Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

Enterobacterales resistentes a carbapenemes: estudio epidemiológico de aislamientos en un hospital público de Santa Fe / Carbapenem-resistant Enterobacterales: Epidemiological study of isolates in a public hospital in Santa Fe

Introducción: La incidencia de Enterobacterales resistentes a carbapenemes (ERC) se elevó en la última década, y en especial durante la pandemia de COVID-19. Objetivo: Conocer el perfil de resistencia antimicrobiana, así como la frecuencia y tipo de carbapenemasas presen-tes en los aislamientos de ERC en un hospital regional.Materiales y métodos: Estudio epidemiológico, observa-cional y retrospectivo. Incluyó ERC aislados en muestras clínicas durante 2021 en un hospital regional de Santa Fe, Argentina. El cálculo de la incidencia (aislamientos/pacien-tes-día) e intervalo de confianza 95% (IC 95%), y las pruebas estadísticas se realizaron con OpenEpi.Resultados: 348 ERC aislados (11,9 aislamientos/1000 pacientes-día; IC95% 10,7-13,2). La incidencia se correla-cionó con los casos de COVID-19 (rho=0,874, p<0,001) y fue a expensas de la Unidad de Cuidados Intensivos (76,4%). El principal ERC aislado fue Klebsiella pneumoniae (71,4%, n=260). KPC fue el principal mecanismo de resistencia (61,2%). Se aislaron dos doble productores de carbapene-masas. La tasa global de resistencia a los antibióticos no betalactámicos evaluados fue superior en Klebsiella pneu-moniae que en el resto de los aislamientos resistentes a carbapenemes (60,6% vs. 38,5%, p<0,001). En KPC hubo mayor resistencia a colistin (44,6% vs. 23,9%, p=0,001) y menor a amikacina (23,9% vs. 72,6%, p<0,001).Conclusión: Frente a las escasas opciones terapéuticas en infecciones por ERC se destaca la importancia de conocer los mecanismos de resistencia implicados y la epidemiología local

Introduction: The incidence of carbapenem-resistant Enterobacterales (CRE) rose in the last decade, and especially during the COVID-19 pandemic.Objective: To identify the antimicrobial resistance profile, as well as the frequency and type of carbapenems that were present in CRE isolations in a tertiary care hospital.Materials and methods: Epidemiological, observational and retrospective study. It included CRE isolated in clinical samples during 2021 in a tertiary care hospital in Argentina. Incidences (isolations/patients-day), confidence intervals of 95% (CI 95%) and statistical comparisons were made with OpenEpi.Results: 348 CRE were isolated (11.9 isolations/1,000 patients-day, IC95% 10.7-13.2). Incidence correlated to COVID-19 cases (rho=0.874, p<0.001). Most isolations were from the Intensive Care Unit (76.4%) and the from respiratory samples (27.6%, n=96) and blood cultures (24.4%, n=92). The main isolated CRE was Klebsiella pneumoniae (71.4%, n=260), with a general carbapenem resistance of 53.4%. KPC was the main resistance mechanism (61.2%). Two double carbapenemase-producing Enterobacterales were isolated. Klebsiella pneumoniae presented a higher overall resistance rate to non-betalactam antibiotics (60.6% vs 38.5%, p<0.001). Among CRE, a higher colistin resistance rate was found in KPC isolations (44.6% vs 23.9%, p=0.001) and lower resistance to amikacin (23.9% vs 72.6%, p<0.001).Conclusion: The difficulty in the selection of antibiotic regimens for CRE forces the treating physicians to put emphasis on the knowledge of resistance mechanisms to optimize them

Detection and correlation of antimicrobial resistance pattern in Enterobacteriaceae from UTI patients in GMERS Medical College, Gujarat

Background: Bacterial resistance to antibiotics is a growing public health threat worldwide. The increasing rate of antimicrobial resistance among bacterial pathogens causing both hospital- and community-acquired infections is a serious threat to public health world-wide. This inappropriate and non-judicious usage of antibiotics has resulted in the development of worldwide antibiotic resistance in bacteria, leading to the emergence of multi-resistant strains of bacterial pathogens. This study focuses on the prevalence of antibiotic resistance in the Enterobacteriaceae group of organisms in urine samples and also detects various methods of antibiotic resistance. Antibiotic resistance detection may be useful for epidemiological and research purposes, as well as for preventing the spread of drug-resistant organisms within hospitals through good infection control practices. Aims and Objectives: The aim of the study was to detect occurrence of ?-lactamases, extended-spectrum beta-lactamases (ESBL) and Carbapenemase by phenotypic methods in Enterobacteriaceae from urine samples along with pattern of antibiotic resistance for various antibiotics in them. Materials and Methods: A descriptive study was conducted at a tertiary-care hospital. Testing of ESBL and carbapenemase production detection done according to CLSI (M100) guideline by the Kirby-Bauer disk diffusion method, combination disc diffusion test, and modified Carbapenem inactivation method. Results: A total of 220 Enterobacteriaceae organisms were isolated from processed urine samples of tertiary care Hospitals. Rate of cephalosporin resistance in ESBL and carbapenem-resistant Enterobacteriaceae (CRE) is more than 90% while in non-ESBL more than 70% and in non-CRE 75–80%. Carbapenem resistance in ESBL and non-ESBL is the same. Resistance to fluoroquinolone group, Aminoglycoside group, and Cotrimoxazole and Tetracycline group of antibiotics were more noticed in ESBL and carbapenemase producing organisms. In our study, fosfomycin and Nitrofurantoin are effective treatment in case of ESBL and CRE producing organism. Conclusion: The ESBL and Carbapenemase producing isolates were multi-drug resistant making therapeutic choices limited. Fosfomycin and Nitrofurantoin are effective treatment in multidrug resistance urinary tract infection.

