Characterization of consumption and costs of antimicrobials in intensive care units in a Brazilian tertiary hospital.

Background: The consumption of antimicrobials and the growing resistance of infectious agents to these drugs are not related only to health issues, but also to economic parameters. Objectives: The study objective was to evaluate the consumption of antimicrobials in General and Covid-19 Intensive Care Units (ICUs) and the impact on institutional costs in the largest institute of a tertiary public hospital. Methods: This is a quantitative and retrospective study, which analyzed consumption, through the Defined Daily Dose (DDD), and the annual direct cost of antimicrobials in Reais (R$) and Dollars (US$), from January to December 2021. Results: The total annual consumption (DDD/1000 patient-day) of antimicrobials in the ICUs was 14,368.85. ß-Lactams had the highest total annual value, with a DDD/1000 patient-day of 7062.98, being meropenem the antimicrobial that reached the highest consumption (3107.20), followed by vancomycin (2322.6). Total consumption was higher in Covid-19 ICUs than in General ICUs, and the annual direct cost of antimicrobials in ICUs was US$560,680.79. Conclusions: The study showed high consumption of broad-spectrum antimicrobials, highlighting the importance of structuring programs to manage the use of antimicrobials, both to reduce antimicrobial consumption and hospital costs, consolidating rational use even in pandemic scenarios.

Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications.

There are concerns with excessive antibiotic prescribing among patients admitted to hospital with COVID-19, increasing antimicrobial resistance (AMR). Most studies have been conducted in adults with limited data on neonates and children, including in Pakistan. A retrospective study was conducted among four referral/tertiary care hospitals, including the clinical manifestations, laboratory findings, the prevalence of bacterial co-infections or secondary bacterial infections and antibiotics prescribed among neonates and children hospitalized due to COVID-19. Among 1237 neonates and children, 511 were admitted to the COVID-19 wards and 433 were finally included in the study. The majority of admitted children were COVID-19-positive (85.9%) with severe COVID-19 (38.2%), and 37.4% were admitted to the ICU. The prevalence of bacterial co-infections or secondary bacterial infections was 3.7%; however, 85.5% were prescribed antibiotics during their hospital stay (average 1.70 ± 0.98 antibiotics per patient). Further, 54.3% were prescribed two antibiotics via the parenteral route (75.5%) for ≤5 days (57.5), with most being 'Watch' antibiotics (80.4%). Increased antibiotic prescribing was reported among patients requiring mechanical ventilation and high WBCs, CRP, D-dimer and ferritin levels (p < 0.001). Increased COVID-19 severity, length of stay and hospital setting were significantly associated with antibiotic prescribing (p < 0.001). Excessive antibiotic prescribing among hospitalized neonates and children, despite very low bacterial co-infections or secondary bacterial infections, requires urgent attention to reduce AMR.

Biologically Inspired: Fighting Germs Using HCIO Hydrogels with Smectites

Hypochlorous acid (HClO) is formed in the white blood cells of all mammals [1]. As part of a mechanism that developed several millions of years ago, it also helps the human body to protect against pathogens that enter it. This makes the weak acid a nature-based option for disinfection. Despite this, a disadvantage of water-thin solutions of hypochlorous acid is that they have significantly limited anti-microbial potential due to the reduced contact time. Hydrogels overcome this limitation and lead to improved and more sustainable use. Due to the high reactivity of hypochlorous acid, common additives such as polymer thickeners and natural clays are not suitable. Synthetic smectite clays -- of which the presented PURABYK-R 5500 is one example -- are very similar in structure to natural clays. However, due to their subsequent technical development, synthetic smectite clays exhibit better stability and are therefore very well suited to forming these hydrogels. They stabilize the hypochlorous acid in the required pH value range and are free from components that impair the activity of HClO. These unique additives are produced under controlled conditions from naturally occurring inorganic mineral sources. They offer the possibility of using structures from nature, paired with a very high purity and consistent quality. Their great potential is presented here using PURABYK-R 5500 as an example. [ FROM AUTHOR]

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Curbing antimicrobial resistance in post-COVID Africa: Challenges, actions and recommendations.

