High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

[Changes in the clinical presentation of Influenza A H1N1pdm09 after the pandemic]. / Cambios en la presentación clínica de la influenza A H1N1pdm09 después de la pandemia.

BACKGROUND: After the 2009 influenza pandemic the H1N1pdm09 strain circulate seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak of both seasonal H3N2 and H1N1pdm09 influenza A (IA). AIM: To evaluate the clinical differences between the two viral strains and recent changes in the behavior of H1N1pdm09 IA. MATERIAL AND METHODS: We set up a retrospective study including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA, confirmed by reverse transcription polymerase chain reaction. We compared epidemiological data, clinical presentation, complications, and the outcome of patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized and analyzed in 2009. RESULTS: Between July and October 2015, 119 adults with confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with IAH1N1pdm09 increased from 40.4 ± 17 to 58.8 ± 16 years (p < 0.01). Pneumonia as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04). Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01). Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and developed septic shock (p = 0.03). Their mortality was non-significantly higher (13 and 5% respectively). CONCLUSIONS: The clinical presentation of H1N1pdm09 IA has varied over time and now affects an older population, with a greater number of comorbidities. It also appears to be adopting the clinical behavior of a classic seasonal influenza virus.

Hantavirus pulmonary syndrome, Southern Chile, 1995-2012.

Hantavirus is endemic to the Region de Los Lagos in southern Chile; its incidence is 8.5 times higher in the communes of the Andean area than in the rest of the region. We analyzed the epidemiologic aspects of the 103 cases diagnosed by serology and the clinical aspects of 80 hospitalized patients during 1995-2012. Cases in this region clearly predominated during winter, whereas in the rest of the country, they occur mostly during summer. Mild, moderate, and severe disease was observed, and the case-fatality rate was 32%. Shock caused death in 75% of those cases; high respiratory frequency and elevated creatinine plasma level were independent factors associated with death. Early clinical suspicion, especially in rural areas, should prompt urgent transfer to a hospital with an intensive care unit and might help decrease the high case-fatality rate.

[Respiratory virus infections in adult patients hospitalized in an internal medicine unit]. / Infección por virus respiratorios en adultos hospitalizados en un Servicio de Medicina Interna.

BACKGROUND: Respiratory viral infections (RVi) can be associated with a wide range of clinical manifestations. AIM: To investigate the frequency and clinical manifestations of RVi among adult patients during winter hospitalizations. PATIENTS AND METHODS: All patients admitted to the hospital with flu like disease and those with fever or exacerbation of any underlying disease during hospitalization without an evident cause, were prospectively enrolled. A direct immunofluorescence (DIF) of nasopharyngeal aspirate for influenza A (IA) and B, parainfluenza 1, 2 and 3, adenovirus, respiratory syncytial virus (RSV) and metapneumovirus, was performed. Epidemiological and clinical data were recorded. RESULTS: Between May and September 2012, 975 adults were admitted to the Internal Medicine Unit of Puerto Montt Hospital and in 128 (13%) patients, DIF was carried out. DIF was positive in 44 patients (34%) aged 65 ± 20 years, 68.2% females, corresponding to 4.5% of total hospitalizations. Eighty six percent of the latter had at least one co-morbidity, mainly asthma and chronic respiratory diseases in 34.1%, diabetes in 29.5%, cardiac problems in 25% and congestive heart failure in 20.5%. The most common RVi were RSV (n = 21, 48%) and IA (n = 17, 39%). Six patients had a nosocomial RVi. Patients infected with IA had a significantly higher frequency of fever and bronchial hyper reactivity than those infected with RSV. RVi were associated with exacerbation of underlying disease in 62% of cases and pneumonia in 27%. Two patients had a viral pericarditis. CONCLUSIONS: RVi are an important cause of adult morbidity and their detection should be routine in adult patients hospitalized during winter.

Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study.

BACKGROUND: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. METHODS: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. FINDINGS: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). INTERPRETATION: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. FUNDING: National Institutes of Health and Agencia de Investigación y Desarrollo. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein.

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection.

Creación del primer biorrepositorio nacional de bacterias multirresistentes disponible para el estudio de la resistencia bacteriana en Chile / Creation of the first national biorepository of multi-resistant bacteria available for the study of bacterial resistance in Chile

La disponibilidad de cepas bacteriana para el estudio de la resistencia bacteriana es clave para los avances en la investigación básica y clínica respecto del tema. Existen pocos biorrepositorios o bancos de bacterias con mecanismos de resistencia conocidos, aisladas de infecciones clínicamente significativas. Una revisión de la literatura revela que sólo en los Estados Unidos de América existe un biobanco de aislados resistentes disponibles para estudios. En esta publicación se cuenta cómo se creó el primer biorrepositorio de bacterias resistentes en Chile asociados a la Red de Laboratorios MICROB-R, con la participación de 11 centros distribuidos a lo largo del país, que a la fecha cuenta con más de 3.500 aislados bacterianos estudiados fenotípica y genotípicamente, disponibles para la comunidad científica chilena.

