Prevalencia de infección del tracto urinario y perfil de susceptibilidad antimicrobiana en Enterobacterias

Resumen Las Infecciones del Tracto Urinario (ITU), constituyen uno de los principales motivos de consulta en el ámbito de atención primaria, debido al aumento de la resistencia antibacteriana. Objetivo . Caracterizar la prevalencia de infección del tracto urinario y el perfil de susceptibilidad antimicrobiana in vitro en Enterobacterias en los pacientes de la provincia de Santa Elena - Ecuador. Método . Esta investigación fue descriptiva de diseño documental. La población fue de 827 registros de urocultivos, recopilados de la base de datos del laboratorio de microbiología del Centro de Especialidades IESS La Libertad, en el período comprendido desde agosto 2019 hasta marzo de 2020. Los datos fueron procesados mediante estadística descriptiva, análisis de frecuencia y chi cuadrado. Resultados . De este estudio indican que la prevalencia de ITU fue 22,1%; los principales agentes etiológicos fueron: E. coli (76,0%), Klebsiella oxytoca (6,5%), Klebsiella pneumoniae (5,8%) y Proteus mirabilis (3,9%). La ITU y la infección por E. coli fueron estadísticamente mayores en mujeres y adultos mayores. La mayor frecuencia de resistencia de E. coli fue para ácido nalidíxico (81,2%), ampicilina (79,9%), ciprofloxacina (72,6%) y sulfametoxazol trimetoprima (61,5%); en Klebsiella oxytoca fue ampicilina (80,0%), sulfametoxazol trimetoprima (70,0%), ácido nalidíxico (60,0%) y ciprofloxacina (40,0%). Mientras que en Klebsiella pneumoniae se halló una resistencia del (100%) para ampicilina y cefalotina, amoxicilina y ácido clavulánico (66,7%), ciprofloxacina (55,6%), ácido nalidíxico (44,4%), meropenem e imipenem (11,1%). Conclusiones. La E. coli continúa siendo el microorganismo más frecuente en ITU. El tratamiento empírico de ITU debería incluir amikacina, nitrofurantoina y piperacilina tazobactam.

Abstract Urinary Tract Infections (UTI) are one of the main reasons for consultation in the primary care setting, due to the increase in antibacterial resistance. Objective . To characterize the prevalence of urinary tract infection and the in vitro antimicrobial susceptibility profile of Enterobacteriaceae in patients in the province of Santa Elena - Ecuador. Method. This was a descriptive research of documentary design. The population was 827 urine culture records, collected from the database of the microbiology laboratory of the Centro de Especialidades IESS La Libertad, in the period from August 2019 to March 2020. The data were processed using descriptive statistics, frequency analysis and chi-square. Results . From this study indicate that the prevalence of UTI was 22.1%; the main etiological agents were: E. coli (76.0%), Klebsiella oxytoca (6.5%), Klebsiella pneumoniae (5.8%) and Proteus mirabilis (3.9%). UTI and E. coli infection were statistically higher in women and older adults. The highest frequency of E. coli resistance was for nalidixic acid (81.2%), ampicillin (79.9%), ciprofloxacin (72.6%) and trimethoprim sulfamethoxazole (61.5%); in Klebsiella oxytoca it was ampicillin (80.0%), trimethoprim sulfamethoxazole (70.0%), nalidixic acid (60.0%) and ciprofloxacin (40.0%). While in Klebsiella pneumoniae, 100% resistance was found for ampicillin and cephalothin, amoxicillin and clavulanic acid (66.7%), ciprofloxacin (55.6%), nalidixic acid (44.4%), meropenem and imipenem (11.1%). Conclusions . E. coli continues to be the most frequent microorganism in UTI. Empirical treatment of UTI should include amikacin, nitrofurantoin and piperacillin tazobactam.

