Population pharmacokinetic/pharmacodynamic target attainment analysis of IV fosfomycin for the treatment of MDR Gram-negative bacterial infections.

BACKGROUND: IV fosfomycin is used against MDR Gram-negative bacilli (GNB) but has dose-limiting side effects, especially in patients with impaired kidney function. OBJECTIVES: To determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function. METHODS: Adult patients receiving IV fosfomycin for treatment of GNB were eligible. Five serial blood samples were collected after at least three doses of fosfomycin; plasma was assayed by LC-MS/MS and modelled by population pharmacokinetic analysis. The PTA for AUC24/MIC of 98.9 for Escherichia coli and Klebsiella pneumoniae, and 40.8 for Pseudomonas aeruginosa were computed by Monte Carlo simulations. Cumulative fractions of response (CFR) were analysed for each pathogen using EUCAST MIC distributions. RESULTS: A total of 24 patients were included. Creatinine clearance (CLCR) and gender significantly influenced fosfomycin clearance. The kidney function-adjusted dosing regimens are proposed by using the lowest dose that can achieve ≥90% PTA for AUC24/MIC of 98.9 at an MIC of ≤32 mg/L (EUCAST v.13 susceptibility breakpoint for Enterobacterales). For patients with normal kidney function (CLCR 91-120 mL/min), a dosage of 15 g/day is suggested. This regimen achieved 97.1% CFR against E. coli, whereas CFR was 72.9% for K. pneumoniae and 76.7% for P. aeruginosa. CONCLUSIONS: A fosfomycin dosage of 15 g/day with adjustment according to kidney function provided high PTA and CFR when treating E. coli. This dosage is lower than that used in current practice and may improve tolerability. Higher dosages may be needed for P. aeruginosa; however, safety data are limited.

Epidemiology of ventilator-associated tracheobronchitis and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria at a tertiary care hospital in Thailand.

Objectives: To investigate the epidemiology of MDR Gram-negative bacilli ventilator-associated tracheobronchitis (MDR GNB-VAT) and MDR GNB ventilator-associated pneumonia (MDR GNB-VAP) among mechanically ventilated patients. Methods: We conducted a retrospective observational study among hospitalized patients who underwent continuous mechanical ventilation for ≥48 h at Siriraj Hospital, Thailand. Results: During the 18 month study period, 1824 unique patients underwent continuous mechanical ventilation (12 216 ventilator-days). The cumulative incidences of MDR GNB-VAT and -VAP were 8.4% and 8.3%, respectively. The incidence rates of MDR GNB-VAT and -VAP were 12.52 and 12.44 episodes/1000 ventilator-days, respectively. Among those with VAT, the cumulative incidence and incidence rate of subsequent VAP development within 7 days were 11.76% and 2.81 episodes/1000 ventilator-days, respectively. The median durations of mechanical ventilation before having VAP and VAT were 9 and 12 days, respectively. Multivariate analysis identified three independently associated factors for patients having VAP compared with having VAT: underlying cerebrovascular disease [adjusted OR (aOR): 0.46; 95% CI: 0.27-0.78; P = 0.04], previous surgery (aOR: 0.68; 95% CI: 0.57-0.8; P < 0.001) and acute renal failure (aOR: 1.75; 95% CI: 1.27-2.40; P = 0.001). Conclusions: The study revealed high incidences of MDR GNB-VAT and -VAP among mechanically ventilated patients. The independent risk factors for having VAP can help identify patients at risk for developing VAP and who need early weaning from mechanical ventilation.

Effectiveness of implementing a locally-developed guideline for antibiotic treatment of lower urinary tract infection in adults in Thailand.

