Antibacterial and antifungal activity of intraoral products containing phthalocyanine: in vitro study

Antibacterial and antifungal activity of intraoral products containing phthalocyanine: in vitro study | 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 Antibacterial and antifungal activity of intraoral products containing phthalocyanine: in vitro study Bernardo da Fonseca Orcina, Verônica Caroline Brito Reia, Caique Andrade Santos, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1097185/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 The present study aimed to evaluate the in vitro antiseptic efficacy of a mouthwash and a dental gel containing phthalocyanine derivatives (Pc) against bacteria and fungi frequently found in patients with ventilator-associated pneumonia. The experiment in this study was conducted following Good Laboratory Practices. The product was tested at concentrations of 0.015% (mouthwash) and 0.100% (dental gel). The contact time of the suspension test ( Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , Salmonella sp. , Candida albicans , and Aspergillus niger ) was 60 s (1 min). In this analysis, the Phtalox® Mouthwash and Dental Gel resulted in a 99.99% reduction against the tested microorganisms after 1 min of contact time in both products. The Pc-containing mouthwash and dental gel were effective against bacteria and fungi found in patients with ventilator-associated pneumonia. Dentistry mouthwash dentifrices pneumonia ventilator-associated in vitro techniques Introduction Ventilator-associated pneumonia (VAP) is defined as pneumonia that occurs at least 48 hours after endotracheal intubation or tracheostomy for mechanical recovery, including pneumonia occurring within 48 hours after extubation. This pneumonia usually occurs in patients admitted to the intensive care unit (ICU). The risk of VAP increases during mechanical ventilation and hospitalization, and can lead to death. VAP is responsible for most antibiotic prescriptions in the ICU ( 1 ). The most important mechanism in the development of VAP is the continuous microaspiration of microorganisms present in the oropharynx. The most frequent microorganisms found in oropharyngeal samples are Acinetobacter , Klebsiella , Enterobacter, Pseudomonas, Staphylococcus aureus, Candida albicans , and Escherichia coli . The last three are found most frequently in patients with VAP ( 2 , 3 ). The normal oropharyngeal flora is overwhelmed by gram-negative pathogens approximately one day after hospitalization. This causes an increase in dental plaque, which is suitable environment for the growth and accumulation of pathogens. The tracheal tube can also act as a conduit for pathogens from the oral cavity to the lungs. The treatment of VAP is mainly antibiotics. However, evidence suggests that its use has generated bacterial resistance and increased the development of resistant bacteria ( 4 , 5 ). The incidence of VAP is reduced by identifying the risk factors and enhancing prevention. Oral hygiene procedures such as combining toothbrushing and mouthwash, are efficient methods for preventing VAP ( 6 ). Chlorhexidine is a broad-spectrum antiseptic agent widely used in patients because of its ease, safety, and slow-release properties that maintain its antimicrobial activity for up to 12 hours. Studies have confirmed that chlorhexidine reduces the incidence of VAP, but there is no consensus on the best concentration, the frequency of use, or the optimal application technique in the oral cavity ( 2 ). Phthalocyanine derivatives (Pc) have been shown to be important antimicrobial agents ( 7 , 8 ). Pc are non-cytotoxic and have no known side effects ( 8 , 9 , 10 ). When incorporated into dental products, Pc have improved clinical symptoms and reduced the length of hospital stay ( 8 , 10 , 11 ). Thus, the present study aimed to evaluate the in vitro antiseptic efficacy of a Pc-containing mouthwash and dental gel against bacteria and fungi frequently found in patients with VAP. Material And Methods For microbiological tests on non-sterile products, aseptic techniques were used for sampling and testing. The test was conducted in a laminar flow hood, and the membrane filtration technique was employed. When a sample showed antimicrobial activity, it was conveniently removed or neutralized. The efficacy of the inactivating agent for the considered microorganisms, and the absence of toxicity were demonstrated. When surfactant substances were used during sample preparation, the absence of microorganism toxicity and compatibility with the inactivating agent were also evaluated by counting the total number of mesophilic microorganisms. With this test, it is possible to determine the total number of mesophilic bacteria and fungi in non-sterile products and raw materials to determine whether the product meets pharmacopeia microbiological requirements. When used for this purpose, the instructions must be followed strictly, including the number of samples and interpretation of the results. The test was not applied to