RESUMO
We characterized five carbapenemase-producing Enterobacterales (CPE) isolates from two health care institutions in Lima, Peru. The isolates were identified as Klebsiella pneumoniae (n = 3), Citrobacter portucalensis (n = 1), and Escherichia coli (n = 1). All were identified as blaOXA-48-like gene carriers using conventional PCR. Whole-genome sequencing found the presence of the blaOXA-181 gene as the only carbapenemase gene in all isolates. Genes associated with resistance to aminoglycosides, quinolones, amphenicols, fosfomycins, macrolides, tetracyclines, sulfonamides, and trimethoprim were also found. The plasmid incompatibility group IncX3 was identified in all genomes in a truncated Tn6361 transposon flanked by ΔIS26 insertion sequences. The qnrS1 gene was also found downstream of blaOXA-181, conferring fluoroquinolone resistance to all isolates. CPE isolates harboring blaOXA-like genes are an increasing public health problem in health care settings worldwide. The IncX3 plasmid is involved in the worldwide dissemination of blaOXA-181, and its presence in these CPE isolates suggests the wide dissemination of blaOXA-181 in Peru. IMPORTANCE Reports of carbapenemase-producing Enterobacterales (CPE) isolates are increasing worldwide. Accurate detection of the ß-lactamase OXA-181 (a variant of OXA-48) is important to initiate therapy and preventive measures in the clinic. OXA-181 has been described in CPE isolates in many countries, often associated with nosocomial outbreaks. However, the circulation of this carbapenemase has yet to be reported in Peru. Here, we report the detection of five multidrug-resistant CPE clinical isolates harboring blaOXA-181 in the IncX3-type plasmid, a potential driver of dissemination in Peru.
Assuntos
Infecções por Enterobacteriaceae , Enterobacteriaceae , Humanos , Enterobacteriaceae/genética , América Latina , Proteínas de Bactérias/genética , beta-Lactamases/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Enterobacteriaceae/epidemiologiaRESUMO
Introduction: Carbapenemase-producing Gram-negative bacilli is a worldwide problem, which represent a health concern, because most of its resistance mechanisms are encoded by plasmids, therefore easily transmissible in hospital settings. Many methods have been proposed to detect such resistance, but screening is still challenging, recently the modified carbapenem inactivation method has shown promising results, however more studies need to be performed. Hence, this study aimed to evaluate the performance of the mCIM in carbapenem-resistant Enterobacteriaceae and nonfermenting Gram-negative bacilli isolates. Materials and methods: From a microbial collection with molecular characterization of carbapenemase genes previously conducted, 100 Gram-negative bacilli isolates were selected, fifty-two non-carbapenemase producing and 48 carbapenemase-producing isolates. The mCIM was performed according to the CLSI guidelines, and to assess the validity of the method sensitivity and specificity were calculated.Results: The sensitivity of the mCIM observed in this study was 96% (46/48) and the specificity was 96,2% (50/52). Most of the Gram-negative bacilli carrying a carbapenemase gene were mCIM-positive, moreover, in carbapenem-resistant isolates that do not produce a carbapenemase (Enterobacteriaceae and non-fermenters) the results of the mCIM were negatives. Conclusion: Overall the mCIM provides a low-cost alternative for the screening of carbapenemase-producing Gram-negative bacilli. Our findings highlight that mCIM is a sensitive and specific method to assess carbapenemase-producing in Gram negative bacilli non-fermenters and Enterobacteriaceae as Enterobacter cloacae.
Introducción: Los bacilos Gram negativos productores de carbapenemasas representan un problema de salud pública mundial. Estos mecanismos de resistencia se encuentran codificados en su mayoría en plásmidos, por lo que son fácilmente transmisibles en el entorno hospitalario. Se han propuesto muchos métodos para detectar la presencia de carbapenemasas; sin embargo, la detección sigue siendo un desafío. Recientemente, el método de inactivación de carbapenémicos modificado (mCIM) ha mostrado resultados prometedores; sin embargo, es necesario realizar más estudios. Este estudio tuvo como objetivo evaluar el rendimiento del mCIM en Enterobacterias y bacilos Gram negativos no fermentadores resistentes a carbapenémicos. Materiales y métodos: A partir de una colección microbiana con previa caracterización molecular de genes que codifican carbapenemasas, se seleccionaron 100 aislados de bacilos Gram negativos, cincuenta y dos aislados no productores de carbapenemasas y 48 productores de carbapenemasas. El mCIM se realizó de acuerdo con las directrices del CLSI, y para evaluar la validez del método se calcularon la sensibilidad y la especificidad. Resultados: La sensibilidad del mCIM observada en este estudio fue del 96% (46/48) y la especificidad del 96,2% (50/52). La mayoría de los bacilos Gram negativos portadores de carbapenemasas fueron mCIM positivos, además, en los aislados resistentes a carbapenémicos no productores de carbapenemasas (Enterobacterias y bacilos Gram negativos no fermentadores) los resultados de mCIM fueron negativos. Conclusión: En general, el mCIM proporciona una alternativa de bajo costo para la detección de carbapenemasas en bacilos gramnegativos. Nuestros hallazgos destacan el mCIM como un método sensible y específico para evaluar la producción de carbapenemasas en bacilos Gram negativos no fermentadores y Enterobacterias como Enterobacter cloacae.
