Efficacy of Povidone-Iodine Nasal and Oral Antiseptic Preparations Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2).

INTRODUCTION: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the global pandemic of coronavirus disease 2019 (COVID-19). From the first reported cases in December 2019, the virus has spread to over 4 million people worldwide. Human-to-human transmission occurs mainly through the aerosolization of respiratory droplets. Transmission also occurs through contact with contaminated surfaces and other fomites. Improved antisepsis of human and nonhuman surfaces has been identified as a key feature of transmission reduction. There are no previous studies of povidone iodine (PVP-I) against SARS-CoV-2. This study evaluated nasal and oral antiseptic formulations of PVP-I for virucidal activity against SARS-CoV-2. This is the first report on the efficacy of PVP-I against the virus that causes COVID-19. METHODS: Povidone iodine nasal antiseptic formulations and PVP-I oral rinse antiseptic formulations from 1% to 5% concentrations as well as controls were studied for virucidal efficacy against the SARS-CoV-2. Test compounds were evaluated for ability to inactivate SARS-CoV-2 as measured in a virucidal assay. SARS-CoV-2 was exposed directly to the test compound for 60 seconds, compounds were then neutralized, and surviving virus was quantified. RESULTS: All concentrations of nasal antiseptics and oral rinse antiseptics evaluated completely inactivated the SARS-CoV-2. CONCLUSIONS: Nasal and oral PVP-I antiseptic solutions are effective at inactivating the SARS-CoV-2 at a variety of concentrations after 60-second exposure times. The formulations tested may help to reduce the transmission of SARS-CoV-2 if used for nasal decontamination, oral decontamination, or surface decontamination in known or suspected cases of COVID-19.

In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2.

Importance: Research is needed to demonstrate the efficacy of nasal povidone-iodine (PVP-I) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To evaluate the in vitro efficacy of PVP-I nasal antiseptic for the inactivation of SARS-CoV-2 at clinically significant contact times of 15 and 30 seconds. Interventions: The SARS-CoV-2, USA-WA1/2020 strain, virus stock was tested against nasal antiseptic solutions consisting of aqueous PVP-I as the sole active ingredient. Povidone-iodine was tested at diluted concentrations of 0.5%, 1.25%, and 2.5% and compared with controls. The test solutions and virus were incubated at mean (SD) room temperature of 22 (2) °C for time periods of 15 and 30 seconds. Design and Setting: This controlled in vitro laboratory research study used 3 different concentrations of study solution and ethanol, 70%, as a positive control on test media infected with SARS-CoV-2. Test media without virus were added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol, 70%, was tested in parallel as a positive control and water only as a negative control. Main Outcomes and Measures: The primary study outcome measurement was the log reduction value after 15 seconds and 30 seconds of given treatment. Surviving virus from each sample was quantified by standard end point dilution assay, and the log reduction value of each compound was compared with the negative (water) control. Results: Povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact as measured by log reduction value of greater than 3 log10 of the 50% cell culture infectious dose of the virus. The ethanol, 70%, positive control did not completely inactivate SARS-CoV-2 after 15 seconds of contact. The nasal antiseptics tested performed better than the standard positive control routinely used for in vitro assessment of anti-SARS-CoV-2 agents at a contact time of 15 seconds. No cytotoxic effects on cells were observed after contact with each of the nasal antiseptics tested. Conclusions and Relevance: Povidone-iodine nasal antiseptic solutions at concentrations as low as 0.5% rapidly inactivate SARS-CoV-2 at contact times as short as 15 seconds. Intranasal use of PVP-I has demonstrated safety at concentrations of 1.25% and below and may play an adjunctive role in mitigating viral transmission beyond personal protective equipment.

Comparison of In Vitro Inactivation of SARS CoV-2 with Hydrogen Peroxide and Povidone-Iodine Oral Antiseptic Rinses.