Resumo As infecções do trato urinário (IU) são um dos principais motivos de consulta no âmbito dos cuidados primários, devido ao aumento da resistência antibacteriana. Objetivo . Caracterizar a prevalência da infecção do trato urinário e o perfil de suscetibilidade antimicrobiana in vitro de Enterobacteriaceae em pacientes da província de Santa Elena - Equador. Método . Esta foi uma pesquisa descritiva do projeto documental. A população era de 827 registros de cultura de urina, coletados do banco de dados do laboratório de microbiologia do Centro de Especialidades IESS La Libertad, no período de agosto de 2019 a março de 2020. Os dados foram processados utilizando estatísticas descritivas, análise de freqüência e qui-quadrado. Resultados. Deste estudo indicam que a prevalência de UTI foi de 22,1%; os principais agentes etiológicos foram: E. coli (76,0%), Klebsiella oxytoca (6,5%), Klebsiella pneumoniae (5,8%) e Proteus mirabilis (3,9%). A infecção por UTI e E. coli foi estatisticamente maior nas mulheres e nos adultos mais velhos. A maior freqüência de resistência do E. coli foi para o ácido nalidíxico (81,2%), ampicilina (79,9%), ciprofloxacina (72,6%) e trimetoprim sulfametoxazol (61,5%); em Klebsiella oxytoca era ampicilina (80,0%), trimetoprim sulfametoxazol (70,0%), ácido nalidíxico (60,0%) e ciprofloxacina (40,0%). Enquanto em Klebsiella pneumoniae, foi encontrada 100% de resistência para ampicilina e cefalotina, amoxicilina e ácido clavulânico (66,7%), ciprofloxacina (55,6%), ácido nalidíxico (44,4%), meropenem e imipenem (11,1%). Conclusões . A E. coli continua sendo o microorganismo mais freqüente na UTI. O tratamento empírico da UTI deve incluir amikacina, nitrofurantoína e piperacilina tazobactam.

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

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

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

Tuberculosis multirresistentediez años después / Multi-drug resistant tuberculosis, ten years later

La tuberculosis con resistencia a fármacos, sobre todo la que conlleva resistencia a rifampicina (TB-RR), se ha convertido en uno de los principales obstáculos para alcanzar el sueño de erradicar esta enfermedad. Y es que, para intentar curar la TB es necesario asociar tres o cuatro fármacos diferentes y, lamentablemente, son pocos los disponibles que se puedan considerar auténticamente eficaces. Pero, afortunadamente, el notable incremento que ha habido en los últimos años de la TB-RR en el mundo, ha motivado que se hayan invertido recursos en el desarrollo de nuevos fármacos para la TB, o que otros antimicrobianos investigados para otras enfermedades se hayan probado con éxito en la TB. Esto ha hecho que el manejo clínico de estos pacientes haya cambiado notablemente en los últimos tres a cuatro años, y resulte ahora más sencillo diseñar esquemas terapéuticos y conseguir mayores tasas de éxito. Todos estos cambios se actualizan en esta revisión. (AU)

Drug-resistant tuberculosis, especially those with resistance to rifampicin (RR-TB), has become one of the main obstacles to achieving the dream of eradicating tuberculosis. Furthermore, it is necessary to combine three or four different drugs in the attempt to cure TB, however, unfortunately, there are few available that can be considered genuinely effective. Fortunately, the notable worldwide increase in RR-TB in recent years has led to the investment of resources in the development of new drugs for TB, and other drugs investigated for other diseases have been successfully tested on TB. This has resulted in a clear change in the clinical management of these patients over the last 3-4 years, and it is now easier to design therapeutic regimens and achieve higher success rates. All these changes are updated in this review. (AU)

Multi-drug resistant tuberculosis, ten years later. / Tuberculosis multirresistentediez años después.

Drug-resistant tuberculosis, especially those with resistance to rifampicin (RR-TB), has become one of the main obstacles to achieving the dream of eradicating tuberculosis. Furthermore, it is necessary to combine three or four different drugs in the attempt to cure TB, however, unfortunately, there are few available that can be considered genuinely effective. Fortunately, the notable worldwide increase in RR-TB in recent years has led to the investment of resources in the development of new drugs for TB, and other drugs investigated for other diseases have been successfully tested on TB. This has resulted in a clear change in the clinical management of these patients over the last 3-4 years, and it is now easier to design therapeutic regimens and achieve higher success rates. All these changes are updated in this review.