The availability of bacterial strains for the study of bacterial resistance is key to advances in basic and clinical research. There are few biobanks of bacteria with known resistance mechanisms, isolated from clinically significant infections. A review of the literature reveals that only in the United States of America is there a biobank of resistant isolates. This publication shows the creation of the first biorepository of resistant bacteria Chile associated with the MICROB-R Laboratory Network, with the participation of 11 centers distributed throughout the country, which to date has more than 3,500 bacterial isolates studied phenotypically and genotypically, available to the Chilean scientific community.

Antimicrobial resistance genes in marine bacteria and human uropathogenic Escherichia coli from a region of intensive aquaculture.

Antimicrobials are heavily used in Chilean salmon aquaculture. We previously found significant differences in antimicrobial-resistant bacteria between sediments from an aquaculture and a non-aquaculture site. We now show that levels of antimicrobial resistance genes (ARG) are significantly higher in antimicrobial-selected marine bacteria than in unselected bacteria from these sites. While ARG in tetracycline- and florfenicol-selected bacteria from aquaculture and non-aquaculture sites were equally frequent, there were significantly more plasmid-mediated quinolone resistance genes per bacterium and significantly higher numbers of qnrB genes in quinolone-selected bacteria from the aquaculture site. Quinolone-resistant urinary Escherichia coli from patients in the Chilean aquacultural region were significantly enriched for qnrB (including a novel qnrB gene), qnrS, qnrA and aac(6')-1b, compared with isolates from New York City. Sequences of qnrA1, qnrB1 and qnrS1 in quinolone-resistant Chilean E. coli and Chilean marine bacteria were identical, suggesting horizontal gene transfer between antimicrobial-resistant marine bacteria and human pathogens.

Cambios en la presentación clínica de la influenza A H1N1pdm09 después de la pandemia / Changes in the clinical presentation of Influenza A H1N1pdm09 after the pandemic

Background: After the 2009 influenza pandemic the H1N1pdm09 strain circulate seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak of both seasonal H3N2 and H1N1pdm09 influenza A (IA). Aim: To evaluate the clinical differences between the two viral strains and recent changes in the behavior of H1N1pdm09 IA. Material and Methods: We set up a retrospective study including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA, confirmed by reverse transcription polymerase chain reaction. We compared epidemiological data, clinical presentation, complications, and the outcome of patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized and analyzed in 2009. Results: Between July and October 2015, 119 adults with confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with IAH1N1pdm09 increased from 40.4 ± 17 to 58.8 ± 16 years (p < 0.01). Pneumonia as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04). Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01). Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and developed septic shock (p = 0.03). Their mortality was non-significantly higher (13 and 5% respectively). Conclusions: The clinical presentation of H1N1pdm09 IA has varied over time and now affects an older population, with a greater number of comorbidities. It also appears to be adopting the clinical behavior of a classic seasonal influenza virus.

Infección por virus respiratorios en adultos hospitalizados en un Servicio de Medicina Interna / Respiratory virus infections in adult patients hospitalized in an internal medicine unit

Background: Respiratory viral infections (RVi) can be associated with a wide range of clinical manifestations. Aim: To investigate the frequency and clinical manifestations of RVi among adult patients during winter hospitalizations. Patients and Methods: All patients admitted to the hospital with flu like disease and those with fever or exacerbation of any underlying disease during hospitalization without an evident cause, were prospectively enrolled. A direct immunofluorescence (DIF) of nasopharyngeal aspirate for influenza A (IA) and B, parainfluenza 1, 2 and 3, adenovirus, respiratory syncytial virus (RSV) and metapneumovirus, was performed. Epidemiological and clinical data were recorded. Results: Between May and September 2012, 975 adults were admitted to the Internal Medicine Unit of Puerto Montt Hospital and in 128 (13%) patients, DIF was carried out. DIF was positive in 44 patients (34%) aged 65 ± 20 years, 68.2% females, corresponding to 4.5% of total hospitalizations. Eighty six percent of the latter had at least one co-morbidity, mainly asthma and chronic respiratory diseases in 34.1%, diabetes in 29.5%, cardiac problems in 25% and congestive heart failure in 20.5%. The most common RVi were RSV (n = 21, 48%) and IA (n = 17, 39%). Six patients had a nosocomial RVi. Patients infected with IA had a significantly higher frequency of fever and bronchial hyper reactivity than those infected with RSV. RVi were associated with exacerbation of underlying disease in 62% of cases and pneumonia in 27%. Two patients had a viral pericarditis. Conclusions: RVi are an important cause of adult morbidity and their detection should be routine in adult patients hospitalized during winter.

