Risk factors for extended-spectrum beta-lactamase- and carbapenem- resistant Enterobacteriaceae in patients with urinary tract infection from a tertiary care hospital

Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings. However, the predisposing factors which are responsible for production of extended spectrum beta-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae makes the treatment option narrow and cause multidrug resistance. Aim and Objectives: This study demonstrate various risk factors associated with multidrug resistance in Enterobacteriaceae from UTI at tertiary care center in Gujarat. Material and Methods: A retrospective observational study was conducted at a tertiary-care hospital. Urine samples were received from various departments and outpatient department (OPD). Organisms from Enterobacteriaceae group were isolated and identified by various biochemical methods. ESBL and Carbapenemase producing organisms were then processed for Antibiotic susceptibility test as per CLSI guideline. Results: A total of 196 Enterobacteriaceae organisms were isolated from processed urine samples of tertiary care Hospitals. The most prevalent in people aged 45–65 years (36%) followed by those aged 17–30 (22%) years. UTI due to ESBL and Carbapenemase producer are more isolated in female (28%, 11%) as compare to male (16%, 6%). Indoor patients had higher prevalence of ESBL (29%) and carbapenemases (10%) isolation compare to OPD patient (ESBL-15%, Carbapenemases-7%) and among them most common ward was medicine department. The most common predisposing factor was catheterization followed by diabetes mellitus and obstructive uropathy. Conclusion: High prevalence of ESBL and Carbapenemase producing Enterobacteriaceae is found in Indoor patients than OPD patients. Most of these patients are from Medicine department. Catheterization is the most common risk factor associated with ESBL and carbapenemase producing organism.

Screening and clinical significance of intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) in patients before haploidentical hematopoietic stem cell transplantation / 中国输血杂志

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

The level and significance of CD64 index, matrix metalloproteinase-9 and serum amyloid A in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae infection / 中国医师杂志

Objective:To investigate the level and significance of CD64 index, matrix metalloproteinase-9 (MMP-9) and serum amyloid A (SAA) in peripheral blood of patients with severe carbapenem resistant Enterobacteriaceae (CRE) infection.Methods:A total of 61 patients with severe CRE infection who were admitted to the neurosurgery department of Kashgar First People′s Hospital from January 2019 to January 2022 were selected as the CRE group, and 100 patients with severe carbapenem sensitive Enterobacteriaceae (CSE) infection were selected as the CSE group. The difference in clinical data between the two groups was compared, and the difference in clinical data between the dead and surviving patients in the CRE group was compared. The value of CD64 index, MMP-9 and SAA in differential diagnosis of CRE was analyzed. Logistic regression was used to analyze the influencing factors of prognosis in patients with CRE infection.Results:The age, hypertension, lung disease, liver and kidney disease, comorbidities≥2, antibiotic use≥2 combinations, antibiotic use time>10 days, proportion of carbapenem use, CD64 index, MMP-9, and SAA of the CRE group patients were significantly higher than those of the CSE group patients (all P<0.05). The area under the receiver operating characteristic (ROC) curve for CD64 index, MMP-9, and SAA differential diagnosis of CRE was 0.857, 0.701, and 0.655, respectively (all P<0.05). In the CRE group, the age , the score of Acute Physiological and Chronic Health Status Ⅱ (APACHE Ⅱ) score at admission, diabetes, liver and kidney diseases, comorbidities≥2, the proportion of carbapenems, CD64 index, MMP-9 and SAA of dead patients were significantly higher than those of survivors (all P<0.05). Logistic regression analysis showed that age, APACHE Ⅱ score at admission, comorbidities≥2, CD64 index, MMP-9, and SAA were influencing factors for the prognosis of severe CRE patients (all P<0.05). Conclusions:The peripheral blood CD64 index, MMP-9, and SAA have certain application value in the diagnosis of neurological severe CRE infection, and are also influencing factors for the prognosis of CRE infected patients.

Programa de prevención de Enterobacterias Productoras de Carbapenemasas en unidades críticas en Argentina durante la pandemia COVID-19 / Program for the prevention of Carbapenemase-Producing Enterobacteria in critical units in Argentina during the COVID-19 pandemic

Resumen Introducción: La problemática de las enterobacterias productoras de carbapenemasas (EPC) se exacerbó con la pandemia por COVID-19 en países con una incidencia previa elevada, como la Argentina. Este estudio describe el desarrollo y resultados de un programa de prevención de EPC, fundamental mente Klebsiellas productoras de carbapenemasas (KPC), en tres unidades críticas de dos hospitales públicos durante 6 meses de la pandemia. Métodos: El objetivo fue reducir la incidencia de KPC en muestras clínicas y de colonización. Este estudio, quasi experimental, se basó en un ciclo de mejora e implementación de tres me didas: higiene de manos, higiene ambiental y vigilancia periódica con hisopados rectales. Resultados: Respecto a las medidas, todas las unidades mejoraron la vigilancia activa y dos de estas tuvieron además mejoría en la higiene de manos e higiene ambiental. Comparando los períodos pre y post intervención en las tres unidades no se observaron cambios significativos en la tasa de muestras clínicas KPC positivas. Se logró disminuir en forma significativa la colonización por KPC en dos unidades (unidad 2: 51.6-18.5 p 0.0004, unidad 3: 62.5-5.2 p < 0.0000001). Todas las unidades mostraron hacia el final del estudio una tendencia al descenso en ambas tasas. Conclusión: Contener o reducir el avance de KPC en nuestra región es posible incluso en escenarios difíciles como el de la pandemia. Se necesitan más estudios en países de ingresos bajos y medianos, para demostrar el impacto de los programas de prevención de KPC en estas situaciones.

