the hour is to explore newer therapies against acne, including non-antibiotics, salicylic acid, phage therapy, levulinic acid, myrtacin (anti-biofilm), low dose antibiotics or narrow spectrum antibiotics like sarecycline in cases where antibiotics are absolutely indicated. The gradual phasing out of injudicious antibiotic usage acne therapy should be incorporated in newer therapeutic guidelines. Ultimately, addressing AMR requires targeted efforts to enhance practitioner awareness about its profound consequences; without this, even the most robust scientific research will fall short of effectively combating this growing threat. Declarations Author Contribution Rochelle Monteiro: study design, wrote the main manuscript, performed the studyBeena Anthony: performed the antimicrobial testing and interpretation of resultsRamesh Bhat: concept, study design and review of the article Acknowledgements: The EWHC program faculty by Harvard Medical School for reviewing the article. Indian Association of Dermatologists, Venereologists & Leprologists (IADVL) Research Grant for funding the study References Zhu T, Zhu W, Wang Q et al (2019) Antibiotic susceptibility of Propionibacterium acnes isolated from patients with acne in a public hospital in Southwest China: prospective cross-sectional study. 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Int J Dermatol 52(4):418–425. 10.1111/j.1365-4632.2011.05371.x Epub 2013 Feb 22. PMID: 23432195 Alkhawaja E, Hammadi S, Abdelmalek M, Mahasneh N, Alkhawaja B, Abdelmalek SM (2020) Antibiotic resistant Cutibacterium acnes among acne patients in Jordan: a cross sectional study. BMC Dermatol 20(1):17. 10.1186/s12895-020-00108-9 PMID: 33203374; PMCID: PMC7673087 Moon SH, Roh HS, Kim YH, Kim JE, Ko JY, Ro YS (2012) Antibiotic resistance of microbial strains isolated from Korean acne patients. J Dermatol. ;39(10):833-7. 10.1111/j.1346-8138.2012.01626.x . Epub 2012 Jul 11. PMID: 22779738 Sardana K, Gupta T, Garg VK, Ghunawat S (2015) Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management. Expert Rev Anti Infect Ther 13(7):883–896 Epub 2015 May 29. PMID: 26025191 Roberts JA, Lipman J (2009) Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. ;37(3):840 – 51; quiz 859. 10.1097/CCM.0b013e3181961bff . PMID: 19237886 Matt Sagransky, Brad AY, Steven R (2009) Feldman Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris, Expert Opinion on Pharmacotherapy, 10:15, 2555-62. 10.1517/14656560903277228 . PMID: 19761357 Hoover WD, Davis SA, Fleischer AB, Feldman SR (2014) Topical antibiotic monotherapy prescribing practices in acne vulgaris. J Dermatolog Treat. ;25(2):97 – 9. 10.3109/09546634.2013.852297 . PMID: 24171409 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5892820","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":407651971,"identity":"45973aff-4a7e-4dce-9b06-19007154b706","order_by":0,"name":"Rochelle Monteiro","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYHACNgaGAgsGfuYDDMxgPjtzA5CUIKDFQIJBsi2BsRnMZ2YkUovBMVQtuIF5e/OzBx8MJOSMjzE/f1xQcS/a4DBj4+MKBos8XFpkzhwzN5xhIGFsdozNsHnGmeLcDYcZmw3PMEgU49IiIZHDJs1jIJG47X6DYTNvWwJIS5tkA4NEIi7ngbX8MZCo39zG/rGZ9x9YS/tPglqA3k8wYOMB2tIAsYURrxaeY2aSPQYShjOO8RTO5jmWkDsT6BfJBgM8Wtibn0n8qLCR529j3/CZpyYht+9488GPDRV1OLXgAgYkqh8Fo2AUjIJRgAIAWhtRaThGCZoAAAAASUVORK5CYII=","orcid":"","institution":"Father Muller Medical College Hospital","correspondingAuthor":true,"prefix":"","firstName":"Rochelle","middleName":"","lastName":"Monteiro","suffix":""},{"id":407651972,"identity":"623a235d-1b29-48d6-851e-bd92c22bdf63","order_by":1,"name":"beena Anthony","email":"","orcid":"","institution":"Father Muller Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"beena","middleName":"","lastName":"Anthony","suffix":""},{"id":407651973,"identity":"1961c942-4a12-4ea1-afa4-8872208071de","order_by":2,"name":"Ramesh Bhat","email":"","orcid":"","institution":"Father Muller Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ramesh","middleName":"","lastName":"Bhat","suffix":""}],"badges":[],"createdAt":"2025-01-24 06:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5892820/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5892820/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75312928,"identity":"c1f4b6a4-4332-4222-8415-049d024eeaf6","added_by":"auto","created_at":"2025-02-03 09:20:50","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":183110,"visible":true,"origin":"","legend":"\u003cp\u003ea. Growth of c acnes on brucella blood agar\u003c/p\u003e\n\u003cp\u003eb. Zones of inhibition seen to all antibiotics except in the center which shows resistance to clindamycin.