Trends and socioeconomic, demographic, and environmental factors associated with antimicrobial resistance: a longitudinal analysis in 39 hospitals in Chile 2008-2017.

Background: Antimicrobial resistance (AMR) is among the most critical global health threats of the 21st century. AMR is primarily driven by the use and misuse of antibiotics but can be affected by socioeconomic and environmental factors. Reliable and comparable estimates of AMR over time are essential to making public health decisions, defining research priorities, and evaluating interventions. However, estimates for developing regions are scant. We describe the evolution of AMR for critical priority antibiotic-bacterium pairs in Chile and examine their association with hospital and community-level characteristics using multivariate rate-adjusted regressions. Methods: Drawing on multiple data sources, we assembled a longitudinal national dataset to analyse AMR levels for critical priority antibiotic-bacterium combinations in 39 private and public hospitals (2008-2017) throughout the country and characterize the population at the municipality level. We first described trends of AMR in Chile. Second, we used multivariate regressions to examine the association of AMR with hospital characteristics and community-level socioeconomic, demographic, and environmental factors. Last, we estimated the expected distribution of AMR by region in Chile. Findings: Our results show that AMR for priority antibiotic-bacterium pairs steadily increased between 2008 and 2017 in Chile, driven primarily by Klebsiella pneumoniae resistant to third-generation cephalosporins and carbapenems, and vancomycin-resistant Enterococcus faecium. Higher hospital complexity, a proxy for antibiotic use, and poorer local community infrastructure were significantly associated with greater AMR. Interpretation: Consistent with research in other countries in the region, our results show a worrisome increase in clinically relevant AMR in Chile and suggest that hospital complexity and living conditions in the community may affect the emergence and spread of AMR. Our results highlight the importance of understanding AMR in hospitals and their interaction with the community and the environment to curtail this ongoing public health crisis. Funding: This research was supported by the Agencia Nacional de Investigación y Desarrollo (ANID), Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT, The Canadian Institute for Advanced Research (CIFAR), and Centro UC de Políticas Públicas, Pontificia Universidad Católica de Chile.

Estrategia de pesquisa sistemática y seguimiento prolongado revela alto número de nuevas infecciones tuberculosas en contactos adultos en la Región Metropolitana, Chile / Systematic screening of adult household contacts of patients with active pulmonary tuberculosis reveals high rates of new infections during follow-up

Background: Contact investigation is cardinal in the control of tuberculosis (TB) since it helps to stop its transmission. In Chile, the National TB Program strategy does not include latent TB infection testing, regular chemoprophylaxis or follow-up in adults. Active TB was found in only 1.2% of contacts at country-level during 2018. Aim: To evaluate the performance of a systematic screening of adult household contacts with targeted chemoprophylaxis and prolonged active follow-up. Material and Methods: Prospective cohort of household contacts in Santiago. Two face-to-face visits (at 0 and 12 weeks) that included QuantiFERON TB-Gold plus tests (QFT), chest radiography (CXR) at 0 and 24 weeks and, periodic text messaging or phone call follow-up for up to 48 weeks were implemented. Contacts with positive QFT were referred for TB chemoprophylaxis. Results: A total of 200 contacts were enrolled, 69% were migrants. At baseline evaluation, 45% had a positive QFT result and 1.6% had co-prevalent active TB. At follow-up, 13% contacts further converted to QFT (+), and 5.1% more were diagnosed with active TB (mean follow-up time 32 weeks). Of these 10 further active TB cases, 6 (60%) had a negative QFT and all (100%) had normal CXR at baseline; while three cases occurred in QFT converters. Conclusions: In this cohort of household contacts, 6.7 % were diagnosed with active TB (more than 2/3 at follow-up) and 13% had a late QFT (+) conversion. Active and prolonged contacts' follow-up are essential to detect new infections and tackle the TB epidemic in Chile.

Vitamin D and Bone Mineral Density in HIV Newly Diagnosed Therapy-Naive Patients Without Any Secondary Causes of Osteoporosis.

