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

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.

Caracterización de aislamientos de Klebsiella pneumoniae doble productores de carbapenemasas en un hospital universitario / Phenotypic and genotypic characterization of double carbapenemase producing Klebsiella pneumoniaeisolates in a University Hospital

La emergencia de aislamientos de Klebsiella pneumoniaedoble productores de carbapenemasas (KPC y NDM) es una de las consecuencias de la pandemia causada por SARS-CoV-2 que ha causado un impacto significativo en las tasas de resistencia a los antimicrobianos en las infecciones intrahospitalarias por esta enterobacteria. Estos aislamientos representan un desafío para los servicios de salud, por su detección y caracterización y posterior tratamiento. En este trabajo se describen los aislamientos portadores de KPC y NDM recuperados durante 2022 aislados de distintas muestras clínicas de pacientes internados en un hospital universitario de la Ciudad de Buenos Aires, se los caracteriza fenotípicamente y genotípicamente como portadores de ambas carbapenemasas y se destaca la excelente actividad in vitro de la combinación ceftazidima-avibactam y aztreonam en el tratamiento de estas infecciones en donde las alternativas terapéuticas estarían limitadas a antibióticos no ß-lactámicos con porcentajes de resistencia que superan el 70%

The emergence of double-carbapenemase (KPC and NDM) producing Klebsiella pneumoniae isolates is one of the consequences derived from the SARS CoV-2 pandemic, which has caused significant impact on the antimicrobial resistance rates in hospital acquired infections. These isolates represent a real challenge for Health Services due to their difficult detection and characterization and subsequent treatment. In the present work we describe the double carbapenemase producing isolates recovered during the year 2022 from clinical samples belonging to hospitalized patients at a University Hospital in Buenos Aires city, we report their phenotypic and genotypic characterization and the excellent "in vitro" activity of the ceftazidime-avibactam-aztreonam combination in the treatment of infections in which the therapeutical options are restricted to non ß- lactamic antimicrobials which hold resistance rates higher than 70%

Emergence and clonal expansión of Klebsiella pneumoniae ST307, simultaneously producing KPC-3 and NDM-1

Abstract MDR Klebsiella pneumoniae ST307 is a high-risk clone, whose genetic features contribute to its adaptation to hospital environments and the human host. This study describesthe emergence and clonal dissemination of K. pneumoniae ST307, recovered during November2018 to February 2019 in a hospital in Buenos Aires city, which concurrently harbored KPC-3and NDM-1. These isolates were resistant to all -lactams and to the ceftazidime/avibactamcombination. Molecular studies showed that blaKPC-3was located in Tn4401a platform, whileblaNDM-1was surrounded upstream by ISKpn14 followed by a partial sequence of ISAba125 anddownstream by bleMBL-trpF, located in a 145.5 kb conjugative plasmid belonging to the Inc A/Cgroup. The dissemination of K. pneumoniae ST307 isolates co-producing KPC-3 and NDM-1 couldlead to a worrisome scenario due to the remarkable features of this clone and its resistanceprofile.

Resumen Klebsiella pneumoniae ST307 es un clon de alto riesgo, cuyas características genéticas contribuyen a su adaptación al entorno hospitalario y al huésped humano. Este estudio describe la emergencia y diseminación clonal de aislamientos de K. pneumoniae ST307 productores de KPC-3 y NDM-1, recuperados en un hospital de Buenos Aires. Estos aislamientos fueron resistentes a todos los p-lactámicos y a la combinación ceftacidima/avibactam. Los estudios moleculares evidenciaron que el contexto genético de blaKPC-3 se correspondió con el Tn4401a, mientras que blaNDM-1 estuvo flanqueado corriente arriba por ISKpn14 y una secuencia parcial de ISAba125 y corriente abajo por bleMBL - trpF, localizado a su vez en un plásmido conjugativo de 145.5 kb perteneciente al grupo Inc A/C. La emergencia de aislamientos de K. pneumoniae ST307 coproductores de KPC-3 y NDM-1 pone de manifiesto una situación altamente preocupante debido a las características de este clon y a su perfil de multirresistencia.

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.

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.