PURPOSE: To evaluate the in vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with hydrogen peroxide (H2 O2 ) and povidone-iodine (PVP-I) oral antiseptic rinses at clinically recommended concentrations and contact times. MATERIALS AND METHODS: SARS-CoV-2, USA-WA1/2020 strain virus stock was prepared prior to testing by growing in Vero 76 cells. The culture media for prepared virus stock was minimum essential medium (MEM) with 2% fetal bovine serum (FBS) and 50 µg/mL gentamicin. Test compounds consisting of PVP-I oral rinse solutions and H2 O2 aqueous solutions were mixed directly with the virus solution so that the final concentration was 50% of the test compound and 50% of the virus solution. Thus PVP-I was tested at concentrations of 0.5%, 1.25%, and 1.5%, and H2 O2 was tested at 3% and 1.5% concentrations to represent clinically recommended concentrations. Ethanol and water were evaluated in parallel as standard positive and negative controls. All samples were tested at contact periods of 15 seconds and 30 seconds. Surviving virus from each sample was then quantified by standard end-point dilution assay and the log reduction value of each compound compared to the negative control was calculated. RESULTS: After the 15-second and 30-second contact times, PVP-I oral antiseptic rinse at all 3 concentrations of 0.5%, 1.25%, and 1.5% completely inactivated SARS-CoV-2. The H2 O2 solutions at concentrations of 1.5% and 3.0% showed minimal viricidal activity after 15 seconds and 30 seconds of contact time. CONCLUSIONS: SARS-CoV-2 virus was completely inactivated by PVP-I oral antiseptic rinse in vitro, at the lowest concentration of 0.5 % and at the lowest contact time of 15 seconds. Hydrogen peroxide at the recommended oral rinse concentrations of 1.5% and 3.0% was minimally effective as a viricidal agent after contact times as long as 30 seconds. Therefore, preprocedural rinsing with diluted PVP-I in the range of 0.5% to 1.5% may be preferred over hydrogen peroxide during the COVID-19 pandemic.

Rapid In-Vitro Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Using Povidone-Iodine Oral Antiseptic Rinse.

PURPOSE: To investigate the optimal contact time and concentration for viricidal activity of oral preparation of povidone-iodine (PVP-I) against SARS-CoV-2 ('corona virus') to mitigate the risk and transmission of the virus in the dental practice. MATERIALS AND METHODS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) USA-WA1/2020 strain, virus stock was tested against oral antiseptic solutions consisting of aqueous povidone-iodine (PVP-I) as the sole active ingredient. The PVP-I was tested at diluted concentrations of 0.5%, 1%, and 1.5%. Test media without any virus was added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol (70%) was tested in parallel as a positive control, and water only as a negative control. The test solutions and virus were incubated at room temperature (22 ± 2 °C) for time periods of 15 and 30 seconds. The solution was then neutralized by a 1/10 dilution in minimum essential medium (MEM) 2% fetal bovine serum (FBS), 50 µg/mL gentamicin. Surviving virus from each sample was quantified by standard end-point dilution assay and the log reduction value (LRV) of each compound compared to the negative (water) control was calculated. RESULTS: PVP-I oral antiseptics at all tested concentrations of 0.5%, 1%, and 1.5%, completely inactivated SARS-CoV-2 within 15 seconds of contact. The 70% ethanol control group was unable to completely inactivate SARS-CoV-2 after 15 seconds of contact, but was able to inactivate the virus at 30 seconds of contact. CONCLUSIONS: PVP-I oral antiseptic preparations rapidly inactivated SARS-CoV-2 virus in vitro. The viricidal activity was present at the lowest concentration of 0.5 % PVP-I and at the lowest contact time of 15 seconds. This important finding can justify the use of preprocedural oral rinsing with PVP-I (for patients and health care providers) may be useful as an adjunct to personal protective equipment, for dental and surgical specialties during the COVID-19 pandemic.

Topical application of povidone-iodine/dimethylsulfoxide ophthalmic gel preparation in Dutch-Belted rabbits.

Purpose: To determine the ocular and systemic toxicity of a novel, topically applied ophthalmic gel preparation of povidone-iodine (PVP-I) and dimethylsulfoxide (DMSO) in Dutch-Belted rabbits. Materials and Methods: Rabbits were administered doses of the test material or control by ocular instillation four times/eye/day, 7 d/week, for a minimum of 14 consecutive days. Dosing consisted of instillation of 50 µl of the appropriate test material solution or control material (saline) into each eye of the rabbit. On the last dose of the day, 250 µl of the appropriate test material solution or control material was applied to the eyelids of each eye. Results: Treatment-related clinical signs observed during the study were limited to mild non-inflammatory changes to the eyelids and eyelashes. There was no associated pathology upon histological examination of ocular or systemic tissues. Body weights and body weight gains were unaffected by treatment. Evaluation of clinical pathology profiles (haematology, coagulation, and clinical chemistry) did not reveal any test article-related toxicity and there were no macroscopic or microscopic findings at the terminal sacrifice. Conclusions: The compositions studied in the present investigation were developed to enable repeat-dosed application to the ocular surface and periocular skin surfaces without ocular, skin or systemic toxicity. The PVP-I/DMSO compositions tested did not cause any toxicity to the ocular surface or the periocular skin. Systemic toxicity from the preparations under study was not observed in any histological or gross pathological examination.

