RESUMO
Introducción: La aparición y diseminación de Enterobacterales resistentes a carbapenémicos ha generado un gran impacto en las infecciones asociadas a la atención de salud en el mundo. Recientemente, en Chile se detectó un brote por Klebsiella pneumoniae productora de carbapenemasas tipo oxacilinasas (OXA) de la subfamilia tipo OXA-48, reportándose los primeros casos en pacientes hospitalizados mayoritariamente en la zona norte del país. Objetivo: Determinar los perfiles fenotípicos, genotípicos y de susceptibilidad antimicrobiana de 16 cepas referidas durante mayo del año 2021 desde las regiones de Antofagasta y Metropolitana al Laboratorio de Referencia del Instituto de Salud Pública. Metodología: Las cepas provenientes de muestras clínicas fueron analizadas mediante técnicas tradicionales (Kirby-Bauer y epsilometría) y automatizadas, además de técnicas colorimétricas, inmunocromatográficas y moleculares (RPC y PFGE). Resultados: Se detectó la presencia de los genes blaoxa-48 y blaoxa-232 con una resistencia inusual, tanto a carbapenémicos (ertapenem, imipenem y meropenem) como a cefalosporinas (cefepime, cefotaxima y ceftazidima), además de piperacilina/tazobactam y temocilina. Se detectaron dos subtipos por PFGE, siendo predominante el clon CL-Kpn-Spe-329 (93,8%) con dos mecanismos de resistencia identificados: carbapenemasa y β-lactamasa de espectro extendido (BLEE). Conclusión: Ante esta alerta epidemiológica es necesario unificar criterios existentes en la red asistencial nacional para la oportuna detección, vigilancia y control de posibles brotes de cepas productores de oxacilinasa tipo OXA-48.
Background: The appearance and spread of carbapenems-resistant Enterobacterales have generated a major impact on health care-associated infections worldwide. Recently, a Klebsiella pneumoniae outbreak expressing OXA-48 like-carbapenemases was detected in Chile, the first reported cases corresponded to hospitalized patients mainly from northern Chile. Aim: To characterize the phenotypic and genotypic profiles of antimicrobial susceptibility of 16 clinical isolates referred during May 2021 from Antofagasta and Metropolitan regions to the Reference Laboratory of Instituto de Salud Publica. Methods: Antimicrobial susceptibility of all strains was analyzed using traditional (Kirby-Bauer and epsilometry) and automated methods, and complemented with colorimetric, immunochromatographic and molecular (PCR and PFGE) techniques. Results: As a result of the genetic characterization, blaoxa-48 and blaoxa-232 genes were detected, showing the isolates an unusual resistance profile to both carbapenems (ertapenem, imipenem, and meropenem) and cephalosporins (cefepime, cefotaxime, and ceftazidine), as well as piperacillin/ tazobactam and temocillin. Two subtypes were detected by PFGE, with a predominant clone CL-Kpn-Spe-329 (93.8%), with two resistance mechanisms identified: carbapenemase and extended-spectrum β-lactamase (ESBL). Conclusion: Due to this epidemiological alert, it is essential the establishment of national guidelines for early detection, surveillance, and control of future outbreaks of OXA-48 like carbapenemases isolates.
RESUMO
BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.