Assuntos
HumanosRESUMO
RESUMEN La diseminación global de carbapenemasas es de importancia en la salud pública. El objetivo del estudio es describir la presencia de genes de resistencia a carbapenémicos tipo KPC y metalobetalactamasas en enterobacterias aisladas de 12 hospitales y remitidos al Laboratorio de Referencia Nacional de Infecciones Intrahospitalarias del Instituto Nacional de Salud de Perú durante los años 2013 al 2017. Las cepas fueron identificadas por métodos convencionales, la resistencia antimicrobiana fue determinada por métodos fenotípicos, bioquímicos y la presencia de genes de resistencia, se detectaron por PCR convencional. Se identificaron 83 cepas con carbapenemasas: 26 (31,3 %) portando el gen blaKPC, 56 (67,5 %) el gen blaNDM y una (1,2 %) cepa con el gen blaIMP. Es el primer reporte que da a conocer los genes de carbapenemasas circulantes en hospitales de Perú, por lo que se requiere mejorar la vigilancia para tener un mejor conocimiento de la situación en Perú.
ABSTRACT The global spread of carbapenemases is a significant public health concern. The aim of this report is to describe the presence of KPC-type carbapenem-resistant genes and enterobacteria isolated in 12 hospitals and forwarded to the Peruvian National Institute of Health's National Infection Reference Laboratory during the period between 2013 and 2017. The strains were identified by conventional methods; antimicrobial resistance was determined by phenotypic and biochemical methods. The presence of resistant genes was detected by conventional PCR. Eighty-three (83) strains harboring carbapenemases were identified: 26 (31.3%) carrying the blaKPC gene, 56 (67.5%) the blaNDM gene, and one strain (1.2%) with the blaIMP gene. This is the first report that shows the circulating carbapenemases genes in Hospitals in Peru of cases submitted for their confirmation to the National Reference Laboratory, so it is necessary to improve the surveillance to better understand their situation in our country.
Assuntos
Humanos , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Peru , Fatores de Tempo , Proteínas de Bactérias/genética , beta-Lactamases/genética , Enterobacteriaceae/enzimologia , HospitaisRESUMO
BACKGROUND: Carbapenemases-producing Enterobacteriaceae (CPE) are a worldwide public health emergency. In Mexico, reports of CPE are limited, particularly in the pediatric population. Here, we describe the clinical, epidemiological, and molecular characteristics of seven consecutive cases in a third-level pediatric hospital in Mexico City over a four-month period during 2016. RESULTS: The Enterobacteriaceae identified were three Escherichia coli strains (producing OXA-232, NDM-1 and KPC-2), two Klebsiella pneumoniae strains (producing KPC-2 and NDM-1), one Klebsiella oxytoca strain producing OXA-48 and one Enterobacter cloacae strain producing NDM-1. The majority of patients had underlying disesases, three were immunocompromised, and three had infections involved the skin and soft tissues. Half patients died as a result of CPE infection. CONCLUSIONS: This study represents the first report of E. coli ST131-O25b clone producing NDM-1 in Latin America. In addition, this study is the first finding of K. oxytoca producing OXA-48 and E. coli producing OXA-232 in Mexican pediatric patients.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Adolescente , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Criança , Pré-Escolar , Enterobacter cloacae/enzimologia , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Enterobacter cloacae/patogenicidade , Infecções por Enterobacteriaceae/mortalidade , Infecções por Enterobacteriaceae/fisiopatologia , Escherichia coli/enzimologia , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Feminino , Genótipo , Hospitais Pediátricos , Humanos , Lactente , Klebsiella oxytoca/enzimologia , Klebsiella oxytoca/genética , Klebsiella oxytoca/isolamento & purificação , Klebsiella oxytoca/patogenicidade , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , América Latina/epidemiologia , Masculino , México/epidemiologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , beta-Lactamases/metabolismoRESUMO