\u003c/p\u003e\n\u003cp\u003ec. C acnes on Gram stain showing gram positive rods\u003c/p\u003e\n\u003cp\u003ed. Cutibacterium selective agar showing sensitive zones to topical clindamycin and benzoyl peroxide and resistance to adapalene and tretinoin\u003c/p\u003e","description":"","filename":"Slide1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5892820/v1/b49b3ff9ab458e31ba8a0be0.jpg"},{"id":75312930,"identity":"c793e685-25be-430c-8f2d-166d4b3a930b","added_by":"auto","created_at":"2025-02-03 09:20:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":270301,"visible":true,"origin":"","legend":"\u003cp\u003eAntibiotic (oral \u0026amp; topical)sensitivity \u0026amp; resistance patterns to C.acnes\u003c/p\u003e\n\u003cp\u003eR-resistant, S-sensitive\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5892820/v1/29d8b75c9c10c2059d10262b.jpg"},{"id":81157993,"identity":"035f2c9b-8ef1-4ff9-833e-a4e3075f35cc","added_by":"auto","created_at":"2025-04-23 01:01:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":822365,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5892820/v1/dd04f1de-b318-4ad3-9fbb-63d76e2d704b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibiogram in Cutibacterium Acnes: A Comprehensive Study of Oral and Topical Treatments for Acne in the Indian Population","fulltext":[{"header":"Background","content":"\u003cp\u003eAcne vulgaris is one of the most common skin disorders worldwide, affecting around 67\u0026ndash;95% of adolescents. Although acne is not an infective disorder, oral and topical antibiotics have remained the mainstay of therapy.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The pathogenesis of acne is multifactorial and involves abnormal follicular keratinization, excessive sebum production, inflammation, and the modification in the distribution of clusters of Cutibacterium acnes (C.acnes). Other important contributing factors are dysseborrhoea, and external triggers such as diet, cosmetics, and stress. Recent focus has been on the skin microbiome wherein changes in the distribution of strains or species, and/or pathogenic alteration of these species despite stable distribution, contribute towards the development of acne. In other words, disruption of the skin barrier with alteration of the skin microbiome results in the proliferation of C. acnes.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eC. acnes is a gram-positive rod, non-spore forming, preferential anaerobe, which is an exclusive bacterial inhabitant of facial sebaceous follicles and an important part of the microbiota of healthy human skin. It acts on multiple stages in acne by modulating keratinocyte differentiation, increasing local inflammation, inducing microcomedo formation, lipogenesis and sebum production.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] C.acnes has additional interactions with markers of innate immunity such as toll-like receptors, matrix metalloproteinase, protease activated receptors, antimicrobial peptides, and pro-inflammatory cytokines[\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Thus C acnes has multiple pathogenic mechanisms in acne.\u003c/p\u003e \u003cp\u003eDespite the non-infective nature of acne, topical and systemic antibiotics form the mainstay of antibiotic therapy in most countries. Antibiotics in acne are used mainly for their anti-inflammatory action. However, indiscriminate usage led to widespread antimicrobial resistance (AMR). Resistance rates increased gradually in the 1970\u0026rsquo;s and 80\u0026rsquo;s up to 25%, increasing to 50\u0026ndash;60% in the 1990\u0026rsquo;s and peaking at 75% in the 2000\u0026rsquo;s. Recent years have shown a gradual decrease in AMR rates probably owing to stringent antibiotic stewardship policies. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Resistance rates vary in different geographical areas, due to differences in prescribing patterns and inconsistent laboratory methods of ascertaining bacterial resistance. However worldwide resistance rates to erythromycin and clindamycin remain elevated. High resistance rates to azithromycin, clarithromycin have been observed in India, Japan and China. Most of the topically used antibiotics in acne have developed resistance over the years due to frequent usage and cross-resistance acquired from oral antibiotic usage.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] We conducted this study to determine the antibiotic sensitivity rates to commonly used oral antibiotics and topical antibiotics and anti-inflammatory agents in our geographic area. Antibiotics are used indiscriminately for acne and other infective conditions. Topical antibiotics are available over the counter in India, and this too has added to the burden of AMR. Thus, we aimed to determine the efficacy of the current prescribing regimens for acne and to ascertain if antibiotic stewardship policies introduced in recent years have been effective in curtailing the burden of AMR.