Bone loss and vitamin D deficiency are common in HIV patients. However, bone health status in newly diagnosed HIV patients has not been thoroughly described. Our aim was to assess the bone mineral density (BMD), bone resorption and vitamin D status in newly diagnosed HIV patients. A prospective observational study in HIV newly diagnosed therapy-naive persons. Patients with secondary causes of osteoporosis were excluded. Bone densitometry (DXA), a bone resorption marker (CTx), 25-hydroxyvitamin D (25OHD), CD4 count and HIV viral load (VL) were done in 70 patients. Vitamin D results were compared with a group of healthy volunteers. All patients were men, mean age 31 years (19-50). Low BMD (Z score ≤ 2.0) was found in 13%, all of them in lumbar spine, and in only one patient also in femoral neck. Bone resorption was high in 16%. One out of four participants had low BMD or high bone resorption. Vitamin D deficiency (25OHD < 20 ng/mL) was found in 66%. Mean 25OHD in patients was significantly lower than in healthy volunteers (p = 0.04). No associations were found between BMD, CTx, 25OHD and VL or CD4 count. We hypothesize that HIV infection negatively affects bone health based on the results we found among newly diagnosed, therapy-naive, HIV-infected patients, without any known secondary causes of osteoporosis. Low BMD or high bone resorption, are significantly prevalent in these patients. HIV-infected patients had a higher prevalence of vitamin D deficiency than controls, which was not correlated with CD4 count or VL.

[Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum ß-lactamase (ESBL) CTX-M]. / Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de ß-lactamasas de espectro extendido (BLEE) CTX-M.

BACKGROUND: Carbapenems are the preferred ß-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum ß-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers. AIM: To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type. METHODS: Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia. RESULTS: We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 µg/ml and 70% with MIC ≤4 µg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%. CONCLUSIONS: Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de β -lactamasas de espectro extendido (BLEE) CTX-M / Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum β -lactamase (ESBL) CTX-M

Resumen Introducción: En las infecciones por enterobacterias productoras de β-lactamasas de espectro extendido (BLEE), los β-lactámicos preferidos para tratamiento son los carbapenémicos. Sin embargo, estudios clínicos muestran eficacia de piperacilina/tazobactam en ciertas infecciones por Escherichia coli productoras de BLEE. Objetivo: Determinar la cura clínica y microbiológica con piperacilina/tazobactam en pacientes con infecciones por E. coli productoras de BLEE, tipo CTX-M. Materiales/Métodos: Estudio descriptivo, retrospectivo, con adultos internados en un hospital universitario. Incluimos infecciones del tracto urinario (ITU), intra-abdominales (IIA) e infecciones de tejidos blandos (ITB). Resultados: Estudiamos 40 pacientes, donde 65% correspondían a ITU, 25% IIA y 10 % ITB. La cura clínica global se logró en 89,4%, con mejores resultados en las ITU (100%), seguidas de ITB (80%) e IIA (70%). El 85% de las cepas tenía concentraciones inhibitorias mínimas (CIM) ≤ 8 μg/mL y 70% con CIM ≤ 4 μg/mL. La tasa de fracaso fue mayor en las infecciones con inóculos altos intraabdominales. La BLEE del tipo CTX-M-15 se encontró en 62,5%. Conclusiones: Piperacilina/tazobactam logró cura clínica y microbiológica, en pacientes con infecciones por E. coli productoras de BLEE susceptibles, especialmente en ITU e IPB y en menor medida en IIA.

Background: Carbapenems are the preferred β-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum β-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers. Aim: To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type. Methods: Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia. Results: We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 μg/ml and 70% with MIC ≤4 μg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%. Conclusions: Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

Association of vitamin D deficiency, season of the year, and latent tuberculosis infection among household contacts.

OBJECTIVES: Vitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure. METHODS: We prospectively enrolled new pulmonary TB cases (n = 107) and their HHC (n = 144) over a 2-year period in Santiago, Chile. We compared plasma 25-hydroxycholecalciferol (25OHD) levels and examined the influence of season, ethnic background, living conditions, and country of origin. RESULTS: Over 77% of TB cases and 62.6% of HHC had VD deficiency (<20 ng/ml). Median 25OHD concentration was significantly lower in TB cases than in HHC (11.7 vs. 18.2 ng/ml, p<0.0001). Migrants HHC had lower 25OHD levels than non-migrants (14.6 vs. 19.0 ng/ml, p = 0.026), and a trend towards a higher burden of latent TB infection (52.9% vs. 35.2%, p = 0.066). Multivariate analysis found VD deficiency in HHC was strongly associated with being sampled in winter/spring (adOR 25.68, 95%CI 7.35-89.7), corresponding to the seasons with lowest solar radiation exposure. Spring enrollment-compared with other seasons-was the chief risk factor for latent TB infection in HHC (adOR 3.14, 95%CI 1.28-7.69). CONCLUSIONS: Hypovitaminosis D was highly prevalent in TB cases and also in HHC. A marked seasonality was found for both VD levels and latent TB in HHC, with winter being the season with lowest VD levels and spring the season with the highest risk of latent TB infection.