Background: Antimicrobial self-medication and use have significantly increased in the COVID-19 era-increasing antibiotic consumption and resulting in a high prevalence of antimicrobial resistance in Africa (AMR). We conducted a narrative review to investigate challenges associated with curbing AMR in a post-COVID-19 setting in Africa, suggesting practical measures applicable for policy-informed implementation. Method: A narrative review was performed to pinpoint AMR challenges and actions on the African continent. A comprehensive search was conducted in the scientific databases that include PubMed, PubMed Central and Google Scholar using predetermined search terms. Results: The emergence of the COVID-19 outbreak has added to the challenges of tackling AMR on the continent, which has jeopardized AMR interventions' hard-won gains. Identified challenges have been Health systems disruption, Irrational Antimicrobial Use, Weak Antimicrobials Regulatory Ecosystem, Inefficient Population Infection Prevention, and Control Practices, Inadequate access to Health Services and data challenge on AMR surveillance. Conclusion: The COVID-19 pandemic fueled AMR in Africa. There is a need for AMR control post-COVID, such as measures for ongoing antimicrobial stewardship and good infection control practices. Further, curbing AMR requires rigorous regulatory enforcement and efficient AMR Surveillance. There should be a body to raise AMR awareness among the population. Research, Innovation and Technology could play an essential role supported by capacity building and global partnership.

The efficacy and safety of electrolyzed water against Covid-19 as an alternative hand sanitizer.

Aim To investigate the efficacy of electrolyzed water against viruses and its safety to the skin. Methods Virus culture was carried out at level-3 Bio-Safety (BSL3) facilities. The test material was prepared at room temperature mixed with one part virus suspension and one organic load. As an antiseptic and disinfectant control, 0.7% formaldehyde was used. Cytotoxic effects of electrolyzed water were performed on Vero cells. In order to assess the safety of electrolyzed water, a skin sensitivity test was conducted for electrolyzed water exposure. Results Electrolyzed water has a higher value of reduction factor than antiseptic and disinfectant control, formaldehyde, and it was statistically different from control. Cytotoxicity test results on Vero cells showed that electrolyzed water demonstrated safety in Vero cell viability. As many as 58 participants who met the inclusion criteria took electrolyzed water sensitivity test to the skin. The sensitivity test showed that participants with reactions to electrolyzed water were all female, with a mean age of 32.6 years. The patch-test was positive in 3 of 4 participants who reacted to the product. Conclusion Electrolyzed water is effective as a new antiseptic and disinfectant against viruses and safe for human skin.

In vitro inactivation of SARS-CoV-2 using a povidone-iodine oral rinse.

BACKGROUND: Healthcare professionals, especially dentists and dental hygienists, are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through air-borne particles and splatter. This study assessed the in vitro virucidal activity of 0.5% (w/v) povidone-iodine (PVP-I) oral rinse against SARS-CoV-2 to demonstrate its utility as a professional oral rinse. METHODS: A 0.5% (w/v) PVP-I oral rinse formulation, placebo oral rinse, and positive (70% [v/v] ethanol and water) and negative (water) controls were assessed using the time-kill method. SARS-CoV-2 was propagated in Vero 76 host cells. Following neutralization validation, triplicate tests were performed for each test formulation and virucidal activity measured at 15, 30, and 60 s and 5 min. RESULTS: The 0.5% (w/v) PVP-I oral rinse demonstrated effective in vitro virucidal activity against SARS-CoV-2 as early as 15 s after exposure; viral titer was reduced to < 0.67 log10 50% cell culture infectious dose (CCID50)/0.1 mL (log10 reduction of > 4.0) at 30 s, whereas the placebo oral rinse reduced the SARS-CoV-2 viral titer to 4.67 and 4.5 log10 CCID50/0.1 mL at the 15- and 30-s time points, with a log10 reduction of 0.63 and 0.17, respectively. No toxicity or cytotoxic effects against Vero 76 host cells were observed with the 0.5% (w/v) PVP-I oral rinse; positive and negative controls performed as expected. CONCLUSIONS: In vitro virucidal activity of 0.5% (w/v) PVP-I oral rinse against SARS-CoV-2 was demonstrated. Rapid inactivation of SARS-CoV-2 was observed with 0.5% (w/v) formulation with a contact duration of 15 s. Clinical investigations are needed to assess the effectiveness of PVP-I oral rinse against SARS-CoV-2 in dental practice.

Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital.

Background: Microbial drug resistance is one of the biggest public health problems. Antibiotic consumption is an essential factor for the emergence and spread of multiresistant bacteria. Therefore, we aimed to analyze the antibiotics consumption in the Intensive Care Unit (ICU), identifying trends in the antibiotics use profile and microbiological isolates throughout the COVID-19 pandemic. Methods: We performed this retrospective observational study in intensive care units of a Brazilian tertiary hospital from January 2019 to December 2020. The primary outcome was antimicrobial consumption in the ICU, measured by defined daily doses (DDDs) per 100 bed-days. As a secondary outcome, bacterial infections (microbiological isolates) were calculated in the same fashion. Outcomes trends were analyzed using Joinpoint regression models, considering constant variance (homoscedasticity) and first-order autocorrelation assumptions. A monthly percent change (MPC) was estimated for each analyzed segment. Results: Seven thousand and nine hundred fifty-three patients had data available on prescribed and received medications and were included in the analyses. Overall, the use of antibiotics increased over time in the ICU. The reserve group (World Health Organization Classification) had an increasing trend (MPC = 7.24) from February to April 2020. The azithromycin consumption (J01FA) increased rapidly, with a MPC of 5.21 from January to April 2020. Polymyxin B showed a relevant increase from March to June 2020 (MPC = 6.93). The peak of the antibiotic consumption of Reserve group did not overlap with the peak of the pathogenic agents they are intended to treat. Conclusion: Overall antimicrobial consumption in ICU has increased in the context of the COVID-19 pandemic. The peaks in the antimicrobial's use were not associated with the rise of the pathogenic agents they intended to treat, indicating an empirical use, which is especially concerning in the context of treating multidrug-resistant (MDR) infections. This fact may contribute to the depletion of the therapeutic arsenal for MDR treatment.

Behavioral Economics and Ambulatory Antibiotic Stewardship: A Narrative Review.

PURPOSE: Behavioral economics recognizes that contextual, psychological, social, and emotional factors powerfully influence decision-making. Behavioral economics has the potential to provide a better understanding of, and, through subtle environmental changes, or "nudges," improve persistent quality-of-care challenges, like ambulatory antibiotic overprescribing. Despite decades of admonitions and educational initiatives, in the United States, up to 50% of ambulatory antibiotic prescriptions remain inappropriate or not associated with a diagnosis. METHODS: We conducted a Medline search and performed a narrative review that examined the use of behavioral economics to understand the rationale for, and improvement of, ambulatory antibiotic prescribing. FINDINGS: Clinicians prescribe antibiotics inappropriately because of perceived patient demand, to maintain patient satisfaction, diagnostic uncertainty, or time pressure, among other reasons. Behavioral economics-informed approaches offer additional improvements in antibiotic prescribing beyond clinician education and communication training. Precommitment, in which clinicians publicize their intent to prescribe antibiotics "only when they are absolutely necessary," leverages clinicians' self-conception and a desire to act in a manner consistent with public statements. Precommitment was associated with a 20% absolute reduction in the inappropriate antibiotic prescribing for acute respiratory infections. Justification alerts, in which clinicians must provide a brief written rationale for prescribing antibiotics, leverages social accountability, redefines the status quo as an active choice, and helps clinicians to shift from fast to slow, careful thinking. With justification alerts, the absolute rate of inappropriate antibiotic prescribing decreased from 23% to 5%. Peer comparison, in which clinicians receive feedback comparing their performance to their top-performing peers, provides evidence of improved performance and leverages peoples' desire to conform to social norms. Peer comparison decreased absolute inappropriate antibiotic prescribing rates from 20% to 4%, a decrease that persisted for 12 months after the end of the intervention. Also, a one-time peer-comparison letter from a high-profile messenger to primary care practices with high rates of prescribing antibiotics, there was a 6-month, 3% decrease inantibiotic prescribing. Future directions in applying behavioral economics to the inappropriate antibiotic prescribing include paying careful attention to design details; improving intervention effectiveness and durability; making harms salient; participants' involvement in the development of interventions (the "Ikea effect"); factoring in patient satisfaction; and patient-facing nudges about antibiotic use and care-seeking. In addition, the COVID pandemic could aid in ambulatory antibiotic prescribing improvements due to changing cognitive frames around respiratory symptom evaluation and antibiotic prescribing. IMPLICATIONS: To improve ambulatory antibiotic prescribing, several behavioral economics-informed approaches-especially precommitment, justification alerts, and peer comparison-have reduced the rates of inappropriate prescribing of antibiotics to low levels.