Resistencia Bacteriana a desinfectantes en áreas comunes de oficinas / Bacterial Resistance to disinfectants in common office areas

Introducción. El uso de diferentes agentes químicos para la atenuación, tratamiento y control de microorganismos ha venido aumentando, la falta de control y conocimiento de estos productos, está generando un cambio del genoma en los microorganismos, provocando resistencia a concentraciones normales de biocidas. Objetivo: Realizar una revisión sistemática sobre la resistencia bacteriana a los desinfectantes en áreas comunes de oficina. Métodos: Revisión sistemática de bases de datos; Scielo, Elsevier, Pubmed y ACS Publications research, y fuentes secundarias como la OPS (organización Panamericana de la Salud) y la OMS (Organización Mundial de la Salud), entre otras, utilizando términos tales como; Resistencia bacteriana, desinfección, enfermedades laborales o profesionales y resistencia a desinfectantes. Resultados: Enterobacter sp. resistente a Amonio Cuaternario (QAC), desinfectantes a base de halógeno y formaldehído al 37%; Pseudomonas aeruginosa 71% de los aislamientos multirresistentes a los antibióticos, 43% susceptibilidad reducida a QAC, a triclosan (TC) y Benzalconio (BAC), y 24 aislamientos resistentes a agentes antimicrobianos. M. massiliense BRA 100 susceptible a ortoftaldehido (OPA), ácido peracético (PA), y a altas concentraciones de glutaraldehído. Aislamientos clínicos de cepas multirresistentes a antibióticos como: MRSA, Enterococcus sp. y Pseudomonas aeruginosa, 52% y 38% cepas fueron resistentes a compuestos de amonio cuaternario y fenol, respectivamente. Conclusiones: La presencia de microorganismos resistente en lugares comunes como; pisos, interruptores de luz, manijas de puertas, escritorios y sillas, entre otras, enuncia un problema de salud pública que se debe comenzar a tratar, cambiando las metodologías utilizadas para la desinfección, y otras medidas de control y prevención.

Introduction. The use of different chemical agents for the attenuation, treatment and control of microorganisms has been increasing, the lack of control and knowledge of these products is generating a change in the genome in microorganisms, causing resistance to normal concentrations of biocides. Objective: To carry out a systematic review on bacterial resistance to disinfectants in common office areas. Methods: Systematic review of databases; Scielo, Elsevier, Pubmed and ACS Publications research, and secondary sources such as PAHO (Pan American Health Organization) and WHO (World Health Organization), among others, using terms such as; Bacterial resistance, disinfection, occupational or professional diseases and resistance to disinfectants. Results: Enterobacter sp.: resistant to Quaternary Ammonium (QAC), halogen-based disinfectants and 37% formaldehyde; Pseudomonas aeruginosa: 71% of isolates multiresistant to antibiotics, 43% reduced susceptibility to QAC, triclosan (TC) and Benzalkonium (BAC), and 24 isolates resistant to antimicrobial agents. M. massiliense BRA 100 susceptible to orthophthaldehyde (OPA), peracetic acid (PA), and high concentrations of glutaraldehyde. Clinical isolates of multiresistant strains to antibiotics such as: MRSA, Enterococcus sp. and Pseudomonas aeruginosa, 52% and 38% strains were resistant to quaternary ammonium and phenol compounds, respectively. Conclusions: The presence of resistant microorganisms in common places such as; floors, light switches, door handles, desks and chairs, among others, enunciates a public health problem that must begin to be addressed, changing the methodologies used for disinfection, and other control and prevention measures.

[Péptidos antimicrobianos, una alternativa prometedora para el tratamiento de enfermedades infecciosas].

Microorganisms that cause diseases in humans are constantly evolving, which represents a challenge in the search for effective treatments against them. Even when currently there are several pharmacological alternatives available, sometimes they are inefficient for the control of infectious diseases, especially because pathogens have generated multiple resistance mechanisms against them. Antimicrobial peptides have been described in many species of organisms, from fungi, plants and insects to humans; currently, there are molecules that appear as a solution that can be effective in modern therapeutics. The advantage of these natural peptides lies in that they have been evolving almost the same amount of time than the species that produce them and their effect on the control of microorganisms is highly significant; some of these molecules are isolated from living organisms, others are starting to be produced by synthetic methods, which allows having access to an endless number of peptides with diverse therapeutic activities.