Lower urinary tract infection (UTI) is still a major concern in clinical practice, but inappropriate antibiotics are commonly prescribed in Thailand. This study aimed to develop, implement, and evaluate the effectiveness of a clinical practice guideline (CPG) for antibiotic treatment of lower UTI in adults at Siriraj Hospital which is a university hospital in Thailand. This study comprised a retrospective cohort study development phase, and a prospective cohort study implementation phase. The outcomes of treatment were compared between phases. The development and implementation phases enrolled 220 and 151 patients, respectively. The CPG compliance rate was significantly increased from 17.3% during the development phase to 43.0% during the implementation phase (p = 0.001). The rates of fluoroquinolones and cotrimoxazole use were significantly lower during implementation than during development (p < 0.001 and p = 0.027, respectively). The rates of nitrofurantoin and fosfomycin use were significantly greater during implementation than during development (p = 0.009 and p = 0.005, respectively). The overall cure rate was not significantly different between the two study phases, but implementation group patients had significantly more unfavorable prognostic factors than development phase patients. CPG-compliance group patients had a significantly higher cure rate than CPG-non-compliance group patients (p = 0.011). The cost of the initial course of antibiotics per episode was significantly higher during the implementation phase because the cost of fosfomycin is more expensive and more fosfomycin was prescribed during implementation (p = 0.047). Implementation of the locally-developed CPG was found to be effective for increasing the appropriate use of empirical antibiotics and increasing the cure rate; however, measures to improve and reinforce CPG compliance are needed.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Characteristics and genomic epidemiology of colistin-resistant Enterobacterales from farmers, swine, and hospitalized patients in Thailand, 2014-2017.

BACKGROUND: Colistin is one of the last resort therapeutic options for treating carbapenemase-producing Enterobacterales, which are resistant to a broad range of beta-lactam antibiotics. However, the increased use of colistin in clinical and livestock farming settings in Thailand and China, has led to the inevitable emergence of colistin resistance. To better understand the rise of colistin-resistant strains in each of these settings, we characterized colistin-resistant Enterobacterales isolated from farmers, swine, and hospitalized patients in Thailand. METHODS: Enterobacterales were isolated from 149 stool samples or rectal swabs collected from farmers, pigs, and hospitalized patients in Thailand between November 2014-December 2017. Confirmed colistin-resistant isolates were sequenced. Genomic analyses included species identification, multilocus sequence typing, and detection of antimicrobial resistance determinants and plasmids. RESULTS: The overall colistin-resistant Enterobacterales colonization rate was 26.2% (n = 39/149). The plasmid-mediated colistin-resistance gene (mcr) was detected in all 25 Escherichia coli isolates and 9 of 14 (64.3%) Klebsiella spp. isolates. Five novel mcr allelic variants were also identified: mcr-2.3, mcr-3.21, mcr-3.22, mcr-3.23, and mcr-3.24, that were only detected in E. coli and Klebsiella spp. isolates from farmed pigs. CONCLUSION: Our data confirmed the presence of colistin-resistance genes in combination with extended spectrum beta-lactamase genes in bacterial isolates from farmers, swine, and patients in Thailand. Differences between the colistin-resistance mechanisms of Escherichia coli and Klebsiella pneumoniae in hospitalized patients were observed, as expected. Additionally, we identified mobile colistin-resistance mcr-1.1 genes from swine and patient isolates belonging to plasmids of the same incompatibility group. This supported the possibility that horizontal transmission of bacterial strains or plasmid-mediated colistin-resistance genes occurs between humans and swine.

The risk of pig and chicken farming for carriage and transmission of Escherichia coli containing extended-spectrum beta-lactamase (ESBL) and mobile colistin resistance (mcr) genes in Thailand.

