Molnupiravir versus favipiravir in at-risk outpatients with COVID-19: A randomized controlled trial in Thailand.

OBJECTIVES: Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. METHODS: In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. RESULTS: Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (-1.0%; Newcombe 95.2% CI: -2.4% to -0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). CONCLUSIONS: Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. THAI CLINICAL TRIALS REGISTRY ID: TCTR20230111009.

Genomic characterization of extended-spectrum ß-lactamase-producing Enterobacterales isolated from abdominal surgical patients.

Rectal swabs of 104 patients who underwent abdominal surgery were screened for ESBL producers. Sequence types (STs) and resistance genes were identified by whole-genome sequencing of 46 isolates from 17 patients. All but seven isolates were assigned to recognized STs. While 18 ESBL-producing E. coli (EPEC) strains were of unique STs, ESBL-producing K. pneumoniae (EPKP) strains were mainly ST14 or ST15. Eight patients harboured strains of the same ST before and after abdominal surgery. The most prevalent resistant genes in E. coli were blaEC (69.57%), blaCTX-M (65.22%), and blaTEM (36.95%), while blaSHV was present in only K. pneumoniae (41.30%). Overall, genes encoding ß-lactamases of classes A (blaCTX-M, blaTEM, blaZ), C (blaSHV, blaMIR, and blaDHA), and D (blaOXA) were identified, the most prevalent variants being blaCTX-M-15, blaTEM-1B, blaSHV-28, and blaOXA-1. Interestingly, blaCMY-2, the most common pAmpC ß-lactamase genes reported worldwide, and mobile colistin resistance genes, mcr-10-1, were also identified. The presence of blaCMY-2 and mcr-10-1 is concerning as they may constitute a potentially high risk of pan-resistant post-surgical infections. It is imperative that healthcare professionals monitor intra-abdominal surgical site infections rigorously to prevent transmission of faecal ESBL carriage in high-risk patients.

The influence of spirituality, religiosity, and self-care on well-being among Thai infection preventionists during the COVID-19 pandemic.

In a national survey of lead infection preventionists in Thai hospitals, spiritual and religious importance were associated with increased odds of career satisfaction. Cultivating environments for spiritual, religious, and self-care practices within the clinical setting may help facilitate emotional well-being-and prevent burnout-among Thai healthcare workers.

Challenges and success stories of the implementation of infection control and antimicrobial stewardship strategies: proceedings of the 5th Global Ministerial Summit on Patient Safety, 2023.

The 5th edition of the Global Ministerial Summit on Patient Safety was held in Montreux, Switzerland, in February 2023, delayed by three years due to the COVID-19 pandemic. The overarching theme of the summit was "Less Harm, Better Care - from Resolution to Implementation", focusing on the challenges of implementation of infection prevention and control (IPC) strategies as well as antimicrobial stewardship programs (ASP) around the world. IPC strategies and ASP are of increasing importance due to the substantial burden of healthcare-associated infections and antimicrobial resistance threatening patient safety. Here, we summarize countries' and regional experiences and activities related to the implementation of IPC strategies and ASP shared at the meeting. Full implementation of effective programs remains a major challenge in all settings due to limited support by political and healthcare leaders, and human and financial constraints. In addition, the COVID-19 pandemic challenged already well-established programs. By enforcing sustained implementation by dedicated, cross-disciplinary healthcare personnel with a broad skill set, a reduction in healthcare-associated infections and multidrug-resistant pathogens can be achieved, leading ultimately to improved patient safety.

Perceptions of organizational culture among infection preventionists in Israel, the United States, and Thailand: Results from national infection prevention surveys.

In national surveys of infection preventionists in Israel (n = 15), the United States (n = 415), and Thailand (n = 100), we found that views of organizational culture track well with these countries' cultural dimension scores of power distance and individualism. Our findings highlight the importance of considering cultural dimensions when implementing infection prevention efforts.

The current state of antimicrobial and urine culture stewardship in Thailand: Results from a national survey.