[Penicillin susceptibility in Streptococcus pneumoniae strains isolated at Puerto Montt Hospital between 1995 and 2003]. / Susceptibilidad a penicilina en cepas de Streptococcus pneumoniae aisladas en el Hospital de Puerto Montt, 1995-2003.

BACKGROUND: The emergence and dissemination of resistance to penicillin among Streptococcus pneumoniae changed the approach to empiric antimicrobial therapy. AIM: To evaluate the in vitro susceptibility to penicillin in all S. pneumoniae strains isolated in Puerto Montt Hospital between 1995 and 2003. MATERIAL AND METHODS: We revised all Microbiology Laboratory files of this period. Identification and antimicrobial susceptibility study methods for S pneumoniae did not change during the study period. RESULTS: Six hundred eighteen S pneumoniae strains were identified. Of these, 66% came from adults and 48% from invasive diseases. Only 1.9% of strains were penicillin resistant and 7.6% had intermediate sensibility. Strains isolated from children and those isolated from non sterile sources had non significantly higher resistance levels. The susceptibility did not change along the years of the study. CONCLUSIONS: Among S pneumoniae strains isolated at Puerto Montt Hospital, the prevalence of penicillin resistance is low.

[Bacteremic pneumococcal pneumonia in 45 immunocompromised hospitalized adults]. / Neumonía neumocócica bacterémica en 45 adultos inmunocompetentes hospitalizados. Cuadro clínico y factores pronósticos.

BACKGROUND: The presence of bacteremia during a pneumococcal pneumonia is a sign of bad prognosis. AIM: To report a clinical experience with bacteremic pneumococcal pneumonia. PATIENTS AND METHODS: We reviewed the clinical and laboratory data from 45 adults (36 male, aged 17 to 97 years) with community acquired pneumonia (CAP) and Streptococcus pneumoniae bacteremia, hospitalized between January 1997 and August 2002 at the Puerto Montt Hospital (Southern Chile). RESULTS: Eighty four percent of patients bad underlying aggravating conditions, mainly alcoholism (40%), chronic obstructive lung disease (17.8%) and renal failure (17.8%). Seven percent were homeless. Fever, cough, dyspnea and sputum were the most common presenting symptoms. Five patients had pleural involvement. Four strains (8.9%) of S. pneumoniae had diminished susceptibility to penicillin. Nine patients died (case-fatality rate of 20%), but mortality was attributed to pneumonia in only three of them. Main factors associated with a higher mortality were renal failure, absence of cough, an arterial pH < 7.3 on admission, ICU hospitalization, shock, mechanical ventilation and an APACHE score > 16. CONCLUSIONS: The high death rate of these patients could be explained mainly by underlying conditions. ICU management and higher cost preventive measures could reduce this rate.

Hantavirus pulmonary syndrome, southern Chile.

We analyzed data from 25 consecutive patients with hantavirus pulmonary syndrome (HPS) admitted to the Puerto Montt and Osorno Regional Hospitals, southern Chile, from 1997 to 2001, emphasizing epidemiologic, clinical, radiographic, treatment, and laboratory aspects. Hemorrhage was frequent (64%), and 48% of patients showed alterations in renal function. Ten patients died (40%). We identified three groups of patients, which included the following: 1) those with the least severe form who had prodromic symptoms without pulmonary involvement; 2) those with moderate illness who had interstitial pulmonary infiltrates, usually needed supplemental nasal oxygen, were hemodynamically stable, and had an APACHE II <12 (none of whom died); and 3) those with the severe form who required mechanical ventilation, frequently had hemodynamic instability (93%), experienced a high mortality rate (77%), and had an APACHE II >12. Mild forms of HPS also exist, which are poorly known; the symptoms could be confounded with those of other viral diseases, leading to underdiagnosis.

Características clínicas y sociodemográficas de una población de pacientes epilépticos consultantes en la unidad de neurología: Hospital San Juan de Dios, 1984-1986 / Clinical and sociodemographic characteristics of a group of epileptic patients consultants at the unit of neurology: San Juan de Dios Hospital, 1984-1986

Se realizó un análisis de las características clínicas y sociodemográficas de 331 pacientes epilépticos cuya primera consulta se realizó entre los años 1984-1986 en el Departamento de Neurología del Hospital San Juan de Dios. La población evaluada resultó ser predominantemente femenina, siendo la edad promedio de 29 ñ 14 años. La forma clínica predominante fue la tónicaclónica generalizada. La mayoría de los pacientes recibió monoterapia, siendo la droga más usada la fenitoína sódica y la asociación más frecuente prescrita la fenitoína sódica más fenobarbital. Se analizaron además antecedentes personales, familiares y factores desencadenantes