Abstract Introduction: The problem of carbapenemase-producing Enterobacteriaceae (CPE) was exacerbated by the COVID-19 pandemic in countries with a previous high incidence, such as Argentina. This study describes the development and results of a CPE prevention program, mainly carbapenemase-producing Klebsiellas (KPC), in three critical units of two public hospitals during 6 months of the pandemic. Methods: The objective was to reduce the incidence of KPC in clinical and colonization samples. This quasi-experimental study was based on a cycle of improvement and implementation of three measures: hand hygiene, environmental hygiene, and periodic surveillance with rectal swabs. Results: Regarding the measures, all the units optimized active surveillance, and two of these also improved hand and environmental hygiene. Comparing the pre- and post-intervention periods in the three units, no significant change was observed in the rate of KPC positive clinical samples. KPC coloni zation was significantly reduced in two units (unit 2: 51.6-18.5 p 0.0004, unit 3: 62.5-5.2 p < 0.0000001). All units showed a downtrend in both rates towards the end of the study. Conclusion: Containing or reducing the advance of the KPC in our region is possible even in difficult scenarios such as the pandemic. More studies are needed in low- and middle-income countries to demonstrate the impact of KPC prevention programs in these situations.

Eficacia de la terapia con aminoglicósidos en infectados por Klelsiella pneumoniae resis-tente a carbapenémicos / Efficacy of aminoglycoside therapy in patients infected with Carbapenem-Resistant Klel-siella pneumoniae

El tratamiento de infecciones por bacterias resistentes a determinados grupos farmacológicos resulta un tema de alto interés para la ciencia. Así, la investigación tuvo el propósito de sistema-tizar la información acerca de la eficacia de los aminoglicósidos en pacientes infectados por Klebsiella pneumoniae resiste a carbapenémicos; para lo que se hizo una revisión sistemática siguiendo el protocolo PRISMA. Las fuentes se ubicaron a partir de una pesquisa se hizo en las bases de datos: PubMed, MEDLINE y SCOPUS; quedando seleccionados 11 artículos que cumplieron con los requisitos establecidos. Se observó un predominio de los artículos provenientes de los Estados Unidos de América (4/11) y Brasil (3/11). La población global fue de 3778 pacientes entre las 11 investigaciones incluidas. El uso de aminoglicósidos resultó más eficaz que otros grupos farmacológicos en la mejoría en el estado clínico, reflejando menores valores de mortalidad en pacientes hospitalizados por la infección en cuestión.

The treatment of infections by bacteria resistant to certain pharmacological groups is a topic of great interest for science. Thus, the research had the purpose of systematizing the information about the efficacy of aminoglycosides in patients infected by Carbapenem-Resistant Klebsiella pneumoniae. This systematic review was carried out following the PRISMA protocol. The sour-ces were located from a search made in the databases: PubMed, MEDLINE, and SCOPUS; 11 articles were selected that met the established requirements. A predominance of articles from the United States of America (4/11) and Brazil (3/11) was observed. The overall population was 3,778 patients among the 11 studies included. The use of aminoglycosides was more effective than other pharmacological groups in improving clinical status, reflecting lower mortality values in patients hospitalized for the infection in question

Occurrence of blaKPC gene in clinical isolates of Pseudomonas aeruginosa from Brazil

Pseudomonas aeruginosa is one of the main microorganisms causing healthcarerelated infections. The rise of carbapenem-resistant P. aeruginosa (CRPA) strains has become a serious public health problem. Dissemination of the enzyme Klebsiella pneumoniae carbapenemase (KPC) encoded by the blaKPC gene cause the inactivation of ß-lactam antibiotics being one of the mechanisms involved in this resistance. Given the above, the objective of this review was to evaluate the occurrence of the blaKPC gene in clinical isolates of P. aeruginosa in Brazil. For this, the online databases used were: Lilacs, SciELO and PubMed. The search for articles included articles published from 2012 to 2020, using the following keywords: blaKPC (KPC), Pseudomonas aeruginosa, and Brazil (in Portuguese and English). Initially, 30 publications eligible for inclusion in this review were identified. After the first analysis, two articles were excluded due to duplication. Subsequently, titles and abstracts were evaluated, 15 articles were excluded because they did not fit the theme, and 13 articles that met the inclusion criteria were read in full. In these studies, the presence of the blaKPC gene was investigated in 566 clinical isolates of P. aeruginosa in Brazil, with 86 (15.2%) positive samples found. Pernambuco was the state with the highest number of articles and positive samples, respectively, 38.5% (5/13), and 65.1% (56/86). This study reinforces the need to investigate the occurrence of this gene in all regions of the country in CRPA, aiming to understand how its dissemination occurs and to promote prevention and therapeutic strategies.