products containing viable microorganisms as an active ingredient. The experiment in this study was conducted following Good Laboratory Practices. In the absence test, homogenization of the A dilution was performed and the volume corresponding to 1 g or 1 mL of the product was transferred to the enterobacteria enrichment broth mossel (Aeromonas and Pseudomonas can also grow in this medium, as well as other types of bacteria) and then incubated at 32.5°C ± 2.5°C for 24 - 48 h. The subculture was prepared on plates containing neutral bile glucose red-violet agar and incubated at 32.5°C ± 2.5°C for 18 - 24 h. The product passed the test if there was no growth of colonies. The dilution-neutralization method was used, in which the neutralizer corresponded to a mixture of Tween, saponin, L-histidine, sodium thiosulfate, and lecithin. The tested product was kept at concentrations of 0.015% (mouthwash) and 0.100% (dental gel) ready to use. The contact time of the suspension test (bacteria/fungus/yeast) was 60 s (1 min) and the interfering substance for cleaning was 1.5 g/1. The substance identification test was evaluated according to the concentration indicated in its use. A sample of the product, either ready to use or diluted with water, was added to a suspension of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella sp., Candida albicans, and Aspergillus niger prepared in a solution of interfering substances. The mixture was maintained at a specified contact temperature and time under mandatory conditions for "hand rub" products. At the end of the contact time, an aliquot was removed, and the bactericidal and/or bacteriostatic action of the portion was immediately neutralized by a validated method. The same procedure was adopted for the control, in which hard water was used. The viable bacteria/fungus/yeast in each sample were counted, and the reduction in the number of viable cells was calculated for relation control. For the substance test to be considered satisfactory, the conditions of the validated test of the "hand rub" products must reduce the number of viable cells to at least 10 × 5 (≥5 logs or ≥99.999%) at 20°C. Results Table 1 demonstrates the results of the positive control for the antiseptic efficacy of the Phtalox® Mouthwash and Dental Gel with a 99.99% reduction against the tested microorganisms after 1 min of contact time. Discussion In discussing VAP is necessary to understand that they are hospital-acquired pneumonia (HAP), and is the main cause of death from hospital infections in critically ill patients and the second most common cause of nosocomial infections (12). As an aggravating factor in the pandemic, it is known that about 33% of hospitalized patients with COVID-19 tend to require ICU care. In addition, up to 20% of these patients may require the use of invasive mechanical ventilation (13). This reaffirms the need for intraoral topical antiseptic measures for preventing infections of those under mechanical ventilation and to act against the imbalance of the intraoral biome (14,15,16). Some studies have demonstrated the application of topical products in patients on mechanical ventilation, such as chlorhexidine and povidone-iodine (17,18,19). Chlorhexidine is the gold standard. However, the reduction in the incidence of VAP and chlorhexidine use remains controversial. There is also insufficient evidence regarding its benefits in decreasing mortality, duration of mechanical ventilation, and reduction in the length of ICU stay (18,20). Moreover, chlorhexidine has side effects that affect patients who use it for long periods, such as dental pigmentation, changes in taste, irritation, dryness, and oral mucosal lesions, teratological effects, allergy, increased bacterial accumulation after its use, pH changes, and burning sensations in the oral mucosa and on the tongue (21,22,23,24,25,26). Due to concerns relating to the side effects of chlorhexidine, particularly reports of anaphylaxis, Japan does not allow its use in the oral mucosa of patients under mechanical ventilation (19). Regarding povidone-iodine, its effectiveness in preventing VAP remains unclear due to the low number of available studies (27). Moreover, povidone-iodine use has been associated with cytotoxicity to the oral mucosal membranes and tooth pigmentation (19). In clinical studies, 0.12% chlorhexidine antiseptic action against gram-negative bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli was not effective in intubated children (17). In contrast, povidone-iodine showed a reduction in microorganisms such as streptococci, MRSA, S. pneumoniae, P. aeruginosa, P. gingivalis, and C. albicans for up to three hours (19). As potential alternatives, a mouthwash and a toothpaste containing Pc were effective in destroying 99.99% of bacteria and fungi in vitro . There is already evidence supporting the use of Pc-containing mouthwash as a complementary therapy against COVID-19, for example, in reducing signs of the disease, reducing the length of hospital stay, as well as avoiding the need for