Use of topical colistin in bacterial keratitis caused by extensively drug-resistant Pseudomonas Aeruginosa: a case report / Uso de colistina tópica em ceratite bacteriana causada por Pseudomonas Aeruginosa extensivamente resistente a medicamentos: relato de caso

ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.

RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.

Colistin resistance in Escherichia coli and Klebsiella pneumoniae in humans and backyard animals in Ecuador / Resistencia a la colistina de las bacterias Escherichia coli y Klebsiella pneumoniae en humanos y animales de granja en Ecuador / Resistência à colistina em Escherichia coli e Klebsiella pneumoniae em humanos e animais de quintal no Equador

ABSTRACT Objective. Colistin is an antibiotic of last resort for treating serious Gram-negative bacterial infections. However, the misuse of colistin, especially as an animal growth promoter, has contributed to increasing antimicrobial resistance, mediated mainly through plasmid transfer of the mcr-1 gene. This study assessed the prevalence of phenotypic and molecular colistin resistance in Escherichia coli and Klebsiella pneumoniae in Ecuador in healthy humans and their chickens and pigs. Methods. Fecal samples were collected from humans and their chickens and pigs in two rural coastal and Amazon regions between April and August 2020. Gram-negative bacteria were isolated and identified using conventional techniques. Phenotypic resistance was determined using the broth microdilution technique, and the mcr-1 gene was detected using conventional polymerase chain reaction. Results. A total of 438 fecal samples were obtained from 137 humans, 147 pigs and 154 chickens. The prevalence of E. coli isolates was 86.3% (378/438) and K. pneumoniae, 37.4% (164/438). Overall, the mcr-1 gene was found in 90% (340/378) of E. coli isolates, with higher prevalences found in isolates from coastal regions (96.5%, 191/198), humans (95.6%, 111/116) and chickens (91.8%, 123/134); for K. pneumoniae, the gene was found in 19.5% (32/164) of isolates, with equal distribution between regions and hosts. Only four isolates, two E. coli and two K. pneumoniae, showed phenotypic resistance: mcr-1 was present in both E. coli strains but absent in the K. pneumoniae strains. Conclusions. Despite a low prevalence of phenotypic resistance to colistin, the high prevalence of the mcr-1 gene in E. coli is of concern. Ecuador's ban on using colistin in animal husbandry must be enforced, and continual monitoring of the situation should be implemented.

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RESUMO Objetivo. A colistina é um antibiótico de último recurso para o tratamento de infecções graves por bactérias Gram-negativas. Entretanto, o uso indevido da colistina, principalmente como promotor de crescimento animal, tem contribuído para o aumento da resistência a antimicrobianos, principalmente por transferência horizontal do gene mcr-1 mediada por plasmídeos. Este estudo avaliou a prevalência de resistência fenotípica e molecular à colistina em Escherichia coli e Klebsiella pneumoniae no Equador em humanos hígidos e em galinhas e porcos por eles criados. Métodos. Entre abril e agosto de 2020, foram coletadas amostras de fezes de habitantes de duas regiões litorâneas e amazônicas do Equador e de galinhas e porcos por eles criados. Bactérias Gram-negativas foram isoladas e identificadas por meio de técnicas convencionais. A resistência fenotípica foi determinada pela técnica de microdiluição em caldo, e o gene mcr-1 foi detectado por reação em cadeia da polimerase convencional. Resultados. Foram obtidas 438 amostras fecais de 137 humanos, 147 suínos e 154 galinhas. A prevalência de isolados de E. coli foi de 86,3% (378/438), e de K. pneumoniae, 37,4% (164/438). Em geral, o gene mcr-1 foi encontrado em 90% (340/378) dos isolados de E. coli, com maiores prevalências encontradas em isolados de regiões litorâneas (96,5%, 191/198), humanos (95,6%, 111/116) e galinhas (91,8%, 123/134); para K. pneumoniae, o gene foi encontrado em 19,5% (32/164) dos isolados, com igual distribuição entre regiões e hospedeiros. Somente quatro isolados, dois de E. coli e dois de K. pneumoniae, demonstraram resistência fenotípica: o gene mcr-1 estava presente em ambas as cepas de E. coli, mas ausente nas de K. pneumoniae. Conclusões. Apesar da baixa prevalência de resistência fenotípica à colistina, a alta prevalência do gene mcr-1 em E. coli é preocupante. É preciso fiscalizar a proibição ao uso agropecuário de colistina no Equador e implementar o monitoramento contínuo da situação.

Mechanisms involved in resistance to carbapenems among Acinetobacter baumannii isolates recovered in Brazil: A systematic review and meta-analysis

SUMMARY Introduction: Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a health problem due to the limited therapeutic options available. This study was carried out to evaluate the main mechanisms of resistance of carbapenems in CRAB in the last 10 years in Brazil and to describe the susceptibility profile to tigecycline and polymyxins in these isolates. Material and methods: A systematic review was carried out according to Prisma in PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) and Cochrane Library. Data regarding enzyme resistance to carbapenems were evaluated by meta-analysis according to the random effect. Results: 21 articles were selected according to inclusion and exclusion criteria that evaluated 1096 CRAB. Most of the studies were carried out in the southern (33.3 %) and southeast (23.8 %) regions of Brazil (33.3 %) and in 2016 and 2018. According to the meta-analyzes, OXA-type carbapenemase was the main mechanism involved in the low susceptibility to carbapenems in CRAB (98%; 95% CI: 0.91, 0.99; I2 = 95%), with bla OXA-23-like (91 %; 95 % CI: 0.76; 0.97; I2 = 97 %) or bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0.15, 0.99; I2 = 98 %) genes, followed by metallo-ß-lactamases (MBL) (12 %, 95 % CI: 0.09, 0.15, I2 = 99 %) and Klebsiella pneumoniae carbapenemase (KPC) (6 %, 95 % CI: 0.04; 0.08; I2 = 87 %). Conclusion: The included studies showed that susceptibility to colistin (99 %) and tigecy-cline (93 %) remains high and was not affected by carbapenem resistance.