Enzyme types and drug resistance of carbapenem-resistant Enterobacteriaceae isolated from Linyi area / 中华检验医学杂志

Objective:To detect the genotype of carbapenase and investigate the drug sensibility of Ceftazidime-avibactam (CAZ/AVI) on carbapenem-resistant Enterobacteriaceae (CRE), and to provide evidence for rational use of antibacterial drugs in clinical practice. Methods:A total of 179 strains of CRE were isolated from clinical specimens of patients treated in Linyi People′s Hospital from January 2019 to December 2020. mCIM/eCIM test and GeneXpert were used to detect the genotype of carbapenemases. The drug sensibility of CAZ/AVI was detected by K-B test.Results:One hundred and seventy-four out of 179 strains of CRE were positive upon to mCIM test (97.2%), 147strains were positive upon to eCIM test (84.5%). There were 27 serine carbapenemase (15.5%) and 147 metallo-β-lactamase (84.5%). The results of Fluorescent quantitative PCR rapid detection system developed by Saipei GeneXpert were consistent with the results detected by mCIM/eCIM. In the drug sensitivity test, 58 out of 174 mCIM positive strains were sensitive to CAZ (33.3%), of which the sensitivity of 27 strains producing serine carbapenemase was 96.3% (26/27) and all 147 strains producing metallo-β-lactamase were drug-resistant to CAZ/AVI.Conclusions:The carbapenase genotype of CRE in Linyi region is mainly metal β-lactamase. The CRE producing serine carbapenemase is highly sensitive to CAZ/AVI. It is helpful to guide the rational clinical use of the CAZ/AVI according to the detection results of CRE with or without carbapenemase production capacities.

Risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children: a Meta analysis / 中国当代儿科杂志

OBJECTIVES@#To systematically assess the risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.@*METHODS@#PubMed, Web of Science, China National Knowledge Infrastructure Database, Wanfang Data, China Biology Medicine disc were searched to obtain the articles on risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children published up to May 31, 2021. RevMan 5.3 software was used to perform the Meta analysis.@*RESULTS@#A total of 13 articles were included, with 1 501 samples in total. The Meta analysis showed that indwelling gastric tube (OR=4.91), tracheal intubation (OR=5.03), central venous catheterization (OR=3.75), indwelling urinary catheterization (OR=4.11), mechanical ventilation (OR=3.09), history of hospitalization in the intensive care unit (OR=2.39), history of surgical operation (OR=3.22), previous use of third-generation cephalosporins (OR=2.62), previous use of carbapenem antibiotics (OR=3.82), previous use of glycopeptide antibiotics (OR=3.48), previous use of β-lactamase inhibitors (OR=2.87), previous use of antifungal drugs (OR=2.48), previous use of aminoglycoside antibiotics (OR=2.54), and Apgar score ≤7 at 1 minute after birth (OR=2.10) were risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children (P<0.05).@*CONCLUSIONS@#Invasive operations, history of hospitalization in the intensive care unit, previous use of antibiotics such as carbapenem antibiotics, and Apgar score ≤7 at 1 minute after birth are risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.

Marcadores hematológicos y bioquímicos para el diagnóstico precoz de bacteriemiascausadas por Enterobacteriaceae resistentes a los carbapenémicos / Haematological and biochemical markers for the early diagnosis of bacteremias caused bycarbapenem-resistant Enterobacteriaceae

INTRODUCCIÓN. Las bacteriemias causadas por Enterobacteriaceae resistentes a carbapenémicos se asocian con altas tasas de mortalidad a diferencia de las bacteriemias causadas por Enterobacteriaceae sensibles a carbapenémicos. Los hallazgos clínicos y de laboratorio son importantes para determinar los esquemas terapéuticos y su pronóstico; su diagnóstico precoz resulta esencial para un manejo adecuado. OBJETIVO. Relacionar valores de marcadores sanguíneos y bioquímicos en bacteriemias causadas por Enterobacteriaceae resistentes a carbapenémicos. MATERIALES Y MÉTODOS. Estudio analítico transversal. Población de 427 y muestra de 224 datos de hemocultivos positivos para Enterobacteriaceae de pacientes atendidos en el Hospital de Especialidades Carlos Andrade Marín en el periodo mayo 2016 a julio 2018. Criterios de inclusión: i) al menos un hemocultivo positivo; ii) recuperación del aislado de CRE o CSE y iii) recolección simultanea de muestras de sangre y pruebas de laboratorio. Criterios de exclusión: i) bacteriemias polimicrobianas; ii) valores fuera de rango y iii) reportes sin valores numéricos. El análisis de datos se realizó mediante el programa estadístico International Business Machines Statistical Package for the Social Sciences versión 24.0. RESULTADOS. Se demostró que el recuento de leucocitos [OR 1,21 (95% IC: 1,03-1,43)], el recuento de plaquetas [OR 1,65 (95% IC: 1,37-1,98)] y el tiempo parcial de tromboplastina [OR 1,29 (95% IC: 1,04-1,60)] fueron buenas variables predictoras independientes, mediante análisis de regresión logística multivariante. CONCLUSIÓN. La trombocitopenia y el tiempo parcial de tromboplastina prolongado se asociaron con bacteremia causada por Enterobacteriaceae resistentes a carbapenémicos.