ICU admission (8,10,11). All of these findings combined with no reports of adverse effects in clinical studies, according to the tolerability questionnaires applied support the use of Pc-containing products in patients with VAP (8,10,11). The promising in vitro results of dental gel and mouthwash containing Pc demonstrate the need for further in vivo studies to determine whether oral care using these products can prevent VAP (27). In this in vitro analysis, both Phtalox® Mouthwash and Phtalox® Dental Gel showed a 99.99% reduction of the tested microorganisms, demonstrating the potency of these antiseptic products. Although this study presents promising results, randomized clinical trials are needed to clarify the specific mechanism of action of these products against the microorganisms found in patients with VAP. Declarations ACKNOWLEDGMENTS This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Finance Code 001). DISCLOSURE Dr Vilhena reports personal fees from TRIALS Inc, during the conduct of the study; in addition, Dr Vilhena has a patent classified pending. Dr da Silva Santos reports grants from CNPq process nº. 309525/2018-7. The other authors claim there are no conflicts of interest. References Koulenti D, Zhang Y, Fragkou PC. Nosocomial pneumonia diagnosis revisited. Curr Opin Crit Care. 2020 Oct;26(5):442-449. doi: 10.1097/MCC.0000000000000756 . PMID: 32739969. Zand F, Zahed L, Mansouri P, Dehghanrad F, Bahrani M, Ghorbani M. The effects of oral rinse with 0.2% and 2% chlorhexidine on oropharyngeal colonization and ventilator associated pneumonia in adults' intensive care units. J Crit Care. 2017 Aug; 40:318-322. doi: 10.1016/j.jcrc.2017.02.029 . Epub 2017 Mar 1. PMID: 28320561. Weber DJ, Rutala WA, Sickbert-Bennett EE, Samsa GP, Brown V, Niederman MS. Microbiology of ventilator-associated pneumonia compared with that of hospital-acquired pneumonia. Infect Control Hosp Epidemiol. 2007 Jul; 28(7):825–31. doi: 10.1086/518460 . Epub 2007 May 17. PMID: 17564985. Ali Karimpour H, Hematpour B, Mohammadi S, Aminisaman J, Mirzaei M, Morteza Karimian S, et al. Effect of Nebulized Eucalyptus for Preventing Ventilator-associated Pneumonia in Patients Under Mechanical Ventilation: A Randomized Double Blind Clinical Trial. Altern Ther Health Med. 2020 Aug; 26(S2):126–130. PMID: 32088670. Xu E, Pérez-Torres D, Fragkou PC, Zahar JR, Koulenti D. Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management. Microorganisms. 2021 Mar 5; 9(3):534. doi: 10.3390/microorganisms9030534 . PMID: 33807623; PMCID: PMC8001201. Andrews T, Steen C. A review of oral preventative strategies to reduce ventilator-associated pneumonia. Nurs Crit Care. 2013 May;18(3):116–22. doi: 10.1111/nicc.12002 . Epub 2013 Jan 30. PMID: 23577946. Santos CA, Novaes PM, Farias, MF, Khouri, S, Vilhena FV, Teodoro GR. Antibiofilm Action of PHTALOX®-containing Oral Care Formulations. J Dent Res. 2020; 99 (SpecIss A). abstract number, 3326, 2020 IADR/AADR/CADR General Session (Washington, D. C., USA). Santos PSS, Orcina BF, Machado RRG, Vilhena FV, Alves LMC, Zangrando MSR, et al. Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19 [Preprint]. Research Square. 2021 Mar 16. DOI: 10.21203/rs.3.rs-330173/v1 Teodoro GR, Santos CA, Carvalho MA, Koga-Ito CY, Khouri S, Vilhena FV. PHTALOX® antimicrobial action and cytotoxicity: in vitro study. J Dent Res. 2020; 99 (SpecIss A). abstract number, 0839, 2020 IADR/AADR/CADR General Session (Washington, D. C., USA). da Fonseca Orcina B, Vilhena FV, Cardoso de Oliveira R, Marques da Costa Alves L, Araki K, Toma SH, et al. A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19: Case Series. Clin Cosmet Investig Dent. 2021 Feb 18; 13:47–50. doi: 10.2147/CCIDE.S295423 . PMID: 33628060; PMCID: PMC7899311. Orcina BF, Santos PSS. Oral manifestation COVID-19 and the rapid resolution of symptoms post-Phtalox treatment: a case series. Int. J. Odontostomat. 2021; 15(1):67–70. Wei HP, Yang K. Effects of different oral care scrubs on ventilator-associated pneumonia prevention for machinery ventilates patient: A protocol for systematic review, evidence mapping, and network meta-analysis. Medicine (Baltimore). 2019 Mar; 98(12):e14923. doi: 10.1097/MD.0000000000014923 . PMID: 30896651; PMCID: PMC6709265. Bastos GAN, Azambuja AZ, Polanczyk CA, Gräf DD, Zorzo IW, Maccari JG, et al. Clinical characteristics and predictors of mechanical ventilation in patients with COVID-19 hospitalized in Southern Brazil. Rev Bras Ter Intensiva. 2020 Oct-Dec; 32(4):487–492. doi: 10.5935/0103-507X.20200082 . PMID: 33263703; PMCID: PMC7853673. Kola A, Gastmeier P. Efficacy of oral chlorhexidine in preventing lower respiratory tract infections. Meta-analysis of randomized controlled trials. J Hosp Infect. 2007 Jul; 66(3):207-16. doi: 10.1016/j.jhin.2007.03.025 . Epub 2007 Jun 1. PMID: 17544168. Li J, Xie D, Li A, Yue J. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. J Hosp Infect. 