Introducción: Las infecciones por Acinetobacter baumannii resistente a carbapenémicos (CRAB) es un problema de salud debido a las limitadas opciones terapéuticas disponibles. Este estudio se realizó para evaluar los principales mecanismos de resistencia de los carbapenémicos en CRAB en los últimos 10 años en Brasil y describir el perfil de susceptibilidad a tigeciclina y polimixinas en estos aislados. Material y métodos: Se realizó una revisión sistemática de acuerdo con Prisma en PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) y Cochrane Library. Los datos referentes a resistencia enzimática a los carbapenémicos se evaluaron mediante metaanálisis según el efecto aleatorio. Resultados: Se seleccionaron 21 artículos según criterios de inclusión y exclusión que evaluaron 1.096 CRAB. La mayoría de los estudios se llevaron a cabo en las regiones sur (33,3%) y sureste (23,8 %) de Brasil (33,3 %) y en los años 2016 y 2018. Según los metaanálisis, la carbapenemasa tipo OXA fue el principal mecanismo implicado en la baja susceptibilidad a los carbapenémicos en CRAB (98 %; IC 95 %: 0,91; 0,99; I² = 95 %), con bla OXA-23-like (91 %; 95 % CI: 0,76; 0,97; I² = 97 %) o bla OXA-51-like / ISAba1 (84 %; 95 % CI: 0,15; 0,99 ; I² = 98 %) genes, seguida de metalo-ß-lactamasas (MBL ) (12 %; IC95 %: 0,09; 0,15; I² = 99 %) y Klebsiella pneumoniae carbapenemase (KPC) (6 %; IC95 %: 0,04; 0,08; I² = 87 %). Conclusión: Los estudios incluidos mostraron que la susceptibilidad a la colistina (99 %) y tigeciclina (93 %) sigue siendo alta y no se ve afectada por la resistencia a los carbapenémicos.

Introdução: As infecções causadas por Acinetobacter baumannii resistente aos carbapenémicos (CRAB) são um problema de saúde devido às limitadas opções terapêuticas disponíveis. Este estudo foi realizado para avaliar os principais mecanismos de resistência aos carbapenêmicos em CRAB nos últimos 10 anos no Brasil e descrever o perfil de susceptibilidade à tigeciclina e às polimixinas nesses isolados. Material e métodos: Foi conduzida uma revisão sistemática segundo o Prisma nas bases de dados PUBMED/MEDLINE, Scopus, SciELO, Biblioteca Virtual de Saúde (BVS) e Biblioteca Cochrane. Os dados relativos à resistência enzimática aos carbapenêmicos foram avaliados por meta-análises de acordo com o efeito aleatório. Resultados: Foram selecionados 21 artigos de acordo com os critérios de inclusão e exclusão que avaliaram 1.096 CRAB. A maioria dos estudos foi realizada nas regiões Sul (33,3 %) e Sudeste (23,8 %) do Brasil e nos anos de 2016 e 2018. De acordo com as metanálises, a carbapenemase do tipo OXA foi o principal mecanismo envolvido na baixa susceptibilidade aos carbapenêmicos em CRAB (98 %; 95% IC: 0.91, 0.99; I² = 95 %), com bla OXA-23-like (91 %; 95 %; IC: 0,76; 0,97; I² = 97 %) ou bla OXA -51-like / ISAba1 (84 %; 95 % IC: 0.15, 0.99; I² = 98 %) genes, seguidos por metalo-ß-lactamases (MBL) (12 %, 95 % IC: 0,09, 0,15, I² = 99 %) e Klebsiella pneumoniae carbapenemase (KPC) (6 %, IC 95 %: 0,04; 0,08; I² = 87 %). Conclusão: Os estudos incluídos mostraram que a susceptibilidade à colistina (99 %) e tigeciclina (93 %) permanece alta e não foi afetada pela resistência aos carbapenêmicos.

Long-term treatment with nebulized colistin in oncological patients with recurrent respiratory infections.

OBJECTIVES: To assess the efficacy of long-term treatment with nebulized colistin in reducing the number of respiratory infections, emergency consultations and hospitalizations in oncological patients. METHODS: A retrospective, observational, single-centre study including patients with solid or haematologic malignancies, or pulmonary GVHD after HSTC who received treatment with nebulized colistin for at least six-months to prevent recurrent respiratory infections (July 2010 to June 2017). RESULTS: Twelve patients were included (median age: 54.4, range: 23-85), 7 with solid malignancies and 5 with haematologic malignancies (2 with pulmonary GVHD). Pseudomonas aeruginosa was the most frequent microorganism in sputum cultures (11/12 patients), all strains were susceptible to colistin. There was a statistically significant reduction (p=0.01) in respiratory infections in the six-month period after starting colistin (median: 1, range: 0-4) compared to the six-month period before (median: 4, range: 1-8). There was also a reduction in emergency consultations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) and hospitalizations (precolistin: median: 1.50, range: 0-3; postcolistin: median: 0, range: 0-3) due to respiratory infections. No colistin-resistant strains were identified. CONCLUSIONS: Long-term treatment with nebulized colistin may be useful to reduce the number of exacerbations in oncological patients with recurrent respiratory infections.