Los microorganismos causantes de enfermedades en humanos evolucionan constantemente, lo que representa un reto en la búsqueda de tratamientos efectivos contra estos patógenos. Aun cuando en la actualidad se cuenta con diversas alternativas farmacológicas, estas en ocasiones resultan ineficientes para el control de las enfermedades infecciosas, sobre todo porque los patógenos han generado múltiples mecanismos de resistencia. Los péptidos antimicrobianos se han descrito en muchas especies de organismos: hongos, plantas, insectos y humanos; en la actualidad se presentan como una solución terapéutica que puede ser efectiva. La ventaja de estos péptidos naturales es que llevan evolucionando casi la misma cantidad de tiempo que las especies que producen y su efecto en el control de los microorganismos es muy notable; algunas de estas moléculas son aisladas de organismos vivos y otras se comienzan a producir por métodos sintéticos, lo que permite tener acceso a un sinfín de posibles péptidos con actividades terapéuticas diversas.

Resistencia bacteriana en urocultivos de una población de embarazadas de control prenatal en Bogotá junio 2013­junio 2015 / Bacterial resistance in urine cultures ina population of pregnant women in prenatal care in bogota june2013 ­june 2015

La infección urinaria baja, específicamente la bacteriuria asintomática afecta el 2 al 7% de los embarazos; sin tratamiento, evoluciona a pielonefritis, aumentala probabilidad de parto pretérmino, bajo peso al nacer y preeclampsia. La identificación y tratamiento de la infección urinaria bajaes prioritaria.Conocer la sensibilidad antibiótica de los diferentes patógenos permiterevisar las estrategias de tratamiento y disminuir los desenlaces adversos perinatales.Objetivo:Determinar el perfil de resistencia de los principales patógenos aislados en los urocultivos de las pacientes embarazadas que acudieron a control prenatal en Clínica Colsanitas. Materiales y Métodos:Se realizó un estudio observacional con pacientes gestantes que asistieron a control prenatal. Se tomaron todos los resultados de urocultivos de las pacientes gestantes y se excluyeron urocultivos sugestivos de contaminación. Se analizaron los patógenos aislados y la sensibilidad a los diferentes antibióticos. Resultados:De 14054 muestras para urocultivo 1177 resultaron positivas.El principal patógeno aislado fue Escherichia colicon una prevalencia del 71,4%, seguido en frecuencia por Enterococcus faecalis, Proteus mirabilis y Klebsiella pneumoniae. La resistenciade Escherichia colia ampicilina fue de 37,3%, atrimetoprim sulfametoxazol 23,3%, cefalotina 11,1%.Lasensibilidad afosfomicina fue de 98%. En general los patógenos más frecuentemente aislados presentaron bajas tasas de expresión de betalactamasas. Conclusiones:E. colifue el patógeno más frecuente.La alta resistencia a la ampicilinacontraindica su uso empírico.El uso de otros antibióticos como cefalexina o nitrofurantoínaes adecuado.Fosfomicina puede ser una opción cuando no sea posible usar los anteriormente descritos.

Urinary tract infection(UTI), specifically asymptomatic bacteriuria, affects 2% to 7% of pregnancies; without treatment, it evolves into pyelonephritis, increases the probability of preterm birth, low birth weight and preeclampsia.Detection and treatment of UTIis a priority. Knowing the antibiotic sensitivity of different pathogens allows us to review treatment strategies and reduce adverse perinatal outcomes.Objective: To determine the resistance profile of the main pathogens isolated in urine cultures of pregnant patients who attended prenatal care in Clinica Colsanitas. Materials and Methods: An observational study was performed with pregnant patients who attended prenatal care. All urine culture results were taken from the pregnant patients and urine cultures suggestive of contamination were excluded. The isolated pathogens and the sensitivity to the different antibiotics were analyzed.Results: Out of 14054 urine samples, 1177 were positive. The main isolated pathogen was Escherichia coli with a prevalence of 71.4%, followed in frequencyby Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumoniae. The resistance of Escherichia coli to ampicillin was 37.3%, trimethoprimsulfamethoxazole 23.3%, cefalotin 11.1%. The sensitivity to fosfomycin was 98%. In general, the most frequently isolated pathogens showed low rates of beta-lactamase expression.Conclusions:E. coli was the most frequent pathogen. The high resistance to ampicillin contraindicates its empirical use. The use of other antibiotics such as cephalexin or nitrofurantoin is adequate. Fosfomycin may be an option when it is not possible to use previously described.

In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates / Actividad in vitro de azoles contra aislamientos clínicos de Mycobacterium tuberculosis

Background: Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. Methods: A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. Results: MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC5o and MIC90 to ECO was 4.0 µg/ml, while MIC50 to CLO was 4.0 µg/ml and MIC90 was 8.0 µg/ml respectively. Conclusion: All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates.