2013 Aug; 84(4):283–93. doi: 10.1016/j.jhin.2013.04.012 . Epub 2013 Jul 8. PMID: 23846238. Zuckerman LM. Oral Chlorhexidine Use to Prevent Ventilator-Associated Pneumonia in Adults: Review of the Current Literature. Dimens Crit Care Nurs. 2016 Jan-Feb; 35(1):25-36. doi: 10.1097/DCC.0000000000000154 . PMID: 26627070. Kusahara DM, Peterlini MA, Pedreira ML. Oral care with 0.12% chlorhexidine for the prevention of ventilator-associated pneumonia in critically ill children: randomised, controlled and double blind trial. Int J Nurs Stud. 2012 Nov; 49(11):1354-63. doi: 10.1016/j.ijnurstu.2012.06.005 . Epub 2012 Jul 7. PMID: 22771160. Zhao T, Wu X, Zhang Q, Li C, Worthington HV, Hua F. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev. 2020 Dec 24; 12(12):CD008367. doi: 10.1002/14651858.CD008367.pub4 . PMID: 33368159; PMCID: PMC8111488. Tsuda S, Soutome S, Hayashida S, Funahara M, Yanamoto S, Umeda M. Topical povidone iodine inhibits bacterial growth in the oral cavity of patients on mechanical ventilation: a randomized controlled study. BMC Oral Health. 2020 Feb 24; 20(1):62. doi: 10.1186/s12903-020-1043-7 . PMID: 32093667; PMCID: PMC7041202. Martin-Loeches I, Rodriguez AH, Torres A. New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe. Curr Opin Crit Care. 2018 Oct; 24(5):347-352. doi: 10.1097/MCC.0000000000000535 . PMID: 30063491. Abedipour A, Abedsaeedi J, Salehi M, Ebrahimi E. Comparison of persica and Chlorhexidine mouthwashes in prevention of stomatitis in patients receiving chemotherapy. I.J.N.R. 2006; 1 (1): 41–46. Baldo BA, Pham NH, Zhao Z. Chemistry of drug allergenicity. Curr Opin Allergy Clin Immunol. 2001 Aug; 1(4):327-35. doi: 10.1097/01.all.0000011034.96839.aa . PMID: 11964708. Hirata K, Kurokawa A. Chlorhexidine gluconate ingestion resulting in fatal respiratory distress syndrome. Vet Hum Toxicol. 2002 Apr; 44(2):89-91. PMID: 11931511. Ostad SN, Gard PR. Cytotoxicity and teratogenicity of chlorhexidine diacetate released from hollow nylon fibres. J Pharm Pharmacol. 2000 Jul; 52(7):779-84. doi: 10.1211/0022357001774633 . PMID: 10933128. Hidalgo E, Dominguez C. Mechanisms underlying chlorhexidine-induced cytotoxicity. Toxicol In Vitro. 2001 Aug-Oct; 15(4-5):271-6. doi: 10.1016/s0887-2333(01)00020-0 . PMID: 11566548. James P, Worthington HV, Parnell C, Harding M, Lamont T, Cheung A, et al. Chlorhexidine mouthrinse as an adjunctive treatment for gingival health. Cochrane Database Syst Rev. 2017 Mar 31; 3(3):CD008676. doi: 10.1002/14651858.CD008676.pub2 . PMID: 28362061; PMCID: PMC6464488. Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011 Nov; 11(11):845–54. doi: 10.1016/S1473-3099(11)70127-X . Epub 2011 Jul 26. PMID: 21798809. Tables Table 1 - Antiseptic efficacy of Phtalox® mouthwash and Phtalox® dental gel Strains Positive control CFU/ml Mouthwash Phtalox® Positive control CFU/ml Dental Gel Phtalox® E. coli 6,0 x 10 8 1,9 x 10 3 8,3 x 10 8 2,0 x 10 2 P. aeruginosa 6,0 x 10 8 1,9 x 10 3 8,3 x 10 8 2,0 x 10 2 S. aureus 6,0 x 10 8 1,9 x 10 3 8,3 x 10 8 2,0 x 10 2 Salmonella sp 6,0 x 10 8 1,9 x 10 3 8,3 x 10 8 2,0 x 10 2 C. albicans 3,9 x 10 8 3,2 x 10 3 7,2 x 10 8 1,5 x 10 2 niger 3,9 x 10 8 3,2 x 10 3 7,2 x 10 8 1,5 x 10 2 CFU (colony-forming unit) 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. 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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-1097185","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":64700703,"identity":"d53fe852-c002-430a-b4da-e1bcbbb4e13c","order_by":0,"name":"Bernardo da Fonseca Orcina","email":"","orcid":"https://orcid.org/0000-0003-3367-483X","institution":"University of Sao Paulo, Bauru School of Dentistry, Bauru, SP, Brazil;","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bernardo","middleName":"da Fonseca","lastName":"Orcina","suffix":""},{"id":64701243,"identity":"bec2c294-2d15-426b-bbe5-0c2e33bc730c","order_by":1,"name":"Verônica Caroline Brito Reia","email":"","orcid":"https://orcid.org/0000-0003-1352-5474","institution":"University of Sao Paulo, Bauru School of Dentistry, Bauru, SP, Brazil;","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Verônica","middleName":"Caroline Brito","lastName":"Reia","suffix":""},{"id":64701244,"identity":"4becca36-089d-42d4-87b4-b957b9a76fee","order_by":2,"name":"Caique Andrade Santos","email":"","orcid":"https://orcid.org/0000-0001-5646-3424","institution":"University of Sao Paulo, Bauru School of Dentistry, Bauru, SP, Brazil;","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Caique","middleName":"Andrade","lastName":"Santos","suffix":""},{"id":64701245,"identity":"9a1ca9c0-323a-4c00-acbe-f0fd6e501c62","order_by":3,"name":"Milena Helen Peres","email":"","orcid":"https://orcid.org/0000-0003-2773-2749","institution":"Sacred Heart University, Bauru, SP, Brazil;","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Milena","middleName":"Helen","lastName":"Peres","suffix":""},{"id":64701246,"identity":"8145bd4a-aff3-45c9-9835-398f10cfc8b6","order_by":4,"name":"Fabiano Vieira Vilhena","email":"","orcid":"https://orcid.org/0000-0003-3840-3633","institution":"TRIALS – Oral Health \u0026 