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eA total of 124 patients diagnosed to have moderate to severe acne vulgaris, attending the Dermatology outpatient department for a period of 2 years, at a tertiary care hospital were included in this prospective study, after obtaining institutional ethics clearance. All ethical procedures were followed with respect to data collection and processing. The study was registered under the Clinical Trial Registry of India (REF/2016/03/010997). A sample size of 124 was included at 10% allowable error (e), 95% confidence interval based on the study by Biswal et al\u003csup\u003e9\u003c/sup\u003e where p\u0026thinsp;=\u0026thinsp;66% and the formula n\u0026thinsp;=\u0026thinsp;z\u003csub\u003eα\u003c/sub\u003e\u003csup\u003e2\u003c/sup\u003e (1-p)/e\u003csup\u003e2\u003c/sup\u003e.The study aimed at isolating C. acnes and evaluating the sensitivity and resistance patterns to commonly used oral antibiotics and topical anti-acne agents. The inclusion criteria were age above 12 years and patients with moderate to severe acne. The following patients were excluded, patients who had used oral or topical antibiotics in the past one month ,intake of oral isotretinoin in the past 2 months, any other facial lesions. The drug washout period was calculated based on the half-life of the oral and topical agents. Basic clinical data (age, gender) were noted at the time of enrolment. An informed consent or assent was obtained as applicable.\u003c/p\u003e \u003cp\u003eSpecimen collection\u003c/p\u003e \u003cp\u003eThe area of collection was cleaned with 70% ethyl alcohol and the specimen was obtained after unroofing the closed papule/pustule with a sterile blood lancet or expressed using a comedone extraction in case of open comedones. The material obtained was transported without delay, under anaerobic conditions to the microbiology laboratory. A tiny quantity of the specimen obtained was transferred onto a sterile slide for gram staining.\u003c/p\u003e \u003cp\u003eProcessing of the sample\u003c/p\u003e \u003cp\u003eThe remaining specimen was transferred to a sterile tube containing 0.5ml of phosphate buffer (pH7.4) and vortex mixed for 30 seconds to disperse the bacteria. For the isolation of Cutibacterium, the vortexed sample was inoculated onto sheep blood agar and Cutibacterium selective agar in 4 quadrants to obtain a semi-quantitation and then placed in a Beckton and Dickinson (BD) Gas Pak EZ sachet (anaerobe gas generating pouch system with indicator) and incubated at 37\u003csup\u003e0\u003c/sup\u003eC for 48 hours. After incubation, the characteristic large, white to yellow dry colonies were presumptively identified as Cutibacterium species using biochemical tests and confirmed with MALDI-TOF (Matrix-Assisted Laser Desorption Ionization- Time of flight) in doubtful cases.\u003c/p\u003e \u003cp\u003eDisc diffusion technique\u003c/p\u003e \u003cp\u003e The Cutibacterium colonies identified were subjected to antimicrobial susceptibility testing on Brucella blood agar in an anaerobic environment using BD Gas Pak EZ sachets by Kirby-Bauer disc diffusion techniques, according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The antimicrobial agents used for testing were as follows: Doxycycline (30\u0026micro;g/disc), Minocycline (30\u0026micro;g/disc), Tetracycline(30\u0026micro;g/disc), Erythromycin (15 \u0026micro;g/disc), Azithromycin (15\u0026micro;g/disc), Roxithromycin (30\u0026micro;g/disc), Ampicillin(10\u0026micro;g/disc) procured from HI-media Pvt Ltd Mumbai. For the topical agents, sterile Whatman No.1 filter paper discs saturated with the respective agents namely: Clindamycin (0.1%), Tretinoin (0.05%), Adapalene (0.1%), Benzoyl peroxide (2.5%), Azelaic acid (10%) were used to test the antimicrobial susceptibility. The zone of inhibition was measured and expressed in millimeters. The results were interpreted as resistant or sensitive according to the zone diameter interpretive chart.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe collected data was summarized by frequency and percentage. The Ch\u0026iacute;-square test was performed for goodness of fit to compare the frequency within the group. Comparison among different groups of antibiotics was not performed. The analysis was performed in SPSS 23 software. The level of significance was 5%.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOut of the 124 cases, most of the patients belonged to the age group 10\u0026ndash;20 years (53.2%), followed by 20\u0026ndash;30 years (45.2%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Females outnumbered males comprising 63.7% of the study group. Most of the patients had grade 3 acne (45.2%), followed by grade 2(28.2%). Bacterial growth was present in 80.6% of the total cases. Cutibacterium acnes was isolated from a majority of the cases (74.2%)(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea,c), staphylococcus epidermidis from 5.6%, and staphylococcus aureus from 0.8% of the cases. In 19.4% of patients there was no bacterial growth.