South-East Asian countries report a high prevalence of extended-spectrum cephalosporin- (ESC-) and colistin-resistant Escherichia coli (Col-R-Ec). However, there are still few studies describing the molecular mechanisms and transmission dynamics of ESC-R-Ec and, especially, Col-R-Ec. This study aimed to evaluate the prevalence and transmission dynamics of Ec containing extended spectrum beta-lactamases (ESBL) and mobile colistin resistance (mcr) genes using a 'One Health' design in Thailand. The ESC-R-Ec and Col-R-Ec isolates of human stool samples (69 pig farmers, 155 chicken farmers, and 61 non-farmers), rectal swabs from animals (269 pigs and 318 chickens), and the intestinal contents of 196 rodents were investigated. Resistance mechanisms and transmission dynamics of Ec isolates (n=638) were studied using short and long read sequencing. We found higher rates of ESBL-Ec isolates among pig farmers (n=36; 52.2%) than among chicken farmers (n=58; 37.4 %; P<0.05) and the control group (n=61; 31.1 %; P<0.05). Ec with co-occurring ESBL and mcr genes were found in 17 (6.0 %), 50 (18.6 %) and 15 (4.7 %) samples from humans, pigs and chickens, respectively. We also identified 39 (13.7 %) human samples with non-identical Ec containing ESBL and mcr. We found higher rates of ESBL-Ec, in particular CTX-M-55, isolates among pig farmers than among non-pig farmers (P<0.01). 'Clonal' animal-human transmission of ESBL-Ec and Ec with mcr genes was identified but rare as we overall found a heterogenous population structure of Ec. The Col-R-Ec from human and animal samples often carried mcr-1.1 on conjugative IncX4 plasmids. The latter has been identified in Ec of many different clonal backgrounds.

Identification and characterization of plasmids carrying the mobile colistin resistance gene mcr-1 using optical DNA mapping.

Objectives: Colistin is a last-resort antibiotic, but there has been a rapid increase in colistin resistance, threatening its use in the treatment of infections with carbapenem-resistant Enterobacterales (CRE). Plasmid-mediated colistin resistance, in particular the mcr-1 gene, has been identified and WGS is the go-to method in identifying plasmids carrying mcr-1 genes. The goal of this study is to demonstrate the use of optical DNA mapping (ODM), a fast, efficient and amplification-free technique, to characterize plasmids carrying mcr-1. Methods: ODM is a single-molecule technique, which we have demonstrated can be used for identifying plasmids harbouring antibiotic resistance genes. We here applied the technique to plasmids isolated from 12 clinical Enterobacterales isolates from patients at a major hospital in Thailand and verified our results using Nanopore long-read sequencing. Results: We successfully identified plasmids encoding the mcr-1 gene and, for the first time, demonstrated the ability of ODM to identify resistance gene sites in small (∼30 kb) plasmids. We further identified bla CTX-M genes in different plasmids than the ones encoding mcr-1 in three of the isolates studied. Finally, we propose a cut-and-stretch assay, based on similar principles, but performed using surface-functionalized cover slips for DNA immobilization and an inexpensive microscope with basic functionalities, to identify the mcr-1 gene in a plasmid sample. Conclusions: Both ODM and the cut-and-stretch assay developed could be very useful in identifying plasmids encoding antibiotic resistance in hospitals and healthcare facilities. The cut-and-stretch assay is particularly useful in low- and middle-income countries, where existing techniques are limited.

Development and Implementation of a Mobile Application for Choosing Empirical Antimicrobial Therapy for Bacteremia, Pneumonia, Urinary Tract Infection, and Skin and Soft Tissue Infection among Hospitalized Patients.

Clinical practice guidelines (CPGs) and computerized clinical decision support programs are effective antimicrobial stewardship strategies. The DigitalAMS™, a mobile-based application for choosing empirical antimicrobial therapy under the hospital's CPGs, was implemented at Siriraj Hospital and evaluated. From January to June 2018, a cross-sectional study was conducted among 401 hospitalized adults who received ≥1 dose of antimicrobials and had ≥1 documented site-specific infection. The antimicrobial regimen prescribed by the ward physician (WARD regimen), recommended by the DigitalAMS™ (APP regimen), and recommended by two independent infectious disease (ID) physicians before (Emp-ID regimen) and after (Def-ID regimen) the final microbiological results became available were compared in a pairwise fashion. The percent agreement of antimicrobial prescribing between the APP and Emp-ID regimens was 85.7% in the bacteremia group, 59.1% in the pneumonia group, 78.6% in the UTI group, and 85.2% in the SSTI group. The percent agreement between the APP and Emp-ID regimens was significantly higher than that between the WARD and Emp-ID regimens in three site-specific infection groups: the bacteremia group (85.7% vs. 47.9%, p < 0.001), the UTI group (78.6% vs. 37.8%, p < 0.001), and the SSTI group (85.2% vs. 40.2%, p < 0.001). Furthermore, the percent agreement between the APP and Def-ID regimens was similar to that between the Emp-ID and Def-ID regimens in all sites of infection. In conclusions, the implementation of DigitalAMS™ seems useful but needs some revisions. The dissemination of this ready-to-use application with customized clinical practice guidelines to other hospital settings may be beneficial.