Demodex Blepharitis Treated with a Novel Dilute Povidone-Iodine and DMSO System: A Case Report.

INTRODUCTION: Povidone-iodine aqueous solution is an antiseptic commonly used in ophthalmology for treatment of the ocular surface. Dimethylsulfoxide (DMSO) is a well-known skin penetration enhancer that is scarcely utilized in ophthalmic drug formulations. We describe here a low-dose formulation of 0.25% PVP-I in a gel containing DMSO for the treatment of Demodex blepharitis. CASE REPORT: A 95-year-old female presented with chronic blepharitis involving both the anterior and posterior eyelid margins. The anterior eyelid margins demonstrated pathognomonic features consistent with Demodex infection, and this diagnosis was confirmed with microscopy. Previous traditional therapies had been ineffective at controlling her signs and symptoms. CONCLUSION: The topical PVP-I/DMSO system was effective at treating the signs and symptoms of Demodex blepharitis. Further investigation of the novel agent is warranted.

Rosacea Blepharoconjunctivitis Treated with a Novel Preparation of Dilute Povidone Iodine and Dimethylsulfoxide: a Case Report and Review of the Literature.

INTRODUCTION: Povidone iodine (PVP-I) 10% aqueous solution is a commonly utilized anti-septic employed for sterilization of the ocular surface prior to interventional procedures. Dimethylsulfoxide (DMSO) is a well-known skin penetration agent scarcely utilized in ophthalmic drug formulations. We describe here a low-dose formulation of 1% PVP-I (w/w) in a gel containing DMSO for use in the setting of recalcitrant rosacea blepharoconjunctivitis. A review of the ocular uses of dimethylsulfoxide is also presented. CASE REPORT: A 78-year-old male presented with chronic, long-standing blepharitis involving both the anterior and posterior lid margins. Posterior lid and skin inflammatory changes were consistent with ocular rosacea. Previous oral and topical therapies had been largely ineffective at controlling his condition. CONCLUSION: The topical PVP-I/DMSO system was effective in abating the signs and symptoms of rosacea blepharoconjunctivitis. Further investigation of this novel agent is warranted.

A Novel Topical 2% Povidone-Iodine Solution for the Treatment of Common Warts: A Randomized, Double-Blind, Vehicle-Controlled Trial.

INTRODUCTION: Verruca vulgaris, also known as common warts, are benign skin growths caused by infection of the skin by human papillomavirus. Warts are common in both childhood and adulthood and are spread by direct contact or autoinoculation. Treatment options vary from locally destructive methods to immuno-modulatory therapy. Common warts are often resistant to treatment. Though many remedies exist, there is no consensus therapy backed by randomized-controlled clinical trials that are FDA approved for the treatment of verruca vulgaris. We describe here the results of a small, randomized, double-blind, vehicle-controlled Phase II clinical trial with a novel topical agent for the treatment of common warts. METHODS: Twenty-one patients aged 8 years and older were enrolled in this single-center, randomized, double-blind, vehicle-controlled Phase II clinical trial to assess the efficacy, safety and tolerability of twice-daily application of a novel 2% topical povidone-iodine solution in a dimethyl sulfoxide vehicle for 12 weeks duration. Patients were block randomized into two groups consisting of 14 patients in the active arm and 7 patients in the vehicle only arm. All patients were evaluated at baseline, week 4, 8 and 12 and the results compared for overall Global Aesthetic Improvement Scale (GAIS) improvement. RESULTS: There were a total of 21 patients included in the study. Sustained improvement in the GAIS scale was observed at the final week 12 exam visit in 77% of subjects in the treatment arm and 33% of patients in the control arm. There were no serious safety or tolerability issues reported. CONCLUSION: Twice-daily topical povidone-iodine solution in the novel vehicle employed for this study is an effective, safe and easy-to-use treatment for common warts. Further study of this agent in expanded Phase II and Phase III clinical trials is warranted. FUNDING: ALC Therapeutics LLC.