Objetivos: Describir las características clínicas, los esquemas de antibiótico empleados y el pronóstico en términos de mortalidad intrahospitalaria y efectos adversos en pacientes con bacteriemia por enterobacterias con prueba fenotípica para carbapenemasas positiva. Material y métodos: Estudio de corte trasversal en un hospital de tercer nivel (Medellín, Colombia), en pacientes con bacteriemia por enterobacterias resistentes a carbapenems (CRE) detectados entre enero del 2010 y diciembre del 2013. Se presentan las variables continuas con medianas y rangos intercuartiles (RIQ) y las categóricas con porcentajes. Resultados: Se incluyeron 64 casos con un promedio de edad de 62 ± 14 años, 66% (n = 42) hombres. El 60% (n = 38) se encontraban en la UCI, y la mediana de APACHE-II fue de 17 (RIQ: 12-22), con alta comorbilidad (puntaje Charlson de 3; RIQ: 2-5). La mediana de estancia previa a la bacteriemia fue de 21 días (RIQ: 13-39). El 64% correspondieron a Klebsiella pneumoniae , el 20% a Serratia marcescens y el 11% a Enterobacter spp. El 45% tenían tamización positiva previa a la bacteriemia. La mortalidad a los 28 días fue del 51,6% (n = 33) y ocurrió con una mediana de 5 días luego de detectada la bacteriemia (RIQ: 2-17). El tratamiento definitivo fue combinado en el 76,6% de los casos, pero no hubo un esquema de combinación prevalente. Se reportaron efectos adversos en uno de cada 3 pacientes, y la mediana de estancia hospitalaria fue de 46 días (RIQ: 26-76). La mortalidad a 28 días de pacientes tratados con carbapenems (n = 27), colistina (n = 27) o tigeciclina (n = 18), solos o en cualquier combinación, fue del 40,7, del 55,2 y del 55,7%, respectivamente. Discusión: Los pacientes incluidos tenían altos índices de comorbilidad y exposición al ambiente nosocomial, como en estudios previamente publicados. La mortalidad a 28 días fue comparable a la reportada en otros estudios. Se encontró menor mortalidad en pacientes tratados con terapias combinadas que incluían carbapenems, similar a lo reportado en un estudio clínico reciente en pacientes con bacteriemia por Klebsiella pneumoniae productora de carbapenemasas. Conclusiones: La bacteriemia por CRE afecta pacientes muy enfermos y se acompaña de elevadamortalidad. Se detecta colonización en casi la mitad de los pacientes antes del desarrollo deinfección. Hay heterogeneidad en el manejo antimicrobiano, pero la inclusión de carbapenemsen el esquema de tratamiento combinado podría asociarse con menor mortalidad.
Objectives: To describe the clinical features, antibiotic regimes and prognosis in terms of inpatient mortality and adverse effects in patients with Enterobacteriaceae bacteremia anda positive carbapenemase-detecting phenotypic test. Materials and methods: A cross-sectional study was conducted at a tertiary hospital (Medellín,Colombia). Patients with blood stream infections by carbapenems-resistant Enterobacteriaceae(CRE) diagnosed from January, 2010 to December, 2013 were included. Continuous variables are presented as medians and interquartile ranges (IQR), and categorical variables are presentedas percentages. Results: Sixty-four cases were included, with a mean age of 62 ± 14; 66% were male (n = 42).A total of 60% (n = 38) were admitted to the ICU and the median APACHE-II score was 17 (IQR:12-22), with high comorbidity (Charlson score = 3, IQR: 2-5). The median hospital stay prior to the diagnosis of bacteremia was 21 days (IQR: 13-39). Klebsiella pneumoniae was isolated in 64%, Serratia marcescens in 20% and Enterobacter spp. in 11% of the cases. Some 45% had apositive screening before the diagnosis of bacteremia. Mortality at 28 days was 51.6% (n = 33)and occurred in a median of 5 days (IQR: 2-17) after bloodstream infection was detected. Definitive treatment was a combination of antibiotics for 76.6%, but no combination scheme was prevalent. Adverse effects were observed in one of 3 patients and the median hospital stay was46 days (IQR: 26-76). Mortality at 28 days was 40.7% when patients were treated with a combination that included carbapenems agents (n = 27), compared with 55.2% for colistin (n = 27) and 55,7% for tigecycline (n = 18). Discussion: A high comorbidity index and nosocomial environment exposure were observed,as in previously published studies. The 28-day mortality was comparable to that reported inother studies. There was less mortality in patients treated with a combination that includeda carbapenem agent, as was reported in a recent clinical study on patients with bacteremia Klebsiella pneumoniae carbapenemase. Conclusions: CRE bacteremia is seen in very ill patients and is associated with high mortality. Bacterial colonization was detected in nearly half the patients prior to development of infection. The current antimicrobial therapy is heterogeneous, but the inclusion of a carbapenems agent in combination therapy may be associated with lower mortality.