RESUMO

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Assuntos

Antibacterianos , Proteínas de Bactérias , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Pseudomonas aeruginosa , beta-Lactamases , Humanos , Colômbia/epidemiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Estudos Retrospectivos , Masculino , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Pessoa de Meia-Idade , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/classificação , Antibacterianos/farmacologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Adulto , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Idoso , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Carbapenêmicos/farmacologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Sequenciamento Completo do Genoma , Adolescente , Adulto Jovem

RESUMO

BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.

Assuntos

Portador Sadio , Nasofaringe , Orofaringe , Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Nasofaringe/microbiologia , Orofaringe/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Adulto , Prevalência , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Adolescente

RESUMO

INTRODUCTION: Understanding the presence and function of a diverse lung microbiome in acute lung infections, particularly ventilator-associated pneumonia (VAP), is still limited, evidencing significant gaps in our knowledge. AREAS COVERED: In this comprehensive narrative review, we aim to elucidate the contribution of the respiratory microbiome in the development of VAP by examining the current knowledge on the interactions among microorganisms. By exploring these intricate connections, we endeavor to enhance our understanding of the disease's pathophysiology and pave the way for novel ideas and interventions in studying the respiratory tract microbiome. EXPERT OPINION: The conventional perception of lungs as sterile is deprecated since it is currently recognized the existence of a diverse microbial community within them. However, despite extensive research on the role of the respiratory microbiome in healthy lungs, respiratory chronic diseases and acute lung infections such as pneumonia are not fully understood. It is crucial to investigate further the relationship between the pathophysiology of VAP and the pulmonary microbiome, elucidating the mechanisms underlying the interactions between the microbiome, host immune response and mechanical ventilation for the development of VAP.

Assuntos

Microbiota , Pneumonia Associada à Ventilação Mecânica , Humanos , Pulmão , Respiração Artificial , Doença Crônica

RESUMO

BACKGROUND: Inflammatory responses contribute to tissue damage in COVID-19 and community-acquired pneumonia (CAP). Although predictive values of different inflammatory biomarkers have been reported in both, similarities and differences of inflammatory profiles between these conditions remain uncertain. Therefore, we aimed to determine the similarities and differences of the inflammatory profiles between COVID-19 and CAP, and their association with clinical outcomes. METHODS: We report a prospective observational cohort study; conducted in a reference hospital in Latin America. Patients with confirmed COVID-19 pneumonia and CAP were included. Multiplex (Luminex) cytokine assays were used to measure the plasma concentration of 14 cytokines at hospital admission. After comparing similarities and differences in the inflammatory profile between COVID-19 and CAP patients, an unsupervised classification method (i.e., hierarchical clustering) was used to identify subpopulations within COVID-19 and CAP patients. RESULTS: A total of 160 patients were included, 62.5% were diagnosed with COVID-19 (100/160), and 37.5% with CAP (60/160). Using the hierarchical clustering, COVID-19 and CAP patients were divided based on its inflammatory profile: pauci, moderate, and hyper-inflammatory immune response. COVID-19 hyper-inflammatory subpopulation had the highest mortality. COVID-19 hyper-inflammatory subpopulation, compared to pauci-inflammatory, had higher levels of IL-10 (median [IQR] 61.4 [42.0-109.4] vs 13.0 [5.0-24.9], P: < 0.001), IL-6 (48.1 [22.3-82.6] vs 9.1 [0.1-30.4], P: < 0.001), among others. Hyper-inflammatory vs pauci-inflammatory CAP patients were characterized by elevation of IFN2 (48.8 [29.7-110.5] vs 3.0 [1.7-10.3], P: < 0.001), TNFα (36.3 [24.8-53.4] vs 13.1 [11.3-16.9], P: < 0.001), among others. Hyper-inflammatory subpopulations in COVID-19 and CAP compared to the corresponding pauci-inflammatory subpopulations had higher MCP-1. CONCLUSIONS: Our data highlights three distinct subpopulations in COVID-19 and CAP, with differences in inflammatory marker profiles and risks of adverse clinical outcomes. TRIAL REGISTRATION: This is a prospective study, therefore no health care intervention were applied to participants and trial registration is not applicable.