Genomic characteristics of a Klebsiella pneumoniae strain coproducing carbapenemases KPC-2 and NDM-5 / 中华微生物学和免疫学杂志

Objective:To analyze the characteristics of drug resistance genes in a Klebsiella pneumoniae strain coproducing carbapenemases KPC-2 and NDM-5. Methods:Klebsiella pneumoniae KPN-hnqyy was separated from the stool specimen of a patient in the Hematology Department of Affiliated Cancer Hospital of Zhengzhou University. The strain was identified with a BD Phenix-M50 automated microbiology system and the minimum inhibitory concentration against the strain was measured as well. The genotypes of the carbapenemases were tested by enzyme immunochromatographic assay and PCR method. The transferability of related plasmids was analyzed by conjugation test. Whole-genome sequencing of the strain was conducted using PacBio and Illumina platforms. The MLST type, resistance gene and plasmid type of the strain were retrieved in BacWGSTdb. The genome and open reading frame sequence of the strain were compared using Easyfig_2.2.3. Visual cycle graphs were generated using BRIG v0.95. Results:Klebsiella pneumoniae KPN-hnqyy was resistant to carbapenem antibiotics. It belonged to ST11 and carried two carbapenemase genes of blaKPC-2 and blaNDM-5. The conjugant only harbored the blaKPC-2 gene. Whole-genome sequencing revealed that the strain contained one chromosome and three plasmids. Its chromosome genome shared more than 99.9% similarity with that of Klebsiella pneumonia KP69 and KP19-2029. Moreover, a similar IncR and IncFⅠ resistance gene fusion region was contained in different types of plasmids carried by them: the blaKPC-2 gene was located in a structure—which evolved from the Tn3-△Tn4401-Tn1721/Tn1722 sequence—inside this fusion region with its ends inserted into the transposase IS26 gene; the blaNDM-5 gene was located on a transposon containing the special plasmids of the insertion fragment in phages, with its ends inserted into the transposase IS26 gene too. Conclusions:The IncR and IncFⅡ resistance gene fusion region of blaKPC-2 carried by Klebsiella pneumoniae ST11 might be widely coexistent with the chromosomal genome. The blaNDM-5 gene carried by special plasmids might be accidentally obtained through gene recombination mediated by transposable element IS26. The wide transmission of Klebsiella pneumoniae ST11 carrying the blaKPC-2 gene in China and its ability to obtain other carbapenemase genes through transposable element IS26 were well worth attention.

Chlorhexidine gluconate bathing of adult patients in intensive care units in São Paulo, Brazil: Impact on the incidence of healthcare-associated infection

Abstract Background There is an increasing use of daily chlorhexidine gluconate (CHG) bathing to decrease healthcare associated infections (HAI). Daily bathing of patients with CHG has been successfully used to prevent multidrug-resistant organisms (MDROs) HAI in intensive care units (ICU). Methods This was a 12-month, single-center, open, cluster randomized trial, conducted at four ICUs of the University Hospital of Universidade Federal de São Paulo, Unifesp, Brazil. ICUs were randomized to either perform daily bathing of the patients with pH neutral soap and water - control units, or daily bathing with 2% CHG detergent solution - intervention units. We evaluated the incidence density rate of central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), catheter associated urinary tract infection (CAUTI), Klebsiella pneumoniae carbapenemase (KPC)-producing enterobacteria HAI, and death in the intervention and control units. Results A total of 1,640 admissions of 1,487 patients occurred during the study period (41.2% control group, and 58.8% intervention group). Incidence density rates of KPC-producing enterobacteria HAI were 5.01 and 2.25 infections/1000 patient-days in the control units and in the intervention units (p = 0.013) and mortality rates were 28.7% and 18.7% in the control units and in the intervention units (p<0.001), respectively. No difference between groups was observed in CLABSI incidence (p = 0.125), VAP incidence (p = 0.247) and CAUTI incidence (p = 0.435). No serious skin reactions were noted in either study group. Daily 2% CHG detergent solution bathing is a feasible, low cost option for HAI prevention in ICU.

MDR Escherichia coli carrying CTX-M-24 (IncF[F-:A1:B32]) and KPC-2 (IncX3/IncU) plasmids isolated from community-acquired urinary trainfection in Brazil

ABSTRACT Acquired antibiotic resistance in bacteria has become an important worldwide challenge. Currently, several bacteria, including Escherichia coli, have multidrug resistance profiles. Genes such as bla CTX-M-24 and bla KPC-2 (carbapenemase) are widespread. This research letter reports about a genomic surveillance study where multidrug-resistant E. coli containing CTX-M-24(IncF [F-:A1:B32]) and KPC-2(IncX3/IncU) plasmids were obtained from community- acquired urinary tract infection in Brazil.