NDM-producing Enterobacterales prevalence associated to COVID-19 in a tertiary hospital

Abstract Colonizations/Infections caused by carbapenem-resistant Enterobacterales are of great clinical and epidemiological importance due to their rapid dissemination and high mortality rates. In this scenario, the use of antibiotics intensified by the COVID-19 pandemic has brought about a great warning on the real impact that this pandemic could have on antimicrobial management programs and long-term antimicrobial resistance rates. The objective of this study was to evaluate the increase of New Delhi Metallo β-Lactamase (NDM)-producing Enterobacterales cases in COVID-19 units of a complex Brazilian tertiary hospital. This retrospective observational study included all patients admitted to the hospital identified as colonized or infected by NDM-producing Gram negative bacilli (GNB), from January 2017 to April 2021. Forty-two NDM-producing Enterobacterales were identified in 39 patients. The rate of NDM cases per total surveillance cultures increased progressively between 2017 and 2021 (chi-2 for trend, p < 0.0001) and was associated with a higher occurrence specifically in COVID units (Fisher exact, p < 0.0001). The molecular investigation of the NDM-producing Klebsiella pneumoniae strains revealed the emergence of diverse clones during the COVID-19 period, also with possible evidence of horizontal transmission among patients within COVID units. NDM-producing Enterobacterales with multiple and different clonalities in the COVID-19 units also raised questions about the importance of other factors besides horizontal clonal transfer, including the increase of antimicrobial consumption by these patients.

In vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa in Latin America: SMART 2018‒2020

Abstract Carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa are being isolated from patient specimens with increasing frequency in Latin America and worldwide. The current study provides an initial description of the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa infecting hospitalized patients in Latin America. From 2018 to 2020, 37 clinical laboratories in nine Latin American countries participated in the SMART global surveillance program and contributed 15,466 NME and 3408 P aeruginosa isolates. MICs for IMR and seven comparators were determined using CLSI broth microdilution and interpreted by CLSI M100 (2022) breakpoints. β-lactamase genes were identified in selected isolate subsets. IMR (96.9% susceptible), amikacin (95.9%), meropenem (90.7%), and imipenem (88.7%) were the most active agents against NME. Among piperacillin/tazobactam-nonsusceptible NME (n= 4124), 90.4% of isolates were IMR-susceptible (range by country, 97.2 [Chile] to 67.0% [Guatemala]) and among meropenem-nonsusceptible NME isolates (n= 1433), 74.0% were IMR-susceptible (94.1% [Puerto Rico] to 5.1% [Guatemala]). Overall, 6.3% of all collected NME isolates carried a KPC (metallo-β-lactamase [MBL]-negative), 1.8% an MBL, 0.4% an OXA-48-like carbapenemase (MBL-negative), and 0.1% a GES carbapenemase (MBL-negative). Amikacin (85.2% susceptible) and IMR (80.1%) were the most active agents against P. aeruginosa; only 56.5% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 22.0% (from 23.9% to 45.9%) in piperacillin/tazobactam-nonsusceptible isolates (n= 1031) and by 35.5% (from 5.5% to 41.0%) in meropenem-nonsusceptible isolates (n= 1128). Overall, 7.6% of all collected P. aeruginosa isolates were MBL-positive and 0.7% carried a GES carbapenemase. In conclusion, in 2018‒2020, almost all NME (97%) and most P. aeruginosa(80%) isolates from Latin America were IMR-susceptible. Continued surveillance of the in vitro activities of IMR and comparator agents against Gram-negative pathogens, and monitoring for β-lactamase changes (in particular for increases in MBLs), is warranted.

Epidemiology and in vitro activity of ceftazidime-avibactam and comparator agents against multidrug-resistant isolates of Enterobacterales and Pseudomonas aeruginosa collected in Latin America as part of the ATLAS surveillance program in 2015‒2020

Abstract Introduction The incidence of antimicrobial resistance is increasing in many parts of the world. The focus of this report is to examine changes in antimicrobial resistance epidemiology among clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in six Latin American countries as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program from 2015 to 2020, with a focus on the in vitro activity of ceftazidime-avibactam against Multidrug-Resistant (MDR) isolates. Methods Non-duplicate, clinical isolates of Enterobacterales (n= 15,215) and P. aeruginosa (n= 4,614) collected by 40 laboratories in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela, from 2015 to 2020, underwent centralized Clinical Lab Standards Institute (CLSI) broth microdilution susceptibility testing. Minimum Inhibitory Concentration (MIC) values were interpreted using 2022 CLSI breakpoints. An MDR phenotype was defined by resistance to ≥ 3 of seven sentinel agents. Results In total, 23.3% of Enterobacterales and 25.1% of P. aeruginosa isolates were MDR. Annual percent MDR values for Enterobacterales were stable from 2015 to 2018 (21.3% to 23.7% year) but markedly increased in 2019 (31.5%) and 2020 (32.4%). Annual percent MDR values for P. aeruginosa were stable from 2015 to 2020 (23.0% to 27.6% year). Isolates were divided into two 3-year time-periods, 2015‒2017 and 2018‒2020, for additional analyses. For Enterobacterales, 99.3% of all isolates and 97.1% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 97.2% and 89.3% of isolates, respectively, from 2018‒2020. For P. aeruginosa, 86.6% of all isolates and 53.9% of MDR isolates from 2015‒2017 were ceftazidime-avibactam-susceptible compared to 85.3% and 45.3% of isolates, respectively, from 2018‒2020. Among individual countries, Enterobacterales and P. aeruginosa collected in Venezuela showed the greatest reductions in ceftazidime-avibactam susceptibility over time. Conclusion MDR Enterobacterales increased in Latin America from 22% in 2015 to 32% in 2020 while MDR P. aeruginosa remained constant at 25%. Ceftazidime-avibactam remains highly active against all clinical isolates of both Enterobacterales (97.2% susceptible, 2018‒2020) and P. aeruginosa (85.3%), and inhibited more MDR isolates (Enterobacterales, 89.3% susceptible, 2018‒2020; P. aeruginosa, 45.3%) than carbapenems, fluoroquinolones, and aminoglycosides.