Colistin Monotherapy versus Colistin plus Sitafloxacin for Therapy of Carbapenem-Resistant Acinetobacter baumannii Infections: A Preliminary Study.

The in vitro study of sitafloxacin against carbapenem-resistant (CR) Acinetobacter baumannii demonstrated activity against most strains of CR A. baumannii, and the combination of colistin and sitafloxacin showed an in vitro synergistic effect against CR A. baumannii. This study aimed to compare efficacy and safety between colistin plus sitafloxacin with colistin alone for therapy for CR A. baumannii infection. This randomized controlled trial enrolled 56 patients with CR A. baumannii infection (28/group) during 2018-2021, and the treatment duration was 7-14 days. The study outcomes were 28-day mortality, clinical and microbiological responses, and adverse events. There was no significant difference in 28-day mortality between groups (32.1% combination vs. 32.1% monotherapy, p = 1.000). Favorable clinical response at the end of treatment was comparable between groups (81.5% combination vs. 77.8% monotherapy, p = 0.788). Microbiological response at the end of treatment was also comparable between groups (73.1% combination vs. 74.1% monotherapy, p = 0.934). Acute kidney injury was found in 53.8% of the combination group, and in 45.8% of the monotherapy group (p = 0.571). In conclusion, there was no significant difference in 28-day mortality between the colistin monotherapy and the colistin plus sitafloxacin groups. There was also no significant difference in adverse events between groups.

Natural history and clinical course of patients with dermographism in a tropical country: a questionnaire-based survey.

Background: Dermographism is the most common form of chronic inducible urticaria. However, the natural history and clinical course of patients with dermographism in tropical countries has not fully been described. Objective: To examine clinical features, natural history and clinical course of dermographism in Thai patients according to their experiences. Methods: A cross-sectional, internet-based survey was conducted in 2021. All study respondents completed a 45-item questionnaire that was circulated on social media regarding dermographism. Results: Among the 2,456 respondents who reported dermographism, 1,900 had symptomatic dermographism (SD), while 556 had simple dermographism (SimD). Of the respondents who reported SD and SimD, the female to male ratio was 2.2:1 and 2.4:1, respectively. The median age of the first episode of SD and SimD was 16 and 15 years, respectively. Older age, greater body weight, cardiovascular diseases, allergic conjunctivitis, atopic dermatitis, changes in temperature, and family history of dermographism were all factors linked to an increased probability of SD. Half of the respondents with SD reported moderate itch severity. Moreover, about half of SD and almost all of SimD respondents let the wheal resolve on its own. Second generation H1-antihistamines were most commonly prescribed while over-the-counter medicines were taken by both SD and SimD respondents. Conclusion: This survey highlights several aspects of dermographism in Thai patients which can be useful for healthcare providers. SD is troublesome and affects the quality of life of many patients, leading some to seek medication themselves.

Influence of occupational exposure to pigs or chickens on human gut microbiota composition in Thailand.

Pig farming's influence on human gut microbiota has been observed previously, but its pervasiveness is unclear. We therefore aimed at studying whether pig farming influenced human gut microbiota composition in Thailand and whether poultry farming did too. We collected human stool samples (71 pig farmers, 131 chicken farmers, 55 non-farmers) for 16S rRNA sequencing and performed subsequent DADA2 analyses of amplicon sequence variants. We found that Alpha diversity values were highest among chicken farmers. Relative abundances of Prevotellaceae were significantly higher among pig farmers than among chicken farmers and non-farmers (p < 0.001). Beta diversity plots revealed different clustering according to occupation. The presence or absence of antimicrobial-resistant Escherichia coli was not associated with changes in gut microbiota composition. In conclusion, occupation was the strongest factor influencing gut microbiota composition in Thailand. We hypothesize that Prevotellaceae amplicon sequence variants are transmitted from pigs to pig farmers.