INTRODUCTION. Bacteremias caused by carbapenem-resistant Enterobacteriaceae are associated with high mortality rates in contrast to bacteremias caused by carbapenem-sensitive Enterobacteriaceae. Clinical and laboratory findings are important in determining therapeutic regimens and prognosis; early diagnosis is essential for appropriate management. OBJECTIVE. To relate blood and biochemical marker values in bacteremia caused by carbapenem-resistant Enterobacteriaceae. MATERIALS AND METHODS. Cross-sectional analytical study. Population of 427 and sample of 224 blood culture data positive for Enterobacteriaceae from patients attended at the Carlos Andrade Marín Specialties Hospital in the period May 2016 to July 2018. Inclusion criteria: i) at least one positive blood culture; ii) recovery of CRE or CSE isolate and iii) simultaneous collection of blood samples and laboratory tests. Exclusion criteria: i) polymicrobial bacteremia; ii) out-of-range values and iii) reports without numerical values. Data analysis was performed using the statistical program International Business Machines Statistical Package for the Social Sciences version 24.0. RESULTS. Leukocyte count [OR 1.21 (95% CI: 1.03-1.43)], platelet count [OR 1.65 (95% CI: 1.37- 1.98)] and partial thromboplastin time [OR 1.29 (95% CI: 1.04-1.60)] were shown to be good independent predictor variables, by multivariate logistic regression analysis. CONCLUSION. Thrombocytopenia and prolonged partial thromboplastin time were associated with bacteremia caused by carbapenem-resistant Enterobacteriaceae.

Resistencia a antibióticos de relevancia clínica en un hospital de Corrientes / Resistance to antibiotics of clinical relevance in a hospital of Corrientes city

Resumen Las bacterias productoras de carbapenemasas están involucradas en infecciones y colonizaciones y se asocian a elevada morbimortalidad. Su identificación facilita el diseño y la implementación de intervenciones dirigidas a reducir el riesgo de infecciones y óbitos. El objetivo de este estudio fue determinar la prevalencia de microorganismos productores de carbapenemasas en el principal hospital público de la ciudad de Corrientes, Argentina, y determinar sus perfiles de susceptibilidad a antibióticos comúnmente usados en la práctica clínica. Fueron incluidos 674 muestras clínicas provenientes del mismo número de adultos de las diferentes unidades de internación del Hospital Escuela Gral. José Francisco de San Martín durante el período septiembre-diciembre 2018. La identificación de las bacterias se realizó mediante pruebas bioquímicas manua les y la susceptibilidad a los antimicrobianos se evaluó según las recomendaciones del Clinical and Laboratory Standars Institute. Fueron identificadas 115 bacterias productoras de carbapenemasas de tipo KPC (90, 78%), OXA-ACI (24, 21%) y OXA-163 (~1%). De los 56 (49%) microorganismos involucrados en infecciones, la mayoría de las del tipo KPC (n=32; 57%) mostró sensibilidad solo a amikacina (27/32; 84%), mientras que la mayoría de las del tipo OXA-ACI (n=24; 43%) solo frente a minociclina (17/24; 71%) y colistina (19/24; 79%). En todas las unidades de hospitalización investigadas se comprobó la presencia de microorganismos productores de carbapenemasas y alta frecuencia de resistencia a antimicrobianos de uso habitual en la práctica clínica. Esta información es relevante para adecuar los esquemas terapéuticos y las medidas higiénico-sanitarias a la realidad local.

Abstract Carbapenemase-producing bacteria are involved in infections and colonizations and associated with high morbidity and mortality. Their identification facilitates the design and implementation of interventions aimed at reducing the risk of infections and deaths. The objective of this study was to determine the prevalence of carbapenemase-producing microorganisms in the main public hospital in the city of Corrientes, Argentina, and to determine their susceptibil ity to antibiotics commonly used in clinical practice. We analyzed 674 clinical samples from the same number of adults admitted to different inpatient units of the Hospital Escuela Gral. José Francisco de San Martín during the period September-December 2018. The bacterial identification was carried out through manual biochemical tests and the susceptibility to antimicrobials was evaluated according to the recommendations of the Clinical and Laboratory Standards Institute. We identified 115 carbapenemase-producing bacteria of the following types: KPC (90, 78%), OXA-ACI (24, 21%) and OXA-163 (~1%). Among the microorganisms involved in infections (n = 56; 49%), most of those of the KPC type (n = 32; 57%) showed sensitivity only against amikacin (27/32; 84%), while most of those of the OXA-ACI type ( 24; 43%) showed significant sensitivity only against minocycline (17/24; 71%) and colistin (n = 19/24; 79%). This study demonstrated the presence of carbapenemase-producing microorgan isms in all the investigated hospital units and a high frequency of resistance to antimicrobials commonly used in clinical practice. This information is relevant to adapt the therapeutic schemes and hygienic-sanitary measures to the local reality.

