An Open Label Randomized Controlled Trial of Ivermectin Plus Favipiravir-Based Standard of Care versus Favipiravir-Based Standard of Care for Treatment of Moderate COVID-19 in Thailand.

BACKGROUND: The role of ivermectin in the treatment of moderate coronavirus disease 2019 (COVID-19) is controversial. We performed an open label randomized controlled trial to evaluate the role of ivermectin plus favipiravir-based standard of care versus favipiravir-based standard of care for the treatment of moderate COVID-19 infection. MATERIALS AND METHODS: An open-label randomized control trial was performed at Thammasat Field Hospital and Thammasat University Hospital from October 1st, 2021 to May 31st, 2022. Patients with moderate COVID-19 infections were randomized to the intervention (ivermectin plus favipiravir-based standard of care) or control group (favipiravir-based standard of care alone). Patients were followed up to 21 days. The primary outcome was the improvement in World Health Organization (WHO) category ordinal scale by 2 points. Secondary outcomes included duration of illness, development of severe COVID-19, and adverse reactions. RESULTS: There were 157 patients in the intervention and 160 patients in the control group. Characteristics, underlying diseases, and risk factors for severe COVID-19 were comparable in both groups. Improvement in the WHO-category ordinal scale by 2 points was achieved in 98.7% of the intervention group and in 99.4% of the control group (relative risk [RR]: 0.487; 95% confidence interval [CI]: 0.044-5.430). The median illness duration was 5.0 days (range, 3 - 28 days) in intervention group versus 5.2 days (range, 3 - 28 days) in control group (P = 0.630). Severe COVID-19 that required intensive care occurred in 2 patients (1.3%) in the intervention group and 1 patient (0.6%) in the control group (RR: 2.052; 95% CI: 0.184 - 22.857). No significant difference in serious drug adverse events was seen. CONCLUSION: In this study ivermectin plus standard of care was not associated with improvement in the WHO-category ordinal scale, reduced illness duration, or development of severe COVID-19 in moderately ill COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: TCTR20220427005.

Real-life effectiveness of COVID-19 vaccine during the Omicron variant-dominant pandemic: how many booster doses do we need?

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of the severe acute respiratory syndrome coronavirus 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures to halt the pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 and presented for nasopharyngeal real-time polymerase chain reaction testing during the Omicron variant-dominant period in Thailand (1 January 2022-15 June 2022). All participants were prospectively followed up for COVID-19 development for 14 days after the enrolment. Vaccine effectiveness was estimated and adjusted for characteristics associated with COVID-19. Of the 7971 included individuals, there were 3104 cases and 4867 controls. The adjusted VE among persons receiving 2-dose, 3-dose, and 4-dose vaccine regimens for preventing infection and preventing moderate-to-critical diseases were 33%, 48%, 62% and 60%, 74%, 76%, respectively. The VE were generally higher among those receiving the last dose of vaccine within 90 days compared to those receiving the last dose more than 90 days prior to the enrolment. The highest VE were observed in individuals receiving the 4-dose regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 for both preventing infection (65%) and preventing moderate-to-critical diseases (82%). Our study demonstrated increased VE along with an increase in number of vaccine doses received. Current vaccination programmes should focus on reducing COVID-19 severity and mandate at least one booster dose. The heterologous boosters with viral vector and mRNA vaccines were highly effective and can be used in individuals who previously received the primary series of inactivated vaccine.

Ten ways to make the most of World Antimicrobial Awareness Week.

One fundamental strategy to address the public health threat of antimicrobial resistance (AMR) is improved awareness among the public, prescribers, and policy makers with the aim of engaging these groups to act. World Antimicrobial Awareness Week is an opportunity for concerted and consistent communication regarding practical strategies to prevent and mitigate AMR. We highlight 10 ways for antimicrobial stewards to make the most of World Antimicrobial Awareness Week.

Gaps and barriers in the implementation and functioning of antimicrobial stewardship programmes: results from an educational and behavioural mixed methods needs assessment in France, the United States, Mexico and India.