Caracterização molecular e fenotípica de Klebsiella spp. produtoras de NDM / Molecular and phenotypic characterization of Klebsiella spp. NDM producers

O perfil de resistência, que algumas das espécies do complexo Klebsiella pneumoniae podem expressar, representa uma grande ameaça à saúde humana, particularmente quando resistentes aos carbapenêmicos, que são amplamente utilizados no tratamento de infecções graves em pacientes hospitalizados. O principal mecanismo de resistência aos carbapenêmicos é a produção de carbapenemases, particularmente dos tipos KPC e NDM. Um dos compostos desenvolvidos para o tratamento de infecções causadas por cepas produtoras de KPC é a combinação ceftazidimaavibactam (CAZ-AVI), mas que não tem atividade inibitória sobre metalo-betalactamases, a exemplo das NDMs. Os objetivos deste trabalho foram determinar a frequência das espécies do complexo K. pneumoniae e da coprodução de KPC, avaliar a clonalidade dos isolados, a sensibilidade ao aztreonam-avibactam (ATM-AVI), o desempenho do disco de meropenem (MEM) com inibidores para detecção de coprodução de NDM e KPC e desenvolver um teste de triagem para prever a sensibilidade ao ATM-AVI. Um total de 113 isolados do complexo K. pneumoniae produtoras de NDM ou coprodutoras de NDM e KPC, provenientes da coleção de bactérias do Grupo Fleury, coletadas períodos pré e pós início do uso de CAZ-AVI no Brasil, foram utilizadas neste estudo. A identificação da espécie e a presença dos genes blaNDM e blaKPC foi confirmada por PCR multiplex. A clonalidade dos isolados foi avaliada por eletroforese em campos pulsados (PFGE) após clivagem com XbaI. A produção de carbapenemases foi confirmada utilizando-se o teste Blue Carba. O desempenho dos discos de meropenem e CAZ-AVI contendo um ou mais inibidores de carbapenemases foi comparado com o teste molecular. A pré-difusão combinada foi realizada pré-incubando-se o ágar não inoculado com disco de CAZ-AVI, e a seguir aplicando-se o inóculo bacteriano e um disco de ATM após remover o disco de CAZ-AVI. Após incubação, os halos foram aferidos e correlacionados com a concentração inibitória mínima para ATM-AVI. As CIMs para ATM e ATM-AVI foram determinadas segundo o EUCAST. A identificação das espécies por PCR evidenciou as seguintes frequências: K. pneumoniae 75,2% (n=85); K. quasipneumoniae 16,8% (n=19), e K. variicola 8% (n=9). Uma fração de 12,4% (n=14) dos isolados apresentaram os genes blaNDM e blaKPC e 87,6% (n=99) apenas blaNDM. A análise dos perfis de PFGE de K. pneumoniae evidenciou a presença de cinco grupos clonais predominantes. Isolados do principal grupo clonal Ap (n=15) foram detectados nas cidades de São Paulo e Porto Alegre durante todo o período analisado. O grupo clonal Lp foi detectado nas cidades de São Paulo e Recife em 2019. Os dois principais grupos clonais no período pré-CAZ-AVI continham maior número de isolados do que aqueles no período de uso do CAZ-AVI. Os perfis de PFGE de K. quasipneumoniae evidenciaram quatro grupos clonais predominantes, e presentes apenas no estado de São Paulo, com persistência do grupo clonal Aq desde 2017. Quanto à K. variicola, foram observados dois grupos clonais predominantes Av e Bv, o primeiro presente apenas em São Paulo desde 2018 e o segundo em Porto Alegre apenas em 2019. Calculando-se a diferença entre os diâmetros de halo do disco MEM contendo EDTA e ácido fenilborônico (AFB) e o maior dos halos obtidos para MEM com EDTA ou AFB, observou-se que todos os isolados com coexpressão de KPC e NDM apresentaram diferença ≥ 5 mm. Uma fração de 42,3% dos isolados positivos apenas para blaNDM apresentaram sensibilidade para ATM (CIM ≤ 4 mg/L). Todos os isolados testados apresentaram CIM para ATM-AVI ≤ 1/4 mg/L, sendo a CIM90 0,125/4 mg/l. No teste de pré-difusão combinada, o menor diâmetro de halo obtido foi de 23 mm. A espécie predominante na amostragem foi K. pneumoniae. A disseminação clonal, observada neste estudo, contrasta com a diversidade clonal descrita em outros locais do mundo para produtores de NDM, exceto Grécia e China. Considerando os pontos de corte atuais para ATM, é provável que haja resposta clínica adequada no uso de ATM-AVI no tratamento de infecções causadas por isolados produtores de NDM e coprodutores de KPC e NDM. Utilizando-se o valor de corte de ≤ 5 mm para a diferença entre halos de inibição, de MEM com AFB e EDTA e o segundo maior halo com inibidor, a sensibilidade foi de 100% e a especificidade foi de 96,1,0%. O método de pré-difusão com CAZ-AVI e ATM é um método simples e o diâmetro ≥ 23 mm tem excelente correlação com a CIM para ATM-AVI ≤ 1/4 mg/L