Mortalidad y desenlaces clínicos en pacientes críticamente enfermos con infecciones por bacterias productoras de carbapenemasas en un hospital de alta complejidad en Bogotá, Colombia / Mortality and clinical outcomes in critically ill patients with carbapenemase-producing bacteria in a tertiary-care hospital in Bogotá, Colombia

Resumen Introducción: Los microorganismos capaces de producir carbapenemasas vienen incrementándose a nivel mundial y se han convertido en un problema de salud pública global. En Colombia actualmente la resistencia a carbapenémicos en las unidades de cuidado intensivo está aumentando y se desconoce su impacto en desenlaces clínicos. Objetivos: Determinar las características demográficas, clínicas, y los desenlaces de los pacientes adultos en estado crítico con infección por microorganismos productores de carbapenemasas en una unidad de cuidado intensivo polivalente de una institución de alta complejidad. Métodos: Estudio observacional, descriptivo y retrospectivo, incluyendo pacientes con infección por bacterias resistentes a carbapenémicos, ingresados a la unidad de cuidado intensivo entre el 1 de Enero de 2014 y el 1 de Enero de 2018. Se excluyeron los pacientes colonizados. Se evaluaron complicaciones clínicas, estancia en UCI y hospitalaria, así como la mortalidad en UCI y hospitalaria. Resultados: Se incluyó 58 pacientes. La mortalidad global fue de 67,2%, de los cuales 55,17% murió durante su estancia en la unidad de cuidado intensivo y 12.06% en hospitalización. La mediana de estancia en la unidad de cuidado intensivo fue de 18 días (RIQ 4-28). La causa más frecuente de mortalidad fue choque séptico en 51% y las complicaciones más comunes fueron lesión renal aguda y delirium en un 55,2% y 43,1%, respectivamente. La mediana de estancia en la UCI fue de 18 días (RIQ 4-28). Conclusiones: Las infecciones por bacterias resistentes a carbapenémicos en pacientes críticamente enfermos se relacionan con altas tasas de mortalidad, complicaciones y estancia prolongada en UCI

Abstract Introduction: Microorganisms able to produce carbapenemases are spreading worldwide and have become a concerning global public-health problem. In Colombia, the Gram-negative resistance to carbapenems at intensive care units is currently increasing and its impact on clinical outcomes is not well known. Objectives: To determine the demographic, clinical characteristics and outcomes of critically ill adult patients with infection by carbapenemase producing bacteria in a polyvalent intensive care unit of a highly complex institution. Methods: Single-center retrospective, descriptive observational study including critically ill adult patients infected by carbapenemase-producing bacteria and transferred to a polyvalent intensive care unit from January 1th 2014 to January 1th 2018. Known colonized patients were excluded. Clinical complications, ICU and in-hospital days of stay were evaluated, as ICU and in-hospital mortality. Results: A total of 58 patients were included. Overall mortality was 67.2%, of which 55.17% died during their stay in the intensive care unit and 12.06% in hospitalization. The median stay in the intensive care unit was 18 days (IQR 4-28). The most frequent cause of death was septic shock in 51% and the most common complications were acute renal injury and delirium in 55.2% and 43.1%, respectively. The median stay in the ICU was 18 days (RIQ 4-28). Conclusions: Infections caused by carbapenem-resistant bacteria in critically ill patients are associated with high mortality rates, complications and long stay in ICU.

Costo-efectividad de ceftazidima/avibactam versus colistin + meropenem en el tratamiento de infecciones por enterobacterias resistentes a carbapenémicos en Chile / Cost-effectiveness of ceftazidime/avibactam versus colistin + meropenem for treatment of carbapenemic-resistant enterobacteria infections in Chile

INTRODUCCIÓN: Ceftazidima-avibactam (C/A), ha demostrado reducir las tasas de mortalidad y el riesgo de nefrotoxicidad, comparado con colistin, la terapia convencional. OBJETIVO: Estimar la costo-efectividad de C/A versus colistin + meropenem en el tratamiento de infecciones por Enterobacteriaceae resistentes a carbapenémicos (ERC) en Chile. MATERIAL Y MÉTODOS: Se adaptó un modelo económico tipo árbol de decisión. Se utilizó la perspectiva del pagador público, un horizonte de tiempo de 30 días con extrapolación a la expectativa de vida. La información clínica se derivó de un estudio observacional. Los costos de los medicamentos y de atención corresponden a reportes locales. Los resultados se expresan como razón de costo-efectividad incremental (RCEI) por año de vida ganado (AVG) y por año de vida ajustado por calidad (AVAC) en pesos chilenos y en dólares estadounidenses (US$ 1,00 = $792,2218). RESULTADOS: Se obtuvieron 8,65 y 6,48 AVGs y 6,44 y 4,27 AVACs, para C/A y colistin + meropenem, respectivamente. La RCEI estimada de C/A fue $940.488 (US$1.187,2) por AVG y $938.715 (US$1.184,9) por AVAC. DISCUSIÓN: Dada la falta de publicaciones o evidencia, el modelo se basa en un estudio observacional. C/A reduciría la proporción de muertes e incrementaría los AVG y los AVAC, resultando en una alternativa costo-efectiva versus colistin + meropenem para ERC.