Technologies, Bauru, SP, Brazil.","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fabiano","middleName":"Vieira","lastName":"Vilhena","suffix":""},{"id":64701247,"identity":"b2a9228a-ec72-4350-bbab-8aabb499a3ff","order_by":5,"name":"Paulo Sérgio da Silva Santos","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYHACxgMgkp/5ABuEL0GEHrAWybYEUrUYHCNWizn7GYMDH/7U2RsfYz72gLGtLo9BuvcBXi2WPTkGB2e2HU7cdowt3YCx7XAxg8xxA7xaDA7kGBzmbTiQYHa/x0yCse1AYoNEGn6HGZx/Y3CYB+SwNh6QljoitNwA2sLDxsy4gQ2shZmwFssZzwrAfpkB8kvCucPFbDLH8Gsx50/e+AAUYvxtwBD7UFaXxy/dRsBhKLwEIGLDrwFdC0TXKBgFo2AUjAJUAAAQbUWNhK6LuAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-0674-3759","institution":"University of Sao Paulo, Bauru School of Dentistry, Bauru, SP, Brazil","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Paulo","middleName":"Sérgio da Silva","lastName":"Santos","suffix":""}],"badges":[],"createdAt":"2021-11-19 20:56:25","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-1097185/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1097185/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":15731750,"identity":"b3168a9e-785a-4c18-a338-80577414b990","added_by":"auto","created_at":"2021-11-19 22:34:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":188957,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1097185/v1/c98c9800-6a5a-4b2a-a460-e556d1a7ec1a.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAntibacterial and antifungal activity of intraoral products containing phthalocyanine: in vitro study\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVentilator-associated pneumonia (VAP) is defined as pneumonia that occurs at least 48 hours after endotracheal intubation or tracheostomy for mechanical recovery, including pneumonia occurring within 48 hours after extubation. This pneumonia usually occurs in patients admitted to the intensive care unit (ICU). The risk of VAP increases during mechanical ventilation and hospitalization, and can lead to death. VAP is responsible for most antibiotic prescriptions in the ICU (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe most important mechanism in the development of VAP is the continuous microaspiration of microorganisms present in the oropharynx. The most frequent microorganisms found in oropharyngeal samples are \u003cem\u003eAcinetobacter\u003c/em\u003e, \u003cem\u003eKlebsiella\u003c/em\u003e, \u003cem\u003eEnterobacter, Pseudomonas, Staphylococcus aureus, Candida albicans\u003c/em\u003e, and \u003cem\u003eEscherichia coli\u003c/em\u003e. The last three are found most frequently in patients with VAP (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The normal oropharyngeal flora is overwhelmed by gram-negative pathogens approximately one day after hospitalization. This causes an increase in dental plaque, which is suitable environment for the growth and accumulation of pathogens. The tracheal tube can also act as a conduit for pathogens from the oral cavity to the lungs. The treatment of VAP is mainly antibiotics. However, evidence suggests that its use has generated bacterial resistance and increased the development of resistant bacteria (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe incidence of VAP is reduced by identifying the risk factors and enhancing prevention. Oral hygiene procedures such as combining toothbrushing and mouthwash, are efficient methods for preventing VAP (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Chlorhexidine is a broad-spectrum antiseptic agent widely used in patients because of its ease, safety, and slow-release properties that maintain its antimicrobial activity for up to 12 hours. Studies have confirmed that chlorhexidine reduces the incidence of VAP, but there is no consensus on the best concentration, the frequency of use, or the optimal application technique in the oral cavity (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePhthalocyanine derivatives (Pc) have been shown to be important antimicrobial agents (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Pc are non-cytotoxic and have no known side effects (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). When incorporated into dental products, Pc have improved clinical symptoms and reduced the length of hospital stay (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThus, the present study aimed to evaluate the \u003cem\u003ein vitro\u003c/em\u003e antiseptic efficacy of a Pc-containing mouthwash and dental gel against bacteria and fungi frequently found in patients with VAP.\u003c/p\u003e"},{"header":"Material And Methods","content":"\u003cp\u003eFor microbiological tests on non-sterile products, aseptic techniques were used for sampling and testing. The test was conducted in a laminar flow hood, and the membrane filtration technique was employed. When a sample showed antimicrobial activity, it was conveniently removed or neutralized. The efficacy of the inactivating agent for the considered microorganisms, and the absence of toxicity were demonstrated. When surfactant substances were used during sample preparation, the absence of microorganism toxicity and compatibility with the inactivating agent were also evaluated by counting the total number of mesophilic microorganisms. With this test, it is possible to determine the total number of mesophilic bacteria and fungi in non-sterile products and raw materials to determine whether the product meets pharmacopeia microbiological requirements. When used for this purpose, the instructions must be followed strictly, including the number of samples and interpretation of the results. The test was not applied to products containing viable microorganisms as an active ingredient.