The resistance profile, which some species of the Klebsiella pneumoniae complex may express, represent a great threat to human health, particularly when resistant to carbapenems, which are widely used in the treatment of severe infections in hospitalized patients. The main mechanism of resistance to carbapenems is the production of carbapenemases, particularly KPCs and NDMs. One of the compounds developed for the treatment of infections caused by KPC-producing strains is the combination ceftazidime-avibactam (CAZ-AVI), but which has no inhibitory activity on metallobetalactamases, as is the case for NDMs. The objectives of this work were to determine the frequency of K. pneumoniae complex species and KPC co-production, evaluate the clonality of isolates, the susceptibility to aztreonam-avibactam (ATM-AVI), the performance of meropenem (MEM) disks with inhibitors for detecting NDM co-production and KPC and develop a screening test to predict sensitivity to ATM-AVI. A total of 113 NDM-producing or NDM and KPC co-producing K. pneumoniae complexes, from the Fleury Group's bacteria collection, collected in the pre- and post-starting periods of CAZ-AVI use in Brazil, were used in this study. Species identification and the presence of the blaNDM and blaKPC genes were confirmed by multiplex PCR. The clonality of the isolates was evaluated by pulsed field electrophoresis (PFGE) after cleavage with XbaI. Carbapenemase production was confirmed using the Blue Carba test. The performance of MEM and CAZ-AVI disks containing one or more carbapenemase inhibitors was compared with the molecular test. Combined pre-diffusion was performed by preincubating the uninoculated agar with a CAZ-AVI disk, and then applying the bacterial inoculum and na ATM disk after removal of the CAZ-AVI disk. After incubation, halos were measured and correlated with the minimum inhibitory concentration (MIC) for ATM-AVI. ATM and ATM-AVI MICs were determined according to EUCAST. The identification of species by PCR evidenced the following frequencies: K. pneumoniae 75.2% (n=85); K. quasipneumoniae 16.8% (n=19), and K. variicola 8% (n=9). A fraction of 12.4% (n=14) of the isolates had the blaNDM and blaKPC genes and 87.6% (n=99) had only blaNDM. The analysis of the PFGE profiles of K. pneumoniae evidenced the presence of five predominant clonal groups. Isolates from the main clonal group Ap (n=16) were detected in the cities of São Paulo and Porto Alegre throughout the analyzed period. The clonal group Lp was detected in the cities of São Paulo and Recife 2019. The PFGE profiles of K. quasipneumoniae showed four predominant clonal groups, present only in the state of São Paulo, with persistence of the clonal group Aq since 2017. As for K. variicola, two predominant clonal groups Av and Bv were observed, the first present only in São Paulo since 2018 and the second in Porto Alegre only in 2019. Calculating the difference between the inhibition zone diameters of the MEM disk containing EDTA and phenylboronic acid (AFB) and the largest of the inhibition zone diameters obtained for MEM with EDTA or AFB, it was observed that all isolates with co-expression of KPC and NDM showed a difference 5 ≥mm. A fraction of 42.3% of isolates positive only for blaNDM showed sensitivity to ATM (MIC ≤ 4 mg/L). All tested isolates presented MIC for ATM-AVI ≤ 1/4 mg/L, being the MIC90 0.125/4 mg/l. In the combined pre-diffusion test, the smallest inhibition zone diameter obtained was 23 mm. The predominant species in the sample was K. pneumoniae, but a significant fraction of the other species in the complex was also observed in the sample. The clonal spread observed in this study contrasts with the clonal diversity described elsewhere in the world for NDM-producing isolates, except Greece and China. Considering the current cut-off points for ATM, it is likely that there is an adequate clinical response in the use of ATM-AVI in infections caused by NDM-producing and KPC-NDM co-producing isolates in Brazil. Using the cutoff value of 5 mm for the difference between inhibition zones, of MEM with AFB and EDTA and the second largest zone of MEM with inhibitor, the sensitivity was 100% and the specificity was 96.1%. The pre-diffusion method with CAZ-AVI and ATM is a simple method and the diameter ≥ 23 mm has excellent correlation with the MIC for ATM-AVI ≤ 1/4 mg/L

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.