Assuntos

COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Estudos Prospectivos , COVID-19/complicações , Pneumonia/diagnóstico , Citocinas , Hospitalização , Infecções Comunitárias Adquiridas/diagnóstico

RESUMO

BACKGROUND: Early and adequate antibiotic treatment is the cornerstone of improving clinical outcomes in patients with bloodstream infections (BSI). Delays in appropriate antimicrobial therapy have catastrophic consequences for patients with BSI. Microbiological characterization of multi-drug resistant pathogens (MDRP) allows clinicians to provide appropriate treatments. Current microbiologic techniques may take up to 96 h to identify causative pathogens and their resistant patterns. Therefore, there is an important need to develop rapid diagnostic strategies for MDRP. We tested a modified protocol to detect carbapenemase and extended-spectrum ß-lactamase (ESBL) producing Gram-negative bacteria (GNB) from positive blood cultures. METHODS: This is a prospective cohort study of consecutive patients with bacteremia. We developed a modified protocol using the HB&L® system to detect MDRP. The operational characteristics were analyzed for each test (HB&L-ESBL/AmpC® and HB&L-Carbapenemase® kits). The kappa coefficient, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratios (LR) with 95% confidence intervals (CI), and reduction in identification time of this novel method were calculated. RESULTS: Ninety-six patients with BSI were included in the study. A total of 161 positive blood cultures were analyzed. Escherichia coli (50%, 81/161) was the most frequently identified pathogen, followed by Klebsiella pneumoniae (15%, 24/161) and Pseudomonas aeruginosa (8%, 13/161). Thirty-three percent of isolations had usual resistance patterns. However, 34/161 (21%) of identified pathogens were producers of carbapenemases and 21/161 (13%) of extended-spectrum ß-lactamases. Concordance between our HB&L® modified protocol and the traditional method was 99% (159/161). Finally, identification times were significantly shorter using our HB&L®-modified protocol than traditional methods: median (IQR) 19 h (18, 22) vs. 61 h (60, 64), p < 0.001. CONCLUSIONS: Here, we provide novel evidence that using our HB&L®-modified protocol is an effective strategy to reduce the time to detect MDRP producers of carbapenemases or extended-spectrum ß-lactamases, with an excellent concordance rate when compared to the gold standard. Further studies are needed to confirm these findings and to determine whether this method may improve clinical outcomes.

RESUMO

BACKGROUND: Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE. METHODS: This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review. RESULTS: The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio [OR] 1, 48; 95% confidence interval [CI] [1.21-2.27]; P = .013) and serotype 9n (OR 1.29; 95% CI [1.08-2.24]; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean [standard deviation], 138 [145] vs 73 [106], P = .01). CONCLUSIONS: MACE are common during IPD with serotype 3 and 9n independently of frequency.

Assuntos

Insuficiência Cardíaca , Infecções Pneumocócicas , Colômbia , Humanos , Lactente , Vacinas Pneumocócicas , Estudos Retrospectivos , Sorogrupo , Sorotipagem

RESUMO

Resumen Introducción. Clostridium difficile es el principal responsable de la diarrea asociada al uso de antibióticos. En Colombia y en Latinoamérica, el conocimiento sobre el comportamiento epidemiológico de la infección por C. difficile todavía es limitado. Objetivo. Describir las características de una serie de pacientes con infección por C.difficile . Materiales y métodos. Se hizo un estudio descriptivo de una serie de casos de pacientes con infección por C. difficile atendidos en la Fundación Clínica Shaio, entre enero de 2012 y noviembre de 2015. Resultados. Se estudiaron 36 pacientes con una edad promedio de 65 años. Se determinaron los siguientes factores relacionados con la infección por C. difficile: uso previo de antimicrobianos (94,4 %), hospitalización en los últimos tres meses (66,7 %) y uso de inhibidores de la bomba de protones (50 %). Las comorbilidades más comunes fueron la enfermedad renal crónica (41,7 %) y la diabetes mellitus (30,6 %). Los síntomas más frecuentes fueron más de tres deposiciones diarreicas (97,1 %) y dolor abdominal (42,9 %). En cuanto a la gravedad de los casos, 44,4 % se clasificó como leve a moderado, 38,9 % como grave, y 11,1 % como complicado o grave. El método de diagnóstico más utilizado (63,8% de los pacientes) fue la identificación de la toxina mediante reacción en cadena de la polimerasa (PCR). La mortalidad global durante la hospitalización fue de 8 %. Se identificaron cuatro cepas del serotipo NAP1/027 y nueve muestras fueron positivas para la toxina binaria. Conclusión. La infección por C. difficile debe sospecharse en pacientes con deposiciones diarreicas y factores asociados tradicionalmente a esta enfermedad. Se reportó la circulación de cepas hipervirulentas del serotipo NAP1/027 en Colombia, lo cual debe enfrentarse con la vigilancia epidemiológica y el diagnóstico temprano.