In Vitro Evaluation of the Virucidal Activity of Different Povidone-Iodine Formulations Against Murine and Human Coronaviruses.

INTRODUCTION: Polyvinylpyrrolidone-iodine (PVP-I) demonstrates broad-spectrum anti-infective activity and is available in different formulations for oral rinse and topical use in medical and personal care settings. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the need to supplement available preventive strategies. METHODS: We assessed virucidal activity of PVP-I formulations, including 0.5% (w/v) solution, 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution, versus placebos when challenged with coronaviruses in two in vitro studies. Murine coronavirus strain A59 (American Type Culture Collection [ATCC]® VR-764™), human coronavirus strain OC43 (ZeptoMetrix Corp. #0810024CF), human coronavirus strain NL63 (ZeptoMetrix Corp. #0810228CF), and human coronavirus strain 229E (ATCC® VR-740™) were used as surrogates for SARS-CoV-2. Both studies used the American Society for Testing and Materials in vitro time-kill method. RESULTS: All active PVP-I formulations in study 1 demonstrated virucidal activity at 15 s, with mean log10 reduction of greater than 4.56 or greater than 99.99% inactivation; a cytotoxic effect against the National Collection of Type Cultures clone 1469 host cells was observed with 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution. Active PVP-I formulations in study 2 demonstrated effective virucidal activity against coronaviruses in less than 15 s; log10 reduction in viral titer for each coronavirus strain was consistently higher for 10.0% (w/v) solution and 0.5% (w/v) solution versus 7.5% (w/v) scrub. CONCLUSION: Both studies demonstrated in vitro virucidal activity of PVP-I formulations when challenged with SARS-CoV-2 surrogate coronaviruses. Although promising, further investigations are needed to evaluate SARS-CoV-2 inactivation.

Soap, water, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): an ancient handwashing strategy for preventing dissemination of a novel virus.

Public Health Agencies worldwide (World Health Organization, United States Centers for Disease Prevention & Control, Chinese Center for Disease Control and Prevention, European Centre for Disease Prevention and Control, etc.) are recommending hand washing with soap and water for preventing the dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In this review, we have discussed the mechanisms of decontamination by soap and water (involving both removal and inactivation), described the contribution of the various components of formulated soaps to performance as cleansers and to pathogen inactivation, explained why adherence to recommended contact times is critical, evaluated the possible contribution of water temperature to inactivation, discussed the advantages of antimicrobial soaps vs. basic soaps, discussed the differences between use of soap and water vs. alcohol-based hand sanitizers for hand decontamination, and evaluated the limitations and advantages of different methods of drying hands following washing. While the paper emphasizes data applicable to SARS-CoV-2, the topics discussed are germane to most emerging and re-emerging enveloped and non-enveloped viruses and many other pathogen types.

Impact of the COVID-19 Pandemic on Antimicrobial Consumption and Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections.

During the COVID-19 pandemic, the implementation of antimicrobial stewardship strategies has been recommended. This study aimed to assess the impact of the COVID-19 pandemic in a tertiary care Spanish hospital with an active ongoing antimicrobial stewardship programme (ASP). For a 20-week period, we weekly assessed antimicrobial consumption, incidence density, and crude death rate per 1000 occupied bed days of candidemia and multidrug-resistant (MDR) bacterial bloodstream infections (BSI). We conducted a segmented regression analysis of time series. Antimicrobial consumption increased +3.5% per week (p = 0.016) for six weeks after the national lockdown, followed by a sustained weekly reduction of -6.4% (p = 0.001). The global trend for the whole period was stable. The frequency of empirical treatment of patients with COVID-19 was 33.7%. No change in the global trend of incidence of hospital-acquired candidemia and MDR bacterial BSI was observed (+0.5% weekly; p = 0.816), nor differences in 14 and 30-day crude death rates (p = 0.653 and p = 0.732, respectively). Our work provides quantitative data about the pandemic effect on antimicrobial consumption and clinical outcomes in a centre with an active ongoing institutional and education-based ASP. However, assessing the long-term impact of the COVID-19 pandemic on antimicrobial resistance is required.