Detección fenotípica y genotípica de la producción de carbapenemasas tipo NDM-1 y KPC en enterobacterias aisladas en un laboratorio clínico en Maracay, Venezuela / Phenotypic and genotypic detection of the production of carbapenemases type NDM-1 and KPC in isolated Enterobacteriaceae in a clinical laboratory in Maracay, Venezuela

INTRODUCCIÓN: La producción de beta-lactamasas capaces de hidrolizar a los carbapenémicos es uno de los mecanismos de resistencia más preocupantes porque eliminan la última opción terapéutica frente a los microorganismos multi-resistentes. OBJETIVO: Determinar la producción de carbapenemasas tipo KPC y NDM-1, empleando métodos fenotípicos y genotípicos, en enterobacterias aisladas en un laboratorio clínico de la ciudad de Maracay, Venezuela. MÉTODOS: Se determinó la producción de carbapenemasas mediante métodos fenotípicos (según algoritmo de Malbrán) y genotípicos (amplificación de los genes blaNDM-1 y blaKPC por RPC) en enterobacterias aisladas en un laboratorio clínico durante el período marzo-agosto 2018. RESULTADOS: Se identificaron 605 enterobacterias de diferentes especies, siendo Escherichia coli la cepa con mayor porcentaje de aislamiento (61,3%), seguida por Klebsiella pneumoniae (14,9%). Diez y seis enterobacterias (2,64%) fueron positivas para la producción de carbapenemasas: 13 cepas de K. pneumoniae y tres del complejo Enterobacter cloacae. La RPC demostró que 14 cepas (87,5%) contienen el gen blaNDM-1 y dos (12,5%) el gen blaKPC; se observó 100% de concordancia entre la determinación fenotípica y la RPC para ambos grupos de enzimas. CONCLUSIONES: Los resultados mostraron mayor incidencia de la metalo-beta-lactamasa tipo NDM-1, reconocida como una alarma epidemiológica debido a que su rápida diseminación dificulta su control, por lo que la identificación del tipo de enzima permitiría establecer estrategias de manejo y control más certeras con la finalidad de erradicar a dichos patógenos.

BACKGROUND: The production of carbapenem-hydrolyzing beta-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms. AIM: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela. METHODS: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018. RESULTS: 605 Enterobacteriaceae of different species were identified, being Escherichia coli the strain with the highest percentage of isolation (61.3%), followed by Klebsiella pneumoniae (14.9%). Sixteen strains (2.64%) were positive for carbapenemases production: 13 strains of K. pneumoniae and three of the Enterobacter cloacae complex. PCR showed that 14 strains (87.5%) carry the blaNDM-1 gene and two strains (12.5%) the blaKPC gene; 100% agreement was observed between phenotypic determination and PCR for both groups of enzymes. CONCLUSIONS: The results of this study showed a higher incidence of metallo-beta-lactamase type NDM-1, which rapid dissemination and consequently difficult control has been cause of epidemiological alert. The identification of the type of enzyme would allow establishing more accurate management and control strategies in order to eradicate these pathogens.

In vitro antibacterial effects of imipenem combined with conventional antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae / 中国基层医药

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae / 药物分析学报

Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance.This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA)against carbapenemase-producing Klebsiella pneumoniae(KPC-KP).LNA alone exhibited bacteri-cidal activity at 2.5％(V/V),and in combination with meropenem(MPM)at 1.25％(V/V).Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells.Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress.Zeta po-tential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability.Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells,inferring membrane damage.Furthermore,intracel-lular leakage of nucleic acid and proteins was detected upon LNA treatment.Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular ma-terials.LNA was found to induce oxidative stress by generating reactive oxygen species(ROS)that initiate lipid peroxidation and damage the bacterial membrane.In conclusion,LNA generates ROS,initiates lipid peroxidation,and damages the bacterial membrane,resulting in intracellular leakage and eventually killing the KPC-KP cells.

Prevalence of carbapenemase production in Pseudomonas aeruginosa isolates causing clinical infections in Lagos University Teaching Hospital, Nigeria

Background: Pseudomonas aeruginosa has been highly associated with carbapenem resistance in which carbapenemases has been suggested to be a major contributory factor. Hence the objective of this study was to phenotypically detect KPC-type carbapenemase, metallo-ß-lactamase and OXA-48 carbapenemase production in clinical isolates of P. aeruginosa in Lagos University Teaching Hospital (LUTH), Nigeria Methodology: One hundred and seventy-one P. aeruginosa isolates consecutively recovered from clinical specimens of patients with infections at the Medical Microbiology and Parasitology laboratory of the hospital were identified using MicrobactTM 24E kit. Preliminary screening for carbapenem resistance was determined by the disc diffusion method on Mueller-Hinton agar using single discs of meropenem and imipenem. Phenotypic detection of carbapenemase production among carbapenem-resistant isolates was performed by the combination disc test of meropenem-phenylboronic acid (MRPBO) and meropenem-dipicolinic acid (MRPDP) as recommended by EUCAST 2013 guideline. Results: Out of the 171 P. aeruginosa isolates, 35 (20.5%) were carbapenem non-susceptible (resistant) while carbapenemase production was detected in 27 (77.1%) of these carbapenem resistant isolates, and no enzyme was detected in 8 (22.9%). Of the 27 carbapenemase producing isolates, 22 (81.5%) produced MBL, 1 (3.7%) produced KPC, while 4 (14.8%) produced both KPC and MBL enzymes. Conclusion: This study revealed that carbapenem resistance among P. aeruginosa clinical isolates in our institution is gradually increasing. The mechanism for this rise is associated with carbapenemases, with MBL being the major carbapenemase involved. There is the need to ensure strict compliance with the LUTH infection control guidelines in order to check the rising incidence of infection caused by carbapenem resistant P. aeruginosa