---

Abstract Introduction: Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. Objective: To describe the characteristics of a series of patients with C. difficile infection. Materials and methods: We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. Results: We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. Conclusion: Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.

Assuntos

Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção Hospitalar/microbiologia , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Proteínas de Bactérias/análise , Toxinas Bacterianas/análise , Virulência , Sorotipagem , Dor Abdominal/etiologia , Comorbidade , Infecção Hospitalar/epidemiologia , Fatores de Risco , Clostridioides difficile/classificação , Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Colômbia/epidemiologia , Diabetes Mellitus/epidemiologia , Diarreia/microbiologia , Diarreia/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Hospitalização , Tempo de Internação/estatística & dados numéricos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico

RESUMO

INTRODUCTION: Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. OBJECTIVE: To describe the characteristics of a series of patients with C. difficile infection. MATERIALS AND METHODS: We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. RESULTS: We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. CONCLUSION: Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.

Assuntos

Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Dor Abdominal/etiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Proteínas de Bactérias/análise , Toxinas Bacterianas/análise , Clostridioides difficile/classificação , Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Colômbia/epidemiologia , Comorbidade , Infecção Hospitalar/epidemiologia , Diabetes Mellitus/epidemiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Hospitalização , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Sorotipagem , Virulência

RESUMO

En 2010, el Instituto Americano de Estándares Clínicos y de Laboratorio (CLSI) inició un proceso de revisión y actualización de los puntos de corte para microdilución y disco difusión para cefalosporinas (cefazolina, cefotaxima, ceftriaxona, ceftizoxima, ceftazidima), monobactámicos (aztreonam) y carbapenémicos (imipenem, meropenem, ertapenem, doripenem). Los cambios se basaron en modelos PK/PD que buscan predecir la respuesta clínica con el uso exclusivo de la concentración inhibitoria mínima (CIM) y esquemas específicos de dosificación de forma independiente al mecanismo de resistencia expresado. Este nuevo paradigma eliminaría la necesidad de realizar pruebas fenotípicas para beta-lactamasas de espectro extendido (BLEE) y carbapenemasas para tomar decisiones terapéuticas y permitiría utilizarlas únicamente para fines epidemiológicos. Sin embargo, ante las limitaciones de las metodologías actuales para pruebas de susceptibilidad en Colombia, el desconocimiento de estos cambios y la alarma epidemiológica por la aparición de nuevas ß-lactamasas en el país, se hace necesario generar recomendaciones para los laboratorios clínicos, con el fi n de unifi car los criterios para la realización e informe de los antibiogramas en bacilos Gram negativos, incluyendo la implementación de los puntos de corte actuales y la aplicación de las pruebas fenotípicas para la detección de BLEE y carbapenemasas.

---

In 2010, the Clinical and Laboratory Standards Institute (CLSI) began a process to revise and update the breakpoints for broth microdilution and disk diffusion for cephalosporins (Cefazolin, Cefotaxime, Ceftriaxone, Ceftazidime), monobactams (Aztreonam) and carbapenems (Imipenem, Meropenem, Ertapenem and Doripenem). The changes made were based on PK/PD models that attempt to predict clinical outcomes using minimum inhibitory concentration (MIC) and specific dosage regimens, regardless of the resistance mechanism expressed by the organism. The new breakpoints would eliminate the need to perform screening and confirmatory testing for ESBLs and carbapenemases for treatment decisions, and thus they would be used only for infection control purposes. Nevertheless, there are limitations to current methods in Colombia, a lack of knowledge regarding the recent changes and epidemiologic alarm over new B-lactamases spreading in our country. Therefore it was necessary to formulate and issue recommendations for clinical laboratories, with the aim of standardizing the criteria for reports on antibiograms in Gram-negative bacilli, including the current CLSI breakpoints and applying phenotypic confirmatory testing to detect ESBLs and Carbapenemases.

Assuntos

Humanos , beta-Lactamases , Cefalosporinas , Epidemiologia , Colômbia , Enzimas , Serviços de Laboratório Clínico