BACKGROUND: Ceftazidime-avibactam (C/A), has shown reduction in mortality rates and risk of nephrotoxicity, compared to colistin, conventional therapy. AIM: To estimate the cost-effectiveness of C/A versus colistin + meropenem in the treatment of infections due to carbapenem-resistant Enterobacteriaceae (CRE) in Chile. METHODS: An economic decision tree type model was adapted. The perspective of the public payer was used with a time horizon of 30 days and extrapolation to life expectancy. The clinical information was derived from an observational study. Medication and care costs correspond to local reports. The results are expressed as incremental cost-effectiveness ratio (ICER) per life year gained (LYG) and per quality adjusted life year (QALY) in Chilean pesos and US dollars (US$ 1.00 = $792.2218). RESULTS: 8.65 and 6.48 LYGs and 6.44 and 4.27 QALYs were obtained, for C/A and colistin + meropenem, respectively. The estimated ICER for C/A was $940,488 (US$1,187.2) per AVG and $938,715 (US$1,184.9) per QALY. DISCUSSION: Given the lack of publications or evidence, the model is based on an observational study. C/A would reduce the death rate and increase LYGs and QALYs, resulting in a cost-effective alternative vs. colistin + meropenem for CRE.

Infecção de loja de cardioversor-desfibrilador implantável (CDI) por klebsiella sp. Carbapenem-resistente / Klebsiella sp. carbapenem-resistant pocket infection of an Implantable Cardioverter Defibrillator (ICD)

RESUMO: As infecções associadas aos Dispositivos Cardíacos Eletrônicos Implantáveis (DCEI) apresentam uma incidência de até 3,4% e notável impacto na morbidade e mortalidade dos pacientes. As bactérias Gram-positivas, especialmente do gênero Staphylococcus sp. representam 60-70% dos agentes isolados. Por sua vez, as Gram-negativas correspondem até 9% dos casos. Relatamos uma infecção de loja de gerador de Cardioversor-desfibrilador implantável (CDI) por uma Klebsiella sp. resistente aos carbapenêmicos, em um paciente masculino jovem, cujo desafiador diagnóstico de certeza desse caso somente foi possível após exploração cirúrgica e cultura do material da loja do CDI, haja vista a apresentação clínica oligossintomática. Embora já descritas, Klebsiella sp. são raras nesse contexto e em nosso conhecimento, esse é o primeiro relato de uma infecção de DCEI por uma enterobactéria resistente a carbapenêmico. (AU)

ABSTRACT: Infections associated with Implantable Electronic Cardiac Devices (IECD) have an incidence of up to 3.4% and a notable impact on patient morbidity and mortality. Gram-positive bacteria, especially Staphylococcus sp. represent 60-70% of isolated agents. In turn, gram-negatives account for up to 9% of cases. We report an Implantable Cardioverter-Defibrillator (ICD) generator pocket infection by a Carbapenem Resistant Klebsiella sp., in a young male patient, whose challenging diagnosis of certainty was only possible after surgical exploration and culture of the material from the ICD pocket, given the oligosymptomatic clinical presentation. Although already described, Klebsiella sp. are rare in this context and to our knowledge, this is the first report of an IECD infection by a carbapenem-resistant enterobacterium. (AU)

Advances in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae in elderly patients / 中华老年医学杂志

The proportion of the elderly infected with carbapenem-resistant Enterobacteriaceae(CRE)has increased in recent years, with prolonged hospitalization, high mortality and various complications.In this paper, the epidemiological characteristics of CRE infections in the elderly, individualized screening of elderly patients at high-risk for CRE infections, multi-drug combination therapy for patients with CRE infections, and recent progress in eliminating CRE infections and colonization are reviewed to provide a reference for clinical practice.

Clinical Characteristics and Risk Factors of CarbapenemResistant Enterobacteriaceae: A Case-Control Study in a Tertiary Hospital in Malaysia

@#Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) is increasingly reported worldwide causing serious threats to healthcare. This study aimed to identify the common organisms associated with CRE, the clinical characteristics and risk factors for acquiring CRE infection and colonisation among hospitalised patients. Methods: This is a matched, case-control study. Patients aged 18 years and above whom were hospitalised from January 2019 to December 2019 and had CRE isolated from clinical specimens were matched with carbapenem-susceptible controls (CSE), based on gender and age. Univariate and multivariate statistical analysis was performed. Results: Among 184 patients, Klebsiella pneumoniae was the most common organism causing CRE infection and colonisation. Chronic kidney disease (p=0.025, OR:3.12, 95% CI:1.15-8.41), urinary catheterisation (p=0.005, OR:3.67, 95% CI:1.49- 9.00), prior use of cephalosporin (p<0.001, OR:4.69, 95% CI:1.96–11.22) and beta-lactam combination agent (p<0.001, OR:7.18, 95% CI:2.98-17.26) were identified as the independent risk factors. Conclusion: Chronic kidney disease, urinary catheterisation, prior use of cephalosporin and beta-lactam combination agents were independently associated with CRE infection and colonisation. These findings enable targeting potential CRE cohorts, hence, necessitate early undertaking of prevention measures to delay the onset of CRE. A rigorous effort by antibiotic stewardship an infection control team are pivotal.