Resistencia a colistina en aislados de Klebsiella pneumoniae resistente a carbapenémicos en un hospital pediátrico de Corrientes / Colistin resistance in carbapenem-resistant Klebsiella pneumoniae isolates from a pediatric hospital from Corrientes, Argentina

INTRODUCCIÓN: Existe un incremento de las infecciones por Klebsiella pneumoniae resistente a carbapenémicos (KPRC) en la población pediátrica y los datos epidemiológicos son limitados. OBJETIVOS: Conocer la frecuencia de KPRC en pacientes pediátricos, determinar la actividad in vitro de colistina y detectar el gen mcr-1 en dichos aislados. MATERIALES Y MÉTODOS: Se estudiaron 220 aislados de K. pneumoniae en un hospital pediátrico durante los años 2018 y 2019. La susceptibilidad antimicrobiana se determinó por microdilución en caldo según CLSI y EUCAST. Los genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 y mcr-1 se analizaron mediante reacción de polimerasa en cadena (RPC). RESULTADOS: El 9,5% (n: 21) de los aislados fueron caracterizados como KPRC, donde se observó una resistencia a colistina de 47,6% (10/21) con valores de CIM50 de 2 μg/mL y CIM90 de > 4 μg/mL. En todos los aislados de KPRC se caracterizó el gen blaKPC y no se detectó el gen mcr-1. El perfil de resistencia observado en otros antimicrobianos fue el siguiente: gentamicina 100% (n: 21), ciprofloxacina 100% (n: 21), cotrimoxazol 100% (n: 21) y amikacina 19% (n: 4). Se observó 100% de sensibilidad a tigeciclina y ceftazidima/avibactam. CONCLUSIÓN: Este estudio demuestra un valor significativo de la resistencia a colistina en comparación a ceftazidima/avibactam y tigeciclina.

BACKGROUND: There is an increase of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the pediatric population and epidemiological data are limited. Aim: To calculate the frequency of CRKP in pediatric patients, to determine the in vitro activity of colistin and to detect the presence of mcr-1 gene in said isolates. METHODS: 220 isolates of K. pneumoniae were studied in a pediatric hospital between January 2018 and December 2019. Antimicrobial susceptibility was determined by microdilution in broth according to guidelines of CLSI and EUCAST. The genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 and mcr-1 were detected by polymerase chain reaction (PCR). RESULTS: 9.5% (n: 21) of the isolates were characterized as CRKP, where was observed a resistance to colistin of 47.6% (10/21) with values of MIC50 of 2 μg/mL and MIC90 of ≥ 4 μg/mL. In 100% of CRKP strains the blaKPC gene was detected and the mcr-1 gene was not found. The resistance profile to other antimicrobials was as follow: gentamicin 100% (n: 21), trimethoprim/sulfamethoxazole 100% (n: 21), ciprofloxacin 100% (n: 21), amikacin 19% (n: 4). All of the isolates were sensitive to ceftazidime/avibactam and tigecycline. CONCLUSION: This study demonstrates a significant value of resistance to colistin in pediatric patients compared to other last line antimicrobial such as ceftazidime/avibactam and tigecycline.

Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin.

Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin.

Frecuencia de resistencia a la colistina en Pseudomonas aeruginosa: primer reporte en el Perú

El objetivo del estudio fue determinar la frecuencia de resistencia a la colistina en Pseudomonas aeruginosa provenientes de tres establecimientos de salud de Lima, criopreservados en el banco de cepas del Laboratorio de Resistencia a Antimicrobianos e Inmunopatología de la Universidad Peruana Cayetano Heredia (UPCH). El método de elución de discos de colistina en caldo fue empleado para la identificación fenotípica de la resistencia a la colistina; la detección de la expresión del gen mcr-1 se realizó mediante el método fenotípico de difusión de discos combinados de colistina y ácido etilendiaminotetraacético (EDTA) y la reacción en cadena de la polimerasa (PCR) para la identificación molecular del gen. De los 97 aislados estudiados, 7 (7,2%) fueron resistentes a la colistina y ninguno fue portador del gen mcr-1. Este estudio constituye el primer reporte en el Perú de aislados clínicos de Pseudomonas aeruginosa resistentes a la colistina, lo que implica la necesidad de implementar metodologías apropiadas para la vigilancia epidemiológica de patógenos resistentes a la colistina.

This study aimed to determine the frequency of colistin resistance in Pseudomonas aeruginosa isolates obtained from three healthcare facilities in Lima and cryopreserved at the Laboratorio de Resistencia Antimicrobianos e Inmunopatología of the Universidad Peruana Cayetano Heredia (UPCH). The colistin broth disk elution method was used for the phenotypic identification of colistin resistance. We detected the expression of the mcr-1 gene by using the phenotypic diffusion method with combined colistin and ethylenediaminetetraacetic acid (EDTA) disks; and polymerase chain reaction (PCR) was used for molecular identification of the gene. Of the 97 isolates, 7 (7.2%) were resistant to colistin; however, none carried the mcr-1 gene. This is the first report from Peru on clinical isolates of colistin-resistant Pseudomonas aeruginosa, which suggests the need for implementation of appropriate methodologies for the epidemiological surveillance of colistin-resistant pathogens.

Colistina en el tratamiento de infecciones por pseudomonas aeruginosa y acinetobacter baumannii extensivamente resistentes (XDR) en un hospital de tercer nivel / Colistin-based treatment for extensively drug resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii infection at a third level hospital

Resumen Objetivo: Describir la respuesta clínica y mortalidad general de Colistina en infecciones por Pseudomonas XDR y Acinetobacter XDR en el Hospital Nacional Arzobispo Loayza in Lima, Peru. Métodos: Estudio observacional, descriptivo y retrospectivo. Se incluyeron los registros de pacientes > 18 años, desde junio del 2014 a junio del 2016, que tuvieron infección por Pseudomonas XDR o Acinetobacter XDR confirmada por cultivo, y que recibieron colistina. Se realizó análisis univariado de las características generales de los pacientes; un análisis bivariado con test de Chi2 , t-student o ANOVA según corresponda, y además se describió los factores asociados a mortalidad. Resultados. Se incluyeron 56 registros de pacientes, la mediana de la edad fue 46,5 [31,5 a 63,5]. El 48,2% tuvo un cultivo positivo para Pseudomonas XDR y el 51,8% para Acinetobacter XDR. La respuesta clínica favorable fue 85,7% a los 15 días y de 78,6% a los 30 días. La mortalidad intrahospitalaria a los 30 días fue 21,4%, la mortalidad en UCI fue de 30,8% y la nefrotoxicidad fue de 5,4%. Conclusiones. Colistina combinada con otro antimicrobiano tuvo una respuesta clínica favorable en infección por Pseudomonas XDR o Acinetobacter XDR.