Molecular epidemiology of clinical isolation of carbapenem-resistant Enterobacterales and application of carbapenemase inhibitor enhancement test / 中南大学学报(医学版)

OBJECTIVES@#The prevalence of carbapenem-resistant Enterobacterales (CRE) presents a significant challenge in clinical anti-infective treatment. This study aims to investigate drug resistance and the molecular epidemiological characteristics of CRE in our area. Additionally, we seek to evaluate practicality of utilizing carbapenemase inhibitor enhancement test in clinical laboratory.@*METHODS@#Non-repeated CREs isolated from clinical specimens at Xiangya Hospital, Central South University, were collected. Minimum inhibitory concentration (MIC) combined with Kirby-Bauer (KB) assay was used to detect the drug susceptibility of the strains, and 13 carbapenemase-producing genes were detected by PCR. The phenotype of 126 strains of carbapenemase-producing Enterobacterales identified by PCR was detected by the carbapenemase inhibitor enhancement test to understand the agreement between the method and the gold standard PCR results.@*RESULTS@#Among 704 CRE strains examined, we observed significant drug resistance in 501 strains dentified as carbapenemase-producing Enterobacterales (CPE). Klebsiella pneumoniae was the predominant CPE strain, followed by Enterobacter cloacae and Escherichia coli. A total of 9 carbapenemase types were detected, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron- encoded metallo-β-lactamases (VIM), imipenemase (IMP), oxacillinase-48 (OXA-48), and rare imipenem-hydrolyzing β-lactamase (IMI), adelaide imipenemase (AIM), Bicêtre carbapenemase (BIC), and guiana extended-spectrum β-lactamase (GES). The detection rate of KPC serine carbapenemase was 61.7% (309/501). The carbapenemase inhibitor enhancement test exhibited a 100% consistency rate for the strains producing Class A serine carbapenemase and/or Class B metallo-β-lactamases.@*CONCLUSIONS@#CRE strains in Changsha, Hunan, China, are wide distribution and exhibit carbapenemase production. The main mechanism of carbapenem resistance in these bacterias is predominatly attributed to the production of KPC serine carbapenemase. The presence of GES and IMI genes carried by Enterobacterales has been detected for the first time in this region. The carbapenemase inhibitor enhancement test has been proven to be an accurate method for detecting CRE producing Class A serine carbapenemase and/or Class B metallo-β-lactamases. This method offers simpicity of operation and ease of results interpretation, making it weel-suited meeting the clinical microbiology laboratory's reguirements for the detection of serine carbapenemase and metallo-β-lactamases.

Isolation of Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum ß-lactamases from dog urine of the Metropolitan Area of the Aburrá Valley (Antioquia, Colombia) / Aislamiento de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido a partir de orina de perros del Área metropolitana del Valle de Aburrá (Antioquia, Colombia)

ABSTRACT Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing urinary tract infections in humans and animals. Close contact between humans and companion animals can facilitate the spread of multidrug resistant pathogens between both species. The objective of the research was to characterize extended-spectrum ß-lactamases (ESBL) -producing E. coli and K. pneumoniae isolated from dogs with urinary tract infections in the metropolitan area of Valle del Aburrá (Antioquia, Colombia). Three-hundred seventy-one urine samples collected from March 2018 to March 2019 in a veterinary clinical laboratory were analyzed. E. coli and K. pneumoniae isolates were detected in chromogenic agar and identified by biochemical tests. Susceptibility testing was performed by disc diffusion and ESBL production was evaluated by the double disk test in all isolates. MIC determination of ESBL-positive isolates were performed on the automated VITEK®2 system. Multiple PCR was used for the detection of CTX-M beta-lactamases (group 1, 2, 9 and 8/25), SHV, TEM, and AmpC of plasmid origin in ESBL-positive isolates. In total 22 out 371 isolates were positive for ESBL production by double disc test, 11 E. coli (ESBL-Ec) and 11 K. pneumoniae (ESBL-Kp). The multiple PCR detected CTX-M group 1 in the 22 ESBL-positive isolates. Multi-drug resistance was observed in all ESBL-producing isolates. In conclusion, a high frequency of antibiotic multi-resistance was found in ESBL-Ec and ESBL-Kp. The main ESBL detected was CTX-M group 1, which also prevails in human isolates.

RESUMEN Escherichia coli y Klebsiella pneumoniae son los patógenos más comunes causantes de infecciones en tracto urinario en humanos y animales. El contacto estrecho con los animales de compañía puede favorecer la diseminación de patógenos multiresistentes entre ambas especies. El objetivo de la investigación fue caracterizar E. coli (Ec -BLEE) y K. pneumo-niae (Kp -BLEE) productores de betalactamasas de espectro extendido provenientes de aislados de caninos con infecciones del tracto urinario del Área Metropolitana del Valle de Aburrá. 371 muestras de orina de caninos colectadas entre marzo de 2018 y marzo 2019 en un laboratorio clínico veterinario fueron analizadas. E. coli y K. pneumoniae se detectaron en agar cromogénico y se identificaron mediante pruebas bioquímicas. La prueba de susceptibilidad se realizó por difusión en disco y la producción de BLEE se evaluó por test de doble disco en todos los aislados. La determinación de la CIM en aislados positivos a BLEE se realizó en el sistema automatizado VITEK®2. Se utilizó PCR múltiple para la detección de betalactamasas tipo CTX-M (grupo 1, 2, 9 y 8/25), SHV, TEM y AmpC de origen plasmídico en aislados positivos a BLEE. Un total de 22 de 371 aislados fueron positivos a BLEE por test de doble disco, 11 E. coli (Ec -BLEE) y 11 K. pneumoniae (Kp-BLEE). La PCR detectó CTX-M grupo 1 en los 22 aislados positivos a BLEE. Se observó multirresistencia en todos los aislamientos productores de BLEE. En conclusión, se encontró una alta frecuencia de multirresistencia en Ec-BLEE y Kp-BLEE. La principal BLEE detectada fue CTX-M grupo 1, que también predomina en aislados humanos.