Agreement between Pentacam and IOL master in patients undergoing toric IOL implantation.

PURPOSE: To investigate inter-device agreement between the Pentacam (Optikgerate GmbH, Wetzlar, Germany) and IOLMaster (Carl Zeiss Meditec, Jena, Germany) in measuring corneal power, cylinder, and axis of astigmatism. METHODS: Retrospective case series reviewing the status of eyes after toric IOL implantation to evaluate inter-device agreement in measuring corneal power, cylinder, and axis of astigmatism. RESULTS: Forty-nine eyes from 41 patients were evaluated. Agreement for corneal power and cylinder were deemed good and moderate, with 95% limits of agreement of -1.02 to +1.13 and -1.37 to +1.09 diopters (D), respectively. Agreement for axis of astigmatism was only fair, with a mean absolute difference of 8.9 degrees (range: 0.3 to 37.7 degrees, standard deviation: 8.79 degrees). Thirty percent of eyes had a 10-degree or greater difference in axis measurements, and 13% of eyes had a 20-degree or greater difference in measurements. Analysis by multivariate logistic regression showed higher cylinder powers associated with discrepant corneal power measurements (odds ratio: 3.46, P = .02), and increasing age was associated with discrepant axis measurements (odds ratio: 1.09, P = .03). Overall, there was no significant difference in accuracy predicting postoperative spherical equivalent refraction. CONCLUSIONS: Pentacam and IOLMaster agree well for corneal power but less so for cylinder and axis of astigmatism and thus cannot be used interchangeably.

In vitro efficacy of a povidone-iodine 0.4% and dexamethasone 0.1% suspension against ocular pathogens.

PURPOSE: To assess the efficacy of a povidone-iodine 0.4%-dexamethasone 0.1% suspension against bacterial, fungal, and Acanthamoeba clinical isolates. SETTING: Bascom Palmer Eye Institute, McKnight Research Building, Miami, Florida, USA. DESIGN: Experimental study. METHODS: One hundred milliliters of 10(4) colony-forming units/mL of ocular isolates of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, Fusarium solani, and Acanthamoeba castellanii were inoculated into 100 µL of a povidone-iodine 0.4%-dexamethasone 0.1% suspension in a 96-well microtiter plate incubated at room temperature. Organism viability was assessed at 15, 30, and 60 seconds by removing 10 µL aliquots and streaking onto a 5.0% sheep blood agar plate (fungi and bacteria) and agar-agar (Acanthamoeba) using a 0.001 calibrated loop. The plates were then incubated at 35 °C and monitored for up to 7 days. Isolates were inoculated into 200 µL of trypticase soy broth as controls. The number of colonies was counted and compared with controls to determine the kill rate. RESULTS: A 99.9% kill was observed for MRSA, P aeruginosa, S marcescens, and C albicans after 15 seconds of exposure and for F solani after 60 seconds. Acanthamoeba castellanii cyst viability was not inhibited by exposure to the povidone-iodine and dexamethasone suspension. Organism growth was achieved on all control broth. CONCLUSIONS: Povidone-iodine 0.4%-dexamethasone 0.1% suspension killed all bacterial and candida isolates within 15 seconds of exposure. It killed Fusarium isolates at 60 seconds but was ineffective against Acanthamoeba cysts. FINANCIAL DISCLOSURE: Drs. Pelletier and Miller have no financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Brevundimonas vesicularis keratitis after laser in situ keratomileusis.

A 45-year-old woman developed a corneal infiltrate 14 months after laser in situ keratomileusis (LASIK) enhancement in the left eye. The LASIK flap was lifted, scraped, and irrigated with fortified vancomycin and ceftazidime. Scraped samples were cultured and grew Brevundimonas vesicularis. The patient remained on topical ceftazidime until improvement was noted and was then switched to topical levofloxacin. The keratitis resolved on antibiotic agents with strong gram-negative coverage and a steroid. To our knowledge, this is the first report of a B vesicularis ocular infection.