Abstract Objective: To describe the clinical response and overall mortality of Colistin in infections by Pseudomonas XDR and Acinetobacter XDR at the Hospital Nacional Arzobispo Loayza in Lima, Peru. Methods: Observational, descriptive, retrospective study. Records of all patients > 18 years old, from June 2014 to June 2016, who had infection by Pseudomonas XDR or Acinetobacter XDR confirmed by culture, and who received colistin, were included. A univariate analysis of the general characteristics of the patients was performed; a bivariate analysis with a Chi2, t-student or ANOVA test as appropriate, and the factors associated with mortality were also determined. Results: 56 patient records were included; the median age was 46,5 [31,5 to 63,5]. The Culture was positive for Pseudomonas XDR in 48,2% and for Acinetobacter XDR in 51,8%. The favorable clinical response was 85,7% at 15 days and 78,6% at 30 days. In-hospital mortality at 30 days was 21,4%, ICU mortality was 30,8% and nephrotoxicity was 5,4%. Conclusions: Colistin combined with another antimicrobial had a favorable clinical response in infection with Pseudomonas XDR and Acinetobacter XDR.

Resistencia a la colistina en cepas de Klebsiella pneumoniae multidrogorresistente del período 2015-2018 en un instituto materno perinatal de Lima, Perú / Colistin resistance in multidrug-resistant Klebsiella pneumoniae strains at a perinatal maternal institute in Lima, Peru, 2015-2018

RESUMEN El objetivo del estudio fue evaluar los niveles y mecanismos de resistencia a la colistina y a los carbapenémicos en cepas de Klebsiella pneumoniae multidrogorresistente aisladas durante el periodo 2015-2018 en el Instituto Materno Perinatal de Lima. Se analizó la sensibilidad mediante difusión en disco y microdilución. La presencia de genes de resistencia a los carbapenémicos y a la colistina se determinó por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés) y se la relacionó con la clonalidad. Se analizaron 36 cepas de K. pneumoniae, cinco (13,8%) fueron resistentes a la colistina, pertenecían a diferentes grupos clonales. Se encontraron dos cepas con carbapenemasas (bla KPC y bla NDM) y no se detectaron genes plasmídicos para la colistina. Los niveles de resistencia al resto de antimicrobianos testados fueron elevados, a excepción de amikacina (13,9%). Los resultados destacan la presencia de cepas resistentes a la colistina (33,3% en 2018), situación preocupante por ser esta parte de las últimas alternativas de tratamiento para las infecciones causadas por patógenos multirresistentes.

ABSTRACT The objective of this study was to evaluate the presence of colistin- and carbapenemic-resistant genes in multidrug-resistant Klebsiella pneumoniae strains isolated at the Instituto Materno Perinatal de Lima (2015-2018). Susceptibility levels were analyzed by disk diffusion and microdilution. The presence of colistin- and carbapenemic-resistant genes was determined by polymerase chain reaction (PCR) and was related to clonality. A total of 36 K. pneumoniae strains were analyzed, 5 (13.8%) were resistant to colistin and belonged to different clonal groups. Only 2 strains were found with carbapenemases (bla KPC and bla NDM), and no colistin plasmid genes were detected. High resistance levels to the other tested antimicrobials were observed, except for amikacin (13.9%). The results highlight the presence of colistin-resistant strains (33.3% in 2018), a worrying situation as they are part of the latest treatment alternatives for infections caused by multiresistant pathogens.

Enterobacterales productores de betalactamasas de espectro extendido portadores del gen mcr-1 en Lima, Perú / Extended-spectrum beta-lactamase-producing enterobacterales carrying the mcr-1 gene in Lima, Peru

RESUMEN Se analizó la presencia del gen mcr-1 en 165 enterobacterales productores de betalactamasas de espectro extendido (EP-BLEE) recuperados en 2017 de sangre (40), orina (57), secreciones respiratorias bajas (12) e hisopados rectales (56) de pacientes hospitalizados en el Instituto Nacional de Enfermedades Neoplásicas (Perú). La identificación y la susceptibilidad antimicrobiana se determinaron por el sistema automatizado Phoenix M50; la resistencia a colistina por Colistin Agar-Spot (CAS); la detección de mrc-1 por el método fenotípico de predifusión de colistina e inhibición con EDTA (CPD-E) y por reacción en cadena de la polimerasa (PCR, por sus siglas en inglés). De los 165 EP-BLEE 25 fueron positivos para mcr-1 por el método CPD-E y se confirmó por PCR. Por el método CAS, 20/165 fueron resistentes a colistina. Además, mostraron resistencia a las fluoroquinolonas y a la gentamicina, y permanecieron sensibles a la amikacina; dos aislamientos presentaron metalocarbapenemasas. La obtención de datos sobre la resistencia a antimicrobianos considerados de última línea (colistina) es crucial para establecer medidas para su control.