Conocimientos y prácticas de los médicos cubanos respecto a Enterobacterales resistentes a carbapenémicos / Knowledge and practice on carbapenem-resistant Enterobacterales in medical doctors from a tertiary hospital in Cuba

Introducción: En el contexto de la pandemia de COVID-19, la infección por Enterobacterales resistentes a carbapenémicos productores de carbapenemasas (ERC-PC) se convierte en un problema de salud pública desafiante a nivel mundial. Los médicos desempeñan un papel fundamental en el manejo clínico de las infecciones por patógenos resistentes a carbapenémicos a nivel hospitalario y por ende en el control de estas. Sin embargo, no existen estudios sobre el conocimiento y prácticas de estos sobre ERC-PC en Cuba. Objetivo: Abordar conocimientos y prácticas sobre las infecciones por ERC-PC, su manejo terapéutico, prevención y control en médicos cubanos en un hospital terciario. Métodos: Se realizó un estudio observacional (descriptivo, de corte transversal) y se aplicó un cuestionario específico elaborado a 70 médicos asistenciales. Resultados: Hubo variabilidad en las opiniones sobre las ERC-PC y un conocimiento medio sobre estas en la mayoría de los encuestados. El 58,6 % de los médicos tenía experiencia en el manejo clínico de la infección por ERC-PC. Las brechas de conocimiento encontradas estuvieron asociadas a la escasa experiencia práctica en el manejo de casos. Hubo diferencia estadísticamente significativa en el nivel de conocimientos sobre los ERC-PC en los médicos con experiencia en el manejo de los ERC-PC en comparación con los médicos sin experiencia (p = 0,039). Conclusiones: Es necesario establecer un plan de formación continua en la temática para mejorar el desempeño de los profesionales de la salud en el control de las infecciones por ERC-PC y en el uso optimizado de los antibióticos.

Introduction: In the context of COVID-19 pandemic, carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) infection becomes a global public health threat. Medical doctors play a fundamental role in the clinical management and control of infections caused by carbapenem-resistant pathogens. However, in Cuba there are not previous studies on the knowledge and practice of medical doctors about CR-CRE. Objective: To study the knowledge and practice of Cuban medical doctors in a tertiary hospital about CR-CRE infections, their clinical management, prevention and control. Methods: It was conducted an observational study (descriptive, cross-sectional) and an specific questionnaire to 70 medical doctors was applied. Results: There was variability on the opinions about CP-CRE and average knowledge in the majority of the respondents. 58.6% of the medical doctors had some experience in the clinical management of CP-CRE infections. Knowledge gaps were associated with the limited practical experience in the management of cases. There was statistically significant difference in the level of knowledge about CP-CRE of medical doctors with experience in the management of CP-CRE compared to inexperienced medical doctors (p = 0.039). Conclusions: It is necessary to establish a continuous training plan on this topic to improve the performance of health professionals in the control of CP-CRE infections and in the appropriate use of antibiotics.

Primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM en un hospital de segundo nivel en la Cuidad de Panamá / First isolates of Enterobacter cloacae complex co-producing KPC and NDM in a second level hospital in City of Panama

Resumen La aparición de Enterobacterales co-productores de dos o más carbapenemasas han despertado las alertas sanitarias en Latinoamérica. Las enterobacterias co-productoras de carbapenemasas KPC y NDM-1 son resistentes a casi todos los antibacterianos existentes. Panamá ha reportado la presencia de carbapenemasas KPC desde 2010 y NDM desde 2011; sin embargo, Enterobacterales con doble producción de carbapenemasas es un fenómeno reciente en nuestros hospitales. Presentamos los dos primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM, en un hospital de segundo nivel de la Ciudad de Panamá. El reforzamiento de los sistemas de vigilancia epidemiológica en los hospitales permite realizar una detección oportuna de estas nuevas combinaciones de mecanismos de resistencia; para así, implementar medidas de prevención y control de brotes.

Abstract Enterobacterales co-producing carbapenemases have awakened health alerts in Latin America. Carbapenemase-producing Enterobacterales harboring KPC and NDM-1 are resistant to almost all existing antibiotics. Panama reports KPC since 2010, and NDM since 2011, however, Enterobacterales with double carbapenemase production is new to our hospitals. We present the first two isolates of Enterobacter cloacae complex co-producing KPC and NDM, in a second level hospital in Panama City. Strengthening epidemiological surveillance systems in hospitals allows to carry out timely detection of these new combinations of resistance; to implement outbreak prevention and control measures.

Mecanismos de resistencia bacteriana frente a ceftazidima avibactam. Revisión Sistemática / Mechanisms of bacterial resistance against ceftazidime avibactam. Systematic Review / Mecanismos de resistência bacteriana contra ceftazidima avibactam. Revisão sistemática

La resistencia a los antibióticos representa una problemática a nivel mundial determinada por la capacidad que poseen las bacterias para desarrollar mecanismos de resistencia que les permitan adaptarse y sobrevivir en el entorno en el que se desenvuelven. La combinación ceftazidima-avibactam (CAZ/AVI) desde su aprobación en 2015 por la Food and Drug Administration (FDA) ha demostrado ser muy eficiente frente a bacilos Gram negativos productores de carbapenemasas, pero al igual que otras estrategias frente a bacterias multirresistentes no está exenta del desarrollo de mecanismos de resistencia. Métodos. Se realizó una revisión sistemática de la literatura en las bases de datos Web of Science, PubMed y Scopus siguiendo la metodología PRISMA, se incluyeron 29 artículos en los que se reportó la resistencia a CAZ/AVI en aislados clínicos. Resultados. los mecanismos de resistencia más relevantes fueron las mutaciones en el gen blaKPC en la posición 179 (D179Y) en el bucle conservado omega estimulada por la exposición previa a CAZ/AVI, generando de esta forma nuevas variantes como blaKPC-31 y blaKPC-33. Conclusiones. la evidente presencia de mecanismos de resistencia a CAZ/AVI a pesar de ser una combinación de uso relativamente reciente hace un llamado al uso adecuado de esta combinación.