BACKGROUND: Antimicrobial stewardship in Thailand has made major progress backed by a national strategic plan. The current study aimed to assess the antimicrobial stewardship program (ASP) composition, reach, and breadth, as well as urine culture stewardship in Thai hospitals. METHODS: We sent an electronic survey to 100 Thai hospitals between February 1, 2021 and August 31, 2021. This hospital sample represented 20 hospitals in each of Thailand's 5 geographical regions. RESULTS: The response rate was 100%. A total of 86 of 100 hospitals had an ASP. These were often multi-disciplinary in nature, with half including infectious disease-trained physicians and pharmacists, infection preventionists, and nursing staff. Urine culture stewardship protocols existed in 51% of hospitals. CONCLUSIONS: The national strategic plan in Thailand has allowed the country to stand up robust ASPs. Further research should examine the effectiveness of such programs and ways to expand them into other medical settings, like nursing homes, urgent care, and outpatient while continuing to grow telehealth and urine culture stewardship.

The impact of environmental cleaning protocol featuring PX-UV in reducing the incidence of multidrug-resistant gram-negative healthcare-associated infection and colonization in intensive care units in Thailand.

In this quasi-experimental study, implementing PX-UV to the standard environmental cleaning protocol was associated with a reduction in the overall incidence of multidrug-resistant (MDR) gram-negative organisms (P = .01) and MDR Acinetobacter baumannii (P = .001) in intervention intensive care units. However, the intervention did not reduce patient length of stay and 30-day mortality.

Clinical utility of procalcitonin in implementation of procalcitonin-guided antibiotic stewardship in the South-East Asia and India: evidence and consensus-based recommendations.

INTRODUCTION: The South-East Asian (SEA) region and India are highly susceptible to antibiotic resistance, which is caused due to lack of antimicrobial stewardship (AMS) knowledge, uncontrolled use of antibiotics, and poor infection control. Nonadherence to national/local guidelines, developed to combat antimicrobial resistance, is a major concern. A virtual advisory board was conducted to understand the current AMS standards and challenges in its implementation in these regions. AREAS COVERED: Procalcitonin (PCT)-guided antibiotic use was discussed in various clinical conditions across initiation, management, and discontinuation stages. Most experts strongly recommended using PCT-driven antibiotic therapy among patients with lower respiratory tract infections, sepsis, and COVID-19. However, additional research is required to understand the optimal use of PCT in patients with organ transplantation and cancer patients with febrile neutropenia. Implementation of the solutions discussed in this review can help improve PCT utilization in guiding AMS in these regions and reducing challenges. EXPERT OPINION: Experts strongly support the inclusion of PCT in AMS. They believe that PCT in combination with other clinical data to guide antibiotic therapy may result in more personalized and precise targeted antibiotic treatment. The future of PCT in antibiotic treatment is promising and may result in effective utilization of this biomarker.

Impact of COVID-19 pandemic on carbapenem-resistant Enterobacterales incidence in the South-East Asia region: an observational study.

The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.

Impact of the COVID-19 pandemic on the Thai population: Delineating the effects of the pandemic and policy measures.

Objectives: This study aimed to determine the impacts of the COVID-19 pandemic and policy measures and delineate the impact of each on a cohort of Thai citizens. Methods: A cross-sectional study was conducted among 2,500 Thai people from October 2020 to January 2021. A questionnaire collecting demographic information and other data was sent to eligible subjects. Results: Overall, 51.6% and 49.5% of participants felt the impacts of COVID-19 and policy measures at the highest level, respectively. The study demonstrated that the weighted effect of the impact of the COVID-19 outbreak was statistically (p < .001) greater than that of policy measures on family (0.664 vs 0.618), education (0.562 vs 0.557), and the economy (0.643 vs 0.572). The weighted effect of the impact of policy measures was statistically (p < .001) greater than that of the COVID-19 pandemic on people's daily activities (0.675 vs 0.651), cultural/traditional or community way of life (0.769 vs 0.736), access to healthcare services and infection prevention supplies (0.410 vs 0.390), and mental health (0.625 vs 0.584). Conclusions: About half of the participants had a high level of impact from both the COVID-19 pandemic and policy measures. The results of this study suggest that policy measures need to be judged with caution, and the government should provide more comprehensive support to reduce the impact on people's lives.

Antibiotic prescribing behavior among physicians in Asia: a multinational survey.