ABSTRACT We analyzed the presence of the mcr-1 gene in 165 extended-spectrum beta-lactamase-producing enterobacterales (ESBL-PE) obtained during 2017, from blood (40), urine (57), lower respiratory secretions (12) and rectal swabs (56) of patients hospitalized in the Instituto Nacional de Enfermedades Neoplásicas (Peru). Antimicrobial identification and susceptibility were determined by the Phoenix M50 automated system; colistin resistance by Colistin Agar-Spot (CAS); mrc-1 detection by colistin pre-diffusion and inhibition with EDTA test (CPD-E) and by polymerase chain reaction (PCR). We found that from the 165 ESBL-PE, 25 were positive for mcr-1 by the CPD-E method and confirmed by PCR. Colistin resistance was found in 20/165 by using the CAS method. Additionally, they showed resistance to fluoroquinolones and gentamicin, while remaining sensitive to amikacin; two isolates presented metallo-carbapenemases. Obtaining data on resistance to last-line antimicrobials (colistin) is crucial to establish measures for its control.

Perfil fenotípico de resistência à colistina e tigeciclina em um hospital público no Brasil / Phenotypical profile of colistin and tigecycline resistance in a public hospital in Brazil / Perfil fenotípico de resistencia a la colistina y tigeciclina en un hospital público de Brasil

Justificativa e objetivos: Infecções Relacionadas à Assistência à Saúde (IRAS) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) são consideradas um problema de saúde pública e um impacto nas taxas de mortalidade nas Unidades de Terapia Intensiva (UTI). O objetivo deste estudo foi verificar o perfil fenotípico de resistência à colistina e à tigeciclina, consideradas como último recurso terapêutico aos BGN-MDR. Métodos: Os dados foram coletados nas fichas de busca ativa do serviço de controle de infecções e prontuários médicos de pacientes internados em duas UTIs de um hospital público de Joinville, entre janeiro de 2016 e junho de 2017. Resultados: Ocorreram 256 IRAS por BGN, acometendo principalmente o gênero masculino (62%), com mediana de idade de 65 anos. Entre os BGN, 37% expressaram MDR; sendo as espécies mais frequentes: Klebsiella pneumoniae e (47%), Acinetobacter baumannii (23%) e Stenotrophomonas maltophilia (11%). A resistência de BGN-MDR à colistina e tigeciclina foi de 5% e de 12%, respectivamente; 5% dos isolados foram resistentes aos dois antibióticos. A taxa de óbito entre os pacientes com IRAS por BGN-MDR resistentes à colistina foi mais alta (60%) que aquelas à tigeciclina (45%). Conclusão: K. pneumoniae e A. baumannii produtores de carbapenemases, resistentes a colistina e tigeciclina prevaleceram entre os BGN-MDR, e estiveram associadas a maioria dos óbitos. Essas observações, junto com o alto uso de carbapenêmicos na terapia empírica, mostra a necessidade do uso racional de antimicrobianos.(AU)

Background and objectives: Healthcare-associated Infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (GNB-MDR) are considered a public health problem and have an impact on mortality rates in Intensive Care Units (ICU). The aim of this study was to verify the phenotypic profile of resistance to colistin and tigecycline, considered as the last antimicrobial choice to treat BGNMDR infections. Methods: Data were collected on the active search records of the infection control service and medical records of patients admitted to two ICUs at a public hospital in Joinville between January 2016 and June 2017. Results: There were 256 HAIs caused by GNB, mainly affecting males (62%), with a median age of 65 years. Among GNBs, 37% expressed MDR; the most frequent species were: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) and Stenotrophomonas maltophilia (11%). The resistance of GNB-MDR to colistin and tigecycline was 5% and 12%, respectively; 5% of the isolates were resistant to both antibiotics. The death rate among patients with HAIs caused by colistin-resistant GNB-MDR was higher (60%) than those to tigecycline (45%). Conclusion: Carbapenemase-producing K. pneumoniae and A. baumannii, resistant to colistin and tigecycline, prevailed among GNB-MDRs, and were associated with most deaths. These observations, coupled with the high use of carbapenems in empirical therapy, show the need for rational use of antimicrobials.(AU)

Justificación y objetivos: Las Infección nosocomial (IHs) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) se consideran un problema de salud pública y un impacto en las tasas de mortalidad en las Unidades de Terapia Intensiva (UTI). El objetivo de este estudio fue verificar el perfil fenotípico de resistencia a la colistina ya la tigeciclina, consideradas como último recurso terapéutico a los BGN-MDR. Métodos: Los datos fueron recolectados en las fichas de búsqueda activa del servicio de control de infecciones y prontuarios médicos de pacientes internados en dos UTIs de un hospital público de Joinville, entre enero de 2016 y junio de 2017. Resultados: Ocurrieron 256 IHs por BGN, que afectan principalmente al género masculino (62%), con mediana de edad de 65 años. Entre los BGN, el 37% expresó MDR; siendo las especies más frecuentes: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) y Stenotrophomonas maltophilia (11%). La resistencia de BGN-MDR a la colistina y tigeciclina fue del 5% y del 12%, respectivamente; 5% de los aislados fueron resistentes a los dos antibióticos. La tasa de muerte entre los pacientes con IH causadas por los BGN-MDR resistentes la colistina fue más alta (60%) que aquellas a tigeciclina (45%). Conclusión: K. pneumoniae y A. baumannii productoras de carbapenemases, resistentes la colistina y la tigeciclina, fueron más frecuentes entre los BGN-MDR y su asociación estuvo presente en la mayoría de las muertes. Estas observaciones, junto con el alto uso de carbapenems en la terapia empírica, muestran la necesidad de un uso racional de los antimicrobianos.(AU)

Colistina intraventricular en infección postoperatoria por Pseudomonas aeruginosa multiresistente:Reporte de un caso / Intraventricular Colistin in postoperative infection by resistant Pseudomonas aeruginosa: Report of a pediatric case.

