Immunogenicity of Intradermal Versus Intramuscular BNT162b2 COVID-19 Booster Vaccine in Patients with Immune-Mediated Dermatologic Diseases: A Non-Inferiority Randomized Controlled Trial.

The intradermal route has emerged as a dose-sparing alternative during the coronavirus disease 2019 (COVID-19) pandemic. Despite its efficacy in healthy populations, its immunogenicity has not been tested in immune-mediated dermatologic disease (IMDD) patients. This assessor-blinded, randomized-controlled, non-inferiority trial recruited patients with two representative IMDDs (i.e., psoriasis and autoimmune bullous diseases) to vaccinate with fractionated-dose intradermal (fID) or standard intramuscular (sIM) BNT162b2 vaccines as a fourth booster dose under block randomization stratified by age, sex, and their skin diseases. Post-vaccination SARS-CoV-2-specific IgG and interferon-γ responses measured 4 and 12 weeks post-intervention were serological surrogates used for demonstrating treatment effects. Mean differences in log-normalized outcome estimates were calculated with multivariable linear regression adjusting for their baseline values, systemic immunosuppressants used, and prior COVID-19 vaccination history. The non-inferiority margin was set for fID to retain >80% immunogenicity of sIM. With 109 participants included, 53 received fID (all entered an intention-to-treat analysis). The fID demonstrated non-inferiority to sIM in humoral (mean outcome estimates of sIM: 3.3, ΔfID-sIM [mean, 95%CI]: -0.1, -0.3 to 0.0) and cellular (mean outcome estimates of sIM: 3.2, ΔfID-sIM [mean, 95%CI]: 0.1, -0.2 to 0.3) immunogenicity outcomes. Two psoriasis patients from the fID arm (3.8%) developed injection-site Koebner's phenomenon. Fewer fID recipients experienced post-vaccination fever (fID vs. sIM: 1.9% vs. 12.5%, p = 0.027). The overall incidence of disease flare-ups was low without a statistically significant difference between groups. The intradermal BNT162b2 vaccine is a viable booster option for IMDD patients troubled by post-vaccination fever; its role in mitigating the risk of flare-ups remains unclear.

Epidemiology of extended-spectrum ß-lactamase-producing Enterobacterales infection in kidney transplant recipients.

BACKGROUND: Extended-spectrum b-lactamase (ESBL)-producing gram-negative bacilli (ESBL-GNB) are the most important pathogenic bacteria infecting kidney transplant patients. Kidney transplantation has been shown to be a risk factor for nosocomial ESBL-GNB bacteremia. The aims of this study were to describe the epidemiology of ESBL-GNB acquisition and to identify factors associated with ESBL-GNB infection in kidney transplant recipients, including pretransplant ESBL-GNB fecal carriage. METHODS: A prospective study of patients undergoing kidney transplantation at Ramathibodi Hospital from March 1, 2019-November 30, 2020 was conducted. During this period, 66 patients who underwent kidney transplantation. Perianal swab cultures and urine cultures for ESBL-GNB were obtained from all subjects upon admission for transplantation and on Days 3, 7, 14 and 21 after surgery to determine the prevalence, incidence, and duration of admission before acquisition of the organisms. RESULTS: Of the 66 patients undergoing kidney transplantation, 18 preoperative perianal swabs were detected to be positive for ESBL-GNB upon admission, representing 27.3% of the cases. The in-hospital perianal swab tests showed a significant increase to 96.8% positive ESBL-GNB cultures at the end of week 3. Approximately one-fourth (27.8%) of patients who acquired ESBL-GNB developed a postoperative symptomatic infection. The infection occurred in 13% of such patients who were not ESBL positive at first. These infections included urinary tract infections (20 cases, [30%], of which 55% were due to ESBL-GNB) and bloodstream infections (13 cases; of which 9 [69.2%] were due to ESBL-GNB). E. coli was the most common pathogen. Previous exposure to antibiotics, including surgical prophylaxis, underlying disease, duration of indwelling urinary catheters and ureteric stents, as well as other operative factors were not found to be significantly associated with the acquisition of ESBL-producing organisms in this dataset. CONCLUSIONS: ESBL carriage may be a risk factor for the development of bacteremia and other serious infections among kidney transplant recipients, although a statistically significant difference could not be demonstrated owing to the small size of the sample. The high rate of ESBL acquisition suggests that more stringent infection prevention and control efforts are needed.

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3).

The durability of a three-dose extended primary series of COVID-19 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136−3083) BAU/mL vs. 373 (188−607) BAU/mL) and PD (1093 (617−1911) BAU/mL vs. 180 (126−320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

An additional dose of viral vector COVID-19 vaccine and mRNA COVID-19 vaccine in kidney transplant recipients: A randomized controlled trial (CVIM 4 study).

Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).

Impact of Carbapenem Peri-Transplant Prophylaxis and Risk of Extended-Spectrum Cephalosporin-Resistant Enterobacterales Early Urinary Tract Infection in Kidney Transplant Recipients: A Propensity Score-Matched Analysis.

Background: Urinary tract infection (UTI) is the most common bacterial infection after kidney transplantation (KT), leading to unfavorable clinical and allograft outcomes. Gram-negative uropathogenic bacteria are frequently encountered especially extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (EB), causing UTI early after KT. Methods: A retrospective single transplant study was conducted between January 2016 and December 2019. We performed 1:1 nearest-neighbor propensity score matching without replacement using recipient age, recipient sex, induction, transplant year, human leukocyte antigen, cold ischemia time, and panel-reactive antibody before analyses. Cumulative incidence of ESC-R EB early (within 14 days after KT) UTI was estimated by the Kaplan-Meier method. Risk factors for ESC-R EB early UTI were analyzed by a Cox proportional hazards model. Variables measured after transplantation were considered time-dependent covariates. Results: We included 620 KT recipients (37% women; mean age ± SD, 43 ± 11 years). Overall, 64% and 76% received deceased-donor allograft and induction therapy. Sixty-five (10%) and 555 (90%) received carbapenems and cefuroxime peri-transplant prophylaxis, respectively. Early UTI occurred in 183 (30%) patients, 52% caused by ESC-R EB. Propensity score matching produced 65 well-balanced pairs. During a 14-day follow-up, the cumulative incidence of ESC-R EB early UTI was 5 and 28% in the carbapenems and cefuroxime groups, respectively (log-rank test = 0.003). Peri-transplant carbapenems prophylaxis was a protective factor against ESC-R EB after KT (hazard ratio, 0.19; 95% confidence interval, 0.05-0.64; p = 0.008). Clinical and allograft outcomes did not differ significantly between the groups. Conclusions: In the setting where ESC-R EB UTI is common among KT recipients, carbapenems peri-transplant prophylaxis could protect against the occurrence of early ESC-R EB UTI after KT. Further prospective studies should focus on this specific infection prevention strategy.

Detectable Duration of Viable SARS-CoV-2, Total and Subgenomic SARS-CoV-2 RNA in Noncritically Ill COVID-19 Patients: a Prospective Cohort Study.

Determination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is important in guiding the infection control and differentiating between reinfection and persistent viral RNA. Although viral culture is the gold standard to determine viral infectivity, the method is not practical. We studied the kinetics of SARS-CoV-2 total RNAs and subgenomic RNAs (sgRNAs) and their potential role as surrogate markers of viral infectivity. The kinetics of SARS-CoV-2 sgRNAs compared to those of the culture and total RNA shedding in a prospective cohort of patients diagnosed with coronavirus disease 2019 (COVID-19) were investigated. A total of 260 nasopharyngeal swabs from 36 patients were collected every other day after entering the study until the day of viral total RNA clearance, as measured by reverse transcription PCR (RT-PCR). Time to cessation of viral shedding was in order from shortest to longest: by viral culture, sgRNA RT-PCR, and total RNA RT-PCR. The median time (interquartile range) to negativity of viral culture, subgenomic N transcript, and N gene were 7 (5 to 9), 11 (9 to 16), and 18 (13 to 21) days, respectively (P < 0.001). Further analysis identified the receipt of steroid as the factors associated with longer duration of viral infectivity (hazard ratio, 3.28; 95% confidence interval, 1.02 to 10.61; P = 0.047). We propose the potential role of the detection of SARS-CoV-2 subgenomic RNA as the surrogate marker of viral infectivity. Patients with negative subgenomic N RNA RT-PCR could be considered for ending isolation. IMPORTANCE Our study, combined with existing evidence, suggests the feasibility of the use of subgenomic RNA RT-PCR as a surrogate marker for SARS-CoV-2 infectivity. The kinetics of SARS-CoV-2 subgenomic RNA should be further investigated in immunocompromised patients.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).

Short-Term Immunogenicity Profiles and Predictors for Suboptimal Immune Responses in Patients with End-Stage Kidney Disease Immunized with Inactivated SARS-CoV-2 Vaccine.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored. METHODS: We conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls. RESULTS: After two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses. CONCLUSIONS: Patients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).

Thailand's national strategic plan on antimicrobial resistance: progress and challenges.

Antimicrobial resistance is a serious threat that affects all countries. The Global Action Plan on antimicrobial resistance and the United Nations Political Declaration on antimicrobial resistance set standards for countries to resolve antimicrobial resistance challenges under the One Health approach. We assess progress and challenges in implementing Thailand's national strategic plan on antimicrobial resistance 2017-2022, discuss interim outcomes and share lessons learnt. Major progress includes: establishing a national governance mechanism that leads high-impact policy on antimicrobial resistance and consolidates actions and multisectoral collaboration; creating a monitoring system and platform to track implementation of the strategic plan; and converting strategies of the strategic plan into actions such as controlling the distribution and use of antimicrobials in humans and animals. Interim results indicate that antimicrobial consumption in animals has nearly halved (exceeding the national goal of a 30% reduction) whereas other goals have not yet reached their targets. We have learnt that elevating antimicrobial resistance to high-level visibility and establishing a national governance mechanism is an important first step, and a monitoring and evaluation system should be developed in parallel with implementation. Securing funds is crucial. Policy coherence is needed to avoid duplication of actions. Highly ambitious goals, although yet to be achieved, can advance actions beyond expectations. Political commitment and collaboration across different sectors will continue to play important roles but might not be sustained without a well-designed governance structure to support long-term actions to address antimicrobial resistance.

La résistance aux antimicrobiens fait peser une sérieuse menace sur la planète tout entière. Le Plan d'action mondial pour combattre la résistance aux antimicrobiens ainsi que la Déclaration politique des Nations Unies sur la résistance aux agents antimicrobiens ont défini des normes pour les pays, afin qu'ils puissent faire face aux enjeux liés à la résistance aux antimicrobiens selon l'approche «One Health¼. Nous avons évalué les progrès et défis de la mise en œuvre du plan stratégique national de la Thaïlande en la matière pour 2017­2022, mais aussi discuté des résultats provisoires et partagé les enseignements tirés. Parmi les principaux progrès accomplis figurent l'établissement d'un mécanisme de gouvernance national pour mener une politique à impact élevé sur la résistance aux antimicrobiens, renforcer les actions et favoriser la collaboration intersectorielle; la création d'un système de surveillance et d'une plateforme pour suivre la mise en œuvre du plan stratégique; et enfin, la conversion des stratégies du plan en actions telles que le contrôle de la distribution et de l'usage des antimicrobiens chez les humains et les animaux. Les résultats provisoires indiquent que la consommation d'antimicrobiens chez les animaux a diminué de moitié (ce qui est supérieur à l'objectif national d'une réduction de 30%), tandis que les autres objectifs n'ont pas encore été atteints. Nous avons constaté qu'accroître la visibilité de la résistance aux antimicrobiens et instaurer un mécanisme de gouvernance national constituaient des étapes cruciales, et qu'un système de surveillance et d'évaluation devait être développé parallèlement à la mise en œuvre. L'obtention de financements est elle aussi essentielle. Une politique cohérente est nécessaire pour éviter de multiplier les actions similaires. Fixer des objectifs très ambitieux, même s'ils ne sont pas encore atteints, permet en outre de faire progresser les actions au-delà des attentes. Enfin, l'engagement politique et la collaboration entre différents secteurs continueront à jouer un rôle prépondérant, mais ne pourront peut-être pas se poursuivre sans une structure de gouvernance bien conçue, capable de soutenir des actions à long terme visant à remédier à la résistance aux antimicrobiens.

La resistencia a los antimicrobianos es una grave amenaza que afecta a todos los países. El Plan de Acción Mundial sobre la resistencia a los antimicrobianos y la Declaración Política de las Naciones Unidas sobre la resistencia a los antimicrobianos establecen normas para que los países resuelvan los problemas de resistencia a los antimicrobianos en el marco del enfoque «Una única salud¼. Evaluamos los avances y los desafíos en la aplicación del plan estratégico nacional de Tailandia sobre la resistencia a los antimicrobianos 2017-2022, analizamos los resultados provisionales y compartimos las lecciones aprendidas. Entre los principales avances se encuentran: el establecimiento de un mecanismo de gobernanza nacional que lidera la política de alto impacto sobre la resistencia a los antimicrobianos y consolida las acciones y la colaboración multisectorial; la creación de un sistema de seguimiento y una plataforma para seguir la aplicación del plan estratégico; y la conversión de las estrategias del plan estratégico en acciones como el control de la distribución y el uso de antimicrobianos en humanos y animales. Los resultados provisionales indican que el consumo de antimicrobianos en animales se ha reducido casi a la mitad (superando el objetivo nacional de una reducción del 30 %), mientras que otros objetivos aún no han alcanzado sus metas. Hemos aprendido que elevar la resistencia a los antimicrobianos a una visibilidad de alto nivel y establecer un mecanismo de gobernanza nacional es un primer paso importante, y que debe desarrollarse un sistema de seguimiento y evaluación en paralelo a la implementación. Asegurar los fondos es crucial. La coherencia política es necesaria para evitar la duplicación de acciones. Unos objetivos muy ambiciosos, aunque todavía no se hayan alcanzado, pueden hacer avanzar las acciones más allá de las expectativas. El compromiso político y la colaboración entre los distintos sectores seguirán desempeñando un papel importante, pero podrían no mantenerse sin una estructura de gobernanza bien diseñada que apoye las acciones a largo plazo para hacer frente a la resistencia a los antimicrobianos.

Perceived roles and barriers to nurses' engagement in antimicrobial stewardship: A Thai qualitative case study.

BACKGROUND: Antimicrobial stewardship is the practice of ensuring the optimal use of antibiotics to prevent antimicrobial resistance. A multidisciplinary approach is considered best practice; however, little is known about nurses' contribution. OBJECTIVES: To explore how organisational multidisciplinary leaders and clinical nurses perceive nurses' roles in AMS in a single organisational site case study based in Thailand, within the current governance, educational and practice context, and the barriers to nurses' engagement in AMS. METHODS: A qualitative descriptive study using thematic analysis approach was conducted in a 1000-bed university hospital in Bangkok, Thailand. The combined number of organisational leaders and nurses was 33 including 15 individual organisational leader interviews and three focus groups involving 18 nurses. RESULTS: Nurses currently participate in AMS by supporting system processes, monitoring safety and optimal antibiotic use and patient education. A lack of clear articulation of nurses' role and traditional professional hierarchies limits active participation. Inconsistent engagement was perceived as due to a failure to prioritise AMS activities, a lack of formal policies and a need for further education. CONCLUSION: Nurses do engage in AMS but there are significant governance, hierarchical and educational impediments. These gaps need to be addressed before clearly defined nurse roles in AMS can be developed and embedded into clinical practice.

Microbial epidemiology and risk factors for relapse in gram-negative bacteria catheter-related bloodstream infection with a pilot prospective study in patients with catheter removal receiving short-duration of antibiotic therapy.

BACKGROUND: Infectious Diseases Society of America (IDSA) guidelines suggest 7-14 days' duration of antibiotic treatment for uncomplicated Gram-negative bacteria (GNB) catheter-related bloodstream infection (CRBSI). The objectives of this study were to review microbial epidemiology, to determine rate and risk factors for relapse, and to compare clinical outcomes in patients receiving long- versus short-duration antibiotic therapy. METHODS: A retrospective phase 1 study was conducted between January 2010 and October 2016 to review microbial epidemiology and to determine the incidence of and risk factors for relapse in patients with GNB CRBSI, according to the IDSA guidelines diagnostic criteria. In phase 2 of the study, patients without risk factors for relapse between November 2016 and October 2017 were prospectively recruited to receive antibiotic therapy for 7 days after catheter removal. Matched patients from the retrospective phase 1 study who had received antibiotic therapy for ≥14 days were selected as a phase 2 control group to compare outcomes. RESULTS: In phase 1, three most common pathogens identified among 174 cases were Pseudomonas aeruginosa (22.0%), Klebsiella pneumoniae (16.7%), and Stenotrophomonas maltophilia (13.4%). Eighty-nine episodes of infection occurred while patients were receiving antibiotic therapy. Of 140 cases, the relapse rate was 6.4%. Catheter retention was the only risk factor strongly associated with relapse (odds ratio = 145.32; 95% confidence interval 12.66-1667.37, P < 0.001). In phase 2, 11 patients with catheter removal were prospectively recruited to receive short-duration therapy. The number of patients with relapse receiving long- or short-duration therapy was 1 (3%) and 0 (0%), respectively (P = 1.000). CONCLUSIONS: For the management of patients with uncomplicated GNB CRBSI, empiric broad-spectrum antibiotic therapy with adequate coverage of P. aeruginosa should be chosen. Catheter removal should be performed to prevent relapse and shortening the duration of treatment could be considered. TRIAL REGISTRATION: Thai Clinical Trial Registry: TCTR20190914001 . Retrospectively registered on 13 September 2019.

Impact of an Antibiotic Stewardship Program on Antibiotic Prescription for Acute Respiratory Tract Infections in Children: A Prospective Before-After Study.

We assessed the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescriptions for acute respiratory tract infection (ARTI) in a medical school. Our ASP included delivering an antibiotic use guideline via e-mail and LINE (an instant messaging app) to faculty staff, fellows, and residents, and posting of the guideline in examination rooms. Medical records of pediatric patients diagnosed with ARTI were reviewed to assess the appropriateness of antibiotic prescription. ASP could increase the rate of appropriateness from 78% (1979 out of 2553 visits) to 83.4% (2449 out of 2935 visits; P < .001). The baseline of appropriateness was higher in residents (95%) compared with fellows (82%) and faculty staff (75%). The ASP significantly increased the appropriateness only in faculty staff, especially in semiprivate clinics (75% to 83%, P < .001). In conclusion, our ASP increased appropriateness of antibiotic prescriptions for ARTI, with the greatest impact among faculty staff in semiprivate clinics.

Rapid screening and early precautions for carbapenem-resistant Acinetobacter baumannii carriers decreased nosocomial transmission in hospital settings: a quasi-experimental study.

Background: Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods: A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results: A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P < 0.02). The calculated hazard ratio of CRAB transmission was 0.65 (95% confidence interval [CI], 0.44-0.97). Risk factors for CRAB acquisition included exposure to carbapenem (hazard ratio, 2.54 [95% CI: 1.61-5.57]). Conclusions: LAMP screening for CRAB upon ICU admission proved feasible for routine clinical practice. Rapid screening using LAMP followed by early intervention may reduce CRAB transmission rates in ICUs when compared to conventional intervention.

PCR-Dipstick-Oriented Surveillance and Characterization of mcr-1- and Carbapenemase-Carrying Enterobacteriaceae in a Thai Hospital.

Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types-IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.

Excess annual economic burdens from nosocomial infections caused by multi-drug resistant bacteria in Thailand.

Background - Antimicrobial resistance (AMR) is a major health threat worldwide as it brings about poorer outcomes and places economic burdens to society. This study aims to estimate the economic burdens from nosocomial infections (NI) caused by multi-drug resistant (MDR) bacteria in Thailand. Research design and methods - A retrospective cohort study was conducted at a tertiary hospital over 2011-2012. A multivariate log-linear regression model was used to estimate the excess treatment costs of AMR to those non-AMR patients. Results - Switching from a non-AMR case to an AMR infection case, resulted in 42% increase in expected average treatment costs per patient. The annual treatment from hospital perspective and antibiotic costs associated with the management of AMR infections were estimated to be US$ 2.3 billion and US$ 262 million, respectively. The estimated annual benefit from eradicating AMR NI were US$ 4.2 billion from a societal perspective with the annual gains in quality-adjusted life years (QALYs) of 0.6 million due to the absence of 111,295 AMR cases each year. Conclusions - Large amount of money was spent on treatment and antibiotic costs to manage AMR infections. Benefit of eliminating these infections was estimated and it would be highly cost-effective.

Correlation between antimicrobial consumption and the prevalence of carbapenem-resistant Escherichia coli and carbapenem-resistant Klebsiella pneumoniae at a university hospital in Thailand.

WHAT IS KNOWN AND OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) are virulent gram-negative bacilli and cause urgent healthcare problems worldwide. One of the main factors leading to the emergence of CRE is antimicrobial consumption. The objective of this study was to assess how closely the rate of antimicrobial consumption and the prevalences of carbapenem-resistant Escherichia coli (CR-EC) and carbapenem-resistant Klebsiella pneumoniae (CR-KP) are correlated. METHODS: A retrospective study was performed at a university hospital in Thailand from January 2013 to September 2016. The prevalence of E coli and K pneumoniae was represented as percentages per species per quarter. The antimicrobial consumption rate per quarter was expressed as the defined daily dose (DDD)/1000 patient-days. Evaluation of the relationships between the rate of antimicrobial consumption and the prevalences of CR-EC and CR-KP was conducted via Pearson's or Spearman's correlation analyses. RESULTS AND DISCUSSION: During the study period, the prevalence of CR-EC and CR-KP was less than 6%; however, significantly increasing prevalences were reported for both CR-EC (r = 0.55, P = 0.03) and CR-KP (r = 0.87, P < 0.01). There was a significant increasing trend in the consumption of meropenem (r = 0.65, P = 0.01), levofloxacin (r = 0.63, P = 0.01), ceftriaxone (r = 0.55, P = 0.03), ertapenem (r = 0.52, P = 0.05) and the carbapenem group (r = 0.64, P = 0.01). A significant correlation was observed between CR-KP prevalence and total carbapenem consumption (r = 0.55, P = 0.04). Moreover, levofloxacin consumption had a significant positive relationship with the prevalence of CR-KP (r = 0.65, P = 0.01). No positive correlation was found with the prevalence of CR-EC. WHAT IS NEW AND CONCLUSION: The rate of consumption of levofloxacin and carbapenems was the important key factor correlated with the rate of emergence of CR-KP. This is the first report demonstrating the correlation between levofloxacin consumption and CR-KP prevalence.

Incidence of Newly Diagnosed Tuberculosis among Healthcare Workers in a Teaching Hospital, Thailand.

BACKGROUND: Data on the incidence of new onset tuberculosis (TB) infection among healthcare workers (HCWs) in Thailand was scarce and not current. OBJECTIVES: To determine the incidence of TB, as well as the impact of TB on HCWs in a teaching hospital in Bangkok, Thailand. METHODS: A time series cross-sectional study was conducted at Ramathibodi Hospital, Bangkok, Thailand. It was a teaching hospital with 9,562 employees. Medical records of personnel with TB infection between October 1st, 2010 and September 30th, 2015 were reviewed to determine the newly diagnosed TB infection. The personnel who were treated in fiscal year 2015 were interviewed about work-related issues, health status and the impact of TB. FINDINGS: In five years, 109 personnel were diagnosed with new onset TB disease. The infection rates were 2.04, 1.97, 2.85, 2.53, and 1.35 per 1,000 persons in 2011, 2012, 2013, 2014, and 2015, respectively. The most prevalent type of TB infection was pulmonary TB. The infection rate in males was higher than in females. Pharmacists had the highest proportion of infected personnel. The second highest rate of infection was in support staff related to patient care. Twenty personnel were interviewed. Most of them worked in patient care units with central-type air-conditioning system without negative-pressure rooms for TB patients. Contracting TB had an impact on productivity at work, health (physically, mentally and socially) and incomes. CONCLUSIONS: Ramathibodi HCWs had higher rate of TB infection than the general Thai population, but the incidence was noted to be decreasing from 2013 to 2015. HCWs suffered from the impact of TB on their lives in multiple ways. Due to the adverse impact of TB on the health and welfare of its employees, hospital administration should apply effective preventive measures and develop a compensation system for HCWs infected with TB.