Background: Evidence shows limited adherence to antimicrobial stewardship (AMS) principles. Objectives: To identify educational gaps and systemic barriers obstructing adherence to AMS principles. Methods: A mixed-methods study combining a thematic analysis of qualitative interviews (January-February 2021) and inferential analysis of quantitative surveys (May-June 2021) was conducted. Participants from France, the USA, Mexico and India were purposively sampled from online panels of healthcare professionals to include infectious disease physicians, infection control specialists, clinical microbiologists, pharmacologists or pharmacists expected to apply AMS principles in their practice setting (e.g. clinic, academic-affiliated or community-based hospital). A gap analysis framework guided this study. Results: The final sample included 383 participants (n = 33 interviews; n = 350 surveys). Mixed-methods findings indicated suboptimal knowledge and skills amongst participants to facilitate personal and collective application of AMS principles. Survey data indicated a gap in ideal versus current knowledge of AMS protocols, especially amongst pharmacologists (Δ0.95/4.00, P < 0.001). Gaps in ideal versus current skill levels were also measured and were highest amongst infectious control specialists (Δ1.15/4.00, P < 0.001), for convincing hospital executives to allocate resources to AMS programmes. Already existing systemic barriers (e.g. insufficient dedicated time/funding/training) were perceived as being aggravated during the COVID-19 pandemic (72% of survey participants agreed). Reported gaps were highest in India and France. Conclusions: The educational needs of professionals and countries included in this study can inform future continuous professional development activities in AMS. Additional funding should be considered to address perceived systemic barriers. Local assessments are warranted to validate results and suitability of interventions.

The role of procalcitonin and Clinical Pulmonary for Infection Score (CPIS) score to reduce inappropriate antibiotics use among moderate to severe coronavirus disease 2019 (COVID-19) pneumonia: A quasi-experimental multicenter study.

In this quasi-experimental study, implementing a procalcitonin and Clinical Pulmonary Infection Score (CPIS) successfully reduced inappropriate antibiotic use among severely-to-critically ill COVID-19 patients, multidrug-resistant organisms, and invasive fungal infections during the intervention period in 2 medical centers. However, this strategy did not improve inappropriate antibiotic use among mildly-to-moderately ill COVID-19 patients.

Status of hospital infection prevention practices in Thailand in the era of COVID-19: Results from a national survey.

BACKGROUND: A 2014 study assessed infection prevention (IP) practices in Thai hospitals for catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP). This study compares current IP practices to results obtained in 2014. METHODS: Between February 1, 2021 and August 31, 2021, we resurveyed Thai hospitals regarding practices to prevent CAUTI, CLABSI, and VAP. We also assessed COVID-19 impact and healthcare worker burnout and coping strategies. We distributed 100 surveys to a convenience sample of infection preventionists. RESULTS: Response rate: 100%. One-third (31%) of hospitals reported excellent leadership support for infection control (ie, responses of "good" or "excellent" to one survey question). Some prevention practices increased between 2014 vs 2021 (CAUTI: catheter reminder/stop-order/nurse-initiated discontinuation [50.0% vs 70.0%, P < .001]; condom catheters [36.3% vs 51.0%, P = .01]; ultrasound bladder scanner [4.7% vs 12.0%, P = .03]; CLABSI: chlorhexidine gluconate insertion site antisepsis [73.6% vs 85.0%, P = .03]; maximum sterile barrier precautions [63.2% vs 80.0%, P = .003]; VAP: selective digestive tract decontamination [26.9% vs 40.0%, P = .02]). Antimicrobial catheter use decreased since 2014 (10.4% vs 3.0%, P < .001). Many other practices remain suboptimal. COVID-19 challenges: staff shortages (71%), financial hardships (67%). Only 46% of infection preventionists felt safe working during COVID-19. CONCLUSIONS: More national strategic support is needed for IP programs to prevent CAUTI, CLABSI, VAP and healthcare worker well-being in Thailand during the COVID-19 pandemic.

Strategies to limit invasive fungal infection in a coronavirus disease 2019 (COVID-19) intensive care unit: The role of infection prevention for renovation and construction in resource-limited settings.

Hospital construction and renovation activities are the main cause of healthcare-associated fungal outbreaks. Infection control risk assessments (ICRAs) for renovation and construction decrease the risk of healthcare-associated fungal outbreaks, but they are typically not performed in developing countries. We reviewed an outbreak investigation to limit the construction-related fungal infections in a COVID-19 ICU in a resource-limited setting.

Impact of an infectious diseases pharmacist-led intervention on antimicrobial stewardship program guideline adherence at a Thai medical center.