Introducción: El surgimiento de bacterias Gram negativas multirresistentes y la aparición de infecciones post quirúrgicas, ha representado un desafío en el manejo antimicrobiano. Las características estructurales de estas bacterias, la formación de biofilms en los dispositivos internos y la presencia de infecciones en órganos de difícil acceso antimicrobiano como el sistema nervioso central, ha obligado a retomar el uso de antibióticos como Colistina por vías de administración poco utilizadas. Caso clínico: Presentamos el caso clínico de un paciente de 2 años de edad con meningo-ventriculitis postquirúrgica causada por Pseudomonas aeruginosa multirresistente manejado con tratamiento combinado de Colistina intraventricular e intravenoso, resultando en éxito terapéutico para el paciente. No se reportó ninguna reacción adversa a la medicación local ni sistémica. Tampoco se reportó recaídas infecciosas posterior al alta. Conclusiones: Los aspectos claves en el manejo de este tipo de infecciones deben ser consideradas: eliminación de la derivación ventrículo peritoneal infectada, óptima cobertura antimicrobiana y elección de la vía de administración más efectiva.

Introduction: The emergence of multi-resistant Gram-negative bacteria and the emergence of post-operative infections has represented a challenge in antimicrobial management. The structural characteristics of these bacteria, the formation of biofilms in internal devices and the presence of infections in organs of difficult antimicrobial access such as the central nervous system, has forced to consider the use of antibiotics such as Colistine through little-used administration routes. Clinical case: We present the clinical case of a 2-year-old patient with post-surgical meningo-ventriculitis caused by multiresistant Pseudomonas aeruginosa managed with combined treatment of intraventricular and intravenous Colistin, resulting in therapeutic success for the patient. No adverse reaction to local or systemic medication was reported. No infectious relapses were reported after discharge. Conclusions: The key aspects in the management of this type of infection have been considered: elimination of the infected peritoneal ventricle derivation, optimal antimicrobial coverage and choice of the most effective route of administration.

Escenario actual de la resistencia a la colistina mediada por plásmidos en América Latina / Current scenario of plasmid-mediated colistin resistance in Latin America

Colistin resistance can occur by chromosomal mutations and by acquisition of plasmid-carrying determinants, mainly mcr-1. In the recent years, we have observed the out-burst of this resistance gene in our region. Due to the risk of the rapid dissemination of mcr-1, this finding has worried and alerted different actors from the health field and has become one of the most prolific topics. Our review compiles available reports of well-documented mcr-1-positive strains of Enterobacteriaceae, obtained from different samples in Argentina and other countries of Latin America. Furthermore, it addresses the association of mcr-1 with ESBL resistance markers and outlines the platforms involved in their dissemination.

La resistencia a la colistina puede ocurrir por mutaciones cromosómicas o por la adquisición de determinantes localizados en plásmidos, el principal es mcr-1. En los últimos años hemos observado la explosiva aparición de este gen de resistencia en nuestra región. Debido al riesgo que implica la rápida diseminación de mcr-1, este hallazgo ha preocupado y alertado a los diferentes actores del área de la salud, y se ha convertido en uno de los temas de investigación más importantes. La presente revisión compila los informes de aislamientos portadores de mcr-1 debidamente documentados en Enterobacteriaceae, obtenidos de diferentes muestras en Argentina y otros países de América Latina. Además, aborda la asociación de mcr-1 con otros marcadores de resistencia, como las BLEE, y describe las plataformas involucradas en su diseminación.

Current scenario of plasmid-mediated colistin resistance in Latin America.

Colistin resistance can occur by chromosomal mutations and by acquisition of plasmid-carrying determinants, mainly mcr-1. In the recent years, we have observed the outburst of this resistance gene in our region. Due to the risk of the rapid dissemination of mcr-1, this finding has worried and alerted different actors from the health field and has become one of the most prolific topics. Our review compiles available reports of well-documented mcr-1-positive strains of Enterobacteriaceae, obtained from different samples in Argentina and other countries of Latin America. Furthermore, it addresses the association of mcr-1 with ESBL resistance markers and outlines the platforms involved in their dissemination.

Relação ancestral e pan-resistoma plasmidial de Escherichia coli produtora de CTX-M-8 e MCR-1 na interface humana, animal e ambiental / Ancestral relationship and plasmid pan-resistome of CTX-M-8- and MCR-1-producing Escherichia coli in human-animal-environmental interface

Linhagens de Escherichia coli produtoras de ß-lactamase de espectro estendido (ESßL) do tipo CTX-M são endêmicas no Brasil, sendo prevalentes em casos de infecções hospitalares e ambulatoriais. Atualmente, cepas produtoras de CTX-M têm sido recuperadas de ambientes urbanos, animais de companhia ou de produção e de alimentos de origem animal, inclusive afetando o agronegócio, o que aponta uma possível rota de disseminação em diferentes ecossistemas. Recentemente, nesta espécie, foi descoberto um novo gene, chamado de mcr-1, que confere resistência transferível à colistina, um dos últimos antibióticos eficazes para o tratamento de infecções causadas por bactérias produtoras de ESBL e carbapenemases. Deste modo, o presente estudo tem como objetivo elucidar os aspectos sobre a caracterização e a relação de plasmídeos que carregam genes do tipo blaCTX-M-8 e mcr- 1 em cepas de E. coli isoladas de seres humanos, animais, ambiente aquático e alimentos, no Brasil. Neste estudo são apresentados os resultados da análise plasmidial de 25 cepas de E. coli, das quais nove apresentaram o genótipo blaCTX-M-8/IncI1, 11 apresentaram o genótipo mcr-1/IncX4 e cinco apresentaram ambos os genótipos blaCTX-M-8/IncI1 e mcr-1/IncX4. Dos resultados, podemos observar que plasmídeos IncI1 (blaCTX-M-8) e IncX4 (mcr-1) estão circulando no Brasil desde o ano de 2009 entre diferentes clones (STs) de E. coli e em diferentes ambientes e hospedeiros. Os plasmídeos IncI1 foram conjugativos e pertencentes ao ST113, exceto o plasmídeo recuperado de um isolado humano, que foi pertencente ao ST131. Os plasmídeos IncI1 apresentaram sua arquitetura conservada, com a presença de genes de replicação, transferência e estabilidade. A partir do alinhamento, os plasmídeos IncI1 apresentaram 94-99% de similaridade genética entre eles. Dentre os plasmídeos IncX4, independente da fonte de isolamento, todos permaneceram com sua arquitetura altamente conservada. Entretanto, apenas dois plasmídeos (um encontrado em uma cepa de animal e outro encontrado em uma cepa de ambiente aquático) apresentaram uma IS1294, truncando o gene de mobilização. Na análise comparativa, todos os plasmídeos IncX4 apresentaram similaridade genética de 95-99,9% entre eles. No alinhamento de plasmídeos IncX4 brasileiros contra plasmídeos de outras regiões geográficas, foi observada similaridade genética > 99,9%, o que confirma a estabilidade e conservação desses plasmídeos. Neste estudo foram reportados dados inéditos da primeira identificação do gene mcr-1 em diferentes ecossistemas no Brasil, assim como a nova variante mcr-5.3. A análise filogenética dos plasmídeos IncI1 e IncX4, destacam que ambos compartilham uma arquitetura conservada, e a evolução é atribuída à aquisição de genes de resistência. Adicionalmente, um novo vetor de disseminação do gene mcr-1 no Brasil foi identificado - o plasmídeo IncHI2. Os resultados desse estudo demonstram o grave problema da resistência bacteriana dentro do conceito One-health e que, com o avanço de ferramentas moleculares, a identificação e a resolução desse problema poderá estar cada vez mais próxima de ser elucidada