Introducción: La tuberculosis (TB) latente ha sido asociada a la persistencia de Mycobacterium tuberculosis durmientes en el organismo de las personas infectadas, las cuales constituyen un reservorio del bacilo y una fuente de diseminación de la enfermedad en la comunidad. Urge la necesidad de contar con nuevos fármacos antituberculosos con acción sobre el bacilo en estado latente/durmiente, a fin de evitar reactivaciones endógenas y para ser incluidas en el tratamiento de la TB multirresistente y extensivamente resistente (M/XDR-TB). Se ha reportado que los azoles son activos contra M. tuberculosis. Por esta razón, los objetivos del presente estudio fueron determinar la actividad in vitro sobre aislamientos clínicos de M/XDR-TB de distintos azoles, incluyendo los imidazoles econazol (ECO) y clotrimazol (CLO) y los 5-nitro-imidazoles ipronidazol (IPZ) y metronidazol (MZ), así como analizar su potencial uso contra las formas latente y activa de esta enfermedad. Métodos: Fueron incluidos 55 aislamientos clínicos de M. tuberculosis MDR y la cepa de referencia H37Rv. Se evaluó la actividad del MZ y el IPZ sobre los aislamientos en condiciones de cultivo anaeróbico, mientras que la actividad del ECO y el CLO fue estimada determinando la concentración inhibitoria mínima (CIM) mediante el método colorimétrico de microdilución en placa. Resultados: El MZ y el IPZ presentaron actividad bacteriostática frente a las cepas de M. tuberculosis. La CIM50 y CIM90 del ECO fue de 4 µg/ml, mientras que el CLO presentó una CIM50 de 4 µg/ml y una CIM90 de 8 µg/ml. Conclusión: Todos los compuestos azólicos evaluados presentaron actividad inhibitoria frente a aislamientos clínicos de M. tuberculosis.

In vitro anti-tuberculosis activity of azole drugs against Mycobacterium tuberculosis clinical isolates.

BACKGROUND: Latent tuberculosis has been associated with the persistence of dormant Mycobacterium tuberculosis in the organism of infected individuals, who are reservoirs of the bacilli and the source for spreading the disease in the community. New active anti-TB drugs exerting their metabolic action at different stages and on latent/dormant bacilli are urgently required to avoid endogenous reactivations and to be part of treatments of multi- and extensively-drug resistant tuberculosis (M/XDR-TB). It was previously reported that azole drugs are active against M. tuberculosis. For that reason, the aims of this study were to determine the in vitro activity of azole drugs, imidazole (clotrimazole, CLO and econazole, ECO) and nitroimidazole (metronidazole, MZ and ipronidazole, IPZ), against a collection of MDR M. tuberculosis clinical isolates; and to analyze their potential use in both the LTB and the active forms of M/XDR-TB treatments. METHODS: A total of 55 MDR M. tuberculosis isolates and H37Rv were included. MZ and IPZ activity against M. tuberculosis isolates were tested using anaerobic culture conditions. The activity of ECO and CLO was measured by the minimal inhibitory concentration (MIC) using a microdilution colorimetric method. RESULTS: MZ and IPZ showed bacteriostatic activity against M. tuberculosis strains. MIC50 and MIC90 to ECO was 4.0µg/ml, while MIC50 to CLO was 4.0µg/ml and MIC90 was 8.0µg/ml respectively. CONCLUSION: All azole compounds tested in the study showed inhibitory activity against MDR M. tuberculosis clinical isolates.

Risk factors for nosocomial infections in patients receiving extracorporeal membrane oxygenation supportive therapy. / Factores de riesgo de las infecciones nosocomiales en pacientes que reciben oxigenación por membrana extracorpórea.