PURPOSE: To evaluate and compare antimicrobial stewardship program (ASP) guideline adherence (primary outcome) as well as length of stay, 30-day all-cause mortality, clinical cure, antimicrobial consumption, and incidence of multidrug-resistant (MDR) pathogens (secondary outcomes) between an infectious diseases (ID) pharmacist-led intervention group and a standard ASP group. METHODS: A quasi-experimental study was performed at Thammasat University Hospital between August 2019 and April 2020. Data including baseline characteristics and primary and secondary outcomes were collected from the electronic medical record by the ID pharmacist. RESULTS: The ASP guideline adherence in the ID pharmacist-led intervention group was significantly higher than in the standard ASP group (79% vs 56.6%; P < 0.001), especially with regard to appropriate indication (P < 0.001), dosage regimen (P = 0.005), and duration (P = 0.001). The acceptance rate of ID pharmacist recommendations was 81.8% (44/54). The most common key barriers to following recommendations were physician resistance (11/20; 55%) and high severity of disease in the patient (6/20; 30%). Compared to the standard ASP group, there was a trend toward clinical cure in the ID pharmacist-led intervention group (63.6% vs 56.1%; P = 0.127), while 30-day all-cause mortality (15.9% vs 1.5%; P = 0.344) and median length of stay (20 vs 18 days; P = 0.085) were similar in the 2 groups. Carbapenem (P = 0.042) and fosfomycin (P = 0.014) consumption declined in the ID pharmacist-led intervention group. A marginally significant decrease in the overall incidence of MDR pathogens was also observed in the ID pharmacist-led intervention group (coefficient, -5.93; P = 0.049). CONCLUSION: Our study demonstrates that an ID pharmacist-led intervention can improve ASP guideline adherence and may reduce carbapenem consumption.

The feasibility of procalcitonin and CPIS score to reduce inappropriate antibiotics use among severe-critically ill COVID-19 pneumonia patients: A pilot study.

Antibiotics have been extensively used in COVID-19 patients without a clear indication. We conducted a study to evaluate the feasibility of procalcitonin along with the "Clinical Pulmonary for Infection Score" (CPIS) as a strategy to reduce inappropriate antibiotic use. Using procalcitonin and CPIS score (PCT-CPIS) successfully reduced inappropriate antibiotics use among severe-critically ill COVID-19 pneumonia patients (45% vs 100%; P < .01). Compared to "non PCT-CPIS" group, "PCT-CPIS" group was associated with a reduction in the incidence of multidrug-resistant organisms and invasive fungal infections (18.3% vs 36.7%; P = .03), shorter antibiotic duration (2 days vs 7 days; P < .01) and length of hospital stay (10 days vs 16 days; P < .01).

Comparing real-life effectiveness of various COVID-19 vaccine regimens during the delta variant-dominant pandemic: a test-negative case-control study.

Data on real-life vaccine effectiveness (VE), against the delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 among various coronavirus disease 2019 (COVID-19) vaccine regimens are urgently needed to impede the COVID-19 pandemic. We conducted a test-negative case-control study to assess the VE of various vaccine regimens for preventing COVID-19 during the period when the delta variant was the dominant causative virus (≥ 95%) in Thailand (25 July 2021-23 Oct 2021). All individuals (age ≥18 years) at-risk for COVID-19, presented for nasopharyngeal real-time polymerase chain reaction (RT-PCR) testing, were prospectively enrolled and followed up for disease development. Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. Of 3353 included individuals, there were 1118 cases and 2235 controls. The adjusted VE among persons receiving two-dose CoronaVac plus one BNT162b2 booster was highest (98%; 95% confidence interval [CI] 87-100), followed by those receiving two-dose CoronaVac plus one ChAdOx1 nCoV-19 booster (86%; 95% CI 74-93), two-dose ChAdOx1 nCoV-19 (83%; 95% CI 70-90), one CoronaVac dose and one ChAdOx1 nCoV-19 dose (74%; 95% CI 43-88) and two-dose CoronaVac (60%; 95% CI 49-69). One dose of CoronaVac or ChAdOx1 nCoV-19 had a VE of less than 50%. Our study demonstrated the incremental VE with the increase in the number of vaccine doses received. The two-dose CoronaVac plus one BNT162b2 or ChAdOx1 nCoV-19 booster regimens was highly effective in preventing COVID-19 during the rise of delta variant.