Antibiotic resistance represents a worldwide problem determined by the ability of batteries to develop resistance mechanisms that allow them to adapt and survive in the environment in which they operate. Since its approval in 2015 by the Food and Drug Administration (FDA), the ceftazidime-avibactam (CAZ/AVI) combination has proven to be very efficient against Gram-negative bacilli that produce carbapenemase, but like other strategies against multiresistant bacteria, it is not exempt from the development of resistance mechanisms. Methods. a systematic review of the literature was carried out in the Web of Science, PubMed and Scopus databases following the PRISMA methodology, including 29 articles in which resistance to CAZ/AVI was reported in clinical isolates. Results. The most relevant resistance mechanisms were mutations in the blaKPC gene at position 179 (D179Y) in the conserved omega loop, stimulated by previous exposure to CAZ/AVI, thus generating new variants such as blaKPC-31 and blaKPC-33. Conclusions. The evident presence of resistance mechanisms to CAZ/AVI, despite being a combination of relatively recent use, calls for the appropriate use of this combination.

A resistência aos antibióticos representa um problema mundial determinado pela capacidade das bactérias desenvolverem mecanismos de resistência que lhes permitem adaptar-se e sobreviver no ambiente em que operam. Desde sua aprovação em 2015 pela Food and Drug Administration (FDA), a combinação ceftazidima-avibactam (CAZ/AVI) tem se mostrado muito eficiente contra bacilos Gram-negativos produtores de carbapenemases, mas como outras estratégias contra bactérias multirresistentes, é não isentos do desenvolvimento de mecanismos de resistência. Métodos. Foi realizada uma revisão sistemática da literatura nas bases de dados Web of Science, PubMed e Scopus seguindo a metodologia PRISMA, incluindo 29 artigos nos quais foi relatada resistência ao CAZ/AVI em isolados clínicos. Resultados. Os mecanismos de resistência mais relevantes foram mutações no gene blaKPC na posição 179 (D179Y) na alça ômega conservada, estimuladas pela exposição prévia ao CAZ/AVI, gerando novas variantes como blaKPC-31 e blaKPC-31. 33. Conclusões. A evidente presença de mecanismos de resistência ao CAZ/AVI, apesar de ser uma combinação de uso relativamente recente, exige o uso adequado dessa combinação.

Enterobacterales productores de carbapenemasas en sifones de lavamanos de una Unidad de Paciente Crítico

Resumen Introducción: Enterobacterales productores de carbapenemasas (EPC) son una importante causa de infecciones asociadas a la atención en salud (IAAS). El principal reservorio de EPC lo constituyen pacientes infectados y colonizados, sin embargo, también se han identificado reservorios ambientales. Objetivo: Detectar la presencia de EPC en los sifones de lavamanos de la unidad de cuidados críticos de pacientes quemados adultos (UPC QMD) y unidad de cuidados críticos de pacientes pediátricos crónicos (UCEP). Método: Se recolectaron cuatro muestras de sifones de los lavamanos ubicados en el interior de las unidades de pacientes en UCEP y 10 de UPC QMD. A las muestras se les realizó estudio fenotípico y molecular para detección de carbapenemasas en el Instituto de Salud Pública de Chile. Resultados: En los sifones estudiados de UCEP no se aislaron cepas de EPC. En UPC QMD, 50% de los sifones estudiados se aislaron cepas de EPC. Conclusiones: En UPC QMD se objetivó la presencia de EPC en una alta proporción de los sifones de lavamanos testeados, lo que demuestra un reservorio ambiental de bacterias multi-resistentes.

Abstract Introduction: Carbapenemase-producing Enterobacterales (CPE) are an important cause of health care associated infections (HAI). The main reservoir is constituted by infected and colonized patients; however, environmental reservoirs have also been identified. Objective: To detect the presence of CPE in the sink traps of the critical care unit for adult burn patients (UPC QMD) and the critical care unit for chronic pediatric patients (UCEP). Material and Method: Four samples of trap were collected from the sinks located inside the patient units at PICU and 10 at UPC QMD. The samples underwent a phenotypic and molecular study for the detection of carbapenemases at the Institute of Public Health of Chile. Results: In the UCEP no EPC strains were isolated. In UPC QMD, CPE was detected in 50% of the traps. Conclusions: In UPC QMD, the presence of CPE was observed in a high proportion of the tested sinks traps, which shows an environmental reservoir of multi-resistant bacteria.

Primer reporte de Enterobacterales dobles productores de carbapenemasas en hospitales de Paraguay. Año 2021

RESUMEN Las carbapenemasas se encuentran ampliamente distribuidas en nuestro país, tanto en bacilos gramnegativos fermentadores como no fermentadores. Durante 2021, se ha reportado incremento de cepas con estas enzimas. Con el objetivo de evaluar la doble producción de carbapenemasas en Enterobacterales y comunicar su circulación, fue puesta a punto una PCR convencional múltiple. Estudio retrospectivo en 128 aislamientos provenientes de 20 centros colaboradores de la Red Nacional de Vigilancia de la RAM (Capital, Central e interior del país), remitidos al LCSP entre febrero y setiembre de 2021, para confirmación y genotipificación de carbapenemasas. Se realizaron pruebas fenotípicas y colorimétricas con sustratos específicos, y pruebas genotípicas (PCR convencional múltiple) para la detección simultánea de varios genes de resistencia (bla NDM, bla KPC, bla OXA-48-like, bla IMP y bla VIM). De los 128 aislamientos estudiados, 107 correspondieron a Klebsiella pneumoniae, 14 a Enterobacter cloacae complex, entre otros; aislados en mayor frecuencia de muestras de orina (30%), respiratorias (30%), sangre y catéter (24%). Los genes de resistencia a los carbapenemes detectados fueron: bla NDM (77,3%), bla KPC (17,2%); siendo confirmada la doble producción de carbapenemasas en 7 aislamientos (5,5%) provenientes de 4 centros diferentes de la capital de país y uno de Central; 6 de ellas (K. pneumoniae) con bla NDM+bla KPC y 1 (E. cloacae complex) con bla NDM+bla OXA-48-like; confirmando circulación de Enterobacterales dobles productores de carbapenemasas en el país (KPC+NDM y OXA+NDM); hallazgos que obligan a proveer de capacidades de detección, de manera a que se puedan tomar medidas oportunas y eficaces de contención y control.