Características clínicas y microbiológicas de infecciones por Klebsiella pneumoniae productora de carbapenemasa MBL, tipo NDM, Hospital Geriátrico San Isidro Labrador EsSalud, 2018 / Clinical and microbiological characteristics of New Delhi MBL (NDM)-producing Klebsiella pneumoniae infections at the Hospital Geriátrico San Isidro Labrador EsSalud, 2018

RESUMEN Objetivo Determinar las características clínico-microbiológicas de 7 casos de infección nosocomial por Klebsiella pneumoniae productora de carbapenemasa MBL, tipo NDM, en el Hospital Geriátrico San Isidro Labrador (HG SIL) en el periodo de febrero a mayo de 2018. Materiales y métodos Es un estudio descriptivo y retrospectivo realizado en adultos mayores con infecciones urinarias, neumonías, úlceras sacras e infecciones de herida operatoria que recibieron terapia antibiótica múltiple no protocolizada. El método usado para detectar la MBL fue el de doble disco con ácido fenilborónico (APB) y ácido etilendiaminotetraacético (EDTA) en los aislados de Klebsiella pneumoniae con sensibilidad disminuida a carbapenémicos. La identificación del gen NDM se realizó en el Instituto Nacional de Salud mediante reacción en cadena de la polimerasa. Resultados En total, fueron 7 casos positivos para el gen NDM y todos resistentes al meropenem lo que confirmó el brote epidémico. La mortalidad fue 28,6 % (2 de 7 pacientes) pero, debido a la existencia de comorbilidades en todos los casos, no se pudo determinar la mortalidad atribuible. Conclusiones Destacan el rol clave inicial del laboratorio para detectar y tipificar las carbapenemasas y las medidas de control integral de las infecciones. Además, son los primeros casos reportados en nuestra red asistencial.

ABSTRACT Objective To determine the clinical and microbiological characteristics of seven (7) cases of New Delhi MBL (NDM)- producing Klebsiella pneumoniae nosocomial infections at the Hospital Geriátrico San Isidro Labrador (HG SIL) from February to May 2018. Materials and methods A descriptive and retrospective study conducted in elderly people with urinary infections, pneumonia, sacral ulcers and surgical wound infection who received multiple non-protocolized antibiotic therapy. The methods used to detect MBLs in the Klebsiella pneumoniae isolates that showed decreased sensitivity to carbapenems were the phenylboronic acid-based (PBA) and ethylenediaminetetraacetic acid-based (EDTA) double disk tests. The identification of the NDM gene was performed by polymerase chain reaction at the Instituto Nacional de Salud. Results In total, the seven cases were positive for the NDM gene and resistant to meropenem, which confirmed the epidemic outbreak. Mortality accounted for 28.6 % (2 of 7 patients) of the cases. However, due to the presence of comorbidities in all cases, the attributable mortality could not be determined. Conclusions Labs have a key initial role for detecting and classifying the carbapenemases and the measures of comprehensive control of infections. The aforementioned cases are the first ones reported in our healthcare network.

Tigecycline Susceptibility of Carbapenem Resistant Enterobacteriaceae and Acinetobacter spp. isolates from Respiratory Tract: A Tertiary Care Centre Study.

Background: Tigecycline is used as a last line ofdefence against Multidrug Resistant (MDR) strains,and increasing rates of resistance are a growing concernglobally. Tigecycline resistance has been reported invarious pathogens including Acinetobacter spp.,Klebsiella spp., Enterobacter spp., E. faecalis, S.aureus, S. pneumoniae and Serratia marcescens. Aimand Objectives: To study Tigecycline susceptibilitypattern of isolates of Enterobacteriaceae andAcinetobacter spp. from Respiratory Tract Infections(RTI) in a tertiary care hospital. Material and Methods:A total of 7573 respiratory samples were received inMicrobiology Department of Govind Ballabh PantInstitute of Postgraduate Medical Education andst st Research (GIPMER) from 1 January 2018 to 31December 2018. The samples were processed as perstandard techniques. Identification and antimicrobialsusceptibility testing was done by VITEK-2 Compactautomated system and Kirby – Bauer Disc DiffusionMethod as per CLSI Guidelines. Results: Out of total7573 respiratory samples received in laboratory, 1017(13.42%) were culture positive for pathogens.Klebsiella pneumoniae 420(41.29%) waspredominantly isolated microorganism followed byPseudomonas aeruginosa 206(20.25%) andAcinetobacter spp. 193(18.97%). Most of Gramnegative organisms were resistant to commonly usedantibiotics. Carbapenem resistance was observed as67.25%. Conclusion: Overall Tigecycline resistanceamong Carbapenem Resistant Enterobacteriaceae(CRE) and Carbapenem Resistant Acinetobacter(CRA) was found to be 15.50% and 10.69%respectively. Although Tigecycline is a promisingantibiotic for the treatment of infections caused by drugresistant problematic pathogens, Tigecycline resistanceis most frequently observed in A. baumannii andEnterobacteriaceae, especially in MDR strains. Hence,we advocate judicious use of Tigecycline in MDRinfections and it should be kept as reserve.

Carbapenemase-producing Enterobacteriaceae: A diagnostic, epidemiological and therapeutic challenge / Enterobacteriaceae productoras de carbapenemasas: Un reto diagnóstico, epidemiológico y terapéutico

The global spread of carbapenemase-producing Enterobacteriaceae (CPE) has become a public health problem. Not all CPE are resistant to carbapenems creating a diagnostic and therapeutic challenge. Furthermore, as resistance to carbapenems can also be mediated by other β-lactamases combined with defects in membrane permeability, their detection can be difficult by microbiology laboratories that lack molecular tools, which may limit and often delay the correct antibiotic selection. There is only limited evidence regarding infection control measures to contain the spread of CPE. However, recomendations have been published from the World Health Organization (WHO) and the European Prevention Center and Disease Control (ECDC). Because of the lack of randomized control trials, treatment regimens are mostly based on observational clinical studies. Several of those studies have reported that combination therapy with two or more in vitro-active agents including a carbapenem is superior to monotherapy. On the other hand, a new β-lactamase inhibitor in combination with ceftazidime has shown clinical efficacy Against KPC and some OXA-type producing Enterobacteriaceae