Active Surveillance for Carbapenem-Resistant Enterobacterales (CRE) Colonization and Clinical Course of CRE Colonization among Hospitalized Patients at a University Hospital in Thailand.

Optimal measures for preventing and controlling carbapenem-resistant Enterobacterales (CRE) depend on their burden. This prospective observational study investigated the prevalence and clinical course of CRE colonization in hospitalized patients at Siriraj Hospital, the largest university hospital in Thailand. Stool/rectal swab samples were collected from the patients upon admission, once weekly during hospitalization and every 1-3 months after discharge, to determine the presence of CRE in the stool. Between 2018 and 2021, a total of 528 patients were included. The prevalence of CRE colonization upon admission was 15.5%, while 28.3% of patients who tested negative for CRE on admission acquired CRE during their hospitalization. CRE colonization upon admission was usually associated with prior healthcare exposure. Among CRE-colonized patients, 4.7% developed a CRE clinical infection, with 60% mortality. No cutoff period that ensured that patients were free of CRE colonization in stool was identified, and isolation precautions should only be ceased if stool tests are negative for CRE. In conclusion, the prevalence of CRE colonization among hospitalized patients at Siriraj Hospital is high. CRE-colonized patients are at risk of developing subsequent CRE infection. To prevent CRE transmission within the hospital, patients at high risk of colonization should undergo CRE screening upon admission.

Epidemiology of Carbapenem-Resistant Enterobacterales Infection and Colonization in Hospitalized Patients at a University Hospital in Thailand.

Purpose: To investigate the epidemiology of carbapenem-resistant Enterobacterales (CRE) colonization or CRE infection relative to the natural history and clinical course of CRE colonization or CRE infection in hospitalized patients during admission and after discharge. Material and Methods: Two adult cohorts were enrolled. Cohort I comprised hospitalized patients who had CRE isolated from their clinical specimens during 2018-2020. CRE colonization or CRE infection was based on the absence/presence of clinical features of infection. Information regarding the natural history and clinical course of these patients was collected during hospitalization. Stool samples were evaluated for CRE once a week during hospitalization, and then once every few months after discharge until negative for CRE. Cohort II comprised patients who had CRE isolated from clinical specimens during hospitalization and who were discharged during 2015-2018. CRE in stool samples collected from these patients every few months was assessed to determine duration of CRE in stool. Results: CRE in stool was detected in 69.7% of 353 patients in cohort I. K. pneumoniae was the predominant CRE isolated from clinical samples (76.8%) and stool samples (65.7%). Among the 225 CRE-colonized patients, 20.4% developed subsequent CRE infections with a median duration from CRE colonization to CRE infection of 14 days. Among 174 CRE-infected patients, the most common infection was pneumonia with mortality at discharge of 47.7%. Duration of CRE colonization in stool was <1 year in 50.0% of cohort I patients, and <2 years in 91.4% of patients in cohort II. Conclusion: CRE isolated from clinical specimens in hospitalized patients are more likely to cause colonization than infection. Patients with CRE colonization are at risk of subsequent CRE infection with high mortality. Stool culture for CRE is needed to verify if contact precautions can be discontinued because the duration of CRE colonization in stool varied from days to years.

Epidemiology and Burden of Sepsis at Thailand's Largest University-Based National Tertiary Referral Center during 2019.