ABSTRACT Carbapenemases are widely distributed in our country, both in fermenting and non-fermenting gram-negative bacilli. During 2021, an increase in strains with these enzymes has been reported. In order to evaluate the double production of carbapenemases in Enterobacterales and communicate their circulation, a multiple conventional PCR was set up. Retrospective study carried out in 128 isolates from 20 collaborating centers of the National AMR Surveillance Network (Capital, Central and interior of the country), sent to the LCSP between February and September 2021, for confirmation and genotyping of carbapenemases. Phenotypic and colorimetric tests were performed with specific substrates, as well as genotypic tests (multiple conventional PCR) for the simultaneous detection of several resistance genes (blaNDM, blaKPC, blaOXA-48-like, blaIMP and blaVIM). Of the 128 isolates studied, 107 corresponded to Klebsiella pneumoniae, 14 to Enterobacter cloacae complex, among others; isolated in higher frequency from urine (30%), respiratory (30%), blood and catheter (24%) samples. The genes for resistance to carbapenems detected were: blaNDM (77.3%), blaKPC (17.2%); the double production of carbapenemases was confirmed in 7 isolates (5.5%) from 4 different centers in the capital of the country and one in Central; 6 of them (K. pneumoniae) with blaNDM + blaKPC and 1 (E. cloacae complex) with blaNDM + blaOXA-48-like; confirming circulation of double Enterobacterales producers of carbapenemases in the country (KPC + NDM and OXA + NDM); findings that require the provision of detection capabilities, so that timely and effective containment and control measures can be taken.

Tipos de carbapenemasas expresadas en Klebsiella spp, y Pseudomonas aeruginosa resistente a carbapenémicos en seis hospitales de alta complejidad de la Ciudad de Bogotá - Colombia / Carbapenemases produced in Klebsiella spp, and Pseudomonas aeruginosa in six hospitals in Bogotá - Colombia

INTRODUCCIÓN: En las últimas décadas, se ha incrementado la prevalencia de infecciones por bacilos gramnegativos resistentes a carbapenémicos. OBJETIVO: Determinar los tipos y la frecuencia de las distintas carbapenemasas en aislados de Klebsiella spp. y Pseudomonas aeruginosa, en seis hospitales de alta complejidad de Bogotá-Colombia. MÉTODOS: Estudio observacional descriptivo en seis hospitales de la ciudad de Bogotá, en el período de enero de 2017 a agosto de 2018. Se realizaron RPC para genes de KPC, GES, VIM, NDM, IMP y OXA-48 en cepas de Klebsiella spp y P aeruginosa resistentes a carbapenémicos. RESULTADOS: 52 aislados de P aeruginosa amplificaron para una carbapenemasa, de los cuales 39 (75%) fueron positivos para KPC, 11 (21%) para VIM y 2 co-producciones de KPC y VIM. En cuanto a Klebsiella spp., 165 cepas amplificaron al menos para una carbapenemasa, 98% expresaron KPC y 4 aislados tuvieron co-producciones de metalo-beta-lactamasas y KPC. DISCUSIÓN: Este estudio aporta información valiosa, como el incremento de producción de KPC en P. aeruginosa y la co-producción de KPC y metalo-beta-lactamasas, locual tiene una implicancia tanto en la selección del tratamiento, las medidas de aislamiento de contacto y el pronóstico de los pacientes.

BACKGROUND: In the last decades, the prevalence of infections by carbapenem resistant gram-negative bacilli has been increased. OBJECTIVE: To determine types and frequency of the different carbapenemases in Klebsiella spp. and Pseudomonas aeruginosa, in six hospitals in Bogotá-Colombia. METHODS: Descriptive and observational study, in six hospitals in the city of Bogotá, in the period ftom January 2017 to August 2018. PCR were performed for KPC, GES, VIM, NDM, IMP and OXA-48 genes, in carbapenem resistant Klebsiella spp. and P aeruginosa. RESULTS: 52 P aeruginosa isolates amplified a carbapenemase gene, of which 39 (75%) were positive for KPC, 11 (21%) for VIM and two co-productions of KPC and VIM. Regarding Klebsiella spp. 165 strains amplified at least one carbapenemase gene, 98% expressed KPC and four isolates had co-productions of metallo-P-lactamases and KPC. DISCUSSION: This study provides valuable information, such as the increased production of KPC in P. aeruginosa información valiosa, como el incremento de producción de KPC en P. aeruginosa and the co-production of KPC plus metallobetalactamases, which has an implication both in treatment selection, isolation precautions and patient prognosisy.

Colonización rectal por Enterobacterales productores de múltiples carbapenemasas: Reporte de un caso de coproducción / Rectal colonization by Enterobacterales producing multiple carbapenemases: a co-production case report

Resumen El constante aumento de Enterobacterales productores de carbapenemasas (CPE) se constituye en un problema de salud pública a nivel mundial, por el impacto generado en la mortalidad de los pacientes. El tracto gastrointestinal es el principal reservorio de este tipo de microorganismos, por lo cual, la colonización rectal se convierte en un importante factor de riesgo para el desarrollo de posteriores infecciones. Una de las estrategias de vigilancia epidemiológica activa, es la búsqueda de pacientes colonizados, a través de cultivos de tamización para detectar estos microrganismos multirresistentes. Reportamos el caso de un paciente, con historia de sepsis de origen pulmonar, colonizado por Klebsiella pneumoniae con coproducción de carbapenemasas NDM + KPC y Escherichia coli con carbapenemasa NDM. Este hallazgo es cada vez más frecuente, lo cual implica un reto en su detección y diagnóstico. Se describen características del paciente, procedimientos realizados y hallazgos microbiológicos.