Caracterización de carbapenemasas en enterobacterias de muestras de pacientes que acudieron al Hospital General San Juan de Dios de la ciudad de Guatemala durante 2014 y 2015 / Characterization of carbapenemases in Enterobacteriaceae of samples of patients who attended the San Juan de Dios General Hospital in Guatemala City during 2014 and 2015

En salud pública a nivel mundial, la producción de carbapenemasas es actualmente el mayor problema de resistencia antimicrobiana. El objetivo de este estudio fue caracterizar las carbapenemasas en enterobacterias en pacientes que acudieron al Hospital General San Juan de Dios de la ciudad de Guatemala y determinar servicios hospitalarios y tipos de muestras más frecuentes. Se usaron datos de 2014 y 2015 del área de bacteriología del hospital; se realizó una revisión sistemática, selección, ordenamiento y cálculo de frecuencias y porcentajes. En 2014, 165/165 (100 %) de las carbapenemasas fueron de tipo metalo-ß-lactamasas (MBL); en 2015, 90/118 (76 %) MBL y 28/118 (24 %) Klebsiella pneumoniae carbapenemasa (KPC). Klebsiella pneumoniae fue la enterobacteria productora de carbapenemasas (CPE) aislada con más frecuencia, 134/165 (81 %) en 2014 y 82/118 (69 %) en 2015. En 2014 la unidad de cuidados intensivos de neonatos obtuvo el mayor porcentaje de aislamientos de CPE, 30/165 (18 %); en 2015, medicina de hombres fue el servicio con el mayor porcentaje de CPE, 13/118 (11 %). El tipo de muestra más frecuente en 2014 fue sangre, 67/165 (41 %); en el 2015 fue orina, 31/118 (26 %). Los resultados evidencian la persistencia de carbapenemasas tipo MBL y la aparición de nuevos tipos, específicamente carbapenemasas tipo KPC, que destacan la necesidad de actuar urgentemente ante el riesgo que suponen para la salud de la población.

In public health worldwide, carbapenemase production is currently the biggest problem of antimicrobial resistance. The objective of this study was to characterize carbapenemases in Enterobacteriaceae of patients who attended the San Juan de Dios General Hospital in Guatemala City and to determine hospital services and types of samples more frequent. Data from 2014 and 2015 of the bacteriology department of the hospital were used; a systematic review, selection, ordering and calculation of frequencies and percentages was conducted. In 2014, 165/165 (100 %) of the carbapenemases were metallo-ß-lactamases (MBL); in 2015, 90/118 (76 %) MBL and 28/118 (24 %) Klebsiella pneumoniae carbapenemase (KPC). Klebsiella pneumoniae was the carbapenemases-producing Enterobacteriaceae (CPE) most frequently isolated, 134/165 (81 %) in 2014 and 82/118 (69 %) in 2015. In 2014 the neonatal intensive care unit obtained the highest percentage in CPE, 30/165 (18 %); in 2015, men's medicine was the service with the highest percentage of carbapenemases, 11/138 (11 %). The most frequent type of sample in 2014 was blood, 67/165 (41 %). In 2015 it was urine, 31/118 (26 %). The results obtained highlight the persistence of MBL-type carbapenemases and the appearance of new types of carbapenemases, specifically KPC. These results underline the need to act urgently in Guatemala in the face of the problems that carbapenemases-producing Enterobacteriaceae pose for the health of the population.