BACKGROUND AND OBJECTIVE: The aim of this study was to analyze risk factors for nosocomial infection (NI) in patients receiving extracorporeal membrane oxygenation (ECMO) support. PATIENTS AND METHODS: Clinical NI data were collected from patients who received ECMO support therapy, and analyzed retrospectively. RESULTS: Among 75 ECMO patients, 20 were found to have developed NI (infection rate 26.7%); a total of 58 pathogens were isolated, including 43 strains of gram-negative bacteria (74.1%) and 15 strains of gram-positive bacteria (25.9%). Multi-drug resistant strains were highly concentrated and were mainly shown to be Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Incidence of NI was related to the duration of ECMO support therapy and the total length of hospital stay, and the differences were statistically significant (P<.05). A prolonged period of ECMO support extended the hospital stay, but it did not increase the mortality rate. However, an elevated level of lactic acid increased the mortality rate in this study population. CONCLUSIONS: ECMO-associated secondary NIs correlated significantly with the length of hospital stay and with the duration of ECMO support. Therefore, to reduce the incidence of ECMO-associated NIs, preventive strategies that aim to shorten the duration of ECMO support therapy and avoid lengthy hospitalization should be applied, wherever possible.

Diagnosis and Treatment of Drug-Resistant Tuberculosis. / Diagnóstico y tratamiento de la tuberculosis con resistencia a fármacos.

In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed.

Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy. / Resistencias al tratamiento no quirúrgico en cáncer cutáneo no melanoma. Parte II: terapia fotodinámica, vismodegib, cetuximab, metotrexato intralesional y radioterapia.

A wide range of treatments is now available for nonmelanoma skin cancer, including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this second article, having covered the topical treatments of nonmelanoma skin cancer, we review resistance to other nonsurgical treatments, such as monoclonal antibodies against basal and squamous cell carcinomas, intralesional chemotherapy, photodynamic therapy, and radiotherapy.

[Efficacy of dolutegravir in treatment-experienced patients: the SAILING and VIKING trials]. / Eficacia de dolutegravir en pacientes experimentados: estudios SAILING y VIKING.

Dolutegravir is an HIV integrase inhibitor with a high genetic barrier to resistance and is active against raltegravir- and/or elvitegravir-resistant strains. The clinical development of dolutegravir for HIV infection rescue therapy is based on 3 clinical trials. In the SAILING trial, dolutegravir (5 mg once daily) in combination with 2 other antiretroviral agents was well tolerated and showed greater virological effect than raltegravir (400 mg twice daily) in the treatment of integrase inhibitor-naïve adults with virological failure infected with HIV strains with at least two-class drug resistance. The VIKING studies were designed to evaluate the efficacy of dolutegravir as rescue therapy in treatment-experienced patients infected with HIV strains with resistance mutations to raltegravir and/or elvitegravir. VIKING-1-2 was a dose-ranging phase IIb trial. VIKING-3 was a phase III trial in which dolutegravir (50 mg twice daily) formed part of an optimized regimen and proved safe and effective in this difficult-to-treat group of patients. Dolutegravir is the integrase inhibitor of choice for rescue therapy in multiresistant HIV infection, both in integrase inhibitor-naïve patients and in those previously treated with raltegravir or elvitegravir.

Resistance to first-line antituberculosis drugs in Spain, 2010-2011. RETUBES Study.

INTRODUCTION: The magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. METHODS: Prospective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. RESULTS: A total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). CONCLUSIONS: The rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

Recent advances in molecular methods for early diagnosis of tuberculosis and drug-resistant tuberculosis

Tuberculosis (TB) remains the main infectious cause of deaths in the world. Due to the slow metabolism of the causative agent, Mycobacterium tuberculosis, the isolation, identification and drug susceptibility testing requires several weeks. New techniques have improved specificity, turnaround time and cost effectiveness. Although these methods yield results within hours from sample collection, the clinical significance of each positive result requires rigorous evaluation in most cases. Herein the advantages and disadvantages of the most promising molecular techniques for detection of TB and drug resistance are discussed.

Avances recientes en métodos moleculares para el diagnóstico precoz y tuberculosis resistente al tratamiento La tuberculosis sigue siendo la principal causa de mortalidad por un agente infeccioso a escala mundial. Debido al metabolismo lento de su agente etiológico, Mycobacterium tuberculosis, el aislamiento, la identificación y las pruebas de susceptibilidad tardan varias semanas. Nuevas técnicas moleculares desarrolladas ofrecen mejorías en la especificidad, el tiempo para la obtención de resultados y su costo-efectividad. Estas pruebas producen resultados en pocas horas a partir de la toma de muestra, pero su relevancia clínica requiere aún ser evaluada rigurosamente en la mayoría de los casos. En esta revisión se discuten las ventajas y las desventajas de las pruebas moleculares más promisorias desarrolladas para el diagnóstico de la tuberculosis y la tuberculosis resistente a medicamentos.