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical \u0026amp; microbiological profile of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAGE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u0026ndash;20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbove 30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGENDER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGRADE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBACTERIAL GROWTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eISOLATE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo growth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC acnes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003estaphylococcus epidermidis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003estaphylococcus aureus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the oral antibiotics studied, the highest antibacterial activity against C. acnes was seen with minocycline (97%) and doxycycline (90.8%)(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). This was followed by ampicillin (72.4%), tetracycline (48%), clindamycin (32.7%),and azithromycin (31.6%). The lowest antimicrobial action against C. acnes was observed with Roxithromycin (17.3%) and Erythromycin (11.2%). As these values were measured as a zone of inhibition, statistical comparisons were not applicable. The highest antimicrobial resistance to C. acnes were noted to the macrolide antibiotics such as erythromycin (88.8%), roxithromycin (82.7%), azithromycin (68.4%) and clindamycin (67.3%).(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) Among the topical agents, the highest antimicrobial action against C. acnes was seen with benzoyl peroxide (48%).Benzoyl peroxide (BP) is an anti-inflammatory agent, with known antimicrobial action against C.acnes. The antibacterial activity noted with BP in our study was higher than a commonly used antibiotic i.e., clindamycin. Topical adapalene (95%), azelaic acid (87%), tretinoin (63.3%), and clindamycin (60.8%) had least efficacy in inhibiting C. acnes in vitro (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed). Topical clindamycin, the only antibacterial agent studied, showed low propensity in inhibiting C.acnes, thus both oral and topical clindamycin are less efficacious in acne.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, most patients were female, with the mean age being 21.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 years. Cutibacterium acnes was the most common bacterial isolate. Among oral antibiotics, minocycline showed the highest antimicrobial activity against C.acnes and erythromycin showed the highest resistance to C.acnes. Topical BP showed higher antimicrobial action against C. acnes in comparison to other topically tested agents and azelaic acid had the lowest antimicrobial activity against C.acnes. Most of these findings are in concordance with previous literature[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], except the sensitivity pattern of azelaic acid, which has been described as possessing significant antimicrobial action to C. acnes in earlier studies.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePrevious studies included patients with a similar age distribution \u003csup\u003e2,10\u0026ndash;15\u003c/sup\u003e, most patients being \u0026lt;\u0026thinsp;25 years of age.\u003csup\u003e1,10,14\u003c/sup\u003e Grade 2 acne was the commonest in previous studies, which contrasts with our study where grade 3 acne lesions were predominant (45%).\u003c/p\u003e \u003cp\u003eThe isolation rates of Cutibacterium from acne lesions were comparable in prior studies, varying from 66% compared to 74.2% in our study.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Cutibacterium acnes (74.2%) was the most common isolate in our study, with a minority of acne lesions harboring staphylococcus epidermidis (5.6%) and staphylococcus aureus (S.aureus) (0.80%).S.aureus had higher isolation rates in previous studies. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Female patients outnumbered males in a majority of previous studies, as observed in our study where 63.7% of recruited patients were female.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Studies by Biswal (37%), Schaffer (42%) showed a lower number of females. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOverall AMR rates between 2010\u0026ndash;2020 were highest in Hong-Kong (58.4%), Greece (42%), Colombia (37.5%), and lowest in Australia (9%). Resistance to the macrolide-lincosamide-streptogramin (MLS) antibiotics such as erythromycin, clindamycin, azithromycin, clarithromycin has showed worsening rates from 2010 onwards, especially in countries like China, India, Greece, and Egypt. Antibiotics with special local interest, used more frequently in a particular geographical area, have also shown to develop high resistance, e.g., azithromycin, clarithromycin in India, Mexico and China.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Our study was in concordance with most of these studies, showing high resistance rates to the macrolide antibiotics. Roxithromycin, although not frequently used for acne and not previously studied, showed high resistance rates to C. acnes. This may be explained by the phenomenon of cross-resistance described to the MLS antibiotics. A previous study in North India[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] showed comparable resistance rates, except to azithromycin (100% vs 68.4% in our study). Even though the study was in the same country, resistance rates have shown variation within the same countries in previous studies.