Abstract The constant increase in carbapenemase-producing Enterobacterales (CPE) constitutes a public health problem worldwide, due to the impact generated on the mortality of patients. The gastrointestinal tract is the main reservoir for this microorganism, which is why, rectal colonization becomes an important risk factor for the development of subsequent infections. One of the active epidemiological surveillance strategies is the search for colonized patients through screening cultures, to detect these multi-resistant microorganisms. We report the case of a patient, with a history of sepsis of pulmonary origin, colonized by Klebsiella pneumoniae with co-production of NDM + KPC carbapenemases and NDM carbapenemase-producing Escherichia coli. This finding is more and more frequent, which implies a challenge in its detection and diagnosis. Patient characteristics, procedures performed and microbiological findings are described.

Caracterización molecular de carbapenemasas en bacilos gramnegativos circulantes en hospitales de Paraguay. Primer cuatrimestre 2021 / Molecular characterization of carbapenemases in Gram-negative bacilli circulating in hospitals of Paraguay. First quarter of 2021

La resistencia a los antimicrobianos (RAM), representa un grave problema por el uso indiscriminado de antimicrobianos de amplio espectro. En nuestro país, durante el primer cuatrimestre del año, se observó un aumento inusual en el número de aislamiento de gérmenes multirresistentes, sobre todo de bacilos gramnegativos, los cuales fueron remitidos al laboratorio de referencia con el objetivo de caracterizar los genes de resistencia a los carbapenemes. Estudio observacional y prospectivo de corte transversal en 456 aislamientos de bacilos gramnegativos provenientes de 11 centros colaboradores de la Red Nacional de Vigilancia de la RAM, remitidos al Laboratorio Central de Salud Pública entre enero y abril de 2021, para la detección molecular (reacción en cadena de la polimerasa múltiple) de los genes de resistencia enzimática bla OXA-51, bla OXA-23, bla OXA-24, bla OXA-48, bla OXA-58, bla NDM, bla KPC, bla IMP, bla VIM. Trescientos sesenta correspondieron a bacilos gramnegativos no fermentadores: 346 Acinetobacter baumannii y 14 Pseudomonas aeruginosa; 96 fueron miembros de Enterobacterales, siendo prevalente Klebsiella pneumoniae (81). Todos los aislamientos de Acinetobacter baumannii resultaron ser productores de carbapenemasas: OXA-23 (94%), NDM (4%), NMD+OXA-58 (2%); en Pseudomonas aeruginosa, 7 de los 14 aislamientos (50%) fueron portadores de metalobetalactamasa del genotipo NDM (100%). Los genotipos NDM (92%) y KPC (8%) fueron confirmados en Enterobacterales. La resistencia plasmídica a carbapenemes es endémica en nuestro país, siendo prevalentes los genotipos OXA-23 en Acinetobacter baumannii y NDM en Pseudomonas aeruginosa y Enterobacterales

Antimicrobial resistance (AMR) represents a serious problem due to the indiscriminate use of broad-spectrum antimicrobials. During the first quarter of the year, an unusual increase in the number of isolation multi-resistant germs, especially gram-negative bacilli was observed, specially of Gram-negative bacilli which were referred to the reference laboratory in order to characterize the carbapenems resistance genes. Observational and prospective cross-sectional study in 456 isolates of Gram-negative bacilli from 11 collaborating centers of the National AMR Surveillance Network, referred to the Central Public Health Laboratory (LCSP) between January and April 2021, for molecular detection (multiple polymerase chain reaction) targeting the enzymatic resistance genes: bla OXA-51, bla OXA-23, bla OXA-24, bla OXA-48, bla OXA-58, bla NDM, bla KPC, bla IMP, bla VIM. Of the 456 isolates studied, 360 corresponded to non-fermenting Gram-negative bacilli, of which 346 were confirmed as Acinetobacter baumannii and 14 Pseudomonas aeruginosa; 96 were Enterobacterales, being Klebsiella pneumoniae (81) the most prevalent. All isolates of Acinetobacter baumannii carried genes encoding carbapenemases, being the OXA-23 (94%) followed by NDM (4%) and NDM +OXA-58 (2%). In Pseudomonas aeruginosa strains, 7 of the 14 isolates (50%) were carriers of NDM metallobetalactamase (100%). No carbapenemase gene was detected in the remaining 7. In all Enterobacterales strains, the presence of carbapenemases of the NDM (92%) and KPC (8%) genotypes were confirmed. Plasmid resistance to carbapenems is endemic in our country, being the OXA-23 genotypes prevalent in Acinetobacter baumannii and NDM in Pseudomonas aeruginosa and Enterobacterales

Caracterización de bacilos gramnegativos multi-resistentes, aislados en pacientes hospitalizados en instituciones de salud de Barranquilla (Colombia) / Characterization of multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions in Barranquilla (Colombia)

Resumen Introducción: La resistencia a carbapenémicos en bacilos gramnegativos es un problema de salud pública mundial, debido a que se asocia con altas tasas de mortalidad, aumento en los niveles de resistencia a otros antimicrobianos, elevación en el potencial de diseminación e incremento en los costos de atención en salud. Objetivo: Caracterizar bacilos gramnegativos multirresistentes, aislados en pacientes hospitalizados en instituciones de salud de Barranquilla (Colombia). Material y Métodos: Estudio descriptivo acerca de la caracterización fenotípica y genotípica de la resistencia bacteriana en las infecciones asociadas a la atención en salud, mediada por carbapenemasas en aislados bacterianos enviados por los laboratorios pertenecientes a la red de laboratorios del Departamento del Atlántico. Resultados: La KPC fue la carbapenemasa más frecuente en las Enterobacterales (27,6%), predominando en Klebsiella pneumoniae (13,1%) sola y asociada a otras carbapenemasas. En Pseudomonas aeruginosa predominó la carbapenemasa VIM (32,8%) y la OXA en Acinetobacter baumannii (17,1%). Conclusión: Se encontró una amplia distribución de cepas multi-resistentes productoras de carbapenemasas en instituciones de salud de Barranquilla, las cuales expresaron los siguientes mecanismos de resistencia: KPC, VIM, NDM, OXA.