\u003c/p\u003e \u003cp\u003eThe experiment in this study was conducted following Good Laboratory Practices. In the absence test, homogenization of the A dilution was performed and the volume corresponding to 1 g or 1 mL of the product was transferred to the enterobacteria enrichment broth mossel (Aeromonas and Pseudomonas can also grow in this medium, as well as other types of bacteria) and then incubated at 32.5\u0026deg;C \u0026plusmn; 2.5\u0026deg;C for 24 - 48 h. The subculture was prepared on plates containing neutral bile glucose red-violet agar and incubated at 32.5\u0026deg;C \u0026plusmn; 2.5\u0026deg;C for 18 - 24 h. The product passed the test if there was no growth of colonies.\u003c/p\u003e \u003cp\u003eThe dilution-neutralization method was used, in which the neutralizer corresponded to a mixture of Tween, saponin, L-histidine, sodium thiosulfate, and lecithin. The tested product was kept at concentrations of 0.015% (mouthwash) and 0.100% (dental gel) ready to use. The contact time of the suspension test (bacteria/fungus/yeast) was 60 s (1 min) and the interfering substance for cleaning was 1.5 g/1.\u003c/p\u003e \u003cp\u003eThe substance identification test was evaluated according to the concentration indicated in its use. A sample of the product, either ready to use or diluted with water, was added to a suspension of \u003cem\u003eEscherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella sp., Candida albicans, and Aspergillus niger\u003c/em\u003e prepared in a solution of interfering substances. The mixture was maintained at a specified contact temperature and time under mandatory conditions for \"hand rub\" products. At the end of the contact time, an aliquot was removed, and the bactericidal and/or bacteriostatic action of the portion was immediately neutralized by a validated method. The same procedure was adopted for the control, in which hard water was used. The viable bacteria/fungus/yeast in each sample were counted, and the reduction in the number of viable cells was calculated for relation control.\u003c/p\u003e \u003cp\u003eFor the substance test to be considered satisfactory, the conditions of the validated test of the \"hand rub\" products must reduce the number of viable cells to at least 10 \u0026times; 5 (\u0026ge;5 logs or \u0026ge;99.999%) at 20\u0026deg;C.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable 1 demonstrates the results of the positive control for the antiseptic efficacy of the Phtalox\u0026reg; Mouthwash and Dental Gel with a 99.99% reduction against the tested microorganisms after 1 min of contact time. \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn discussing VAP is necessary to understand that they are hospital-acquired pneumonia (HAP), and is the main cause of death from hospital infections in critically ill patients and the second most common cause of nosocomial infections (12). As an aggravating factor in the pandemic, it is known that about 33% of hospitalized patients with COVID-19 tend to require ICU care. In addition, up to 20% of these patients may require the use of invasive mechanical ventilation (13). This reaffirms the need for intraoral topical antiseptic measures for preventing infections of those under mechanical ventilation and to act against the imbalance of the intraoral biome (14,15,16).\u003c/p\u003e\n\u003cp\u003eSome studies have demonstrated the application of topical products in patients on mechanical ventilation, such as chlorhexidine and povidone-iodine (17,18,19). Chlorhexidine is the gold standard. However, the reduction in the incidence of VAP and chlorhexidine use remains controversial. There is also insufficient evidence regarding its benefits in decreasing mortality, duration of mechanical ventilation, and reduction in the length of ICU stay (18,20). Moreover, chlorhexidine has side effects that affect patients who use it for long periods, such as dental pigmentation, changes in taste, irritation, dryness, and oral mucosal lesions, teratological effects, allergy, increased bacterial accumulation after its use, pH changes, and burning sensations in the oral mucosa and on the tongue (21,22,23,24,25,26). Due to concerns relating to the side effects of chlorhexidine, particularly reports of anaphylaxis, Japan does not allow its use in the oral mucosa of patients under mechanical ventilation (19). Regarding povidone-iodine, its effectiveness in preventing VAP remains unclear due to the low number of available studies (27). Moreover, povidone-iodine use has been associated with cytotoxicity to the oral mucosal membranes and tooth pigmentation (19).