Objective: To evaluate antibiotic prescribing behavior (APB) among physicians with various specialties in five Asian countries. Design: Survey of antibiotics prescribing behavior in three stages (initial, on-treatment, and de-escalation stages). Methods: Participants included internists, infectious diseases (ID) specialists, hematologists, intensivists, and surgeons. Participants' characteristics, patterns of APB, and perceptions of antimicrobial stewardship were collected. A multivariate analysis was conducted to evaluate factors associated with appropriate APB. Results: There were 367 participants. The survey response rate was 82.5% (367/445). For the initial stage, different specialties had different choices for empiric treatment. For the on-treatment stage, if the patient does not respond to empiric treatment, most respondents will step up to broader-spectrum antibiotics (273/367: 74.39%). For the de-escalation stage, the rate of de-escalation was 10%-60% depending on the specialty. Most respondents would de-escalate antibiotics based on guidelines (250/367: 68.12%). De-escalation was mostly reported by ID specialists (66/106: 62.26%). Respondents who reported that they performed laboratory investigations prior to empirical antibiotic prescriptions (aOR = 2.83) were associated with appropriate use, while respondents who reported ID consultation were associated with appropriate antibiotic management for infections not responding to empiric treatment (aOR = 40.87); adherence with national guidelines (aOR = 2.57) was associated with reported successful carbapenem de-escalation. Conclusion: This study highlights the variation in practices and gaps in appropriate APB on three stages of antibiotic prescription among different specialties. Education on appropriate investigation, partnership with ID specialist, and availability and adherence with national guidelines are critical to help guide appropriate APB among different specialties.

Rapid Diagnostic Test Value and Implementation in Antimicrobial Stewardship Across Low-to-Middle and High-Income Countries: A Mixed-Methods Review.

Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

Efficacy of Environmental Cleaning Protocol Featuring Real-Time Feedback with and without PX-UV in Reducing the Contamination of Gram-Negative Microorganisms on High-Touch Surfaces in Four Intensive Care Units in Thailand.

Environmental cleaning and disinfection practices have been shown to reduce microorganism bioburden in the healthcare environment. This study was performed in four intensive care units in Thailand. Five high-touch surfaces were sampled before and after terminal manual cleaning and disinfection, and after pulsed xenon UV (PX-UV). Five nursing station sites were collected on a weekly basis before and after terminal manual cleaning. There were 100 patient rooms-50 rooms in the intervention arm and 50 rooms in the control arm-plus 32 nursing station sites. In the intervention arm, rooms with positive Gram-negative microorganisms were reduced by 50% after terminal manual cleaning and disinfection (p = 0.04) and 100% after PX-UV disinfection (p < 0.001). On five nursing station sites, colony counts of Gram-negative contamination decreased by 100% (p < 0.001) in the intervention arm while decreasing by 65.2% (p = 0.03) in the control arm after terminal manual cleaning and disinfection. The in-room time use was 15.6 min per room. A PX-UV device significantly reduced the level of Gram-negative microorganisms on high-touch surfaces in intensive care units. The application of a PX-UV device was practical a in resource-limited setting without compromising cleaning and disinfection times.

Impact of Pharmacist-Led Multidisciplinary Team to Attain Targeted Vancomycin Area under the Curved Monitoring in a Tertiary Care Center in Thailand.

Vancomycin Area Under the Curve (AUC) monitoring has been recommended to ensure successful clinical outcomes and minimize the risk of nephrotoxicity, rather than traditional trough concentration. However, vancomycin AUC monitoring by a pharmacist-led multidisciplinary team (PMT) has not been well established in Southeast Asia. This study was conducted at Thammasat University Hospital. Adult patients aged ≥ 18 years who were admitted and received intravenous vancomycin ≥48 h were included. The pre-PMT period (April 2020-September 2020) was defined as a period using traditional trough concentration, while the post-PMT period (October 2020-March 2021) was defined as a period using PMT to monitor vancomycin AUC. The primary outcome was the rate of achievement of the therapeutic target of an AUC/MIC ratio of 400-600. There was a significantly higher rate of achievement of therapeutic target vancomycin AUC during post-PMT period (66.7% vs. 34.3%, p < 0.001). Furthermore, there was a significant improvement in the clinical cure rate (92.4% vs. 69.5%, p < 0.001) and reduction in 30-day ID mortality (2.9% vs. 12.4%, p = 0.017) during the post-PMT period. Our study demonstrates that PMT was effective to help attain a targeted vancomycin AUC, improve the clinical cure rate, and reduce 30-day ID mortality. This intervention should be encouraged to be implemented in Southeast Asia.

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.