CTX-M-type extended-spectrum-ß-lactamase (ESßL)-producing-Escherichia coli are endemic in Brazil and are prevalent in cases of nosocomial and ambulatory infections. Currently, CTXM-producing strains have been recovered from urban environments, companion/production animals and animal source foods, which indicates a possible route of dissemination in different ecosystems. Recently, in this species, a new gene, called mcr-1, has been discovered, conferring transferable resistance to colistin, one of the last effective antibiotics for the treatment of infections caused by ESBL- and carbapenemases -producing bacteria. Thus, the present study aims to elucidate unknown aspects of the pan-resistome and ancestral relationship of plasmids carrying blaCTX-M-8 and mcr-1 genes in strains of E. coli isolated from humans, animals, aquatic environment and food, in Brazil. In this study, we present results from the plasmidial analysis of 25 E. coli strains, from which nine presented the blaCTX-M-8/IncI1 genotype, 11 presented the mcr-1/IncX4, and five presented both blaCTX-M-8/IncI1 and mcr-1/IncX4 genotypes. Among these results, we can observe that IncI1 (blaCTX-M-8) and IncX4 (mcr-1) plasmids are circulating in Brazil since 2009, between different E. coli clones (STs) and different hosts and environments. IncI1 plasmids were conjugative and assigned to ST113, with exception of a plasmid recovered from a human isolate, which was assigned to ST131. IncI1 plasmids presented conserved architecture, with the presence of genes of replication, transference, and stability. From the alignment analysis, IncI1 plasmids presented 94-99% genetic similarity among them. Among the IncX4 plasmids, regardless the isolation source, their architecture remained highly conserved. However, only two plasmids (one detected in an animal's strain and another detected in an aquatic environment's strain) presented an IS1294, truncating the mobilization gene. In the comparative analysis, all IncX4 plasmids presented 95-99,9% genetic similarity among them. In the alignment of Brazilian IncX4 plasmids against plasmids from other geographic regions, >99.9% genetic similarity was observed, confirming the stability and conservation of these plasmids. In this study, unprecedented data from the first identification of the mcr-1 gene in different ecosystems in Brazil, as well as the new variant, mcr-5.3. Additionally, it was identified a new dissemination vector of the mcr-1 gene in Brazil - the IncHI2 plasmid. Phylogenetic analysis of IncI1and IncX4 plasmids highlight that both share a conserved backbone, and evolution is attributed to the acquisition of clinically relevant antimicrobial resistance genes. The results from this study demonstrate the serious problem of the bacterial resistance within the "One-Health" concept and that, with the advance of molecular tools, identification and resolution of this problem may be increasingly closer to being elucidate

Dosis de colistina en multirresistencia: reporte de caso / Colistin dose in multiresistance: case report

RESUMEN Ante la alta resistencia a los antibióticos por infecciones bacterianas multirresistentes a nivel intrahospitalario, se debe pensar en alternativas terapéuticas que requieren el uso de antibióticos potentes y dosis mayores. Presentamos el caso de un paciente de 56 años con múltiples intervenciones quirúrgicas quien había recibido manejo antibiótico previo. Al presentar deterioro clínico se aísla en hemocultivos Pseudomonas aeruginosa resistente a carbapenémicos, se inicia manejo con colistina intravenosa y doripenem, con el posterior desarrollo de una falla renal que se revierte al disminuir la dosis de colistina. Finalmente el paciente culmina el tratamiento con un ajuste de antibiótico de 10 días, con la respuesta clínica favorable.

SUMMARY Given the high resistance to antibiotics due to multiresistant bacterial infections at the hospital level, therapeutic alternatives that require the use of more potent antibiotics and higher doses should be considered. We presented the case of a 56-year-old patient with multiple surgeries and several previous antibiotic treatments. After clinical deterioration, a blood culture yield Pseudomonas aeruginosa resistant to carbapenems, treated with intravenous colistin and doripenem. The patient then developed acute renal failure, which reverts when the colistin dose decreases. Finally, the patient finishes the treatment with 10-day antibiotic adjustment and favorable clinical response.