\u003c/p\u003e\n\u003cp\u003eIn clinical studies, 0.12% chlorhexidine antiseptic action against gram-negative bacteria such as \u003cem\u003eAcinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp.\u003c/em\u003e and \u003cem\u003eEscherichia coli\u0026nbsp;\u003c/em\u003ewas not effective in intubated children (17). In contrast, povidone-iodine showed a reduction in microorganisms such as \u003cem\u003estreptococci, MRSA, S. pneumoniae, P. aeruginosa, P. gingivalis,\u0026nbsp;\u003c/em\u003eand\u003cem\u003e\u0026nbsp;C. albicans\u003c/em\u003e for up to three hours (19).\u003c/p\u003e\n\u003cp\u003eAs potential alternatives, a mouthwash and a toothpaste containing Pc were effective in destroying 99.99% of bacteria and fungi \u003cem\u003ein vitro\u003c/em\u003e. There is already evidence supporting the use of Pc-containing mouthwash as a complementary therapy against COVID-19, for example, in reducing signs of the disease, reducing the length of hospital stay, as well as avoiding the need for ICU admission (8,10,11). All of these findings combined\u0026nbsp;with no reports of adverse effects in clinical studies, according to the tolerability questionnaires applied support the use of Pc-containing products in patients with VAP (8,10,11).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;The promising \u003cem\u003ein vitro\u003c/em\u003e results of dental gel and mouthwash containing Pc demonstrate the need for further \u003cem\u003ein vivo\u003c/em\u003e studies to determine whether oral care using these products can prevent VAP (27).\u003c/p\u003e\n\u003cp\u003eIn this \u003cem\u003ein vitro\u003c/em\u003e analysis, both Phtalox\u0026reg; Mouthwash and Phtalox\u0026reg; Dental Gel showed a 99.99% reduction of the tested microorganisms, demonstrating the potency of these antiseptic products. Although this study presents promising results, randomized clinical trials are needed to clarify the specific mechanism of action of these products against the microorganisms found in patients with VAP.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eACKNOWLEDGMENTS\u003c/p\u003e\n\u003cp\u003eThis study was financed in part by the Coordena\u0026ccedil;\u0026atilde;o de Aperfei\u0026ccedil;oamento de Pessoal de N\u0026iacute;vel Superior (CAPES), Brazil (Finance Code 001).\u003c/p\u003e\n\u003cp id=\"isPasted\"\u003eDISCLOSURE\u003c/p\u003e\n\u003cp\u003eDr Vilhena reports personal fees from TRIALS Inc, during the conduct of the study; in addition, Dr Vilhena has a patent classified pending. Dr da Silva Santos reports grants from CNPq process n\u0026ordm;. 309525/2018-7. The other authors claim there are no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKoulenti D, Zhang Y, Fragkou PC. 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Cochrane Database Syst Rev. 2017 Mar 31; 3(3):CD008676. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/14651858.CD008676.pub2\u003c/span\u003e\u003c/span\u003e. PMID: 28362061; PMCID: PMC6464488.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLabeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011 Nov; 11(11):845\u0026ndash;54. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1473-3099(11)70127-X\u003c/span\u003e\u003c/span\u003e. Epub 2011 Jul 26. PMID: 21798809.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ch1 style='margin-top:12.0pt;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:150%;font-size:27px;font-family:\"Arial\",sans-serif;font-weight:normal;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eTable 1 - Antiseptic efficacy of Phtalox\u0026reg; mouthwash and Phtalox\u0026reg; dental gel\u003c/span\u003e\u003c/h1\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003eStrains\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003ePositive control CFU/ml\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003eMouthwash Phtalox\u0026reg;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003ePositive control CFU/ml\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003eDental Gel Phtalox\u0026reg;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eE. coli\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e6,0 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e1,9 x 10\u003csup\u003e3\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e8,3 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e2,0 x 10\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eP. aeruginosa\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e6,0 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e1,9 x 10\u003csup\u003e3\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e8,3 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e2,0 x 10\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n 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style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e1,9 x 10\u003csup\u003e3\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e8,3 