Data specific to the epidemiology and burden of sepsis in low- and middle-income countries are limited. This study aimed to determine the epidemiology and burden of adult patients with sepsis at Siriraj Hospital during 2019. Randomly selected adult patients who had blood cultures performed at our center during January−December 2019 were enrolled. A Quick Sepsis-related Organ Failure Assessment (qSOFA) score was used to determine the presence of sepsis. Demographic data and clinical outcome data were collected, and the annual incidence of sepsis or septic shock and death was estimated. Of the 987 subjects who had blood cultures performed, 798 had infections, 341 had sepsis, and 104 had septic shock. The prevalence of sepsis or septic shock was 34.9% among blood cultured patients, and 42.7% among those with infections. The prevalence of septic shock was 30.5% among subjects with sepsis. Approximately 63% of sepsis subjects were hospital-acquired infections. The factors independently associated with 28-day mortality in sepsis were receiving an immunosuppressive agent (adjusted odds ratio [aOR]: 2.37, 95% confidence interval [CI]: 1.27−4.45; p = 0.007), septic shock (aOR: 2.88, 95% CI: 1.71−4.87; p < 0.001), and proven infection (aOR: 2.88, 95% CI: 1.55−5.36; p = 0.001). Receiving appropriate, definitive antibiotic therapy (ABT) was independently associated with lower mortality in sepsis (aOR: 0.50, 95% CI: 0.27−0.93; p = 0.028) and septic shock subjects (aOR: 0.21, 95% CI: 0.06−0.72; p = 0.013). Achievement of mean arterial pressure (MAP) ≥ 65 mmHg (aOR: 0.09, 95% CI: 0.01−0.77; p = 0.028) and urine output ≥ 0.5 mL/kg/h (aOR: 0.15, 95% CI: 0.04−0.51; p = 0.006) were independently associated with lower mortality in septic shock patients. The incidence and mortality of sepsis remains high. Appropriate choice of definitive ABT and achievement of MAP and urine output goals may lower mortality in patients with sepsis or septic shock.

Implementation of Clinical Practice Guidelines for Empirical Antibiotic Therapy of Bacteremia, Urinary Tract Infection, and Pneumonia: A Multi-Center Quasi-Experimental Study.

A quasi-experimental study was conducted on the implementation of locally developed clinical practice guidelines (CPGs) for empirical antibiotic (ATB) therapy of common infections (bacteremia, urinary tract infection (UTI), pneumonia) in the hospitals from January 2019 to December 2020. The CPGs were developed using data from patients with these infections at individual hospitals. Relevant CPG data pre- and post-implementation were collected and compared. Of the 1644 patients enrolled in the study, 808 and 836 were in the pre- and post-implementation periods, respectively, and patient outcomes were compared. Significant reductions in the mean durations of intensive care unit stay (3.44 ± 9.08 vs. 2.55 ± 7.89 days; p = 0.035), ventilator use (5.73 ± 12.14 vs. 4.22 ± 10.23 days; p = 0.007), piperacillin/tazobactam administration (0.954 ± 3.159 vs. 0.660 ± 2.217 days, p = 0.029), and cefoperazone/sulbactam administration (0.058 ± 0.737 vs. 0.331 ± 1.803 days, p = 0.0001) occurred. Multivariate analysis demonstrated that CPG-implementation was associated with favorable clinical outcomes (adjusted odds ratio 1.286, 95% confidence interval: 1.004-1.647, p = 0.046). Among patients who provided follow-up cultures (n = 284), favorable microbiological responses were significantly less frequent during the pre-implementation period than the post-implementation period (80.35% vs. 91.89%; p = 0.01). In conclusion, the locally developed CPG implementation is feasible and effective in improving patient outcomes and reducing ATB consumption. Hospital antimicrobial stewardship teams should be able to facilitate CPG development and implementation for antimicrobial therapy for common infections.

Mortality in Thai Nursing Homes Based on Antimicrobial-Resistant Enterobacterales Carriage and COVID-19 Lockdown Timing: A Prospective Cohort Study.

Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing homes.

Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study.

The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400−600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; Δ = −0.4%; 95% CI; −4.3−3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.

A simple cut and stretch assay to detect antimicrobial resistance genes on bacterial plasmids by single-molecule fluorescence microscopy.