First characterization of K. pneumoniae ST11 clinical isolates harboring blaKPC-3 in Latin America / Primera caracterización de aislamientos clínicos de K. pneumoniae ST11 portadoresde blaKPC-3en América Latina

Abstract Antimicrobial resistance due to carbapenemase production in Enterobacteriaceaeclinical isolates is a global threat. Klebsiella pneumoniae harboring the blaKPCgene is one ofthe major concerns in hospital settings in Latin America.The aim of this study was to characterize the antibiotic resistance mechanisms and to typifyfour carbapenem-resistant K. pneumoniae clinical isolates from the city of Manizales, Colombia.We identified blaKPC-3in all four isolates by polymerase chain reaction and subsequentsequencing. The plasmid-mediated quinolone resistance genes qnrB19-like and aac(6)Ib-cr;fosfomycin resistance gene fosA and an insertion sequence IS5-like in mgrB (colistin resistance)were also detected. Sequence types ST11 with capsular type wzi75, and ST258 with wzi154,were characterized. The blaKPC-3gene was mobilized in a 100-kb IncFIB conjugative plasmidwith vagCD toxin-antitoxin system.This work reports multiple resistance genes in blaKPC-producing K. pneumoniae and the firstoccurrence of ST11 clinical isolates harboring blaKPC-3in Latin America.

Resumen La resistencia a antibióticos mediada por la producción de carbapenemasas en aislamientos clínicos de Enterobacteriaceae es una amenaza mundial. Klebsiella pneumoniae portador de blaKPC es uno de los mayores problemas a nivel hospitalario en Latinoamérica. El objetivo de este estudio fue caracterizar los mecanismos de resistencia antibiótica y tipificar cuatro aislamientos clínicos de K. pneumoniae resistentes a carbapenems obtenidos en la ciudad de Manizales, Colombia. Se identificó blaKPC-3 en todos los aislamientos mediante reacción en cadena de polimerasa y secuenciación. También se detectaron los genes de resistencia transferible a quinolonas qnrB19-like y aac(6')Ib-cr y a fosfomicina fosA, y la secuencia de inserción /S5-like en mgrB (asociada a la resistencia a colistina). Se caracterizaron los secuenciotipos ST11 (cápsula wzi75) y ST258 (cápsula wzi154). Se comprobó que blaKPC-3 fue movilizado por un plásmido conjugativo IncFIB-vagCD de 100kb. En este trabajo se reportan múltiples genes de resistencia en K. pneumoniae productor de blaKPC y se describen por primera vez aislamientos clínicos ST11 productores de blaKPC-3 en Latinoamérica.

Caracterización clínica, epidemiológica y microbiológica de bacteriemias producidas por enterobacterias resistentes a carbapenems en un hospital universitario de Córdoba, Argentina / Clinical, epidemiological and microbiological characterization of bacteremia produced by carbapenem-resistant enterobacteria in a university hospital in Córdoba, Argentina

Resumen Introducción: Las enterobacterias son una causa principal de infecciones del torrente sanguíneo y su resistencia antimicrobiana se encuentra en aumento. Esto lleva a un incremento de la morbilidad-mortalidad y de los costos en la salud pública. Las enterobacterias resistentes a carbapenems representan un grave desafío a nivel global ya que existen escasas opciones terapéuticas disponibles. Objetivo: Caracterización clínico/microbiológica de las bacteriemias resistentes a carbapenémicos observadas en un período de 4 años. Material y Método: Estudio retrospectivo, observacional y descriptivo, sobre las bacteriemias por enterobacterias resistentes y sensibles a carbapenems. Resultados: Se analizó un total de 84 pacientes con bacteriemia por enterobacterias resistentes y sensibles a carbapenems. Entre las resistentes, observamos una mayor proporción de: tratamiento antimicrobiano previo, hospitalización en unidad de terapia intensiva (UTI), inicio de la bacteriemia en UTI y antecedentes de β-lactamasas de espectro extendido. Además, se detectó un amplio predominio de Klebsiella pneumoniae productor de KPC y una mortalidad atribuible de 52,4%. Discusión: El estudio posibilitó profundizar el conocimiento de una enfermedad emergente de elevada mortalidad, en vistas al diseño y aplicación de estrategias de control de infecciones y de esquemas de tratamiento efectivos adaptados a la epidemiologia local.

Abstract Background: Enterobacteriaceae are a major cause of bloodstream infections and their antimicrobial resistance continues to increase. This leads to higher morbidity-mortality rates and public health costs. Carbapenem-resistant Enterobacteriaceae represent a serious challenge globally, since there are few therapeutic options available. Aim: Clinical/microbiological characterization of the carbapenem-resistant bacteremia observed over a period of 4 years. Methods: Retrospective, observational and descriptive study about bacteremia caused by carbapenem-resistant and susceptible Enterobacteriaceae. Results: A total of 84 patients with bacteremia including carbapenem-resistant and susceptible Enterobacteriaceae were analyzed. We found that patients infected with carbapenem-resistant strains presented a higher proportion of: previous antibiotic treatment, hospitalization in intensive care unit (ICU), onset of the bacteremia during hospitalization in ICU and previous infection with extended-spectrum-beta-lactamase producing Enterobacteriaceae. Additionally, we observed a predominance of KPC-producing Klebsiella pneumoniae and an attributable mortality rate of 52.4%. Discussion: This study allowed for a better understanding of an emerging problem with high mortality, which in turn is useful for the design and adoption of infection control strategies and effective treatment regimens adapted to our local epidemiology.