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e2,0 x 10\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eSalmonella sp\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e6,0 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e1,9 x 10\u003csup\u003e3\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e8,3 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border: medium none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e2,0 x 10\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90.15pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cem\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003eC. albicans\u003c/span\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e3,9 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid none;border-width: 1pt medium;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family: \"Times New Roman\",serif;'\u003e3,2 x 10\u003csup\u003e3\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: rgb(127, 127, 127) currentcolor;border-style: solid 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127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 3.4pt;vertical-align: top;\"\u003e\n \u003cdiv style='margin:0in;line-height:115%;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\n \u003col start=\"1\" style=\"margin-bottom:0in;list-style-type: upper-alpha;\"\u003e\n \u003cli style='margin:0in;line-height:115%;font-size:15px;font-family:\"Arial\",sans-serif;'\u003e\u003cem\u003e\u003cspan style='line-height:150%;font-family:\"Times New Roman\",serif;font-size:16px;'\u003eniger\u003c/span\u003e\u003c/em\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/div\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 3.4pt;vertical-align: top;\"\u003e\n \u003cp 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medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 3.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e7,2 x 10\u003csup\u003e8\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90.2pt;border-color: currentcolor currentcolor rgb(127, 127, 127);border-style: none none solid;border-width: medium medium 1pt;border-image: none 100% / 1 / 0 stretch;padding: 0in 5.4pt;height: 3.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;line-height:150%;font-size:15px;font-family:\"Arial\",sans-serif;text-align:center;'\u003e\u003cspan style='font-size:16px;line-height:150%;font-family:\"Times New Roman\",serif;'\u003e1,5 x 10\u003csup\u003e2\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch1 style='margin-top:12.0pt;margin-right:0in;margin-bottom:3.0pt;margin-left:0in;line-height:150%;font-size:27px;font-family:\"Arial\",sans-serif;font-weight:normal;'\u003e\u003cspan style='font-size: 16px; line-height: 150%; font-family: \"Times New Roman\", serif; color: rgb(0, 0, 0);'\u003eCFU (colony-forming unit)\u003c/span\u003e\u003c/h1\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Bauru School of Dentistry - University of São Paulo","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":"mouthwash, dentifrices, pneumonia, ventilator-associated, in vitro techniques","lastPublishedDoi":"10.21203/rs.3.rs-1097185/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1097185/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe present study aimed to evaluate \u003cem\u003ethe in vitro\u003c/em\u003e antiseptic efficacy of a mouthwash and a dental gel containing phthalocyanine derivatives (Pc) against bacteria and fungi frequently found in patients with ventilator-associated pneumonia. The experiment in this study was conducted following Good Laboratory Practices. The product was tested at concentrations of 0.015% (mouthwash) and 0.100% (dental gel). The contact time of the suspension test (\u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eSalmonella sp.\u003c/em\u003e, \u003cem\u003eCandida albicans\u003c/em\u003e, and \u003cem\u003eAspergillus niger\u003c/em\u003e) was 60 s (1 min). In this analysis, the Phtalox® Mouthwash and Dental Gel resulted in a 99.99% reduction against the tested microorganisms after 1 min of contact time in both products. The Pc-containing mouthwash and dental gel were effective against bacteria and fungi found in patients with ventilator-associated pneumonia.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","manuscriptTitle":"Antibacterial and antifungal activity of intraoral products containing phthalocyanine: in vitro study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-11-19 22:34:05","doi":"10.21203/rs.3.rs-1097185/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":"38ad1762-a47f-45e1-9c0b-5076d432c06a","owner":[],"postedDate":"November 19th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":8637658,"name":"Dentistry"}],"tags":[],"updatedAt":"2021-11-19T22:34:05+00:00","versionOfRecord":[],"versionCreatedAt":"2021-11-19 22:34:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1097185","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1097185","identity":"rs-1097185","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}