Antimicrobial resistance (AMR) is a fast-growing threat to global health. The genes conferring AMR to bacteria are often located on plasmids, circular extrachromosomal DNA molecules that can be transferred between bacterial strains and species. Therefore, effective methods to characterize bacterial plasmids and detect the presence of resistance genes can assist in managing AMR, for example, during outbreaks in hospitals. However, existing methods for plasmid analysis either provide limited information or are expensive and challenging to implement in low-resource settings. Herein, we present a simple assay based on CRISPR/Cas9 excision and DNA combing to detect antimicrobial resistance genes on bacterial plasmids. Cas9 recognizes the gene of interest and makes a double-stranded DNA cut, causing the circular plasmid to linearize. The change in plasmid configuration from circular to linear, and hence the presence of the AMR gene, is detected by stretching the plasmids on a glass surface and visualizing by fluorescence microscopy. This single-molecule imaging based assay is inexpensive, fast, and in addition to detecting the presence of AMR genes, it provides detailed information on the number and size of plasmids in the sample. We demonstrate the detection of several ß-lactamase-encoding genes on plasmids isolated from clinical samples. Furthermore, we demonstrate that the assay can be performed using standard microbiology and clinical laboratory equipment, making it suitable for low-resource settings.

One Health Surveillance of Antimicrobial Resistance Phenotypes in Selected Communities in Thailand.

Integrated surveillance of antimicrobial resistance (AMR) using the One Health approach that includes humans, animals, food, and the environment has been recommended by responsible international organizations. The objective of this study was to determine the prevalence of AMR phenotypes in Escherichia coli and Klebsiella species isolated from humans, pigs, chickens, and wild rodents in five communities in northern Thailand. Rectal swabs from 269 pigs and 318 chickens; intestinal contents of 196 wild rodents; and stool samples from 69 pig farmers, 155 chicken farmers, and 61 non-farmers were cultured for E. coli and Klebsiella species, which were then tested for resistance to ceftriaxone, colistin, and meropenem. The prevalence of ceftriaxone-resistant E. coli and Klebsiella species in pigs, chickens, rodents, pig farmers, chicken farmers, and non-farmers was 64.3%, 12.9%, 4.1%, 55.1%, 38.7%, and 36.1%, respectively. Colistin resistance in pigs, chickens, rodents, pig farmers, chicken farmers, and non-farmers was 41.3%, 9.8%, 4.6%, 34.8%, 31.6%, and 24.6%, respectively. Meropenem resistance was not detected. The observed high prevalence of AMR, especially colistin resistance, in study food animals/humans is worrisome. Further studies to identify factors that contribute to AMR, strengthened reinforcement of existing regulations on antimicrobial use, and more appropriate interventions to minimize AMR in communities are urgently needed.

Feasibility, Challenges, and Benefits of Global Antimicrobial Resistance Surveillance System Implementation: Results from a Multicenter Quasi-Experimental Study.

The Global Antimicrobial Resistance Surveillance System (GLASS) is one of the pillars of the global action plan on antimicrobial resistance launched by the World Health Organization in 2015. This study was conducted to determine the feasibility and benefits of GLASS as a component of antimicrobial stewardship strategies in three provincial hospitals in Thailand. Data on the types of bacteria isolated and their antibiotic susceptibility during January-December 2019 and January-April 2020 were retrieved from the microbiology laboratory of each participating hospital. Laboratory-based antibiograms from 2019 and GLASS-based antibiograms from 2020 were created and compared. A total of 14,877 and 3580 bacterial isolates were obtained during January-December 2019 and January-April 2020, respectively. The common bacteria isolated in both periods were Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus. Hospital-acquired infection (HAI)-related bacteria were observed in 59.0%, whereas community-acquired infection (CAI)-related bacteria were observed in 41.0% of isolates. Antibiotic resistance in CAIs was high and may have been related to the misclassification of colonized bacteria as true pathogens and HAIs as CAIs. The results of this study on AMR surveillance using GLASS methodology may not be valid owing to several inadequate data collections and the problem of specimen contamination. Given these considerations, related personnel should receive additional training on the best practices in specimen collection and the management of AMR surveillance data using the GLASS approach.