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] This can explain the differing AMR rates between our study and the aforementioned study. The antibiotic prescribing practices vary greatly among different regions, also a highlighted awareness about the resistance to azithromycin in the last few years has led to reduction in the usage of this drug for acne in our region. This may explain the difference in resistance rates, along with other factors, such as sampling techniques, laboratory methods, and interpretation of growth. The most sensitive oral antibiotics were minocycline (97%), and doxycycline (90.8%) as reported by previous studies.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Thus, fortunately AMR has not yet been acquired by the newer tetracyclines, hence stringent guidelines should be continued to be enforced to sustain this.\u003c/p\u003e \u003cp\u003eAlthough ampicillin showed a high sensitivity rate (72%) in vitro, this does not translate into clinical efficacy. Ampicillin is a hydrophilic drug, hence its limited penetration into the sebum rich acne follicle reduces its clinical efficacy in acne. In contrast, the macrolide and tetracycline antibiotics are lipophilic, which explain their increased efficacy due to their ability to penetrate the lipid-rich acne lesion.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAmong the topical anti-acne agents, a majority were sensitive to benzoyl peroxide (48%). BP is known to have bactericidal activity against C. acnes[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], however in our study the antimicrobial activity was found to be lower in comparison. BP has no reported resistance to date; hence the reduced sensitivity may be a matter of concern.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]The antimicrobial activity of azelaic acid has been attributed to maintenance of an optimum pH and higher concentrations in vitro to exert its maximum bactericidal activity.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Since we did not mimic these conditions, it may explain the reduced efficacy against C. acnes in vitro. In our study azelaic acid showed high resistance to C.acnes (87%). Whether this resistance translates to in vivo usage, or azelaic acid has indeed developed resistance to C. acnes, need to be further elucidated in future studies. Retinoids although used extensively in acne for their keratolytic and comedolytic effects,[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] have no activity against inhibition of C. acnes as evidenced by their resistance rates, adapalene (95%) and tretinoin (63.3%). The only topical antibiotic studied was clindamycin, and akin to its oral counterpart, showed high resistance rates (60.8%). Topical monotherapy of clindamycin[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], along with over-the-counter prescribing practices in our region and widespread usage in acne are the possible causes.\u003c/p\u003e \u003cp\u003eAntibiotic resistance to C. acnes has been reported worldwide, however resistance rates vary according to the geographical area, the prevalent antibiotic prescribing patterns, methods of isolation of C. acnes and cross-resistance. The heterogeneity in the available data from various studies, makes interpretation and comparison of resistance patterns challenging.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Even within the same country and during the same chronological period of the study, differences in resistance patterns have shown great variation, especially in large countries like China and India. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe present study was not without limitations. Current practices involve usage of genotypic analysis by Polymerase chain reaction, study of the phylotype 1 of C.acnes which is associated with acne which we could not incorporate due to financial constraints. Our study was performed in a tertiary care teaching hospital where the laboratory facilities are limited. Other AMR evaluation methods such as E-strip, EUCLAST (European Committee on Antimicrobial Susceptibility Testing) to determine the minimum inhibitory concentration (MIC) are not standardized, many drugs used against acne are not included, the cut-off values very in different countries making comparison to other studies difficult to interpret. The p values vary because differences in prescribing patterns in different countries lead to different resistance patterns and MIC values. Country or region-specific MIC values to C.acnes would make comparison more standardized. Thus, standardized determination of AMR is difficult to achieve.