Identificación de los mecanismos resistencia enzimáticos en uropatógenos de pacientes ambulatorios de un hospital público de San Lorenzo, Paraguay; 2015-2019 / Identification of enzyme resistance mechanisms in pathogens from an outpatient clinic in a public hospital in San Lorenzo, Paraguay; 2015-2019

Introducción: El propósito del estudio es determinar en los urocultivos, la prevalencia de los mecanismos enzimáticos de resistencia encontrados in vitro. Materiales y métodos: Se realizó un estudio retrospectivo, de ambos sexos, mayores de 18 años, que acudieron al Consultorio Externo de Clínica Médica y Urgencias por síntomas de infección urinaria. Se incluyeron todos los urocultivos en los que se aislaron uropatógenos con recuento ≥ 105 UFC/mL. Se excluyeron los urocultivos polimicrobianos, los que no contaban con antibiograma o aquellos con datos clínicos incompletos. Resultados: Se identificaron 1031 urocultivos que cumplieron con los criterios establecidos para la realización del estudio. El 56% correspondió al sexo femenino y el 43% al masculino. La edad media de las mujeres fue de 52± 20 años y el de los hombres fue de 62±16 años. Los uropatógenos más frecuentes fueron Escherichia coli 553 (52% en promedio) seguida de Klebsiella pneumoniae con 148 (14% en promedio). Urocultivos de varones: El principal mecanismo de resistencia de Escherichia coli fueron las BLEE, 55 aislamientos (91%); seguida de las MBL, 3 aislamientos (5%) y KPC, 2 aislamientos (3%). En Klebsiella pneumoniae en 53 aislamientos se puedo observar: BLEE, 31 aislamientos (58%); seguida de las KPC 13 aislamientos (25%) y MBL, 9 aislamientos en (16%). Urocultivos en mujeres: Las enzimas de Escherichia coli fueron 81 aislamientos, de los cuales fueron BLEE, 79 aislamientos (97%); seguido de las KPC, 1 aislamiento (1%) y las MBL, 1 aislamiento (1%). En Klebsiella pneumoniae se pudo observar los siguientes mecanismos enzimáticos en base a 35 aislamientos; BLEE, 19 aislamientos (54%), seguida de las KPC, 12 aislamientos (34%) y por último, MBL, 4 aislamientos (13%). Conclusión: En las IVU de nuestro estudio, Escherichia coli y Klebsiella pneumoniae fueron las principales bacterias que originan resistencia a los antibióticos y la BLEE fue la enzima más frecuentemente identificada en ambos sexos.

Introduction: The objective of this study was to assess frequency of enzymatic resistance mechanisms isolated from community urinary tract infections (UTI) determined in vitro in urine cultures. Objectives: This is a retrospective study, a total of 1031 urine samples were included from patients with urinary tract infection who had consulted at the Outpatient Clinic and Emergencies Services. The following information was recorded, age, sex, urine sample. All urine cultures in which pathogens with a count of ≥ 105 CFU / mL were included. Were excluded polymicrobial urine cultures, those without an antibiogram or those with incomplete clinical data. Results: A total of 1031 urine samples met inclusion criteria, 56% of patients were female and 43% male. The mean age of the women was 52 ± 20 years and in men was 62 ± 16 years. 553 (52%) E. coli and 148 (14%) Klebsiella strains were isolated from community samples. Male urine cultures: The main resistance mechanism of Escherichia coli was ESBLs, 55 isolates (91%); followed by MBL, 3 isolates (5%) and KPC, 2 isolates (3%). In Klebsiella pneumoniae (53 isolates); ESBL, 31 isolates (58%); followed by KPC 13 isolates (25%) and MBL, 9 isolates in (16%). Female urine culture: Escherichia coli enzymes 81 isolates, of which ESBLs were 79 isolates (97%); followed by KPC, 1 isolate (1%) and MBL, 1 isolate (1%). In Klebsiella pneumoniae the following enzymatic mechanisms could be observed based on 35 isolates; ESBL, 19 isolates (54%), followed by KPCs, 12 isolates (34%) and finally, MBL, 4 isolates (13%). Conclusion: The result of our study showed high prevalence of Escherichia coli and Klebsiella pneumoniae causing resistance to antibiotics in culture bacteria from urine samples of patients with UTI, and ESBL was the main ß-lactamase resistance mechanism in Klebsiella and E. coli isolates in both male and female.