La diseminación global de las Enterobacteriaceae productoras de carbapenemasas (EPC) se ha convertido en un problema de salud pública. No todas las EPC son resistentes a los carbapenémicos, por lo que representan un reto diagnóstico y terapéutico. Adicionalmente, como la resistencia a los carbapenémicos puede ser mediada por otras β-lactamasas en combinación con cambios de la permeabilidad de la membrana plasmática, su detección puede ser difícil en laboratorios de microbiología que no cuentan con técnicas de diagnóstico molecular, lo que puede restringir y frecuentemente retrasar el inicio de la terapia antimicrobiana adecuada. La evidencia respecto a las medidas para la contención de las EPC es escasa. Sin embargo, existen recomendaciones por parte de la Organización Mundial de la Salud y del European Prevention Center and Disease Control (ECDC). Debido a la ausencia de estudios controlados y aleatorizados, los esquemas terapéuticos se basan en estudios clínicos observacionales. Varios de estos estudios han reportado mejores resultados con la terapia combinada de dos o más agentes activos in vitro, incluyendo a los carbapenémicos, en comparación con la monoterapia. Por otra parte, un nuevo inhibidor de β-lactamasas en combinación con ceftazidime, ha mostrado eficacia clínica contra infecciones por Enterobacteriaceae productoras de KPC y algunas carbapenemasas de tipo OXA.

Fecal carriage of carbapenem resistant Enterobacteriaceae among the intensive care unit patients

Background: The war against multidrug-resistant bacteria is challenging and of global concern. Hospitals are increasingly plagued by resistant gram negative pathogens. Bacteria of the family Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae are part of the normal human intestinal flora but are also often responsible for community- and healthcare-associated infections. These bacteria are prone to acquiring resistance genes.Methods: Rectal swabs/swabs from the peri-anal area of the patients who were admitted in the Intensive Care Unit (ICU) of the accident and emergency department of this teaching hospital. Swabs were collected first on day 1 of admission, then day 4, and thereafter weekly during the period of stay in the ICU. All the swabs were immediately inoculated into trypticase soy broth with one 10μg  meropenem disc and were incubated overnight at 35±2ºC, ambient air. Next day, the broth was vortexed, and then sub-cultured onto a MacConkey agar plate. On the third day, MacConkey agar plates were examined for lactose fermenting (pink-coloured) colonies. The representative isolated colonies were subjected to conventional antimicrobial susceptibility testing by the Kirby Bauer Disc diffusion method following the CLSI guidelines to know the susceptibility to carbapenem and other antimicrobial agents. Carbapenemase production was done by a Modified Hodge Test (MHT) and Imipenem-EDTA test.Results: Out of 89 patients, carbapenem resistant Klebsiella pneumoniae and E. coli isolates were recovered from 35 (39.3%) patients i.e. Klebsiella pneumoniae isolates from fifteen patients and carbapenem resistant E. coli isolates from twenty patients. Prevalence of carbapenemase producing isolates was found to be 1.42%.  Conclusions: Surveillance for CRE can definitely help reduce rates of healthcare associated infections.

Contribution of acrB upregulation & OmpC/Ompk36 loss over the presence of blaNDM towards carbapenem resistance development among pathogenic Escherichia coli & Klebsiella spp.

Background & objectives: The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is an emerging clinical problem. Hence, in this study, the plausible role of extended-spectrum beta-lactamases (ESBLs)/carbapenemases, OmpC/Ompk36, acrB and their combinations was explored among CRE. Methods: The minimum inhibitory concentration (MIC) of meropenem, enzyme-phenotypes (ESBLs/IR and metallo-beta-lactamase (MBL)/non-MBL carbapenemase), genotypes (blaTEM, blaSHV and blaCTX-M; blaNDM and blaVIM; blaKPC and blaOXA-48-like variants), acrB and outer membrane protein (OMP) expressions were analyzed with a total of 101 non-duplicate clinical isolates, obtained from various samples of patients visiting two tertiary care units of Eastern India during May 2013 - October 2016. This included Escherichia coli (n=36) and Klebsiella pneumoniae (n=65), categorized into two groups, namely Group I (resistant to all carbapenems; n=93; E. coli=34 and Klebsiella spp.=59) and Group II (non-resistant to all the carbapenems; n=8; E. coli=2 and Klebsiella spp.=6). Results: Though 88.17 per cent of Group I isolates exhibited ESBL property, the presence of carbapenemase activity (70.96%) and that of blaNDM gene (42/66: 63.63%) indicated their contributions towards the emergence of CRE. Further, porin loss and/or efflux pump activation among ESBL/carbapenemase-producing isolates heightened the MIC of meropenem from 64 to 256 mg/l (range exhibited by only ESBL/carbapenemase-producing isolates) to >256 mg/l. Interpretation & conclusions: These findings implied the major contribution of porin loss and/or efflux pump activation over the presence of ESBLs/carbapenemases in imparting carbapenem resistance in pathogenic bacteria.