Colistin induced neurotoxity: a case report and review of literature / Neurotoxicidade induzida pela colistina: relato de caso e revisão de literatura

OBJECTIVE: To describe a case of neurotoxity associated to Colistin. CASE DESCRIPTION: A 29-year-old black male under treatment for urinary tract infection with identification of Klebsiella pneumoniae in urine culture resistant to all carbapenem antibiotics, presented visual turbidity, paresthesia on the face and upper left limb, slowed and discordant speech in the fourth day of Colistin use. Symptoms improved after reduction of the dose of colistin with adjustment for renal function, with complete reversion after discontinuation of the drug. CONCLUSIONS: Colistin-mediated neurotoxicity must be suspected in patients with altered mental status of unknown etiology and therapy promptly interrupted.

OBJETIVO: Descrever um caso de neurotoxidade associada à Colistina. DESCRIÇÃO DO CASO (desnecessário repetição): Um homem negro de 29 anos sob tratamento para infecção do trato urinário com identificação de Klebsiella pneumoniae (escrever corretamente) em cultura de urina resistente a carbapenêmicos, apresentou turvação visual, parestesia em face e membro superior esquerdo, discurso lento e discordante na quarto dia de uso da Colistina. Os sintomas melhoraram após a redução da dose de colistina com ajuste para a função renal, com reversão completa após a descontinuação do fármaco. CONCLUSÕES: A neurotoxicidade mediada por colistina deve ser suspeitada em pacientes com estado mental alterado de etiologia desconhecida e a terapia prontamente interrompida.

Toxicidad por colistina: hiperpigmentación cutánea, neurotoxicidad y nefrotoxicidad: Reporte de caso / Colistin toxicity: skin hyperpigmentation, neuro and renal toxicity: A case report

La colistina o polimixina E es un antibiótico cuyo uso fue descontinuado por la toxicidad renal y neurológica relacionadas al uso de colistina sulfato. Estos efectos adversos han disminuido con el uso del profármaco colistimetato sódico. Actualmente el uso de colistina es más frecuente debido al incremento de infecciones ocasionadas por bacilos Gram negativos multirresistentes, sobre todo en las unidades de cuidados intensivos. Presentamos el caso de una mujer de 50 años de edad con antecedente de consumo de anti-inflamatorios no esteroideos y corticoides, pos- operada de perforación gástrica que evolucionó con colecciones abdominales por Acinetobacter sp. multirresistente. Recibió 34 días de colistina endovenosa y desarrolló hiperpigmentación cutánea, ataxia (neurotoxicidad) y falla renal (nefrotoxicidad) de forma secuencial secundaria a la administración de colistina, los efectos adversos desaparecieron con la suspensión del antibiótico. (AU)

Colistin or polymycin E is an antibiotic that was discontinued due to its renal and neurologic toxicity related to its colistin sulfate content. These adverse effects have been reduced with the use of sodium colistemathe. There is currently a more frequent use of colistin due to an increase of multi-resistant Gram negative infections, particularly in intensive care units. We present the case of a 50-year-old woman with history of surgery due to gastric perforation, use of steroids and non-steroidal anti-inflammatory drugs, that developed intra-abdominal abscesses due to multidrug resistant Acinetobacter spp. She received 34 days of intravenous colistin and developed skin hyperpigmentation, ataxia and renal failure. These adverse effects disappeared with discontinuation of the drug. (AU)

Prevalencia de injuria renal aguda en pacientes tratados con colistina

RESUMEN Introducción: la colistina es un antibiótico eficaz para tratar infecciones causadas por bacterias Gram negativas multirresistentes pero tiende a producir injuria renal aguda. Objetivos: determinar la frecuencia de injuria renal aguda en pacientes adultos tratados con colistina e identificar la presencia de afecciones comórbidas asociadas. Metodología: estudio observacional retrospectivo de pacientes tratados con colistina en el Hospital Nacional, Paraguay, en 2016-2017. Resultados: se estudiaron 80 pacientes, siendo 64% del sexo masculino. La edad media fue 50±17 años. La prevalencia de injuria renal aguda fue 70%. Según los criterios RIFLE hubo lesión en 45% de los casos, riesgo de lesión en 25% y no riesgo/no lesión en 30%. Las afecciones comórbidas más frecuentes fueron la hipertensión arterial (61%) y diabetes mellitus (31%). El germen aislado con mayor frecuencia fue Acinetobacter baumannii (57%), Pseudomonas aeruginosa (24%) y Klebsiella pneumoniae (19%). Los antibióticos más utilizados en forma combinada con la colistina fueron la vancomicina (46%) y los carbapenémicos (43%). Conclusiones: la prevalencia de injuria renal aguda fue 70%. Según los criterios RIFLE predominó la lesión. Las afecciones comórbidas más frecuentes fueron la hipertensión arterial y la diabetes mellitus.

ABSTRACT Introduction: Colistin is an effective antibiotic to treat infections caused by multiresistant Gram-negative bacteria but tends to produce acute renal injury. Objectives: To determine the frequency of acute renal injury in adult patients treated with colistin and to identify the presence of associated comorbid conditions. Methodology: Retrospective observational study of patients treated with colistin in the National Hospital, Paraguay in 2016-2017. Results: Eighty patients were studied and 64% of them were male. The mean age was 50±17 years. The prevalence of acute renal injury was 70%. According to the RIFLE criteria there was an injury in 45% of the cases, risk of injury in 25% and no risk/no injury in 30%. The most common comorbid conditions were hypertension (61%) and diabetes mellitus (31%). The most frequently isolated germs were Acinetobacter baumannii (57%), Pseudomonas aeruginosa (24%) and Klebsiella pneumoniae (19%). The most commonly used antibiotics in combination with colistin were vancomycin (46%) and carbapenems (43%). Conclusions: The prevalence of acute renal injury was 70%. According to the RIFLE criteria, the injury predominated. The most common comorbid conditions were hypertension and diabetes mellitus.