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.

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.

Chemotherapy-associated paronychia treated with a dilute povidone-iodine/dimethylsulfoxide preparation.

BACKGROUND: Nail changes associated with chemotherapy in general, and particularly with taxane and epidermal growth factor receptor inhibitor-based regimens, are common presentations in our clinical population. Currently, there are no consensuses about therapies supported by clinical trials nor are there any US Food and Drug Administration-approved treatments for this indication. FINDINGS: A 42-year-old woman with stage 2A breast cancer presented to our clinic with chemotherapy-induced paronychia. Symptoms were severe enough that cessation of chemotherapy was being considered. The patient's chemotherapy regimen included doxorubicin, cyclophosphamide, and docetaxel. CONCLUSION: The topical povidone-iodine/dimethylsulfoxide system is very effective in alleviating the signs and symptoms of severe paronychia associated with chemotherapy. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility.

Onychomycosis treated with a dilute povidone-iodine/dimethyl sulfoxide preparation.

BACKGROUND: Povidone-iodine (PVP-I) 10% aqueous solution is a well-known, nontoxic, commonly used topical antiseptic with no reported incidence of fungal resistance. We have been using a low-dose formulation of 1% PVP-I (w/w) in a solution containing dimethyl sulfoxide (DMSO) in our clinical practice for a variety of indications. Presented here is our clinical experience with this novel formulation in a severe case of onychomycosis that was resistant to any other treatment. FINDINGS: A 49-year-old woman who had been suffering from severe onychomycosis for years presented after failing to find any remedy including over the counter (OTC), topical, and systemic oral prescribed therapies. CONCLUSION: The topical povidone-iodine/DMSO system was very effective in this case at alleviating the signs and symptoms of onychomycosis. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility.

Combination immunotherapy in the treatment of chronic bilateral panuveitis and uveitic glaucoma during acute dengue fever infection in the Caribbean.

BACKGROUND: Ocular manifestations of the dengue fever virus include bilateral panuveitis that can occur after the acute systemic infection has resolved. In most reported cases, the inflammation resolves with topical or systemic steroid therapy. We report a case of chronic, refractory bilateral panuveitis and uveitic glaucoma that began during the acute phase of the systemic infection and required treatment with oral steroids, multiple steroid-sparing agents, and surgical therapy for glaucoma. FINDINGS: A 22-year-old male with acute systemic dengue fever presented with bilateral pain and decreased vision. Clinical examination revealed bilateral panuveitis with elevated intraocular pressures. Management required oral steroids, mycophenolate mofetil, cyclosporine, and bilateral glaucoma valve implantation. CONCLUSION: This case highlights the fact that dengue-associated panuveitis can begin in the acute stage of systemic infection and persist long after convalescence with progression to chronic bilateral panuveitis and uveitic glaucoma. Dengue-associated chronic panuveitis with uveitic glaucoma may be effectively managed with a combination of steroid-sparing oral immunosuppression and glaucoma surgery. This is, to our knowledge, the first case of bilateral refractory dengue-associated panuveitis from the Caribbean treated with combination steroid-sparing oral immunosuppression and bilateral glaucoma valve implantation.

Topical iodophor preparations: chemistry, microbiology, and clinical utility.

Iodophor preparations are commonly used in all medical specialties for antisepsis of the skin prior to injections, invasive procedures, and surgery. Povidone-iodine has some very intriguing properties that make it extremely effective as a broad spectrum bacteriocidal agent with no known bacterial resistance, potentially lending itself to broader applications than its current uses. In this article the background, formulations, chemistry, and microbiology of iodine will be reviewed and recent clinical investigations of utility beyond skin antisepsis will be discussed.

Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology.

Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology.

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.

Clinical and antiviral efficacy of an ophthalmic formulation of dexamethasone povidone-iodine in a rabbit model of adenoviral keratoconjunctivitis.

PURPOSE: To determine the efficacy of a new formulation of topical dexamethasone 0.1%/povidone-iodine 0.4% (FST-100) in reducing clinical symptoms and infectious viral titers in a rabbit model of adenoviral keratoconjunctivitis. METHODS: Rabbit corneas were inoculated bilaterally with 2×10(6) plaque-forming-units (PFU) of adenovirus type 5 (Ad5) after corneal scarification. Animals were randomized 1:1:1:1 (five rabbits per group) to FST-100, 0.5% cidofovir, tobramycin/dexamethasone (Tobradex; Alcon Laboratories, Fort Worth, TX) ophthalmic suspension, and balanced salt solution (BSS; Alcon Laboratories). Treatment began 12 hours after viral inoculation and continued for 7 consecutive days. The eyes were clinically scored daily for scleral inflammation (injection), ocular neovascularization, eyelid inflammation (redness), friability of vasculature, inflammatory discharge (pus), and epiphora (excessive tearing). Eye swabs were collected daily before treatment for the duration of the study. Virus was eluted from the swabs and PFU determined by titration on human A549 cells, according to standard procedures. RESULTS: The FST-100 treatment resulted in significantly lower clinical scores (P<0.05) than did the other treatments. The 0.5% cidofovir exhibited the most ocular toxicity compared with FST-100, tobramycin/dexamethasone, and balanced salt solution treatments. FST-100 and 0.5% cidofovir significantly (P<0.05) reduced viral titers compared with tobramycin/dexamethasone or balanced salt solution. CONCLUSIONS: FST-100 was the most efficacious in minimizing the clinical symptoms of adenovirus infection in rabbit eyes. FST-100 and 0.5% cidofovir were both equally effective in reducing viral titers and decreasing the duration of viral shedding. By providing symptomatic relief in addition to reducing infectious virus titers, FST-100 should be a valuable addition to treatment of epidemic adenoviral keratoconjunctivitis.