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAMR in acne continues to be a threat. Resistance to MLS antibiotics is high, similar to previous studies. Minocycline and doxycycline continue to be the most sensitive antibiotics against C. acnes. Topical BP, although effective, does not show very high efficacy against C. acnes. Unlike previous reports, our study shows limited antimicrobial action of azelaic acid in acne. Resistance to topical clindamycin persists. Although few drugs show efficacy against C.acnes, their irrational usage may induce resistance in the near future. Topical monotherapy should be avoided and combination therapies, preferably a retinoid with BP or clindamycin may be used. The need of the hour is to explore newer therapies against acne, including non-antibiotics, salicylic acid, phage therapy, levulinic acid, myrtacin (anti-biofilm), low dose antibiotics or narrow spectrum antibiotics like sarecycline in cases where antibiotics are absolutely indicated. The gradual phasing out of injudicious antibiotic usage acne therapy should be incorporated in newer therapeutic guidelines. Ultimately, addressing AMR requires targeted efforts to enhance practitioner awareness about its profound consequences; without this, even the most robust scientific research will fall short of effectively combating this growing threat.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRochelle Monteiro: study design, wrote the main manuscript, performed the studyBeena Anthony: performed the antimicrobial testing and interpretation of resultsRamesh Bhat: concept, study design and review of the article\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u0026nbsp;\u003c/h2\u003e\n\u003cul\u003e\n \u003cli\u003eThe EWHC program faculty by Harvard Medical School for reviewing the article.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eIndian Association of Dermatologists, Venereologists \u0026amp; Leprologists (IADVL) Research Grant for funding the study\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhu T, Zhu W, Wang Q et al (2019) Antibiotic susceptibility of Propionibacterium acnes isolated from patients with acne in a public hospital in Southwest China: prospective cross-sectional study. 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PMID: 24171409\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5892820/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5892820/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eInjudicious antibiotic therapy in acne has resulted in significant dissemination of cross-resistant strains of Cutibacterium acnes (C. acnes). Resistance patterns vary in different studies, corresponding to the geographic location, and study methods. Prior studies have shown a high resistance to azithromycin, erythromycin and clindamycin and high sensitivity to macrolide antibiotics. There is a paucity of studies evaluating the efficacy of topical anti-acne agents.Our objective was to isolate C.acnes from acne lesions ,and to evaluate the antibiotic susceptibility of oral and topical antibiotics in acne. As antibiotic sensitivity patterns vary with time and prescribing practices, our study aimed to evaluate these patterns, as there is limited data available on Antimicrobial resistance(AMR) in India. Swabs from acne pustules from 124 patients, aged 12 years and above, were obtained and inoculated into selective media for C. acnes and blood agar for isolation of aerobic organisms, gram staining and species identification of Cutibacterium. The isolated bacteria were cultured and evaluated for antibiotic sensitivity using standard disc diffusion techniques. Statistical analysis was performed on SPSS23 software. In our study, the average age of the patients was 21.34\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 years, a majority (63.7%) were females. Cutibacterium was isolated in 74.19% of patients. Among oral antibiotics minocycline was the most sensitive to C. acnes (97%); the highest resistance to C. acnes was seen with erythromycin (84%). Topically, benzoyl peroxide had higher sensitivity (48%), and adapalene (95%) and azelaic acid (83%) showed the least antimicrobial activity against C. acnes.The results prove that sensitivity patterns to oral antibiotics remain similar to previous studies. Topical Clindamycin resistance is lower than previously reported resistance rates. Topical benzoyl peroxide showed lower antimicrobial activity in comparison to prior studies. AMR in acne continues to be a concern. Hence the need to maintain stringent guidelines for antibiotic usage in acne.\u003c/p\u003e","manuscriptTitle":"Antibiogram in Cutibacterium Acnes: A Comprehensive Study of Oral and Topical Treatments for Acne in the Indian Population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-03 09:12:46","doi":"10.21203/rs.3.rs-5892820/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"631ac8b0-c492-4172-8758-dabc7a231bd4","owner":[],"postedDate":"February 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-23T00:53:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-03 09:12:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5892820","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5892820","identity":"rs-5892820","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}