Abstract Background: The emergence of carbapenem resistant gramnegative bacilli has become a problem of public health worldwide, because it is associated with high mortality rates, increased levels of resistance to other antimicrobials, increased potential for dissemination transition and increase in health care costs. Aim: To characterize multiresistant gram-negative bacilli, isolated in patients hospitalized in health institutions of Barranquilla (Colombia). Methods: A descriptive study was conducted on the phenotypic and genotypic characterization of bacterial resistance in infections associated with health care, mediated by carbapenemases in bacterial isolates sent by laboratories belonging to the laboratory network of the Department of Atlántico. Results: KPC was the most frequent carbapenemase in Enterobacterales (27.6%), predominantly in Klebsiella pneumoniae (13.1%) alone and associated with other carbapenemases. In Pseudomonas aeruginosa, VIM carbapenemase (32.8%) predominated and OXA in Acinetobacter baumannii (17.1%). Conclusion: A wide distribution of multi-resistant strains producing carbapenemases in Atlantic health institutions was found, which expressed the following resistance mechanisms: KPC, VIM, NDM, OXA.

Active surveillance and molecular epidemiological study of intestinal colonization of carbapenem-resistant Enterobacterales / 中华传染病杂志

Objective:To investigate the detection rate of intestinal colonization of carbapenem-resistant Enterobacterales (CRE) in inpatients, and to analyze the molecular epidemiological characteristics of CRE strains.Methods:This was a prospective study. Stool, rectal swab or perianal swab specimens of 213 inpatients in the surgical intensive care unit (SICU), medical intensive care unit (MICU) and the department of hematology (transplantation ward) in The Second Hospital of Anhui Medical University were collected from March to December, 2019. MacConkey plate containing carbapenems was used to screen CRE strains, and bacteria identification and drug susceptibility test were conducted. Key strains were selected for whole genome sequencing (WGS). Besides, multilocus sequence typing, capsular serotype, drug resistance gene, virulence gene and plasmid carrying characteristics of these strains were analyzed. Using KPN FJ723042 sequence as a reference, the single-nucleotide polymorphism (SNP) of all strains was analyzed.Results:Twenty-three CRE strains were detected, with a detection rate of 10.8%(23/213), which included 15(65.2%) carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates, three (13.0%) Escherichia coli strains, three (13.0%) Enterobacter cloacae strains and two (8.7%) Citrobacter freundii strains. SNP cluster analysis showed that the 15 CRKP strains had two main clonotypes, which were both predominant in SICU. Fifteen strains of CRKP were type ST11-K64. All these strains carried β-lactamase Klebsiella pneumoniae carbapenemase 2 ( blaKPC-2 ), and 12 strains carried regulator of mucoid phenotype gene A2 ( rmpA2) and iucABCD. Conclusions:The detection rate of intestinal colonization of CRE in inpatients is high, and most strains are CRKP of type ST11-K64. These CRKP strains have both multidrug resistance and virulence characteristics, which are risks for hospital transmission.

Resistance and transmission mechanisms of carbapenem-resistant Enterobacterales / 中华微生物学和免疫学杂志

Objective:To investigate the resistance and transmission mechanism of carbapenem-resistant Enterobacterales (CRE), so as to provide the scientific evidence for the treatment and prevention of CRE infection.Methods:Seventy-six isolates of CRE isolated from Shaoxing Second Hospital between May 2016 and August 2018 were included. The isolates were re-identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The minimum inhibitory concentrations (MICs) of colistin, tigecycline, ceftazidime-avibactam, fosfomycin and other antibacterial drugs were determined using broth microdilution or agar dilution methods. PCR and sequencing analysis were performed to detect carbapenemase encoding genes ( blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48). Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to analyze homology of strains. S1-PFGE combined with Southern blot hybridization were used to locate the carbapenamase genes. Filter mating test were performed to determine the horizontal transfer ability of plasmids harboring carbapenamase genes. Results:Among the 76 isolates of CRE, 51 isolates were Klebsiella pneumoniae; 10 isolates were Escherichia coli; 15 isolates were other Enterobacterales. The 76 CREs were mainly isolated from urine, sputum and blood samples. The distribution rate of ICU was the highest (55.26%). The 76 CREs showed low resistance rates (0%, 1.33%, 18.42%) to colistin, tigecycline and ceftazidime-avibactam. The resistance rates to amikacin and fosfomycin were <45%, and the resistance rates to other drugs were >97%. The detection rate of KPC-2 carbapenemase was the highest (85.33%). The ST11 CRKP producing KPC-2 carbapenemase accounted for the highest proportion (62.75%), mainly distributed in the ICU (62.50%). Southern blot hybridization showed that blaKPC-2 was mainly located on a plasmid about 90 kb (39/63). Filter mating test showed that blaKPC, blaNDM and blaIMP could be transferred horizontally to recipient bacteria through plasmids. Conclusions:The 76 CRE isolates were only susceptible to a few antibacterial drugs, such as colistin, tigecycline and ceftazidime-avibactam. The production of KPC-2 carbapenemase was the main reason for the resistance of Enterobacterales to carbapenems. KPC-2 carbapenemase-producing ST11 Klebsiella pneumoniae was the main epidemic clone of carbapenem-resistant Klebsiella pneumoniae (CRKP). The 90 kb size plasmid was the main plasmid encoding blaKPC-2 gene. Carbapenemase genes can be transferred horizontally through plasmids. The hospital should strengthen prevention of nosocomial infections to control the clonal prevalence of CRE.

Evaluation of in vitro activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil - the EM200 study

ABSTRACT Background: The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane-tazobactam against clinical bacterial isolates from Brazil. Methods: A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane-tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria. Results: Susceptibility rates to ceftolozane-tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane-tazobactam was 84.9% (MIC50/90, 1/16 µg/mL) and 99.2% to colistin. For E. coli, ceftolozane-tazobactam inhibited 94.9% (MIC50/90, 0.25/1 µg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane-tazobactam was 40.4% (MIC50/90, 16/>32 µg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC50/90, 0.5/16 µg/mL) to ceftolozane-tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates. Conclusions: Ceftolozane-tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.