Tolerability and effectiveness of povidone-iodine or mupirocin versus saline sinus irrigations for chronic rhinosinusitis.

OBJECTIVES: The role of topical anti-infectives in acute exacerbations of chronic rhinosinusitis is controversial. Povidone-iodine is an anti-bacterial and anti-viral that is affordable and available over-the-counter and may demonstrate advantages over mupirocin as a sinus irrigation therapy. The objective was to compare povidone-iodine or mupirocin versus saline sinus irrigations for sinusitis exacerbations in post-surgery subjects as well as to assess tolerability of povidone-iodine sinus irrigations. MATERIALS AND METHODS: This was a prospective single-blinded (clinician only) randomized controlled trial. Subjects were post-surgery with acute exacerbations of chronic rhinosinusitis and gram-positive bacteria on culture. They received povidone-iodine, mupirocin, or saline sinus irrigations, twice daily for 30 days. Outcomes were post-treatment culture negativity (primary) and Sinonasal Outcome Test-20 and Lund-Kennedy endoscopic score change (secondary). RESULTS: Of the 62 subjects analyzed, post-treatment culture negativity rate was higher in the MUP (14/20, 70%) group compared to the PI (9/21, 43%) and SAL (9/19, 47%) groups, although this was not significant (p = 0.29). Povidone-iodine sinus irrigations at the 1% concentration were very well-tolerated, similar to saline irrigations. There were no significant differences in Sinonasal Outcome Test-20 score (povidone-iodine -0.3 [-0.6, 0.05] vs. mupirocin -0.3 [-0.7, 0.05] vs. saline -0.4 [-0.8, 0.05]; p = 0.86) or Lund-Kennedy endoscopic score (povidone-iodine -3.5 [-7, -0.5] vs. mupirocin -2 [-4, 2] vs. saline -3 [-5, 0]; p = 0.45) change. No serious adverse effects were reported. CONCLUSIONS: In patients who have had prior sinus surgery with acute exacerbations of CRS and gram-positive bacteria on culture, mupirocin sinus irrigations achieved a better post-treatment culture "control" rate compared to saline and povidone-iodine. In addition, 1% povidone-iodine solution was well-tolerated as a sinus irrigation and may represent a feasible method for temporarily disinfecting the sinonasal cavity of bacteria and viruses such as COVID-19.

Can Immunization of Hens Provide Oral-Based Therapeutics against COVID-19?

In the current worldwide pandemic situation caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the newest coronavirus disease (COVID-19), therapeutics and prophylactics are urgently needed for a large population. Some of the prophylaxis strategies are based on the development of antibodies targeting viral proteins. IgY antibodies are a type of immunoglobulin present in birds, amphibians, and reptiles. They are usually obtained from egg yolk of hyper-immunized hens and represent a relatively inexpensive source of antibodies. Specific IgY can be produced by immunizing chickens with the target antigen and then purifying from the egg yolk. Chicken IgY has been widely explored as a clinical anti-infective material for prophylaxis, preventive medicine, and therapy of infectious diseases. Administered non-systemically, IgY antibodies are safe and effective drugs. Moreover, passive immunization with avian antibodies could become an effective alternative therapy, as these can be obtained relatively simply, cost-efficiently, and produced on a large scale. Here, we highlight the potential use of polyclonal avian IgY antibodies as an oral prophylactic treatment for respiratory viral diseases, such as COVID-19, for which no vaccine is yet available.

Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease.

INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50)/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved ≥ 99.99% virucidal activity against SARS-CoV-2, corresponding to ≥ 4 log10 reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings.