Completed genome and emergence scenario of the multidrug-resistant nosocomial pathogen Staphylococcus epidermidis ST215.

BACKGROUND: A multidrug-resistant lineage of Staphylococcus epidermidis named ST215 is a common cause of prosthetic joint infections and other deep surgical site infections in Northern Europe, but is not present elsewhere. The increasing resistance among S. epidermidis strains is a global concern. We used whole-genome sequencing to characterize ST215 from healthcare settings. RESULTS: We completed the genome of a ST215 isolate from a Swedish hospital using short and long reads, resulting in a circular 2,676,787 bp chromosome and a 2,326 bp plasmid. The new ST215 genome was placed in phylogenetic context using 1,361 finished public S. epidermidis reference genomes. We generated 10 additional short-read ST215 genomes and 11 short-read genomes of ST2, which is another common multidrug-resistant lineage at the same hospital. We studied recombination's role in the evolution of ST2 and ST215, and found multiple recombination events averaging 30-50 kb. By comparing the results of antimicrobial susceptibility testing for 31 antimicrobial drugs with the genome content encoding antimicrobial resistance in the ST215 and ST2 isolates, we found highly similar resistance traits between the isolates, with 22 resistance genes being shared between all the ST215 and ST2 genomes. The ST215 genome contained 29 genes that were historically identified as virulence genes of S. epidermidis ST2. We established that in the nucleotide sequence stretches identified as recombination events, virulence genes were overrepresented in ST215, while antibiotic resistance genes were overrepresented in ST2. CONCLUSIONS: This study features the extensive antibiotic resistance and virulence gene content in ST215 genomes. ST215 and ST2 lineages have similarly evolved, acquiring resistance and virulence through genomic recombination. The results highlight the threat of new multidrug-resistant S. epidermidis lineages emerging in healthcare settings.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

[Precision medicine in infectious diseases]. / Präzisionsmedizin in der Infektiologie.

Infectious medicine faces a variety of challenges, such as the increase in antibiotic resistance and the emergence and spread of infectious diseases fueled by climate change and globalization. Precision medicine can provide solutions to many of these challenges. Since an untargeted request for diagnostic tests can lead to test results without clinical relevance, which can increase the use of non-indicated antibiotics, the principle aimed at is: targeted diagnostics (the right test) and consideration of patient characteristics (the right person) to optimize management (the right action). At the same time, one must always decide whether empirical therapy must be immediately initiated, even if the results of the initiated diagnostics are not yet available. In addition, many new diagnostics as well as therapies have recently been developed for the rapid detection and more specific treatment of bacterial infections. Molecular genetic methods, which offer more rapid results than classical bacterial cultures, are gaining ground as new diagnostics. New therapeutics such as bacteriophages, antibodies or antibacterial peptides allow increasingly precise treatment of certain bacterial infections. Precision medicine will also play an increasingly important role in infectious medicine in the future.

Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure （ACLF） and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1， 2010 to December 31， 2021， and according to the drug susceptibility results， the patients were divided into multidrug-resistant （MDR） bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic （ROC） curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection， sputum （27.7%） was the most common specimen for detection， followed by blood （24.6%）， urine （18.5%）， and ascites （17.7%）. Bacterial infections were dominated by Gram-negative bacteria （58.5%）. Of all bacteria， Escherichia coli （18.5%）， Klebsiella pneumoniae （14.6%）， and Enterococcus faecium （13.8%） were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin （72.2%）， penicillin （57.4%）， ampicillin （55.6%）， and ciprofloxacin （53.7%）， while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin （73.3%）， cefazolin （50.0%）， and cefepime （47.4%）. The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection （61.5%）. Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection， the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase （Z=2.089， P=0.037）， aspartate aminotransferase （Z=2.063， P=0.039）， white blood cell count （Z=2.207， P=0.027）， and monocyte count （Z=4.413， P<0.001）. The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection （odds ratio=7.120， 95% confidence interval ［CI］： 2.478‍ ‍—‍ ‍20.456，P<0.001） and had an area under the ROC curve of 0.686 （95%CI： 0.597‍ ‍—‍ ‍0.776） in predicting ACLF with MDR bacterial infection（P<0.001）， with the optimal cut-off value of 0.50×109/L， a sensitivity of 0.725， and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria， with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.

Drug-resistant tuberculosis in Colombia, 2013-2018: Case-control study

Abtract Introduction. Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult to control, has high morbidity and mortality, and demands priority public health intervention. In Colombia, MDR/RR-TB has been becoming more widespread annually. Before the COVID-19 pandemic, over an 8-year period, the number of cases of multidrug-resistant tuberculosis in Colombia was close to a thousand cases. Timely identification of the different risk factors for MDR/RR-TB will contribute fundamentally to the systematic management. Objective. To determine which risk factors were associated with the presentation of MDR in Colombia between 2013 and 2018. Materials and methods. A retrospective case-control study was carried out, for which the data from the routine surveillance of MDR/events in the country were used. Results. The cases of multidrug-resistant tuberculosis were mainly in young people, Afrodescendants, and males. Of the clinical conditions, comorbidities such as malnutrition, diabetes, and HIV, presence of at least one factor, such as drug dependence, taking immunosuppressive medications, belonging to the black race, afro, and living in an area of high disease burden were risk factors. Conclusion. In addition to the diagnosis and timely provision of MDR-TB treatment, it is necessary that public health programs at the local level pay special attention to patients with the identified risk factors.

Introducción. La tuberculosis multirresistente-resistente a la rifampicina (TB-MDR/RR) es difícil de controlar, tiene una alta morbilidad y mortalidad y exige una intervención prioritaria en salud pública. En Colombia, la TB-MDR/RR se ha ido extendiendo cada año. Antes de la pandemia de COVID-19, en un periodo de 8 años, el número de casos de TB-MDR/RR en Colombia se acercaba a los mil. La identificación oportuna de los diferentes factores de riesgo de TB-MDR/RR contribuirá de manera fundamental al manejo sistemático de la enfermedad. Objetivo. Determinar los factores de riesgo que se asociaron a la presentación de la TB- MDR/RR en Colombia entre 2013 y 2018. Materiales y métodos. Se realizó un estudio retrospectivo de casos y controles, para el cual se utilizaron los datos de la vigilancia rutinaria de eventos de TB MDR/RR en el país. Resultados. Los casos de TB MDR se presentaron principalmente en jóvenes, afrodescendientes y varones. De las condiciones clínicas, fueron factores de riesgo las comorbilidades como la desnutrición, la diabetes y el VIH, y la presencia de, al menos, un factor como la farmacodependencia, el consumo de medicamentos inmunosupresores, el ser de raza negra o afro y el vivir en una zona del país de alta carga de tuberculosis. Conclusiones. Además del diagnóstico y la provisión oportuna del tratamiento de la TB MDR, es necesario que los programas de salud pública a nivel local presten especial atención a los pacientes con los factores de riesgo identificados.

Empiric Anti-Pseudomonal ß-Lactam Monotherapy Versus Fluoroquinolone Combination Therapy in Patients With Hospital-Acquired Pneumonia: A Multicenter Cohort Study With Propensity Score Matching.

BACKGROUND: There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric anti-pseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. METHODS: This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019. Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem ß-lactam monotherapy and fluoroquinolone combination therapy groups. Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. RESULTS: In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286). There was no significant difference in 30-day mortality between the two groups (16.8% vs. 18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782-3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. CONCLUSION: Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to ß-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.

Respuesta de procalcitonina ante co-infección e infección secundaria por bacterias multirresistentes en pacientes COVID -19 / Procalcitonin response in co-infection and secondary infection by multidrug resistant bacteria in COVID -19 patients

INTRODUCCIÓN. La procalcitonina, es un biomarcador que puede usarse como apoyo diagnóstico en infecciones bacterianas y la monitorización del tratamiento antibiótico, sobre todo en pacientes con sepsis. De ahí que, fue utilizado durante la pandemia COVID-19 OBJETIVO. Determinar los valores de procalcitonina en pacientes con COVID-19 y definir una p osible correlación entre su incremento y vinculación en coinfección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa con multidrogo resistencia y resistencia extendida a los antibióticos. MATERIALES Y MÉTODOS. Estudio retrospectivo observacional, descriptivo transversal, realizado del 1 de mayo al 31 de octubre del 2020 en el Hospital de Especialidades Carlos Andrade Marín sobre 7028 pacientes adultos, hospitalizados, con diagnóstico de COVID-19, y resultados de procalcitonina, cuyas muestras de secreción traqueal y/o hemocultivo presentaron desarrollo de Klebsiella pneumoniae y Pseudomonas aeruginosa. Su análisis estadístico fue desarrollado mediante la prueba Chi Cuadrado de Pearson. RESULTADOS. Se recibieron 861 muestras de hemocultivo y 391 de secreción traqueal, obteniéndose: 32% aislamientos de Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente. Entre los pacientes COVID-19 que fallecieron, 34,4% mostraron incrementos de procalcitonina. Al contrario, entre los pacientes que sobrevivieron sólo en 8,8% se observó incrementos de procalcitonina evidenciándose un vínculo entre el incremento de procalcitonina y mortalidad. CONCLUSIONES. No existe diferencia en relación al incremento en los valores de procalcitonina en pacientes COVID-19 con co-infección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente y los valores de procalcitonina en pacientes con coinfección e infección secundaria con otro tipo de aislamientos bacterianos.

INTRODUCTION. Procalcitonin is a biomarker that can be used as a diagnostic support in bacterial infections and the monitoring of antibiotic treatment, especially in patients with sepsis. Hence, it was used during the COVID-19 pandemic OBJECTIVE. To determine the values of procalcitonin in patients with COVID-19 and to define a possible correlation between its increase and linkage in co-infection or secondary infection by Klebsiella pneumoniae and Pseudomonas aeruginosa with multidrug resistance and extended resistance to antibiotics. MATERIALS AND METHODS. Retrospective observational, descriptive cross-sectional study, conducted from May 1 to October 31, 2020 at the Hospital de Especialidades Carlos Andrade Marín on 7028 adult patients, hospitalized, with diagnosis of COVID-19, and procalcitonin results, whose tracheal secretion and/or blood culture samples presented development of Klebsiella pneumoniae and Pseudomonas aeruginosa. Their statistical analysis was developed using Pearson's Chi-squared test. RESULTS. We received 861 blood culture and 391 tracheal secretion samples, obtaining: 32% isolates of Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa. Among the COVID-19 patients who died, 34.4% showed increased procalcitonin levels. On the contrary, among patients who survived, only 8.8% showed increased procalcitonin levels, showing a link between increased procalcitonin levels and mortality. CONCLUSIONS. There is no difference in relation to the increase in procalcitonin values in COVID-19 patients with co-infection or secondary infection by Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa and procalcitonin values in patients with co-infection and secondary infection with other types of bacterial isolates.

Factores asociados a tuberculosis pre extensamente resistente en pacientes del Hospital Nacional Dos de Mayo, Lima, Perú / Factors associated with pre-extensively drug-resistant tuberculosis in patients at Dos de Mayo National Hospital, Lima - Perú

INTRODUCCIÓN: La resistencia a fármacos antituberculosos está influenciada por las características personales y las condiciones de salud de países en vías de desarrollo. OBJETIVO: Determinar los factores asociados a TB-pre extensamente resistente (TB-PRE XDR) en pacientes del Hospital Nacional Dos de Mayo (HNDM) entre 2017 y 2019. PACIENTES Y MÉTODO: Se desarrolló un estudio caso control no pareado, definiendo como caso al paciente con TB- PRE XDR y como control al paciente con TB-S. Se recolectaron variables epidemiológicas, clínicas y radiológicas. RESULTADOS: Se analizaron 51 casos y 102 controles. El análisis bivariado determinó como factores con p 51 años (OR: 0,17, IC95%: 0,05-0,51), uso de drogas (OR:2,5, IC95%: 1,1-5,4), antecedente de TB (OR: 20, IC95%: 8,4-47), reclusión previa (OR: 8, IC95%: 2,7-23,8), infección por VIH (OR: 0,2, IC95%: 0,08-1) y uso previo de fármacos antituberculosos (OR: 21, IC95%: 8,8-50). El análisis de regresión logística identificó como factores asociados a TB-PRE XDR al contacto de TB, antecedente de TB, tiempo de enfermedad y uso previo de fármacos antituberculosos. CONCLUSIÓN: Las medidas para limitar el desarrollo de TB-PRE XDR en pacientes con TB-S deben incidir sobre el antecedente de TB, contacto con TB, tiempo de enfermedad y uso previo de anti-TB no controlados; sin embargo, existen resultados no concluyentes sobre el hábito nocivo y la comorbilidad, siendo necesario más estudios para determinar su influencia como factores asociados identificables.

BACKGROUND: Resistance to anti-TB drugs is influenced by personal characteristics and health conditions in developing countries. AIM: To determine the factors associated with pre-extensively drug-resistant tuberculosis (PRE XDR-TB) at Hospital Nacional Dos de Mayo (HNDM) in patients between the 2017 and 2019. METHODS: An unpaired case control study was developed; defining as case PRE XDR-TB patient and as control S-TB patient. Epidemiological, clinical and radiological variables were collected. RESULTS: We analyzed 51 cases and 102 controls. The bivariate analysis showed as factors with p 51 years (OR: 0.17, 95% CI: 0.05-0.51), drug use (OR: 2.5, 95% CI: 1.1-5.4), previous history of TB (OR: 20, 95% CI: 8.4-47), previous confinement (OR: 8, 95% CI: 2.7-23.8), HIV infection (OR: 0.2, 95% CI: 0.08-1) and previous use of antiTB drugs (OR: 21, 95% CI: 8.8-50). The logistic regression analysis identified as associated factors with PRE XDR-TB the previous contact with TB, a history of TB, length of illness and previous use of tuberculosis antibiotics. CONCLUSION: The measures to limit the development of TB-PRE XDR in patients with TB-S must include the previous history of TB, TB contact, length of illness and previous use of uncontrolled antibiotics against TB; however, there are inconclusive results about the harmful habits and comorbidity, requiring more studies to determine their influence as identifiable associated factors.

Clinical efficacy of Buzhong Yiqi decoction in the treatment of hospital-acquired pneumonia with multi-drug resistant bacteria: a prospective, randomized, multicenter controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Buzhong Yiqi decoction (, BZYQ) in the treatment of hospital-acquired pneumonia (HAP) with multi-drug-resistant bacteria (MDRB). METHODS: This 28-day study was conducted at 5 clinical centers in Shanghai. The eligible patients were randomly assigned (1:1) into the intervention group (BZYQ plus conventional Western Medicine therapy) and control group (conventional Western Medicine therapy). The primary outcomes were the clinical response, clinical pulmonary infection score (CPIS), and microbiologic response. The secondary outcomes were the 28-day all-cause mortality (ACM), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, ventilator weaning rate, length of mechanical ventilation (MV), length of hospital stay, and changes of infection indicators. RESULTS: Altogether 83 subjects in the intervention group and 85 subjects in the control group were analyzed. The clinical success rate (48.2%) and the pathogen eradication rate (59.0%) of the intervention group were all better than those of the control group (32.9% and 38.9%, respectively) with statistically significant differences (<0.05). The CPIS score of the intervention group (8.9 ± 1.7) was lower than that of the control group (9.6 ± 2.5) (<0.05). The length of MV in the intervention group [(13.7 ± 6.4) d] was significantly shorter than that of the control group [ (17.2 ± 7.2) d] (<0.05). The 28-day ACM of the intervention group (13.33%) was lower than that of the control group (21.2%) with no statistically significant difference (>0.05). The differences between two groups in ventilator weaning rate, length of hospital stay, and APACHE Ⅱ score were not statistically significant (> 0.05). The intervention group displayed decreases in white blood cell count, C-reactive protein, neutrophil percentage, and procalcitonin at day 28 compared with baseline (<0.05). No serious adverse events occurred in either group during the 28-day follow-up. CONCLUSION: BZYQ may be an effective therapeutic option for the management of HAP with MDRB.

Reducing the duration of antibiotic therapy in surgical patients through a specific nationwide antimicrobial stewardship program. A prospective, interventional cohort study.

BACKGROUND: Guidelines recommend 5-7 days of antibiotic treatment in patients with surgical infection and adequate source control. This nationwide stewardship intervention aimed to reduce the duration of treatments in surgical patients to <7 days. METHODS: Prospective cohort study evaluating surgical patients receiving antibiotics ≥7 days in 32 hospitals. Indication for treatment, quality of source control, type of recommendations issued, and adherence to the recommendations were analysed. Temporal trends in the percentages of patients with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients. RESULTS: A total of 32 499 patients were included. Of these, 13.7% had treatments ≥7 days. In all, 3912 stewardship interventions were performed, primarily in general surgery (90.7%) and urology (8.1%). The main types of infection were intra-abdominal (73.4%), skin/soft tissues (9.8%) and urinary (9.2%). The septic focus was considered controlled in 59.9% of cases. Out of 5458 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (21.7%), metronidazole (11.2%), amoxicillin/clavulanate (10.3%), meropenem (10.7%), ceftriaxone (9.3%) and ciprofloxacin (6.7%). The main recommendations issued were: treatment discontinuation (35.0%), maintenance (40.0%) or de-escalation (15.5%), and the overall adherence rate was 91.5%. With adequate source control, the most frequent recommendation was to terminate treatment (51.2%). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (Pc=-0.69;P < 0.001). CONCLUSIONS: This stewardship programme reduced the duration of treatments in surgical departments. Preference was given to general surgery services, intra-abdominal infection, and beta-lactam antibiotics, including carbapenems. Adherence to the issued recommendations was high.

Decreasing Antibiotic Resistance Trends Nationally in Gram-Negative Bacteria Across United States Veterans Affairs Medical Centers, 2011-2020.

INTRODUCTION: Gram-negative resistance is a well-acknowledged public health threat. Surveillance data can be used to monitor resistance trends and identify strategies to mitigate their threat. The objective of this study was to assess antibiotic resistance trends in Gram-negative bacteria. METHODS: The first cultures of Pseudomonas aeruginosa, Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, and Serratia marcescens per hospitalized patient per month collected from 125 Veterans Affairs Medical Centers (VAMCs) between 2011 to 2020 were included. Time trends of resistance phenotypes (carbapenem, fluoroquinolone, extended-spectrum cephalosporin, multi-drug, and difficult-to-treat) were analyzed with Joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals and p values. A 2020 antibiogram of reported antibiotic percent susceptibilities was also created to evaluate resistance rates at the beginning of the COVID-19 pandemic. RESULTS: Among 40 antimicrobial resistance phenotype trends assessed in 494,593 Gram-negative isolates, there were no noted increases; significant decreases were observed in 87.5% (n = 35), including in all P. aeruginosa, Citrobacter, Klebsiella, M. morganii, and S. marcescens phenotypes (p < 0.05). The largest decreases were seen in carbapenem-resistant phenotypes of P. mirabilis, Klebsiella, and M. morganii (AAPCs: - 22.9%, - 20.7%, and - 20.6%, respectively). In 2020, percent susceptibility was over 80% for all organisms tested against aminoglycosides, cefepime, ertapenem, meropenem, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. CONCLUSION: We observed significant decreases in antibiotic resistance for P. aeruginosa and Enterobacterales over the past decade. According to the 2020 antibiogram, in vitro antimicrobial activity was observed for most treatment options. These results may be related to the robust infection control and antimicrobial stewardship programs instituted nationally among VAMCs.

Resistencia antimicrobiana, una pandemia silenciosa / Antimicrobial resistance, a silent pandemic / Resistência antimicrobiana, uma pandemia silenciosa

Introducción: la resistencia a los antimicrobianos ha sido una problemática creciente a nivel global, la problemática afecta no solo la salud de personas, animales y el ambiente en general, sino que ha generado impactos de índole productivo y comercial. Una de las estrategias para abordar esta problemática es el enfoque de una salud. Este enfoque destaca la participación multidisciplinaria para combatir la resistencia antimicrobiana; y es así que cada profesión o actividad laboral genera unas responsabilidades innatas para la profesión veterinaria. Los veterinarios tienen un rol fundamental para este propósito, ya que son ellos quienes integran la aplicabilidad de estrategias de promoción y prevención a nivel agropecuario, y de consolidación e interlocución entre los diferentes componentes del enfoque (animal, humano, ambiente) desde el ámbito de la salud pública veterinaria. Materiales y Método: se realizó una búsqueda de la literatura en diferentes bases de datos, con el objetivo de realizar una revisión actualizada sobre la resistencia antimicrobiana. Resultados: dentro de las principales estrategias se debería fomentar un uso adecuado y bajo prescripción de antimicrobianos en la producción animal. Promover buenas prácticas de higiene, bioseguridad y vacunación, facilitando un correcto diagnóstico de enfermedades infecciosas en animales. Discusión: la adopción de normas internacionales para el uso responsable de los antibióticos y las directrices establecidas por la Organización Mundial de la Salud y Organización de las Naciones Unidas para la Alimentación y la Agricultura, a través del Codex Alimentarius y la Organización Mundial de Sanidad Animal, son fundamentales para hacer frente al desafío que representa el problema de la resistencia a los antimicrobianos.

Introduction: Antimicrobial resistance has been a growing problem at a global level, affecting not only the health of people, animals and the environment in general, but it has also generated impacts of a productive and commercial nature. One of the strategies to address this problem is the one-health approach. This approach emphasizes multidisciplinary participation to combat antimicrobial resistance; and thus, each profession or work activity generates innate responsibilities for the veterinary profession. Veterinarians have a fundamental role for this purpose, since they are the ones who integrate the applicability of promotion and prevention strategies at the agricultural level, and of consolidation and interlocution between the different components of the approach (animal, human, environment) from the field of veterinary public health. Materials and Method: a literature search was carried out in different databases, with the aim of carrying out an updated review on antimicrobial resistance. Results: one of the main strategies should be to promote an adequate use and under prescription of antimicrobials in animal production. Promote good hygiene, biosecurity and vaccination practices, facilitating a correct diagnosis of infectious diseases in animals. Discussion: the adoption of international standards for the responsible use of antibiotics and the guidelines established by the World Health Organization and the Food and Agriculture Organization of the United Nations, through Codex Alimentarius and the World Organization for Animal Health, are fundamental to face the challenge posed by the problem of antimicrobial resistance.

Introdução: A resistência antimicrobiana tem sido um problema crescente em todo o mundo, afetando não apenas a saúde dos seres humanos, dos animais e do meio ambiente em geral, mas também causando impactos na produção e no comércio. Uma das estratégias para lidar com esse problema é a abordagem One Health. Essa abordagem enfatiza o envolvimento multidisciplinar no combate à resistência antimicrobiana, com cada profissão ou atividade de trabalho gerando responsabilidades inatas à profissão veterinária. Os veterinários têm um papel fundamental nesse sentido, pois são eles que integram a aplicabilidade das estratégias de promoção e prevenção em nível agropecuário e de consolidação e interlocução entre os diferentes componentes da abordagem (animal, humano, ambiental) do campo da saúde pública veterinária. Materiais e Métodos: foi realizada uma pesquisa bibliográfica em diferentes bases de dados, com o objetivo de realizar uma revisão atualizada sobre a resistência antimicrobiana. Resultados: uma das principais estratégias deve ser a promoção do uso adequado e com baixa prescrição de antimicrobianos na produção animal. Promover boas práticas de higiene, biossegurança e vacinação, facilitando o diagnóstico correto de doenças infecciosas em animais. Discussão: A adoção de padrões internacionais para o uso responsável de antibióticos e as diretrizes estabelecidas pela Organização Mundial da Saúde e pela Organização das Nações Unidas para Agricultura e Alimentação, por meio do Codex Alimentarius e da Organização Mundial de Saúde Animal, são essenciais para enfrentar o desafio representado pelo problema da resistência antimicrobiana.

Multidrug-resistant Salmonella spp. in fecal samples of pigs with suspected salmonellosis in Antioquia, Colombia, 2019-2021.

Objectives: To determine the proportion of Salmonella enterica in fecal samples of live pigs with suspected salmonellosis analyzed at the diagnostic unit of the University of Antioquia, Colombia between 2019 and 2021, and examine the serotypes and antimicrobial resistance patterns. Methods: This was a laboratory-based cross-sectional study of routine data on fecal samples received from pig farms in all nine subregions of Antioquia state, Colombia. Salmonella spp. detection at the university is done using enrichment, selective culture, and polymerase chain reaction. Serotypes were identified using the Kauffmann-White scheme and isolates were tested for antimicrobial susceptibility using broth microdilution. Results: Of 653 samples tested, 149 (23%) were positive for S. enterica. Nine serotypes were identified. The most common were Salmonella Typhimurium (56%) and its monophasic variant (35%). Resistance to ampicillin (70%) was most frequently observed, followed by ciprofloxacin (55%), and sulfamethoxazole-trimethoprim (52%). No isolates were resistant to amikacin and gentamicin. Multidrug resistance (resistance to ≥ 3 classes of antibiotics) was observed in 61 (44%) isolates. Multidrug resistance was highest in S. Typhimurium (57%) compared with the other serotypes. Serotype was associated with multidrug resistance (p = 0.01), but age of the pig and sub-region were not. Conclusions: The proportion of Salmonella spp. and the associated high levels of multidrug resistance are of concern and may indicate irrational use of antimicrobials and poor management practices in pig production systems in the region. Strengthened surveillance is needed to monitor and improve farm management practices and the use of antimicrobials in farms in Colombia.

Risk factors for hospital mortality in intensive care unit survivors: a retrospective cohort study.

BACKGROUND: Deaths can occur after a patient has survived treatment for a serious illness in an intensive care unit (ICU). Mortality rates after leaving the ICU can be considered indicators of health care quality. This study aims to describe risk factors and mortality of surviving patients discharged from an ICU in a university hospital. METHODS: Retrospective cohort study carried out from January 2017 to December 2018. Data on age, sex, length of hospital stay, diagnosis on admission to the ICU, hospital discharge outcome, presence of infection, and Simplified Acute Physiology Score (SAPS) III prognostic score were collected. Infected patients were considered as those being treated for an infection on discharge from the ICU. Patients were divided into survivors and non-survivors on leaving the hospital. The association between the studied variables was performed using the logistic regression model. RESULTS: A total of 1,025 patients who survived hospitalization in the ICU were analyzed, of which 212 (20.7%) died after leaving the ICU. When separating the groups of survivors and non-survivors according to hospital outcome, the median age was higher among non-survivors. Longer hospital stays and higher SAPS III values were observed among non-survivors. In the logistic regression, the variables age, length of hospital stay, SAPS III, presence of infection, and readmission to the ICU were associated with hospital mortality. CONCLUSIONS: Infection on ICU discharge, ICU readmission, age, length of hospital stay, and SAPS III increased risk of death in ICU survivors.

Antibiogram of Multidrug-Resistant Bacteria Based on Sepsis Onset Location in Korea: A Multicenter Cohort Study.

BACKGROUND: Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea. METHODS: We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 university-affiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed. RESULTS: MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-term-care hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR gram-positive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15-1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%). CONCLUSION: Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospital-acquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.

Colonization with multidrug-resistant organisms is associated with impaired survival of patients with surgically resected cholangiocarcinoma.

BACKGROUND & AIMS: Colonization with multidrug-resistant organisms (MDRO) has been shown to impair survival in patients with various malignancies. Despite the increasing spread of MDRO, its impact on patients with cholangiocarcinoma (CCA) is unclear. Aim of this study was to analyse the impact of MDRO-colonization on overall prognosis in CCA patients. METHODS: All patients with surgically resected CCA diagnosed between August 2005 and November 2021 at the University Hospital Frankfurt were screened for MDRO. CCA patients with a positive MDRO screening before or within the first 90 days after diagnosis of CCA were defined as colonized. Patients with a negative MDRO screening were defined as non-colonized. RESULTS: Hundred and sixty nine patients were included. 32% (n = 54) were screened MDRO positive, while 68% (115) were non-colonized. Median overall survival (OS) for colonized patients was 17.1 months (95% CI = 9-25.2 months) compared to 50 months (95% CI = 37.1-62.8) for MDRO-negative patients (p ≤ .001). Non-cancer-related mortality (p ≤ .001) and infectious-related death (p ≤ .001) was significantly higher in the MDRO-colonized group. In multivariate analysis, MDRO colonization (HR = 2.1, 95% CI = 1.4-3.3, p = .001), ECOG 1 (HR = 2.5, 95% CI = 1.6-4, p ≤ .001) and N1 status (HR = 1.7, 95% CI = 1.1-2.6, p = .017) were independent risk factors for OS. CONCLUSION: MDRO-colonization contributes to poor survival in patients with surgically resected CCA. MDRO surveillance is necessary to optimize clinical management of infections and to potentially reduce mortality in this critical population.

Multidrug-resistant Salmonella spp. in fecal samples of pigs with suspected salmonellosis in Antioquia, Colombia, 2019-2021 / Salmonella spp. multirresistentes en muestras fecales de cerdos con presunta salmonelosis en Antioquia, Colombia, 2019-2021 / Salmonella spp. multirresistente em amostras fecais de suínos com suspeita de salmonelose em Antioquia, Colômbia, 2019-2021

ABSTRACT Objectives. To determine the proportion of Salmonella enterica in fecal samples of live pigs with suspected salmonellosis analyzed at the diagnostic unit of the University of Antioquia, Colombia between 2019 and 2021, and examine the serotypes and antimicrobial resistance patterns. Methods. This was a laboratory-based cross-sectional study of routine data on fecal samples received from pig farms in all nine subregions of Antioquia state, Colombia. Salmonella spp. detection at the university is done using enrichment, selective culture, and polymerase chain reaction. Serotypes were identified using the Kauffmann-White scheme and isolates were tested for antimicrobial susceptibility using broth microdilution. Results. Of 653 samples tested, 149 (23%) were positive for S. enterica. Nine serotypes were identified. The most common were Salmonella Typhimurium (56%) and its monophasic variant (35%). Resistance to ampicillin (70%) was most frequently observed, followed by ciprofloxacin (55%), and sulfamethoxazole-trimethoprim (52%). No isolates were resistant to amikacin and gentamicin. Multidrug resistance (resistance to ≥ 3 classes of antibiotics) was observed in 61 (44%) isolates. Multidrug resistance was highest in S. Typhimurium (57%) compared with the other serotypes. Serotype was associated with multidrug resistance (p = 0.01), but age of the pig and sub-region were not. Conclusions. The proportion of Salmonella spp. and the associated high levels of multidrug resistance are of concern and may indicate irrational use of antimicrobials and poor management practices in pig production systems in the region. Strengthened surveillance is needed to monitor and improve farm management practices and the use of antimicrobials in farms in Colombia.

RESUMEN Objetivos. Determinar la proporción de Salmonella enterica en muestras fecales de cerdos vivos con presunta salmonelosis analizadas en la unidad de diagnóstico de la Universidad de Antioquia (Colombia) entre el 2019 y el 2021, así como examinar los serotipos y los patrones de resistencia a los antimicrobianos. Métodos. Se trata de un estudio transversal de laboratorio sobre datos ordinarios de muestras fecales provenientes de granjas porcinas de las nueve subregiones del departamento de Antioquia (Colombia). La detección de Salmonella spp. en la universidad se realiza mediante el enriquecimiento, el cultivo selectivo y la reacción en cadena de la polimerasa. Se identificaron los serotipos con el esquema de Kauffmann-White y se examinaron las cepas aisladas para determinar la susceptibilidad antimicrobiana mediante microdilución en caldo. Resultados. De las 653 muestras analizadas, 149 (23%) dieron un resultado positivo para S. enterica. Se identificaron nueve serotipos. Los más comunes fueron Salmonella typhimurium (56%) y su variante monofásica (35%). La resistencia a la ampicilina fue la observada con mayor frecuencia (70%), seguida de la resistencia al ciprofloxacino (55%) y al sulfametoxazol-trimetoprima (52%). Ninguna cepa aislada fue resistente a la amikacina y la gentamicina. Se observó resistencia a múltiples fármacos (resistencia a tres o más clases de antibióticos) en 61 cepas (44%). La resistencia a múltiples fármacos fue más elevada en el caso de S. typhimurium (57%) en comparación con los otros serotipos. Se asoció el serotipo con la resistencia a múltiples fármacos (p = 0,01), a diferencia de la edad del cerdo y la subregión. Conclusiones. La proporción de Salmonella spp. y los elevados niveles asociados de resistencia a múltiples fármacos son preocupantes y pueden ser un indicativo de uso irracional de antimicrobianos y malas prácticas de gestión en los sistemas de producción porcina de la región. Es necesario reforzar la vigilancia para dar seguimiento y mejorar las prácticas de gestión agropecuaria y el uso de antimicrobianos en las granjas en Colombia.

RESUMO Objetivos. Determinar a proporção de Salmonella enterica em amostras de fezes de suínos vivos com suspeita de salmonelose analisadas na unidade de diagnóstico da Universidade de Antioquia, Colômbia, entre 2019 e 2021, e examinar seus sorotipos e padrões de resistência a antimicrobianos. Métodos. Estudo transversal, de base laboratorial, utilizando dados de rotina de amostras de fezes recebidas de suinocultores em todas as nove sub-regiões do estado de Antioquia, Colômbia. A detecção de Salmonella spp. na Universidade é feita por enriquecimento, cultura seletiva e reação em cadeia da polimerase. Os sorotipos foram identificados usando o esquema de Kauffmann-White, e os isolados foram testados quanto à suscetibilidade aos antimicrobianos pelo método de microdiluição em caldo. Resultados. Das 653 amostras testadas, 149 (23%) foram positivas para S. enterica. Foram identificados nove sorotipos. Os mais comuns foram Salmonella Typhimurium (56%) e sua variante monofásica (35%). A resistência à ampicilina (70%) foi observada com maior frequência, seguida pela resistência ao ciprofloxacino (55%) e ao sulfametoxazol/trimetoprima (52%). Nenhum isolado apresentou resistência à amicacina ou gentamicina. Multirresistência (resistência a ≥ 3 classes de antibióticos) foi observada em 61 isolados (44%). A multirresistência foi mais comum em S. Typhimurium (57%), em comparação aos outros sorotipos. Foi constatada associação da multirresistência com sorotipos (p = 0,01), mas não com idade do suíno ou sub-região. Conclusões. A proporção de Salmonella spp. e os níveis elevados associados de multirresistência a antimicrobianos aqui constatados são preocupantes, e podem indicar uso irracional de antimicrobianos e práticas inadequadas de manejo nos sistemas de suinocultura da região. É preciso fortalecer a vigilância para monitorar e melhorar as práticas de manejo agrícola e o uso de antimicrobianos em fazendas na Colômbia.

Prevalence, outcomes, and predictors of multidrug-resistant nosocomial lower respiratory tract infections among patients in an ICU / Prevalência, desfechos e preditores de infecções nosocomiais do trato respiratório inferior multirresistentes em pacientes em uma UTI

ABSTRACT Objective: To determine the prevalence, outcomes, and predictors of multidrug-resistant nosocomial lower respiratory tract infections (LRTI) in patients in an ICU. Methods: This was an observational cohort study involving patients with nosocomial LRTI (health care-associated pneumonia, hospital-acquired pneumonia, or ventilator-associated pneumonia). Data were prospectively collected between 2015 and 2019. The multidrug-resistant pathogens (MDRPs) identified in the isolates studied included resistant to extended-spectrum cephalosporin-resistant and carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus at microbiological diagnosis. Results: During the study period, 267 patients in the ICU were diagnosed with LRTI, microbiological confirmation of LRTI having been obtained in 237. Of these, 146 (62%) had at least one MDRP isolate. Patients infected with MDRP were found to have poorer outcomes than patients infected with susceptible strains, such as prolonged mechanical ventilation (18.0 days vs. 12.0 days; p < 0.001), prolonged ICU length of stay (23.0 days vs.16.0 days; p < 0.001), and higher mortality (73% vs. 53%; p < 0.001) when compared with patients infected with susceptible strains. Hospital length of stay ≥ 5 days (OR = 3.20; 95% CI: 1.39-7.39; p = 0.005) and prolonged use vasoactive drugs (OR = 3.15; 95% CI: 1.42-7.01; p = 0.004) were independent predictors of LRTI caused by MDRPs (LRTI-MDRP). The presence of LRTI-MDRP was found to be an independent predictor of death (OR = 2.311; 95% CI: 1.091-4.894; p = 0.028). Conclusions: Prolonged use of vasoactive drugs and prolonged hospital length of stay were independent predictors of LRTI-MDRP in this population of critically ill patients with very poor outcomes.

RESUMO Objetivo: Determinar a prevalência, os desfechos e os preditores de infecções do trato respiratório inferior (ITRI) nosocomiais em pacientes em uma UTI. Métodos: Estudo observacional de coorte com pacientes com ITRI nosocomiais (pneumonia associada à assistência à saúde, pneumonia adquirida no hospital ou pneumonia associada à ventilação mecânica). Os dados foram coletados prospectivamente entre 2015 e 2019. Os patógenos multirresistentes (PMR) identificados nos isolados estudados incluíram Acinetobacter baumannii, Klebsiella pneumoniae e Pseudomonas aeruginosa resistentes a cefalosporinas de espectro estendido e carbapenêmicos, enterobactérias resistentes a carbapenêmicos e Staphylococcus aureus resistente à meticilina no diagnóstico microbiológico. Resultados: Durante o período do estudo, 267 pacientes internados na UTI foram diagnosticados com ITRI, 237 dos quais tiveram confirmação microbiológica de ITRI. Destes, 146 (62%) apresentaram pelo menos um isolado de PMR. Os pacientes infectados por PMR tiveram piores desfechos do que os infectados por cepas sensíveis, como ventilação mecânica prolongada (18,0 dias vs. 12,0 dias; p < 0,001), tempo prolongado de internação na UTI (23,0 dias vs. 16,0 dias; p < 0,001) e maior mortalidade (73% vs. 53%; p < 0,001). Tempo de internação hospitalar ≥ 5 dias (OR = 3,20; IC95%: 1,39-7,39; p = 0,005) e uso prolongado de drogas vasoativas (OR = 3,15; IC95%: 1,42-7,01; p = 0,004) foram preditores independentes de ITRI por PMR (ITRI-PMR). A presença de ITRI-PMR foi um preditor independente de óbito (OR = 2,311; IC95%: 1,091-4,894; p = 0,028). Conclusões: O uso prolongado de drogas vasoativas e o tempo prolongado de internação hospitalar foram preditores independentes de ITRI-PMR nesta população de pacientes críticos com desfechos muito ruins.

Recent advances in the development of antibacterial potentiators / 中华检验医学杂志

Multidrug-resistant bacteria that can′t be treated with any common antibacterial drugs have become a global medical crisis. Therefore, there is an urgent need for new antibacterial potentiators to restore the sensitivity of bacteria to the antibacterial drug. This review elaborates on the novel antibacterial synergistic methods and their underlying mechanisms, clinical experimental data and efficacy, and the progress of drug research and development. This review aims to raise awareness about antibacterial potentiators among the public.

Systematic review on efficacy of preventive measures for surgical site infection by multiple-drug resistant gram-negative bacilli.

BACKGROUND: There are no specific recommendations for prevention of surgical site infection (SSI) caused by multidrug resistant Gram-negative bacilli (MDR-GNB). Our objective was to systematically review the literature evaluating the efficacy and safety of measures specifically designed to prevent MDR-GNB SSI. METHODS: We searched MEDLINE, EMBASE, CINAHL and LILACS databases up to February 18, 2020. Randomized trials and observational cohort studies evaluating the efficacy of preventive measures against MDR-GNB SSI in adult surgical patients were eligible. We evaluated methodological quality of studies and general quality of evidence using Newcastle-Ottawa scale, Cochrane ROBINS-I and GRADE method. Random-effects meta-analyses were performed using Review Manager V.5.3 software. RESULTS: A total of 10,663 titles by searching databases were identified. Two retrospective observational studies, comparing surgical antibiotic prophylaxis (SAP) with or without aminoglycoside in renal transplantation recipients, and one non-randomized prospective study, evaluating ertapenem vs. cephalosporin plus metronidazole for SAP in extended spectrum beta-lactamase producing Enterobacteriales carriers undergoing colon surgery, were included. Risk of bias was high in all studies. Meta-analysis was performed for the renal transplantation studies, with 854 patients included. Combined relative risk (RR) for MDR GNB SSI was 0.57 (95%CI: 0.25-1.34), favoring SAP with aminoglycoside (GRADE: moderate). CONCLUSIONS: There are no sufficient data supporting specific measures against MDR-GNB SSI. Prospective, randomized studies are necessary to assess the efficacy and safety of SAP with aminoglycoside for MDR-GNB SSI prevention among renal transplantation recipients and other populations. PROSPERO 2018 CRD42018100845.